Leaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

Archive for the ‘Physics’ Category

Hybrid lipid bioelectronic membranes

Posted in Bioengineering & reverse engineering design, BioTechnology - Venture Creation, Cell Biology, Signaling & Cell Circuits, Curation, Electrophysiology, Innovations, Innovations in Neurophysiology & Neuropsychology, Ionic Transporters Na+, Lipid metabolism, Lipidomics, Lipids, Liposome, Metabolism, Microvesicle, Na-K transport, Nephrology, Neurohumoral Transmission, Physics, Proteins, Proteomics, Signaling, Signaling & Cell Circuits, Synaptic vesicle, tagged bioengineering, Biological sciences, Biophysics, Biotechnology, ion transport, lipid bilayers on December 14, 2015| Leave a Comment »

Hybrid lipid bioelectronic membranes

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Hybrid solid-state chips and biological cells integrated at molecular level

Biological ion channels combine with solid-state transistors to create a new kind of hybrid bioelectronics. Imagine chips with dog-like capability to taste and smell, or even recognize specific molecules.
http://www.kurzweilai.net/hybrid-solid-state-chips-and-biological-cells-integrated-at-molecular-level

http://www.kurzweilai.net/images/biocell-CMOS-.jpg

Illustration depicting a biocell attached to a CMOS integrated circuit with a membrane containing sodium-potassium pumps in pores. Energy is stored chemically in ATP molecules. When the energy is released as charged ions (which are then converted to electrons to power the chip at the bottom of the experimental device), the ATP is converted to ADP + inorganic phosphate. (credit: Trevor Finney and Jared Roseman/Columbia Engineering)

Columbia Engineering researchers have combined biological and solid-state components for the first time, opening the door to creating entirely new artificial biosystems.

In this experiment, they used a biological cell to power a conventional solid-state complementary metal-oxide-semiconductor (CMOS) integrated circuit. An artificial lipid bilayer membrane containing adenosine triphosphate (ATP)-powered ion pumps (which provide energy for cells) was used as a source of ions (which were converted to electrons to power the chip).

The study, led by Ken Shepard, Lau Family Professor of Electrical Engineering and professor of biomedical engineering at Columbia Engineering, was published online today (Dec. 7, 2015) in an open-access paper in Nature Communications.

How to build a hybrid biochip

Living systems achieve this functionality with their own version of electronics based on lipid membranes and ion channels and pumps, which act as a kind of “biological transistor.” Charge in the form of ions carry energy and information, and ion channels control the flow of ions across cell membranes.

Solid-state systems, such as those in computers and communication devices, use electrons; their electronic signaling and power are controlled by field-effect transistors.

To build a prototype of their hybrid system, Shepard’s team packaged a CMOS integrated circuit (IC) with an ATP-harvesting “biocell.” In the presence of ATP, the system pumped ions across the membrane, producing an electrical potential (voltage)* that was harvested by the integrated circuit.

“We made a macroscale version of this system, at the scale of several millimeters, to see if it worked,” Shepard notes. “Our results provide new insight into a generalized circuit model, enabling us to determine the conditions to maximize the efficiency of harnessing chemical energy through the action of these ion pumps. We will now be looking at how to scale the system down.”

While other groups have harvested energy from living systems, Shepard and his team are exploring how to do this at the molecular level, isolating just the desired function and interfacing this with electronics. “We don’t need the whole cell,” he explains. “We just grab the component of the cell that’s doing what we want. For this project, we isolated the ATPases because they were the proteins that allowed us to extract energy from ATP.”

The capability of a bomb-sniffing dog, no Alpo required

Next, the researchers plan to go much further, such as recognizing specific molecules and giving chips the potential to taste and smell.

The ability to build a system that combines the power of solid-state electronics with the capabilities of biological components has great promise, they believe. “You need a bomb-sniffing dog now, but if you can take just the part of the dog that is useful — the molecules that are doing the sensing — we wouldn’t need the whole animal,” says Shepard.

The technology could also provide a power source for implanted electronic devices in ATP-rich environments such as inside living cells, the researchers suggest.

*  “In general, integrated circuits, even when operated at the point of minimum energy in subthreshold, consume on the order of 10⁻² W mm⁻² (or assuming a typical silicon chip thickness of 250 μm, 4 × 10⁻² W mm⁻³). Typical cells, in contrast, consume on the order of 4 × 10⁻⁶ W mm⁻³. In the experiment, a typical active power dissipation for the IC circuit was 92.3 nW, and the active average harvesting power was 71.4 fW for the biocell (the discrepancy is managed through duty-cycled operation of the IC).” — Jared M. Roseman et al./Nature Communications

 

references:

Jared M. Roseman et al. Hybrid integrated biological–solid-state system powered with adenosine triphosphate. Nature Communications 6, 10070 doi:10.1038/ncomms10070. 07 December 2015 (open access)

Topics: Biotech | Electronics | Synthetic Biology

Hybrid integrated biological–solid-state system powered with adenosine triphosphate

Jared M. Roseman, Jianxun Lin, Siddharth Ramakrishnan, Jacob K. Rosenstein & Kenneth L. Shepard
Nature Communications 7 Dec 2015; 6(10070)     http://dx.doi.org:/10.1038/ncomms10070

There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na⁺/K⁺ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 × 10⁶ mm⁻²) are able to sustain a short-circuit current of 32.6 pA mm⁻² and an open-circuit voltage of 78 mV, providing for a maximum power transfer of 1.27 pW mm⁻² from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.

 

Figure 1: Fully hybrid biological–solid-state system.

 

 

http://www.nature.com/ncomms/2015/151207/ncomms10070/images/ncomms10070-f1.jpg

(a) Illustration depicting biocell attached to CMOS integrated circuit. (b) Illustration of membrane in pore containing sodium–potassium pumps. (c) Circuit model of equivalent stacked membranes, =2.1 pA, =98.6 GΩ, =575 GΩ and =75 pF, Ag/AgCl electrode equivalent resistance R_WE+R_CE<20 kΩ, energy-harvesting capacitor C_STOR=100 nF combined with switch as an impedance transformation network (only one switch necessary due to small duty cycle), and CMOS IC voltage doubler and resistor representing digital switching load. R_L represents the four independent ring oscillator loads. (d) Equivalent circuit detail of stacked biocell. (e) Switched-capacitor voltage doubler circuit schematic.

 

The energetics of living systems are based on electrochemical membrane potentials that are present in cell plasma membranes, the inner membrane of mitochondria, or the thylakoid membrane of chloroplasts¹. In the latter two cases, the specific membrane potential is known as the proton-motive force and is used by proton adenosine triphosphate (ATP) synthases to produce ATP. In the former case, Na⁺/K⁺-ATPases hydrolyse ATP to maintain the resting potential in most cells.

While there have been recent efforts to harness power from some naturally occurring potentials in living systems that are the result of ion pump action both in plants² and animals^{3, 4} to power complementary metal-oxide semiconductor (CMOS) integrated circuits (ICs), this work is the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitroenvironment to power such an artificial system. Prior efforts to harness power from in vitromembrane systems incorporating ion-pumping ATPases^{5, 6, 7, 8, 9} and light-activated bacteriorhodopsin^{9, 10, 11} have been limited by difficulty in incorporating these proteins in sufficient quantity to attain measurable current and in achieving sufficiently large membrane resistances to harness these currents. Both problems are solved in this effort to power an IC from ATP in an in vitro environment. The resulting measurements provide new insight into a generalized circuit model, which allows us to determine the conditions to maximize the efficiency of harnessing chemical energy through the action of electrogenic ion pumps.

