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Biomedical subjects

B Fry

Publications and source records attributed to B Fry.

At least 19 recordsLinked to original sources

Positive natural selection in the human lineage.

Positive natural selection is the force that drives the increase in prevalence of advantageous traits, and it has played a central role in our development as a species. Until recently, the study of natural selection in humans has largely been restricted to comparing individual candidate genes to theoretical expectations. The advent of genome-wide sequence and polymorphism data brings fundamental new tools to the study of natural selection. It is now possible to identify new candidates for selection and to reevaluate previous claims by comparison with empirical distributions of DNA sequence variation across the human genome and among populations. The flood of data and analytical methods, however, raises many new challenges. Here, we review approaches to detect positive natural selection, describe results from recent analyses of genome-wide data, and discuss the prospects and challenges ahead as we expand our understanding of the role of natural selection in shaping the human genome.

Alleles↗

Interprofessional postgraduate education in primary health care: is it making a difference?

This paper explores attitudes to, and perceptions of, the impact of interprofessional postgraduate education for primary health care professionals, based on a postal survey of 153 primary health care professionals undertaking postgraduate qualifications in New Zealand. The response rate was 75% (114/153 responses); comprising 79 doctors, 28 nurses, 7 other health professionals. As a result of their postgraduate education, 92% (104/113) reported improvement in their own practice; 68% (72/106) reported a positive influence on their workplace practice. Forty-eight percent (53/111) increased their understanding of their own professional role; 79% (77/98) increased their understanding of another professional groups' skills and competencies. Twenty-two percent (25/114) perceived increased career opportunities within a year; 56% (64/114) in the longer term. Only 12% (14/114) perceived future increases in income as a result of their study. Interprofessional postgraduate qualification study for primary health care professionals in New Zealand resulted in personal and professional benefit for individuals and their clinical practice, and increased understanding about their own and other health professionals' roles. The interprofessional nature of the education was seen as positive, contributing to a modest increase in collaboration between health professional groups. Barriers to furthering participation in interprofessional learning and increasing intersectorial collaboration in the workplace are identified and discussed.

Adult↗

Haploview: analysis and visualization of LD and haplotype maps.

UNLABELLED: Research over the last few years has revealed significant haplotype structure in the human genome. The characterization of these patterns, particularly in the context of medical genetic association studies, is becoming a routine research activity. Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface. AVAILABILITY: http://www.broad.mit.edu/mpg/haploview/ CONTACT: jcbarret@broad.mit.edu

Algorithms↗

Steady state models of stable isotopic distributions.

This study reviews common calculations and mathematical models used in stable isotopic studies. Some approximations are adopted to simplify the algebra for use in steady state models, with more rigorous mathematics outlined in an Appendix. Review shows that steady-state isotopic models are easy to construct, provide good approximations of system behavior, and are very helpful in evaluating isotopic cycling in many kinds of systems.

Carbon Isotopes↗

Using stable isotopes in mangrove fisheries research--a review and outlook.

Mangrove forests are important coastal wetlands in most of the tropics, but their importance to fisheries is poorly understood. Rationales for conserving these ecosystems are partly based on ideas that mangroves are important to food webs that support fisheries. Here we review use of stable isotopes to test the strength of the mangrove forest-fish connection, suggesting that a dual focus on both food web ecology and habitat use may be most profitable in future studies of this type.

Animals↗

Characterization of growth and acid formation in a Bacillus subtilis pyruvate kinase mutant.

Based on measurements and theoretical analyses, we identified deletion of pyruvate kinase (PYK) activity as a possible route for elimination of acid formation in Bacillus subtilis cultures grown on glucose minimal media. Evidence consistent with the attenuation of PYK flux has come from metabolic flux calculations, metabolic pool and enzymatic activity measurements, and a series of nuclear magnetic resonance experiments, all suggesting a nearly complete inhibition of PYK activity for glucose-citrate fed cultures in which the amount of acid formation was nearly zero. In this paper, we report the construction and characterization of a pyk mutant of B. subtilis. Our results demonstrate an almost complete elimination of acid production in cultures of the pyk mutant in glucose minimal medium. The substantial reduction in acid production is accompanied by increased CO(2) production and a reduced rate of growth. Metabolic analysis indicated a dramatic increase in intracellular pools of phosphoenolpyruvate (PEP) and glucose-6-P in the pyk mutant. The high concentrations of PEP and glucose-6-P could explain the decreased growth rate of the mutant. The substantial accumulation of PEP does not occur in Escherichia coli pyk mutants. The very high concentration of PEP which accumulates in the B. subtilis pyk mutant could be exploited for production of various aromatics.

Bacillus subtilis↗

Microbial utilization of estuarine dissolved organic carbon: a stable isotope tracer approach tested by mass balance.

