Sequence-specific Solution Structures of the Four Isosequential Pairs of Single-stranded DNAs and RNAs

The role of the sequence-context in the self-organization of four single-stranded (ss) isosequential pairs of DNAs (1 – 4) and RNAs (5 – 8), [d/r-(5'C^1^A^2^X^3^G^4^Y^5^A^6^C^7^): X^3^ = A or C, Y^5^ = A or C; sequence variations: 2^2^ = 4], has been elucidated by NMR-constrained Molecular Dynamics (MD) simulations (2 ns). Following sequence-specific observations have been made from the solution NMR and the NMR constrained MD simulation study: (i) Analysis of the NOESY footprints, mainly (H8/H6)~n~ to (H1' and H3')~n-1~ contacts, of ssDNAs (1 - 4) and ssRNAs (5 – 8) in the aqueous medium have shown that all ssDNAs (1 - 4) and ssRNAs (5 - 8) adopt right handed stacked helical structures in the NMR time scale. (ii) Intra-residual cross-peak intensities for the H(8/6)~n-~ H(1'/2'/2''/H3')~n~ contacts in ssDNAs and ssRNAs are stronger at the 3'-ends in comparison with those at the 5'-ends, suggesting that the dynamics of the nucleobases at the 3'-end are more restricted, whereas those at the 5'-end are more flexible. (iii) This relative NMR found mobility is consistent with the final RMSd calculations of the final NMR-MD structures of ssDNAs and ssRNAs. They show that the 5'-end nucleobases have higher RMSd values compared to those at the 3'-end, except for the sequence d/r(5'C^1^A^2^A^3^G^4^A^5^A^6^C^7^). (iv) Relative nOe intensities of inter-residual H(8/6)~n~ - H(1')~n-1~ and H(8/6)~n~ - H(3')~n-1~ contacts, as well as NMR observed fluctuations in the sugar conformations, for ssDNAs (1 – 4) and ssRNAs (5 – 8) show that no ssDNA or ssRNA adopts either a typical B-type DNA or A-type RNA form. (v) In the final NMR-MD structures all the [H8/6N~(n)~ -- H1'N~(n-1)~/ H3'N~(n-1)~, N = A, G, C] distances in different isosequential pairs of ssDNA (1 – 4) and ssRNA (5 – 8) change depending upon the sequence context of the single-stranded nucleic acids. Both in the deoxy and ribo series, it is the purine-rich sequences [d/r-(5'C^1^A^2^A^3^G^4^A^5^A^6^C^7^) which form the most stable self-organized right-handed helical structures because of the favorable purine-purine stacking interactions. (vi) Stacking pattern at each of the dinucleotide steps show that the base-base nearest neighbor stacking interactions depend solely upon the sequence contexts of the respective ssDNAs (1 – 4) and ssRNAs (5 – 8). See pages 47 – 145 for Supplementary Information for detailed spectroscopic data

L’encadrement juridique des biobanques populationnelles et leurs obligations au Québec

