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41.
Dengue is a major cause of morbidity in Puerto Rico and is well-known to its physicians. Early case identification and timely initiation of treatment for patients with severe dengue can reduce medical complications and mortality. To determine clinical management and reporting practices, and assess knowledge of dengue and its management, a survey was sent to 2,512 physicians with a medical license in Puerto Rico. Of the 2,313 physicians who received the survey, 817 (35%) completed the questionnaire. Of the respondents, 708 were currently practicing medicine; 138 were board certified (Group 1), 282 were board eligible (Group 2), and 288 had not finished residency (Group 3). Although respondents clinically diagnosed, on average, 12 cases of dengue in the preceding three months, 31% did not report any suspected cases to public health officials while about half (56%) reported all cases. Overall, 29% of respondents correctly identified early signs of shock and 48% identified severe abdominal pain and persistent vomiting as warning signs for severe dengue with the proportion of correct respondents highest in Group 1. Reportedly about sixty percent (57%) appropriately never give corticosteroids or prophylactic platelet transfusions to dengue patients. One third (30%) of respondents correctly identified administration of intravenous colloid solution as the best treatment option for dengue patients with refractory shock and elevated hematocrit after an initial trial of intravenous crystalloids, and nearly one half (46%) correctly identified administration of a blood transfusion as the best option for dengue patients with refractory shock and decreased hematocrit after a trial of intravenous crystalloids. Even though dengue has been endemic in Puerto Rico for nearly 4 decades, knowledge of dengue management is still limited, compliance with WHO treatment guidelines is suboptimal, and underreporting is significant. These findings were used to design a post graduate training course to improve the clinical management of dengue.  相似文献   
42.
One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.  相似文献   
43.
Four patients with overhydrated cation leak stomatocytosis (OHSt) exhibited the heterozygous RhAG missense mutation F65S. OHSt erythrocytes were osmotically fragile, with elevated Na and decreased K contents and increased cation channel-like activity. Xenopus oocytes expressing wild-type RhAG and RhAG F65S exhibited increased ouabain and bumetanide-resistant uptake of Li(+) and (86)Rb(+), with secondarily increased (86)Rb(+) influx sensitive to ouabain and to bumetanide. Increased RhAG-associated (14)C-methylammonium (MA) influx was severely reduced in RhAG F65S-expressing oocytes. RhAG-associated influxes of Li(+), (86)Rb(+), and (14)C-MA were pharmacologically distinct, and Li(+) uptakes associated with RhAG and RhAG F65S were differentially inhibited by NH(4)(+) and Gd(3+). RhAG-expressing oocytes were acidified and depolarized by 5 mM bath NH(3)/NH(4)(+), but alkalinized and depolarized by subsequent bath exposure to 5 mM methylammonium chloride (MA/MA(+)). RhAG F65S-expressing oocytes exhibited near-wild-type responses to NH(4)Cl, but MA/MA(+) elicited attenuated alkalinization and strong hyperpolarization. Expression of RhAG or RhAG F65S increased steady-state cation currents unaltered by bath Li(+) substitution or bath addition of 5 mM NH(4)Cl or MA/MA(+). These oocyte studies suggest that 1) RhAG expression increases oocyte transport of NH(3)/NH(4)(+) and MA/MA(+); 2) RhAG F65S exhibits gain-of-function phenotypes of increased cation conductance/permeability, and loss-of-function phenotypes of decreased and modified MA/MA(+) transport, and decreased NH(3)/NH(4)(+)-associated depolarization; and 3) RhAG transports NH(3)/NH(4)(+) and MA/MA(+) by distinct mechanisms, and/or the substrates elicit distinct cellular responses. Thus, RhAG F65S is a loss-of-function mutation for amine transport. The altered oocyte intracellular pH, membrane potential, and currents associated with RhAG or RhAG F65S expression may reflect distinct transport mechanisms.  相似文献   
44.
Aquatic species can experience different selective pressures on morphology in different flow regimes. Species inhabiting lotic regimes often adapt to these conditions by evolving low‐drag (i.e., streamlined) morphologies that reduce the likelihood of dislodgment or displacement. However, hydrodynamic factors are not the only selective pressures influencing organismal morphology and shapes well suited to flow conditions may compromise performance in other roles. We investigated the possibility of morphological trade‐offs in the turtle Pseudemys concinna. Individuals living in lotic environments have flatter, more streamlined shells than those living in lentic environments; however, this flatter shape may also make the shells less capable of resisting predator‐induced loads. We tested the idea that “lotic” shell shapes are weaker than “lentic” shell shapes, concomitantly examining effects of sex. Geometric morphometric data were used to transform an existing finite element shell model into a series of models corresponding to the shapes of individual turtles. Models were assigned identical material properties and loaded under identical conditions, and the stresses produced by a series of eight loads were extracted to describe the strength of the shells. “Lotic” shell shapes produced significantly higher stresses than “lentic” shell shapes, indicating that the former is weaker than the latter. Females had significantly stronger shell shapes than males, although these differences were less consistent than differences between flow regimes. We conclude that, despite the potential for many‐to‐one mapping of shell shape onto strength, P. concinna experiences a trade‐off in shell shape between hydrodynamic and mechanical performance. This trade‐off may be evident in many other turtle species or any other aquatic species that also depend on a shell for defense. However, evolution of body size may provide an avenue of escape from this trade‐off in some cases, as changes in size can drastically affect mechanical performance while having little effect on hydrodynamic performance. J. Morphol. 2011. © 2011 Wiley‐Liss, Inc.  相似文献   
45.
In order to assess the frequency of C-anaphases in colchicine-arrested lymphocyte cultures, the authors studied 100 patients classified in four groups: spontaneous abortion (n = 17), subfertility (n = 12), aneuploidy (n = 18) and miscellaneous (n = 53). At least 300 mitotic G-banded cells were scored by individual. In 12 individuals no C-anaphases were observed; in 87 individuals the range was 1-7 with a mode of 2 and a mean of 2.14; the remaining individual had 19 C-anaphases in 330 cells (5.7%). The statistical analysis did not show significant differences between the groups (p > 0.05). These data along with previous studies indicate that normally most individuals have < or = 3% of C-anaphases in habitual lymphocyte cultures. Moreover, there exists an autosomal dominant form in which individuals with the trait have > 5% of the cells with such mitotic configurations. We conclude that both the low frequency common and the high frequency familiar forms are mitotic variants without pathological significance.  相似文献   
46.
The encapsulated fungus Cryptococcus neoformans is a common cause of life-threatening disease in immunocompromised individuals. Its major virulence determinant is the polysaccharide (PS) capsule. An unsolved problem in cryptococcal biology is whether the PSs composing the capsule are linear or complex branched polymers, as well as the implications of this structural composition in pathogenesis. In this study we approached the problem by combining static and dynamic light scattering, viscosity analysis, and high-resolution microscopy and correlated the findings with biological properties. Analysis of the dependence of capsular PS molecular mass and the radius of gyration provided strong evidence against a simple linear PS configuration. Shape factors calculated from light scattering measurements in solution revealed values consistent with polymer branching. Furthermore, viscosity measurements provided complementary evidence for structural branching. Electron microscopy showed PS spherical-like structures similar to other branched PS. Finally, we show that the capacity of capsular PS to interfere in complement-mediated phagocytosis, inhibit nitric oxide production by macrophage-like cells, protect against reactive oxygen species, antibody reactivity and half-life in serum were influenced by the degree of branching, providing evidence for the notion that PS branching is an important parameter in determining the biological activity of C. neoformans PS.  相似文献   
47.

