Barcoding of Asian seabass across its geographic range provides evidence for its bifurcation into two distinct species

Asian seabass or barramundi (Lates calcarifer) is an important food fish with commercial value and a wide geographic distribution. Though some reports based on molecular and/or morphological data exist, a comprehensive effort to establish species identity across its range is lacking. In order to address this issue and especially to ascertain whether the wide-spread distribution has resulted in bifurcation of the species, we collected Asian seabass samples from various locations representing the Western and Eastern Coastline of India, Andaman and Nicobar Islands, Bangladesh and Australia. Samples from Malaysia, Indonesia, Thailand and Singapore were collected as part of a previous study. DNA sequence variations, including cytochrome c oxidase subunit 1 (COI), 16S rDNA and the highly variable D-loop (or control region), were examined to establish species delineation. Data from all the sequences analyzed concordantly point to the existence of at least two distinct species—one representing the Indian subcontinent plus Myanmar, and a second, representing Southeast Asia (Singapore, Malaysia, Thailand and Indonesia) plus Northern Australia. These data are useful for conservation ecology, aquaculture management, for establishing the extent of genetic diversity in the Asian seabass and implementing selective breeding programs for members of this species complex

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21

Meta-AnalysisThis is the final version of the article. Available from the American Diabetes Association via the DOI in this record.Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.The major funding for this work comes from Council for Scientific and Industrial Research, Government of India, in the form of the grant “Diabetes mellitus—New drug discovery R&D, molecular mechanisms, and genetic and epidemiological factors” (NWP0032-19). R.T. received a postdoctoral fellowship from the Fogarty International Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (D43-HD-065249)

Characterization of monoolein-based lipoplexes using fluorescence spectroscopy

Lipoplexes are commonly used as delivery systems in vitro and in vivo, the role of a neutral lipid as helper being of extreme importance in these systems. Cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB) with monoolein (MO) as a helper, at different molar ratios (1:2; 1:1 and 1:0.5) were prepared, and subsequently titrated to DNA. The structural and physicochemical properties of the lipid/DNA complexes were assessed by Ethidium Bromide (EtBr) exclusion, 90º Static Light Scattering (90º SLS) assays and Fluorescence Resonance Energy Transfer (FRET). In EtBr exclusion assays, the steady-state fluorescence spectra of EtBr were decomposed into the sum of two lognormal emissions, emanating from two different environments – H2O and DNA, and the effect of charge ratio (+/-) was observed. 90º SLS assays gave an important contribution, detecting size variations in systems with different MO fractions on the lipoplexes. In FRET assays, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (DPH-HPC) was used as donor and EtBr as acceptor. The DNA component previously calculated by EtBr exclusion, was used to determine the energy transfer efficiency, as an indirect measurement of the lipoplexes structural and physicochemical properties. Our results demonstrate that the inclusion of monoolein in the cationic liposomes formulation significantly modifies the rate of DNA complexation, being DODAB:MO (1:1) the system with higher DNA condensation efficiency.Fundação para a Ciência e a Tecnologia (FCT

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Inactivation of the dnaK gene in Clostridium difficile 630 Δerm yields a temperature-sensitive phenotype and increases biofilm-forming ability

Abstract Clostridium difficile infection is a growing problem in healthcare settings worldwide and results in a considerable socioeconomic impact. New hypervirulent strains and acquisition of antibiotic resistance exacerbates pathogenesis; however, the survival strategy of C. difficile in the challenging gut environment still remains incompletely understood. We previously reported that clinically relevant heat-stress (37–41 °C) resulted in a classical heat-stress response with up-regulation of cellular chaperones. We used ClosTron to construct an insertional mutation in the dnaK gene of C. difficile 630 Δerm. The dnaK mutant exhibited temperature sensitivity, grew more slowly than C. difficile 630 Δerm and was less thermotolerant. Furthermore, the mutant was non-motile, had 4-fold lower expression of the fliC gene and lacked flagella on the cell surface. Mutant cells were some 50% longer than parental strain cells, and at optimal growth temperatures, they exhibited a 4-fold increase in the expression of class I chaperone genes including GroEL and GroES. Increased chaperone expression, in addition to the non-flagellated phenotype of the mutant, may account for the increased biofilm formation observed. Overall, the phenotype resulting from dnaK disruption is more akin to that observed in Escherichia coli dnaK mutants, rather than those in the Gram-positive model organism Bacillus subtilis

Virus Adaptation by Manipulation of Host's Gene Expression

Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit. Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence. Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host. However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host. This situation would represent a case for a new emerging virus. Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a naïve host. After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous. An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity. DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways. A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses

25 years of HIV-1 research – progress and perspectives

Twenty-five years after the discovery and isolation of the human immunodeficiency virus by French and American scientists, much progress has been made in basic research, clinical treatment, and public health prevention measures for acquired immunodeficiency syndrome. Here, we summarize, in brief, advances that have been achieved and provide some perspectives on future challenges