La mise en banque d’échantillons humains et de données connexes n’est pas une pratique récente. Toutefois, dans les dernières décennies, ce phénomène a pris une ampleur sans précédent avec la création des biobanques populationnelles. Défini comme étant des infrastructures de recherche conçues pour durer plusieurs décennies, ce type de biobanques invite des milliers et, dans certains cas, des centaines de milliers de personnes à y participer en fournissant des échantillons, en se soumettant à des tests physiques et biochimiques, et en répondant à diverses questions sur leur santé et leur environnement sociodémographique. Mais quelles sont les obligations des biobanques et de leurs chercheurs face aux participants? Considérant leur longue durée, quel est l’encadrement juridique de ces biobanques populationnelles au Québec? Ce sont les deux questions que pose ce mémoire. Quant à l’encadrement, nous utilisons trois axes d’analyse : i) les lois, les règlements, la déontologie professionnelle et les normes applicables; ii) la qualification juridique de l’acte de mise en banque d’échantillons et de données; et iii) les obligations découlant de la nature même de l’objet de la relation juridique. Notre analyse révèle que cet encadrement est une mosaïque législative, contractuelle, déontologique et normative qui, malgré ses complexités et ses défis d’accessibilité pour les participants, assure une certaine protection pour ces derniers. Quant aux obligations incombant à la biobanque et à ses chercheurs, elles sont pour la majorité teintées par des caractéristiques particulières aux biobanques populationnelles. Ainsi, il existe des défis particuliers en ce qui concerne notamment le consentement, le devoir d’information, le retour de résultats et la sécurité des échantillons et des données. Étant donné la nature évolutive de ces obligations, nous proposons une approche basée sur le meilleur intérêt du participant pour déterminer la nature et l’intensité des obligations incombant à une biobanque et à ses chercheurs.The collection of human samples and related data is not a recent practice. However, in the last few decades, such practices have taken much importance mainly due to the creation of population type biobanks. Defined as research infrastructures, they are conceived to last several decades. They invite thousands and, in some cases, hundreds of thousands of participants to contribute their samples, undergo physical and biochemical tests and answer various questions regarding their health and socio-demographic environment. In this context, what are the obligations of these initiatives and the researchers involved therein towards the participants? Considering their duration, what is the legal setting surrounding such biobanks in Québec? These are the two questions addressed by this study. With respect to the legal setting, we propose an analysis based on three axes: i) laws, rules, professional deontology and norms; ii) the legal qualification of the act of banking samples and data; and iii) obligations resulting from the nature of the object of the legal relation. Our analysis reveals that the legal setting surrounding biobanks is a mosaic composed of legislative, contractual, deontological and normative obligations that, despite its complexities and challenges of accessibility for the participant, ensure a certain level of protection for the latter. Regarding the obligations of the biobank and its researchers, they are, for the majority, affected by particularities of population type biobanks. Indeed, specific challenges exist with respect to consent, the obligation to inform, the return of results and the security of samples and data. Given the evolving nature of the theses obligations, we propose to consider an approach based on the best interests of the participants when determining the nature and the intensity of the different obligations applicable to the biobank and its researchers

Prevalence of musculoskeletal pain and environmental health hazards among tea pluckers of Maddekanda tea estate in Balangoda Pradeshiya Saba Division, Sri Lanka

Background: Tea pluckers in Sri Lanka play a prominent role in supplying tea for the local and foreign demand. Long standing, bearing weight on back, repetitive hand movements, slip and falls due to walking on uneven grounds lead to various health problems among them. Thus, this study was aimed to assess the prevalence of musculoskeletal pain and environmental health hazards among tea pluckers of Maddekanda tea estate in Balangoda area, Sri Lanka. Design and Methods: A descriptive cross-sectional study was carried out among 378 tea pluckers, recruited using simple random sampling method. Data were collected by validated, pre-tested interviewer administered questionnaire and descriptive and inferential statistical analyses were performed by using SPSS v20.Results: The prevalence of musculoskeletal pain in any region of the body was 68.5% (95% CI 63.6-73.2) among all participants and prevalence of lower back pain 43.4% (95% CI 38.3-48.8) was high compared to other site of pain. Nearly 98.4% had experienced of leech biting during their work as a main health hazard. Participants who had experienced stress (OR=2.12, 95% CI: 1.119-3.764), and worked for more than 20 years (OR=2.28, 95% CI: 1.37- 3.81) were nearly 2 times more likely to have musculoskeletal pain when compared to their counterparts.Conclusions: Prevalence of musculoskeletal pain were high among tea pluckers and lower back region was the common site of pain. Leech bite was the other dominant health problem faced by them. Stress, duration of work and age were associated with musculoskeletal pain

Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture

BACKGROUND: Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial mixture (CM-HBCD) composed of three main stereoisomers: α-HBCD (10%), β-HBCD (10%), and γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife. OBJECTIVES: Considering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, we performed metabolomics on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures and developmental outcomes and to predict health risks. METHODS: Six female C57BL/6 mice at postnatal day (PND) 10 were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. Nuclear magnetic resonance metabolomics was used to analyze 60 μL serum aliquots of blood collected 4 days post-oral exposure. RESULTS: Infantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment and dose groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate, and acetoacetate, were nonstatistically elevated, when compared with mean control levels, in all treatment and dose groups, while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD and was nonsignificantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment and dose group. Metabolites significant in differentiating treatment and dose groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively. CONCLUSIONS: We demonstrated that 4 days following a single neonatal oral exposure to α-, γ-, and CM-HBCD resulted in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action

