Genome-wide study predicts promoter-G4 DNA motifs regulate selective functions in bacteria: radioresistance of D. radiodurans involves G4 DNA-mediated regulation

A remarkable number of guanine-rich sequences with potential to adopt non-canonical secondary structures called G-quadruplexes (or G4 DNA) are found within gene promoters. Despite growing interest, regulatory role of quadruplex DNA motifs in intrinsic cellular function remains poorly understood. Herein, we asked whether occurrence of potential G4 (PG4) DNA in promoters is associated with specific function(s) in bacteria. Using a normalized promoter-PG4-content (PG4P) index we analysed >60 000 promoters in 19 well-annotated species for (a) function class(es) and (b) gene(s) with enriched PG4P. Unexpectedly, PG4-associated functional classes were organism specific, suggesting that PG4 motifs may impart specific function to organisms. As a case study, we analysed radioresistance. Interestingly, unsupervised clustering using PG4P of 21 genes, crucial for radioresistance, grouped three radioresistant microorganisms including Deinococcus radiodurans. Based on these predictions we tested and found that in presence of nanomolar amounts of the intracellular quadruplex-binding ligand N-methyl mesoporphyrin (NMM), radioresistance of D. radiodurans was attenuated by ∼60%. In addition, important components of the RecF recombinational repair pathway recA, recF, recO, recR and recQ genes were found to harbour promoter-PG4 motifs and were also down-regulated in presence of NMM. Together these results provide first evidence that radioresistance may involve G4 DNA-mediated regulation and support the rationale that promoter-PG4s influence selective functions

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Effect of transportation on the quality of the donor corneal buttons

The aim of this study is to see the effect of transportation on corneoscleral buttons and to correlate them with the weight of ice used during transportation. This is a prospective cross-sectional study. A total of 119 corneas were graded using slit-lamp examination and specular microscopy before and after transportation. Groups were made based on the weight of ice used during transportation and the number of hours of storage in McCarey-Kaufman (MK) media. The overall median percentage of endothelial cell loss (ECL) was 11.33%. The median percentage of ECL was significantly more with <500 g of ice as compared to ≥500 g (13.6% vs. 7.56%) with P = 0.006. There was no significant difference in percentage of ECL on storage in MK media for ≤48 h, ≤72 h, and ≤96 h. Corneal buttons have ECL on storage and transportation which can be minimized using the appropriate weight of ice during transportation

Melanogenesis Inhibitors

Abnormally high production of melanin or melanogenesis in skin melanocytes results in hyperpigmentation disorders, such as melasma, senile lentigines or freckles. These hyperpigmentary skin disorders can significantly impact an individual’s appearance, and may cause emotional and psychological distress and reduced quality of life. A large number of melanogenesis inhibitors have been developed, but most have unwanted side-effects. Further research is needed to better understand the mechanisms of hyperpigmentary skin disorders and to develop potent and safe inhibitors of melanogenesis. This review summarizes the current understanding of melanogenesis regulatory pathways, the potential involvement of the immune system, various drugs in current use, and emerging treatment strategies to suppress melanogenesis

Modulating the optical and electrical properties of all metal oxide solar cells through nanostructuring and ultrathin interfacial layers

The benefits and drawbacks of nanostructuring in all oxide ZnO/Cu2O solar cells were studied. The solar cells were fabricated on fluorine doped tin oxide substrates, with solution processed deposition methods. Both planar ZnO layer and Cu2O were deposited by electrodeposition while ZnO nanorods were grown by chemical bath deposition technique. It is shown that short circuit current (Jsc) of the devices increases with nanostructuring of ZnO due to electrical and optical gains. Despite improving the photocurrent, nanostructuring decreases the Voc of the device due to carrier recombination. The introduction of a thin TiO2 interfacial layer through atomic layer deposition was able to reduce the recombination

New insights into acne pathogenesis: Exploring the role of acne-associated microbial populations

AbstractAcne vulgaris, a prevalent disorder of the skin, is found to increase the incidence of suicidal ideation in acne patients (∼7.1%). This creates a dilemma in the mind whether acne is a life threatening disease among humans. The main inducer for this multifactorial disease is microbial fluctuation of common resident microbes on the skin with each microbe possessing their own purpose and style in protecting the human body. For acne progression, the microbial population has to get around the defense barriers of the host skin and be able to also resist them in order to survive. These matters have been resolved by their pathogenic lifecycle and associated virulence factors coded within their pathogenic islands in the single circular chromosome. This review addresses the different microbial populations residing in acne lesions and promoting acne by emphasizing their pathogenic mechanisms and the genes associated with virulence factors involved in the development of acne. Model systems such as animal models and cell culture models in studying the pathogenic lifestyle of the microbes are also addressed

Impact of gout on in-hospital outcomes of acute coronary syndrome-related hospitalizations and revascularizations: Insights from the national inpatient sample

