Prolyl and lysyl hydroxylases in collagen synthesis

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.     

SARS-CoV-2 host diversity: An update of natural infections and experimental evidence

Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat. This virus is supposed to be spread by human to human transmission. Cellular angiotensin-converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. Moreover, a recent study predicted that dogs might be secondary hosts during the evolution of SARS-CoV-2 from bat to human. Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets. There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks. Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne routes. Based on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to humans; needs to be deeply investigated. Humans showing clinical symptoms of respiratory infections have been undergoing for the COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic. In this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field. This review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for seroprevalence studies, especially in companion animals.     

Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.