Feeds:
Posts
Comments

Archive for the ‘Bio Instrumentation in Experimental Life Sciences Research’ Category

SHARK TANK FOR WOMEN Entrepreneurs in LIFE SCIENCES

Posted in Bio Instrumentation in Experimental Life Sciences Research, BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital on March 10, 2016| Leave a Comment »

SHARK TANK FOR WOMEN Entrepreneurs in LIFE SCIENCES

Reporter: Aviva Lev-Ari, PhD, RN

 

 

Next week Women in Bio (WIB), JLABs, and Johnson & Johnson Innovation are co-hosting The LobsterPot. This will be a “Shark Tank” style event eight female executives from startups raising funds will pitch to five senior-level women at investment firms.

 

Here’s some additional info on the event:

 

Date: March 16th, 2016

Time: 6:00 pm – 9:00 pm (ET)

6:00 pm – 6:30 pm Registration & Networking

6:30 pm – 8:00 pm Company Pitches & Investor Feedback

8:00 pm – 9:00 pm Networking

Location: 255 Main Street, 4th Floor, Cambridge

 

You can register for the event here

  

List of Participants:

 

MODERATOR: Marian Nakada, Vice President, Venture Investments, J&J Innovation (JJDC)

 

INVESTORS:

1.       Maria Berkman, Director, Broadview Ventures

2.       Patricia Gray, Member, Mass Medical Angels

3.       Christine Brennan, Principal, Novartis Venture Fund

4.       Barbara Sosnowski, VP External R&D Inflammation, Worldwide Research & Development External Partnerships, Pfizer

5.       Laura Davis, Managing Director, Golden Seeds

 

PRESENTING COMPANIES:

 

Devices:

1.       Georgia Mitsi, CEO, Apptomics

2.       Abigail Barnes, Co-Founder & CEO, Allergy Amulet

Diagnostics:

1.       Joyce Lonergan, CEO & Co-Founder, Mellitus, LLC

2.       Barbara Davis, Chief Executive Officer and President, Innogenics

Therapeutics:

1.         Maria Vilenchik, Founder & CEO, Felicitex Therapeutics

2.         Ailis Tweed-Kent, CEO & Founder, Cocoon Biotech

Healthcare IT:

1.         Tiffany Kelley, Founder & CEO, Nightingale Apps

2.         Elizabeth Asai, CEO & Co-Founder, 3Derm Systems

 

 

Hope to see you there next week!

Spread the word.  Sent to me by:

 

Danielle Silva

Founding Team

VP of Business Development

LIFE SCIENCE NATION

SOURCE

From: Shelley Amster <shelley@shelleyco.com>

Date: Thursday, March 10, 2016 at 11:00 AM

To: Shelley Amster <shelley@shelleyco.com>

Subject: SHARK TANK FOR WOMEN Entrepreneurs in LIFE SCIENCES – The Lobster Pot

Read Full Post »

Christopher J. Lynch, MD, PhD, the New Office of Nutrition Research, Director

Posted in Apoptosis, Autophagy, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Cardiomyopathy, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Clinical & Translational, Clinical Diagnostics, Clinical Genomics, Curation, Cytokines, Diabetes Mellitus, Disease Biology, Drug Toxicity, Endocrine Diseases, Enzyme Induction, Epigenetics and Cardiovascular Risks, Gastroenterology, Heart Failure (HF), Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Pre-Clinical Animal Model Development, tagged , , , on March 2, 2016| Leave a Comment »

Christopher J. Lynch, MD, PhD, the New Office of Nutrition Research, Director

Curator: Larry H. Bernstein, MD, FCAP

 

Christopher J. Lynch to direct Office of Nutrition Research

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

http://www.nih.gov/news-events/news-releases/christopher-j-lynch-direct-office-nutrition-research

 

Christopher J. Lynch, Ph.D., has been named the new director of the Office of Nutrition Research (ONR) and chief of the Nutrition Research Branch within the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Lynch officially assumed his new roles on Feb. 21, 2016. NIDDK is part of the National Institutes of Health.

Lynch will facilitate nutrition research within NIDDK and — through ONR — across NIH, in part by forming and leading a trans-NIH strategic working group. He will also continue and extend ongoing efforts at NIDDK to collaborate widely to advance nutrition research.

“Dr. Lynch is a leader in the nutrition community and his expertise will be vital to guiding the NIH strategic plan for nutrition research,” said NIH Director Francis S. Collins, M.D., Ph.D.  “As NIH works to expand nutrition knowledge, Dr. Lynch’s understanding of the field will help identify information gaps and create a framework to support future discoveries to ultimately improve human health.”

NIH supports a broad range of nutrition research, including studies on the effects of nutrient and dietary intake on human growth and disease, genetic influences on human nutrition and metabolism and other scientific areas. ONR was established in August 2015 to help NIH develop a strategic plan to expand mission-specific nutrition research.

“Every day, we learn more about the links between diet and life-threatening diseases such as type 2 diabetes, heart disease, and stroke, and how our gut microbiome may determine food preferences,” Lynch said. “These are exciting times for nutrition research and I’m delighted to help advance NIH-funded nutrition research.”

Lynch joins NIH after 27 years at Pennsylvania State University’s College of Medicine, Hershey, Pennsylvania, most recently serving as professor and vice chair of the Department of Cellular and Molecular Physiology. His research focuses on how what we eat and drink influences processes leading to obesity and type 2 diabetes. He has also investigated the relationship between antipsychotic therapy and obesity and type 2 diabetes and how gastric bypass surgery changes metabolism. Lynch also led efforts to increase nutrition education in the medical school curriculum.

“Nutrition research is a key to increasing our understanding of the causes of many diseases studied by NIDDK, including diabetes, obesity, inflammatory bowel disease, and others,” said NIDDK Director Griffin P. Rodgers, M.D. “With Dr. Lynch’s guidance, we hope to strengthen our research in nutrition, encourage innovative research through novel partnerships and help the public to better understand how nutrition influences their health.”

The NIDDK, a component of the NIH, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans. For more information about the NIDDK and its programs, visit www.niddk.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov

NARRATIVE:
Our laboratory is dedicated to developing cures for metabolic diseases like Obesity, Diabetes and MSUD. We have several projects:
Project 1: How Antipsychotic Drugs Exert Obesity and Metabolic Disease Side effects
Project 2: Impact of Branched Chain Amino Acid (BCAA) signaling and metabolism in obesity and diabetes.
Project 3: Adipose tissue transplant as a treatment for Maple Syrup Urine Disease.
Project 4: How Gastric Bypass Surgery Provides A Rapid Cure For Diabetes And Other Obesity Co-Morbidities Like Hypertension
Project 5: Novel Mechanism Of Action Of Cannabinoid Receptor 1 Blockers For Improvement Of Diabetes

Timeline

  1. Klingerman CM, Stipanovic ME, Hajnal A, Lynch CJ. Acute Metabolic Effects of Olanzapine Depend on Dose and Injection Site. Dose Response. 2015 Oct-Dec; 13(4):1559325815618915.

View in: PubMed

  1. Lynch CJ, Kimball SR, Xu Y, Salzberg AC, Kawasawa YI. Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover. Physiol Genomics. 2015 Nov; 47(11):569-80.

View in: PubMed

  1. Lynch CJ, Xu Y, Hajnal A, Salzberg AC, Kawasawa YI. RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats. PLoS One. 2015; 10(4):e0123966.

View in: PubMed

  1. Shin AC, Fasshauer M, Filatova N, Grundell LA, Zielinski E, Zhou JY, Scherer T, Lindtner C, White PJ, Lapworth AL, Ilkayeva O, Knippschild U, Wolf AM, Scheja L, Grove KL, Smith RD, Qian WJ, Lynch CJ, Newgard CB, Buettner C. Brain Insulin Lowers Circulating BCAA Levels by Inducing Hepatic BCAA Catabolism. Cell Metab. 2014 Nov 4; 20(5):898-909.

View in: PubMed

  1. Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014 Dec; 10(12):723-36.

View in: PubMed

  1. Olson KC, Chen G, Xu Y, Hajnal A, Lynch CJ. Alloisoleucine differentiates the branched-chain aminoacidemia of Zucker and dietary obese rats. Obesity (Silver Spring). 2014 May; 22(5):1212-5.

View in: PubMed

  1. Zimmerman HA, Olson KC, Chen G, Lynch CJ. Adipose transplant for inborn errors of branched chain amino acid metabolism in mice. Mol Genet Metab. 2013 Aug; 109(4):345-53.

View in: PubMed

  1. Olson KC, Chen G, Lynch CJ. Quantification of branched-chain keto acids in tissue by ultra fast liquid chromatography-mass spectrometry. Anal Biochem. 2013 Aug 15; 439(2):116-22.

View in: PubMed

  1. She P, Olson KC, Kadota Y, Inukai A, Shimomura Y, Hoppel CL, Adams SH, Kawamata Y, Matsumoto H, Sakai R, Lang CH, Lynch CJ. Leucine and protein metabolism in obese Zucker rats. PLoS One. 2013; 8(3):e59443.

View in: PubMed

  1. Lackey DE, Lynch CJ, Olson KC, Mostaedi R, Ali M, Smith WH, Karpe F, Humphreys S, Bedinger DH, Dunn TN, Thomas AP, Oort PJ, Kieffer DA, Amin R, Bettaieb A, Haj FG, Permana P, Anthony TG, Adams SH. Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity. Am J Physiol Endocrinol Metab. 2013 Jun 1; 304(11):E1175-87.

View in: PubMed

  1. Klingerman CM, Stipanovic ME, Bader M, Lynch CJ. Second-generation antipsychotics cause a rapid switch to fat oxidation that is required for survival in C57BL/6J mice. Schizophr Bull. 2014 Mar; 40(2):327-40.

View in: PubMed

  1. Carr TD, DiGiovanni J, Lynch CJ, Shantz LM. Inhibition of mTOR suppresses UVB-induced keratinocyte proliferation and survival. Cancer Prev Res (Phila). 2012 Dec; 5(12):1394-404.

View in: PubMed

  1. Lynch CJ, Zhou Q, Shyng SL, Heal DJ, Cheetham SC, Dickinson K, Gregory P, Firnges M, Nordheim U, Goshorn S, Reiche D, Turski L, Antel J. Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 K(ATP) channels. Am J Physiol Endocrinol Metab. 2012 Mar 1; 302(5):E540-51.

View in: PubMed

  1. Albaugh VL, Singareddy R, Mauger D, Lynch CJ. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers. PLoS One. 2011; 6(8):e22662.

View in: PubMed

  1. She P, Zhang Z, Marchionini D, Diaz WC, Jetton TJ, Kimball SR, Vary TC, Lang CH, Lynch CJ. Molecular characterization of skeletal muscle atrophy in the R6/2 mouse model of Huntington’s disease. Am J Physiol Endocrinol Metab. 2011 Jul; 301(1):E49-61.

View in: PubMed

  1. Fogle RL, Hollenbeak CS, Stanley BA, Vary TC, Kimball SR, Lynch CJ. Functional proteomic analysis reveals sex-dependent differences in structural and energy-producing myocardial proteins in rat model of alcoholic cardiomyopathy. Physiol Genomics. 2011 Apr 12; 43(7):346-56.

View in: PubMed

  1. Zhou Y, Jetton TL, Goshorn S, Lynch CJ, She P. Transamination is required for {alpha}-ketoisocaproate but not leucine to stimulate insulin secretion. J Biol Chem. 2010 Oct 29; 285(44):33718-26.

View in: PubMed

  1. Agostino NM, Chinchilli VM, Lynch CJ, Koszyk-Szewczyk A, Gingrich R, Sivik J, Drabick JJ. Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J Oncol Pharm Pract. 2011 Sep; 17(3):197-202.

View in: PubMed

  1. Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y. Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab. 2010 Aug 4; 12(2):154-65.

