Advertisements
Feeds:
Posts
Comments

Archive for the ‘Developmental biology’ Category


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

 

Long interspersed nuclear elements 1 (LINE1) is repeated half a million times in the human genome, making up nearly a fifth of the DNA in every cell. But nobody cared to study it and may be the reason to call it junk DNA. LINE1, like other transposons (or “jumping genes”), has the unusual ability to copy and insert itself in random places in the genome. Many other research groups uncovered possible roles in early mouse embryos and in brain cells. But nobody quite established a proper report about the functions of LINE1.

 

Geneticists gave attention to LINE1 when it was found to cause cancer or genetic disorders like hemophilia. But researchers at University of California at San Francisco suspected there was more characteristics of LINE1. They suspected that if it can be most harmless then it can be worst harmful also.

 

Many reports showed that LINE1 is especially active inside developing embryos, which suggests that the segment actually plays a key role in coordinating the development of cells in an embryo. Researchers at University of California at San Francisco figured out how to turn LINE1 off in mouse embryos by blocking LINE1 RNA. As a result the embryos got stuck in the two-cell stage, right after a fertilized egg has first split. Without LINE1, embryos essentially stopped developing.

 

The researchers thought that LINE1 RNA particles act as molecular “glue,” bringing together a suite of molecules that switch off the two-cell stage and kick it into the next phase of development. In particular, it turns off a gene called Dux, which is active in the two-cell stage.

 

LINE1’s ability to copy itself, however, seems to have nothing to do with its role in embryonic development. When LINE1 was blocked from inserting itself into the genome, the embryonic stem cells remained unaffected. It’s possible that cells in embryos have a way of making LINE1 RNA while also preventing its potentially harmful “jumping” around in the genome. But it’s unlikely that every one of the thousands of copies of LINE1 is actually being used to regulate embryonic development.

 

LINE1 is abundant in the genomes of almost all mammals. Other transposons, also once considered junk DNA, have turned out to have critical roles in development in human cells too. There are differences between mice and humans, so, the next obvious step is to study LINE1 in human cells, where it makes up 17 percent of the genome.

 

References:

 

https://www-theatlantic-com.cdn.ampproject.org/c/s/www.theatlantic.com/amp/article/563354/

 

https://www.ncbi.nlm.nih.gov/pubmed/29937225

 

https://www.nature.com/scitable/topicpage/transposons-the-jumping-genes-518

 

https://www.sciencedaily.com/releases/2018/06/180621141038.htm

 

https://www.ncbi.nlm.nih.gov/pubmed/16015595

 

Advertisements

Read Full Post »


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

 

Hepatitis B virus can cause serious, long-term health problems, such as liver disease and cancer, and can spread from mother-to-child during delivery. According to the latest estimates from the World Health Organization (WHO), approximately 257 million people in 2015 were living with the virus. Countries in Asia have a high burden of hepatitis B. There is no cure, and antiviral drugs used to treat the infection usually need to be taken for life.

 

To prevent infection, WHO recommends that all newborns receive their first dose of hepatitis B vaccine within 24 hours of delivery. Infants born to hepatitis B-infected mothers are also given protective antibodies called hepatitis B immune globulin (HBIG). However, mother-to-child transmission can still occur in women with high levels of virus in their blood, as well as those with mutated versions of the virus.

 

Tenofovir disoproxil fumarate (TDF), an antiviral drug commonly prescribed to treat hepatitis B infection, does not significantly reduce mother-to-child transmission of hepatitis B virus when taken during pregnancy and after delivery, according to a phase III clinical trial in Thailand funded by the National Institutes of Health. The study tested TDF therapy in addition to the standard preventative regimen — administration of hepatitis B vaccine and protective antibodies at birth — to explore the drug’s potential effects on mother-to-child transmission rates. The results appear in the New England Journal of Medicine.

 

The present study was conducted at 17 hospitals of the Ministry of Public Health in Thailand. It screened more than 2,500 women for eligibility and enrolled 331 pregnant women with hepatitis B. The women received placebo (163) or TDF (168) at intervals from 28 weeks of pregnancy to two months after delivery. All infants received standard hepatitis B preventatives given in Thailand, which include HBIG at birth and five doses of the hepatitis B vaccine by age 6 months (which differs from the three doses given in the United States). A total of 294 infants (147 in each group) were followed through age 6 months.

 

Three infants in the placebo group had hepatitis B infection at age 6 months, compared to zero infants in the TDF treatment group. Given the unexpectedly low transmission rate in the placebo group, the researchers concluded that the addition of TDF to current recommendations did not significantly reduce mother-to-child transmission of the virus.

