Publication

NaV1.1 is essential for proprioceptive signaling and motor behaviors

The voltage-gated sodium channel (NaV), NaV1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for NaV1.1 in mammalian proprioception. RNAscope analysis and in vitro patch clamp recordings in genetically identified mouse proprioceptors show ubiquitous channel expression and significant contributions to intrinsic excitability.

Recalibrating vision-for-action requires years after sight restoration from congenital cataracts

Being able to perform adept goal-directed actions requires predictive, feed-forward control, including a mapping between the visually estimated target locations and the motor commands reaching for them. When the mapping is perturbed, e.g., due to muscle fatigue or optical distortions, we are quickly able to recalibrate the sensorimotor system to update this mapping. Here, we investigated whether early visual and visuomotor experience is essential for developing sensorimotor recalibration.

Muc16 depletion diminishes KRAS-induced tumorigenesis and metastasis by altering tumor microenvironment factors in pancreatic ductal adenocarcinoma

MUC16, membrane-bound mucin, plays an oncogenic role in pancreatic ductal adenocarcinoma (PDAC). However, the pathological role of MUC16 in the PDAC progression, tumor microenvironment, and metastasis in cooperation with KrasG12D and Trp53R172H mutations remains unknown.

Albumin, filamin-A and cytokeratin 19 help distinguish intrahepatic cholangiocarcinoma from extrahepatic adenocarcinoma

The differential diagnosis of intrahepatic cholangiocarcinomas (iCCAs) from metastatic adenocarcinomas from organs adjacent to the liver (gallbladder, pancreas, and stomach) is difficult due to histopathological similarity and a lack of specific markers.

Sparcl1/Hevin drives pathological pain through spinal cord astrocyte and NMDA receptor signaling

Hevin/Sparcl1 is an astrocyte-secreted protein and regulates synapse formation. Here we show that astrocytic hevin signaling plays a critical role in maintaining chronic pain. Compared to wild-type mice, hevin-null mice exhibited normal mechanical and heat sensitivity but reduced inflammatory pain. Interestingly, hevin-null mice have faster recovery than wild-type mice from neuropathic pain after nerve injury. Intrathecal injection of wild-type hevin was sufficient to induce persistent mechanical allodynia in naïve mice.

Subtype C HIV-1 reservoirs throughout the body in ART-suppressed individuals

Subtype B HIV-1 reservoirs have been intensively investigated, but reservoirs in other subtypes and how they respond to antiretroviral therapy (ART) is substantially less established. To characterize subtype C HIV-1 reservoirs, we implemented postmortem frozen, as well as formalin fixed paraffin embedded (FFPE) tissue sampling of central nervous system (CNS) and peripheral tissues. HIV-1 LTR, gag, envelope (env) DNA and RNA was quantified using genomic DNA and RNA extracted from frozen tissues. RNAscope was used to localize subtype C HIV-1 DNA and RNA in FFPE tissue.

Intestinal epithelial BLT1 promotes mucosal repair

Acute and chronic intestinal inflammation is associated with epithelial damage, resulting in mucosal wounds in the forms of erosions and ulcers in the intestinal tract. Intestinal epithelial cells (IECs) and immune cells in the wound milieu secrete cytokines and lipid mediators to influence repair. Leukotriene B4 (LTB4), a lipid chemokine, binds to its receptor BLT1 and promotes migration of immune cells to sites of active inflammation, however a role for intestinal epithelial BLT1 during mucosal wound repair is not known.

ISGylation is induced in neurons by demyelination driving ISG15-dependent microglial activation

The causes of grey matter pathology and diffuse neuron injury in MS remain incompletely understood. Axonal stress signals arising from white matter lesions has been suggested to play a role in initiating this diffuse grey matter pathology. Therefore, to identify the most upstream transcriptional responses in neurons arising from demyelinated axons, we analyzed the transcriptome of actively translating neuronal transcripts in mouse models of demyelinating disease. Among the most upregulated genes, we identified transcripts associated with the ISGylation pathway.

Cardiometabolic Consequences of Deleting the Regulator of G protein Signaling-2 (Rgs2) From Cells Expressing Agouti-Related Peptide or the ANG (Angiotensin) II Type 1A Receptor in Mice

RGS (regulator of G protein signaling) family members catalyze the termination of G protein signaling cascades. Single nucleotide polymorphisms in the RGS2 gene in humans have been linked to hypertension, preeclampsia, and anxiety disorders. Mice deficient for Rgs2 (Rgs2Null) exhibit hypertension, anxiety, and altered adipose development and function.To study cell-specific functions of RGS2, a novel gene-targeted mouse harboring a conditional allele for the Rgs2 gene (Rgs2Flox) was developed.

Stellate cell expression of SPARC-related modular calcium-binding protein 2 is associated with human non-alcoholic fatty liver disease severity

Background & Aims Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the hepatic manifestations of metabolic syndrome. Histological assessment of liver biopsies is the gold standard for diagnosis of NASH. A Liver biopsy is resource heavy, can lead to complications such as bleeding, and does not fully capture tissue heterogeneity of the fibrotic liver. Therefore, non-invasive biomarkers that can reflect an integrated state of the liver are highly needed to improve diagnosis and sampling bias.

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