View in: PubMed

  1. Culnan DM, Albaugh V, Sun M, Lynch CJ, Lang CH, Cooney RN. Ileal interposition improves glucose tolerance and insulin sensitivity in the obese Zucker rat. Am J Physiol Gastrointest Liver Physiol. 2010 Sep; 299(3):G751-60.

View in: PubMed

  1. Hajnal A, Kovacs P, Ahmed T, Meirelles K, Lynch CJ, Cooney RN. Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats. Am J Physiol Gastrointest Liver Physiol. 2010 Oct; 299(4):G967-79.

View in: PubMed

  1. Lang CH, Lynch CJ, Vary TC. BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein synthesis and improves survival in septic mice. Am J Physiol Regul Integr Comp Physiol. 2010 Sep; 299(3):R935-44.

View in: PubMed

  1. Albaugh VL, Vary TC, Ilkayeva O, Wenner BR, Maresca KP, Joyal JL, Breazeale S, Elich TD, Lang CH, Lynch CJ. Atypical antipsychotics rapidly and inappropriately switch peripheral fuel utilization to lipids, impairing metabolic flexibility in rodents. Schizophr Bull. 2012 Jan; 38(1):153-66.

View in: PubMed

  1. Fogle RL, Lynch CJ, Palopoli M, Deiter G, Stanley BA, Vary TC. Impact of chronic alcohol ingestion on cardiac muscle protein expression. Alcohol Clin Exp Res. 2010 Jul; 34(7):1226-34.

View in: PubMed

  1. Lang CH, Frost RA, Bronson SK, Lynch CJ, Vary TC. Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine. Am J Physiol Endocrinol Metab. 2010 Jun; 298(6):E1283-94.

View in: PubMed

  1. Albaugh VL, Judson JG, She P, Lang CH, Maresca KP, Joyal JL, Lynch CJ. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis. Mol Psychiatry. 2011 May; 16(5):569-81.

View in: PubMed

  1. Lang CH, Lynch CJ, Vary TC. Alcohol-induced IGF-I resistance is ameliorated in mice deficient for mitochondrial branched-chain aminotransferase. J Nutr. 2010 May; 140(5):932-8.

View in: PubMed

  1. She P, Zhou Y, Zhang Z, Griffin K, Gowda K, Lynch CJ. Disruption of BCAA metabolism in mice impairs exercise metabolism and endurance. J Appl Physiol (1985). 2010 Apr; 108(4):941-9.

View in: PubMed

  1. Herman MA, She P, Peroni OD, Lynch CJ, Kahn BB. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels. J Biol Chem. 2010 Apr 9; 285(15):11348-56.

View in: PubMed

  1. Li P, Knabe DA, Kim SW, Lynch CJ, Hutson SM, Wu G. Lactating porcine mammary tissue catabolizes branched-chain amino acids for glutamine and aspartate synthesis. J Nutr. 2009 Aug; 139(8):1502-9.

View in: PubMed

  1. Lu G, Sun H, She P, Youn JY, Warburton S, Ping P, Vondriska TM, Cai H, Lynch CJ, Wang Y. Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. J Clin Invest. 2009 Jun; 119(6):1678-87.

View in: PubMed

  1. Nairizi A, She P, Vary TC, Lynch CJ. Leucine supplementation of drinking water does not alter susceptibility to diet-induced obesity in mice. J Nutr. 2009 Apr; 139(4):715-9.

View in: PubMed

  1. Meirelles K, Ahmed T, Culnan DM, Lynch CJ, Lang CH, Cooney RN. Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat. Ann Surg. 2009 Feb; 249(2):277-85.

View in: PubMed

  1. Culnan DM, Cooney RN, Stanley B, Lynch CJ. Apolipoprotein A-IV, a putative satiety/antiatherogenic factor, rises after gastric bypass. Obesity (Silver Spring). 2009 Jan; 17(1):46-52.

View in: PubMed

  1. She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab. 2007 Dec; 293(6):E1552-63.

View in: PubMed

  1. She P, Reid TM, Bronson SK, Vary TC, Hajnal A, Lynch CJ, Hutson SM. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 2007 Sep; 6(3):181-94.

View in: PubMed

  1. Vary TC, Lynch CJ. Nutrient signaling components controlling protein synthesis in striated muscle. J Nutr. 2007 Aug; 137(8):1835-43.

View in: PubMed

  1. Vary TC, Deiter G, Lynch CJ. Rapamycin limits formation of active eukaryotic initiation factor 4F complex following meal feeding in rat hearts. J Nutr. 2007 Aug; 137(8):1857-62.

View in: PubMed

  1. Vary TC, Anthony JC, Jefferson LS, Kimball SR, Lynch CJ. Rapamycin blunts nutrient stimulation of eIF4G, but not PKCepsilon phosphorylation, in skeletal muscle. Am J Physiol Endocrinol Metab. 2007 Jul; 293(1):E188-96.

View in: PubMed

  1. Vary TC, Lynch CJ. Meal feeding stimulates phosphorylation of multiple effector proteins regulating protein synthetic processes in rat hearts. J Nutr. 2006 Sep; 136(9):2284-90.

View in: PubMed

  1. Lynch CJ, Gern B, Lloyd C, Hutson SM, Eicher R, Vary TC. Leucine in food mediates some of the postprandial rise in plasma leptin concentrations. Am J Physiol Endocrinol Metab. 2006 Sep; 291(3):E621-30.

View in: PubMed

  1. Albaugh VL, Henry CR, Bello NT, Hajnal A, Lynch SL, Halle B, Lynch CJ. Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents. Obesity (Silver Spring). 2006 Jan; 14(1):36-51.

View in: PubMed

  1. Vary TC, Lynch CJ. Meal feeding enhances formation of eIF4F in skeletal muscle: role of increased eIF4E availability and eIF4G phosphorylation. Am J Physiol Endocrinol Metab. 2006 Apr; 290(4):E631-42.

View in: PubMed

  1. Vary TC, Goodman S, Kilpatrick LE, Lynch CJ. Nutrient regulation of PKCepsilon is mediated by leucine, not insulin, in skeletal muscle. Am J Physiol Endocrinol Metab. 2005 Oct; 289(4):E684-94.

View in: PubMed

  1. Vary TC, Lynch CJ. Biochemical approaches for nutritional support of skeletal muscle protein metabolism during sepsis. Nutr Res Rev. 2004 Jun; 17(1):77-88.

View in: PubMed

  1. Lynch CJ, Halle B, Fujii H, Vary TC, Wallin R, Damuni Z, Hutson SM. Potential role of leucine metabolism in the leucine-signaling pathway involving mTOR. Am J Physiol Endocrinol Metab. 2003 Oct; 285(4):E854-63.

View in: PubMed

  1. Lynch CJ, Hutson SM, Patson BJ, Vaval A, Vary TC. Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats. Am J Physiol Endocrinol Metab. 2002 Oct; 283(4):E824-35.

View in: PubMed

  1. Lynch CJ, Patson BJ, Anthony J, Vaval A, Jefferson LS, Vary TC. Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue. Am J Physiol Endocrinol Metab. 2002 Sep; 283(3):E503-13.

View in: PubMed

  1. Vary TC, Lynch CJ, Lang CH. Effects of chronic alcohol consumption on regulation of myocardial protein synthesis. Am J Physiol Heart Circ Physiol. 2001 Sep; 281(3):H1242-51.

View in: PubMed

  1. Lynch CJ, Patson BJ, Goodman SA, Trapolsi D, Kimball SR. Zinc stimulates the activity of the insulin- and nutrient-regulated protein kinase mTOR. Am J Physiol Endocrinol Metab. 2001 Jul; 281(1):E25-34.

View in: PubMed

 

Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover.

Lynch CJ1, Kimball SR2, Xu Y2, Salzberg AC3, Kawasawa YI4.   Author information
Physiol Genomics. 2015 Nov;47(11):569-80.  http://dx.doi.org:/10.1152/physiolgenomics.00055.2015

Consumption of a protein-containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, α-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), which interconverts leucine and α-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wild-type mice were compared by next-generation RNA sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1,486/∼39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis [eukaryotic initiation factor (eIF)-2, mammalian target of rapamycin, eIF4, and p70S6K pathways including 40S and 60S ribosomal proteins], protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy, and cell death) were upregulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body size, glycemia, plasma insulin, and lipid signaling pathways was altered in BCATm KO mice. Consistently, genes encoding anaerobic and/or oxidative metabolism of carbohydrate, fatty acids, and branched chain amino acids were modestly but systematically reduced. Although there was no indication that muscle fiber type was different between KO and wild-type mice, a difference in the abundance of mRNAs associated with a muscular dystrophy phenotype was observed, consistent with the published exercise intolerance of these mice. The results suggest transcriptional adaptations occur in BCATm KO mice that along with altered nutrient signaling may contribute to their previously reported protein turnover, metabolic and exercise phenotypes.

 

RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.

Lynch CJ1, Xu Y1, Hajnal A2, Salzberg AC3, Kawasawa YI4. Author information
PLoS One. 2015 Apr 20;10(4):e0123966. http://dx.doi.org:/10.1371/journal.pone.0123966. eCollection 2015.

Second generation antipsychotics (SGAs), like olanzapine, exhibit acute metabolic side effects leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. Understanding how SGAs affect the skeletal muscle transcriptome could elucidate approaches for mitigating these side effects. Male Sprague-Dawley rats were infused intravenously with vehicle or olanzapine for 24h using a dose leading to a mild hyperglycemia. RNA-Seq was performed on gastrocnemius muscle, followed by alignment of the data with the Rat Genome Assembly 5.0. Olanzapine altered expression of 1347 out of 26407 genes. Genes encoding skeletal muscle fiber-type specific sarcomeric, ion channel, glycolytic, O2- and Ca2+-handling, TCA cycle, vascularization and lipid oxidation proteins and pathways, along with NADH shuttles and LDH isoforms were affected. Bioinformatics analyses indicate that olanzapine decreased the expression of slower and more oxidative fiber type genes (e.g., type 1), while up regulating those for the most glycolytic and least metabolically flexible, fast twitch fiber type, IIb. Protein turnover genes, necessary to bring about transition, were also up regulated. Potential upstream regulators were also identified. Olanzapine appears to be rapidly affecting the muscle transcriptome to bring about a change to a fast-glycolytic fiber type. Such fiber types are more susceptible than slow muscle to atrophy, and such transitions are observed in chronic metabolic diseases. Thus these effects could contribute to the altered body composition and metabolic disease olanzapine causes. A potential interventional strategy is implicated because aerobic exercise, in contrast to resistance exercise, can oppose such slow to fast fiber transitions.

 

Brain insulin lowers circulating BCAA levels by inducing hepatic BCAA catabolism.

Shin AC1, Fasshauer M1, Filatova N1, Grundell LA1, Zielinski E1, Zhou JY2, Scherer T1, Lindtner C1, White PJ3, Lapworth AL3,Ilkayeva O3, Knippschild U4, Wolf AM4, Scheja L5, Grove KL6, Smith RD2, Qian WJ2, Lynch CJ7, Newgard CB3, Buettner C8. Author information
Cell Metab. 2014 Nov 4;20(5):898-909. http://dx.doi.org:/10.1016/j.cmet.2014.09.003   Epub 2014 Oct 9

Circulating branched-chain amino acid (BCAA) levels are elevated in obesity/diabetes and are a sensitive predictor for type 2 diabetes. Here we show in rats that insulin dose-dependently lowers plasma BCAA levels through induction of hepatic protein expression and activity of branched-chain α-keto acid dehydrogenase (BCKDH), the rate-limiting enzyme in the BCAA degradation pathway. Selective induction of hypothalamic insulin signaling in rats and genetic modulation of brain insulin receptors in mice demonstrate that brain insulin signaling is a major regulator of BCAA metabolism by inducing hepatic BCKDH. Short-term overfeeding impairs the ability of brain insulin to lower BCAAs in rats. High-fat feeding in nonhuman primates and obesity and/or diabetes in humans is associated with reduced BCKDH protein in liver. These findings support the concept that decreased hepatic BCKDH is a major cause of increased plasma BCAAs and that hypothalamic insulin resistance may account for impaired BCAA metabolism in obesity and diabetes.