 

According to the study, the clinical trial had enough participants to detect statistical differences if the transmission rate in the placebo group reached at least 12 percent, a rate observed in previous studies. Though the reasons are unknown, the researchers speculate that the lower transmission rate seen in the study may relate to the number of doses of hepatitis B vaccine given to infants in Thailand, lower rates of amniocentesis and Cesarean section deliveries in this study, or the lower prevalence of mutated viruses that result in higher vaccine efficacy in Thailand compared to other countries.

 

References:

 

https://www.nih.gov/news-events/news-releases/antiviral-drug-not-beneficial-reducing-mother-child-transmission-hepatitis-b-when-added-existing-preventatives

 

https://www.ncbi.nlm.nih.gov/pubmed/29514030

 

https://www.ncbi.nlm.nih.gov/pubmed/29514035

 

https://www.ncbi.nlm.nih.gov/pubmed/25240752

 

https://www.ncbi.nlm.nih.gov/pubmed/28188612

 

Read Full Post »


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

 

Babies born at or before 25 weeks have quite low survival outcomes, and in the US it is the leading cause of infant mortality and morbidity. Just a few weeks of extra ‘growing time’ can be the difference between severe health problems and a relatively healthy baby.

 

Researchers from The Children’s Hospital of Philadelphia (USA) Research Institute have shown it’s possible to nurture and protect a mammal in late stages of gestation inside an artificial womb; technology which could become a lifesaver for many premature human babies in just a few years.

 

The researchers took eight lambs between 105 to 120 days gestation (the physiological equivalent of 23 to 24 weeks in humans) and placed them inside the artificial womb. The artificial womb is a sealed and sterile bag filled with an electrolyte solution which acts like amniotic fluid in the uterus. The lamb’s own heart pumps the blood through the umbilical cord into a gas exchange machine outside the bag.

 

The artificial womb worked in this study and after just four weeks the lambs’ brains and lungs had matured like normal. They had also grown wool and could wiggle, open their eyes, and swallow. Although this study is looking incredibly promising but getting the research up to scratch for human babies still requires a big leap.

 

Nevertheless, if all goes well, the researchers hope to test the device on premature humans within three to five years. Potential therapeutic applications of this invention may include treatment of fetal growth retardation related to placental insufficiency or the salvage of preterm infants threatening to deliver after fetal intervention or fetal surgery.

 

The technology may also provide the opportunity to deliver infants affected by congenital malformations of the heart, lung and diaphragm for early correction or therapy before the institution of gas ventilation. Numerous applications related to fetal pharmacologic, stem cell or gene therapy could be facilitated by removing the possibility for maternal exposure and enabling direct delivery of therapeutic agents to the isolated fetus.

 

References:

 

https://www.nature.com/articles/ncomms15112

 

 

https://www.sciencealert.com/researchers-have-successfully-grown-premature-lambs-in-an-artificial-womb

 

http://www.npr.org/sections/health-shots/2017/04/25/525044286/scientists-create-artificial-womb-that-could-help-prematurely-born-babies

 

http://www.telegraph.co.uk/science/2017/04/25/artificial-womb-promises-boost-survival-premature-babies/

 

https://www.theguardian.com/science/2017/apr/25/artificial-womb-for-premature-babies-successful-in-animal-trials-biobag

 

http://www.theblaze.com/news/2017/04/25/new-artificial-womb-technology-could-keep-babies-born-prematurely-alive-and-healthy/

 

http://www.theverge.com/2017/4/25/15421734/artificial-womb-fetus-biobag-uterus-lamb-sheep-birth-premie-preterm-infant

 

http://www.abc.net.au/news/2017-04-26/artificial-womb-could-one-day-keep-premature-babies-alive/8472960

 

https://www.theatlantic.com/health/archive/2017/04/preemies-floating-in-fluid-filled-bags/524181/

 

http://www.independent.co.uk/news/health/artificial-womb-save-premature-babies-lives-scientists-create-childrens-hospital-philadelphia-nature-a7701546.html

 

https://www.cnet.com/news/artificial-womb-births-premature-lambs-human-infants/

 

https://science.slashdot.org/story/17/04/25/2035243/an-artificial-womb-successfully-grew-baby-sheep—-and-humans-could-be-next

 

http://newatlas.com/artificial-womb-premature-babies/49207/

 

https://www.geneticliteracyproject.org/2015/06/12/artificial-wombs-the-coming-era-of-motherless-births/

 

http://news.nationalgeographic.com/2017/04/artificial-womb-lambs-premature-babies-health-science/

 

https://motherboard.vice.com/en_us/article/artificial-womb-free-births-just-got-a-lot-more-real-cambridge-embryo-reproduction

 

http://www.disclose.tv/news/The_Artificial_Womb_Is_Born_Welcome_To_The_WORLD_Of_The_MATRIX/114199

 

 

Read Full Post »


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

 

Scientists think excessive population growth is a cause of scarcity and environmental degradation. A male pill could reduce the number of unintended pregnancies, which accounts for 40 percent of all pregnancies worldwide.