 

ATP-powered IC

Figure 1a shows the complete hybrid integrated system, consisting of a CMOS IC packaged with an ATP-harvesting ‘biocell’. The biocell consists of two series-stacked ATPase bearing suspended lipid bilayers with a fluid chamber directly on top of the IC. Series stacking of two membranes is necessary to provide the required start-up voltage for IC and eliminates the need for an external energy source, which is typically required to start circuits from low-voltage supplies^{2, 3}. As shown inFig. 1c, a matching network in the form of a switched capacitor allows the load resistance of the IC to be matched to that presented by the biocell. In principle, the switch S can be implicit. The biocell charges C_STOR until the self start-up voltage, V_start, is reached. The chip then operates until the biocell voltage drops below the minimum supply voltage for operation, V_min. Active current draw from the IC stops at this point, allowing the charge to build up again on C_STOR. In our case, however, the IC leakage current exceeds 13.5 nA at V_start, more than can be provided by the biocell. As a result, an explicit transistor switch and comparator (outside of the IC) are used for this function in the experimental results presented here, which are not powered by the biocell and not included in energy efficiency calculations (see Supplementary Discussion for additional details). The energy from the biocell is used to operate a voltage converter (voltage doubler) and some simple inverter-based ring oscillators in the IC, which receive power from no other sources.

http://www.nature.com/ncomms/2015/151207/ncomms10070/images/ncomms10070-f1.jpg

 

……..   Prior to the addition of ATP, the membrane produces no electrical power and has an R_m of 280 GΩ. A 1.7-pA short-circuit (SC) current (Fig. 2b) through the membrane is observed upon the addition of ATP (final concentration 3 mM) to the cis chamber where functional, properly oriented enzymes generate a net electrogenic pump current. To perform these measurements, currents through each membrane of the biocell are measured using a voltage-clamp amplifier (inset of Fig. 2b) with a gain of 500 GΩ with special efforts taken to compensate amplifier leakage currents. Each ATPase transports three Na⁺ ions from the cis chamber to the trans chamber and two K⁺ ions from thetrans chamber to the cis chamber (a net charge movement of one cation) for every molecule of ATP hydrolysed. At a rate of 100 hydrolysis events per second under zero electrical (SC) bias¹³, this results in an electrogenic current of ~16 aA. The observed SC current corresponds to about 10⁵ active ATPases in the membrane or a concentration of about 2 × 10⁶ mm⁻², about 5% of the density of channels occurring naturally in mammalian nerve fibres¹⁴. It is expected that half of the channels inserted are inactive because they are oriented incorrectly.

Figure 2: Single-cell biocell characterization.

http://www.nature.com/ncomms/2015/151207/ncomms10070/images_article/ncomms10070-f2.jpg

(a)…Pre-ATP data linear fit (black line) slope yield R_m=280 GΩ. Post ATP data fit to a Boltzmann curve, slope=0.02 V (blue line). Post-ATP linear fit (red line) yields I_p=−1.8 pA and R_p=61.6 GΩ, which corresponds to a per-ATP source resistance of 6.16 × 10¹⁵. The current due to membrane leakage through R_{m} is subtracted in the post-ATP curve…. (b)…

 

Current–voltage characteristics of the ATPases

Figure 2a shows the complete measured current–voltage (I–V) characteristic of a single ATPase-bearing membrane in the presence of ATP. The current due to membrane leakage through R_m is subtracted in the post-ATP curve. The I–V characteristic fits a Boltzmann sigmoid curve, consistent with sodium–potassium pump currents measured on membrane patches at similar buffer conditions^{13, 15, 16}. This nonlinear behaviour reflects the fact that the full ATPase transport cycle (three Na⁺ ions from cis to trans and two K⁺ ions from trans to cis) time increases (the turn-over rate, k_ATP, decreases) as the membrane potential increases¹⁶. No effect on pump current is expected from any ion concentration gradients produced by the action of the ATPases (seeSupplementary Discussion). Using this Boltzmann fit, we can model the biocell as a nonlinear voltage-controlled current source I_ATPase (inset Fig. 2a), in which the current produced by this source varies as a function of V_m. In the fourth quadrant, where the cell is producing electrical power, this model can be linearized as a Norton equivalent circuit, consisting of a DC current source (I_p) in parallel with a current-limiting resistor (R_p), which acts to limit the current delivered to the load at increasing bias (I_ATPase~I_p−V_m/R_p). Figure 2c shows the measured and simulated charging of C_m for a single membrane (open-circuited voltage). A custom amplifier with input resistance R_in>10 TΩ was required for this measurement (see Electrical Measurement Methods).

 

Reconciling operating voltage differences

The electrical characteristics of biological systems and solid-state systems are mismatched in their operating voltages. The minimum operating voltage of solid-state systems is determined by the need for transistors to modulate a Maxwell–Boltzmann (MB) distribution of carriers by several orders of magnitude through the application of a potential that is several multiples of kT/q (where kis Boltzmann’s constant, T is the temperature in degrees Kelvin and q is the elementary charge). Biological systems, while operating under the same MB statistics, have no such constraints for operating ion channels since they are controlled by mechanical (or other conformational) processes rather than through modulation of a potential barrier. To bridge this operating voltage mismatch, the circuit includes a switched-capacitor voltage doubler (Fig. 1d) that is capable of self-startup from voltages as low V_start=145 mV (~5.5 kT/q) and can be operated continuously from input voltages from as low as V_min=110 mV (see Supplementary Discussion)…..

 

Maximizing the efficiency of harvesting energy from ATP

Solid-state systems and biological systems are also mismatched in their operating impedances. In our case, the biocell presents a source impedance, =84.2 GΩ, while the load impedance presented by the complete integrated circuit (including both the voltage converter and ring oscillator loads) is approximately R_IC=200 kΩ. (The load impedance, R_L, of the ring oscillators alone is 305 kΩ.) This mismatch in source and load impedance is manifest in large differences in power densities. In general, integrated circuits, even when operated at the point of minimum energy in subthreshold, consume on the order of 10⁻² W mm⁻² (or assuming a typical silicon chip thickness of 250 μm, 4 × 10⁻² W mm⁻³) (ref. 17). Typical cells, in contrast, consume on the order of 4 × 10⁻⁶ W mm⁻³ (ref. 18). In our case, a typical active power dissipation for our circuit is 92.3 nW, and the active average harvesting power is 71.4 fW for the biocell. This discrepancy is managed through duty-cycled operation of the IC in which the circuit is largely disabled for long periods of time (T_charge), integrating up the power onto a storage capacitor (C_STOR), which is then expended in a very brief period of activity (T_run), as shown in Fig. 3a.

The overall efficiency of the system in converting chemical energy to the energy consumed in the load ring oscillator (η) is given by the product of the conversion efficiency of the voltage doubler (η_converter) and the conversion efficiency of chemical energy to electrical energy in the biocell (η_biocell), η=η_converter × η_biocell. η_converter is relatively constant over the range of input voltages at ~59%, as determined by various loading test circuits included in the chip design (Supplementary Figs 1–6). η_biocell, however, varies with transmembrane potential V_m. η is the efficiency in transferring power to the power ring oscillator loads from the ATP harvested by biocell.

…….

To first order, the energy made available to the Na⁺/K⁺-ATPase by the hydrolysis of ATP is independent of the chemical or electric potential of the membrane and is given by |ΔG_ATP|/(qN_A), where ΔG_ATP is the Gibbs free energy change due to the ATP hydrolysis reaction per mole of ATP at given buffer conditions and N_A is Avogadro’s number. Since every charge that passes through I_ATPase corresponds to a single hydrolysis event, we can use two voltage sources in series with I_ATPase to independently account for the energy expended by the pumps both in moving charge across the electric potential difference and in moving ions across the chemical potential difference. The dependent voltage source V_loss in this branch fixes the voltage across I_ATPase, and the total power produced by the pump current source is (|ΔG_ATP|/N_A)(Nk_ATP), which is the product of the energy released per molecule of ATP, the number of active ATPases and the ATP turnover rate. The power dissipated in voltage source V_chem models the work performed by the ATPases in transporting ions against a concentration gradient. In the case of the Na⁺/K⁺ ATPase,V_chem is given by . The power dissipated in this source is introduced back into the circuit in the power generated by the Nernst independent voltage sources, and . The power dissipated in the dependent voltage source V_loss models any additional power not used to perform chemical or electrical work. ……

 

Integration of ATP-harvesting ion pumps could provide a means to power future CMOS microsystems scaled to the level of individual cells²². In molecular diagnostics, the integration of pore-forming proteins such as alpha haemolysin²³ or MspA porin²⁴ with CMOS electronics is already finding application in DNA sequencing²⁵. Exploiting the large diversity of function available in transmembrane proteins in these hybrid systems could, for example, lead to highly specific sensing platforms for airborne odorants or soluble molecular entities^{26, 27}. Heavily multiplexed platforms could become high-throughput in vitro drug-screening platforms against this diversity of function. In addition, integration of transmembrane proteins with CMOS may become a convenient alternative to fluorescence for coupling to synthetic biological systems²⁸.

 

Roseman, J. M. et al. Hybrid integrated biological–solid-state system powered with adenosine triphosphate. Nat. Commun. 6:10070      http://dx.doi.org:/10.1038/ncomms10070 (2015).