 

Branched-chain amino acids in metabolic signalling and insulin resistance.

Lynch CJ1, Adams SH2.  Author information
Nat Rev Endocrinol. 2014 Dec; 10(12):723-36. http://dx.doi.org:/10.1038/nrendo.2014.171

Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM.

 

Leucine and protein metabolism in obese Zucker rats.

She P1, Olson KC, Kadota Y, Inukai A, Shimomura Y, Hoppel CL, Adams SH, Kawamata Y, Matsumoto H, Sakai R, Lang CH, Lynch CJ.  Author information
PLoS One. 2013;8(3):e59443. http://dx.doi.org:/10.1371/journal.pone.0059443   Epub 2013 Mar 20.

Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-(14)C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW, 53%), liver (107%) and fat (∼300%), but lower plantaris and gastrocnemius masses (-21-24%). Plasma BCAAs and BCKAs were elevated 45-69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%), leucine (Leu) turnover and proteolysis [35% per g fat free mass (FFM), urinary markers of proteolysis: 3-methylhistidine (183%) and 4-hydroxyproline (766%)] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (-47-66%). A process disposing of circulating BCAAs, protein synthesis, was increased 23-29% by obesity in whole-body (FFM corrected), gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193-418%) than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein turnover along with impaired BCKDC activity. Elevated BCAAs/BCKAs may contribute to observed elevations in protein synthesis and BCAA oxidation.

 

Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity.

Lackey DE1, Lynch CJ, Olson KC, Mostaedi R, Ali M, Smith WH, Karpe F, Humphreys S, Bedinger DH, Dunn TN, Thomas AP, Oort PJ, Kieffer DA, Amin R, Bettaieb A, Haj FG, Permana P, Anthony TG, Adams SH.
Am J Physiol Endocrinol Metab. 2013 Jun 1; 304(11):E1175-87. http://dx.doi.org:/10.1152/ajpendo.00630.2012

Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35-50% in various obesity models (fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals.

 

Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 K(ATP) channels.

Lynch CJ1, Zhou Q, Shyng SL, Heal DJ, Cheetham SC, Dickinson K, Gregory P, Firnges M, Nordheim U, Goshorn S, Reiche D,Turski L, Antel J.   Author information
Am J Physiol Endocrinol Metab. 2012 Mar 1;302(5):E540-51.
http://dx.doi.org:/10.1152/ajpendo.00258.2011

Here, we examined the chronic effects of two cannabinoid receptor-1 (CB1) inverse agonists, rimonabant and ibipinabant, in hyperinsulinemic Zucker rats to determine their chronic effects on insulinemia. Rimonabant and ibipinabant (10 mg·kg⁻¹·day⁻¹) elicited body weight-independent improvements in insulinemia and glycemia during 10 wk of chronic treatment. To elucidate the mechanism of insulin lowering, acute in vivo and in vitro studies were then performed. Surprisingly, chronic treatment was not required for insulin lowering. In acute in vivo and in vitro studies, the CB1 inverse agonists exhibited acute K channel opener (KCO; e.g., diazoxide and NN414)-like effects on glucose tolerance and glucose-stimulated insulin secretion (GSIS) with approximately fivefold better potency than diazoxide. Followup studies implied that these effects were inconsistent with a CB1-mediated mechanism. Thus effects of several CB1 agonists, inverse agonists, and distomers during GTTs or GSIS studies using perifused rat islets were unpredictable from their known CB1 activities. In vivo rimonabant and ibipinabant caused glucose intolerance in CB1 but not SUR1-KO mice. Electrophysiological studies indicated that, compared with diazoxide, 3 μM rimonabant and ibipinabant are partial agonists for K channel opening. Partial agonism was consistent with data from radioligand binding assays designed to detect SUR1 K(ATP) KCOs where rimonabant and ibipinabant allosterically regulated ³H-glibenclamide-specific binding in the presence of MgATP, as did diazoxide and NN414. Our findings indicate that some CB1 ligands may directly bind and allosterically regulate Kir6.2/SUR1 K(ATP) channels like other KCOs. This mechanism appears to be compatible with and may contribute to their acute and chronic effects on GSIS and insulinemia.

 

Transamination is required for {alpha}-ketoisocaproate but not leucine to stimulate insulin secretion.

Zhou Y1, Jetton TL, Goshorn S, Lynch CJ, She P.  Author information
J Biol Chem. 2010 Oct 29;285(44):33718-26. http://dx.doi.org:/10.1074/jbc.M110.136846

It remains unclear how α-ketoisocaproate (KIC) and leucine are metabolized to stimulate insulin secretion. Mitochondrial BCATm (branched-chain aminotransferase) catalyzes reversible transamination of leucine and α-ketoglutarate to KIC and glutamate, the first step of leucine catabolism. We investigated the biochemical mechanisms of KIC and leucine-stimulated insulin secretion (KICSIS and LSIS, respectively) using BCATm(-/-) mice. In static incubation, BCATm disruption abolished insulin secretion by KIC, D,L-α-keto-β-methylvalerate, and α-ketocaproate without altering stimulation by glucose, leucine, or α-ketoglutarate. Similarly, during pancreas perfusions in BCATm(-/-) mice, glucose and arginine stimulated insulin release, whereas KICSIS was largely abolished. During islet perifusions, KIC and 2 mM glutamine caused robust dose-dependent insulin secretion in BCATm(+/+) not BCATm(-/-) islets, whereas LSIS was unaffected. Consistently, in contrast to BCATm(+/+) islets, the increases of the ATP concentration and NADPH/NADP(+) ratio in response to KIC were largely blunted in BCATm(-/-) islets. Compared with nontreated islets, the combination of KIC/glutamine (10/2 mM) did not influence α-ketoglutarate concentrations but caused 120 and 33% increases in malate in BCATm(+/+) and BCATm(-/-) islets, respectively. Although leucine oxidation and KIC transamination were blocked in BCATm(-/-) islets, KIC oxidation was unaltered. These data indicate that KICSIS requires transamination of KIC and glutamate to leucine and α-ketoglutarate, respectively. LSIS does not require leucine catabolism and may be through leucine activation of glutamate dehydrogenase. Thus, KICSIS and LSIS occur by enhancing the metabolism of glutamine/glutamate to α-ketoglutarate, which, in turn, is metabolized to produce the intracellular signals such as ATP and NADPH for insulin secretion.

 

Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice.

Agostino NM1, Chinchilli VM, Lynch CJ, Koszyk-Szewczyk A, Gingrich R, Sivik J, Drabick JJ.
J Oncol Pharm Pract. 2011 Sep; 17(3):197-202. http://dx.doi.org:/10.1177/1078155210378913

Tyrosine kinase is a key enzyme activity utilized in many intracellular messaging pathways. Understanding the role of particular tyrosine kinases in malignancies has allowed for the design of tyrosine kinase inhibitors (TKIs), which can target these enzymes and interfere with downstream signaling. TKIs have proven to be successful in the treatment of chronic myeloid leukemia, renal cell carcinoma and gastrointestinal stromal tumor, and other malignancies. Scattered reports have suggested that these agents appear to affect blood glucose (BG). We retrospectively studied the BG concentrations in diabetic (17) and nondiabetic (61) patients treated with dasatinib (8), imatinib (39), sorafenib (23), and sunitinib (30) in our clinical practice. Mean declines of BG were dasatinib (53 mg/dL), imatinib (9 mg/dL), sorafenib (12 mg/dL), and sunitinib (14 mg/dL). All these declines in BG were statistically significant. Of note, 47% (8/17) of the patients with diabetes were able to discontinue their medications, including insulin in some patients. Only one diabetic patient developed symptomatic hypoglycemia while on sunitinib. The mechanism for the hypoglycemic effect of these drugs is unclear, but of the four agents tested, c-kit and PDGFRβ are the common target kinases. Clinicians should keep the potential hypoglycemic effects of these agents in mind; modification of hypoglycemic agents may be required in diabetic patients. These results also suggest that inhibition of a tyrosine kinase, be it c-kit, PDGFRβ or some other undefined target, may improve diabetes mellitus BG control and it deserves further study as a potential novel therapeutic option.

 

Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity.

Li J1, Romestaing C, Han X, Li Y, Hao X, Wu Y, Sun C, Liu X, Jefferson LS, Xiong J, Lanoue KF, Chang Z, Lynch CJ, Wang H, Shi Y.    Author information
Cell Metab. 2010 Aug 4;12(2):154-65. http://dx.doi.org:/10.1016/j.cmet.2010.07.003

Oxidative stress causes mitochondrial dysfunction and metabolic complications through unknown mechanisms. Cardiolipin (CL) is a key mitochondrial phospholipid required for oxidative phosphorylation. Oxidative damage to CL from pathological remodeling is implicated in the etiology of mitochondrial dysfunction commonly associated with diabetes, obesity, and other metabolic diseases. Here, we show that ALCAT1, a lyso-CL acyltransferase upregulated by oxidative stress and diet-induced obesity (DIO), catalyzes the synthesis of CL species that are highly sensitive to oxidative damage, leading to mitochondrial dysfunction, ROS production, and insulin resistance. These metabolic disorders were reminiscent of those observed in type 2 diabetes and were reversed by rosiglitazone treatment. Consequently, ALCAT1 deficiency prevented the onset of DIO and significantly improved mitochondrial complex I activity, lipid oxidation, and insulin signaling in ALCAT1(-/-) mice. Collectively, these findings identify a key role of ALCAT1 in regulating CL remodeling, mitochondrial dysfunction, and susceptibility to DIO.

 

BCATm deficiency ameliorates endotoxin-induced decrease in muscle protein synthesis and improves survival in septic mice.

Lang CH1, Lynch CJ, Vary TC.   Author information
Am J Physiol Regul Integr Comp Physiol. 2010 Sep; 299(3):R935-44.
http://dx.doi.org:/10.1152/ajpregu.00297.2010

Endotoxin (LPS) and sepsis decrease mammalian target of rapamycin (mTOR) activity in skeletal muscle, thereby reducing protein synthesis. Our study tests the hypothesis that inhibition of branched-chain amino acid (BCAA) catabolism, which elevates circulating BCAA and stimulates mTOR, will blunt the LPS-induced decrease in muscle protein synthesis. Wild-type (WT) and mitochondrial branched-chain aminotransferase (BCATm) knockout mice were studied 4 h after Escherichia coli LPS or saline. Basal skeletal muscle protein synthesis was increased in knockout mice compared with WT, and this change was associated with increased eukaryotic initiation factor (eIF)-4E binding protein-1 (4E-BP1) phosphorylation, eIF4E.eIF4G binding, 4E-BP1.raptor binding, and eIF3.raptor binding without a change in the mTOR.raptor complex in muscle. LPS decreased muscle protein synthesis in WT mice, a change associated with decreased 4E-BP1 phosphorylation as well as decreased formation of eIF4E.eIF4G, 4E-BP1.raptor, and eIF3.raptor complexes. In BCATm knockout mice given LPS, muscle protein synthesis only decreased to values found in vehicle-treated WT control mice, and this ameliorated LPS effect was associated with a coordinate increase in 4E-BP1.raptor, eIF3.raptor, and 4E-BP1 phosphorylation. Additionally, the LPS-induced increase in muscle cytokines was blunted in BCATm knockout mice, compared with WT animals. In a separate study, 7-day survival and muscle mass were increased in BCATm knockout vs. WT mice after polymicrobial peritonitis. These data suggest that elevating blood BCAA is sufficient to ameliorate the catabolic effect of LPS on skeletal muscle protein synthesis via alterations in protein-protein interactions within mTOR complex-1, and this may provide a survival advantage in response to bacterial infection.

