Helical Conformation of the SEVI Precursor Peptide PAP248-286, a Dramatic Enhancer of HIV Infectivity, Promotes Lipid Aggregation and Fusion

AbstractIn previous in vivo studies, amyloid fibers formed from a peptide ubiquitous in human seminal fluid (semen-derived enhancer of viral infection (SEVI)) were found to dramatically enhance the infectivity of the HIV virus (3–5 orders of magnitude by some measures). To complement those studies, we performed in vitro assays of PAP248-286, the most active precursor to SEVI, and other polycationic polymers to investigate the physical mechanisms by which the PAP248-286 promotes the interaction with lipid bilayers. At acidic (but not at neutral) pH, freshly dissolved PAP248-286 catalyzes the formation of large lipid flocculates in a variety of membrane compositions, which may be linked to the promotion of convective transport in the vaginal environment rather than transport by a random Brownian motion. Furthermore, PAP248-286 is itself fusiogenic and weakens the integrity of the membrane in such a way that may promote fusion by the HIV gp41 protein. An α-helical conformation of PAP248-286, lying parallel to the membrane surface, is implicated in promoting bridging interactions between membranes by the screening of the electrostatic repulsion that occurs when two membranes are brought into close contact. This suggests that nonspecific binding of monomeric or small oligomeric forms of SEVI in a helical conformation to lipid membranes may be an additional mechanism by which SEVI enhances the infectivity of the HIV virus

Allelic diversity and patterns of selection at the major histocompatibility complex class I and II loci in a threatened shorebird, the Snowy Plover (Charadrius nivosus)

Background: Understanding the structure and variability of adaptive loci such as the major histocompatibility complex (MHC) genes is a primary research goal for evolutionary and conservation genetics. Typically, classical MHC genes show high polymorphism and are under strong balancing selection, as their products trigger the adaptive immune response in vertebrates. Here, we assess the allelic diversity and patterns of selection for MHC class I and class II loci in a threatened shorebird with highly flexible mating and parental care behaviour, the Snowy Plover (Charadrius nivosus) across its broad geographic range. Results: We determined the allelic and nucleotide diversity for MHC class I and class II genes using samples of 250 individuals from eight breeding population of Snowy Plovers. We found 40 alleles at MHC class I and six alleles at MHC class II, with individuals carrying two to seven different alleles (mean 3.70) at MHC class I and up to two alleles (mean 1.45) at MHC class II. Diversity was higher in the peptide-binding region, which suggests balancing selection. The MHC class I locus showed stronger signatures of both positive and negative selection than the MHC class II locus. Most alleles were present in more than one population. If present, private alleles generally occurred at very low frequencies in each population, except for the private alleles of MHC class I in one island population (Puerto Rico, lineage tenuirostris). Conclusion: Snowy Plovers exhibited an intermediate level of diversity at the MHC, similar to that reported in other Charadriiformes. The differences found in the patterns of selection between the class I and II loci are consistent with the hypothesis that different mechanisms shape the sequence evolution of MHC class I and class II genes. The rarity of private alleles across populations is consistent with high natal and breeding dispersal and the low genetic structure previously observed at neutral genetic markers in this species

Population differentiation and historical demography of the threatened snowy plover Charadrius nivosus (Cassin, 1858)

Delineating conservation units is a complex and often controversial process that is particularly challenging for highly vagile species. Here, we reassess population genetic structure and identify those populations of highest conservation value in the threatened snowy plover (Charadrius nivosus, Cassin, 1858), a partial migrant shorebird endemic to the Americas. We use four categories of genetic data—mitochondrial DNA (mtDNA), microsatellites, Z-linked and autosomal single nucleotide polymorphisms (SNPs)—to: (1) assess subspecies delineation and examine population structure (2) compare the sensitivity of the different types of genetic data to detect spatial genetic patterns, and (3) reconstruct demographic history of the populations analysed. Delineation of two traditionally recognised subspecies was broadly supported by all data. In addition, microsatellite and SNPs but not mtDNA supported the recognition of Caribbean snowy plovers (C. n. tenuirostris) and Floridian populations (eastern C. n. nivosus) as distinct genetic lineage and deme, respectively. Low migration rates estimated from autosomal SNPs (m < 0.03) reflect a general paucity of exchange between genetic lineages. In contrast, we detected strong unidirectional migration (m = 0.26) from the western into the eastern nivosus deme. Within western nivosus, we found no genetic differentiation between coastal Pacific and inland populations. The correlation between geographic and genetic distances was weak but significant for all genetic data sets. All demes showed signatures of bottlenecks occurring during the past 1000 years. We conclude that at least four snowy plover conservation units are warranted: in addition to subspecies nivosus and occidentalis, a third unit comprises the Caribbean tenuirostris lineage and a fourth unit the distinct eastern nivosus deme

Recent advances in organic synthesis using light-mediated n-heterocyclic carbene catalysis

The combination of photocatalysis with other ground state catalytic systems have attracted much attention recently due to the enormous synthetic potential offered by a dual activation mode. The use of N-heterocyclic carbene (NHC) as organocatalysts emerged as an important synthetic tool. Its ability to harness umpolung reactivity by the formation of the Breslow intermediate has been employed in the synthesis of thousands of biologically important compounds. However, the available coupling partners are relatively restricted, and its combination with other catalytic systems might improve its synthetic versatility. Thus, merging photoredox and N-heterocyclic carbene (NHC) catalysis has emerged recently as a powerful strategy to develop new transformations and give access to a whole new branch of synthetic possibilities. This review compiles the NHC catalyzed methods mediated by light, either in the presence or absence of an external photocatalyst, that have been described so far, and aims to give an accurate overview of the potential of this activation modeL.M. acknowledges the Autonomous Community of Madrid (CAM) for the financial support (PEJD-2019-PRE/AMB-16640 and SI1/PJI/ 2019-00237) and for an “Atracción de Talento Investigador” contract (2017-T2/AMB-5037

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion