RNAscope

Ca2+ sensor proteins in spontaneous release and synaptic plasticity: Limited contribution of Doc2c, Rabphilin-3a and Synaptotagmin 7 in hippocampal glutamatergic neurons

Presynaptic neurotransmitter release is strictly regulated by SNARE proteins, Ca2+ and a number of Ca2+ sensors including synaptotagmins (Syts) and Double C2 domain proteins (Doc2s). More than seventy years after the original description of spontaneous release, the mechanism that regulates this process is still poorly understood. Syt-1, Syt7 and Doc2 proteins contribute predominantly, but not exclusively, to synchronous, asynchronous and spontaneous phases of release.

Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH

Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer1,2. The accumulation of metabolites leads to cell stress and inflammation in the liver3, but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displays key features of human NASH (hereafter, NASH mice), we found an indispensable role for T cells in liver immunopathology.

ROC Analysis of p16 Expression in Cell Blocks of Metastatic Head and Neck Squamous Cell Carcinoma

Background Oropharyngeal squamous cell carcinoma is associated with human papillomavirus (HPV) and often presents with early metastasis to cervical neck lymph nodes which are amenable to fine needle aspiration (FNA). The most common method of HPV status determination is p16 immunohistochemistry (IHC). The literature suggests that a lower threshold is needed for p16 positivity on cell block. We examined and quantified p16 IHC staining on cell block and used ROC curve analysis to determine an optimal cut off value with high sensitivity and specificity.

The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr

Silencing of nuclear DNA is an essential feature of innate immune responses to invading pathogens. Early in infection, unintegrated lentiviral cDNA accumulates in the nucleus yet remains poorly expressed. In HIV-1-like lentiviruses, the Vpr accessory protein enhances unintegrated viral DNA expression, suggesting Vpr antagonizes cellular restriction. We previously showed how Vpr remodels the host proteome, identifying multiple cellular targets.

A primary nasopharyngeal three-dimensional air-liquid interface cell culture model of the pseudostratified epithelium reveals differential donor- and cell type-specific susceptibility to Epstein-Barr virus infection

Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection.

Cannabinoid CB2 receptors are expressed in glutamate neurons in the red nucleus and functionally modulate motor behavior in mice

Cannabinoids produce a number of central nervous system effects via the CB2 receptor (CB2R), including analgesia, antianxiety, anti-reward, hypoactivity and attenuation of opioid-induced respiratory depression. However, the cellular distributions of the CB2Rs in the brain remain unclear. We have reported that CB2Rs are expressed in midbrain dopamine (DA) neurons and functionally regulate DA-mediated behavior(s). Unexpectedly, high densities of CB2-like signaling were also found in a neighboring motor structure - the red nucleus (RN) of the midbrain.

Activation of notch signaling in dorsal root ganglia innervating knee joints in experimental osteoarthritis

Purpose: Surgical destabilization of the medial meniscus (DMM) is a widely used mouse model of knee osteoarthritis (OA). The cell bodies of primary sensory neurons innervating the knee joints are located in the lumbar dorsal root ganglia (L3-L5 DRG). Analysis of the gene expression profile of L3-L5 DRG after DMM or sham surgery revealed that innate neuro-immune pathways were strongly regulated, especially in the later stages of the model, 8-16 weeks after DMM, when persistent pain is associated with severe joint damage.

Association of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene expression and rs2383207 variant with breast cancer risk and survival

The expression signature of deregulated long non-coding RNAs (lncRNAs) and related genetic variants is implicated in every stage of tumorigenesis, progression, and recurrence. This study aimed to explore the association of lncRNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene expression and the rs2383207A>G intronic variant with breast cancer (BC) risk and prognosis and to verify the molecular role and networks of this lncRNA in BC by bioinformatics gene analysis.

Nox3-derived superoxide in cochleae induces sensorineural hearing loss Mechanisms of Nox3-dependent hearing loss

Reactive oxygen species (ROS) produced by NADPH oxidases (Nox) contribute to the development of different types of sensorineural hearing loss (SNHL), a common impairment in humans with no established treatment. Although the essential role of Nox3 in otoconia biosynthesis and its possible involvement in hearing have been reported in rodents, immunohistological methods targeted at detecting Nox3 expression in inner ear cells reveal ambiguous results. Therefore, the mechanism underlying Nox3-dependent SNHL remains unclear and warrants further investigation.

Emerging role of lncRNA ELDR in development and cancer

Whole-genome sequencing and transcriptome analysis revealed more than 90% of the human genome transcribes noncoding RNAs including lncRNAs. From the beginning of the 21st century, lncRNAs have gained widespread attention as a new layer of regulation in biological processes. lncRNAs are > 200 nucleotides in size, transcribed by RNA polymerase II, and share many similarities with mRNAs. lncRNA interacts with DNA, RNA, protein, and miRNAs, thereby regulating many biological processes.

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