Hi-plex deep amplicon sequencing for identification, high-resolution genotyping and multidrug resistance prediction of Mycobacterium leprae directly from patient biopsies by using Deeplex Myc-Lep.

Background: Expansion of antimicrobial resistance monitoring and epidemiological surveillance are key components of the WHO strategy towards zero leprosy. The inability to grow Mycobacterium leprae in vitro precludes routine phenotypic drug susceptibility testing, and only limited molecular tests are available. We evaluated a culture-free targeted deep sequencing assay, for mycobacterial identification, genotyping based on 18 canonical SNPs and 11 core variable-number tandem-repeat (VNTR) markers, and detection of rifampicin, dapsone and fluoroquinolone resistance-associated mutations in rpoB/ctpC/ctpI, folP1, gyrA/gyrB, respectively, and hypermutation-associated mutations in nth.

Genome-wide DNA methylation predicts environmentally driven life history variation in a marine fish.

Epigenetic modifications are thought to be one of the molecular mechanisms involved in plastic adaptive responses to environmental variation. However, studies reporting associations between genome-wide epigenetic changes and habitat-specific variations in life history traits (e.g.

Leveraging PEPFAR-Supported Health Information Systems for COVID-19 Pandemic Response.

Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response.

Epidemiology and risk factors related to severity of clinical manifestations of COVID-19 in outpatients: A retrospective study in Haiti.

Background: Haiti's first COVID-19 cases were confirmed on March 18, 2020, and subsequently spread throughout the country. The objective of this study was to describe clinical manifestations of COVID-19 in Haitian outpatients and to identify risk factors for severity of clinical manifestations.

Methods: We conducted a retrospective study of COVID-19 outpatients diagnosed from March 18-August 4, 2020, using demographic, epidemiological, and clinical data reported to the Ministry of Health (MoH).

Gender Dysphoria and Dissociative Identity Disorder: A Case Report and Review of Literature.

Background: World Professional Association for Transgender Health guidelines support the importance of a mental health assessment before providing medical treatment for Gender Dysphoria (GD). During this assessment, patients without GD but with mental health disorder and who request treatment for GD should be excluded. Dissociative Identity Disorder (DID) is a poorly known mental disorder which can be confused for GD.

Thermal adaptation rather than demographic history drives genetic structure inferred by copy number variants in a marine fish.

Increasing evidence shows that structural variants represent an overlooked aspect of genetic variation with consequential evolutionary roles. Among those, copy number variants (CNVs), including duplicated genomic regions and transposable elements (TEs), may contribute to local adaptation and/or reproductive isolation among divergent populations. Those mechanisms suppose that CNVs could be used to infer neutral and/or adaptive population genetic structure, whose study has been restricted to microsatellites, mitochondrial DNA and Amplified fragment length polymorphism markers in the past and more recently the use of single nucleotide polymorphisms (SNPs).

Shared ancestral polymorphisms and chromosomal rearrangements as potential drivers of local adaptation in a marine fish.

Gene flow has tremendous importance for local adaptation, by influencing the fate of de novo mutations, maintaining standing genetic variation and driving adaptive introgression. Furthermore, structural variation as chromosomal rearrangements may facilitate adaptation despite high gene flow. However, our understanding of the evolutionary mechanisms impending or favouring local adaptation in the presence of gene flow is still limited to a restricted number of study systems.

Divergent and linked selection shape patterns of genomic differentiation between European and North American Atlantic salmon (Salmo salar).

As populations diverge many processes can shape genomic patterns of differentiation. Regions of high differentiation can arise due to divergent selection acting on selected loci, genetic hitchhiking of nearby loci, or through repeated selection against deleterious alleles (linked background selection); this divergence may then be further elevated in regions of reduced recombination. Atlantic salmon (Salmo salar) from Europe and North America diverged >600,000 years ago and despite some evidence of secondary contact, the majority of genetic data indicate substantial divergence between lineages.

Gold(i)-silver(i)-calix[8]arene complexes, precursors of bimetallic alloyed Au-Ag nanoparticles.

In this paper, we report the first synthesis and characterisations of bimetallic gold(i)-silver(i) calix[8]arene complexes. We show that the radiolytic reduction of these complexes leads to the formation of small bimetallic nanoparticles with an alloyed structure, as evidenced by XPS, HR-TEM and STEM/HAADF-EDX measurements.

Chromosome polymorphisms track trans-Atlantic divergence and secondary contact in Atlantic salmon.

Pleistocene glaciations drove repeated range contractions and expansions shaping contemporary intraspecific diversity. Atlantic salmon (Salmo salar) in the western and eastern Atlantic diverged >600,000 years before present, with the two lineages isolated in different southern refugia during glacial maxima, driving trans-Atlantic genomic and karyotypic divergence. Here, we investigate the genomic consequences of glacial isolation and trans-Atlantic secondary contact using 108,870 single nucleotide polymorphisms genotyped in 80 North American and European populations.

Environmental extremes drive population structure at the northern range limit of Atlantic salmon in North America.

Conservation of exploited species requires an understanding of both genetic diversity and the dominant structuring forces, particularly near range limits, where climatic variation can drive rapid expansions or contractions of geographic range. Here, we examine population structure and landscape associations in Atlantic salmon (Salmo salar) across a heterogeneous landscape near the northern range limit in Labrador, Canada. Analysis of two amplicon-based data sets containing 101 microsatellites and 376 single nucleotide polymorphisms (SNPs) from 35 locations revealed clear differentiation between populations spawning in rivers flowing into a large marine embayment (Lake Melville) compared to coastal populations.

Genotyping-by-sequencing of genome-wide microsatellite loci reveals fine-scale harvest composition in a coastal Atlantic salmon fishery.

