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91.
In eukaryotes, GPI (glycosylphosphatidylinositol) lipid anchoring of proteins is an abundant post-translational modification. The attachment of the GPI anchor is mediated by GPI-T (GPI transamidase), a multimeric, membrane-bound enzyme located in the ER (endoplasmic reticulum). Upon modification, GPI-anchored proteins enter the secretory pathway and ultimately become tethered to the cell surface by association with the plasma membrane and, in yeast, by covalent attachment to the outer glucan layer. This work demonstrates a novel in vivo assay for GPI-T. Saccharomyces cerevisiae INV (invertase), a soluble secreted protein, was converted into a substrate for GPI-T by appending the C-terminal 21 amino acid GPI-T signal sequence from the S. cerevisiae Yapsin 2 [Mkc7p (Y21)] on to the C-terminus of INV. Using a colorimetric assay and biochemical partitioning, extracellular presentation of GPI-anchored INV was shown. Two human GPI-T signal sequences were also tested and each showed diminished extracellular INV activity, consistent with lower levels of GPI anchoring and species specificity. Human/fungal chimaeric signal sequences identified a small region of five amino acids that was predominantly responsible for this species specificity.  相似文献   
92.

Objective

To determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship.

Methods

This prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay.

Results

All 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001].

Conclusions

Although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length.  相似文献   
93.
Marine sponges are diverse, abundant and provide a crucial coupling point between benthic and pelagic habitats due to their high filtration rates. They also harbour extensive microbial communities, with many microbial phylotypes found exclusively in sponge hosts and not in the seawater or surrounding environment, i.e. so‐called sponge‐specific clusters (SCs) or sponge‐ and coral‐specific clusters (SCCs). We employed DNA (16S rRNA gene) and RNA (16S rRNA)‐based amplicon pyrosequencing to investigate the effects of sublethal thermal stress on the bacterial biosphere of the Great Barrier Reef sponge Rhopaloeides odorabile. A total of 8381 operational taxonomic units (OTUs) (97% sequence similarity) were identified, affiliated with 32 bacterial phyla from seawater samples, 23 bacterial phyla from sponge DNA extracts and 18 bacterial phyla from sponge RNA extracts. Sublethal thermal stress (31°C) had no effect on the present and/or active portions of the R. odorabile bacterial community but a shift in the bacterial assemblage was observed in necrotic sponges. Over two‐thirds of DNA and RNA sequences could be assigned to previously defined SCs/SCCs in healthy sponges whereas only 12% of reads from necrotic sponges could be assigned to SCs/SCCs. A rapid decline in host health over a 1°C temperature increment suggests that sponges such as R. odorabile may be highly vulnerable to the effects of global climate change.  相似文献   
94.
Sleep spindles and K-complexes (KCs) define stage 2 NREM sleep (N2) in humans. We recently showed that KCs are isolated downstates characterized by widespread cortical silence. We demonstrate here that KCs can be quasi-synchronous across scalp EEG and across much of the cortex using electrocorticography (ECOG) and localized transcortical recordings (bipolar SEEG). We examine the mechanism of synchronous KC production by creating the first conductance based thalamocortical network model of N2 sleep to generate both spontaneous spindles and KCs. Spontaneous KCs are only observed when the model includes diffuse projections from restricted prefrontal areas to the thalamic reticular nucleus (RE), consistent with recent anatomical findings in rhesus monkeys. Modeled KCs begin with a spontaneous focal depolarization of the prefrontal neurons, followed by depolarization of the RE. Surprisingly, the RE depolarization leads to decreased firing due to disrupted spindling, which in turn is due to depolarization-induced inactivation of the low-threshold Ca2+ current (IT). Further, although the RE inhibits thalamocortical (TC) neurons, decreased RE firing causes decreased TC cell firing, again because of disrupted spindling. The resulting abrupt removal of excitatory input to cortical pyramidal neurons then leads to the downstate. Empirically, KCs may also be evoked by sensory stimuli while maintaining sleep. We reproduce this phenomenon in the model by depolarization of either the RE or the widely-projecting prefrontal neurons. Again, disruption of thalamic spindling plays a key role. Higher levels of RE stimulation also cause downstates, but by directly inhibiting the TC neurons. SEEG recordings from the thalamus and cortex in a single patient demonstrated the model prediction that thalamic spindling significantly decreases before KC onset. In conclusion, we show empirically that KCs can be widespread quasi-synchronous cortical downstates, and demonstrate with the first model of stage 2 NREM sleep a possible mechanism whereby this widespread synchrony may arise.  相似文献   
95.
To investigate the adaptation of plasma cortisol profiles to an abrupt phase advance of the rest-activity cycle, eight normal young subjects were submitted in a sleep laboratory to an 8-h advance shift of their sleep-wake and dark-light cycles. The shift was achieved by advancing bedtimes from 2300-0700 to 1500-2300. Blood samples were obtained at 20-min intervals for 68 consecutive hours. The shift resulted within 6-9 h in a 3- to 4-h advance of timings of the nadir of the cortisol profile and of the end of the quiescent period but had no immediate effect on the timing of cortisol acrophase. The quiescent period of cortisol secretion was shortened and fragmented. Thus a major advance shift achieved without enforcing sleep deprivation results in a rapid partial adaptation of the temporal profiles of cortisol but also in a marked disruption of the cortisol quiescent period. Sleep onset was consistently followed by a decrease in cortisol concentrations. Conversely, both sleep-wake and dark-light transitions were consistently associated with cortisol secretory pulses.  相似文献   
96.