Previous studies have established a role of gout in predicting risk and prognosis of cardiovascular diseases. However, large-scale data on the impact of gout on inpatient outcomes of acute coronary syndrome (ACS)-related hospitalizations and post-revascularization is inadequate. AIM To evaluate the impact of gout on in-hospital outcomes of ACS hospitalizations, subsequent healthcare burden and predictors of post-revascularization inpatient mortality. METHODS We used the national inpatient sample (2010-2014) to identify the ACS and gout-related hospitalizations, relevant comorbidities, revascularization and post-revascularization outcomes using the ICD-9 CM codes. A multivariable analysis was performed to evaluate the predictors of post-revascularization in-hospital mortality. RESULTS We identified 3144744 ACS-related hospitalizations, of which 105198 (3.35%) also had gout. The ACS-gout cohort were more often older white males with a higher prevalence of comorbidities. Coronary artery bypass grafting was required more often in the ACS-gout cohort. Post-revascularization complications including cardiac (3.2% vs 2.9%), respiratory (3.5% vs 2.9%), and hemorrhage (3.1% vs 2.7%) were higher whereas all-cause mortality was lower (2.2% vs 3.0%) in the ACS-gout cohort (P < 0.001). An older age (OR 15.63, CI: 5.51-44.39), non-elective admissions (OR 2.00, CI: 1.44-2.79), lower household income (OR 1.44, CI: 1.17-1.78), and comorbid conditions predicted higher mortality in ACS-gout cohort undergoing revascularization (P < 0.001). Odds of post-revascularization inhospital mortality were lower in Hispanics (OR 0.45, CI: 0.31-0.67) and Asians (OR 0.65, CI: 0.45-0.94) as compared to white (P < 0.001). However, post-operative complications significantly raised mortality odds. Mean length of stay, transfer to other facilities, and hospital charges were higher in the ACS-gout cohort. CONCLUSION Although gout was not independently associated with an increased risk of post-revascularization in-hospital mortality in ACS, it did increase post-revascularization complications

Zinc Oxide Nanoparticles Dispersed in Ionic Liquids Show High Antimicrobial Efficacy to Skin-Specific Bacteria

Zinc oxide (ZnO) nanoparticles have been shown in the literature to have antibacterial properties and have been widely used in antibacterial formulations. However, one of the problems with ZnO nanoparticles is their tendency to aggregate, thereby causing damage to normal cells and lowering their antibacterial efficacy during application. In this work, we have attempted to avoid this by using a combination of ZnO nanoparticles and ionic liquids, a class of low melting salts containing organic cations and organic/inorganic anions that show antibacterial property as well, and tested the antibacterial activity of this dispersion. ZnO nanoparticles of 60 nm were dispersed in two different ionic liquidscholine acetate (IL1) and 1-butyl-3-methylimidazolium chloride (IL2)to achieve high dispersibility, whereas ZnO dispersed in phosphate-buffered saline was taken as a control. These dispersions were tested on four strainsEscherichia coli, Bacillus subtilis, Klebsiella pneumoniae, and Staphylococcus epidermidis. Maximum efficiency was obtained for ZnO nanoparticles dispersed in imidazolium-based ionic liquids against skin-specific S. epidermidis. Skin infections induced by S. epidermidis are prevalent in hospital-acquired diseases. In most cases, traditional antibiotic-based therapies fail to combat such infections. Our strategy of developing a dispersion of ZnO nanoparticles in ionic liquids shows superior antibacterial efficacy in comparison to that shown individually by ZnO nanoparticles or ionic liquids. We have also established that the mechanism of killing this skin-specific bacterium is possibly through the production of reactive oxygen species leading to bacterial cell lysis. Further, we showed that this formulation is biocompatible and nontoxic to normal keratinocyte cells even under coculture conditions

Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies

Given the spasmodic increment in antimicrobial resistance (AMR), world is on the verge of "post-antibiotic era". It is anticipated that current SARS-CoV2 pandemic would worsen the situation in future, mainly due to the lack of new/next generation of antimicrobials. In this context, nanoscale materials with antimicrobial potential have a great promise to treat deadly pathogens. These functional materials are uniquely positioned to effectively interfere with the bacterial systems and augment biofilm penetration. Most importantly, the core substance, surface chemistry, shape, and size of nanomaterials define their efficacy while avoiding the development of AMR. Here, we review the mechanisms of AMR and emerging applications of nanoscale functional materials as an excellent substitute for conventional antibiotics. We discuss the potential, promises, challenges and prospects of nanobiotics to combat AMR.Ministry of Health (MOH)Nanyang Technological UniversityNational Medical Research Council (NMRC)Published versionThis study was supported by research grant from OLP1149. NC is thankful to the Council of Scientifc and Industrial Research (CSIR), Government of India for providing research fellowship support. O-TN received salary support from NMRC Clinician Scientist Award (MOH-000276). NKV thanks funding support from the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore (LKC Operating budget). RL thanks funding support from the Singapore Ministry of Health’s National Medical Research Council under its Centre Grant Programme—Optimization of Core Platform Technologies for Ocular Research (INCEPTOR)-NMRC/CG/M010/2017_SERI and R1875/3/2022