Spin Drag Mechanism of Giant Thermal Magnetoresistance.

We study hydrodynamic thermal transport in high-mobility two-dimensional electron systems placed in an in-plane magnetic field and identify a new mechanism of thermal magnetotransport. This mechanism is caused by drag between the electron populations with opposite spin polarization, which arises in the presence of a hydrodynamic flow of heat. In high mobility systems, spin drag results in strong thermal magnetoresistance, which becomes of the order of 100% at relatively small spin polarization of the electron liquid.

Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for adult screening.

Purpose: As population-based screening programs to identify genetic conditions in adults using genomic sequencing (GS) are increasingly available, validated patient-centered outcome measures are needed to understand participants' experience. We aimed to develop and validate an instrument to assess the perceived utility of GS in the context of adult screening.

Methods: Informed by a 5-domain conceptual model, we used a 5-step approach to instrument development and validation: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity.

Specification of human regional brain lineages using orthogonal gradients of WNT and SHH in organoids.

The repertory of neurons generated by progenitor cells depends on their location along antero-posterior and dorso-ventral axes of the neural tube. To understand if recreating those axes was sufficient to specify human brain neuronal diversity, we designed a mesofluidic device termed Duo-MAPS to expose induced pluripotent stem cells (iPSC) to concomitant orthogonal gradients of a posteriorizing and a ventralizing morphogen, activating WNT and SHH signaling, respectively. Comparison of single cell transcriptomes with fetal human brain revealed that Duo-MAPS-patterned organoids generated the major neuronal lineages of the forebrain, midbrain, and hindbrain.

Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for pediatric diagnostic testing.

Purpose: Measuring the effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents' perceived utility of pediatric diagnostic GS.

Methods: Informed by a 5-domain conceptual model, the study comprised 5 steps: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity.

TGF-β1 Drives Integrin-Dependent Pericyte Migration and Microvascular Destabilization in Fibrotic Disease.

Interactions between endothelial cells (ECs) and mural pericytes (PCs) are critical in maintaining the stability and function of the microvascular wall. Abnormal interactions between these two cell types are a hallmark of progressive fibrotic diseases such as systemic sclerosis (also known as scleroderma). However, the role of PCs in signaling microvascular dysfunction remains underexplored.

Spatial-temporal order-disorder transition in angiogenic NOTCH signaling controls cell fate specification.

Angiogenesis is a morphogenic process resulting in the formation of new blood vessels from pre-existing ones, usually in hypoxic micro-environments. The initial steps of angiogenesis depend on robust differentiation of oligopotent endothelial cells into the Tip and Stalk phenotypic cell fates, controlled by NOTCH-dependent cell-cell communication. The dynamics of spatial patterning of this cell fate specification are only partially understood.

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations.

Research Participants' Perspectives on Precision Diagnostics for Alzheimer's Disease.

Background: Understanding research participants' responses to learning Alzheimer's disease (AD) risk information is important to inform clinical implementation of precision diagnostics given rapid advances in disease modifying therapies.

Objective: We assessed participants' perspectives on the meaning of their amyloid positron emission tomography (PET) imaging results for their health, self-efficacy to understand their results, psychological impact of learning their results, experience receiving their results from the clinical team, and interest in genetic testing for AD risk.

Methods: We surveyed individuals who were being clinically evaluated for AD and received PET imaging six weeks after the return of results.

Solid tumor growth depends on an intricate equilibrium of malignant cell states.

Control of cell identity and number is central to tissue function, yet principles governing organization of malignant cells in tumor tissues remain poorly understood. Using mathematical modeling and candidate-based analysis, we discover primary and metastatic pancreatic ductal adenocarcinoma (PDAC) organize in a stereotypic pattern whereby PDAC cells responding to WNT signals (WNT-R) neighbor WNT-secreting cancer cells (WNT-S). Leveraging lineage-tracing, we reveal the WNT-R state is transient and gives rise to the WNT-S state that is highly stable and committed to organizing malignant tissue.

Experimental and phylogenetic evidence for correlated gene expression evolution in endometrial and skin fibroblasts.

Gene expression change is a dominant mode of evolution. Mutations, however, can affect gene expression in multiple cell types. Therefore, gene expression evolution in one cell type can lead to similar gene expression changes in another cell type.

Single-Cell Measurements and Modeling and Computation of Decision-Making Errors in a Molecular Signaling System with Two Output Molecules.

A cell constantly receives signals and takes different fates accordingly. Given the uncertainty rendered by signal transduction noise, a cell may incorrectly perceive these signals. It may mistakenly behave as if there is a signal, although there is none, or may miss the presence of a signal that actually exists.

Meeting Contemporary Challenges: Development of Nanomaterials for Veterinary Medicine.

In recent decades, nanotechnology has been rapidly advancing in various fields of human activity, including veterinary medicine. The review presents up-to-date information on recent advancements in nanotechnology in the field and an overview of the types of nanoparticles used in veterinary medicine and animal husbandry, their characteristics, and their areas of application. Currently, a wide range of nanomaterials has been implemented into veterinary practice, including pharmaceuticals, diagnostic devices, feed additives, and vaccines.

Coulomb Drag and Heat Transfer in Strange Metals.

