Genotype-Phenotype Correlation in Junctional Epidermolysis Bullosa: Signposts to Severity.

Junctional epidermolysis bullosa (JEB) is a rare autosomal recessive genodermatosis with a broad spectrum of phenotypes. Current genotype-phenotype paradigms are insufficient to accurately predict JEB subtype and characteristics from genotype, particularly for splice site variants, which account for over a fifth of disease-causing variants in JEB. This study evaluated the genetic and clinical findings from a JEB cohort, investigating genotype-phenotype correlations through bioinformatic analyses and comparison with previously reported variants.

IgA nephropathy in adults with epidermolysis bullosa.

Epidermolysis bullosa (EB) is a devastating genetic condition caused by mutations in genes that give rise to aberrant proteins. There are 16 different such proteins implicated in EB that are important in maintaining the integrity of the dermoepidermal junction. It is classified into four major subtypes: (i) EB simplex; (ii) junctional EB (JEB); (iii) dystrophic EB (DEB); and (iv) Kindler EB.

Subspecies Differ in Biofilm Forming Ability .

Development of dysbiosis in complex multispecies bacterial biofilms forming on teeth, known as dental plaque, is one of the factors causing periodontitis. () is recognised as a key microorganism in subgingival dental plaque, and is linked to periodontitis as well as colorectal cancer and systemic diseases. Five subspecies of have been identified: , and .

Iron-mediated epigenetic activation of NRF2 targets.

The toxic effects of excess dietary iron within the colonic lumen are well documented, particularly in the context of Inflammatory Bowel Disease (IBD) and Colorectal Cancer (CRC). Proposed mechanisms that underpin iron-associated intestinal disease include: (1) the pro-inflammatory and ROS-promoting nature of iron, (2) gene-expression alterations, and (3) intestinal microbial dysbiosis. However, to date no studies have examined the effect of iron on the colonic epigenome.

Repeated exposure of nosocomial pathogens to silver does not select for silver resistance but does impact ciprofloxacin susceptibility.

The rise of antimicrobial resistant bacteria coupled with a void in antibiotic development marks Antimicrobial Resistance as one of the biggest current threats to modern medicine. Antimicrobial metals are being developed and used as alternative anti-infectives, however, the existence of known resistance mechanisms and limited data regarding bacterial responses to long-term metal exposure are barriers to widespread implementation. In this study, a panel of reference and clinical strains of major nosocomial pathogens were subjected to serial dosage cycles of silver and ciprofloxacin.

Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4-]pyrimidines Kinase Inhibitors.

Pyrazolo[3,4-]pyrimidines represent an important class of heterocyclic compounds well-known for their anticancer activity exerted by the inhibition of eukaryotic protein kinases. Recently, pyrazolo[3,4-]pyrimidines have become increasingly attractive for their potential antimicrobial properties. Here, we explored the activity of a library of in-house pyrazolo[3,4-]pyrimidines, targeting human protein kinases, against and and their interaction with ampicillin and kanamycin, representing important classes of clinically used antibiotics.

The mA Writer: Rise of a Machine for Growing Tasks.

The central dogma of molecular biology introduced by Crick describes a linear flow of information from DNA to mRNA to protein. Since then it has become evident that RNA undergoes several maturation steps such as capping, splicing, 3'-end processing, and editing. Likewise, nucleotide modifications are common in mRNA and are present in all organisms impacting on the regulation of gene expression.

PDZD8 is not the 'functional ortholog' of Mmm1, it is a paralog.

Authors of a recent paper demonstrate that, like ERMES (ER-mitochondria encounter structure) in fungal cells, PDZD8 (PDZ domain containing 8) tethers mitochondria to the ER in mammalian cells. However, identifying PDZD8 as a "functional ortholog" of yeast Mmm1 (maintenance of mitochondrial morphology protein 1) is at odds with the phylogenetic data. PDZD8 and Mmm1 are paralogs, not orthologs, which affects the interpretation of the data with respect to the evolution of ER-mitochondria tethering.

Heterogeneity and complexity within the nuclease module of the Ccr4-Not complex.

The shortening of the poly(A) tail of cytoplasmic mRNA (deadenylation) is a pivotal step in the regulation of gene expression in eukaryotic cells. Deadenylation impacts on both regulated mRNA decay as well as the rate of mRNA translation. An important enzyme complex involved in poly(A) shortening is the Ccr4-Not deadenylase.