 

Alcohol-induced IGF-I resistance is ameliorated in mice deficient for mitochondrial branched-chain aminotransferase.

Lang CH1, Lynch CJ, Vary TC.  Author information
J Nutr. 2010 May;140(5):932-8. http://dx.doi.org:/10.3945/jn.109.120501

Acute alcohol intoxication decreases skeletal muscle protein synthesis by impairing mammalian target of rapamycin (mTOR). In 2 studies, we determined whether inhibition of branched-chain amino acid (BCAA) catabolism ameliorates the inhibitory effect of alcohol on muscle protein synthesis by raising the plasma BCAA concentrations and/or by improving the anabolic response to insulin-like growth factor (IGF)-I. In the first study, 4 groups of mice were used: wild-type (WT) and mitochondrial branched-chain aminotransferase (BCATm) knockout (KO) mice orally administered saline or alcohol (5 g/kg, 1 h). Protein synthesis was greater in KO mice compared with WT controls and was associated with greater phosphorylation of eukaryotic initiation factor (eIF)-4E binding protein-1 (4EBP1), eIF4E-eIF4G binding, and 4EBP1-regulatory associated protein of mTOR (raptor) binding, but not mTOR-raptor binding. Alcohol decreased protein synthesis in WT mice, a change associated with less 4EBP1 phosphorylation, eIF4E-eIF4G binding, and raptor-4EBP1 binding, but greater mTOR-raptor complex formation. Comparable alcohol effects on protein synthesis and signal transduction were detected in BCATm KO mice. The second study used the same 4 groups, but all mice were injected with IGF-I (25 microg/mouse, 30 min). Alcohol impaired the ability of IGF-I to increase muscle protein synthesis, 4EBP1 and 70-kilodalton ribosomal protein S6 kinase-1 phosphorylation, eIF4E-eIF4G binding, and 4EBP1-raptor binding in WT mice. However, in alcohol-treated BCATm KO mice, this IGF-I resistance was not manifested. These data suggest that whereas the sustained elevation in plasma BCAA is not sufficient to ameliorate the catabolic effect of acute alcohol intoxication on muscle protein synthesis, it does improve the anabolic effect of IGF-I.

 

Impact of chronic alcohol ingestion on cardiac muscle protein expression.

Fogle RL1, Lynch CJ, Palopoli M, Deiter G, Stanley BA, Vary TC.  Author information
Alcohol Clin Exp Res. 2010 Jul;34(7):1226-34. http://dx.doi.org:/10.1111/j.1530-0277.2010.01200.x

BACKGROUND:

Chronic alcohol abuse contributes not only to an increased risk of health-related complications, but also to a premature mortality in adults. Myocardial dysfunction, including the development of a syndrome referred to as alcoholic cardiomyopathy, appears to be a major contributing factor. One mechanism to account for the pathogenesis of alcoholic cardiomyopathy involves alterations in protein expression secondary to an inhibition of protein synthesis. However, the full extent to which myocardial proteins are affected by chronic alcohol consumption remains unresolved.

METHODS:

The purpose of this study was to examine the effect of chronic alcohol consumption on the expression of cardiac proteins. Male rats were maintained for 16 weeks on a 40% ethanol-containing diet in which alcohol was provided both in drinking water and agar blocks. Control animals were pair-fed to consume the same caloric intake. Heart homogenates from control- and ethanol-fed rats were labeled with the cleavable isotope coded affinity tags (ICAT). Following the reaction with the ICAT reagent, we applied one-dimensional gel electrophoresis with in-gel trypsin digestion of proteins and subsequent MALDI-TOF-TOF mass spectrometric techniques for identification of peptides. Differences in the expression of cardiac proteins from control- and ethanol-fed rats were determined by mass spectrometry approaches.

RESULTS:

Initial proteomic analysis identified and quantified hundreds of cardiac proteins. Major decreases in the expression of specific myocardial proteins were observed. Proteins were grouped depending on their contribution to multiple activities of cardiac function and metabolism, including mitochondrial-, glycolytic-, myofibrillar-, membrane-associated, and plasma proteins. Another group contained identified proteins that could not be properly categorized under the aforementioned classification system.

CONCLUSIONS:

Based on the changes in proteins, we speculate modulation of cardiac muscle protein expression represents a fundamental alteration induced by chronic alcohol consumption, consistent with changes in myocardial wall thickness measured under the same conditions.

 

Read Full Post »

3-D Printed Liver

Posted in 3D Printing for Medical Application, Bio Instrumentation in Experimental Life Sciences Research, Biochemical pathways, BioIT: BioInformatics, Biological Networks, Biomedical Measurement Science, BioTechnology - Venture Creation, Cell Biology, Curation, Disease Biology, Drug Development using MultiOrgan Chip, Drug Toxicity, Innovations, Intellectual Property, Lab-on-a-chip, Metabolism, Metabolomics, Methods, MicroEngineering Cell-Tissue & Systems, Micronutrients, Pharmaceutical Analytics, Pharmacologic toxicities, Tissue Engineering, tagged , on February 28, 2016| Leave a Comment »

3-D Printed Liver

Curator: Larry H. Bernstein, MD, FCAP

 

 

3D-printing a new lifelike liver tissue for drug screening

Could let pharmaceutical companies quickly do pilot studies on new drugs
February 15, 2016    http://www.kurzweilai.net/3d-printing-a-new-lifelike-liver-tissue-for-drug-screening

Images of the 3D-printed parts of the biomimetic liver tissue: liver cells derived from human induced pluripotent stem cells (left), endothelial and mesenchymal supporing cells (center), and the resulting organized combination of multiple cell types (right). (credit: Chen Laboratory, UC San Diego)

 

University of California, San Diego researchers have 3D-printed a tissue that closely mimics the human liver’s sophisticated structure and function. The new model could be used for patient-specific drug screening and disease modeling and could help pharmaceutical companies save time and money when developing new drugs, according to the researchers.

The liver plays a critical role in how the body metabolizes drugs and produces key proteins, so liver models are increasingly being developed in the lab as platforms for drug screening. However, so far, the models lack both the complex micro-architecture and diverse cell makeup of a real liver. For example, the liver receives a dual blood supply with different pressures and chemical constituents.

So the team employed a novel bioprinting technology that can rapidly produce complex 3D microstructures that mimic the sophisticated features found in biological tissues.

The liver tissue was printed in two steps.

  • The team printed a honeycomb pattern of 900-micrometer-sized hexagons, each containing liver cells derived from human induced pluripotent stem cells. An advantage of human induced pluripotent stem cells is that they are patient-specific, which makes them ideal materials for building patient-specific drug screening platforms. And since these cells are derived from a patient’s own skin cells, researchers don’t need to extract any cells from the liver to build liver tissue.
  • Then, endothelial and mesenchymal supporting cells were printed in the spaces between the stem-cell-containing hexagons.

The entire structure — a 3 × 3 millimeter square, 200 micrometers thick — takes just seconds to print. The researchers say this is a vast improvement over other methods to print liver models, which typically take hours. Their printed model was able to maintain essential functions over a longer time period than other liver models. It also expressed a relatively higher level of a key enzyme that’s considered to be involved in metabolizing many of the drugs administered to patients.

“It typically takes about 12 years and $1.8 billion to produce one FDA-approved drug,” said Shaochen Chen, NanoEngineering professor at the UC San Diego Jacobs School of Engineering. “That’s because over 90 percent of drugs don’t pass animal tests or human clinical trials. We’ve made a tool that pharmaceutical companies could use to do pilot studies on their new drugs, and they won’t have to wait until animal or human trials to test a drug’s safety and efficacy on patients. This would let them focus on the most promising drug candidates earlier on in the process.”

The work was published the week of Feb. 8 in the online early edition of Proceedings of the National Academy of Sciences.

Abstract of Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

references:

Topics: Synthetic Biology

Fernando

I wonder how equivalent are these hepatic cells derived from human induced pluripotent stem cells (hiPSCs) compared with the real hepatic cell populations.
All cells in our organism share the same DNA info, but every tissue is special for what genes are expressed and also because of the specific localization in our body (which would mean different surrounding environment for each tissue). I am not sure about how much of a step forward this is. Induced hepatic cells are known, but this 3-D print does not have liver shape or the different cell sub-types you would find in the liver.

larryhbern

I agree with your observation that having the same DNA information doesn’t account for variability of cell function within an organ. The regulation of expression is in RNA translation, and that is subject to regulatory factors related to noncoding RNAs and to structural factors in protein folding. The result is that chronic diseases that are affected by the synthetic capabilities of the liver are still problematic – toxicology, diabetes, and the inflammatory response, and amino acid metabolism as well. Nevertheless, this is a very significant step for the testing of pharmaceuticals. When we look at the double circulation of the liver, hypoxia is less of an issue than for heart or skeletal muscle, or mesothelial tissues. I call your attention to the outstanding work by Nathan O. Kaplan on the transhydrogenases, and his stipulation that there are significant differences between organs that are anabolic and those that are catabolic in TPNH/DPNH, that has been ignored for over 40 years. Nothing is quite as simple as we would like.

Fernando commented on 3-D printed liver

3-D printed liver Larry H. Bernstein, MD, FCAP, Curator LPBI 3D-printing a new lifelike liver tissue for drug …

I wonder how equivalent are these hepatic cells derived from human induced pluripotent stem cells (hiPSCs) compared with the real hepatic cell populations.
All cells in our organism share the same DNA info, but every tissue is special for what genes are expressed and also because of the specific localization in our body (which would mean different surrounding environment for each tissue). I am not sure about how much of a step forward this is. Induced hepatic cells are known, but this 3-D print does not have liver shape or the different cell sub-types you would find in the liver.

 

Read Full Post »

3-D molecular structures

Posted in Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, BioTechnology - Venture Creation, Cancer - General, Cell Biology, Computational Biology/Systems and Bioinformatics, Curation, Image Processing/Computing, Innovations, tagged , , , , , on February 28, 2016| Leave a Comment »

3-D molecular structures, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

3-D molecular structures

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

New method enables discovery of 3D structures for molecules important to medicine

February 19, 2016  http://www.kurzweilai.net/new-method-enables-discovery-of-3d-structures-for-molecules-important-to-medicine

 

If you zap a crystal (green, left) containing highly ordered protein molecules with X-rays, the X-rays scatter and produce useful regular patterns of spots known as Bragg peaks (red dots). But if the protein in the crystal is less ordered or disordered (right), the X-rays produce some spots along with patterns of light and shade known as a continuous diffraction pattern that’s not useful. (credit: Eberhard Reimann/DESY)

Researchers have overcome a long-standing technical barrier to imaging 3D structures of thousands of molecules important to medicine and biology.

The 3D structures of many protein molecules have been discovered using a technique called X-ray crystallography, but the method relies on scientists being able to produce highly ordered crystals containing the protein molecules in a regular arrangement. When X-rays are shone on highly ordered crystals, the X-rays scatter and produce regular patterns of spots called Bragg peaks (see figure above, left). High-quality Bragg peaks contain the information to produce high-resolution 3D structures of proteins.

Unfortunately, many important and complex biomolecules do not form highly ordered crystals; instead, the protein arrangements are slightly disordered. When X-rays are shone on these more disordered crystals, a smaller number of Bragg peaks are produced, along with a vague pattern of light and shadow known as a continuous diffraction pattern (right).

In the past, scientists discarded these less-than-perfect crystals. Unfortunately, many of the molecules forming disordered crystals are important molecular complexes such as those that span cell membranes.

X-raying crystal patterns to detect hidden protein structures

Analysis of Bragg peaks alone (top) reveals far less details than analysis of the high-res continuous diffraction pattern (bottom). Magnifying glasses show actual data. (credit: DESY, Eberhard Reimann)

So a team led by Professor Henry Chapman from the Center for Free-Electron Laser Science at DESY in Hamburg, Germany turned to the world’s most powerful X-ray laser: the SLAC LCLS at Stanford University.