 

 

• Rottenberg, H. The measurement of membrane potential and deltapH in cells, organelles, and vesicles. Methods Enzymol. 55, 547–569 (1979).
  • CAS
  • PubMed
  • Show context
• Himes, C., Carlson, E., Ricchiuti, R. J., Otis, B. P. & Parviz, B. A. Ultralow voltage nanoelectronics powered directly, and solely, from a tree. IEEE Trans. Nanotechnol. 9, 2–5(2010).
  • Article
  • Show context
• Mercier, P. P., Lysaght, A. C., Bandyopadhyay, S., Chandrakasan, A. P. & Stankovic, K. M.Energy extraction from the biologic battery in the inner ear. Nat. Biotechnol. 30, 1240–1243(2012).
  • CAS
  • ISI
  • PubMed
  • Article
  • Show context
• Halámková, L. et al. Implanted Biofuel Cell Operating in a Living Snail. J. Am. Chem. Soc.134, 5040–5043 (2012).
  • CAS
  • PubMed
  • Article
  • Show context

 

 

Share this:

• X
• LinkedIn
• Facebook
• Print
• Email

Like this:

Like Loading...

Read Full Post »

Topology of Protein Complexes

Posted in Physics, Proteins, Proteomics, Sensors & Analytics, Signaling, Translational Science, Unfolded Protein Response (UPR), tagged classification of protein assemblies, Inflammasome, mRNA, protein, protein-protein interactions, tertiary structure, transcription on December 11, 2015| Leave a Comment »

Topology of Protein Complexes

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Periodic Table of Protein Complexes Unveiled

http://www.genengnews.com/gen-news-highlights/periodic-table-of-protein-complexes-unveiled/81252091/

 

 

http://www.genengnews.com/Media/images/GENHighlight/thumb_Dec11_2015_EMBLEBI_ProteinComplexesPeriodicTable1692141643.jpg

A new periodic table presents a systematic, ordered view of protein assembly, providing a visual tool for understanding biological function. [EMBL-EBI / Spencer Phillips]

 

Move over Mendeleev, there’s a new periodic table in science. Unlike the original periodic table, which organized the chemical elements, the new periodic table organizes protein complexes, or more precisely, quaternary structure topologies. Though there are other differences between the old and new periodic tables, they share at least one important feature—predictive power.

When Mendeleev introduced his periodic table, he predicted that when new chemical elements were discovered, they would fill his table’s blank spots. Analogous predictions are being ventured by the scientific team that assembled the new periodic table. This team, consisting of scientists from the Wellcome Genome Campus and the University of Cambridge, asserts that its periodic table reveals the regions of quaternary structure space that remain to be populated.

The periodic table of protein complexes not only offers a new way of looking at the enormous variety of structures that proteins can build in nature, it also indicates which structures might be discovered next. Moreover, it could point protein engineers toward entirely novel structures that never occurred in nature, but could be engineered.

The new table appeared December 11 in the journal Science, in an article entitled, “Principles of assembly reveal a periodic table of protein complexes.” The “principles of assembly” referenced in this title amount to three basic assembly types: dimerization, cyclization, and heteromeric subunit addition. In dimerization, one protein complex subunit doubles, and becomes two; in cyclization, protein complex subunits from a ring of three or more; and in heteromeric subunit addition, two different proteins bind to each other.

These steps, repeated in different combinations, gives rise to enormous number of proteins of different kinds. “Evolution has given rise to a huge variety of protein complexes, and it can seem a bit chaotic,” explained Joe Marsh, Ph.D., formerly of the Wellcome Genome Campus and now of the MRC Human Genetics Unit at the University of Edinburgh. “But if you break down the steps proteins take to become complexes, there are some basic rules that can explain almost all of the assemblies people have observed so far.”

The authors of the Science article noted that many protein complexes assemble spontaneously via ordered pathways in vitro, and these pathways have a strong tendency to be evolutionarily conserved. “[There] are strong similarities,” the authors added, “between protein complex assembly and evolutionary pathways, with assembly pathways often being reflective of evolutionary histories, and vice versa. This suggests that it may be useful to consider the types of protein complexes that have evolved from the perspective of what assembly pathways are possible.”

To explore this rationale, the authors examined the fundamental steps by which protein complexes can assemble, using electrospray mass spectrometry experiments, literature-curated assembly data, and a large-scale analysis of protein complex structures. Ultimately, they derived their approach to explaining the observed distribution of known protein complexes in quaternary structure space. This approach, they insist, provides a framework for understanding their evolution.

“In addition, it can contribute considerably to the prediction and modeling of quaternary structures by specifying which topologies are most likely to be adopted by a complex with a given stoichiometry, potentially providing constraints for multi-subunit docking and hybrid methods,” the authors concluded. “Lastly, it could help in the bioengineering of protein complexes by identifying which topologies are most likely to be stable, and thus which types of essential interfaces need to be engineered.”

The rows and columns of the periodic table of the elements, called periods and groups, were originally determined by each element’s atomic mass and chemical properties, later by atomic number and electron configuration. In contrast, the rows and columns of the periodic table of protein complexes correspond to the number of different subunit types and the number of times these subunits are repeated. The new table is not, it should be noted, periodic in the same sense as the periodic table of the elements. It is in principle open-ended.

Although there are no theoretical limitations to quaternary structure topology space in either dimension, the abridged version of the table presented in the Science article can accommodate the vast majority of known structures. Moreover, when the table’s creators compared the large variety of countenanced topologies to observed structures, they found that about 92% of known protein complex structures were compatible with their model.

“Despite its strong predictive power, the basic periodic table model does not account for about 8% of known protein complex structures,” the authors conceded. “More than half of these exceptions arise as a result of quaternary structure assignment errors.

“A benefit of this approach is that it highlights likely quaternary structure misassignments, particularly by identifying nonbijective complexes with even subunit stoichiometry. However, this still leaves about 4% of known structures that are correct but are not compatible with the periodic table.” The authors added that the exceptions to their model are interesting in their own right, and are the subject of ongoing studies.

 

 

http://phys.org/news/2015-12-periodic-table-protein-complexes.html

The Periodic Table of Protein Complexes, published today in Science, offers a new way of looking at the enormous variety of structures that proteins can build in nature, which ones might be discovered next, and predicting how entirely novel structures could be engineered. Created by an interdisciplinary team led by researchers at the Wellcome Genome Campus and the University of Cambridge, the Table provides a valuable tool for research into evolution and protein engineering.

Different ballroom dances can be seen as an endless combination of a small number of basic steps. Similarly, the ‘dance’ of protein complex assembly can be seen as endless variations on dimerization (one doubles, and becomes two), cyclisation (one forms a ring of three or more) and subunit addition (two different proteins bind to each other). Because these happen in a fairly predictable way, it’s not as hard as you might think to predict how a novel protein would form.

“We’re bringing a lot of order into the messy world of protein complexes,” explains Sebastian Ahnert of the Cavendish Laboratory at the University of Cambridge, a physicist who regularly tangles with biological problems. “Proteins can keep go through several iterations of these simple steps, , adding more and more levels of complexity and resulting in a huge variety of structures. What we’ve made is a classification based on these underlying principles that helps people get a handle on the complexity.”

The exceptions to the rule are interesting in their own right, adds Sebastian, as are the subject of on-going studies.

“By analysing the tens of thousands of protein complexes for which three-dimensional structures have already been experimentally determined, we could see repeating patterns in the assembly transitions that occur – and with new data from mass spectrometry we could start to see the bigger picture,” says Joe.

“The core work for this study is in theoretical physics and computational biology, but it couldn’t have been done without the mass spectrometry work by our colleagues at Oxford University,” adds Sarah Teichmann, Research Group Leader at the European Bioinformatics Institute (EMBL-EBI) and the Wellcome Trust Sanger Institute. “This is yet another excellent example of how extremely valuable interdisciplinary research can be.”

Read more at: http://phys.org/news/2015-12-periodic-table-protein-complexes.html#jCp

 

More information: “Principles of assembly reveal a periodic table of protein complexes” www.sciencemag.org/lookup/doi/10.1126/science.aaa2245

PRINCIPLES OF ASSEMBLY REVEAL A PERIODIC TABLE OF PROTEIN COMPLEXES

Sebastian E. Ahnert¹,*, Joseph A. Marsh²,³,*, Helena Hernández⁴, Carol V. Robinson⁴, Sarah A. Teichmann¹,³,⁵,†
Science 11 Dec 2015; 350(6266): aaa2245         DOI:http://dx.doi.org:/10.1126/science.aaa2245      

INTRODUCTION

The assembly of proteins into complexes is crucial for most biological processes. The three-dimensional structures of many thousands of homomeric and heteromeric protein complexes have now been determined, and this has had a broad impact on our understanding of biological function and evolution. Despite this, the organizing principles that underlie the great diversity of protein quaternary structures observed in nature remain poorly understood, particularly in comparison with protein folds, which have been extensively classified in terms of their architecture and evolutionary relationships.

