Estimation of the total peripheral resistance baroreflex impulse response from spontaneous hemodynamic variability

We previously developed a mathematical analysis technique for estimating the static gain values of the arterial total peripheral resistance (TPR) baroreflex (G(A)) and the cardiopulmonary TPR baroreflex (G(C)) from small, spontaneous beat-to-beat fluctuations in arterial blood pressure, cardiac output, and stroke volume. Here, we extended the mathematical analysis so as to also estimate the entire arterial TPR baroreflex impulse response [h(A)(t)] as well as the lumped arterial compliance (AC). The extended technique may therefore provide a linear dynamic characterization of TPR baroreflex systems during normal physiological conditions from potentially noninvasive measurements. We theoretically evaluated the technique with respect to realistic spontaneous hemodynamic variability generated by a cardiovascular simulator with known system properties. Our results showed that the technique reliably estimated h(A)(t) [error = 30.2 +/- 2.6% for the square root of energy (E(A)), 19.7 +/- 1.6% for absolute peak amplitude (P(A)), 37.3 +/- 2.5% for G(A), and 33.1 +/- 4.9% for the overall time constant] and AC (error = 17.6 +/- 4.2%) under various simulator parameter values and reliably tracked changes in G(C). We also experimentally evaluated the technique with respect to spontaneous hemodynamic variability measured from seven conscious dogs before and after chronic arterial baroreceptor denervation. Our results showed that the technique correctly predicted the abolishment of h(A)(t) [E(A) = 1.0 +/- 0.2 to 0.3 +/- 0.1, P(A) = 0.3 +/- 0.1 to 0.1 +/- 0.0 s(-1), and G(A) = -2.1 +/- 0.6 to 0.3 +/- 0.2 (P < 0.05)] and the enhancement of G(C) [-0.7 +/- 0.44 to -1.8 +/- 0.2 (P < 0.05)] following the chronic intervention. Moreover, the technique yielded estimates whose values were consistent with those reported with more invasive and/or experimentally difficult methods.     

Icescape-scale metabolomics reveals cyanobacterial and topographic control of the core metabolism of the cryoconite ecosystem of an Arctic ice cap

Glaciers host ecosystems comprised of biodiverse and active microbiota. Among glacial ecosystems, less is known about the ecology of ice caps since most studies focus on valley glaciers or ice sheet margins. Previously we detailed the microbiota of one such high Arctic ice cap, focusing on cryoconite as a microbe-mineral aggregate formed by cyanobacteria. Here, we employ metabolomics at the scale of an entire ice cap to reveal the major metabolic pathways prevailing in the cryoconite of Foxfonna, central Svalbard. We reveal how geophysical and biotic processes influence the metabolomes of its resident cryoconite microbiota. We observed differences in amino acid, fatty acid, and nucleotide synthesis across the cap reflecting the influence of ice topography and the cyanobacteria within cryoconite. Ice topography influences central carbohydrate metabolism and nitrogen assimilation, whereas bacterial community structure governs lipid, nucleotide, and carotenoid biosynthesis processes. The prominence of polyamine metabolism and nitrogen assimilation highlights the importance of recycling nitrogenous nutrients. To our knowledge, this study represents the first application of metabolomics across an entire ice mass, demonstrating its utility as a tool for revealing the fundamental metabolic processes essential for sustaining life in supraglacial ecosystems experiencing profound change due to Arctic climate change-driven mass loss.     

Marine Bacterial Compounds Evaluated by In Silico Studies as Antipsychotic Drugs Against Schizophrenia

Schizophrenia (SCZ) is one of the brain disorders which affects the thinking and behavioral skills of patients. This disorder comes along with an overproduction of kynurenic acid in the cerebrospinal fluid and the prefrontal cortex of SCZ patients. In this study, marine bacterial compounds were screened for their suitability as antagonists against human kynurenine aminotransferase (hKAT-1) which causes the synthesis of kynurenic acid downstream which ultimately causes the SCZ disorder according to the kynurenic hypothesis of SCZ. The marine actinobacterial compound bonactin shows more promising results than other tested marine compounds such as the histamine H2 blocker famotidine and indole-3-acetic acid (IAC) from docking and in silico toxicological studies carried out here. The obtained results of the Grid-based Ligand Docking with Energetics (Glide) scores of extra-precision (XP) Glide against the target protein hKAT-1 on IAC, famotidine, and bonactin were ??6.581, ??6.500 and ??7.730 kcal/mol where Glide energies were ??29.84, ??28.391, and ??47.565 kcal/mol, respectively. Bonactin is known as an antibacterial and antifungal compound being extracted from a marine Streptomyces sp. Comparing tested compounds against the drug target hKAT-1, bonactin alone showed the best Glide score and Glide energy on the target protein hKAT-1.     