Kartik Ayyer, PhD., lead author of the article in Nature, explains that the method uses an approach similar to that used to image a single molecule.

“If you would shoot X-rays on a single molecule, it would produce a continuous diffraction pattern free of any Bragg spots,” he says. “The pattern would be extremely weak, however, and very difficult to measure. But the ‘background’ in our crystal analysis is like accumulating many shots from individually aligned single molecules. We essentially just use the crystal as a way to get a lot of single molecules, aligned in common orientations, into the beam.”

As the model protein, the researchers crystallized photosystem II (PSII), a large membrane–protein complex of photosynthesis that plants use to produce oxygen for life on Earth.

After exposing the crystal to X-rays, the researchers first analyzed the Bragg peaks of PSII to produce a low-resolution outline of the 3D structure (figure above, top). They then improved this data, using an algorithm, to analyze the continuous diffraction pattern and produced a higher-resolution 3D structure (figure, bottom).

This novel method means that imperfect crystals containing a slightly disordered protein arrangement can now be used to “directly view large protein complexes in atomic detail,” says Chapman. “This kind of continuous diffraction has actually been seen for a long time from many different poorly diffracting crystals,” says Chapman. “It wasn’t understood that you can get structural information from it and so analysis techniques suppressed it.

“We’re going to be busy to see if we can solve [additional] structures of molecules from old discarded data.”

Abstract of Macromolecular diffractive imaging using imperfect crystals

The three-dimensional structures of macromolecules and their complexes are mainly elucidated by X-ray protein crystallography. A major limitation of this method is access to high-quality crystals, which is necessary to ensure X-ray diffraction extends to sufficiently large scattering angles and hence yields information of sufficiently high resolution with which to solve the crystal structure. The observation that crystals with reduced unit-cell volumes and tighter macromolecular packing often produce higher-resolution Bragg peaks suggests that crystallographic resolution for some macromolecules may be limited not by their heterogeneity, but by a deviation of strict positional ordering of the crystalline lattice. Such displacements of molecules from the ideal lattice give rise to a continuous diffraction pattern that is equal to the incoherent sum of diffraction from rigid individual molecular complexes aligned along several discrete crystallographic orientations and that, consequently, contains more information than Bragg peaks alone. Although such continuous diffraction patterns have long been observed—and are of interest as a source of information about the dynamics of proteins—they have not been used for structure determination. Here we show for crystals of the integral membrane protein complex photosystem II that lattice disorder increases the information content and the resolution of the diffraction pattern well beyond the 4.5-ångström limit of measurable Bragg peaks, which allows us to phase the pattern directly. Using the molecular envelope conventionally determined at 4.5 ångströms as a constraint, we obtain a static image of the photosystem II dimer at a resolution of 3.5 ångströms. This result shows that continuous diffraction can be used to overcome what have long been supposed to be the resolution limits of macromolecular crystallography, using a method that exploits commonly encountered imperfect crystals and enables model-free phasing.

references:

Read Full Post »

Dissolvable Sensor for Determining Temperature and Pressure

Posted in Bio Instrumentation in Experimental Life Sciences Research, Bio-MEMS, Biodegradable Drug-eluting Material, Medical Devices R&D and Inventions, Uncategorized, tagged on February 17, 2016| Leave a Comment »

Dissolvable sensor for determining temperature and pressure

Curator: Danut Dragoi, PhD

The Concept

The concept of dissolvable sensor in human body fluid and its experimentation was a successful task of electrical engineers at the University of Illinois at Urbana-Champaign. The device is intended to be implanted inside the head of human body in order to measure important parameters such as temperature and pressure.

Based on actual silicon technology, the device is built on a very thin silicon crystal, which is dissolvable in human body fluids after a given period and after  the measurements are done. The need for such device is required by a medical intervention, a surgery, or a special medication.

For measuring the temperature,the device uses the principle of variation of current / voltage of a silicon diode with temperature see link in here . To illustrate how the diode works as a thermometer, see the link in here  in which the curve voltage output versus temperature, variable T, is a decreasing linear function as a function of temperature.The other variable pressure P can be obtained from the base material, the thin silicon substrate, even if silicon is not a traditional piezoelectric material. Knowing that silicon can be a piezorezistive material, link in here,  a signal output can be obtained from an engineered part of the silicon chip that has the resistance as a function of pressure P.

Two Variable Sensor: Temperature and Pressure

The picture bellow, IMAGE CREDIT::JOHN A. ROGERS, UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN AND MDTMAG.COM,

T and P on Brain

is the actual device made by electrical engineers at the University of Illinois at Urbana-Champaign. The device shown in the picture, SOA in the field,  is based on silicon and is bioresorbable. The coil in the center is for transmission data purposes. The link in here  describes in more details the device.

According with Prof Rogers of University of Illinois at Urbana-Champaign, a new class of small, thin electronic sensors can monitor temperature and pressure within the skull – which are crucial health parameters after a brain injury or surgery – then melt away when they are no longer needed, eliminating the need for additional surgery to remove the monitors and reducing the risk of infection and hemorrhage. Similar sensors can be adapted for postoperative monitoring in other body systems as well.  John A. Rogers and Wilson Ray, a professor of neurological surgery at the Washington University School of Medicine in St. Louis,  published their work in the journal Nature.

Applications of the device

After a traumatic brain injury or brain surgery, it is crucial to monitor the patient for swelling and pressure on the brain. Current monitoring technology is bulky and invasive,and the wires restrict the patient’s movement and hamper physical therapy as they recover.

Because they require continuous, hard-wired access into the head, such implants also carry the risk of allergic reactions, infection and hemorrhage, and even could exacerbate the inflammation they are meant to monitor. Professor Rogers mentioned that the demonstration was done on animal models, with a measurement precision that’s just as good as that of conventional devices.

The sensors, smaller than a grain of rice, are built on extremely thin sheets of silicon – which are naturally biodegradable – that are configured to function normally for a few weeks, then dissolve away, completely and harmlessly, in the body’s own fluids.

Rogers’ group teamed with Illinois materials science and engineering professor Paul V. Braun to make the silicon platforms sensitive to clinically relevant pressure levels in the intracranial fluid surrounding the brain. They also added a tiny temperature sensor and connected it to a wireless transmitter roughly the size of a postage stamp, implanted under the skin but on top of the skull.

The Illinois group worked with clinical experts in traumatic brain injury at Washington University to implant the sensors in rats, testing for performance and bio-compatibility. They found that the temperature and pressure readings from the dissolvable sensors matched conventional monitoring devices for accuracy.

The researchers are moving toward human trials for this technology, as well as extending its functionality for other bio-medical applications.

Source

Nature(2016), Published online 18 January 2016, Bioresorbable silicon electronic sensors for the brain, Seung-Kyun Kang, Rory K. J. Murphy, Suk-Won Hwang, Seung Min Lee, Daniel V. Harburg, Neil A. Krueger, Jiho Shin, Paul Gamble, Huanyu Cheng, Sooyoun Yu, Zhuangjian Liu, Jordan G. McCall, Manu Stephen, Hanze Ying, Jeonghyun Kim, Gayoung Park, R. Chad Webb, Chi Hwan Lee, Sangjin Chung, Dae Seung Wie, Amit D. Gujar, Bharat Vemulapalli, Albert H. Kim, Kyung-Mi Lee, Jianjun Cheng, Younggang Huang, Sang Hoon Lee, Paul V. Braun, Wilson Z. Ray & John A. Rogers,

http://www.nature.com/nature/journal/v530/n7588/fig_tab/nature16492_SF1.html

http://www.pveducation.org/pvcdrom/pn-junction/diode-equation

Click to access ME189_Chapter%207.pdf

https://news.illinois.edu/blog/view/6367/312684

 

Read Full Post »

Continuous diffraction crystallographics analysis

Posted in Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, Clinical Diagnostics, Curation, Disease Biology, Lasers and photonics, Proteomics, tagged , , on February 11, 2016| Leave a Comment »

Continuous diffraction crystallographics analysis

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Biomolecular Structure Emerges from the Crystallographic Shadows

http://www.genengnews.com/gen-news-highlights/biomolecular-structure-emerges-from-the-crystallographic-shadows/81252359/

 

http://www.genengnews.com/Media/images/GENHighlight/thumb_Feb11_2016_DESY_DisorderedCrystals7411016594.jpg

Here’s the caption/credit for the image: Slightly disordered crystals of complex biomolecules like that of the photosystem II molecule shown here produce a complex continous diffraction pattern (right) under X-ray light that contains far more information than the so-called Bragg peaks of a strongly ordered crystal alone (left). The degree of disorder is greatly exaggerated in the crystal on the right. [Eberhard Reimann/DESY]

 

In keeping with the adage, “If life gives you lemons, make lemonade,” an international team of scientists has shown that if X-crystallography relies on low-quality crystals, it can still derive high-quality structural information. In fact, resolutions can be achieved that surpass the Bragg diffraction limit.

The key, it turns out, is to make the most out of continuous diffraction data, which is ordinarily considered a nuisance in crystallographic analysis. Continuous diffraction data could be obtained from a single molecule, but would be too weak to yield any kind of analysis. But if such data could be combined from a collection of molecules, analyses would be possible. Each of the molecules in the collection, however, would have to be misaligned only in the translational sense. That is, the molecules could not be misaligned rotationally or differ intramolecularly.

With these limitations in mind, scientists based at the Center for Free-Electron Laser Science, DESY, in Germany “read” the atomic structure of complex biomolecules by crystallography without the usual need for prior knowledge and chemical insight. “This discovery has the potential to become a true revolution for the crystallography of complex matter,” said the chairman of DESY’s board of directors, Professor Helmut Dosch.

The work of the DESY-led scientific team appeared February 10 in Nature, in an article entitled “Macromolecular diffractive imaging using imperfect crystals.” The article described how the scientists took advantage of a phenomenon called continuous diffraction.

Protein crystals, particularly imperfect protein crystals, do not always “diffract,” in the traditional Bragg sense. A proper, perfect crystal scatters X-rays in many different directions, producing an intricate and characteristic pattern of numerous bright spots, called Bragg peaks (named after the British crystallography pioneers William Henry and William Lawrence Bragg). The positions and strengths of these spots contain information about the structure of the crystal and of its constituents. Using this approach, researchers have already determined the atomic structures of tens of thousands of proteins and other biomolecules.

“Continuous” scattering arises when crystals become disordered. Usually, this non-Bragg continuous diffraction is not used to derive structural information. Instead, it is used to provide insights into vibrations and dynamics of molecules. But when the disorder consists only of displacements of the individual molecules from their ideal positions in the crystal, the “background” takes on a much more complex character—and its rich structure is anything but diffuse. It then offers a much bigger prize than the analysis of the Bragg peaks: The continuously modulated “background” fully encodes the diffracted waves from individual “single” molecules.

The possibility of using continuous diffraction for structural determinations leads to a paradigm shift in crystallography—the most ordered crystals are no longer the best to analyze with the novel method. “For the first time we have access to single molecule diffraction—we have never had this in crystallography before,” explained DESY’s Professor Henry Chapman. “But we have long known how to solve single-molecule diffraction if we could measure it.” The field of coherent diffractive imaging, spurred by the availability of laser-like beams from X-ray free-electron lasers, has developed powerful algorithms to directly solve the phase problem in this case, without having to know anything at all about the molecule.

“We show for crystals of the integral membrane protein complex photosystem II that lattice disorder increases the information content and the resolution of the diffraction pattern well beyond the 4.5-ångström limit of measurable Bragg peaks, which allows us to phase the pattern directly,” wrote the authors of the Nature article. “Using the molecular envelope conventionally determined at 4.5 ångströms as a constraint, we obtain a static image of the photosystem II dimer at a resolution of 3.5 ångströms. This result shows that continuous diffraction can be used to overcome what have long been supposed to be the resolution limits of macromolecular crystallography.”