RATIONALE

In this work, we sought a comprehensive understanding of the general principles underlying quaternary structure organization. Our approach was to consider protein complexes in terms of their assembly. Many protein complexes assemble spontaneously via ordered pathways in vitro, and these pathways have a strong tendency to be evolutionarily conserved. Furthermore, there are strong similarities between protein complex assembly and evolutionary pathways, with assembly pathways often being reflective of evolutionary histories, and vice versa. This suggests that it may be useful to consider the types of protein complexes that have evolved from the perspective of what assembly pathways are possible.

RESULTS

We first examined the fundamental steps by which protein complexes can assemble, using electrospray mass spectrometry experiments, literature-curated assembly data, and a large-scale analysis of protein complex structures. We found that most assembly steps can be classified into three basic types: dimerization, cyclization, and heteromeric subunit addition. By systematically combining different assembly steps in different ways, we were able to enumerate a large set of possible quaternary structure topologies, or patterns of key interfaces between the proteins within a complex. The vast majority of real protein complex structures lie within these topologies. This enables a natural organization of protein complexes into a “periodic table,” because each heteromer can be related to a simpler symmetric homomer topology. Exceptions are mostly the result of quaternary structure assignment errors, or cases where sequence-identical subunits can have different interactions and thus introduce asymmetry. Many of these asymmetric complexes fit the paradigm of a periodic table when their assembly role is considered. Finally, we implemented a model based on the periodic table, which predicts the expected frequencies of each quaternary structure topology, including those not yet observed. Our model correctly predicts quaternary structure topologies of recent crystal and electron microscopy structures that are not included in our original data set.

CONCLUSION

This work explains much of the observed distribution of known protein complexes in quaternary structure space and provides a framework for understanding their evolution. In addition, it can contribute considerably to the prediction and modeling of quaternary structures by specifying which topologies are most likely to be adopted by a complex with a given stoichiometry, potentially providing constraints for multi-subunit docking and hybrid methods. Lastly, it could help in the bioengineering of protein complexes by identifying which topologies are most likely to be stable, and thus which types of essential interfaces need to be engineered.

http://www.sciencemag.org/content/350/6266/aaa2245/F1.small.gif

Protein assembly steps lead to a periodic table of protein complexes and can predict likely quaternary structure topologies.

Three main assembly steps are possible: cyclization, dimerization, and subunit addition. By combining these in different ways, a large set of possible quaternary structure topologies can be generated. These can be arranged on a periodic table that describes most known complexes and that can predict previously unobserved topologies.

Ahnert SE, et. al. ‘Principles of assembly reveal a periodic table of protein complexes.’
Science (2015).   DOI: http://dx.doi.org:/10.1126/science.aaa2245    http://www.cam.ac.uk/research/news/the-periodic-table-of-proteins

 

Evolution, classification and dynamics of protein complexes

• Sarah Teichmann
• Thursday 15 October 2015, 12:00–13:00
• TCM Seminar room, 530 Mott building.

This talk is included in these lists:

• Biological and Statistical Physics discussion group (BSDG)
• Combined TCM Seminars and TCM blackboard seminar listing
• PMRFPS’s
• TCM Seminar room, 530 Mott building

This talk is part of the Biological and Statistical Physics discussion group (BSDG) series.

Classification of protein structure has had a broad impact on our understanding of biological function and evolution, yet this work has largely focused on individual protein domains and their pairwise interactions. In contrast, the assembly of individual polypeptides into protein complexes, which are ubiquitous in cells, has received comparatively little attention. The periodic table of protein complexes is a new framework for analysis of complexes based on the principles of self-assembly. This reveals that sequence-identical subunits almost always have identical assembly roles within a complex and allows us to unify the vast majority of complexes of known structure (~32,000) into about 120 topologies. This facilitates the exhaustive enumeration of unobserved protein complex topologies and has significant practical applications for quaternary structure prediction, modelling and engineering.

http://talks.cam.ac.uk/talk/index/61632

 

 

Genome-wide analysis of thylakoid-bound ribosomes in maize reveals principles of cotranslational targeting to the thylakoid membrane

Reimo Zoschke1 and Alice Barkan2
http://www.pnas.org/content/112/13/E1678.full.pdf

Chloroplast genomes encode ∼37 proteins that integrate into the thylakoid membrane. The mechanisms that target these proteins to the membrane are largely unexplored. We used ribosome profiling to provide a comprehensive, high-resolution map of ribosome positions on chloroplast mRNAs in separated membrane and soluble fractions in maize seedlings. The results show that translation invariably initiates off the thylakoid membrane and that ribosomes synthesizing a subset of membrane proteins subsequently become attached to the membrane in a nucleaseresistant fashion. The transition from soluble to membraneattached ribosomes occurs shortly after the first transmembrane segment in the nascent peptide has emerged from the ribosome. Membrane proteins whose translation terminates before emergence of a transmembrane segment are translated in the stroma and targeted to the membrane posttranslationally. These results indicate that the first transmembrane segment generally comprises the signal that links ribosomes to thylakoid membranes for cotranslational integration. The sole exception is cytochrome f, whose cleavable N-terminal cpSecA-dependent signal sequence engages the thylakoid membrane cotranslationally. The distinct behavior of ribosomes synthesizing the inner envelope protein CemA indicates that sorting signals for the thylakoid and envelope membranes are distinguished cotranslationally. In addition, the fractionation behavior of ribosomes in polycistronic transcription units encoding both membrane and soluble proteins adds to the evidence that the removal of upstream ORFs by RNA processing is not typically required for the translation of internal genes in polycistronic chloroplast mRNAs.

 

Significance Proteins in the chloroplast thylakoid membrane system are derived from both the nuclear and plastid genomes. Mechanisms that localize nucleus-encoded proteins to the thylakoid membrane have been studied intensively, but little is known about the analogous issues for plastid-encoded proteins. This genome-wide, high-resolution analysis of the partitioning of chloroplast ribosomes between membrane and soluble fractions revealed that approximately half of the chloroplast encoded thylakoid proteins integrate cotranslationally and half integrate posttranslationally. Features in the nascent peptide that underlie these distinct behaviors were revealed by analysis of the position on each mRNA at which elongating ribosomes first become attached to the membrane.

 

 

Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor

Tengchuan Jin, Andrew Perry, Jiansheng Jiang, Patrick Smith, James A. Curry, et al.
Immunity 20 Apr 2012; 36(4):561–571    http://dx.doi.org/10.1016/j.immuni.2012.02.014

http://www.cell.com/cms/attachment/2007963858/2030721291/fx1.jpg

Highlights

• Electrostatic attraction underlies innate dsDNA recognition by the HIN domains
• Both OB folds and the linker between them engage the dsDNA backbone
• An autoinhibited state of AIM2 is activated by DNA that liberates the PYD domain
• DNA serves as an oligomerization platform for the inflammasome assembly

 

Summary

Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.

Share this:

• X
• LinkedIn
• Facebook
• Print
• Email

Like this:

Like Loading...

Read Full Post »

« Newer Posts

• Follow Blog via Email

  Enter your email address to follow this blog and receive notifications of new posts by email.

  Email Address

  Follow

  Join 2,056 other subscribers

• Recent Posts

  • Grok thinks like PhDs – Hybrid Model for Autonomous Update of Doctoral Dissertations with Original PhD Student Author editing and acceptance of Grok’s updated output. 3rd Joint article, a pilot study for Validation of an Autonomous Journal Articles Updating System (AJAUS) tested on Autonomous Update of Aviva Lev-Ari, PhD, RN Doctoral Thesis, UC, Berkeley, 1983. January 31, 2026
  • 2026 World Economic Forum, 1/19 – 1/23/2026, Davos, Switzerland, LPBI Group’s KOLs interpretation of AI in Health Videos January 24, 2026
  • Evolving LPBI Group’s Portfolio of Intellectual Properties (IP): From 2021 Vision to 2026 Reality January 12, 2026
  • Aviva Lev-Ari, PhD, RN – Biography ->> Grokepedia Entry January 11, 2026
  • List of Articles included in the Article SELECTION from Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com for Training Small Language Models (SLMs) in Domain-aware Content of Medical, Pharmaceutical, Life Sciences and Healthcare by 15 Subjects Matter January 10, 2026
  • Article SELECTION from Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com for Training Small Language Models (SLMs) in Domain-aware Content of Medical, Pharmaceutical, Life Sciences and Healthcare by 15 Subjects Matter January 10, 2026
  • Collection of Aviva Lev-Ari, PhD, RN Scientific Articles on PULSE on LinkedIn.com January 10, 2026
  • The youngest leader in AI in Health: Tanishq Mathew Abraham, Ph.D. (@iScienceLuvr) January 8, 2026
  • 2026 Grok Multimodal Causal Reasoning on Proprietary Cariovascular Corpus: From 2021 Wolfram NLP Baseline to Thousands of Novel Relationships – A Second Head-to-Head Validation of LPBI’s Domain-Aware Training Advantage January 6, 2026
  • Workflow for Dynamic Linkage and Transition between two Authoring Systems: LPBI Group’s WordPress.com Multi-Authors Authoring System and Microsoft PowerPoint product for Slide show presentation – Part 10.1 in Composition of Methods January 6, 2026