In the geological record, fossil phosphatic stromatolites date back to the Great Oxidation Event in the Paleoproterozoic, but living phosphatic stromatolites have not been described previously. Here, we report on cyanobacterial stromatolites in a supratidal freshwater environment at Cape Recife, South African southern coast, precipitating Ca carbonate alternating with episodes of Ca phosphate deposition. In their structure and composition, the living stromatolites from Cape Recife closely resemble their fossilized analogues, showing phosphatic zonation, microbial casts, tunnel structures and phosphatic crusts of biogenic origin. The microbial communities appear to be also similar to those proposed to have formed fossil phosphatic stromatolites. Phosphatic domains in the material from Cape Recife are spatially and texturally associated with carbonate precipitates, but form distinct entities separated by sharp boundaries. Electron Probe Micro‐Analysis shows that Ca/P ratios and the overall chemical compositions of phosphatic precipitates are in the range of octacalcium phosphate, amorphous tricalcium phosphate and apatite. The coincidence in time of the emergence of phosphatic stromatolites in the fossil record with a major episode of atmospheric oxidation led to the assumption that at times of increased oxygen release the underlying increased biological production may have been linked to elevated phosphorus availability. The stromatolites at Cape Recife, however, form in an environment where ambient phosphorus concentrations do not exceed 0.28 μM, one to two orders of magnitude below the previously predicted minimum threshold of >5 μM for biogenic phosphate precipitation in paleo‐systems. Accordingly, we contest the previously proposed suitability of phosphatic stromatolites as a proxy for high ambient phosphate concentrations in supratidal to shallow ocean settings in earth history.  相似文献   
97.
With climate change leading to poleward range expansion of species, populations are exposed to new daylength regimes along latitudinal gradients. Daylength is a major factor affecting insect life cycles and activity patterns, so a range shift leading to new daylength regimes is likely to affect population dynamics and species interactions; however, the impact of daylength in isolation on ecological communities has not been studied so far. Here, we tested for the direct and indirect effects of two different daylengths on the dynamics of experimental multitrophic insect communities. We compared the community dynamics under “southern” summer conditions of 14.5‐hr daylight to “northern” summer conditions of 22‐hr daylight. We show that food web dynamics indeed respond to daylength with one aphid species (Acyrthosiphon pisum) reaching much lower population sizes at the northern daylength regime compared to under southern conditions. In contrast, in the same communities, another aphid species (Megoura viciae) reached higher population densities under northern conditions. This effect at the aphid level was driven by an indirect effect of daylength causing a change in competitive interaction strengths, with the different aphid species being more competitive at different daylength regimes. Additionally, increasing daylength also increased growth rates in M. viciae making it more competitive under summer long days. As such, the shift in daylength affected aphid population sizes by both direct and indirect effects, propagating through species interactions. However, contrary to expectations, parasitoids were not affected by daylength. Our results demonstrate that range expansion of whole communities due to climate change can indeed change interaction strengths between species within ecological communities with consequences for community dynamics. This study provides the first evidence of daylength affecting community dynamics, which could not be predicted from studying single species separately.  相似文献   
98.
One commonly studied behavioral syndrome is the correlation between aggression and boldness. Studies in song sparrows (M. melodia) have found greater aggression and boldness in urban populations and a correlation between aggression and boldness in rural populations, but not within urban populations. In previous studies, boldness was measured as flight initiation distance (FID), which may reflect habituation by urban birds to human presence. In this study, we measured boldness using playbacks of heterospecific alarm calls and investigated whether higher boldness is a general trait of urban birds and whether the same pattern of correlations between aggression and boldness would be seen. We conducted trials involving FID, alarm call playbacks and conspecific song playbacks on 25 birds from both an urban and a rural site. The results showed that urban birds were bolder, as measured by FID and response to alarm calls. Boldness and aggression were correlated in rural birds with each method of measuring boldness but were correlated in urban birds only when using alarm call playbacks. Our results suggest that a behavioral syndrome exists in both urban and rural populations but that urban birds are able to decrease their response to human disturbance.  相似文献   
99.
The sequence of the Moulin Quignon quarry yielded archaeological findings (faunal remains, artefacts) and some of them are well located in the stratigraphy thanks to Jacques Boucher de Perthes and colleagues. These remains are often used to attest the early age of the site and the human remains. Some bifaces have been found in close relationship to the human remains and, in particular, the mandible found in 1863. Thanks to the handwritten label put on the pieces and their deposit at the National Museum of Natural History (Paris), it is possible to study them again in relation with the sequence. The study concerns the rare faunal remains and the bifaces given, among others, by Boucher de Perthes to the Museum. The paleontological and technological analyses allow us replacing the lithic material among the north-western European data. The material is presented according to the historical context of his discovery.  相似文献   
100.
Johnson RM  Rath A  Melnyk RA  Deber CM 《Biochemistry》2006,45(28):8507-8515
Interactions between transmembrane helices are mediated by the concave Gly-xxx-Gly motif surface. Whether Gly residues per se are sufficient for selection of this motif has not been established. Here, we used the in vivo TOXCAT assay to measure the relative affinities of all 18 combinations of Gly, Ala, and Ser "small-xxx-small" mutations in glycophorin A (GpA) and bacteriophage M13 major coat protein (MCP) homodimers. Affinity values were compared with the accessibility to a methylene-sized probe of the total surface area of each helix monomer as a measure of solvation by membrane components. A strong inverse correlation was found between nonpolar-group lipid accessibility and dimer affinity (R = 0.75 for GpA, p = 0.013, and R = 0.81 for MCP, p = 0.004), suggesting that lipid as a poor membrane protein solvent, conceptually analogous to water in soluble protein folding, can contribute to dimer stability and help to define helix-helix interfaces.  相似文献   
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