Interplay of Nkx3.2, Sox9 and Pax3 Regulates Chondrogenic Differentiation of Muscle Progenitor Cells

Muscle satellite cells make up a stem cell population that is capable of differentiating into myocytes and contributing to muscle regeneration upon injury. In this work we investigate the mechanism by which these muscle progenitor cells adopt an alternative cell fate, the cartilage fate. We show that chick muscle satellite cells that normally would undergo myogenesis can be converted to express cartilage matrix proteins in vitro when cultured in chondrogenic medium containing TGFß3 or BMP2. In the meantime, the myogenic program is repressed, suggesting that muscle satellite cells have undergone chondrogenic differentiation. Furthermore, ectopic expression of the myogenic factor Pax3 prevents chondrogenesis in these cells, while chondrogenic factors Nkx3.2 and Sox9 act downstream of TGFß or BMP2 to promote this cell fate transition. We found that Nkx3.2 and Sox9 repress the activity of the Pax3 promoter and that Nkx3.2 acts as a transcriptional repressor in this process. Importantly, a reverse function mutant of Nkx3.2 blocks the ability of Sox9 to both inhibit myogenesis and induce chondrogenesis, suggesting that Nkx3.2 is required for Sox9 to promote chondrogenic differentiation in satellite cells. Finally, we found that in an in vivo mouse model of fracture healing where muscle progenitor cells were lineage-traced, Nkx3.2 and Sox9 are significantly upregulated while Pax3 is significantly downregulated in the muscle progenitor cells that give rise to chondrocytes during fracture repair. Thus our in vitro and in vivo analyses suggest that the balance of Pax3, Nkx3.2 and Sox9 may act as a molecular switch during the chondrogenic differentiation of muscle progenitor cells, which may be important for fracture healing

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

INTRODUCTION: Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear.METHODS: This multi-centre cohort study involved patients aged 18years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables.RESULTS: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54-83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18-49: HR 3.57, CI 2.54-5.02), frailty (CFS 8 vs 1-3: HR 3.03, CI 2.29-4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1-3: OR 7.00, CI 5.27-9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9.CONCLUSIONS: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age

A prospective hospital based study showing prevalence of eye manifestations in patients having systemic inflammatory autoimmune disease

Aim: To outline several common ocular complications and their prevalence in patients with systemic inflammatory autoimmune disease.Material and Methods:The study included 135 patients having systemic inflammatory autoimmune disease (rheumatoid arthritis) who attended ophthalmology out patient department in Govt. Medical College Jammu. The patients underwent detailed ocular examination, slit lamp biomicroscopy, ophthalmoscopy. The tear function of all the patients was assessed using Schirmer’s test, tear film breakup time and ocular surface staining.Results: Fifty three (39%) patients out of the 135 patients had ocular manifestations of rheumatoid arthritis. Dry eye was the most common manifestation which was seen in about 28 patients (53%). The ocular manifestations were more common in females (78%).The manifestations were bilateral in 45 patients(85%).Ten patients (19%) had features of scleritis, three (6%) with episcleritis, 10 patients having anterior uveitis (19%) and other manifestations peripheral ulcerative  keratitis (PUK) ,retinal vasculitis, keratitis contributed 1% each or less. Conclusion: Ocular manifestations contribute significantly to the extra articular manifestations of the Rheumatoid Arthritis. Dry eye is the commonest complication. There was a female preponderance in the study and also the manifestations were more frequently found bilaterally. Keywords: Ocular manifestations, Rheumatoid Arthritis, Episcleritis,Uveitis

L-Ascorbic Acid Restricts Vibrio cholerae Survival in Various Growth Conditions

Cholera, a deadly diarrheal disease, continues to ravage various parts of the world. It is caused by Vibrio cholerae, an important member of the gamma-proteobacteria. Based on certain genetic and phenotypic tests, the organism is classified into two major biotypes, namely classical and El Tor. The El Tor and its variants are majorly responsible for the ongoing seventh pandemic across the globe. Previously, we have shown that cross-feeding of glucose metabolic acidic by-products of gut commensals can severely affect the viability of the biotypes. In this work, we examined the effect of L-ascorbic acid on the survival of Vibrio cholerae strains belonging to both biotypes and different serotypes. We observed that L-ascorbic acid effectively restricts the growth of all strains under various conditions including strains adapted to acid stress. In addition, L-ascorbic acid is also effective in decreasing bile-induced biofilms of Vibrio cholerae

Detection of Acid-Fast Bacilli in Postlysis Debris of Clinical Specimens Improves the Reliability of PCR

This article does not have an abstract

Identification of critical amino acids in the DNA binding domain of LuxO: Lessons from a constitutive active LuxO.

Quorum sensing plays a vital role in the environmental and host life cycles of Vibrio cholerae. The quorum-sensing circuit involves the consorted action of autoinducers, small RNAs, and regulatory proteins to control a plethora of physiological events in this bacterium. Among the regulatory proteins, LuxO is considered a low-cell-density master regulator. It is a homolog of NtrC, a two-component response regulator. NtrC belongs to an evolving protein family that works with the alternative sigma factor σ54 to trigger gene transcription. Structurally, these proteins comprise 3 domains: a receiver domain, a central AAA+ATPase domain, and a C-terminal DNA-binding domain (DBD). LuxO communicates with its cognate promoters by employing its DNA binding domain. In the present study, we desired to identify the critical residues in the DBD of LuxO. Our combined mutagenesis and biochemical assays resulted in the identification of eleven residues that contribute significantly to LuxO regulatory function

Orbital ectopic glial tissue in relation to medial rectus: a rare entity

Heterotopic brain tissue is a rare entity and it is rarer still in the orbit. There have been very few case reports of orbital ectopic glial tissue. The case is described herein of a 3-month-old baby presenting with an orbital glial hamartoma inseparable from the medial rectus muscle. The diagnosis was based on the histopathological features and a positive GFAP stain. The features of this case and the previously reported cases are discussed