Publication

Morphological Object Localization: A Novel Image Analysis Pipeline for Quantitative Spatial Localization of Biomolecule Signal from Fluorescence Microscopy Data

The spatial distribution of biomolecules (BMs) within cells and tissues is often a significant determinant of biological / physiological function. Thus, its assessment is not only a ubiquitous feature in the life sciences but also a vital component in the clinical diagnosis and treatment of many pathologies. This typically entails microscopic imaging of fluorescently labeled biomolecules within biological specimens and analysis and interpretation of the resulting images.

Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease

People of recent sub-Saharan African ancestry develop kidney failure much more frequently than other groups. A large fraction of this disparity is due to two coding sequence variants in the APOL1 gene. Inheriting two copies of these APOL1 risk variants, known as G1 and G2, causes high rates of focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy and hypertension-associated end-stage kidney disease. Disease risk follows a recessive mode of inheritance, which is puzzling given the considerable data that G1 and G2 are toxic gain-of-function variants.

Mouse papillomavirus type 1 (MmuPV1) DNA is frequently integrated in benign tumors by microhomology-mediated end-joining

MmuPV1 is a useful model for studying papillomavirus-induced tumorigenesis. We used RNA-seq to look for chimeric RNAs that map to both MmuPV1 and host genomes. In tumor tissues, a higher proportion of total viral reads were virus-host chimeric junction reads (CJRs) (1.9‰ - 7‰) than in tumor-free tissues (0.6‰ - 1.3‰): most CJRs mapped to the viral E2/E4 region.

ERα determines the chemoresistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2 expressions

Mutant p53 (mutp53) commonly loses their DNA binding affinity to p53 response elements (p53REs) and fails to induce apoptosis fully. However, the p53 mutation does not predict chemoresistance in all subtypes of breast cancers, and the critical determinants remain to be identified. In this study, mutp53 was found to mediate chemotherapy-induced lincRNA-p21 expression by targeting the G-quadruplex structure rather than the p53RE on its promoter to promote chemosensitivity.

Circular RNA circ-TNPO3 suppresses metastasis of gastric cancer by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL

Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-TNPO3 was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues.

Leptin brain entry via a tanycytic LepR-EGFR shuttle controls lipid metabolism and pancreas function

Metabolic health depends on the brain's ability to control food intake and nutrient use versus storage, processes that require peripheral signals such as the adipocyte-derived hormone, leptin, to cross brain barriers and mobilize regulatory circuits. We have previously shown that hypothalamic tanycytes shuttle leptin into the brain to reach target neurons.

A neural substrate of compulsive alcohol use

Alcohol intake remains controlled in a majority of users but becomes "compulsive," i.e., continues despite adverse consequences, in a minority who develop alcohol addiction. Here, using a footshock-punished alcohol self-administration procedure, we screened a large population of outbred rats to identify those showing compulsivity operationalized as punishment-resistant self-administration.

Acute Liver Failure in a Healthy Young Female With COVID-19

Liver biopsy on HD15 showed an acute hepatitis pattern of injury with predominantly centrizonal areas of confluent necrosis and lobular cholestasis. Necrotic areas were focally hemorrhagic and showed mild lymphoplasmacytic infiltrate with admixed histiocytes, few eosinophils, and neutrophils. Portal inflammation was minimal and interlobular bile ducts were largely intact. No fibrin thrombi were identified. Residual hepatocytes showed ballooning degeneration, some with prominent nucleoli, apoptosis, pseudoacini formation, and mild steatosis (

CACHD1-deficient mice exhibit hearing and balance deficits associated with a disruption of calcium homeostasis in the inner ear

CACHD1 recently was shown to be an α2δ-like subunit that can modulate the activity of some types of voltage-gated calcium channels, including the low-voltage activated, T-type CaV3 channels. CACHD1 is widely expressed in the central nervous system but its biological functions and relationship to disease states are unknown. Here, we report that mice with deleterious Cachd1 mutations are hearing impaired and have balance defects, demonstrating that CACHD1 is functionally important in the peripheral auditory and vestibular organs of the inner ear.

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