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991.
High-altitude freshwater ecosystems and their biocoenosis are ideal sentinel systems to detect global change. In particular, pond communities are likely to be highly responsive to climate warming. For this reason, the Swiss National Park has included ponds as part of a long-term monitoring programme of the high-alpine Macun cirque. This cirque covers 3.6 km2, has a mean altitude of 2,660 m a.s.l., and includes a hydrographic system composed of a stream network and more than 35 temporary and permanent ponds. The first two steps in the programme were to (i) make an inventory of the macroinvertebrates of the waterbodies in the Macun cirque, and (ii) relate the assemblages to local or regional environmental variables. Sampling was conducted in 25 ponds between 2002 and 2004. The number of taxa characterising the region (Macun cirque) was low, represented by 47 lentic taxa. None of them was endemic to the Alps, although several species were cold stenothermal. Average pond richness was low (11.3 taxa). Assemblages were dominated by Chironomidae (Diptera), and Coleoptera and Oligochaeta were also relatively well represented. Other groups, which are frequent in lowland ponds, had particularly poor species richness (Trichoptera, Heteroptera) or were absent (Gastropoda, Odonata, Ephemeroptera). Macroinvertebrate assemblages (composition, richness) were only weakly influenced by local environmental variables. The main structuring processes were those operating at regional level and, namely, the connectivity between ponds, i.e. the presence of a physical connection (tributary) and/or small geographical distance between ponds. The results suggest that during the long-term monitoring of the Macun ponds (started in 2005), two kinds of change will affect macroinvertebrate assemblages. The first change is related to the natural dynamics, with high local-scale turnover, involving the metapopulations characterising the Macun cirque. The second change is related to global warming, leading to higher local and regional richness through an increase in the number of colonisation events resulting from the upward shift of geographical ranges of species. At the same time the cold stenothermal species from Macun will be subject to extinction. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Guest editors: R. Céréghino, J. Biggs, B. Oertli & S. Declerck The ecology of European ponds: defining the characteristics of a neglected freshwater habitat  相似文献   
992.
Intracellular signaling events are often organized around PDZ (PSD-95/Drosophila Disc large/ZO-1 homology) domain-containing scaffolding proteins. The ubiquitously expressed multi-PDZ protein MUPP1, which is composed of 13 PDZ domains, has been shown to interact with multiple viral and cellular proteins and to play important roles in receptor targeting and trafficking. In this study, we show that MUPP1 binds to the G protein-coupled MT(1) melatonin receptor and directly regulates its G(i)-dependent signal transduction. Structural determinants involved in this interaction are the PDZ10 domain of MUPP1 and the valine of the canonical class III PDZ domain binding motif DSV of the MT(1) carboxyl terminus. This high affinity interaction (K(d) approximately 4 nm), which is independent of MT(1) activation, occurs in the ovine pars tuberalis of the pituitary expressing both proteins endogenously. Although the disruption of the MT(1)/MUPP1 interaction has no effect on the subcellular localization, trafficking, or degradation of MT(1), it destabilizes the interaction between MT(1) and G(i) and abolishes G(i)-mediated signaling of MT(1). Our findings highlight a previously unappreciated role of PDZ proteins in promoting G protein coupling to receptors.  相似文献   
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Brown rust, caused by Puccinia melanocephala, has had devastating effects on sugarcane (Saccharum spp.) breeding programs and commercial production. The discovery of Bru1, a major gene conferring resistance to brown rust, represented a substantial breakthrough. Markers for Bru1 are the first available for sugarcane molecular breeding. The contribution of Bru1 towards brown rust resistance in the Canal Point (CP) sugarcane breeding program was determined as a means of directing future breeding strategies. Bru1 was detected in 285 of 1,072 (27 %) clones used for crossing; this germplasm represents the genetic base for cultivar development in Florida. The frequency of Bru1 was greatest in CP clones (42 %) and lowest among Louisiana clones (6 %). Bru1 was not detected in clones with year assignments before 1953. However, Bru1 frequency increased from 15 % (assignments 1975–1985) to 47 % in the current decade. The increase coincided with the introduction of brown rust to Florida. Bru1 was detected in 155 (32 %) of 485 parental clones tested for brown rust susceptibility at two field locations. Of clones classed resistant to brown rust, 154 (59 %) contained Bru1, yet none of 100 susceptible clones contained the gene. Bru1 was detected in 667 (44 %) clones in the second clonal stage of selection, 87 % of which were free of brown rust symptoms. Bru1 is the predominant source of resistance in the Florida sugarcane genetic base. Efforts to identify and integrate new brown rust resistance genes must be pursued to minimize risks associated with a future breakdown in major gene resistance provided by Bru1.  相似文献   
997.
The phage T4 morphogenetic gene 31 has been sequenced. Its deduced gene product is a polypeptide of 111 aa, with a predicted Mr of 12064 and a pI of 4.88. The proof that the assigned open reading frame (ORF) encodes Gp31 rests on the sequencing of two known gene 31 amber mutations, amN54 and NG71, demonstrating that these mutations result in translational termination within the assigned ORF. Furthermore, the sequencing of four different T4 epsilon mutations, isolated on the basis of allowing the phage to propagate on Escherichia coli groEL- hosts, showed that they are either missense mutations or 3-bp deletions in the gene 31 reading frame. The sequencing of neighboring DNA revealed the presence of five other ORFs, one of which overlaps gene 31 substantially, but in the opposite orientation.  相似文献   
998.
Thirty patients receiving haemodialysis, including two who had undergone bilateral nephrectomy, showed significant increases (p less than 0.001) in packed cell volume, haemoglobin concentration, and reticulocyte count during an episode of viral or toxic liver cytolysis. In 19 cases the episode lasted a mean of 5.0 +/- SD 2.9 months and was accompanied by improved haematological values for a mean of 12.0 +/- 6.0 weeks. Of the remaining patients, in whom the episode lasted a mean of 8.0 +/- 3.5 months (p less than 0.02), seven showed continued improvement a mean of 30.0 +/- 16.0 weeks after cytolysis. In eight patients in this group there was an apparent correlation between persistently increased haemoglobin concentrations and biopsy evidence of chronic hepatitis. The findings suggest that the reduction in anaemia resulted from enhanced red-cell production mediated by secretion of erythropoietin from regenerating liver cells. If confirmed this might have important implications for the treatment of anaemia in chronic renal insufficiency.  相似文献   
999.