Individual assignment and genetic mixture analysis are commonly utilized in contemporary wildlife and fisheries management. Although microsatellite loci provide unparalleled numbers of alleles per locus, their use in assignment applications is increasingly limited. However, next-generation sequencing, in conjunction with novel bioinformatic tools, allows large numbers of microsatellite loci to be simultaneously genotyped, presenting new opportunities for individual assignment and genetic mixture analysis.

Applications of random forest feature selection for fine-scale genetic population assignment.

Genetic population assignment used to inform wildlife management and conservation efforts requires panels of highly informative genetic markers and sensitive assignment tests. We explored the utility of machine-learning algorithms (random forest, regularized random forest and guided regularized random forest) compared with ranking for selection of single nucleotide polymorphisms (SNP) for fine-scale population assignment. We applied these methods to an unpublished SNP data set for Atlantic salmon () and a published SNP data set for Alaskan Chinook salmon ().

Range-wide parallel climate-associated genomic clines in Atlantic salmon.

Clinal variation across replicated environmental gradients can reveal evidence of local adaptation, providing insight into the demographic and evolutionary processes that shape intraspecific diversity. Using 1773 genome-wide single nucleotide polymorphisms we evaluated latitudinal variation in allele frequency for 134 populations of North American and European Atlantic salmon (). We detected 84 (4.

Systematic neonatal screening for severe combined immunodeficiency and severe T-cell lymphopenia: Analysis of cost-effectiveness based on French real field data.

Background: The inclusion of severe combined immunodeficiency (SCID) in a Europe-wide screening program is currently debated.

Objective: In making a case for inclusion in the French newborn screening program, we explored the costs incurred and potentially saved by early management of SCID.

Methods: For test costs, a microcosting study documented the resources used in a laboratory piloting a newborn screening test on Guthrie cards using the T-cell receptor excision circle quantification method.

Platinum(II) olefin hydroarylation catalysts: tuning selectivity for the anti-Markovnikov product.

Pt(II) complexes containing unsymmetrical (pyridyl)pyrrolide ligands are shown to catalyze the hydroarylation of unactivated alkenes with selectivity for the anti-Markovnikov product. Substitution on the pyrrolide portion of the ligand allows effective tuning of the selectivity to anti-Markovnikov alkylarene products, whereas substitution on the pyridyl portion can promote competitive alkenylarene production.

What otolith microchemistry and stable isotope analysis reveal and conceal about anguillid eel movements across salinity boundaries.

Otolith microchemistry studies indicate that growth-phase (yellow stage) anguillid eels commonly shift at irregular intervals between fresh and saline waters, but this technique has not detected regular seasonal migrations across salinity zones. We tested the ability of otolith microchemistry and stable isotope analysis to detect migrations of American eels (Anguilla rostrata) between salinity boundaries in two small stream-estuary systems in Canada's Bay of Fundy. Although the two methods showed concordant classifications of recent residence history, most eels caught in fresh water in spring (68.

Manganese superoxide dismutase is a promising target for enhancing chemosensitivity of basal-like breast carcinoma.

Aims: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype.

Results: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression.

NHE-1: a promising target for novel anti-cancer therapeutics.

Among the many factors involved in the maintenance of homeostatic growth is the tight regulation of cellular pH. Intracellular pH of normal cells is maintained within a physiological range thanks to the activity of a number of pH regulators that respond to the acidbase shifts associated with normal cellular metabolic processes. Interestingly, there is a preponderance of evidence that dysregulation of intracellular pH is associated with processes that favor cell transformation such as cell cycle progression, enhanced proliferation, insensitivity to growth inhibitory stimuli, resistance to apoptosis, genomic instability and angiogenesis.

Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human.

Background: Activation of PPARs has been reported to inhibit the proliferation of malignant cells from different lineages. They are involved in transcription regulation of genes upon activation by a ligand. The binding of PPARs to the promoter sequence either represses or activates the gene.

Heterocyclization by catalytic carbonickelation of alkynes: a domino sequence involving vinylnickels.

Reaction of Ni(0) in the presence of iodoarylethers leads, after syn intramolecular carbonickelation of the triple bond, to nucleophilic vinylnickels which can be trapped, in a tandem process, by various electrophiles introduced at the onset of the reaction.

Caspase inhibitor Z-VAD-FMK enhances the freeze-thaw survival rate of human embryonic stem cells.

Previous study demonstrated that the low survival of human embryonic stem cells (hESC) under conventional slow-cooling cryopreservation protocols is predominantly due to apoptosis rather than cellular necrosis. Hence, this study investigated whether a synthetic broad-spectrum irreversible inhibitor of caspase enzymes, Z-VAD-FMK can be used to enhance the post-thaw survival rate of hESC. About 100 mM Z-VAD-FMK was supplemented into either the freezing solution, the post-thaw culture media or both.

Induction of apoptosis by crambene protects mice against acute pancreatitis via anti-inflammatory pathways.

Apoptosis is a teleologically beneficial form of cell death in acute pancreatitis. Our previous work has demonstrated that induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis. However, little is known about how the induction of apoptosis reduces the severity of acute pancreatitis.

Mycobacterium szulgai infection in a captive population of African clawed frogs (Xenopus tropicalis).

A colony of captive Xenopus tropicalis became infected with Mycobacterium szulgai. Clinical signs, when observed, were lethargy, weight loss, and emaciation. Visceral granulomas were common findings at laparoscopy and necropsy.

Crambene induces pancreatic acinar cell apoptosis via the activation of mitochondrial pathway.

We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3-butene), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V-FITC staining, crambene treatment for 3 h induced the apoptosis but not necrosis of pancreatic acini. Caspase-3, -8, and -9 activities in acini treated with crambene were significantly higher than in untreated acini.