Probes for INS

A unique set of features and characteristics of species of the Cnidaria phylum is the one reason that makes them a model for a various studies. The plasticity of a life cycle and the processes of cell differentiation and development of an integral multicellular organism associated with it are of a specific scientific interest. A new stage of development of molecular genetic methods, including methods for high-throughput genome, transcriptome, and epigenome sequencing, both at the level of the whole organism and at the level of individual cells, makes it possible to obtain a detailed picture of the development of these animals. This review examines some modern approaches and advances in the reconstruction of the processes of ontogenesis of cnidarians by studying the regulatory signal transduction pathways and their interactions.

Spinal cord dorsal horn (DH) inhibition is critical to the processing of sensory inputs, and its impairment leads to mechanical allodynia. How this decreased inhibition occurs and whether its restoration alleviates allodynic pain is poorly understood. Here, we show that the calcium (Ca2+)-binding protein, parvalbumin (PV), controls the activity of inhibitory PV-expressing neurons (PVNs) by enabling them to sustain high-frequency tonic firing patterns. Upon nerve injury, PVNs transition to adaptive firing and decrease their PV expression. Interestingly, decreased PV is necessary and sufficient to the development of mechanical allodynia and the transition of PVNs to adaptive firing. This transition of firing pattern is due to the recruitment of calcium-activated potassium (SK) channels and blocking them during chronic pain restores normal tonic firing. Our findings indicate that PV is essential to the firing activity of PVNs and in preventing allodynia, these observations may lead to novel strategies for chronic pain relief.

Although great efforts to characterize the embryonic phase of brain microvascular system development have been made, its postnatal maturation has barely been described. Here, we compared the molecular and functional properties of brain vascular cells on postnatal day (P)5 vs. P15, via a transcriptomic analysis of purified mouse cortical microvessels (MVs) and the identification of vascular-cell-type-specific or -preferentially expressed transcripts. We found that endothelial cells (EC), vascular smooth muscle cells (VSMC) and fibroblasts (FB) follow specific molecular maturation programs over this time period. Focusing on VSMCs, we showed that the arteriolar VSMC network expands and becomes contractile resulting in a greater cerebral blood flow (CBF), with heterogenous developmental trajectories within cortical regions. Samples of the human brain cortex showed the same postnatal maturation process. Thus, the postnatal phase is a critical period during which arteriolar VSMC contractility required for vessel tone and brain perfusion is acquired and mature.

High-quality mouse dorsal root ganglion (DRG) cryostat sections are crucial for proper immunochemistry staining and RNAscope studies in the research of inflammatory and neuropathic pain, itch, as well as other peripheral neurological conditions. However, it remains a challenge to consistently obtain high-quality, intact, and flat cryostat sections onto glass slides because of the tiny sample size of the DRG tissue. So far, there is no article describing an optimal protocol for DRG cryosectioning. This protocol presents a step-by-step method to resolve the frequently encountered difficulties associated with DRG cryosectioning. The presented article explains how to remove the surrounding liquid from the DRG tissue samples, place the DRG sections on the slide facing the same orientation, and flatten the sections on the glass slide without curving up. Although this protocol has been developed for cryosectioning the DRG samples, it can be applied for the cryosectioning of many other tissues with a small sample size.

The reported enterovirus A 71 (EVA71) vaccines and immunoglobin G (IgG) antibodies have no cross-antiviral efficacy against other enterovirus A (EV-A) which caused hand, foot and mouth disease (HFMD). Here we constructed an IgM antibody (20-IgM) based on our previous discovery to address the resistance encountered by IgG-based immunotherapy. Although binding to the same conserved neutralizing epitope within the GH loop of EV-As VP1, the antiviral breath and potency of 20-IgM are still higher than its parental 20-IgG1. The 20-IgM blocks the interaction between the EV-As and its receptors, scavenger receptor class B, member 2 (SCARB2) and Kringle-containing transmembrane protein 1(KREMEN1) of the host cell. The 20-IgM also neutralizes the EV-As at the post-attachment stages, including postattachment neutralization, uncoating and RNA release inhibition after internalization. Mechanistically, the dual blockage effect of 20-IgM is dependent on both a conserved site targeting and high affinity binding. Meanwhile, 20-IgM provides cross-antiviral efficacy in EV-As orally infected neonatal ICR mice. Collectively, 20-IgM and its property exhibit excellent antiviral activity with a dual-blockage inhibitory effect at both the pre- and post-attachment stages. The finding enhances our understanding of IgM-mediated immunity and highlights the potential of IgM subtype antibodies against enterovirus infections.