Background

We have previously proposed triosephosphate isomerase of Giardia lamblia (GlTIM) as a target for rational drug design against giardiasis, one of the most common parasitic infections in humans. Since the enzyme exists in the parasite and the host, selective inhibition is a major challenge because essential regions that could be considered molecular targets are highly conserved. Previous biochemical evidence showed that chemical modification of the non-conserved non-catalytic cysteine 222 (C222) inactivates specifically GlTIM. The inactivation correlates with the physicochemical properties of the modifying agent: addition of a non-polar, small chemical group at C222 reduces the enzyme activity by one half, whereas negatively charged, large chemical groups cause full inactivation.

Results

In this work we used mutagenesis to extend our understanding of the functional and structural effects triggered by modification of C222. To this end, six GlTIM C222 mutants with side chains having diverse physicochemical characteristics were characterized. We found that the polarity, charge and volume of the side chain in the mutant amino acid differentially alter the activity, the affinity, the stability and the structure of the enzyme. The data show that mutagenesis of C222 mimics the effects of chemical modification. The crystallographic structure of C222D GlTIM shows the disruptive effects of introducing a negative charge at position 222: the mutation perturbs loop 7, a region of the enzyme whose interactions with the catalytic loop 6 are essential for TIM stability, ligand binding and catalysis. The amino acid sequence of TIM in phylogenetic diverse groups indicates that C222 and its surrounding residues are poorly conserved, supporting the proposal that this region is a good target for specific drug design.

Conclusions

The results demonstrate that it is possible to inhibit species-specifically a ubiquitous, structurally highly conserved enzyme by modification of a non-conserved, non-catalytic residue through long-range perturbation of essential regions.  相似文献   
1000.

Objective

To investigate the factors associated with HIV1 RNA plasma viral load (pVL) below 40 copies/mL at the third trimester of pregnancy, as part of prevention of mother-to-child transmission (PMTCT) in Benin.

Design

Sub study of the PACOME clinical trial of malaria prophylaxis in HIV-infected pregnant women, conducted before and after the implementation of the WHO 2009 revised guidelines for PMTCT.

Methods

HIV-infected women were enrolled in the second trimester of pregnancy. Socio-economic characteristics, HIV history, clinical and biological characteristics were recorded. Malaria prevention and PMTCT involving antiretroviral therapy (ART) for mothers and infants were provided. Logistic regression helped identifying factors associated with virologic suppression at the end of pregnancy.

Results

Overall 217 third trimester pVLs were available, and 71% showed undetectability. Virologic suppression was more frequent in women enrolled after the change in PMTCT recommendations, advising to start ART at 14 weeks instead of 28 weeks of pregnancy. In multivariate analysis, Fon ethnic group (the predominant ethnic group in the study area), regular job, first and second pregnancy, higher baseline pVL and impaired adherence to ART were negative factors whereas higher weight, higher antenatal care attendance and longer ART duration were favorable factors to achieve virologic suppression.

Conclusions

This study provides more evidence that ART has to be initiated before the last trimester of pregnancy to achieve an undetectable pVL before delivery. In Benin, new recommendations supporting early initiation were well implemented and, together with a high antenatal care attendance, led to high rate of virologic control.  相似文献   
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