The rockefeller university

Differential cross sections for top quark pair (t (t) over bar) production are measured in proton-proton collisions at a center-of-mass energy of 13 TeV using a sample of events containing two oppositely charged leptons. The data were recorded with the CMS detector at the CERN Large Hadron Collider and correspond to an integrated luminosity of 138 fb(-1). The differential cross sections are measured as functions of kinematic observables of the t (t) over bar system, the top quark and antiquark and their decay products, as well as of the number of additional jets in the event. The results are presented as functions of up to three variables and are corrected to the parton and particle levels. When compared to standard model predictions based on quantum chromodynamics at different levels of accuracy, it is found that the calculations do not always describe the observed data. The deviations are found to be largest for the multi-differential cross sections.

The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces. This phenomenon is known as face pareidolia. Behavioral experiments have suggested that macaques, like humans, perceive illusory faces in such objects. However, it is an open question whether such stimuli would naturally stimulate neurons residing in cortical face patches. To address this question, we recorded single unit activity from four fMRI-defined face-selective regions: the anterior medial (AM), anterior fundus (AF), prefrontal orbital (PO), and perirhinal cortex (PRh) face patches. We compared neural responses elicited by images of real macaque faces, pareidolia-evoking objects, and matched control objects. Contrary to expectations, we found no evidence of a general preference for pareidolia-evoking objects over control objects. Although a subset of neurons exhibited stronger responses to pareidolia-evoking objects, the population responses to both categories of objects were similar, and collectively much less than to real macaque faces. These results suggest that neural responses in the four regions we tested are principally concerned with the analysis of realistic facial characteristics, whereas the special attention afforded to face-like pareidolia stimuli is supported by activity elsewhere in the brain.

Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species. We found that GP-NPC1 binding correlated poorly with phylogeny. By integrating binding assays with machine learning, we identified genetic factors influencing virus-receptor-binding and predicted GP-NPC1-binding avidity for additional filoviruses and bats. Moreover, combining receptor-binding avidities with bat geographic distribution and the locations of previous Ebola outbreaks allowed us to rank bats by their potential as Ebola virus hosts. This study represents a comprehensive investigation of filovirus-receptor binding in bats (1,484 GP-NPC1 pairs, 11 filoviruses, and 135 bats) and describes a multidisciplinary approach to predict susceptible species and guide filovirus host surveillance.

Background: Lichenification, common in moderate to severe atopic dermatitis (AD) at any age, is often difficult to treat. This analysis assessed dupilumab vs placebo in AD lichenification by age and race-defined groups. Methods: This post hoc analysis included pooled data from 5 clinical trials of dupilumab (NCT03054428, NCT03345914, NCT02277743, NCT02277769, NCT02395133), including 1,997 patients aged 6 to 88 years of all races with moderate to severe AD. Results: Placebo/dupilumab randomized groups analyzed by age (n=1,535) included 123/244 children, 85/166 adolescents, and 460/457 adults; groups analyzed by self-reported racial background (n=1,902) included 132/234 Asian, 74/112 Black/African American, and 427/923 White patients. Dupilumab treatment resulted in nominally significant reductions vs placebo in Global Individual Signs Score lichenification from week 1 (adults/adolescents) or week 2 (children) through week 16. Lichenification measured by SCORing Atopic Dermatitis and Eczema Area and Severity Index improved similarly. By week 16, dupilumab significantly improved lichenification, with nominal significance vs placebo across all racial groups. Conclusion: Dupilumab treatment resulted in rapid and sustained improvement in lichenification across anatomic regions in all ages. Lichenification improved to a similar extent across racial groups.

Across species, a major axis of variation in social behaviour relates to how offspring are reared. Parental care behaviours have independently evolved in hundreds of animal lineages. Care is usually limited to one or both parents, but in some lineages parenting is a highly cooperative endeavour. In social insects, for example, entire societies have evolved around parenting, complete with distinct adult morphs that specialize in reproduction, nursing, foraging and defence. Recent advances in omic technologies have enabled data collection across diverse taxa, revealing broad patterns in the molecular regulation of parental behaviour. These studies indicate that evolution has systematically co-opted molecular machinery that pleiotropically regulates three deeply interlinked biological processes: feeding, growth and reproduction. Where more sophisticated social systems have evolved, the same factors have been further co-opted to additionally regulate the developmental differentiation of distinct morphs, division of labour between adults and behavioural changes associated with ageing. These findings suggest that complex behaviours evolve through repeated and predictable co-option of ancient molecular systems.