Multivariate drug resistance and microbial risk assessment in tropical coastal communities

Multivariate water quality parameters and statistical analysis were used to evaluate the factors controlling coastal drinking water quality and associated health risks among fisherfolks. Multidrug-resistant strains noticed in 400 isolates show 62% Salmonella; 53% Shigella sp.; 48% E. coli; and 36% Vibrio sp. in groundwater sample. In component analysis seawater intrusion, redox reaction, anthropogenic pollution, and weather factors were responsible for more than 93.3% in postmonsoon and 89.4% in summer season, respectively, for Cumulative %. In epidemiology study, 66% and 76% of municipally supplied drinking water were used in Pondicherry and Rameshwaram, respectively, compared to the amount of groundwater (34% and 20%) used in the study area. Similarly, Pondicherry and Rameshwaram areas recorded open defecation instances of 94% and 82%, respectively where less than 5% of the population used hygienic sanitation as part of the Clean India Mission in rural areas.     

Effect of afforestation and reforestation of pastures on the activity and population dynamics of methanotrophic bacteria

We investigated the effect of afforestation and reforestation of pastures on methane oxidation and the methanotrophic communities in soils from three different New Zealand sites. Methane oxidation was measured in soils from two pine (Pinus radiata) forests and one shrubland (mainly Kunzea ericoides var. ericoides) and three adjacent permanent pastures. The methane oxidation rate was consistently higher in the pine forest or shrubland soils than in the adjacent pasture soils. A combination of phospholipid fatty acid (PLFA) and stable isotope probing (SIP) analyses of these soils revealed that different methanotrophic communities were active in soils under the different vegetations. The C18 PLFAs (signature of type II methanotrophs) predominated under pine and shrublands, and C16 PLFAs (type I methanotrophs) predominated under pastures. Analysis of the methanotrophs by molecular methods revealed further differences in methanotrophic community structure under the different vegetation types. Cloning and sequencing and terminal-restriction fragment length polymorphism analysis of the particulate methane oxygenase gene (pmoA) from different samples confirmed the PLFA-SIP results that methanotrophic bacteria related to type II methanotrophs were dominant in pine forest and shrubland, and type I methanotrophs (related to Methylococcus capsulatus) were dominant in all pasture soils. We report that afforestation and reforestation of pastures caused changes in methane oxidation by altering the community structure of methanotrophic bacteria in these soils.     

Expression of conserved signalling pathway genes during spontaneous vascular differentiation of R1 embryonic stem cells and in Py-4-1 endothelial cells

Embryonic stem (ES) cells are an invaluable model for identifying subtle phenotypes as well as severe outcomes of perturbing gene function that may otherwise result in lethality. However, though ES cells of different origins are regarded as equally pluripotent, their in vitro differentiation potential varies, suggesting that their response to developmental signals is different. The R1 cell line is widely used for gene manipulation due to its good growth characteristics and highly efficient germline transmission. Hence, we analysed the expression of Notch, Wnt and Sonic Hedgehog (Shh) pathway genes during differentiation of R1 cells into early vascular lineages. Notch-, Wnt-and Shh-mediated signalling is important during embryonic development. Regulation of gene expression through these signalling molecules is a frequently used theme, resulting in context-dependent outcomes during development. Perturbing these pathways can result in severe and possibly lethal developmental phenotypes often due to primary cardiovascular defects. We report that during early spontaneous differentiation of R1 cells, Notch-1 and the Wnt target Brachyury are active whereas the Shh receptor is not detected. This expression pattern is similar to that seen in a mouse endothelial cell line. This temporal study of expression of genes representative of all three pathways in ES cell differentiation will aid in further analysis of cell signalling during vascular development.     

Analytical techniques for vancomycin—A review

Vancomycin belongs to the vancomycin-ristocetin family of glycopeptides, and is a subclass of linear sugar containing peptides composed of seven amino acids. Its stereochemical configuration forms the basis of a particular mode of action, though its complexation with the D-alanyl-D-alanine terminus of peptidoglycon monomer. The glycosylated hexapeptide chain consists of chloro-β-hydroxytyrosines, p-hydroxyphenylglycines, N-methylleucine and aspartic acid forms a rigid molecular frame work and gives the difficulty in the analysis. Vancomycin in the serum samples is usually estimated by liquid chromatography and the bacterial sensitivity was genereally tested by the microbiological assay. The present review deals with the qualitative, quantitative, microbiological and immunological assays and the comparison of the quantitative methods. Clinical implications of vancomycin have also been cited in the review.