513 research outputs found
Prediction of N Fractions of Warm-Season Grasses with Near-Infrared Reflectance Spectroscopy
Warm-season (C4), the most common forage for beef production in much of the U.S.A., although having a higher productivity than temperate forages are of a lower quality. Current feeding standards (NRC, 1996) have adapted the Cornell Net Carbohydrate and Protein System (Sniffen et al., 1992) to more accurately characterize forage quality. As these procedures are tedious, data is limited on genetic and management factors influencing quality parameters in C4 species. The objective of this research was to determine if near-infrared reflectance spectroscopy (NIRS) could be used to predict the various N fractions in three C4 grasses
B789: A Breakeven Analysis of Two Rural Health Maintenance Organization Models
This report uses breakeven analysis to assess the financial feasibility of two health maintenance organization (HMO) models which have received considerable support from health-care professionals as potentially viable organizations in rural areas. The two models analyzed, the individual practice association and satellite clinic, represent quite different organizational and financial structures. Enrollment levels required for each HMO model to attain financial viability for specified premium rates are calculated. In addition, the effects of varying key health-care utilization rates on an HMO\u27s financial position are assessed. This information should be of interest to extension agents and others who are working with groups contemplating a variety of health initiatives.https://digitalcommons.library.umaine.edu/aes_bulletin/1067/thumbnail.jp
Inhibitors of Aspartate Transcarbamoylase Inhibit Mycobacterium tuberculosis Growth
Aspartate transcarbamoylase (ATCase) plays a key role in the second step of de novo pyrimidine biosynthesis in eukaryotes and has been proposed to be a target to suppress cell proliferation in E. coli, human cells and the malarial parasite. We hypothesized that a library of ATCase inhibitors developed for malarial ATCase (PfATCase) may also contain inhibitors of the tubercular ATCase and provide a similar inhibition of cellular proliferation. Of the 70 compounds screened, 10 showed single-digit micromolar inhibition in an in vitro activity assay and were tested for their effect on M. tuberculosis cell growth in culture. The most promising compound demonstrated a MIC 90 of 4 μM. A model of MtbATCase was generated using the experimental coordinates of PfATCase. In silico docking experiments showed this compound can occupy a similar allosteric pocket on MtbATCase to that seen on PfATCase, explaining the observed species selectivity seen for this compound series. </p
Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries
The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity
Healthcare designers’ use of prescriptive and performance-based approaches
In the UK, healthcare built environment design is guided by a series of long-established design standards and guidance issued by the Department of Health. More recently, healthcare design focus has broadened to encompass new approaches, supported by large bodies of credible research evidence. It is therefore timely to rethink how healthcare design standards and guidance should be best expressed to suit ‘designerly ways’ of using evidence, to improve their use and effectiveness in practice. This research explored how designers use performance and prescriptive approaches during the healthcare design process. Three in-depth healthcare built environment case studies were used to explore how designers employed such approaches during the design of selected exemplar design elements. Results show that design elements in the pre and conceptual design phases significantly employed performance-based approaches, and due to project-unique circumstances, prescriptive solutions were often significantly modified based on performance criteria. For design elements in the detailed and technical design phases, there was a significant use of solutions based on prescriptive approaches, whilst performance-based criteria were used to evaluate design solutions. This research proposes a performance-based, specification-driven healthcare design with supplementary prescriptive specifications provided for optimum healthcare environment design
Opsonising antibodies to P. falciparum Merozoites associated with immunity to clinical malaria
Naturally acquired humoral immunity to the malarial parasite Plasmodium falciparum can protect against disease, although the precise mechanisms remain unclear. Although antibody levels can be measured by ELISA, few studies have investigated functional antibody assays in relation to clinical outcomes. In this study we applied a recently developed functional assay of antibody-mediated opsonisation of merozoites, to plasma samples from a longitudinal cohort study conducted in a malaria endemic region of Papua New Guinea (PNG). Phagocytic activity was quantified by flow cytometry using a standardized and high-throughput protocol, and was subsequently evaluated for association with protection from clinical malaria and high-density parasitemia. Opsonising antibody responses were found to: i) increase with age, ii) be enhanced by concurrent infection, and iii) correlate with protection from clinical episodes and high-density parasitemia. Stronger protective associations were observed in individuals with no detectable parasitemia at baseline. This study presents the first evidence for merozoite phagocytosis as a correlate of acquired immunity and clinical protection against P. falciparum malaria
Growth response to ozone of annual species from Mediterranean pastures
Ozone (O3) phytotoxicity has been reported on a wide range of plant species. However, scarce information has been provided regarding the sensitivity of semi-natural grassland species, especially those from dehesa Mediterranean grasslands, in spite of their great biological diversity and the high O3 levels recorded in the region. A screening study was carried out in open-top chambers (OTCs) to assess the O3-sensitivity of representative therophytes of these ecosystems based on the response of selected growth-related parameters. Three O3 treatments and 3 OTCs per treatment were used. Legume species were very sensitive to O3, because 78% of the tested species showed detrimental effects on their total biomass relative growth rate (RGR) following their exposure to O3. The Trifolium genus was particularly sensitive showing O3-induced adverse effects on most of the assessed parameters. Gramineae plants were less sensitive than Leguminosae species because detrimental effects on total biomass RGR were only observed in 14% of the assessed species. No relationship was found between relative growth rates when growing in clean air and O3 susceptibility. The implications of these effects on the performance of dehesa acidic grasslands and on the definition of ozone critical levels for the protection of semi-natural vegetation are discussed
High-throughput Screening and Sensitized Bacteria Identify an M. tuberculosis Dihydrofolate Reductase Inhibitor with Whole Cell Activity
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a bacterial pathogen that claims roughly 1.4 million lives every year. Current drug regimens are inefficient at clearing infection, requiring at least 6 months of chemotherapy, and resistance to existing agents is rising. There is an urgent need for new drugs that are more effective and faster acting. The folate pathway has been successfully targeted in other pathogens and diseases, but has not yielded a lead drug against tuberculosis. We developed a high-throughput screening assay against Mtb dihydrofolate reductase (DHFR), a critical enzyme in the folate pathway, and screened a library consisting of 32,000 synthetic and natural product-derived compounds. One potent inhibitor containing a quinazoline ring was identified. This compound was active against the wild-type laboratory strain H37Rv (MIC99 = 207 µM). In addition, an Mtb strain with artificially lowered DHFR levels showed increased sensitivity to this compound (MIC99 = 70.7 µM), supporting that the inhibition was target-specific. Our results demonstrate the potential to identify Mtb DHFR inhibitors with activity against whole cells, and indicate the power of using a recombinant strain of Mtb expressing lower levels of DHFR to facilitate the discovery of antimycobacterial agents. With these new tools, we highlight the folate pathway as a potential target for new drugs to combat the tuberculosis epidemic
A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila
Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2)) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses
Effects of GCK, GCKR, G6PC2 and MTNR1B Variants on Glucose Metabolism and Insulin Secretion
were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion.). genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion
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