COVID-19: Impact on undergraduate nursing education in Sri Lanka

“Novel Corona Virus” (COVID-19) is a new infectious disease spreading all around the world that has a globally significant morbidity and mortality at present. Nurses as frontline care providers in hospitals and community are exposed to a major risk. This brief report aims at providing an overview of COVID-19 impacts on Sri Lanka and to highlight educational implications from the perspective of nursing degree programs. The major impacts of COVID-19 on nursing education were unequal access to online distance learning, disruption of academic calendars, cancellation of clinical placements, teaching and learning gap, lack of facilities for online learning, disruption towards professional development, and inability to conduct proper clinical assessments and standard operationalization procedures. It suggests that higher education institutions should take actions to provide material support for students from low-income households to close the gap between teaching and learning and training academics on different online teaching and learning strategies and assessments

DOES PROXIMITY TO WATER BODIES IMPACTS MARKET VALUES OF RESIDENTIAL PROPERTIES? CASE STUDY OF DIYAWANNAWA LAKE AREA

This study examined the impact of water bodies with a scenic view on residential property values around Diyawannawa lake located within Sri Jayewardenepura Kotte Municipal council (a suburban area of Colombo district). The study employed both primary (structural and environmental data related to properties, different types of benefits generated from waterbodies) and secondary data (market evidence) whilst the data analysis included content analysis and a regression analysis (hedonic pricing model). Water bodies with scenic views generate multiple utilities for residents such as observing nature, relaxation, and playing, pleasant views, appreciation of colour and sounds, relationships with family members and neighbors, a place to exercise and cycling, stress relief likewise. According to the study, between 2019-2020, a residential property with a scenic view of 600 or more to Diyawannawa Lake had a premium market value of Rs. 803,433.05 compared to other properties. Furthermore, the residential properties one meter away from such water body showed a decrease in market value of Rs. 23049.65. These findings will raise awareness on the benefits of water bodies with scenic views and it will lead to greater acceptance by residents, developers, local authorities to invest and protect them, which could contribute to overcoming one of the barriers to maintaining such water bodies in good condition. Keywords: water bodies; residential property; market valu

Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

Metabolic factors may contribute to osteoarthritis (OA).This study employed metabolomics analyses to determine if differences in metabolite profiles could distinguish people with knee OA who exhibited radiographic progression

Regiochemical control in the addition of aryl N-sulphinylamines to juglone and juglone derivatives

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Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects

Associations between the gut microbiome and metabolome in early life

Background: The infant intestinal microbiome plays an important role in metabolism and immune development with impacts on lifelong health. The linkage between the taxonomic composition of the microbiome and its metabolic phenotype is undefined and complicated by redundancies in the taxon-function relationship within microbial communities. To inform a more mechanistic understanding of the relationship between the microbiome and health, we performed an integrative statistical and machine learning-based analysis of microbe taxonomic structure and metabolic function in order to characterize the taxa-function relationship in early life. Results: Stool samples collected from infants enrolled in the New Hampshire Birth Cohort Study (NHBCS) at approximately 6-weeks (n = 158) and 12-months (n = 282) of age were profiled using targeted and untargeted nuclear magnetic resonance (NMR) spectroscopy as well as DNA sequencing of the V4-V5 hypervariable region from the bacterial 16S rRNA gene. There was significant inter-omic concordance based on Procrustes analysis (6 weeks: p = 0.056; 12 months: p = 0.001), however this association was no longer significant when accounting for phylogenetic relationships using generalized UniFrac distance metric (6 weeks: p = 0.376; 12 months: p = 0.069). Sparse canonical correlation analysis showed significant correlation, as well as identifying sets of microbe/metabolites driving microbiome-metabolome relatedness. Performance of machine learning models varied across different metabolites, with support vector machines (radial basis function kernel) being the consistently top ranked model. However, predictive R2 values demonstrated poor predictive performance across all models assessed (avg: − 5.06% -- 6 weeks; − 3.7% -- 12 months). Conversely, the Spearman correlation metric was higher (avg: 0.344–6 weeks; 0.265–12 months). This demonstrated that taxonomic relative abundance was not predictive of metabolite concentrations. Conclusions: Our results suggest a degree of overall association between taxonomic profiles and metabolite concentrations. However, lack of predictive capacity for stool metabolic signatures reflects, in part, the possible role of functional redundancy in defining the taxa-function relationship in early life as well as the bidirectional nature of the microbiome-metabolome association. Our results provide evidence in favor of a multi-omic approach for microbiome studies, especially those focused on health outcomes