 

But, big drug companies long ago dropped out of the search for a male contraceptive pill which is able to chemically intercept millions of sperm before they reach a woman’s egg. Right now the chemical burden for contraception relies solely on the female. There’s not much activity in the male contraception field because an effective solution is available on the female side.

 

Presently, male contraception means a condom or a vasectomy. But researchers from Center for Drug Discovery at Baylor College of Medicine, USA are renewing the search for a better option—an easy-to-take pill that’s safe, fast-acting, and reversible.

 

The scientists began with lists of genes active in the testes for sperm production and motility and then created knockout mice that lack those genes. Using the gene-editing technology called CRISPR, in collaboration with Japanese scientists, they have so far made more than 75 of these “knockout” mice.

 

They allowed these mice to mate with normal (wild type) female mice, and if their female partners don’t get pregnant after three to six months, it means the gene might be a target for a contraceptive. Out of 2300 genes that are particularly active in the testes of mice, the researchers have identified 30 genes whose deletion makes the male infertile. Next the scientists are planning a novel screening approach to test whether any of about two billion chemicals can disable these genes in a test tube. Promising chemicals could then be fed to male mice to see if they cause infertility.

 

Female birth control pills use hormones to inhibit a woman’s ovaries from releasing eggs. But hormones have side effects like weight gain, mood changes, and headaches. A trial of one male contraceptive hormone was stopped early in 2011 after one participant committed suicide and others reported depression. Moreover, some drug candidates have made animals permanently sterile which is not the goal of the research. The challenge is to prevent sperm being made without permanently sterilizing the individual.

 

As a better way to test drugs, Scientists at University of Georgia, USA are investigating yet another high-tech approach. They are turning human skin cells into stem cells that look and act like the spermatogonial cells in the testes. Testing drugs on such cells might provide more accurate leads than tests on mice.

 

The male pill would also have to start working quickly, a lot sooner than the female pill, which takes about a week to function. Scientists from University of Dundee, U.K. admitted that there are lots of challenges. Because, a women’s ovary usually release one mature egg each month, while a man makes millions of sperm every day. So, the male pill has to be made 100 percent effective and act instantaneously.

 

References:

 

https://www.technologyreview.com/s/603676/the-search-for-a-perfect-male-birth-control-pill/

 

https://futurism.com/videos/the-perfect-male-birth-control-pill-is-coming-soon/?utm_source=Digest&utm_campaign=c42fc7b9b6-EMAIL_CAMPAIGN_2017_03_20&utm_medium=email&utm_term=0_03cd0a26cd-c42fc7b9b6-246845533

 

http://www.telegraph.co.uk/women/sex/the-male-pill-is-coming—and-its-going-to-change-everything/

 

http://www.mensfitness.com/women/sex-tips/male-birth-control-pill-making

 

http://health.howstuffworks.com/sexual-health/contraception/male-bc-pill.htm

 

http://europe.newsweek.com/male-contraception-side-effects-study-pill-injection-518237?rm=eu

 

http://edition.cnn.com/2016/01/07/health/male-birth-control-pill/index.html

 

http://www.nhs.uk/Conditions/contraception-guide/Pages/male-pill.aspx

Read Full Post »


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

Researchers have classified a brand-new organ inside human body. Known as the mesentery, the new organ is found in our digestive systems, and was long thought to be made up of fragmented, separate structures. But recent research has shown that it’s actually one, continuous organ. The evidence for the organ’s reclassification is now published in The Lancet Gastroenterology & Hepatology. Although we now know about the structure of this new organ, its function is still poorly understood, and studying it could be the key to better understanding and treatment of abdominal and digestive disease.

mesentery

J Calvin Coffey, a researcher from the University Hospital Limerick in Ireland, who first discovered that the mesentery was an organ. In 2012, Coffey and his colleagues showed through detailed microscopic examinations that the mesentery is actually a continuous structure. Over the past four years, they’ve gathered further evidence that the mesentery should actually be classified as its own distinct organ, and the latest paper makes it official. Mesentery is a double fold of peritoneum – the lining of the abdominal cavity – that holds our intestine to the wall of our abdomen. It was described by the Italian polymath Leanardo da Vinci in 1508, but it has been ignored throughout the centuries, until now. Although there are generally considered to be five organs in the human body, there are in fact now 79, including the mesentery. The heart, brain, liver, lungs and kidneys are the vital organs, but there are another 74 that play a role in keeping us healthy. The distinctive anatomical and functional features of mesentery have been revealed that justify designation of the mesentery as an organ. Accordingly, the mesentery should be subjected to the same investigatory focus that is applied to other organs and systems. This provides a platform from which to direct future scientific investigation of the human mesentery in health and disease.