• Archives

  Archives Select Month January 2026  (10) December 2025  (8) November 2025  (8) October 2025  (12) September 2025  (2) July 2025  (4) June 2025  (8) May 2025  (4) April 2025  (2) March 2025  (1) February 2025  (2) January 2025  (3) December 2024  (1) November 2024  (5) October 2024  (7) September 2024  (7) August 2024  (1) June 2024  (1) May 2024  (2) April 2024  (2) January 2024  (1) November 2023  (1) October 2023  (3) September 2023  (3) August 2023  (2) July 2023  (2) June 2023  (7) May 2023  (4) April 2023  (2) March 2023  (5) February 2023  (2) January 2023  (3) December 2022  (2) October 2022  (6) September 2022  (2) August 2022  (1) July 2022  (3) June 2022  (3) May 2022  (8) April 2022  (10) March 2022  (7) February 2022  (7) January 2022  (3) December 2021  (3) November 2021  (4) October 2021  (11) September 2021  (5) August 2021  (8) July 2021  (21) June 2021  (8) May 2021  (10) April 2021  (8) March 2021  (15) February 2021  (17) January 2021  (20) December 2020  (10) November 2020  (12) October 2020  (26) September 2020  (17) August 2020  (22) July 2020  (27) June 2020  (33) May 2020  (26) April 2020  (42) March 2020  (22) February 2020  (11) January 2020  (7) December 2019  (20) November 2019  (13) October 2019  (11) September 2019  (3) August 2019  (8) July 2019  (25) June 2019  (47) May 2019  (40) April 2019  (27) March 2019  (29) February 2019  (17) January 2019  (50) December 2018  (14) November 2018  (17) October 2018  (18) September 2018  (17) August 2018  (8) July 2018  (20) June 2018  (22) May 2018  (17) April 2018  (12) March 2018  (20) February 2018  (26) January 2018  (16) December 2017  (6) November 2017  (20) October 2017  (13) September 2017  (16) August 2017  (16) July 2017  (19) June 2017  (20) May 2017  (32) April 2017  (21) March 2017  (10) February 2017  (24) January 2017  (21) December 2016  (43) November 2016  (8) October 2016  (40) September 2016  (67) August 2016  (59) July 2016  (75) June 2016  (37) May 2016  (95) April 2016  (152) March 2016  (175) February 2016  (196) January 2016  (139) December 2015  (90) November 2015  (287) October 2015  (237) September 2015  (115) August 2015  (96) July 2015  (63) June 2015  (44) May 2015  (53) April 2015  (76) March 2015  (95) February 2015  (83) January 2015  (75) December 2014  (75) November 2014  (88) October 2014  (135) September 2014  (117) August 2014  (88) July 2014  (88) June 2014  (109) May 2014  (60) April 2014  (85) March 2014  (58) February 2014  (72) January 2014  (107) December 2013  (104) November 2013  (136) October 2013  (62) September 2013  (32) August 2013  (46) July 2013  (74) June 2013  (110) May 2013  (112) April 2013  (86) March 2013  (92) February 2013  (63) January 2013  (63) December 2012  (46) November 2012  (71) October 2012  (84) September 2012  (82) August 2012  (122) July 2012  (59) June 2012  (34) May 2012  (46) April 2012  (2)

