Single-cell analysis reveals ESX-1-mediated accumulation of permissive macrophages in infected mouse lungs.

(MTB) ESX-1, a type VII secretion system, is a key virulence determinant contributing to MTB's survival within lung mononuclear phagocytes (MNPs), but its effect on MNP recruitment and differentiation remains unknown. Here, using multiple single-cell RNA sequencing techniques, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden.

Type 1 lymphocytes and interferon-γ accumulate in the thalamus and restrict seizure susceptibility after traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide and can lead to secondary sequelae such as increased seizure susceptibility. Emerging work suggests that the thalamus, the relay center of the brain that undergoes secondary damage after cortical TBI, is involved with heightened seizure risks after TBI. TBI also induces the recruitment of peripheral immune cells, including T cells, to the site(s) of injury, but it is unclear how these cells impact neurological sequelae post-TBI.

CZ CELLxGENE Discover: a single-cell data platform for scalable exploration, analysis and modeling of aggregated data.

Hundreds of millions of single cells have been analyzed using high-throughput transcriptomic methods. The cumulative knowledge within these datasets provides an exciting opportunity for unlocking insights into health and disease at the level of single cells. Meta-analyses that span diverse datasets building on recent advances in large language models and other machine-learning approaches pose exciting new directions to model and extract insight from single-cell data.

Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior.

The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the developing mouse brain.

BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection.

The Endoplasmic Reticulum (ER)-resident HSP70 chaperone BiP (HSPA5) plays a crucial role in maintaining and restoring protein folding homeostasis in the ER. BiP's function is often dysregulated in cancer and virus-infected cells, conferring pro-oncogenic and pro-viral advantages. We explored BiP's functions during infection by the Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic gamma-herpesvirus associated with cancers of immunocompromised patients.

How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs.

Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. ESX-1, a type VII secretion system, acts as a virulence determinant that contributes to MTB's ability to survive within MNPs, but its effect on MNP recruitment and/or differentiation remains unknown. Here, using single-cell RNA sequencing, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM).

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined.

Group 2 innate lymphoid cells promote inhibitory synapse development and social behavior.

The innate immune system plays essential roles in brain synaptic development, and immune dysregulation is implicated in neurodevelopmental diseases. Here we show that a subset of innate lymphocytes (group 2 innate lymphoid cells, ILC2s) is required for cortical inhibitory synapse maturation and adult social behavior. ILC2s expanded in the developing meninges and produced a surge of their canonical cytokine Interleukin-13 (IL-13) between postnatal days 5-15.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined.

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice.

Microglia are critical regulators of brain development that engulf synaptic proteins during postnatal synapse remodeling. However, the mechanisms through which microglia sense the brain environment are not well defined. Here, we characterized the regulatory program downstream of interleukin-33 (IL-33), a cytokine that promotes microglial synapse remodeling.

Variation in suspected cancer referral pathways in primary care: comparative analysis across the International Benchmarking Cancer Partnership.

Background: International variations in cancer outcomes persist and may be influenced by differences in the accessibility and organisation of cancer patient pathways. More evidence is needed to understand to what extent variations in the structure of primary care referral pathways for cancer investigation contribute to differences in the timeliness of diagnoses and cancer outcomes in different countries.

Aim: To explore the variation in primary care referral pathways for the management of suspected cancer across different countries.

In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain.

Microglia are brain resident macrophages that play vital roles in central nervous system (CNS) development, homeostasis, and pathology. Microglia both remodel synapses and engulf apoptotic cell corpses during development, but whether unique molecular programs regulate these distinct phagocytic functions is unknown. Here we identify a molecularly distinct microglial subset in the synapse rich regions of the zebrafish (Danio rerio) brain.

Seal bomb explosion sound source characterization.

Small explosive charges, called seal bombs, used by commercial fisheries to deter marine mammals from depredation and accidental bycatch during fishing operations, produce high level sounds that may negatively impact nearby animals. Seal bombs were exploded underwater and recorded at various ranges with a calibrated hydrophone to characterize the pulse waveforms and to provide appropriate propagation loss models for source level (SL) estimates. Waveform refraction became important at about 1500 m slant range with approximately spherical spreading losses observed at shorter ranges.

Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.

Synapse remodeling is essential to encode experiences into neuronal circuits. Here, we define a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus. We find that the cytokine interleukin-33 (IL-33) is expressed by adult hippocampal neurons in an experience-dependent manner and defines a neuronal subset primed for synaptic plasticity.

Demystifying Microglia: And Now the Work Begins.

Microglia actively shape the developing brain, but their transcriptional diversity is not well understood. Complementary studies by Hammond et al. (2018) and Li et al.

Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development.

Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus.

PA10 What i need you to know. building a collaborative communication tool.

Background: During strategy consultation in Northern Ireland an "End of Life Care Passport" was suggested as a way to address myriad communication difficulties involved in living with evolving illness.

Aim: To build a patient-owned communication tool to facilitate important conversations and capture key information as health changes.

Methods: Participatory action methods used to engage service users, carers, patient advocates, and healthcare professionals.

In vitro effects of bmp-2, bmp-7, and bmp-13 on proliferation and differentation of mouse mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have the capabilities to proliferate and differentiate into osteoblastic and chondrogenic lineages when stimulated with bone morphogenic proteins (BMPs). BMPs play a vital role in skeletal development. BMPs bind to their cell surface receptors on MSCs and send signals to the cell nucleus which results to the synthesis of macromolecules involved in cartilage and bone formation and then the mesenchymal cell differentiates into chondrocytes or osteoblasts.

Development and validation of the smoking abstinence expectancies questionnaire.

Introduction: Despite evidence that expectancies influence the use and effects of drugs, there are no questionnaires that assess abstinence expectancies among smokers. Such a questionnaire may assist prediction models of successful quitting, enable clinicians to target specific expectancies, and give researchers a broader understanding of cognitive processes that influence smoking.

Methods: We aimed to develop a questionnaire that assesses, among daily smokers, expected short-term psychological and physiological consequences to (hypothetically) abstaining from smoking.

Heat balance and cumulative heat storage during exercise performed in the heat in physically active younger and middle-aged men.

On separate days, eight physically active younger (22 +/- 2 years) and eight highly trained middle-aged (45 +/- 4 years) men matched for physical fitness and body composition performed 90 min of semi-recumbent cycling at a constant rate of heat production (290 W) followed by 60 min of seated recovery in either a temperate (T, 30 degrees C), warm (W, 35 degrees C) or hot (H, 40 degrees C) ambient condition. Rectal temperature (T (re)) was measured continuously, while the rate of whole-body heat loss (H (L)), as well as changes in body heat content (H (b)) was measured simultaneously using direct whole-body and indirect calorimetry. No difference in H (L) was observed between age groups for all ambient conditions.