We address Coulomb drag and near-field heat transfer in a double-layer system of incoherent metals. Each layer is modeled by an array of tunnel-coupled SYK dots with random interlayer interactions. Depending on the strength of intradot interactions and interdot tunneling, this model captures the crossover from the Fermi liquid to a strange metal phase.

SPAK-dependent cotransporter activity mediates capillary adhesion and pressure during glioblastoma migration in confined spaces.

The invasive potential of glioblastoma cells is attributed to large changes in pressure and volume, driven by diverse elements, including the cytoskeleton and ion cotransporters.  However, how the cell actuates changes in pressure and volume in confinement, and how these changes contribute to invasive motion is unclear. Here, we inhibited SPAK activity, with known impacts on the cytoskeleton and cotransporter activity and explored its role on the migration of glioblastoma cells in confining microchannels to model invasive spread through brain tissue.

CTLA-4 tail fusion enhances CAR-T antitumor immunity.

Chimeric antigen receptor (CAR)-T cells are powerful therapeutics; however, their efficacy is often hindered by critical hurdles. Here utilizing the endocytic feature of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail, we reprogram CAR function and substantially enhance CAR-T efficacy in vivo. CAR-T cells with monomeric, duplex or triplex CTLA-4 cytoplasmic tails (CCTs) fused to the C terminus of CAR exhibit a progressive increase in cytotoxicity under repeated stimulation, accompanied by reduced activation and production of proinflammatory cytokines.

Anomalous High-Temperature Magnetoresistance in a Dilute 2D Hole System.

We report an unusual magnetoresistance that strengthens with the temperature in a dilute two-dimensional (2D) hole system in GaAs/AlGaAs quantum wells with densities p=1.98-0.99×10^{10}/cm^{2} where r_{s}, the ratio between Coulomb energy and Fermi energy, is as large as 20-30.

[Comparative analysis of the intestinal microbiota in patients with exocrine pancreatic insufficiency of various severity].

Background: Exocrine pancreatic insufficiency (EPI) is a critical host factor in determining the composition of the gut microbiota. Diseases that cause exocrine insufficiency can affect the gut microbiome, which can potentiate disease progression and complications. To date, the relationship of exocrine insufficiency in various pancreatic (PA) pathologies, in chronic pancreatitis (CP), with dysbiotic changes in the intestinal microbiota (IM) has not been reliably studied.

CTLA-4 tail fusion enhances CAR-T anti-tumor immunity.

Chimeric antigen receptor (CAR) T cells are powerful therapeutics; however, their efficacy is often hindered by critical hurdles. Here, utilizing the endocytic feature of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail (CT), we reprogram CAR function and substantially enhance CAR-T efficacy . CAR-T cells with monomeric, duplex, or triplex CTLA-4 CTs (CCTs) fused to the C-terminus of CAR exhibit a progressive increase in cytotoxicity under repeated stimulation, accompanied by reduced activation and production of pro-inflammatory cytokines.

Genetic diseases: How the noise fits in.

Many disease-causing mutations can have mild or no effects in some people. This incomplete phenotype penetrance phenomenon is still poorly understood, but model animal studies now show that it is stochastic, with the outcome akin to flipping a coin. These findings can affect how genetic diseases are understood and treated.

Genomic regulatory sequences in the pathogenesis of bipolar disorder.

The lifetime prevalence of bipolar disorder is estimated to be about 2%. Epigenetics defines regulatory mechanisms that determine relatively stable patterns of gene expression by controlling all key steps, from DNA to messenger RNA to protein. This Mini Review highlights recent discoveries of modified epigenetic control resulting from genetic variants associated with bipolar disorder in genome-wide association studies.

Imaging the breaking of electrostatic dams in graphene for ballistic and viscous fluids.

The charge carriers in a material can, under special circumstances, behave as a viscous fluid. In this work, we investigated such behavior by using scanning tunneling potentiometry to probe the nanometer-scale flow of electron fluids in graphene as they pass through channels defined by smooth and tunable in-plane p-n junction barriers. We observed that as the sample temperature and channel widths are increased, the electron fluid flow undergoes a Knudsen-to-Gurzhi transition from the ballistic to the viscous regime characterized by a channel conductance that exceeds the ballistic limit, as well as suppressed charge accumulation against the barriers.

SARS-CoV-2 leverages airway epithelial protective mechanism for viral infection.

Despite much concerted effort to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, relatively little is known about the dynamics of early viral entry and infection in the airway. Here we analyzed a single-cell RNA sequencing dataset of early SARS-CoV-2 infection in a humanized model, to elucidate key mechanisms by which the virus triggers a cell-systems-level response in the bronchial epithelium. We find that SARS-CoV-2 virus preferentially enters the tissue via ciliated cell precursors, giving rise to a population of infected mature ciliated cells, which signal to basal cells, inducing further rapid differentiation.

Epigenetics as a mediator of plasticity in cancer.

The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light of experiments showing nondeterministic outcomes of regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to epigenetic and gene regulation landscapes and the associated ideas of entropy and attractor states, illustrating how their definitions are both more precise and relevant to understanding cancer etiology and the plasticity of cancerous states. We address the interplay between different types of regulatory landscapes and how their changes underlie cancer progression.