The rockefeller university

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 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.

Immune cells rely on transient physical interactions with other immune and non-immune populations to regulate their function(1). To study these 'kiss-and-run' interactions directly in vivo, we previously developed LIPSTIC (labelling immune partnerships by SorTagging intercellular contacts)(2), an approach that uses enzymatic transfer of a labelled substrate between the molecular partners CD40L and CD40 to label interacting cells. Reliance on this pathway limited the use of LIPSTIC to measuring interactions between CD4(+) T helper cells and antigen-presenting cells, however. Here we report the development of a universal version of LIPSTIC (uLIPSTIC), which can record physical interactions both among immune cells and between immune and non-immune populations irrespective of the receptors and ligands involved. We show that uLIPSTIC can be used, among other things, to monitor the priming of CD8(+) T cells by dendritic cells, reveal the steady-state cellular partners of regulatory T cells and identify germinal centre-resident T follicular helper cells on the basis of their ability to interact cognately with germinal centre B cells. By coupling uLIPSTIC with single-cell transcriptomics, we build a catalogue of the immune populations that physically interact with intestinal epithelial cells at the steady state and profile the evolution of the interactome of lymphocytic choriomeningitis virus-specific CD8(+) T cells in multiple organs following systemic infection. Thus, uLIPSTIC provides a broadly useful technology for measuring and understanding cell-cell interactions across multiple biological systems.

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.

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.

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.

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 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.

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

The properties of the cell types that are selectively vulnerable in Huntington's disease (HD) cortex, the nature of somatic CAG expansions of mHTT in these cells, and their importance in CNS circuitry have not been delineated. Here, we employed serial fluorescence-activated nuclear sorting (sFANS), deep molecular profiling, and single-nucleus RNA sequencing (snRNA-seq) of motor-cortex samples from thirteen predominantly early stage, clinically diagnosed HD donors and selected samples from cingulate, visual, insular, and prefrontal cortices to demonstrate loss of layer 5a pyramidal neurons in HD. Extensive mHTT CAG expansions occur in vulnerable layer 5a pyramidal cells, and in Betz cells, layers 6a and 6b neurons that are resilient in HD. Retrograde tracing experiments in macaque brains identify layer 5a neurons as corticostriatal pyramidal cells. We propose that enhanced somatic mHTT CAG expansion and altered synaptic function act together to cause corticostriatal disconnection and selective neuronal vulnerability in HD cerebral cortex.