• Categories

  Categories Select Category 3D Printing for Medical Application  (239)    3D Plotting Scaffolds  (44)    BioInks  (34)       Biopolymer Blend Open Porous  (18)       Dental Applications  (10)    BioPrinting in Regenerative Medicine  (77)       Cell Level  (16)       MicroEngineering Cell-Tissue & Systems  (31)       Tissue Engineering  (37)    Cardiovascular and Vascular Systems  (30)       Artificial Vascular Structures  (9)       Cardiovascular Tissue  (8)    Drug Development using MultiOrgan Chip  (11)    Drug Development/Formulation using 3D Printing  (10)    MEMS  (16)       Bio-MEMS  (12)    Organ-on-a-Chip  (11)    Programmable Sensors (Carbon Nano Tubes)  (5) 3rd Party IP: Drug DIscovery  (1) 4D Printing and Meta Materials  (10) Academic Publishing  (223)    Key Opinion Leaders in eScientific Publishing – Interviews with  (8) Advanced Drug Manufacturing Technology  (96)    Antimalarial Preparation  (8)    Autologous Cell Therapy  (14)    Automated Cell Processing  (13) Allergy and Infectious Diseases  (12) Alzheimer’s Disease  (163)    Etiology  (77)    Medical Device Therapies for Altzheimer’s Disease  (15)    Pharmacotherapy and Cell Activity  (51) Anticancer Resistance  (31) Art Exhibits on the Human Condition  (1) Art Inspires Science  (4) Article Type  (2)    Authored  (1)    Curated  (2)    Scientific report  (1) Artificial Heart  (2) Artificial Intelligence – General  (232)    An executive’s guide to AI  (10)    Artificial Intelligence – Breakthroughs in Theories and Technologies  (115)    Artificial Intelligence Applications in Health Care  (125)       Artificial Intelligence in CANCER  (39)       Artificial Intelligence in Health Care – Tools & Innovations  (74)    Artificial Intelligence in Medicine – Application for Diagnosis  (69)       Artificial intelligence applications for cardiology  (31)          AI-assisted Cardiac MRI  (10)       Artificial Intelligence in Psychiatry  (6)       Deep Learning in Pathology  (18)    Artificial Intelligence in Medicine – Applications in Therapeutics  (64)    ChatGPT, GPT-4  (7)       ChatGPT at LPBI Group  (3)       ChatGPT in Academic Education  (3)    Machine Learning  (71)       Deep Learning  (25)       Natural Language Processing (NLP)  (45)    Machine learning in predicting type 2 diabetes  (5) Auditory and vision  (13) Autism Spectrum Disorders  (10) Autoimmune Inflammatory DIseases  (24)    Crohn’s disease  (5)    Tolerance-inducing Autoimmune Disease Therapeutics  (6)    Ulcerative Colitis  (3) Autophagosome  (4) Bacterial Resistance  (25) Behavior  (26) Behavioral Genetics  (21) Big Data  (88)    Intelligent Information Systems  (51) Bio Instrumentation in Experimental Life Sciences Research  (368)    Analytical Instruments Industry  (5)    Microfuidics  (8) Bio-Ethics  (15) BioBanking  (36) Biodegradable Drug-eluting Material  (8) Bioengineering & reverse engineering design  (43) BioIT: BioInformatics  (147) BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics  (135)    Advanced Computing Platform  (32)       Blockchain Transactions System  (6)          Platform for Content Monetization embedded Content Promotion  (1)    Pancreatic adenocarcinoma classifier  (4)    Simulation Modeling in NGS  (5) Biological Engineering  (43) Biological Networks  (193) Biological Networks, Gene Regulation and Evolution  (479)    Virology  (10) Biomarkers & Medical Diagnostics  (571)    VOC – Volatile Organic Compounds as BioMarkers  (2) Biomedical Measurement Science  (173) BioSimilars  (112) BioTechnology – Venture Creation  (131)    Foundations for supporting Science and Education  (14)    Philanthropy to Academic Institution  (3) BioTechnology – Venture Creation, Venture Capital  (108)    Seeking Talent  (3) BiVAD  (1) Blindness  (6) Bone Disease and Musculoskeletal Disease  (82) Brain Basis of Emotion  (5) Business Career Consideration  (1) Ca2+ triggered activation  (61) Calcium  (21) Calcium Signaling  (71) Calmodulin Kinase and Contraction  (36) Cancer – General  (186) Cancer and Current Therapeutics  (411)    interventional oncology  (49)       Breast Cancer – impalpable breast lesions  (20)       Prostate Cancer: Monitoring vs Treatment  (9) CANCER BIOLOGY & Innovations in Cancer Therapy  (1,122)    Anaerobic Glycolysis  (51)    Cachexia  (18)    Cancer Genomics  (84)       Circulating Tumor Cells (CTC)  (27)          Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood  (17)             mRNA  (6)          MagSifter chip  (1)       KRAS Mutation  (9)       Li-fraumeni syndrome.  (3)       TP53 – Germline mutations  (8)    cancer metabolism  (28)    Funding Opportunities for Cancer Research  (12)    Genomic Expression  (150)    Glioblastoma  (7)    Hexokinase  (14)    Loss of function gene  (18)    Metabolic Immuno-Oncology  (21)    Metastasis Process  (15)    Methylation  (33)    Microbiome and Responses to Cancer Therapy  (10)    Monoclonal Immunotherapy  (29)    mtDNA  (13)    Oxidative phosphorylation  (56)    Pancreatic cancer  (10)    Pyruvate Kinase  (27)    The NCI Formulary  (1)    tumor microenvironment  (16)    Warburg effect  (50) Cancer Informatics  (104) Cancer Prevention: Research & Programs  (131) Cancer Screening  (108) Cancer Vaccines: Targeting Cancer Genes for Immunotherapy  (30)    Engineering Enhanced Cancer Vaccines  (3) cancer-general  (6) Cardiac and Cardiovascular Surgical Procedures  (328)    Aortic Valve: TAVR, TAVI vs Open Heart Surgery  (91)       Prosthesis-Patient Mismatch (PPM) in TAVI vs SAVR  (2)       TAVI vs Open Heart Surgery  (6)       Transcatheter Aortic Valve Replacement via the Transcarotid Access  (3)       Transcaval TAVR Procedure  (3)       Valve-in-Valve Procedure  (5)    Atrial Fibrilation (a-Fib), Cardiac Pacing and Arrhythmias  (18)    BackBeat’s Cardiac Neuromodulation Therapy (CNT) bioelectronic therapy  (1)    CABG  (47)    Cancer Surgery of the Heart  (10)    Cardiovascular Fluid Management: algorithms  (1)    Heart Transplant  (16)    Heart-Lung Transplant  (11)    Implantation  (3)    Left Main Coronary Artery Disease (LMCAD)  (3)    Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart  (22)    Mitral Valve: Repair and Replacement  (64)       TMVR – Transcatheter Mitral Valve Repair  (5)    PCI  (108)       Bioresorbable Vascular Scaffold (BVS)  (4)       Invasive FFR for PCI  (2)       Multivessel PCI FFR Guidance  (1)       Robotic-assisted percutaneous coronary intervention  (2)       Stent Retriever in endovascular thrombectomy  (3)    Peripheral Arterial Disease & Peripheral Vascular Surgery  (65)       Abdominal Aorta  (20)       Carotid Artery  (15)       Limb ischemia  (4)       Thoracic Aorta  (16)    Pulmonary Valve Replacement and Repair  (3)    Renal Denervation  (20)    Replacement  (1)    Robotically assisted Cardiothoracic Surgery  (2)    Tricuspid Valve Repair  (7)    Vena Caval Filters: Device for Prevention of Pulmonary Embolism and Thrombosis  (2) Cardiovascular Pharmacogenomics  (171) Cargo  (3) Cell Biology  (323) Cell Biology, Signaling & Cell Circuits  (672)    Apoptosis  (17)    Autophagy-Modulating Proteins  (6)    “Antibody–enzyme conjugates”  (6)    Cell Processing System in Cell Therapy Process Development  (27)    Endoplasmic reticulum  (3)    Enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)  (3)    Ubiquitin  (11) Cerebrovascular and Neurodegenerative Diseases  (123)    Stroke  (9) Chemical Biology and its relations to Metabolic Disease  (464)    #BIGAxisSummit  (1)    Gut Microbiome and Obesity  (8) Chemical Genetics  (350) Child and Adolescent Psychiatry  (13) Childhood cancer  (17) Childhood malnutrition  (3) children  (3) Circulating Progenitor Cells  (27)    Bone marrow derived cells  (17)    Endothelial cells  (7)    Umbilical cord cells  (6) Clinical & Translational  (238) Clinical Diagnostics  (220)    Mass automation of plasma proteins  (13) Clinical Genomics  (144) Coagulation Therapy and Internal Bleeding  (83) Cognition  (47) Commercialization  (20) Components and IRB related issues  (4) Computational Biology/Systems and Bioinformatics  (470)    Computational Histopathology  (3)    Meta-analysis of transcriptome data  (10) Conference Coverage with Social Media  (494)    MassBio  (3) coronavirus  (18) COVID-19  (20) CRISPR/Cas9 & Gene Editing  (192)    CRISPR alternative for editing genes without cutting  (14)       CAST – Alternative to CRISPR/Cas9  (3)       Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration  (4)    CRISPR applied to Human Germ Line  (13)       Gene Editing Impact on Longevity  (6) CT  (20) Cytokines  (20) Cytoskeleton  (85) Developmental biology  (107) Diabetes Mellitus  (146)    Artificial Pancreas for Type 2 Diabetes  (4)    Artificial Pancreas for Type1 Diabetes  (8)    Gestational diabetes  (5) Diagnostic Immunology  (61) Diagnostics and Lab Tests  (128)    Liquid Biopsy: Circulating Tumor Cells in Urine and Blood  (9) Digital HealthCare – biotech & internet joint ventures  (47) Disease Biology  (334) Disease Biology, Small Molecules in Development of Therapeutic Drugs  (487) DNA repair  (73)    Apoptosis  (13)    Autophagy  (13)    Cell death pathways  (19)    Proteolysis  (8)    Proteosome  (8) Drug Delivery Platform Technology  (157)    Drug Carrier Design  (21)       Medication Remote Compliance Monitoring  (3)    Exosomes: Natural Carriers for siRNA Delivery  (9) Drug Toxicity  (74) Ecosystems & Industrial Concentration in the Medical Device Sector  (172)    Cardiac & Vascular Repair Tools Subsegment  (128)    Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment  (14)    Massachusetts Niche Suppliers and National Leaders  (20) Electronic Health Record  (10) Embryology  (24) Empathy  (6) Endocrine Diseases  (60) Enzyme Induction  (46)    ion-transporting enzyme  (2)    K + -ATPase.  (1)    Na +  (2) Epigenetics and Environmental Factors  (35) Ethics and Leadership  (10) Executive Compensation – Big Pharma  (3) Fat soluble vitamins  (4) FDA  (71) FDA Regulatory Affairs  (358)    FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP, GLP, ISO 14155  (52)    ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics  (30) Fetal Ultrasound  (2) Fiction and medicine  (5) Frontiers in Cardiology and Cardiovascular Disorders  (929)    Acute Myocardial Infarction  (63)       Cardiogenic Shock  (5)    Anemia in CVD Patients  (6)    Cardio-Oncology  (4)    Cardiomyopathy  (57)    Cardiovascular Research  (187)       Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism  (64)       Pre-Clinical Animal Model Development  (23)    Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH)  (20)    Cost of Inpatient Stay for Cardiovascular Diagnosis for Admission  (1)    Electrophysiology  (111)       Ablation Procedure vs Drug Therapy  (2)       Arrhythmia Detection with Machine Learning Algorithms  (7)       Cardiotoxic Risks of Immune Checkpoint Inhibitors  (1)       Genomic Analysis of EKG Electrophysiology Genomics  (3)       implantable cardioverter defibrillator (ICD) and External Defibrillation  (1)       implantable pacemaker  (2)       Rare heart rhythm disorders and Long QT syndrome (LQTS)  (7)    Epigenetics and Cardiovascular Risks  (57)    Heart Failure (HF)  (51)       Acute coronary syndrome  (7)       congestive heart failure  (19)       Hypertensive Disorders of Pregnancy  (1)    Medical Devices R&D and Inventions  (212)       Assist Devices: LV  (3)       RV  (1)       Stents & Tools  (90)       Valves & Tools  (67)    Origins of Cardiovascular Disease  (422)       Atherogenic Processes & Pathology  (180)       Congenital Heart Disease  (34)          Genetic Mutations in Congenital Heart Disease  (4)       inflammation independent of lipid levels  (13)       Systemic Inflammatory Diseases as CVD Risk  (12)    Pharmacotherapy of Cardiovascular Disease  (356)       HTN  (176)       HTN in Youth  (8)       Resident-cell-based  (43)       Subarachnoid Hemorrhage (SAH)  (1)       Transthyretin amyloid cardiomyopathy (ATTR-CM)  (1)    Spontaneous Coronary Artery Dissection (SCAD)  (6)    Stroke  (15)       endovascular thrombectomy  (6)    Vascular Diseases  (21)       mesenteric ischemia  (3) Future Pandemics Inform-graphics  (1) Gastroenterology  (38) Gene Regulation  (232) Gene Regulation and Evolution  (137) Genetics & Innovations in Treatment  (176) Genetics & Pharmaceutical  (203) Genome Biology  (967)    Exosomes  (25)    Gene Therapy & Gene Editing Development  (42)    mRNA Therapeutics  (20)    Mutagenesis  (27)    Single Cell Genomics  (25)    Single-cell sequencing  (20)    Variation in human protein-coding regions  (35) Genomic Endocrinology  (42) Genomic Testing: Methodology for Diagnosis  (416) Genomics Pharmacy  (40) Global Market of Medical Devices Technology  (2) Global Medical Publishers by Country  (3) Global Partnering & Biotech Investment  (47) GLP  (4) Glycobiology: Biopharmaceutical Production  (16) Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics  (28) Health Care System by Country  (58)    AI Models in Healthcare  (12)    Centers for Medicare & Medicaid Services  (8)    Health in Israel  (2)    India  (1)    United States  (27)       Hospital-based Medical Innovations  (10)       Medical Recertification and Maintenance of Certification (MOC)  (1) Health Economics and Outcomes Research  (384)    Women Health  (18)       Heart and Brain Disease in Women  (3) Health Law & Patient Safety  (165)    and Bioethics  (14)    Biotechnology  (12)    Health Law Policy  (13) HealthCare IT  (138) Healthcare Reform  (117)    Accountable Care Organizations  (26)    Affordable Care Act  (29)       Repair  (1)       Repeal ACA  (1)       Replace  (1)    Federal Budget Appropriations  (26)    Healthcare costs and reimbursement  (59)    Indigent Nutrition  (14)    Medicare and Medicaid  (20)    Prescription Drugs Costs  (21)    Skilled Nursing Facilities  (6)    Technology Capital Expenses  (15)    Uninsured and Underinsured  (20) Hematology  (100)    Acute lymphocytic leukemia  (18)    Acute myelocytic leukemia  (21)    Hematopoiesis  (48)    Lymphoma  (21) History and physical exam  (6) Human aging  (27) Human Immune System in Health and in Disease  (246) Human Sensation and Cellular Transduction: Physiology and Therapeutics  (21) Image Processing/Computing  (41) Imaging-based Cancer Patient Management  (116) Immuno-Oncology & Genomics  (133)    mRNA platform in Drug DIscovery  (6) Immunodiagnostics  (139)    Cancer-Immune Interactions  (29)    CNS-Immune Interface  (5)    Neuronal Circuits  (4) Immunology  (123)    Adaptive Immune Response to Biomaterials and Tissue Repair  (13)    Antibody Responses Predict Antigen Exposure  (17)    Cytokine Receptor Structure  (8)    Human Antibody Response  (18)    Human Circulating Antibody Repertoire  (11)    Human Naive B Cell Repertoire  (8)    MHC Repertoires for Antigen Prediction  (8)    Protection Against Autoimmune Disease  (11)    Synthetic Immunology: Hacking Immune Cells  (15) Immunotherapy  (133)    CAR-T  (14)    combination immunotherapies.  (14)    Efficacy of Anti-Tumor T Cells  (13)    Engineering Better T Cells  (8)    Immune Engineering  (17)    Immune Modulatory  (15)    Integrin-targeted Combination Immunotherapy  (6)    Modulating Macrophages in Cancer Immunotherapy  (16)    NK Cell-Based Cancer Immunotherapy  (19)    Synergistic Innate and Adaptive Immunotherapy  (14) Income Disparity  (2) Infectious Disease & New Antibiotic Targets  (162)    Antibiotic resistance  (7)    Viral diseases  (37)       Myocarditis  (1) Infectious Disease Immunodiagnostics  (58)    Virology – Vector-borne DIsease  (17) Inflammasome  (29)    Anti-tumor necrosis factor drugs (TNF inhibitors)  (3) Innovation in Immunology Diagnostics  (111)    Universal Immune Cell Therapies (uICT)  (11) Innovations  (186)    R&D Expenditure  (8) Innovations in Neurophysiology & Neuropsychology  (145)    Age and Life Expectancy  (3)    autism spectrum disorder  (1)    Circadian Rhythm and Sleep  (6)    hNPCs  (1)    Nervous System Function  (2)    Relapsing Multiple Sclerosis  (1) Intellectual Property  (83)    Disputes and Settlements  (9)    IP Valuation Models – Pricing Intangible Assets  (7)    Patent Law in Biotech  (12) Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough  (119) International Global Work in Pharmaceutical  (190) Interventional Oncology: Radiofrequency Ablation, Transarterial Chemoembolization, Microwave Ablation and Irreversible Electroporation (IRE)  (12) Interviews with Scientific Leaders  (315)    Albany Medical Center Prize in Medicine and Biomedical Research  (2)    Annual Breakthrough Prize  (4)    Annual Lewis S. Rosenstiel Award  (2)    Awards in Cardiology and Cardiovascular Medicine  (6)    CEOs of Biotech Companies  (3)    Gerald D Aurbach Award for Outstanding Translational Research  (2)    Interviews with Key Opinion Leaders (KOLs)  (10)    James Prize in Science and Technology Integration  (2)    Jessie Stevenson Kovalenko Medal – Medical Sciences  (2)    Lemelson-MIT Prize  (2)    Life Sciences Breakthrough Prize  (5)    Mosteller Statistician of the Year Award  (2)    Mourning the Loss of a Scientific Leader  (3)    National Academy of Sciences AWARDS  (4)    Nobel Prize Winners  (29)    Noble Prize (Not Nobel Prize)  (2)    Paul Marks Prize for Cancer Research  (2)    Russ Prize recognizes bioengineering achievements worldwide  (2)    The Dan David Prize  (6)    Warren Alpert Foundation Prize Recipients  (4)    Wolf Prize  (2)    Wolf Prize in Medicine  (2)    women in science  (5) Investment in Technological Breakthrough  (60) Ionic Transporters Na+  (25) IP Development by LPBI Group Team  (14) IP Development by LPBI Group Team & Other Organizations  (8) ISO 14155  (3) Joint Venture – SBH & M3DP: SOP and Arrangements  (1) Justice & Law  (1) K  (15) Lab-on-a-chip  (2) Landscape  (1) Lasers and photonics  (18)    Midrange IR spectroscopy  (1) Law and Medicine Conflicts  (14) Leadership, Power, Social Interlocking Connections  (13) Lipid metabolism  (109)    Fatty acids  (38)    Lipids  (38)    PCSK9 Inhibitor Therapy  (19) Lipidomics  (11) Liposome  (4) Liver & Digestive Diseases Research  (122) LPBI Group, e-Scientific Media, DFP, R&D-M3DP, R&D-Drug Discovery, US Patents: SOPs and Team Management  (143)    Award Nominations  (5)    BioMed e-Books e-Series by LPBI Group  (9)    Feedback from Investors: LPBI Portfolio of Five Businesses  (2)    LPBI Group Founder – Aviva Lev-Ari  (27)    PhD  (1)    