References:

http://www.thelancet.com/journals/langas/article/PIIS2468-1253(16)30026-7/abstract

http://www.sciencealert.com/it-s-official-a-brand-new-human-organ-has-been-classified

http://www.bbc.com/news/health-38506708

http://www.independent.co.uk/news/science/new-organ-mesentery-found-human-body-digestive-system-classified-abdominal-grays-anatomy-a7507396.html

https://in.news.yahoo.com/scientists-discover-human-organ-064207997.html

https://en.wikipedia.org/wiki/Mesentery

Read Full Post »


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

 

MicroRNAs (miRNAs) are a group of small non-coding RNA molecules that play a major role in posttranscriptional regulation of gene expression and are expressed in an organ-specific manner. One miRNA can potentially regulate the expression of several genes, depending on cell type and differentiation stage. They control every cellular process and their altered regulation is involved in human diseases. miRNAs are differentially expressed in the male and female gonads and have an organ-specific reproductive function. Exerting their affect through germ cells and gonadal somatic cells, miRNAs regulate key proteins necessary for gonad development. The role of miRNAs in the testes is only starting to emerge though they have been shown to be required for adequate spermatogenesis. In the ovary, miRNAs play a fundamental role in follicles’ assembly, growth, differentiation, and ovulation.

 

Deciphering the underlying causes of idiopathic male infertility is one of the main challenges in reproductive medicine. This is especially relevant in infertile patients displaying normal seminal parameters and no urogenital or genetic abnormalities. In these cases, the search for additional sperm biomarkers is of high interest. This study was aimed to determine the implications of the sperm miRNA expression profiles in the reproductive capacity of normozoospermic infertile individuals. The expression levels of 736 miRNAs were evaluated in spermatozoa from normozoospermic infertile males and normozoospermic fertile males analyzed under the same conditions. 57 miRNAs were differentially expressed between populations; 20 of them was regulated by a host gene promoter that in three cases comprised genes involved in fertility. The predicted targets of the differentially expressed miRNAs unveiled a significant enrichment of biological processes related to embryonic morphogenesis and chromatin modification. Normozoospermic infertile individuals exhibit a specific sperm miRNA expression profile clearly differentiated from normozoospermic fertile individuals. This miRNA cargo has potential implications in the individuals’ reproductive competence.

 

Circulating or “extracellular” miRNAs detected in biological fluids, could be used as potential diagnostic and prognostic biomarkers of several disease, such as cancer, gynecological and pregnancy disorders. However, their contributions in female infertility and in vitro fertilization (IVF) remain unknown. Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women. PCOS is associated with altered features of androgen metabolism, increased insulin resistance and impaired fertility. Furthermore, PCOS, being a syndrome diagnosis, is heterogeneous and characterized by polycystic ovaries, chronic anovulation and evidence of hyperandrogenism, as well as being associated with chronic low-grade inflammation and an increased life time risk of type 2 diabetes. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that these might serve as potential biomarkers and a new approach for the diagnosis of PCOS. Presence of miRNA in mammalian follicular fluid has been demonstrated to be enclosed within microvesicles and exosomes or they can also be associated to protein complexes. The presence of microvesicles and exosomes carrying microRNAs in follicular fluid could represent an alternative mechanism of autocrine and paracrine communication inside the ovarian follicle. The investigation of the expression profiles of five circulating miRNAs (let-7b, miR-29a, miR-30a, miR-140 and miR-320a) in human follicular fluid from women with normal ovarian reserve and with polycystic ovary syndrome (PCOS) and their ability to predict IVF outcomes showed that these miRNAs could provide new helpful biomarkers to facilitate personalized medical care for oocyte quality in ART (Assisted Reproductive Treatment) and during IVF (In Vitro Fertilization).