Read Full Post »

Advanced Nanospectroscopy

Posted in Bio Instrumentation in Experimental Life Sciences Research, tagged , , , on February 6, 2016| Leave a Comment »

Advanced Nanospectroscopy

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Graphene Enables Nanoelectromechanical Systems Integration

http://www.photonics.com/Article.aspx?AID=58224&refer=Spectroscopy&utm_source=Spectroscopy_2016_02_03

BARCELONA, Spain, Jan. 21, 2016 — Combining nanoelectromechanical (NEMS) systems with on-chip optics holds promise as a method to actively control light at the nanoscale, and now a hybrid system has overcome the challenges of integrating such nanoscale devices with optical fields thanks to the material graphene.

Researchers from the Institute of Photonic Sciences (ICFO) have demonstrated an on-chip graphene NEMS suspended a few tens of nanometers above nitrogen-vacancy centres (NVCs), which are stable single-photon emitters embedded in nanodiamonds. The work confirms that graphene is an ideal platform for both nanophotonics and nanomechanics, the researchers said.

Due to its electromechanical properties, graphene NEMS can be actuated and deflected electrostatically over a few tens of nanometers with modest voltages applied to a gate electrode, the researchers found. The graphene motion can thus be used to modulate the light emission by the NVC, while the emitted field can be used as a universal probe of the graphene position. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field, dipole-dipole interaction.

64

http://www.photonics.com/images/Web/Articles/2016/1/21/PIC_ICFO.jpg

False color scanning electronic micrograph of a hybrid graphene-nitrogen-vacancy nearfield nano-optomechanical system. Courtesy of ICFO.

The researchers observed that the coupling strength increased strongly for shorter distances and was enhanced because of graphene’s 2D character and linear dispersion. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, and integrated optomechanical information processing. The ICFO team also said the hybrid device could advance quantum optomechanics.

The research was published in Nature Communications (doi: 10.1038/ncomms10218).

Electromechanical control of nitrogen-vacancy defect emission using graphene NEMS

Antoine Reserbat-Plantey, Kevin G. Schädler, Louis Gaudreau, Gabriele Navickaite, Johannes Güttinger, et al.

Nature Communications 2016; 7(10218)      http://dx.doi.org:/10.1038/ncomms10218

Despite recent progress in nano-optomechanics, active control of optical fields at the nanoscale has not been achieved with an on-chip nano-electromechanical system (NEMS) thus far. Here we present a new type of hybrid system, consisting of an on-chip graphene NEMS suspended a few tens of nanometres above nitrogen-vacancy centres (NVCs), which are stable single-photon emitters embedded in nanodiamonds. Electromechanical control of the photons emitted by the NVC is provided by electrostatic tuning of the graphene NEMS position, which is transduced to a modulation of NVC emission intensity. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field dipole–dipole interaction. This class of optomechanical coupling increases strongly for smaller distances, making it suitable for nanoscale devices. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, integrated optomechanical information processing and open new avenues towards quantum optomechanics.

 

Graphene is ideal substrate for brain electrodes, researchers find

February 1, 2016  http://www.kurzweilai.net/graphene-is-ideal-substrate-for-brain-electrodes-researchers-find

This illustration portrays neurons interfaced with a sheet of graphene molecules in the background (credit: Graphene Flagship)

An international study headed by the European Graphene Flagship research consortium has found that graphene is a promising material for use in electrodes that interface with neurons, based on its excellent conductivity, flexibility for molding into complex shapes, biocompatibility, and stability within the body.

The graphene-based substrates they studied* promise to overcome problems with “glial scar” tissue formation (caused by electrode-based brain trauma and long-term inflammation). To avoid that, current electrodes based on tungsten or silicon use a protective coating on electrodes, which reduces charge transfer. Current electrodes are also rigid (resulting in tissue detachment and preventing neurons from moving) and generate electrical noise, with partial or complete loss of signal over time, the researchers note in a paper published recently in the journal ACS Nano.

Electrodes are used as neural biosensors and for prosthetic applications — such as deep-brain intracranial electrodes used to control motor disorders (mainly epilepsy or Parkinson’s) and for brain-computer interfaces (BCIs), used to recover sensory functions or control robotic arms for paralyzed patients. These applications require an interface with long-term, minimal interference.

Interfacing graphene to neurons directly

Scanning electron microscope image of rat hippocampal neurons grown in the lab on a graphene-based substrate, showing normal morphology characterized by well-defined round neural soma, extended neurite arborization (branching), and cell density similar to control substrates (credit: A. Fabbro et al./ACS Nano)

“For the first time, we interfaced graphene to neurons directly, without any peptide-coating,” explained lead neuroscientist Prof. Laura Ballerini of the International School for Advanced Studies (SISSA/ISAS) and the University of Trieste.

Using electron microscopy and immunofluorescence, the researchers found that the neurons remained healthy, transmitting normal electric impulses and, importantly, no adverse glial reaction, which leads to damaging scar tissue, was seen.

As a next step, Ballerini says the team plans to investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons,  and “whether tuning the graphene material properties might alter the synapses and neuronal excitability in new and unique ways.”

Prof. Andrea C. Ferrari, Director of the Cambridge Graphene Centre and Chair of the Graphene Flagship Executive Board, said the Flagship will “support biomedical research and development based on graphene technology with a new work package and a significant cash investment from 2016.”

The interdisciplinary collaboration also included the University Castilla-La Mancha and the Cambridge Graphene Centre.

* The study used two methods of creating graphene-based substrates (GBSs).  Liquid phase exfoliation (LPE) — peeling off graphene from graphite — can be performed without the potentially hazardous chemical treatments involved in graphene oxide production, is scalable, and operates at room temperature, with high yield. LPE dispersions can also be easily deposited on target substrates by drop-casting, filtration, or printing. Ball milling (BM), with the help of melamine (which forms large hydrogen-bond domains, unlike LPE), can be performed in a solid environment. “Our data indicate that both GBSs are promising for next-generation bioelectronic systems, to be used as brain interfaces,” the paper concludes.

references:

Topics: Cognitive Science/Neuroscience | Nanotech/Materials Science

 

 

 

Read Full Post »

Tau and IGF1 in Alzheimer’s Disease

Posted in Alzheimer's Disease, Bio Instrumentation in Experimental Life Sciences Research, Biomedical Measurement Science, Curation, Etiology, Neurological Diseases, Neuroscience, tagged , , , on February 6, 2016| Leave a Comment »

Tau and IGF1 in Alzheimer’s Disease

Larry H. Bernstein, MD, FCAP, Curator

LPBI

TAU links growth factor to development of Alzheimer’s disease

https://english.tau.ac.il/sites/default/files/styles/reaserch_main_image_580_x_330/public/alz2580.jpg

 

The mechanisms underlying the stability and plasticity of neural circuits in the hippocampus, the part of the brain responsible for spatial memory and the memory of everyday facts and events, has been a major focus of study in the field of neuroscience. Understanding precisely how a “healthy” brain stores and processes information is crucial to preventing and reversing the memory failures associated with Alzheimer’s disease (AD), the most common form of late-life dementia.

 

Hyperactivity of the hippocampus is known to be associated with conditions that confer risk for AD, including amnestic mild cognitive impairment. A new Tel Aviv University study finds that the insulin-like growth factor 1 receptor (IGF-1R), the “master” lifespan regulator, plays a vital role in directly regulating the transfer and processing of information in hippocampal neural circuits. The research reveals IGF-1R as a differential regulator of two different modes of transmission — spontaneous and evoked — in hippocampal circuits of the brain. The researchers hope their findings can be used to indicate a new direction for therapy used to treat patients in the early stages of Alzheimer’s disease.

 

The study was led by Dr. Inna Slutsky of TAU’s Sagol School of Neuroscience and Sackler School of Medicine and conducted by doctoral student Neta Gazit. It was recently published in the journal Neuron. “People who are at risk for AD show hyperactivity of the hippocampus, and our results suggest that IGF-1R activity may be an important contributor to this abnormality,” Dr. Slutsky concluded.

 

Resolving a controversy

“We know that IGF-1R signaling controls growth, development and lifespan, but its role in AD has remained controversial,” said Dr. Slutsky. “To resolve this controversy, we had to understand how IGF-1R functions physiologically in synaptic transfer and plasticity.”

 

Using brain cultures and slices, the researchers developed an integrated approach characterizing the brain system on different scales — from the level of protein interactions to the level of single synapses, neuronal connections and the entire hippocampal network. The team sought to address two important questions: whether IGF-1Rs are active in synapses and transduce signalling at rest, and how they affect synaptic function.

 

“We used fluorescence resonance energy transfer (FRET) to estimate the receptor activation at the single-synapse level,” said Dr. Slutsky. “We found IGF-1Rs to be fully activated under resting conditions, modulating release of neurotransmitters from synapses.”

 

While acute application of IGF-1 hormone was found to be ineffective, the introduction of various IGF-1R blockers produced robust dual effects — namely, the inhibition of a neurotransmitter release evoked by spikes, electrical pulses in the brain, while enhancement of spontaneous neurotransmitter release.

 

A test for Alzheimer’s?

“When we modified the level of IGF-1R expression, synaptic transmission and plasticity were altered at hippocampal synapses, and an increase in the IGF-1R expression caused an augmented release of glutamate, enhancing the activity of hippocampal neurons,” said Gazit.

 

“We suggest that IGF-1R small inhibitors, which are currently under development for cancer, be tested for reduction aberrant brain activity at early stages of Alzheimer’s disease,” said Dr. Slutsky.

 

The researchers are currently planning to study how IGF-1R signaling controls the stability of neural circuits over an extended timescale.

 

Dr. Irena Vertkin, Dr. Ilana Shapira, Edden Slomowitz, Maayan Sheiba and Yael Mor of Dr. Slutsky’s lab at TAU, and Martin Helm and Prof. Silvio Rizzoli of the University of Göttingen in Germany, contributed to this research.

 

This article was originally published by AFTAU.

 

“We know that IGF-1R signaling controls growth, development and lifespan, but its role in AD has remained controversial,” said Dr. Slutsky. “To resolve this controversy, we had to understand how IGF-1R functions physiologically in synaptic transfer and plasticity.”

Using brain cultures and slices, the researchers developed an integrated approach characterizing the brain system on different scales — from the level of protein interactions to the level of single synapses, neuronal connections and the entire hippocampal network. The team sought to address two important questions: whether IGF-1Rs are active in synapses and transduce signalling at rest, and how they affect synaptic function.

“We used fluorescence resonance energy transfer (FRET) to estimate the receptor activation at the single-synapse level,” said Dr. Slutsky. “We found IGF-1Rs to be fully activated under resting conditions, modulating release of neurotransmitters from synapses.”

While acute application of IGF-1 hormone was found to be ineffective, the introduction of various IGF-1R blockers produced robust dual effects — namely, the inhibition of a neurotransmitter release evoked by spikes, electrical pulses in the brain, while enhancement of spontaneous neurotransmitter release.

A test for Alzheimer’s?

“When we modified the level of IGF-1R expression, synaptic transmission and plasticity were altered at hippocampal synapses, and an increase in the IGF-1R expression caused an augmented release of glutamate, enhancing the activity of hippocampal neurons,” said Gazit.

“We suggest that IGF-1R small inhibitors, which are currently under development for cancer, be tested for reduction aberrant brain activity at early stages of Alzheimer’s disease,” said Dr. Slutsky.

The researchers are currently planning to study how IGF-1R signaling controls the stability of neural circuits over an extended timescale.