The natural stable isotope values of different plants have been used to trace the fate of organic carbon that enters estuarine ecosystems. Experiments were designed to determine the magnitude of (delta) (sup13)C changes of dissolved organic carbon (DOC) derived from tidal marsh vegetation that occurred during bacterial decomposition. Bacteria were grown on DOC leached from estuarine Spartina alterniflora and Typhus angustifolia plants. In four experiments, 25 to 80% of the initial carbon (2.6 to 9.1 mM organic C) was converted to bacterial biomass and CO(inf2). Mass balance calculations showed good recovery of total C and (sup13)C at the end of these experiments (100% (plusmn) 14% total C; (plusmn) 1(permil) (delta) (sup13)C). The (delta) (sup13)C values of DOC, bacterial biomass, and respired CO(inf2) changed only slightly in the four experiments by average values of -0.6, +1.4, and +0.5(permil), respectively. These changes are small relative to the range of (delta) (sup13)C values represented by different organic carbon sources to estuaries. Thus, microbial (delta) (sup13)C values determined in the field helped to identify the source of the carbon assimilated by bacteria.

Journal Article↗

Contribution of superficial nephron segments to sodium excretion in experimental glomerulonephritis.

The present study examined the contribution of individual superficial nephron segments to sodium excretion in antiglomerular basement membrane nephritis in the rat by sampling the same nephron successively from the end and beginning of the distal tubule and end of the proximal tubule. Whole kidney GFR in glomerulonephritic rats was reduced by approximately 40% from controls; absolute sodium excretion was about 25% of normal. Metabolic balance studies in the awake state had suggested that the animals were in sodium balance. Plasma renin levels before and during micropuncture were similar to controls. These findings suggest that the defect in sodium handling is intrinsic to the kidney. Glomerulotubular balance was maintained along the proximal tubule. Sodium reabsorption in the loop of Henle was reduced in absolute terms but was proportional to the load delivered. Due to the decreased absolute sodium reabsorption in the preceding segments, sodium delivery to the beginning of the distal tubule was comparable in the two groups of animals. Along the distal tubule sodium reabsorption was comparable to control animals. Therefore, the avid urinary sodium retention seen during micropuncture was due to increased sodium reabsorption by segments past the superficial proximal tubule and/or by deep nephrons.

Animals↗

Sulfur isotope effects associated with oxidation of sulfide by O2 in aqueous solution.

Normal sulfur isotope effects averaging epsilon = -5.2 +/- 1.4% (s.d.) were consistently observed for the oxidation of sulfide in aqueous solution. Reaction products were sulfate, thiosulfate and sulfite at pH 10.8-11 in distilled water; S0 was formed in two experiments with synthetic seawater at pH 8-9.5. Because the -5.2% normal isotope effect differs significantly from the previously measured +2% inverse effect associated with anaerobic oxidation of sulfide by photosynthetic bacteria, stable sulfur isotopic measurements are potentially useful for distinguishing aerobic vs. anaerobic sulfide oxidation in marine and freshwater sulfureta.

Bacteria, Anaerobic↗

34S/32S fractionation in sulfur cycles catalyzed by anaerobic bacteria.

Stable isotopic distributions in the sulfur cycle were studied with pure and mixed cultures of the anaerobic bacteria, Chlorobium vibrioforme and Desulfovibrio vulgaris. D. vulgaris and C. vibrioforme can catalyze three reactions constituting a complete anaerobic sulfur cycle: reduction of sulfate to sulfide (D. vulgaris), oxidation of sulfide to elemental sulfur (C. vibrioforme), and oxidation of sulfur to sulfate (C. vibrioforme). In all experiments, the first and last reactions favored concentration of the light 32S isotope in products (isotopic fractionation factor epsilon = -7.2 and -1.7%, respectively), whereas oxidation of sulfide favored concentration of the heavy 34S isotope in products (epsilon = +1.7%). Experimental results and model calculations suggest that elemental sulfur enriched in 34S versus sulfide may be a biogeochemical marker for the presence of sulfide-oxidizing bacteria in modern and ancient environments.

Desulfovibrio vulgaris↗

Ammonia loss from rat proximal tubule in vivo: effects of luminal pH and flow rate.