The prognostic impact of human papillomavirus (HPV) infection or smoking on oropharyngeal high-grade neuroendocrine carcinoma (HG-NEC) is not established.Retrospective study with patients with oropharyngeal HG-NEC seen at MD Anderson Cancer Center from 1997 to 2020, and previously reported patients with oropharyngeal HG-NEC and known p16 and HPV status from the literature review. Survival was estimated with the Kaplan-Meier method, and survival differences assessed with the log-rank test and Cox proportional hazards models.Thirty patients were included; most had a heavy (≥10 pack-years) smoking history (52%), locoregional disease (stage III-IVB; 77%), and p16-positive tumor (92%). HPV was positive in 65% of tested samples (15/23). Of 24 patients treated with curative intent, the objective response rates was 90% (9/10) and 81% (17/21), respectively, for induction chemotherapy and definitive radiotherapy. During follow-up, 54% (13/24) recurred, mostly (11/13) at distant sites. Median overall survival (OS) was 46 months (95% CI, 14.3 - NA). OS was not associated with HPV status (HR 0.73, P = 0.6) or smoking (HR 1.16, P = 0.8). Among 63 patients with known HPV status after the literature review (19 HPV- and 44 HPV + ), HPV status remained unassociated with OS (P = 0.92).This is the largest retrospective cohort of oropharyngeal HG-NEC. Distant recurrence rate after curative treatment was high, suggesting that multimodality treatment including systemic therapy may benefit patients with locally advanced disease. HPV infection did not affect survival outcomes, therefore should not lead to therapy de-intensification for this histology.

Introduction Le virus ZIKA (ZIKV) est un virus transmis par les moustiques et par le sperme, avec un fort potentiel d’émergence. Lors d’une infection pendant la grossesse, ce virus peut entraîner des anomalies fœtales cérébrales mais aussi uro-génitales, comme révélé lors de l’épidémie de 2015-2016 dans les Amériques. Description L’objectif de notre étude est de déterminer la permissivité du rein fœtal au ZIKV et les conséquences de cette infection. Méthodes Pour cela nous avons infecté ex vivo avec ZIKV des cultures organotypiques de reins fœtaux disséqués à partir de produits d’IVG obtenus entre 11 et 14 semaines d’aménorrhée. Résultats Nos résultats montrent que le ZIKV se réplique efficacement dans le rein fœtal, comme attesté par l’augmentation de l’ARN viral dans les cultures au cours du temps et par la détection in situ en RNAscope de l’ARN brin négatif produit lors de la réplication du virus. L’ARN réplicatif du ZIKV a été retrouvé dans le tissu interstitiel ainsi que dans des tubules et des glomérules en formation. Les cellules cibles du virus ont été identifiées par immunohistochimie à l’aide d’anticorps contre la protéine virale non structurale NS2b et contre des marqueurs cellulaires. Le virus est retrouvé au niveau du compartiment interstitiel dans des macrophages CD68+ et des fibroblastes SMA+ et au niveau des cellules épithéliales tubulaires CK18+. La localisation dans des cellules glomérulaires WT1+ reste à déterminer. L’infection virale n’a pas d’effet délétère majeur sur la morphologie, la viabilité et la prolifération cellulaire du rein à 6 jours post-infection. Conclusion En conclusion, ces résultats révèlent pour la première fois que le rein fœtal est permissif au virus Zika. Il serait nécessaire d’évaluer l’effet à plus long terme de l’infection sur le rein en développement. Notre modèle ex vivo pourrait permettre de tester l’efficacité d’antiviraux visant à empêcher la réplication du ZIKV dans le rein foetal.

The afferent innervation of the cochlea is comprised of spiral ganglion neurons (SGNs), which are characterized into four subtypes (Type 1A, B, and C and Type 2). However, little is known about the factors and/or processes that determine each subtype. Here, we present a transcriptional analysis of approximately 5,500 single murine SGNs collected across four developmental time points. All four subtypes are transcriptionally identifiable prior to the onset of coordinated spontaneous activity, indicating that the initial specification process is under genetic control. Trajectory analysis indicates that SGNs initially split into two precursor types (Type 1A/2 and Type 1B/C), followed by subsequent splits to give rise to four transcriptionally distinct subtypes. Differential gene expression, pseudotime, and regulon analyses were used to identify candidate transcription factors which may regulate the subtypes specification process. These results provide insights into SGN development and comprise a transcriptional atlas of SGN maturation across the prenatal period.

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Currently, there are approximately 38.4 million individuals living with the Human Immunodeficiency Virus (HIV), of which 36.7 million adults, 1.7 million children (

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