 

References:

 

http://link.springer.com/chapter/10.1007%2F978-3-319-31973-5_12

 

http://onlinelibrary.wiley.com/doi/10.1111/andr.12276/abstract;jsessionid=F805A89DCC94BDBD42D6D60C40AD4AB0.f03t03

 

http://www.sciencedirect.com/science/article/pii/S0009279716302241

 

http://link.springer.com/article/10.1007%2Fs10815-016-0657-9

 

http://www.nature.com/articles/srep24976

 

 

Read Full Post »


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

 

Mitochondrial disease

 

Mitochondria are present in almost all human cells, and vary in number from a few tens to many thousands. They generate the majority of a cell’s energy supply which powers every part of our body. Mitochondria have their own separate DNA, which carries just a few genes. All of these genes are involved in energy production but determine no other characteristics. And so, any faults in these genes lead only to problems in energy production. Around 1 in 6500 children is thought to be born with a serious mitochondrial disorder due to faults in mitochondrial DNA.

 

Unlike nuclear genes, mitochondrial DNA is inherited only from our mothers. Mothers can carry abnormal mitochondria and be at risk of passing on serious disease to their children, even if they themselves show only mild or no symptoms. It is for such women who by chance have a high proportion of faulty mitochondrial DNA in their eggs for which the methods of mitochondrial replacement or “donation” have been developed. This technique is also referred as the three parent technique and it involves a couple and a donor.

 

Mitochondrial Donation

 

The most developed techniques, maternal spindle transfer (MST) and pro-nuclear transfer (PNT), are based on an IVF cycle but have additional steps. Other techniques are being developed.

 

In both MST and PNT, nuclear DNA is moved from a patient’s egg or embryo containing unhealthy mitochondria to a donor’s egg or embryo containing healthy mitochondria, from which the donor’s nuclear DNA has been removed.

 

mst

Maternal spindle transfer Bredenoord, A and P. Braude (2010) “Ethics of mitochondrial gene replacement: from bench to bedside” BMJ 341.

 

pnt

Pronuclear transfer Bredenoord, A and P. Braude (2010) “Ethics of mitochondrial gene replacement: from bench to bedside” BMJ 341.

 

Research Carried Out and Safety Issues

 

There have been many experiments conducted using MST and PNT in animals. PNT has been carried out since the mid-1980s in mice. MST has been carried out in a wide range of animals. More recently mice, monkeys and human embryos have been created with the specific aim of developing MST and PNT for avoiding mitochondrial disease.

 

  • There is no evidence to show that mitochondrial donation is unsafe
  • Research is progressing well and the recommended further experiments are expected to confirm this view.

 

The main area of research needed is to observe cells derived from embryos created by MST and PNT, to see how mitochondria behave.

 

Concerns about Mitochondrial Donation

 

The scientific evidence raises some potential concerns about mitochondrial donation. Just as we all have different blood groups, we also have different types of mitochondria, called haplotypes. Some scientists have suggested that if the patient and the mitochondria donor have different mitochondrial haplotypes, there is a theoretical risk that the donor’s mitochondria won’t be able to ‘talk’ properly to the patient’s nuclear DNA, which could cause problems in the embryo and resulting child. So, mitochondria haplotype matching in the process of selecting donors may be done to avoid problems.

 

Another potential concern is that a small amount of unhealthy mitochondrial DNA may be transferred into the donor’s egg along with the mother’s nuclear DNA. Studies carried out on MST and PNT show that some so-called mitochondrial ‘carry-over’ occurs. However, the carry-over is lower than 2% of the mitochondria in the resulting embryo, an amount which is very unlikely to be problematic for the children born.

 

References:

 

http://mitochondria.hfea.gov.uk/mitochondria/what-is-mitochondrial-disease/

 

http://mitochondria.hfea.gov.uk/mitochondria/what-is-mitochondrial-disease/new-techniques-to-prevent-mitochondrial-disease/

 

https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/

 

https://www.newscientist.com/article/2108549-exclusive-3-parent-baby-method-already-used-for-infertility/

 

http://www.frontlinegenomics.com/news/7889/ethical-concerns-raised-first-three-parent-ivf-baby/

 

http://www.hfea.gov.uk/docs/2011-04-18_Mitochondria_review_-_final_report.PDF

 

http://www.hfea.gov.uk/docs/Mito-Annex_VIII-science_review_update.pdf

 

http://www.hfea.gov.uk/docs/Third_Mitochondrial_replacement_scientific_review.pdf

 

https://pharmaceuticalintelligence.com/2014/02/26/three-parent-baby-making-practice-of-modifying-oocytes-for-use-in-in-vitro-fertilization-fda-hearing/

 

 

Read Full Post »

Older Posts »