Transcription elongation by RNA polymerase II (Pol II) is an integral step in eukaryotic gene expression. The speed of Pol II is controlled by a multitude of elongation factors, but the exact regulatory mechanisms remain incompletely understood, especially for higher eukaryotes. Here we develop a single-molecule platform to visualize the dynamics of individual mammalian transcription elongation complexes (ECs) reconstituted from purified proteins. This platform allows us to follow the elongation and pausing behavior of EC in real time and unambiguously determine the role of each elongation factor in the kinetic control of Pol II. We find that the mammalian EC harbors multiple speed gears dictated by its associated factors and phosphorylation status. Moreover, the elongation factors are not functionally redundant but act hierarchically and synergistically to achieve optimal elongation activity. We propose that such elaborate kinetic regulation underlies the major speed-changing events during the transcription cycle and enables cells to adapt to a changing environment.

ObjectiveSystemic sclerosis (SSc) is a rare but severe autoimmune disease characterized by immune dysregulation, fibrosis, and vasculopathy. Although previous studies have highlighted the presence of functional autoantibodies targeting the angiotensin II receptor type 1 (AT1) and endothelin-1 type A receptor (ETAR), leading to autoantibody-mediated receptor stimulation and subsequent activation of endothelial cells (ECs), a comprehensive understanding of the direct interaction between these autoantibodies and their receptors is currently lacking. Moreover, existing data confirming the presence of these autoantibodies in SSc often rely on similar methodologies and assays. Our aim was to replicate previous findings and to investigate the functional effects of IgG derived from patients with SSc (SSc IgG) on AT1 and ETAR signaling, the downstream EC response, and the presence of AT1-binding autoantibodies in circulation.MethodsQuantitative polymerase chain reaction and cytokine enzyme-linked immunosorbent assay, alongside a real-time cell analyzer, were used to assess receptor-specific functional characteristics of purified SSc IgG (n = 18). Additionally, a novel protein capture assay using solubilized epitope-tagged AT1 was developed to detect AT1-binding autoantibodies in plasma samples from patients with SSc (n = 28) and healthy donors (n = 14).ResultsNo evidence for EC activation in an AT1- or ETAR-dependent manner was revealed. Furthermore, stimulation with SSc IgG did not induce receptor activation or alter G protein-coupled receptor signaling on agonist stimulation in a model with receptor overexpression. Lastly, no AT1-binding autoantibodies were detected in plasma samples from patients with SSc when using epitope-tagged solubilized AT1.ConclusionOverall, our study did not provide evidence to support the presence of AT1- or ETAR-activating autoantibodies in purified SSc IgG or AT1-binding autoantibodies in the circulation of patients with SSc.

In the arboviral vector Aedes aegypti, adaptation to anthropogenic environments has led to a major evolutionary shift separating the domestic Aedes aegypti aegypti (Aaa) ecotype from the wild Aedes aegypti formosus (Aaf) ecotype. Aaa mosquitoes are distributed globally and have higher vectorial capacity than Aaf, which remained in Africa. Despite the evolutionary and epidemiological relevance of this separation, inconsistent morphological data and a complex population structure have hindered the identification of genomic signals distinguishing the two ecotypes. Here we assessed the correspondence between the geographic distribution, population structure and genome-wide selection of 511 Aaf and 123 Aaa specimens and report adaptive signals in 186 genes that we call Aaa molecular signatures. Our results indicate that Aaa molecular signatures arose from standing variation associated with extensive ancestral polymorphisms in Aaf populations and have been co-opted for self-domestication through genomic and functional redundancy and local adaptation. Overall, we show that the behavioural shift of Ae. aegypti mosquitoes to live in association with humans relied on the fine regulation of chemosensory, neuronal and metabolic functions, as seen in the domestication processes of rabbits and silkworms. Our results also provide a foundation for the investigation of new genic targets for the control of Ae. aegypti populations.