RNAscope 2.5 HD Brown Assay

TRIM40 is a pathogenic driver of inflammatory bowel disease subverting intestinal barrier integrity

The cortical actin cytoskeleton plays a critical role in maintaining intestinal epithelial integrity, and the loss of this architecture leads to chronic inflammation, as seen in inflammatory bowel disease (IBD). However, the exact mechanisms underlying aberrant actin remodeling in pathological states remain largely unknown. Here, we show that a subset of patients with IBD exhibits substantially higher levels of tripartite motif-containing protein 40 (TRIM40), a gene that is hardly detectable in healthy individuals.

ASH2L Controls Ureteric Bud Morphogenesis via Regulation of RET/GFRA1 Signaling Activity in a Mouse Model

Ureteric bud induction and branching morphogenesis is fundamental to the establishment of the renal architecture and is a key determinant of nephron number. Defective ureteric bud morphogenesis could give rise to a spectrum of malformations associated with congenital anomalies of the kidney and urinary tract (CAKUT). Signaling involving glial cell line-derived neurotrophic factor and its receptor RET and coreceptor GFRA1 appears to be particularly important in ureteric bud development.

Analysis of gene expression in poultry red mite, Dermanyssus gallinae, by RNAscope in situ hybridization

The poultry red mite (PRM; Dermanyssus gallinae) is a hematophagous ectoparasite that mainly infests chickens, and its infestation causes significant economic losses to the poultry industry. In this study, we examined the use of RNAscope-based in situ hybridization (ISH) to characterize gene expression in PRM. We analyzed the mRNA expression of Dermanyssus gallinaecathepsin D-1 (Dg-CatD-1) and Dermanyssus gallinae cystatin (Dg-Cys).

Mathematical Modelling of Cervical Precancerous Lesion Grade Risk Scores: Linear Regression Analysis of Cellular Protein Biomarkers and Human Papillomavirus E6/E7 RNA Staining Patterns

The current practice of determining histologic grade with a single molecular biomarker can facilitate differential diagnosis but cannot predict the risk of lesion progression. Cancer is caused by complex mechanisms, and no single biomarker can both make accurate diagnoses and predict progression risk. Modelling using multiple biomarkers can be used to derive scores for risk prediction. Mathematical models (MMs) may be capable of making predictions from biomarker data.

Identification of GPI-anchored protein LYPD1 as an essential factor for odontoblast differentiation in tooth development

Lipid rafts are membrane microdomains rich in cholesterol, sphingolipids, glycosylphosphatidylinositol-anchored proteins (GPI-APs), and receptors. These lipid raft components are localized at the plasma membrane and are essential for signal transmission and organogenesis. However, few reports have been published on the specific effects of lipid rafts on tooth development. Using microarray and single-cell RNA sequencing methods, we found that a GPI-AP, lymphocyte antigen-6 (Ly6)/Plaur domain-containing 1 (Lypd1), was specifically expressed in preodontoblasts.

Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies

Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy.

Abnormal p53 Immunohistochemical Patterns Shed Light on the Aggressiveness of Oral Epithelial Dysplasia

The diagnosis of oral epithelial dysplasia is based on the degree of architectural and cytologic atypia in the squamous epithelium. The conventional grading system of mild, moderate, and severe dysplasia is considered by many the gold standard in predicting the risk of malignant transformation. Unfortunately, some low-grade lesions, with or without dysplasia, progress to squamous cell carcinoma (SCC) in short periods. As a result, we are proposing a new approach to characterize oral dysplastic lesions that will help identify lesions at high risk for malignant transformation.

Radiotherapy exposure directly damages the uterus and causes pregnancy loss

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells.

Stress keratin 17 and estrogen support viral persistence and modulate the immune environment during cervicovaginal murine papillomavirus infection

A murine papillomavirus, MmuPV1, infects both cutaneous and mucosal epithelia of laboratory mice and can be used to model high-risk human papillomavirus (HPV) infection and HPV-associated disease. We have shown that estrogen exacerbates papillomavirus-induced cervical disease in HPV-transgenic mice. We have also previously identified stress keratin 17 (K17) as a host factor that supports MmuPV1-induced cutaneous disease. Here, we sought to test the role of estrogen and K17 in MmuPV1 infection and associated disease in the female reproductive tract.

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and the mechanisms involved remain unknown. Here we show that SARS-CoV-2 causes DNA damage and elicits an altered DNA damage response. Mechanistically, SARS-CoV-2 proteins ORF6 and NSP13 cause degradation of the DNA damage response kinase CHK1 through proteasome and autophagy, respectively.

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