Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.

Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis, and as drug targets. Here, we show that membrane proteins have dramatically fewer detectable orthologs than water-soluble proteins, less than half in most species analyzed. This sparse distribution could reflect rapid divergence or gene loss. We find that both mechanisms operate. First, membrane proteins evolve faster than water-soluble proteins, particularly in their exterior-facing portions. Second, we demonstrate that predicted ancestral membrane proteins are preferentially lost compared with water-soluble proteins in closely related species of archaea and bacteria. These patterns are consistent across the whole tree of life, and in each of the three domains of archaea, bacteria, and eukaryotes. Our findings point to a fundamental evolutionary principle: membrane proteins evolve faster due to stronger adaptive selection in changing environments, whereas cytosolic proteins are under more stringent purifying selection in the homeostatic interior of the cell. This effect should be strongest in prokaryotes, weaker in unicellular eukaryotes (with intracellular membranes), and weakest in multicellular eukaryotes (with extracellular homeostasis). We demonstrate that this is indeed the case. Similarly, we show that extracellular water-soluble proteins exhibit an even stronger pattern of low homology than membrane proteins. These striking differences in conservation of membrane proteins versus water-soluble proteins have important implications for evolution and medicine

Distanciamiento social ante la COVID-19: Simulación del aforo máximo de personas mediante PHP

Population confluence in internal or external areas considerably increases transmission of COVID-19, due to not respecting the social distancing established by the health system. The objective of this work was to make use of programming techniques, using the PHP language (hypertext preprocessor), for the development of an application that simulates the maximum capacity of people who can enter an internal or external area. The methodology allowed recognizing common internal and external areas, configurating to the development environment, coding, simulation proposing and executing of the simulator where a practical case and ten places were evaluated to determine its reliability. The simulator provided the maximum capacity of people who can enter an internal or external area, complying with the social distancing of 2 m. The results made it possible to know that the use of information technologies through programming techniques and the PHP language contributed to being a technological alternative for the fight against the spread of the virus.La confluencia poblacional en áreas internas o externas incrementa considerablemente la trasmisión de la COVID-19, por no respetar el distanciamiento social que establece el sistema de salud. El objetivo de este trabajo fue hacer uso de técnicas de programación, empleando el lenguaje PHP (preprocesador de hipertexto), para el desarrollo de una aplicación que simule el aforo máximo de personas que pueden ingresar a un área interna o externa. La metodología permitió el reconocimiento de áreas internas y externas comunes, configuración al entorno de desarrollo, codificación, propuesta de simulación y ejecución del simulador donde se ha evaluado un caso práctico y diez lugares para determinar su confiabilidad. El simulador brindó el aforo máximo de personas que pueden ingresar a un lugar de área interna o externa cumpliendo el distanciamiento social de 2 m. Los resultados permitieron conocer que el uso de las tecnologías de información a través de las técnicas de programación y el lenguaje PHP contribuyó en ser una alternativa tecnológica para la lucha contra la propagación del virus

Microfluidic Reactors for Carbon Fixation under Ambient-Pressure Alkaline-Hydrothermal-Vent Conditions

The alkaline-hydrothermal-vent theory for the origin of life predicts the spontaneous reduction of CO₂, dissolved in acidic ocean waters, with H₂ from the alkaline vent effluent. This reaction would be catalyzed by Fe(Ni)S clusters precipitated at the interface, which effectively separate the two fluids into an electrochemical cell. Using microfluidic reactors, we set out to test this concept. We produced thin, long Fe(Ni)S precipitates of less than 10 µm thickness. Mixing simplified analogs of the acidic-ocean and alkaline-vent fluids, we then tested for the reduction of CO₂. We were unable to detect reduced carbon products under a number of conditions. As all of our reactions were performed at atmospheric pressure, the lack of reduced carbon products may simply be attributable to the low concentration of hydrogen in our system, suggesting that high-pressure reactors may be a necessity

CO₂ reduction driven by a pH gradient

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life's emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog-and proposed evolutionary predecessor-of the Wood-Ljungdahl acetyl-CoA pathway of modern archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate (HCOO-), which has proven elusive in mild abiotic settings. Here we show the reduction of CO2 with H2 at room temperature under moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labeling with 13C confirmed formate production. Separately, deuterium (2H) labeling indicated that electron transfer to CO2 does not occur via direct hydrogenation with H2 but instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, removing H2, or eliminating the precipitate yielded no detectable product. Our work demonstrates the feasibility of spatially separated yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches

Distanciamiento social ante la COVID-19: Simulación del aforo máximo de personas mediante PHP

La confluencia poblacional en áreas internas o externas incrementa considerablemente la trasmisión de la COVID-19, por no respetar el distanciamiento social que establece el sistema de salud. El objetivo de este trabajo fue hacer uso de técnicas de programación, empleando el lenguaje PHP (preprocesador de hipertexto), para el desarrollo de una aplicación que simule el aforo máximo de personas que pueden ingresar a un área interna o externa. La metodología permitió el reconocimiento de áreas internas y externas comunes, configuración al entorno de desarrollo, codificación, propuesta de simulación y ejecución del simulador donde se ha evaluado un caso práctico y diez lugares para determinar su confiabilidad. El simulador brindó el aforo máximo de personas que pueden ingresar a un lugar de área interna o externa cumpliendo el distanciamiento social de 2 m. Los resultados permitieron conocer que el uso de las tecnologías de información a través de las técnicas de programación y el lenguaje PHP contribuyó en ser una alternativa tecnológica para la lucha contra la propagación del virus.//Population confluence in internal or external areas considerably increases transmission of COVID-19, due to not respecting the social distancing established by the health system. The objective of this work was to make use of programming techniques, using the PHP language (hypertext preprocessor), for the development of an application that simulates the maximum capacity of people who can enter an internal or external area. The methodology allowed recognizing common internal and external areas, configurating to the development environment, coding, simulation proposing and executing of the simulator where a practical case and ten places were evaluated to determine its reliability. The simulator provided the maximum capacity of people who can enter an internal or external area, complying with the social distancing of 2 m. The results made it possible to know that the use of information technologies through programming techniques and the PHP language contributed to being a technological alternative for the fight against the spread of the virus

Promotion of protocell self-assembly from mixed amphiphiles at the origin of life

Vesicles formed from single-chain amphiphiles (SCAs) such as fatty acids probably played an important role in the origin of life. A major criticism of the hypothesis that life arose in an early ocean hydrothermal environment is that hot temperatures, large pH gradients, high salinity and abundant divalent cations should preclude vesicle formation. However, these arguments are based on model vesicles using 1–3 SCAs, even though Fischer–Tropsch-type synthesis under hydrothermal conditions produces a wide array of fatty acids and 1-alkanols, including abundant C10–C15 compounds. Here, we show that mixtures of these C10–C15 SCAs form vesicles in aqueous solutions between pH ~6.5 and >12 at modern seawater concentrations of NaCl, Mg2+ and Ca2+. Adding C10 isoprenoids improves vesicle stability even further. Vesicles form most readily at temperatures of ~70 °C and require salinity and strongly alkaline conditions to self-assemble. Thus, alkaline hydrothermal conditions not only permit protocell formation at the origin of life but actively favour it

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation

Twenty-Five Years of Convoluted Health Reforms in Mexico

Núria Homedes and Antonio Ugalde discuss 25 years of reform to the Mexican health care system and argue that although costs and accessibility have increased, health inequities, efficiency, productivity, and quality of care have not improved