Background:The TRPV1 ion channel alters its ionic selectivity in an activity-dependent manner. Results: Mutations in multiple subregions of the TRPV1 pore selectively augment or reduce large cation permeability changes. Conclusion: Side chain identities within the pore shape conformational changes underlying dynamic ionic selectivity. Significance: Understanding TRPV1 dynamic ionic selectivity will provide crucial insight into channel activation and nociceptive signaling.

The sodium/iodide symporter (NIS) mediates active I− transport in the thyroid—the first step in thyroid hormone biosynthesis—with a 2 Na+: 1 I− stoichiometry. The two Na+ binding sites (Na1 and Na2) and the I− binding site interact allosterically: when Na+ binds to a Na+ site, the affinity of NIS for the other Na+ and for I− increases significantly. In all Na+-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na+ ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues—S66, D191, Q194, and Q263—are also involved in Na+ coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I−. These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance.

The objective of this study is to discuss selected viruses including COVID-19 and their potential elimination processes in hot springs. Studies in Colombia are limited and this scientific discussion provides necessary information regarding these viruses. This includes studies both in Colombia and international levels on the following subjects: i) the presence of viruses in hot springs, ii) the non-oxidative water treatment in hot springs, iii) the elimination strategies of viruses; and iv) the influence of COVID-19 in hot springs. The results of this discussion indicate that in order for thermal waters to guarantee the elimination of the viruses originating from faecal and nonfaecal derived, and the COVID-19 virus, a monitoring scheme is required to identify an effective disinfection of waters to control these pathogens.

The ladybird Cheilomenes sexmaculata is reported for the first time from Colombia. Previously, this species was recorded in Asia and Australia, then introduced to South America and reported from countries such as Chile, Ecuador, Perú, and Venezuela, where it is used for biological control.

Through the study of neurotransmitter secretion at the single-vesicle resolution, we can advance the understanding of membrane fusion dynamics, the positive and negative side effects from drug treatments, and the mechanisms of neurological diseases on synaptic transmissions, such as Parkinson's disease. To monitor these rapid events from neurosecretory cells, on the scale of milliseconds or less, amperometry is widely used and has the fine temporal resolution necessary through oxidation of neurotransmitters at an electrode. However, traditional single-cell amperometry methods are low-throughput and time-consuming in order to gather a large set of data to develop statistically significant conclusions. In this work, a monolithic CMOS device is developed which integrates 1024 electrochemical detectors. The CMOS chip is designed with 1024 transimpedance amplifiers arranged in a 32 Â 32 array and using post-CMOS fabrication, 1024 on-chip platinum microelectrodes are integrated onto the surface of the CMOS chip. The electrochemical detector array operates at a sampling rate of 10 kS/s (can operate as fast as 40 kS/s) and achieves a noise level of $450 fA RMS when dry, and $ 2 pA RMS when electrolytic solution is in contact. We successfully demonstrated massively parallelized neurotransmitter measurements from human neuroblastoma cells (SH-SY5Y), a cell model often used to study Parkinson's disease. A single set of measurements in less than a minute collected over 7000 secretion events at a single-vesicle resolution. The revealed characteristics of the SY5Y cells in our study show an average half-width of 1.63 ms, an average of 94 secretion events per cell, and an average of 1.86 attomoles of released neurotransmitter. We also demonstrated that this technology can be used to accelerate the studies of drug effects on exocytosis.

As the IAU heads towards its second century, many changes have simultaneously transformed Astronomy and the human condition world-wide. Amid the amazing recent discoveries of exoplanets, primeval galaxies, and gravitational radiation, the human condition on Earth has become blazingly interconnected, yet beset with ever-increasing problems of over-population, pollution, and never-ending wars. Fossil-fueled global climate change has begun to yield perilous consequences. And the displacement of people from war-torn nations has reached levels not seen since World War II.

Platelet-derived growth factor receptor alpha (PDGFRalpha) interacts with PDGFs A, B, C and AB, while PDGFRbeta binds to PDGFs B and D, thus suggesting that PDGFRalpha is more promiscuous than PDGFRbeta. The structural analysis of PDGFRalpha-PDGFA and PDGFRalpha-PDGFB complexes and a molecular explanation for the promiscuity of PDGFRalpha and the specificity of PDGFRbeta remain unclear. In the present study, we modeled the three extracellular domains of PDGFRalpha using a previous crystallographic structure of PDGFRbeta as a template. Additionally, we analyzed the interacting residues of PDGFRalpha-PDGFA and PDGFRalpha-PDGFB complexes using docking simulations. The validation of the resulting complexes was evaluated by molecular dynamics simulations. Structural analysis revealed that changes of non-aromatic amino acids in PDGFRalpha to aromatic amino acids in PDGFRbeta (I139F, P267F and N204Y) may be involved in the promiscuity of PDGFRalpha. Indeed, substitution of amino acids with few probabilities of rotamer changes in PDGFRbeta (M133A, N163E and N179S) and energy stability due to the formation of hydrogen bond in PDGFRbeta could explain the specificity of PDGFRbeta. These results may be used as an input for a better and more specific drug and peptide design targeting diseases related with the malfunction of PDGFs and PDGFRalpha such as cancer and atherosclerosis.

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