Publication

Huntington's disease (HD) is a severe neurodegenerative disorder caused by the expansion of the CAG trinucleotide repeat tract in the huntingtin gene. Inheritance of expanded CAG repeats is needed for HD manifestation, but further somatic expansion of the repeat tract in non-dividing cells, particularly striatal neurons, hastens disease onset. Called somatic repeat expansion, this process is mediated by the mismatch repair (MMR) pathway.

Patients with mutations in the TMPRSS3 gene suffer from recessive deafness DFNB8/DFNB10. For these patients, cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knockin mouse model with a frequent human DFNB8 TMPRSS3 mutation. The Tmprss3A306T/A306T homozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients.

While persistence of fear memories is essential for survival, a failure to inhibit fear in response to harmless stimuli is a feature of anxiety disorders. Extinction training only temporarily suppresses fear memory recovery in adults, but it is highly effective in juvenile rodents. Maturation of GABAergic circuits, in particular of parvalbumin-positive (PV+) cells, restricts plasticity in the adult brain, thus reducing PV+ cell maturation could promote the suppression of fear memories following extinction training in adults.

IL-17A has a pivotal pathogenic role in several immune-mediated inflammatory diseases. Despite sharing 50% sequence homology with IL-17A, the role of IL-17F remains less clear.

METHODS : Gene expression of ABCA1 and ApoA1 on human donor tissue and iPSC-RPE were examined by qPCR (n=3). Bulk RNAseq examined transcript changes in key RCT genes on donor retinas across different stages of disease progression. RNAscope probes (ACDBio) were designed against abca1 transcripts with appropriate mismatch controls. Neutral lipid stain with oil-red O on 10um cryo-sections of abca1 KO and wild type (WT) eyes (N= 5). Two siRNAs knocked down abca1 in iPSC-RPE cells to assess abca1 contribution to cholesterol efflux (n=3).

METHODS : To induce OIR, C57BL/6J mice were exposed to 75% oxygen from postnatal day (p) 7 to p12 and then maintained under normal room air conditions. Control mice were kept under room air conditions throughout. At p12, p17, and p25, one eye of each mouse was harvested to prepare retinal flatmounts to analyze retinal vascular changes. From the contralateral eye, total RNA was isolated and reverse transcribed into cDNA for relative quantification of miRNA expression using qRT-PCR.

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC’s systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality.

Methods: In this proof-of-concept study, we performed bedside ultrasound-guided minimally invasive autopsies (US-MIA) of patients that had died from critical COVID-19 in the intensive care unit (ICU) using a structured protocol to obtain almost autolytic-free tissue. Biopsies were assessed for quality (vitality and length) and for diagnosis. The efficiency of the procedure was monitored in five cases by recording the time of each step and safety issues by swabbing personal protective equipment and devices for viral contamination. 

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 (

(1) Background: There are no high-throughput microtissue platforms for generating bone marrow micro-ossicles. Herein, we describe a method for the assembly of arrays of microtissues from bone marrow stromal cells (BMSC) in vitro and their maturation into bone marrow micro-ossicles in vivo. (2) Methods: Discs with arrays of 50 microwells were used to assemble microtissues from 3 × 105 BMSCs each on a nylon mesh carrier.