The rockefeller university

A search for dark matter particles is performed using events with a pair of W bosons and large missing transverse momentum. Candidate events are selected by requiring one or two leptons (l = electrons or muons). The analysis is based on proton-proton collision data collected at a center-of-mass energy of 13TeV by the CMS experiment at the LHC and corresponding to an integrated luminosity of 138 fb(-1). No significant excess over the expected standard model background is observed in the l nu qq and 2l2 nu final states of the W+W- boson pair. Limits are set on dark matter production in the context of a simplified dark Higgs model, with a dark Higgs boson mass above the W+W- mass threshold. The dark matter phase space is probed in the mass range 100-300 GeV, extending the scope of previous searches. Current exclusion limits are improved in the range of dark Higgs masses from 160 to 250 GeV, for a dark matter mass of 200 GeV.

One of the tenets of molecular biology is that dynamic transitions between three-dimensional structures determine the function of proteins. Therefore, it seems only natural that evolutionary analysis of proteins, presently based mainly on their primary sequence, needs to shift its focus toward their function as assessed by corresponding structural transitions. This can be facilitated by recent progress in cryogenic electron microscopy that provides atomic structures of multiple conformational states for proteins and protein assemblies isolated from evolutionarily related species. In this work, we study evolutionary conservation of multiprotein assembly function by using mechanical strain as a quantitative footprint of structural transitions. We adopt the formalism of finite strain theory, developed in condensed matter physics, and apply it, as a case study, to a classical multiprotein assembly, the ATP synthase. Protein strain analysis provides a precise characterization of rotation domains that agrees with the present biophysical knowledge. In addition, we obtain a strain distribution on the protein structure associated with functional transitions. By analyzing in detail the strain patterns of the chains responsible for ATP synthesis across distinct species, we show that they are evolutionarily conserved for the same functional transition. Such conservation is not revealed by displacement or rotation patterns. Furthermore, within each functional transition, we can identify conserved strain patterns for ATP synthases isolated from different organisms. The observed strain conservation across evolutionary distant species indicates that strain should be essential in future structure- based evolutionary studies of protein function.

The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)-infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb-treated macaques. Viral control was correlated with the reprogramming of CD8+ T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

Visual preferences are important drivers of mate choice and sexual selection, but little is known of how they evolve at the genetic level. In this study, we took advantage of the diversity of bright warning patterns displayed by Heliconius butterflies, which are also used during mate choice. Combining behavioral, population genomic, and expression analyses, we show that two Heliconius species have evolved the same preferences for red patterns by exchanging genetic material through hybridization. Neural expression of regucalcin1 correlates with visual preference across populations, and disruption of regucalcin1 with CRISPR-Cas9 impairs courtship toward conspecific females, providing a direct link between gene and behavior. Our results support a role for hybridization during behavioral evolution and show how visually guided behaviors contributing to adaptation and speciation are encoded within the genome.

The azimuthal anisotropy of gamma(1S) mesons in high-multiplicity proton-lead collisions is studied using data collected by the CMS experiment at a nucleon-nucleon center-of-mass energy of 8.16 TeV. The gamma(1S) mesons are reconstructed using their dimuon decay channel. The anisotropy is characterized by the second Fourier harmonic coefficients, found using a two-particle correlation technique, in which the gamma(1S) mesons are correlated with charged hadrons. A large pseudorapidity gap is used to suppress short-range correlations. Nonflow contamination from the dijet background is removed using a low-multiplicity subtraction method, and the results are presented as a function of gamma(1S) transverse momentum. The azimuthal anisotropies are smaller than those found for charmonia in proton-lead collisions at the same collision energy, but are consistent with values found for gamma(1S) mesons in lead-lead interactions at a nucleon-nucleon center-of-mass energy of 5.02 TeV.

A search is reported for near-threshold structures in the J=psi J=psi invariant mass spectrum produced in proton-proton collisions at ffiffi s p 1/4 13 TeV from data collected by the CMS experiment, corresponding to an integrated luminosity of 135 fb-1. Three structures are found, and a model with quantum interference among these structures provides a good description of the data. A new structure is observed with a local significance above 5 standard deviations at a mass of 6638 thorn 43 -38 ostat thorn thorn 16 -31 osyst thorn MeV. Another structure with even higher significance is found at a mass of 6847 thorn 44 -28 ostat thorn thorn 48 -20 osyst thorn MeV, which is consistent with the Xo6900 thorn resonance reported by the LHCb experiment and confirmed by the ATLAS experiment. Evidence for another new structure, with a local significance of 4.7 standard deviations, is found at a mass of 7134 thorn 48 -25 ostat thorn thorn 41 -15 osyst thorn MeV. Results are also reported for a model without interference, which does not fit the data as well and shows mass shifts up to 150 MeV relative to the model with interference

Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-alpha T cell receptor (pre-TCR alpha) expression. Low circulating naive alpha beta T cell counts at birth persisted over time, with normal memory alpha beta and high gamma delta T cell counts. Their TCR alpha repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue alpha beta T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive alpha beta T cell counts but high gamma delta T cell counts. Although residual pre-TCR alpha expression drove the differentiation of more alpha beta T cells, autoimmune conditions were more frequent in these patients compared with the general population.

We explored the gravity dual of a rotating quark-gluon plasma by transforming the boundary coordinates of the large black hole limit of Schwarchild-AdS5 metric. The Euler-Lagrange equation of the Nambu-Goto action and its solution become more complex than those without rotation. For small angular velocity, we obtained an analytical form of the drag force acting on a quark moving in the direction of the rotation axis and found it stronger than that without rotation. We also calculated the heavy quark potential under the same approximation. For the quarkonium symmetric with respect to the rotation axis, the depth of the potential is reduced by the rotation. For the quarkonium oriented in parallel to the rotation axis, the binding force is weakened and the force range becomes longer. We also compared our holographic formulation with others in the literature.

During DNA replication, the proliferating cell nuclear antigen (PCNA) clamps are loaded onto primed sites for each Okazaki fragment synthesis by the AAA+ heteropentamer replication factor C (RFC). PCNA encircling duplex DNA is quite stable and is removed from DNA by the dedicated clamp unloader Elg1-RFC. Here, we show the cryo-EM structure of Elg1-RFC in various states with PCNA. The structures reveal essential features of Elg1-RFC that explain how it is dedicated to PCNA unloading. Specifically, Elg1 contains two external loops that block opening of the Elg1-RFC complex for DNA binding, and an "Elg1 plug" domain that fills the central DNA binding chamber, thereby reinforcing the exclusive PCNA unloading activity of Elg1-RFC. Elg1-RFC was capable of unloading PCNA using non-hydrolyzable AMP-PNP. Both RFC and Elg1-RFC could remove PCNA from covalently closed circular DNA, indicating that PCNA unloading occurs by a mechanism that is distinct from PCNA loading. Implications for the PCNA unloading mechanism are discussed.