Palladium-Catalyzed Synthesis of Bis-Substituted Sulfoxonium Ylides

The lack of general access to bis-substituted sulfoxonium ylides is addressed by developing a palladium-catalyzed C–H cross-coupling of α-ester sulfoxonium ylides with (hetero)­aryl iodides, bromides, and triflates. Three different catalysts have been evaluated. This method is amenable to the late-stage functionalization of active pharmaceutical ingredients

Disentangling serology to elucidate henipa- and filovirus transmission in Madagascar fruit bats.

Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food. We aimed to (a) document the extent of henipa- and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data. To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa- and filovirus dynamics in three Madagascar fruit bat species. We uncovered serological evidence of exposure to Hendra-/Nipah-related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar-related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola-related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population-level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age-structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult-age bats. Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population-level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.National Geographic Society (Young Explorer’s and Waitt grants to CEB) PIVOT (research grant to CEB) National Science Foundation (Dissertation Improvement Grant and Graduate Research Fellowship to CEB) Princeton University (Walbridge Research Fund Grant to CEB; Center for Health and Well-being Grant to CJM) a Biological Defense Research Directorate of the Naval Medical Research Center and the Department of Health and Human Services, National Institutes of Health (research grant AI054715 to CCB) Queensland Government Accelerate Postdoctoral Research Fellowship to AJP The Alborada Trust (JLNW

Structure of a single-chain Fv bound to the 17 N-terminal residues of huntingtin provides insights into pathogenic amyloid formation and suppression.

Huntington's disease is triggered by misfolding of fragments of mutant forms of the huntingtin protein (mHTT) with aberrant polyglutamine expansions. The C4 single-chain Fv antibody (scFv) binds to the first 17 residues of huntingtin [HTT(1-17)] and generates substantial protection against multiple phenotypic pathologies in situ and in vivo. We show in this paper that C4 scFv inhibits amyloid formation by exon1 fragments of huntingtin in vitro and elucidate the structural basis for this inhibition and protection by determining the crystal structure of the complex of C4 scFv and HTT(1-17). The peptide binds with residues 3-11 forming an amphipathic helix that makes contact with the antibody fragment in such a way that the hydrophobic face of this helix is shielded from the solvent. Residues 12-17 of the peptide are in an extended conformation and interact with the same region of another C4 scFv:HTT(1-17) complex in the asymmetric unit, resulting in a β-sheet interface within a dimeric C4 scFv:HTT(1-17) complex. The nature of this scFv-peptide complex was further explored in solution by high-resolution NMR and physicochemical analysis of species in solution. The results provide insights into the manner in which C4 scFv inhibits the aggregation of HTT, and hence into its therapeutic potential, and suggests a structural basis for the initial interactions that underlie the formation of disease-associated amyloid fibrils by HTT.E.D.G. and C.M.D. are grateful for support by the Medical Research Council (G1002272). We also thank the Hereditary Disease Foundation (A.M.). D.Y.C. is supported by the Crystallographic X-ray Facility at the Department of Biochemistry, University of Cambridge. We would like to acknowledge Dr. Katherine Stott at the Biophysics Facility at the Department of Biochemistry, University of Cambridge, for her help with the ultracentrifugation experiments and Prof. Weiss and Dr. Desplancq at the Ecole Supérieure de Biotechnologie de Strasbourg for the kind gift of the gankyrin-specific scFv, scFvR19 as a control for our in vitro aggregation experiments.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S002228361500217X#

Dynamics of tournaments: the soccer case

A random walk-like model is considered to discuss statistical aspects of tournaments. The model is applied to soccer leagues with emphasis on the scores. This competitive system was computationally simulated and the results are compared with empirical data from the English, the German and the Spanish leagues and showed a good agreement with them. The present approach enabled us to characterize a diffusion where the scores are not normally distributed, having a short and asymmetric tail extending towards more positive values. We argue that this non-Gaussian behavior is related with the difference between the teams and with the asymmetry of the scores system. In addition, we compared two tournament systems: the all-play-all and the elimination tournaments.Comment: To appear in EPJ

Conservation and economic benefits of a road around the Serengeti

No abstract available

Anthropogenic modifications to fire regimes in the wider Serengeti‐Mara ecosystem

