Thorpetalley2255

Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. GYY4137 molecular weight Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.Early embryogenesis is a conserved and self-organized process. In the mammalian embryo, the potential for self-organization is manifested in its extraordinary developmental plasticity, allowing a correctly patterned embryo to arise despite experimental perturbation. The underlying mechanisms enabling such regulative development have long been a topic of study. In this Review, we summarize our current understanding of the self-organizing principles behind the regulative nature of the early mammalian embryo. We argue that geometrical constraints, feedback between mechanical and biochemical factors, and cellular heterogeneity are all required to ensure the developmental plasticity of mammalian embryo development.In this issue of Cell, Zuccaro and colleagues show that on-target Cas9-mediated double-strand breaks cause chromosome loss or mis-repair of the disease allele in > 90% of human embryos. End joining repair pathways dominate, causing small insertions or deletions, which raises serious questions about using double-strand breaks for "gene surgery".Defining the principles underlying the organization of biomolecules within cells is a key challenge of current cell biology research. Persson et al. now identify a powerful layer of regulation that allows cells to decouple diffusion from temperature by modulating their intracellular viscosity. This so-called viscoadaptation is mediated through trehalose and glycogen activities, which alter diffusion dynamics and self-assembly propensity inside the cell globally.Coral reefs are on a steep trajectory of decline, with natural recovery in many areas unlikely.1-3 Eutrophication, overfishing, climate change, and disease have fueled the supremacy of seaweeds on reefs,4,5 particularly in the Caribbean, where many reefs have undergone an ecological phase shift so that seaweeds now dominate previously coral-rich reefs.6-8 Discovery of the powerful grazing capability of the Caribbean's largest herbivorous crab (Maguimithrax spinosissimus)9 led us to test the effectiveness of their grazing on seaweed removal and coral reef recovery in two experiments conducted sequentially at separate locations 15 km apart in the Florida Keys (USA). In those experiments, we transplanted crabs onto several patch reefs, leaving others as controls (n = 24 reefs total; each 10-20 m2 in area) and then monitored benthic cover, coral recruitment, and fish community structure on each patch reef for a year. We also compared the effectiveness of crab herbivory to scrubbing reefs by hand to remove algae. Crabs reduced the cover of seaweeds by 50%-80%, resulting in a commensurate 3-5-fold increase in coral recruitment and reef fish community abundance and diversity. Although laborious hand scrubbing of reefs also reduced algal cover, that effect was transitory unless maintained by the addition of herbivorous crabs. With the persistence of Caribbean coral reefs in the balance, our findings demonstrate that large-scale restoration that includes enhancement of invertebrate herbivores can reverse the ecological phase shift on coral reefs away from seaweed dominance.The basal ganglia (BG) inhibit movements through two independent circuits the striatal neuron-indirect and the subthalamic nucleus-hyperdirect pathways. These pathways exert opposite effects onto external globus pallidus (GPe) neurons, whose functional importance as a relay has changed drastically with the discovery of two distinct cell types, namely the prototypic and the arkypallidal neurons. However, little is known about the synaptic connectivity scheme of different GPe neurons toward both motor-suppressing pathways, as well as how opposite changes in GPe neuronal activity relate to locomotion inhibition. Here, we optogenetically dissect the input organizations of prototypic and arkypallidal neurons and further define the circuit mechanism and behavioral outcome associated with activation of the indirect or hyperdirect pathways. This work reveals that arkypallidal neurons are part of a novel disynaptic feedback loop differentially recruited by the indirect or hyperdirect pathways and that broadcasts inhibitory control onto locomotion only when arkypallidal neurons increase their activity.Failure of homologous chromosomes to recombine is arguably the most important cause of human meiotic nondisjunction, having been linked to numerous autosomal and sex chromosome trisomies of maternal origin. However, almost all information on these "exchangeless" homologs has come from genetic mapping studies of trisomic conceptuses, so the incidence of this defect and its impact on gametogenesis are not clear. If oocytes containing exchangeless homologs are selected against during meiosis, the incidence may be much higher in developing germ cells than in zygotes. To address this, we initiated studies of exchangeless chromosomes in fetal ovarian samples from elective terminations of pregnancy. In total, we examined more than 7,000 oocytes from 160 tissue samples, scoring for the number of foci per cell of the crossover-associated protein MLH1. We identified a surprisingly high level of recombination failure, with more than 7% of oocytes containing at least one chromosome pair that lacked an MLH1 focus. Detailed analyses indicate striking chromosome-specific differences, with a preponderance of MLH1-less homologs involving chromosomes 21 or 22.