Skin autonomous antibody production regulates host-microbiota interactions.

The microbiota colonizes each barrier site and broadly controls host physiology. However, when uncontrolled, microbial colonists can also promote inflammation and induce systemic infection. The unique strategies employed at each barrier tissue to control the coexistence of the host with its microbiota remain largely elusive.

Simulating the Landau-Zener sweep in deeply sub-Ohmic environments.

With the goal to study dissipative Landau-Zener (LZ) sweeps in realistic solid-state qubits, we utilize novel methods from non-Markovian open quantum system dynamics that enable reliable long-time simulations for sub-Ohmic environments. In particular, we combine a novel representation of the dynamical propagator, the uniform time evolving matrix product operator method, with a stochastic realization of finite temperature fluctuations. The latter greatly reduces the computational cost for the matrix product operator approach, enabling convergence in the experimentally relevant deeply sub-Ohmic regime.

Open Quantum System Dynamics from Infinite Tensor Network Contraction.

Approaching the long-time dynamics of non-Markovian open quantum systems presents a challenging task if the bath is strongly coupled. Recent proposals address this problem through a representation of the so-called process tensor in terms of a tensor network. We show that for Gaussian environments highly efficient contraction to a matrix product operator (MPO) form can be achieved with infinite MPO evolution methods, leading to significant computational speed-up over existing proposals.

The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota.

The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. The roles of sensory neurons in controlling the adaptive immune system, and more specifically immunity to the microbiota, however, remain elusive. Here, we identified a mechanism for direct neuroimmune communication between commensal-specific T lymphocytes and somatosensory neurons mediated by the neuropeptide calcitonin gene-related peptide (CGRP) in the skin.

Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans.

Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ).

The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota.

Unlabelled: The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. The roles of sensory neurons in controlling the adaptive immune system, and more specifically immunity to the microbiota, however, remain elusive. Here, we identified a novel mechanism for direct neuroimmune communication between commensal-specific T lymphocytes and somatosensory neurons mediated by the neuropeptide Calcitonin Gene-Related Peptide (CGRP) in the skin.

A TLR4/TRAF6-dependent signaling pathway mediates NCoR coactivator complex formation for inflammatory gene activation.

The nuclear receptor corepressor (NCoR) forms a complex with histone deacetylase 3 (HDAC3) that mediates repressive functions of unliganded nuclear receptors and other transcriptional repressors by deacetylation of histone substrates. Recent studies provide evidence that NCoR/HDAC3 complexes can also exert coactivator functions in brown adipocytes by deacetylating and activating PPARγ coactivator 1α (PGC1α) and that signaling via receptor activator of nuclear factor kappa-B (RANK) promotes the formation of a stable NCoR/HDAC3/PGC1β complex that coactivates nuclear factor kappa-B (NFκB)- and activator protein 1 (AP-1)-dependent genes required for osteoclast differentiation. Here, we demonstrate that activation of Toll-like receptor (TLR) 4, but not TLR3, the interleukin 4 (IL4) receptor nor the Type I interferon receptor, also promotes assembly of an NCoR/HDAC3/PGC1β coactivator complex.

Tree-based QTL mapping with expected local genetic relatedness matrices.

Understanding the genetic basis of complex phenotypes is a central pursuit of genetics. Genome-wide association studies (GWASs) are a powerful way to find genetic loci associated with phenotypes. GWASs are widely and successfully used, but they face challenges related to the fact that variants are tested for association with a phenotype independently, whereas in reality variants at different sites are correlated because of their shared evolutionary history.

Microsatellites used in forensics are in regions enriched for trait-associated variants.

The 20 short tandem repeat (STR) loci of the combined DNA index system (CODIS) are the basis of the vast majority of forensic genetics in the United States. One argument for permissive rules about the collection of CODIS genotypes is that the CODIS loci are thought to contain little information about ancestry or traits. However, in the past 20 years, a growing field has identified hundreds of thousands of genotype-trait associations.

RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1β- and RNA-dependent co-activator of osteoclast gene expression.

The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on histone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor κB (RANK) converts the NCoR/HDAC3 co-repressor complex to a co-activator of AP-1 and NF-κB target genes that are required for mouse osteoclast differentiation. Accordingly, the dominant function of NCoR/HDAC3 complexes in response to RANK signaling is to activate, rather than repress, gene expression.

Tree-based QTL mapping with expected local genetic relatedness matrices.

Understanding the genetic basis of complex phenotypes is a central pursuit of genetics. Genome-wide Association Studies (GWAS) are a powerful way to find genetic loci associated with phenotypes. GWAS are widely and successfully used, but they face challenges related to the fact that variants are tested for association with a phenotype independently, whereas in reality variants at different sites are correlated because of their shared evolutionary history.

Microsatellites used in forensics are located in regions unusually rich in trait-associated variants.

The 20 short tandem repeat (STR) markers of the combined DNA index system (CODIS) are the basis of the vast majority of forensic genetics in the United States. One argument for permissive rules about the collection of CODIS genotypes is that the CODIS markers are thought to contain information relevant to identification only (such as a human fingerprint would), with little information about ancestry or traits. However, in the past 20 years, a quickly growing field has identified hundreds of thousands of genotype-trait associations.

Immunity to the microbiota promotes sensory neuron regeneration.

Tissue immunity and responses to injury depend on the coordinated action and communication among physiological systems. Here, we show that, upon injury, adaptive responses to the microbiota directly promote sensory neuron regeneration. At homeostasis, tissue-resident commensal-specific T cells colocalize with sensory nerve fibers within the dermis, express a transcriptional program associated with neuronal interaction and repair, and promote axon growth and local nerve regeneration following injury.

Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function.

Increasing evidence indicates close interaction between immune cells and the brain, revising the traditional view of the immune privilege of the brain. However, the specific mechanisms by which immune cells promote normal neural function are not entirely understood. Mucosal-associated invariant T cells (MAIT cells) are a unique type of innate-like T cell with molecular and functional properties that remain to be better characterized.

Immune checkpoint inhibitors unleash pathogenic immune responses against the microbiota.

Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects are of unclear etiology and impact virtually all organ systems, with the most common being sites colonized by the microbiota such as the skin and gastrointestinal tract.

The genomic origins of the world's first farmers.

The precise genetic origins of the first Neolithic farming populations in Europe and Southwest Asia, as well as the processes and the timing of their differentiation, remain largely unknown. Demogenomic modeling of high-quality ancient genomes reveals that the early farmers of Anatolia and Europe emerged from a multiphase mixing of a Southwest Asian population with a strongly bottlenecked western hunter-gatherer population after the last glacial maximum. Moreover, the ancestors of the first farmers of Europe and Anatolia went through a period of extreme genetic drift during their westward range expansion, contributing highly to their genetic distinctiveness.

Non-Markovian Quantum Dynamics in a Squeezed Reservoir.

We study non-Markovian dynamics of an open quantum system system interacting with a nonstationary squeezed bosonic reservoir. We derive exact and approximate descriptions for the open system dynamics. Focusing on the spin boson model, we compare exact dynamics with Redfield theory and a quantum optical master equation for both short and long time dynamics and in non-Markovian and Markov regimes.