Fire is a key driver in savannah systems and widely used as a land management tool. Intensifying human land uses are leading to rapid changes in the fire regimes, with consequences for ecosystem functioning and composition. We undertake a novel analysis describing spatial patterns in the fire regime of the Serengeti‐Mara ecosystem, document multidecadal temporal changes and investigate the factors underlying these patterns. We used MODIS active fire and burned area products from 2001 to 2014 to identify individual fires; summarizing four characteristics for each detected fire: size, ignition date, time since last fire and radiative power. Using satellite imagery, we estimated the rate of change in the density of livestock bomas as a proxy for livestock density. We used these metrics to model drivers of variation in the four fire characteristics, as well as total number of fires and total area burned. Fires in the Serengeti‐Mara show high spatial variability—with number of fires and ignition date mirroring mean annual precipitation. The short‐term effect of rainfall decreases fire size and intensity but cumulative rainfall over several years leads to increased standing grass biomass and fuel loads, and, therefore, in larger and hotter fires. Our study reveals dramatic changes over time, with a reduction in total number of fires and total area burned, to the point where some areas now experience virtually no fire. We suggest that increasing livestock numbers are driving this decline, presumably by inhibiting fire spread. These temporal patterns are part of a global decline in total area burned, especially in savannahs, and we caution that ecosystem functioning may have been compromised. Land managers and policy formulators need to factor in rapid fire regime modifications to achieve management objectives and maintain the ecological function of savannah ecosystems

Comparisons of host mitochondrial, nuclear and endosymbiont bacterial genes reveal cryptic fig wasp species and the effects of Wolbachia on host mtDNA evolution and diversity

Background Figs and fig-pollinating wasp species usually display a highly specific one-to-one association. However, more and more studies have revealed that the "one-to-one" rule has been broken. Co-pollinators have been reported, but we do not yet know how they evolve. They may evolve from insect speciation induced or facilitated by Wolbachia which can manipulate host reproduction and induce reproductive isolation. In addition, Wolbachia can affect host mitochondrial DNA evolution, because of the linkage between Wolbachia and associated mitochondrial haplotypes, and thus confound host phylogeny based on mtDNA. Previous research has shown that fig wasps have the highest incidence of Wolbachia infection in all insect taxa, and Wolbachia may have great influence on fig wasp biology. Therefore, we look forward to understanding the influence of Wolbachia on mitochondrial DNA evolution and speciation in fig wasps. Results We surveyed 76 pollinator wasp specimens from nine Ficus microcarpa trees each growing at a different location in Hainan and Fujian Provinces, China. We found that all wasps were morphologically identified as Eupristina verticillata, but diverged into three clades with 4.22-5.28% mtDNA divergence and 2.29-20.72% nuclear gene divergence. We also found very strong concordance between E. verticillata clades and Wolbachia infection status, and the predicted effects of Wolbachia on both mtDNA diversity and evolution by decreasing mitochondrial haplotypes. Conclusions Our study reveals that the pollinating wasp E. verticillata on F. microcarpa has diverged into three cryptic species, and Wolbachia may have a role in this divergence. The results also indicate that Wolbachia strains infecting E. verticillata have likely resulted in selective sweeps on host mitochondrial DNA

Nuclear recoil response of liquid xenon and its impact on solar 8B neutrino and dark matter searches

Knowledge of the ionization and scintillation responses of liquid xenon (LXe) to nuclear recoils is crucial for LXe-based dark matter experiments. Current calibrations carry large uncertainties in the low-energy region below $\sim3$ keV$_nr$ where signals from dark matter particles of $<$10 GeV/c$^2$ masses are expected. The coherent elastic neutrino-nucleus scattering (CE$\nu$NS) by solar $^8$B neutrinos also results in a continuum of nuclear recoil events below 3.0 keV$_{nr}$ (99\% of events), which further complicates low-mass dark matter searches in LXe experiments. In this paper, we describe a method to quantify the uncertainties of low-energy LXe responses using published calibration data, followed by case studies to evaluate the impact of yield uncertainties on ${^8}$B searches and low-mass dark matter sensitivity in a typical ton-scale LXe experiment. We conclude that naively omitting yield uncertainties leads to overly optimistic limits by factor $\sim2$ for a 6 GeV/c$^2$ WIMP mass. Future nuclear recoil light yield calibrations could allow experiments to recover this sensitivity and also improve the accuracy of solar ${^8}$B flux measurements