The roles of luminal pH and flow rate in determining ammonia loss from proximal tubules perfused with solutions containing 10 mM NH4Cl were examined using in vivo microperfusion. Perfusate bicarbonate concentration was varied between 5, 25, and 40 mM in tubules perfused at 50 nl/min. As expected, ammonia loss from the 25 or 40 mM bicarbonate-containing perfusates was greater than from that containing 5 mM bicarbonate. Furthermore, there was a correlation between ammonia loss and the log mean luminal bicarbonate concentration (r = 0.39, P less than 0.01). From the collected fluid ammonia and bicarbonate concentrations, the transtubular gradients for NH+4 and NH3 were estimated, allowing a calculation of the apparent permeability coefficients for NH3 (PNH3) and NH+4 (PNH+4). The calculated PNH3 of 2.2 +/- 0.5 X 10(-2) cm/s was similar to previous estimates in the rabbit; the calculated PNH+4 of 5.5 +/- 0.8 X 10(-4) cm/s was approximately 10 times that previously found in the rabbit proximal straight tubule in vitro. Next, flow rate was varied between 25 and 50 nl/min using the 5 mM bicarbonate perfusate. Ammonia loss was significantly higher from the latter. Thus these studies suggest that NH+4 loss from the proximal tubule may be an important determinant of ammonia movement along this segment. Ammonia loss is flow-rate dependent, similar to ammonia entry in previous studies.

Ammonia↗

Sources of carbon and sulfur nutrition for consumers in three meromictic lakes of New York State.

The trophic importance of bacterioplankton as a source of carbon and sulfur nutrition for consumers in meromictic lakes was tested using stable carbon (delta 13C) and sulfur (delta 34S) isotopic measurements. Studies in three lakes near Syracuse, New York, showed that most consumers ultimately derive their C and S nutrition from a mixture of terrestrial detritus, phytoplankton, and littoral vegetation, rather than from bacterioplankton. Food webs in these meromictic lakes are thus similar to those in other lakes that lack dense populations of bacterioplankton.

Animals↗

Sulfur isotope effects associated with protonation of HS- and volatilization of H2S.

The isotope effects associated with: (1) formation of H2S from HS- by protonation in aqueous solution; and (2) volatilization of H2S have been experimentally determined. Both isotopic distributions in closed systems at equilibrium and differential rates of volatilization of isotopic species in open systems were measured at 22 +/- 1 degrees C. It was found that, at equilibrium aqueous H2S is enriched in 34S by 2.0 - 2.7% relative to HS- and that H2S volatilized from solution is depleted in 34S by 0.5% relative to dissolved H2S. A small kinetic isotope effect accompanying volatilization of H2S was observed in the open-system experiments.

Geological Phenomena↗

Isotope effects associated with the anaerobic oxidation of sulfite and thiosulfate by the photosynthetic bacterium, Chromatium vinosum.

The purple photosynthetic bacterium Chromatium vinosum, strain D, catalyzes several oxidations of reduced sulfur compounds under anaerobic conditions in the light: e.g., sulfide --> sulfur --> sulfate, sulfite --> sulfate, and thiosulfate --> sulfur + sulfate. Here it is shown that no sulfur isotope effect is associated with the last of these processes; isotopic compositions of the sulfur and sulfate produced can differ, however, if the sulfane and sulfonate positions within the thiosulfate have different isotopic compositions. In the second process, an observed change from an inverse to a normal isotope effect during oxidation of sulfite may indicate the operation of 2 enzymatic pathways. In contrast to heterotrophic anaerobic reduction of oxidized sulfur compounds, anaerobic oxidations of inorganic sulfur compounds by photosynthetic bacteria are characterized by relatively small isotope effects.

Anaerobiosis↗

In vivo anti-nuclear antibodies in epithelial biopsies in SLE and other connective tissue diseases.

In vivo anti-nuclear antibody (ANA) was observed by direct immunofluorescence microscopy in epithelial cell nuclei in forty-four biopsies from thirty-three patients. The tissue containing the ANA was macroscopically normal in twenty-seven patients. The thirty-three patients with in vivo biopsy ANA included twenty-three with SLE, three with mixed connective tissue disease, two each with multi-system Sjögren's syndrome, dermatomyositis, and progressive systemic sclerosis, and one with rheumatoid arthritis. Features of sicca syndrome were noted in seventeen patients. The patterns of the in vivo biopsy ANA in the thirty-three patients were speckled (21), homogeneous (6), nodular (2), and both speckled and homogeneous (4). Complement was not detected in the epithelial cell nuclei. Immunoglobulin(s) and/or complement were deposited along the dermoepidermal junction in thirty-two of the forty-four biopsies, and in dermal blood vessels in twenty-two biopsies. Each patient had serum ANA against rat liver substrate; twenty-seven had high titre ANA (1 in 1000 or greater). Elevated levels of DNA-binding were found in twenty patients (61%), but the level of DNA-binding did not correlate with the intensity of in vitro biopsy ANA staining. Serum antibody to ribonucleoprotein (RNP) was present in eight of the twenty-three patients tested (35%), all eight patients having clinical features of sicca syndrome. Hypocomplementaemia was found in thirteen patients (40%), all of whom had active SLE. In vivo biopsy ANA appears to be a real phenomenon of unknown aetiology, and not an artifact, which is found in some patients with active multisystem autoimmune disease, especially SLE.

Adult↗