Background

Bacterial mercury resistance is based on enzymatic reduction of ionic mercury to elemental mercury and has recently been demonstrated to be applicable for industrial wastewater clean-up. The long-term monitoring of such biocatalyser systems requires a cultivation independent functional community profiling method targeting the key enzyme of the process, themerAgene coding for the mercuric reductase. We report on the development of a profiling method formerAand its application to monitor changes in the functional diversity of the biofilm community of a technical scale biocatalyzer over 8 months of on-site operation.

Results

Based on an alignment of 30merAsequences from Gram negative bacteria, conserved primers were designed for amplification ofmerAfragments with an optimized PCR protocol. The resulting amplicons of approximately 280 bp were separated by thermogradient gelelectrophoresis (TGGE), resulting in strain specific fingerprints for mercury resistant Gram negative isolates with differentmerAsequences. ThemerAprofiling of the biofilm community from a technical biocatalyzer showed persistence of some and loss of other inoculum strains as well as the appearance of new bands, resulting in an overall increase of the functional diversity of the biofilm community. One predominant new band of themerAcommunity profile was also detected in a biocatalyzer effluent isolate, which was identified asPseudomonas aeruginosa. The isolated strain showed lower mercury reduction rates in liquid culture than the inoculum strains but was apparently highly competitive in the biofilm environment of the biocatalyzer where moderate mercury levels were prevailing.

Conclusions

ThemerAprofiling technique allowed to monitor the ongoing selection for better adapted strains during the operation of a biocatalyzer and to direct their subsequent isolation. In such a way, a predominant mercury reducingPs. aeruginosastrain was identified by its unique mercuric reductase gene.  相似文献   
48.
Marine mammals are known to dive up to 2000 m and, therefore, tolerate as much as 200 atm. of hydrostatic pressure. To examine possible metabolic adaptations to these elevated pressures, fresh blood samples from marine and terrestrial mammals were incubated for 2 h at 37 degrees C under 136 atm (2000 psi) of hydrostatic pressure. The consumption of plasma glucose and the production of lactate over the 2-h period were used to assess glycolytic flux in the red cells. The results indicate that glycolytic flux as measured by lactate production under pressure can be significantly depressed in most terrestrial mammals and either not altered or accelerated in marine mammals. The data also suggest that there is a significant shift in the ratio of lactate produced to glucose consumed under pressure. Interestingly, human and dolphin blood do not react to pressure. These combined data imply a metabolic adaptation to pressure in marine mammal RBC that may not be necessary in human or dolphin cells due to their unique patterns of glucose metabolism.  相似文献   
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