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A dedicated hypothalamic oxytocin circuit controls aversive social learning

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity. In mice, the neural mechanisms underlying aversive social learning, specifically avoidance and fear after defeat, involve oxytocin signalling in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part.

Syria , Syrian , Development-team , California-institute-of-technology , Brain-funct , Early-childhood-education , Brain-res , Cell-rep , Tissue-res , Multimodal-analysis , Cell-types

Thymic mimetic cells function beyond self-tolerance

Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2–7. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations. Multiomic analyses of mouse thymic epithelial cells identify several unconventional subsets that are mimetics of various populations of terminally differentiated parenchymal cells and provide insights into their development, molecular features and function.

Tissue-res , Acids-res , Genome-biol , Gene-ontology ,

Cartilage-like protein hydrogels engineered via entanglement

Load-bearing tissues, such as muscle and cartilage, exhibit high elasticity, high toughness and fast recovery, but have different stiffness (with cartilage being significantly stiffer than muscle)1–8. Muscle achieves its toughness through finely controlled forced domain unfolding–refolding in the muscle protein titin, whereas articular cartilage achieves its high stiffness and toughness through an entangled network comprising collagen and proteoglycans. Advancements in protein mechanics and engineering have made it possible to engineer titin-mimetic elastomeric proteins and soft protein biomaterials thereof to mimic the passive elasticity of muscle9–11. However, it is more challenging to engineer highly stiff and tough protein biomaterials to mimic stiff tissues such as cartilage, or develop stiff synthetic matrices for cartilage stem and progenitor cell differentiation12. Here we report the use of chain entanglements to significantly stiffen protein-based hydrogels without compromising their toughness. By introducing chain entanglements13 into the hydrogel network made of folded elastomeric proteins, we are able to engineer highly stiff and tough protein hydrogels, which seamlessly combine mutually incompatible mechanical properties, including high stiffness, high toughness, fast recovery and ultrahigh compressive strength, effectively converting soft protein biomaterials into stiff and tough materials exhibiting mechanical properties close to those of cartilage. Our study provides a general route towards engineering protein-based, stiff and tough biomaterials, which will find applications in biomedical engineering, such as osteochondral defect repair, and material sciences and engineering. The introduction of chain entanglements into protein-based hydrogels yields hydrogels with high stiffness, high toughness, fast recovery and ultrahigh compressive strength, with mechanical properties close to those of cartilage.

International-cartilage-repair-society , Mechanical-design , Rubber-elasticity , Synovial-fluid , Sports-exerc , Soft-matter , Tissue-res , Cartilage-repair-society , Bone-joint ,

Peptides For Healing | Ultimate Guide In 2023

Several peptides have stood out from the rest for their potential benefits in wound healing, tissue repair, and regeneration. These best healing peptides include BPC-157, Thymosin Beta-4/TB500, Melanotan 2 (II), Sermorelin, and GHK-Cu.

Biomedecine-pharmacother , Peptide-sciences , Body-protective , Basel-switz , Tissue-res , Pharmacokinetics-trial , Text-view , Injectable-hydrogels , Varying-collagen , Myocardial-infarction-therapy , Protective-actions

Effects of SARS-CoV-2 on prenatal lung growth assessed by fetal MRI

Effects of SARS-CoV-2 on prenatal lung growth assessed by fetal MRI
thelancet.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from thelancet.com Daily Mail and Mail on Sunday newspapers.

Germany , Munich , Bayern , Prenat-diagn , Glaxosmithkline , Pfizer , Astrazeneca , Elsevier-ltd , Novartis , Tissue-res , Sensor-kinesis , Physician-scientists

Frontiers | Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus


2School of Biological Sciences, University of Western Australia, Crawley, WA, Australia
3Perron Institute for Neurological and Translational Research, Crawley, WA, Australia
Tinnitus, a phantom auditory perception that can seriously affect quality of life, is generally triggered by cochlear trauma and associated with aberrant activity throughout the auditory pathways, often referred to as hyperactivity. Studies suggest that non-auditory structures, such as prefrontal cortex (PFC), may be involved in tinnitus generation, by affecting sensory gating in auditory thalamus, allowing hyperactivity to reach the cortex and lead to perception. Indeed, human studies have shown that repetitive transcranial magnetic stimulation (rTMS) of PFC can alleviate tinnitus. The current study investigated whether this therapeutic effect is achieved through inhibition of thalamic hyperactivity, comparing effects of two common clinical rTMS protocols with sham treatment, in a guinea pig tinnitus model. Animals underwent acoustic trauma and once tinnitus developed were treated with either intermittent theta burst stimulation (iTBS), 20 Hz rTMS, or sham rTMS (10 days, 10 min/day; weekdays only). Tinnitus was reassessed and extracellular recordings of spontaneous tonic and burst firing rates in auditory thalamus made. To verify effects in PFC, densities of neurons positive for calcium-binding proteins, calbindin and parvalbumin, were investigated using immunohistochemistry. Both rTMS protocols significantly reduced tinnitus compared to sham. However, spontaneous tonic firing decreased following 20 Hz stimulation and increased following iTBS in auditory thalamus. Burst rate was significantly different between 20 Hz and iTBS stimulation, and burst duration was increased only after 20 Hz treatment. Density of calbindin, but not parvalbumin positive neurons, was significantly increased in the most dorsal region of PFC indicating that rTMS directly affected PFC. Our results support the involvement of PFC in tinnitus modulation, and the therapeutic benefit of rTMS on PFC in treating tinnitus, but indicate this is not achieved solely by suppression of thalamic hyperactivity.

Germany , Australia , Somersby , New-south-wales , Bruel , Mecklenburg-vorpommern , United-states , Glenorie , Denmark , United-kingdom , Missouri , Praha