A PKC that controls polyphosphate levels, pinocytosis and exocytosis, regulates stationary phase onset in Dictyostelium.

Many cells can pause their growth cycle, a topic much enriched by studies of the stationary phase (SP) of model microorganisms. Although several kinases are implicated in SP onset, whether protein kinase C has a role remains unknown. We show that Dictyostelium discoideum cells lacking pkcA entered SP at a reduced cell density, but only in shaking conditions. Precocious SP entry occurs because levels of extracellular polyphosphate (polyP) reach the threshold needed to induce the SP onset at a lower cell density than seen in wild-type cells; adding exopolyphosphatase to pkcA- cells reverses the effect and mimics wild-type growth. PkcA-mediated regulation of polyP depended on inositol hexakisphosphate kinase and phospholipase D. PkcA- mutants also had higher F-actin levels, higher rates of exocytosis and lower pinocytosis rates. Postlysosomes were smaller and present in fewer pkcA- cells compared to the wild type. Overall, the results suggest that a reduced PkcA level triggers SP primarily because cells do not acquire or retain nutrients as efficiently, thus mimicking, or amplifying, the conditions of actual starvation. This article has an associated First Person interview with the first author of the paper.

Prevalence of immune mediated vesiculobullous lesions among patients visiting a private dental hospital with special emphasis on gingival manifestation.

Background and Aim: Vesiculobullous lesions are a group of mucocutaneous lesions that are predominantly immune-mediated but may also have a genetic or viral origin. The most common site of occurrence is buccal mucosa, whereas the number of cases involving gingiva is comparatively low. Based on the literature, although numerous studies have reported the prevalence of vesiculobullous lesions in the nonkeratinized epithelium, there is a dearth of knowledge about its occurrence in keratinized oral mucosa, especially gingiva. The objective of the study was to assess the prevalence of immune-mediated oral vesiculobullous lesions emphasizing the occurrence in keratinized mucosa, especially the gingiva, among patients visiting a private dental hospital. Materials and Methods: The study was conducted in a private teaching dental institute and hospital setting. Out of 615 incisional biopsies received in the department of oral pathology, between June 2019 and April 2021, n = 22 samples were immune-mediated vesiculobullous lesions confirmed by clinical and histopathological diagnosis after eliminating lesions of viral origin. Patient details including age, gender, site, duration, and systemic illness were collected from the digital information archiving software and analyzed by appropriate statistics using SPSS software. Results: Based on the results, 95.5% of the patients had histopathological features of intraepithelial clefting and only 4.5% of them showed subepithelial clefting. Female predilection was 6.3:1. The most common site of involvement was nonkeratinized mucosa (36.36%) and 59.09% of the patients presented with systemic illness. Conclusion: The study shows most of the features of pemphigus is consistent in gingiva and other parts of oral mucosa. The dental practitioners should be aware of the various oral manifestations of such lesions to ensure accurate diagnosis and adequate treatment.

PARK2 gene mutations in early onset Parkinson's disease patients of South India.

With the etiology being unclear till date, a combination of age, genetic and environmental factors are known to play a significant role in the pathogenesis of Parkinson's disease. Mutations in PARK2 gene have been implicated to cause autosomal recessive early onset PD. We analyzed the 12 coding exons of PARK2 gene in 16 early onset PD patients of South Indian ethnicity. PARK2 mutations were present in 68% of the early onset cases. We report the presence of four PARK2 sequence variants c.1239G>C, c.171+25T>C, c.202A>G, c.601G>A, and a novel insertion mutation, c.798_799insA in the exon 7 of PARK2 gene. These results suggest that mutations in PARK2 gene may be a common cause of PD among South Indian early onset patients.

Altered angiogenic balance in keloids: a key to therapeutic intervention.

Keloids are manifestations of abnormal wound repair with unresolved clinical complications. An effective therapeutic regimen has not been established for keloids, and current strategies are plagued by problems such as recurrence and side effects. Keloids, being a human-specific dermal fibroproliferative disorder are characterized by an excessive accumulation of extracellular matrix (ECM), thickened basement membrane, unregulated expression of matrix metalloproteases, growth factors, and cytokines. The internal milieu in a keloid bears a strong resemblance to a tumor with both exhibiting striking similarities with respect to tissue environment and unregulated vasculature. Abnormal angiogenesis manifested by an imbalance between proangiogenic and antiangiogenic factors has been recognized as a "common denominator" underlying many pathological conditions. However, such an imbalance has not been investigated in keloids. In this study, the angiogenic imbalance in keloids was explored with reference to circulating and tissue level expression of vascular endothelial growth factor (VEGF) and endostatin/collagen XVIII. It was observed that VEGF levels were upregulated and endostatin levels were downregulated in keloid patients in comparison to normal controls in both sera and tissue. Hence, antiangiogenic therapeutics based on endostatin in combination with current curative strategies as in tumors would present a scope for the effective management of keloids.