 

 

Read Full Post »

BioMEMS The Market aspects of Oligonucleotide-Chips, Products, Applications and Competition, January 21, 2016

Posted in 3D Printing for Medical Application, Big Data, Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Informatics, Cell Biology, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Commercialization, Computational Biology/Systems and Bioinformatics, CRISPR/Cas9 & Gene Editing, Digital HealthCare – biotech & internet joint ventures, DNA repair, Exosomes, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Genetics & Pharmaceutical, Genome Biology, Genomic Expression, Genomic Testing: Methodology for Diagnosis, Intelligent Information Systems, MEMS, Mutagenesis, Proteosome, tagged , , , , , , , , on February 2, 2016| Leave a Comment »

BioMEMS The Market aspects of Oligonucleotide-Chips, Products and Applications, Competition, January 21, 2016

Curator: Gérard LOISEAU, ESQ

 

BioMEMS

The Market aspects of Oligonucleotide-Chips, Products, Applications, Competition 

January 21, 2016

2015-2020

The oligonucleotide synthesis market is expected to reach USD 1.918.6Billion at a CAGR of 10.1% by 2020 from USD 1.078.1Billion in 2015.

SOURCE

MARKETSANDMARKETS marketsandmarkets.com/

 

PLAYERS

  • Agilent Technologies Inc.
  • BioAutomation Corp.
  • Biosearch Technologies
  • Gen9 Inc.
  • GenScript Inc.
  • Illumina Inc.
  • Integrated DNA Technologies
  • New England Biolabs Inc.
  • Nitto Denko Avecia Inc.
  • OriGene Technologies Inc.
  • Sigma-Aldrich Corporation
  • Thermo Fisher Scientific Inc.
  • TriLink Biotechnologies

 

Agilent Technologies
 CA NYSE :A


http://www.agilent.com/

  • Agilent was created as a spin off from Hewlett-Packard Company in 1999.
  • Agilent Technologies Inc. is engaged in the life sciences, diagnostics and applied chemical markets. The Company provides application focused solutions that include instruments, software, services and consumables for the entire laboratory workflow. The Company has three business segments:

the life sciences and applied markets business,

the diagnostics and genomics business, and

the Agilent Cross Lab business

  • The Company’s life sciences and applied markets business segment brings together the Company’s analytical laboratory instrumentation and informatics.
  • The Company’s diagnostics and genomics business segment consists of three businesses: the Dako business, the genomics business and the nucleic acid solutions business.
  • The Company’s Agilent Cross Lab business segment combines its analytical laboratory services and consumables business

SOURCE

http://reuters.com/

PRODUCTS AND SERVICES

https://www.agilent.com/en-us/default#collapse-0

  • October 09, 2015 03:21 PM Eastern Daylight Time
  • CARPINTERIA, Calif.–(BUSINESS WIRE)–Dako, an Agilent Technologies company and a worldwide provider of cancer diagnostics, today announced the U.S. Food and Drug Administration has approved a new test that can identify PD-L1 expression levels on the surface of non-small cell lung cancer tumor cells and provide information on the survival benefit with OPDIVO® (nivolumab) for patients with non-squamous NSCLC.

SOURCE

BUSINESS WIRE busibesswire.com/

 

BioAutomation Corp.

 TX


 

http://bioautomation.com/

          PRODUCTS AND SERVICES

  • DNA and RNA synthesis reagents for the MerMades

 

Note: The MerMade 192E Oligonucleotide synthesizer is designed to synthesize DNA, RNA & LNA oligonucleotides in a column format

          PARTNERSHIPS

  • HONGENE BIOTECH : BIOAUTOMATION is the exclusive distributor for the Americas
  • EMD MILLIPORE
  • BIOSEARCH TECHNOLOGIES

 

DISTRIBUTORS

  • LINK TECHNOLOGIES : UK
  • AME BIOSCIENCE : UK
  • BOSUNG SCIENCE : KOREA
  • DNA CHEM : CHINA
  • WAKO : JAPAN
  • ACE PROBE : INDIA

SOURCE

bioautomation.com/

 

Biosearch Technologies
 CA


http://biosearchtech.com/

          PRODUCTS

  • qPCR & SNP Genotyping
  • Custom Oligonucleotides
  • – highly sophisticated oligonucleotides
  • – simple PCR primers
  • Oligos in Plates
  • RNA FISH
  • Synthesis Reagents
  • Immunochemicals
  • Primers
  • Probes
  • Large-Scale Synthesis Oligos
  • Intermediate-Scale Synthesis Oligos

          SERVICES

  • GMP & Commercial Services
  • OEM & Kit Manufacturing
  • qPCR Design Collaborations

          DISTRIBUTORS

Argentina | Australia | Austria | Brazil | Canada |Chile | China | Colombia | Czech Republic | Denmark | Ecuador | Finland | Germany |Hong Kong | Israel | Italy | Japan | Korea | Malaysia | Mexico | New Zealand | Norway | Paraguay | Peru| Philippines | Poland | Romania | Singapore | South Africa | Spain | Sweden |Switzerland | Taiwan ROC | Thailand | Turkey | United Kingdom | Uruguay | Vietnam

SOURCE

biosearchtech.com/

 

Gen9 Inc.
 MA 


http://www.gen9bio.com/

          PRODUCTS

Gen9 is building on advances in synthetic biology to power a scalable fabrication capability that will significantly increase the world’s capacity to produce DNA content. The privately held company’s next-generation gene synthesis technology allows for the high-throughput, automated production of DNA constructs at lower cost and higher accuracy than previous methods on the market. Founded by world leaders in synthetic biology, Gen9 aims to ensure the constructive application of synthetic biology in industries ranging from enzyme and chemical production to pharmaceuticals and biofuels.

          SERVICES

  • Synthetic Biology
  • Gene Synthesis Services
  • Variant Libraries
  • Gene Sequence Design Services

         INVESTORS

  • Agilent Technologies : Private Equity
  • CAMBRIDGE, Mass. and SANTA CLARA, Calif. — April 24, 2013 —Gen9 Receives $21 Million Strategic Investment from Agilent Technologies

SOURCE

gen9bio.com/

 

GenScript Inc.
 NJ 


http://www.genscript.com/

  • GenScript is the largest gene synthesis provider in the USA
  • GenScript Corporation, a biology contract research organization, provides biological research and drug discovery services to pharmaceutical companies, biotech firms, and research institutions in the United States, Europe, and Japan. It offers bio-reagent, custom molecular biology, custom peptide, protein production, custom antibody production, drug candidates testing, assay development and screening, lead optimization, antibody drug development, gene synthesis, and assay-ready cell line production services.
  • The company also offers molecular biology, peptide, protein, immunoassay, chemicals, and cell biology products. It offers its products through distributors in Tokyo, Japan; and Seoul, Korea. GenScript Corporation has a strategic partnership with Immunologix, Inc. The company was founded in 2002 and is based in Piscataway, New Jersey. It has subsidiaries in France, Japan, and China.

 

Note: As of October 24, 2011, Immunologix, Inc. was acquired by Intrexon Corporation. Immunologix, Inc. develops and produces antibody-based therapeutics for various biological targets. It produces human monoclonal antibodies against viral, bacterial, and tumor antigens, as well as human auto antigens.

Intrexon Corporation, founded in 1998, is a leader in synthetic biology focused on collaborating with companies in Health, Food, Energy, Environment and Consumer sectors to create biologically based products that improve quality of life and the health of the planet.

 

 

             PRODUCTS AND SERVICES

  • Gene synthesis
  • Antibody services
  • Protein Services
  • Peptide services

 

               INVESTORS


Note: The Balloch Group (‘TBG’) was established in 2001 by Howard Balloch (Canada‘s ambassador to China from 1996 to 2001). TBG has since grown from a market-entry consultancy working with North American clients in China to a leading advisory and merchant banking firm serving both domestic Chinese companies and multinational corporations. TBG was ranked as the number one boutique investment bank in China by ChinaVenture in 2008.

Kleiner, Perkins, Caufield and Byers

 

Illumina
Inc. CA


http://illumina.com/

 

Monica Heger : SAN FRANCISCO (GenomeWeb) – Illumina today announced two new next-generation sequencing platforms, a targeted sequencing system called MiniSeq and a semiconductor sequencer that is still under development.

Illumina disclosed the initiatives during a presentation at the JP Morgan Healthcare conference held here today. During the presentation, Illumina CEO Jay Flatley also announced a new genotyping array called Infinium XT; a partnership with Bio-Rad to develop a single-cell sequencing workflow; preliminary estimates of its fourth-quarter 2015 revenues; and an update on existing products. The presentation followed the company’s announcement on Sunday that it has launched a new company called Grail to develop a next-generation sequencing test for early cancer detection from patient blood samples.

The MiniSeq system, which is based on Illumina’s current sequencing technology, will begin shipping early this quarter and has a list price of $49,500. It can perform a variety of targeted DNA and RNA applications, from single-gene to pathway sequencing, and promises “all-in” prices, including library prep and sequencing, of $200 to $300 per sample, Flatley said during the JP Morgan presentation.

SOURCES

https://www.genomeweb.com/sequencing-technology/illumina-unveils-mini-targeted-sequencer-semiconductor-sequencing-project-jp

http://investor.biospace.com/biospace/quote?Symbol=ILMN

 

              PRODUCTS AND SERVICES

  •               Mid to large scale manufacturing assets
  •               Analytical Labs
  •               Pre-clinical
  •               Clinical
  •               Launched products

 

              COMPETITORS

https://finance.yahoo.com/q/co?s=ILMN+Competitors Tue, Feb 2, 2016, 2:16pm EST – US Markets

ILMN PVT1 AFFX LMNX Industry
Market Cap: 22.75B N/A 1.13B 835.66M 134.14M
Employees: 3,700 10,000 1,200 745 45.00
Qtrly Rev Growth (yoy): 0.14 N/A -0.01 0.07 0.18
Revenue (ttm): 2.14B 3.80B1 357.74M 235.37M 8.47M
Gross Margin (ttm): 0.73 N/A 0.63 0.71 0.58
EBITDA (ttm): 770.84M N/A 46.64M 52.99M -12.31M
Operating Margin (ttm): 0.30 N/A 0.08 0.17 -1.62
Net Income (ttm): 510.36M 430.90M1 11.22M 39.29M N/A
EPS (ttm): 3.42 N/A 0.13 0.93 -0.34
P/E (ttm): 45.43 N/A 104.40 20.91 25.33
PEG (5 yr expected): 2.68 N/A 4.66 0.55 N/A
P/S (ttm): 10.87 N/A 3.13 3.45 13.65

 

Pvt1 = Life Technologies Corporation (privately held)

AFFX = Affymetrix Inc.

LMNX = Luminex Corporation

 

 

Integrated DNA Technologies (IDT)
IOWA + CA

http://www.com/

 

Integrated DNA Technologies, Inc. (IDT), the global leader in nucleic acid synthesis, serving all areas of life sciences research and development, offers products for a broad range of genomics applications. IDT’s primary business is the production of custom, synthetic nucleic acids for molecular biology applications, including qPCR, sequencing, synthetic biology, and functional genomics. The company manufactures and ships an average of 44,000 custom nucleic acids per day to more than 82,000 customers worldwide. For more information, visit idtdna.com.

 

               PRODUCTS AND SERVICES

               https://eu.idtdna.com/site

  • DNA & RNA Synthesis
  • Custom DNA Oligos 96- & 384-Well Plates Ultramer Oligos Custom RNA Oligos SameDay Oligos HotPlates ReadyMade Primers Oligo Modifications Freedom
  • Dyes GMP for Molecular Diagnostics Large Scale Oligo Synthesis

 

Note : Skokie, IL – December 1, 2015. Integrated DNA Technologies Inc. (“IDT”), the global leader in custom nucleic acid synthesis, has entered into a definitive agreement to acquire the oligonucleotide synthesis business of AITbiotech Pte. Ltd. in Singapore (“AITbiotech”). With this acquisition, IDT expands its customer base across Southeast Asia making it possible for these additional customers to now have access to its broad range of products for genomic applications. AITbiotech will continue operations in its other core business areas.