RN  (1) LPBI Management  (23) Massachusetts Academy of Sciences (MAS)    (2) Materials Science & Engineering  (37)    Organic BioElectronics  (2) Math  (13)    Great Discoveries  (7) Mechanical Assist Devices: LVAD  (4) Medical and Population Genetics  (193) Medical Devices R&D Investment  (242)    21st Century Cures Act  (2)    CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP  (14)    Rhythm management device hardware: dual-chamber pacemakers  (1)       Systolic HTN  (1) Medical Imaging Technology  (59) Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound  (164)    Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI)  (3)    Echocardiography  (3)    MRI  (18)    Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT  (6)    Ultra Sound  (10) Melatonin & Circadian Regulation  (9) memory loss  (1) Metabolism  (239)    Biochemical pathways  (144)       Enzymes and isoenzymes  (73)          Dehydrogenase  (16)          Kinase  (28)          Phosphatase  (9)          Phosphorylase  (22)          tyrosine decarboxylases  (3)    Inosine nucleotides  (9)    Leloir pathway  (6)    microbiome  (7)    Pentose monophosphate shunt  (14)    Pyridine nucleotides  (28)       Pyridine nucleotide transhydrogenase  (7) Metabolomics  (321) Methods  (37) Mg++  (10) Microbiologial genetics  (36) Microbiology  (68)    Virology  (14) Micronutrients  (16) Microvesicle  (7) Microwave Ablation and Irreversible Electroporation (IRE)  (1) Mobile Healthcare  (5) Molecular Genetics & Pharmaceutical  (377)    Organoids  (3) Monoclonal antibody therapy  (14) Mutant Gene Expression  (42) Myocardial adenine nucleotide metabolism  (6) Myocardial Ischemia  (26) Myocardial Metabolism  (36) Na-K transport  (40) Na-K-ATPase  (27) Nanotechnology for Drug Delivery  (99) Nephrology  (46) Nephrology & Regenerative medicine  (9) Neurodegenerative Diseases  (89)    hNPCs  (3)    MS  (5) Neurohumoral Transmission  (68)    Ca2+ triggered activation  (21)    Calmodulin  (13)    Parkinson’s disease dyskinesia levodopa  (3)    PKC  (13)    Synaptic vesicle  (20) Neurological Diseases  (121) Neuroscience  (126) Next Generation Sequencing (NGS)  (27)    Nanopore sequencing  (1) NIH Common Fund  (1) Nitric Oxide in Health and Disease  (136) Nuclear Medicine  (11) Nutrigenomics  (68) Nutrition  (195)    Nutritional Supplements: Atherogenesis, lipid metabolism  (50) Nutrition and Phytochemistry  (62)    Minerals in Medicine  (4)    Plant extract  (22) Nutrition Disorders  (31) Nutritional Supplements: Atherogenesis  (31) Obesity  (19) Oligonucleotide Therapeutics & Delivery  (7) Oncolytic virus & OncoViro-Therapy  (22)    Synthetic Virology  (1) Organ-on-a-Chip & 3D Printing in Life Sciences  (7) Pain: Etiology, Genetics & Innovations in Treatment  (24) Parasitology  (5)    Malaria  (4)    Tropical diseases  (1) Patents  (34) Patient Experience  (66)    Art therapy  (1)    Hospital reputation  (7)    Humor  (1)    Music therapy  (2)    Pain Alleviation  (7)    Patient Outlook  (28)    Reputation of Interventionist  (4)    Support Staff  (13)    Supportive therapies  (6)       laughfter  (1)    Surgical Procedure  (9) Patient Experience: Personal Memories of Invasive Medical Intervantion  (30) Patient’s Voice: Personal Experience with Invasive Medical Procedures  (18) Perioperative Statins at Noncardiac Surgery  (2) Personal Health Applications: Tech Innovations serves HealhCare  (43) Personalized and Precision Medicine & Genomic Research  (736)    Longevity  (3)    New Drug Approval  (5)    Patient-centered Medicine  (39)       cell-based therapy  (9)       stem cell biology and patient-specific  (7)    Personalized Medicine Coalition  (10)    Precision Cancer Medicine  (31) Phagophore  (2) Pharmaceutical Analytics  (261)    Pharmacologic toxicities  (62) Pharmaceutical Discovery  (109)    Rapid automation of plasma protein pools  (17) Pharmaceutical Drug Discovery  (200)    Drug Development Process  (55)       Drug Discovery Chemistry  (29)    drug repurposing  (10) Pharmaceutical Industry Competitive Intelligence  (343)    Pharmacovigilance  (7)    Value-based Drug Pricing  (8) Pharmaceutical R&D Informatics  (44) Pharmaceutical R&D Investment  (299) Pharmacodynamics and Pharmacokinetics  (24) Pharmacogenomics  (159) Photography Collection  (1) Physics  (12) Placenta  (7) Population genetics  (27) Population Health Management  (204)    Evolution of Biology Through Culture  (14)    U.S. Employment-to-Population Ratio  (8) Population Health Management, Genetics & Pharmaceutical  (643)    COVID-19  (157)       Biomarkers: Inflammation  (37)       Cancer Researchers Fighting COVID-19  (14)       COVID-19 effects on Human Heart  (15)       COVID-19: Pandemic Surgery Guidance  (19)       Economic Impact of Coronavirus Pandemic  (41)       number of asymptomatic infections  (27)       Treatment Protocols for COVID-19  (62)    SARS-CoV-2  (141)       Coronavirus Gene Expression  (66)          SARS-CoV-2 circulating variants   (14)          SARS-CoV-2 Viral Variants  (19)       Glycosylation and its Role in SARS-CoV-2 Viral Pathogenesis  (2)       Immune-Mediation (independent immunopathology: lung and reticuloendothelial system)  (30)       Mechanisms of infection by SARS-CoV-2  (21)       SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus  (35)          SARS-COV2 Hijacking the Complement and Coagulation Systems  (19)       Seasonality & Environmental Factors in Resurgence  (26)       Serology tests for coronavirus antibodies  (44)       T-cell response to SARS-CoV-2 infection  (14)       Vaccinology  (51)          Mechanism of Thrombosis with AZ & J&J COVID-19 Vaccines  (5)       Virtual Drug Molecule Screening targeting SAR-CoV-2 proteins  (8)    Virus Infective Acute Respiratory Syndrome: SARS-CoV  (92) Population Health Management, Nutrition and Phytochemistry  (162) Preimplantation Genetic Diagnosis and Reproductive Genomics  (13) Protein-energy malnutrition  (12) Proteomics  (367)    Amino acids  (54)    Proteins  (138) Pulmonary diseases  (16)    Lung and pulmonology  (15) Pulmonary pathology  (8) Radio Frequency (RF)-based Surgical Solutions  (2) REAL TIME Conference Coverage Twitter’s Hashtags and Handles per Presentation/session  (50) Regenerative Biology and Medicine  (92) Regulated Clinical Trials: Design, Methods, Components and IRB related issues  (265) Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics  (113) Reproductive Biology & Bio Instrumentation  (78) RNA Biology  (81)    RNA interference (RNAi) therapeutic  (4) RNA Biology, Cancer and Therapeutics  (64) RVAD  (1) SBIR, SBA, NIH, NSF  (3) Schizophrenia  (16) Scientific & Biotech Conferences: Press Coverage  (182) Scientific Publishing  (609)    Curation  (585)       Curation methodology  (40)       De novo synthesis  (16)       Dialectic  (17)       Discovery process  (72)       Evolutionary cognition  (52)       Experimental validation  (91)       Explanatory  (91)       Historical relevance  (71)       Technology Advance Assessment of  (69)       Theoretic convergence  (27)    Open Access Journals  (37) Scientist: Career considerations  (197)    Big Data & Analytics  (17)    Data Science  (13)    Women in Life Sciences  (12) Scoop.it  (19) Sensors & Analytics  (18) Sepsis  (2) Severe Autism  (3) Signaling  (102)    Phosphorylation  (43)    S-nitrosylation  (13)    Ubiquitinylation  (34) Signaling & Cell Circuits  (130) single cell sequencing  (3) Small Molecules in Development of Therapeutic Drugs  (71) Social Development  (15) Specialized 3D BioPrinters (Cornea  (1) Statistical Methods for Research Evaluation  (137) Stem Cells for Regenerative Medicine  (177)    Cardiac muscle regeneration  (19)    Competition in regenerative stem cell science  (18)    Human neural progenitor cells  (8)    Skeletal muscle regeneration  (9) STORM  (2) Stress Disorders  (19) Substance Abuse  (4) Systemic Inflammatory Response Related Disorders  (161)    Inflammatory Pathophysiology  (9) Technology Transfer: Biotech and Pharmaceutical  (354) therapeutics  (3) Tissue Engineering and Regenerative Medicine  (22) Tissue Microenvironment  (5) Transarterial Chemoembolization  (2) Transcriptomics  (47) Transformative Technologies in Healthcare  (23) Translational Science  (230)    Best evidence  (52)    Bias measurement tools  (2)    Evidence-based decision-making  (29)    Inferential analysis  (25)    Intra-rater error  (1)    Quality Assurance  (8)    Random Error  (2)    Systematic Error (Bias)  (6)    Total error  (2)    Translational Effectiveness  (49)    Translational Research  (92) Trends in Global Economy  (6) Uncategorized  (1,019) Unfolded Protein Response (UPR)  (6) US and Global Economy: Trends and Findings  (9) Venture Capital  (47)    Income Geographic Distribution  (3)    Institutional Capital Raised by Female Founders  (6) virology  (10) Vision  (7) Voices of Patients and Healthcare Providers  (22) Water Transporters  (8) Wearable Tech + Digital Health  (5) Anemia  (22) Neutropenia  (8) Neutrophilia  (9) Platelet count disorder  (9) Folate and B12  (7) Iron deficiency  (5) Myelodysplasia  (13) Myelofibrosis  (10)

• Meta

  • Log in
  • Entries feed
  • Comments feed
  • WordPress.org

• • 2012pharmaceutical
  • sjwilliamspa