RNAscope

Cell-type specific molecular architecture for mu opioid receptor function in pain and addiction circuits

Opioids are potent analgesics broadly used for pain management; however, they can produce dangerous side effects including addiction and respiratory depression. These harmful effects have led to an epidemic of opioid abuse and overdose deaths, creating an urgent need for the development of both safer pain medications and treatments for opioid use disorders. Both the analgesic and addictive properties of opioids are mediated by the mu opioid receptor (MOR), making resolution of the cell types and neural circuits responsible for each of the effects of opioids a critical research goal.

Double-stranded RNA immunohistochemistry as a screening tool for viral encephalitis

Viral infections of the central nervous system can be challenging to diagnose because of the wide range of causative agents and nonspecific histologic features.

Nucleobindin-2 Mediates Transforming Growth Factor-β1-Driven Phenotypes in ZEB1-High Uterine Carcinosarcoma

Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, we used shotgun proteomics analysis to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS, and found up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells.

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease

Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies lack a large animal model. This study validates ISC isolation in a new porcine Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5) reporter line and demonstrates the use of these pigs as a novel colorectal cancer (CRC) model.

Aging Changes the Efficacy of Central Urocortin 2 to Induce Weight Loss in Rats

Middle-aged obesity and aging cachexia present healthcare challenges. Central responsiveness to body-weight-reducing mediators, e.g., to leptin, changes during aging in a way, which may promote middle-aged obesity and aging cachexia. Leptin is connected to urocortin 2 (Ucn2), an anorexigenic and hypermetabolic member of the corticotropin family. We aimed to study the role of Ucn2 in middle-aged obesity and aging cachexia.

"ThermoTRP" Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist)

Temperature-sensitive transient receptor potential (TRP) channels (so-called "thermoTRPs") are multifunctional signaling molecules with important roles in cell growth and differentiation. Several "thermoTRP" channels show altered expression in cancers, though it is unclear if this is a cause or consequence of the disease. Regardless of the underlying pathology, this altered expression may potentially be used for cancer diagnosis and prognostication. "ThermoTRP" expression may distinguish between benign and malignant lesions.

Emerging roles of brain tanycytes in regulating blood-hypothalamus barrier plasticity and energy homeostasis

Seasonal changes in food intake and adiposity in many animal species are triggered by changes in the photoperiod. These latter changes are faithfully transduced into a biochemical signal by melatonin secreted by the pineal gland. Seasonal variations, encoded by melatonin, are integrated by third ventricular tanycytes of the mediobasal hypothalamus through the detection of the thyroid-stimulating hormone (TSH) released from the pars tuberalis.

Forward genetic screening using fundus spot scale identifies an essential role for Lipe in murine retinal homeostasis

Microglia play a role in the pathogenesis of many retinal diseases. Fundus spots in mice often correlate with the accumulation of activated subretinal microglia. Here we use a semiquantitative fundus spot scoring scale in combination with an unbiased, state-of-the-science forward genetics pipeline to identify causative associations between chemically induced mutations and fundus spot phenotypes. Among several associations, we focus on a missense mutation in Lipe linked to an increase in yellow fundus spots in C57BL/6J mice.

Osteocytes: New Kids on the Block for Cancer in Bone Therapy

The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where they interact with different cells of the bone marrow. These interactions transform the bone into an ideal niche for cancer cell migration, proliferation, and survival and cause an imbalance in bone homeostasis that severely affects the integrity of the skeleton.

CHIP inhibits odontoblast differentiation through promoting DLX3 polyubiquitylation and degradation

Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects.

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