 

New England Biolabs Inc.
 MA 


http://www.neb.com/

 

                PRODUCTS AND SERVICES

  •                 Restriction Endonucleases
  •                 PCR, Polymerases & Amplification Technologies
  •                 DNA Modifying Enzymes
  •                 Library Preparation for Next Generation Sequencing
  •                 Nucleic Acid Purification
  •                 Markers & Ladders
  •                 RNA Reagents
  •                 Gene Expression
  •                 Cellular Analysis

SOURCE

neb.com/

 

Nitto Denko Avecia Inc.
 MA


http://avecia.com/

 

With over 20 years of experience in oligonucleotide development and production, and over 1000 sequences manufactured, Avecia has played an integral role in the advancing oligo therapeutic market. Our mission is to continue to build value for our customers, as they progress through drug development into commercialization. And as a member of the Nitto Denko Corporation (nitto.com), Avecia is committed to the future of the oligonucleotide market. We are driven by innovative ideas and flexible solutions, designed to provide our customers with the best in service, quality, and technology.

 

SOURCE

http://avecia.com/

 

Note : 1918 Nitto Electric Industrial Co., Ltd. forms in Ohsaki, Tokyo, to produce electrical insulating materials in Japan.

2011 Acquires Avecia Biotechnology Inc. in the U.S.A.

 

 

OriGene Technologies Inc.
 CA

http://www.com/

 

OriGene Technologies, Inc. develops, manufactures, and sells genome wide research and diagnostic products for pharmaceutical, biotechnology, and academic research applications. The company offers cDNA clones, including TrueORF cDNA, viral ORF, destination vectors, TrueClones (human), TrueClones (mouse), organelle marker plasmids, MicroRNA tools, mutant and variant clones, plasmid purification kits, transfection reagents, and gene synthesis service; and HuSH shRNA, siRNA, miRNA, qPCR reagents, plasmid purification products, transfection reagents, PolyA+ and total RNA products, first-strand cDNA synthesis, and CRISPR/Cas9 genome products. It also provides proteins and lysates, such as purified human proteins, over-expression cell lysates, mass spectrometry standard proteins, and protein purification reagents; UltraMAB IHC antibodies, TrueMAB primary antibodies, anti-tag and fluorescent proteins, ELISA antibodies, luminex antibodies, secondary antibodies, and controls and others; and anatomic pathology products, including IHC antibodies, detection systems, and IHC accessories

The company offers luminex and ELISA antibody pairs, autoantibody profiling arrays, ELISA kits, cell assay kits, assay reagents, custom development, and fluorogenic cell assays; TissueFocus search tools; tissue sections; tissue microarrays, cancer protein lysate arrays, TissueScan cDNA arrays, tissue blocks, and quality control products, as well as tissue RNA, DNA, and protein lysates; and lab essentials. Its research areas include cancer biomarker research, RNAi, pathology IHC, stem cell research, ion channels, and protein kinase products. The company provides gene synthesis and molecular biology services, genome editing, custom cloning, custom shRNA, purified protein, monoclonal antibody development, and assay development. It sells its products through distributors worldwide, as well as online. OriGene Technologies, Inc. was incorporated in 1995 and is based in Rockville, Maryland.

SOURCE

http://BLOOMBERG.com

               PRODUCTS AND SERVICES

  •                cDNA Clones
Human, mouse, rat
Expression validated
  •                RNAi
shRNA, siRNA
microRNA & 3’UTR clones
  •                Gene Synthesis
Codon optimization
Variant libraries
  •                Real-time PCR
Primer pairs, panels
SYBR green reagents
  •                Lab Essentials
DNA/RNA purification kits
Transfection reagents
  •                Anatomic Pathology
UltraMAB antibodies
Specificity validated
  •                Recombinant Proteins
10,000 human proteins
from mammalian system
  •                Antibodies
TrueMAB primary antibodies
Anti-tag antibodies
  •                Assays and Kits
ELISA & Luminex antibodies
Autoantibody Profiling Array
  •                Cancer & Normal Tissues
Pathologist verified
gDNA, RNA, sections, arrays

SOURCE

origene.com/

 

Sigma-Aldrich Corporation 
MI 


http://www.sigmaaldrich.com/

Louis, MO – November 18, 2015 Merck KGaA, Darmstadt, Germany, Completes Sigma-Aldrich Acquisition

Merck KGaA today announced the completion of its $17 billion acquisition of Sigma-Aldrich, creating one of the leaders in the $130 billion global industry to help solve the toughest problems in life science.

Press Release: 18-Nov-2015

Letter to our Life Science Customers from Dr. Udit Batra

The life science business of Merck KGaA, Darmstadt, Germany brings together the world-class products and services, innovative capabilities and exceptional talent of EMD Millipore and Sigma-Aldrich to create a global leader in the life science industry.

“Everything we do starts with our shared purpose – to solve the toughest problems in life science by collaborating with the global scientific community. 

This combination is built on complementary strengths, which will enable us to serve you even better as one organization than either company could alone.

This means providing a broader portfolio with a catalog of more than 300,000 products, including many of the most respected brands in the industry, greater geographic reach, and an unmatched combination of industry-leading capabilities.”

                PRODUCTS AND SERVICES

                http://www.sigmaaldrich.com/configurator/servlet/DesignCenter?btnOpen_0.x=1

                http://www.sigmaaldrich.com/content/dam/sigma-aldrich/common/quality-products.jpg

 

Thermo Fisher Scientific Inc.
 MA 
NYSE :TMO


http://thermofisher.com/


Thermo Fisher Scientific Inc. is a provider of analytical instruments, equipment, reagents and consumables, software and services for research, manufacturing, analysis, discovery and diagnostics. The company operates through four segments: Life Sciences Solutions, provides reagents, instruments and consumables used in biological and medical research, discovery and production of new drugs and vaccines as well as diagnosis of disease; Analytical Instruments, provides instruments, consumables, software and services that are used in the laboratory; Specialty Diagnostics, offers diagnostic test kits, reagents, culture media, instruments and associated products, and Laboratory Products and Services, offers self-manufactured and sourced products for the laboratory.

SOURCE

http://REUTERS.com

 

                PRODUCTS AND SERVICES

  •                 Oligos Value – Standard – Plate
  •                 Primers
  •                 Probes
  •                 Nucleotides

 

                BRANDS

  1.                THERMO SCIENTIFIC
  2.                 APPLIED BIOSYSTEMS
  3.                 INVITROGEN
  4.                 FISHER SCIENTIFIC
  5.                 UNITY LAB SERVICES

 

                 PARTNERSHIPS

AFFYMETRIX : NASDAQ : AFFX : affymetrix.com/

WALTHAM, Mass. & SANTA CLARA, Calif.–(BUSINESS WIRE)–Jan. 8, 2016– Thermo Fisher Scientific Inc. (NYSE:TMO), the world leader in serving science, and Affymetrix Inc. (NASDAQ:AFFX), a leading provider of cellular and genetic analysis products, today announced that their boards of directors have unanimously approved Thermo Fisher’s acquisition of Affymetrix for $14.00 per share in cash. The transaction represents a purchase price of approximately $1.3 billion.

SOURCE

http://BUSINESSWIRE.com

 

TriLink Biotechnologies
 CA 


http://www.com/

 

              PRODUCTS

              Oligonucleotides

  •               DNA Oligos
  •               RNA Oligos
  •               Modified Oligos
  •               Specialty Oligos

              Nucleotides

  •               NTPs (Nucleoside Triphosphates)
  •               Biphosphates
  •               Monophosphates

 

              SERVICES

  •              Custom Chemistry
  •              Reagents
  •              Aptamers

 

             PARTNERSHIPS

  • LIFE TECHNOLOGIES,
  • TERMO FISHER SCIENTIFIC since July 2015 thermofisher.com/
  • GENMARK genmarkdx.com/

SOURCE

http://trilinkbiotech.com/

 

Other related articles published in this Open Access Online Scientific Journal include the following:

Gene Editing: The Role of Oligonucleotide Chips

http://pharmaceuticalintelligence.com/2016/01/07/gene-editing-the-role-of-oligonucleotide-chips/

Gene Editing for Exon 51: Why CRISPR Snipping might be better than Exon Skipping for DMD

http://pharmaceuticalintelligence.com/2016/01/23/gene-editing-for-exon-51-why-crispr-snipping-might-be-better-than-exon-skipping-for-dmd/

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Read Full Post »

A Magnetically controlled Mechanical Propeller for Immotile Sperm

Posted in Bio Instrumentation in Experimental Life Sciences Research, Bioengineering & reverse engineering design, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cell Biology, Innovations, Medical Devices R&D and Inventions, Population Health Management, Reproductive Biology & Bio Instrumentation, tagged , , , , , , , , , , , on January 30, 2016| Leave a Comment »

A Magnetically controlled Mechanical Propeller for Immotile Sperm

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Researchers from the Institute for Integrative Nanosciences, IFW Dresden, Germany and Material Systems for Nanoelectronics, Chemnitz University of Technology, Germany have developed something known as the spermbot, a remotely controlled sperm movement controlling robot that could help create babies of the future. It is a magnetically powered robotic “suit” that can strap itself to individual sperm and help guide it faster towards the egg. According to the inventors all the initial tests with the spermbot have delivered promising results.

The purpose of the spermbot is to solve one of the widely talked about causes of infertility in men which is poor motility of sperm. Low sperm motility, or otherwise healthy sperm that just can’t swim, can be a big factor in infertility. While the development of the spermbot is in its early stages, this is already being talked about as a promising alternative to existing popular techniques that are expensive and come with a high failure rate. These include methods like in-vitro fertilization and artificial insemination. Only 30 percent of the traditional “spray-and-pray” approach ends up with success, which warranted the need for an alternative procedure like the spermbot. According to the report, initial experiments show a marked increase in the probability of the spermbot-assisted sperm to reach its intended destination. The process of fertilization can be completed inside the body or in the lab, inside a petri-dish.

The spermbot is a coat of microscopic metal polymers shaped into a helix. It can attach itself to the tail of the spermatozoid, and then, using a hybrid micromotor, it can help propel the sperm faster towards the egg. The direction the sperm needs to take is controlled using a rotating magnetic field. In fact, even the motion of the sperm can be remote-controlled by simply adjusting this magnetic field. Once the spermbot propels the sperm towards the egg and the sperm manages to implant itself into the egg, the bionic part of the spermbot detaches itself from the tail.

While the initial experiments look promising, there is still some way to go before the spermbot technique is regularly used. To start off, scientists have very few sample size to correctly evaluate the results, and unless more comprehensive tests are carried out, it would not be possible to start using them on human subjects. Another major stumbling block is that there is currently no way to film the spermbot in action while it is moving inside the body. This also means that doctors would not be able to correctly direct it towards the egg. Another concern is the response of the body’s own immune system to the spermbot. The use of the spermbot could trigger a reaction from the body’s immune system, the results of which cannot be predicted without comprehensive clinical trials. The idea of the spermbot looks promising right now, but it is still too early to call it a replacement to the tried and tested methods like in-vitro fertilization and artificial insemination. In fact, it would take a few years for the procedure to be made available to patients if clinical trials are successfully completed.

References:

http://pubs.acs.org/doi/abs/10.1021/acs.nanolett.5b04221

http://www.acs.org/content/acs/en/pressroom/presspacs/2016/acs-presspac-january-13-2016/spermbots-could-help-women-trying-to-conceive-video.html

http://www.inquisitr.com/2711435/spermbot-robot-sperm-infertility-treatment/#utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+google%2FyDYq+%28The+Inquisitr+-+News%29

http://www.slate.com/articles/video/video/2016/01/spermbot_attached_to_sperm_and_delivers_it_quickly_to_an_egg_video.html

http://www.sciencemag.org/news/2016/01/video-motorized-spermbot-helps-sperm-reach-egg

Read Full Post »

« Newer Posts - Older Posts »