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101.
Myeloid cells express the TNF family ligands BAFF/BLyS and APRIL, which exert their effects on B cells at different stages of differentiation via the receptors BAFFR, TACI (Transmembrane Activator and CAML-Interactor) and/or BCMA (B Cell Maturation Antigen). BAFF and APRIL are proteins expressed at the cell membrane, with both extracellular and intracellular domains. Therefore, receptor/ligand engagement may also result in signals in ligand-expressing cells via so-called “reverse signalling”. In order to understand how TACI-Fc (atacicept) technically may mediate immune stimulation instead of suppression, we investigated its potential to activate reverse signalling through BAFF and APRIL. BAFFR-Fc and TACI-Fc, but not Fn14-Fc, reproducibly stimulated the ERK and other signalling pathways in bone marrow-derived mouse macrophages. However, these effects were independent of BAFF or APRIL since the same activation profile was observed with BAFF- or APRIL-deficient cells. Instead, cell activation correlated with the presence of high molecular mass forms of BAFFR-Fc and TACI-Fc and was strongly impaired in macrophages deficient for Fc receptor gamma chain. Moreover, a TACI-Fc defective for Fc receptor binding elicited no detectable signal. Although these results do not formally rule out the existence of BAFF or APRIL reverse signalling (via pathways not tested in this study), they provide no evidence in support of reverse signalling and point to the importance of using appropriate specificity controls when working with Fc receptor-expressing myeloid cells.  相似文献   
102.
Various studies have shown that eicosapentaenoic acid (EPA) has beneficial effects on obesity and associated disorders. Apelin, the ligand of APJ receptor also exerts insulin-sensitizing effects especially by improving muscle metabolism. EPA has been shown to increase apelin production in adipose tissue but its effects in muscle have not been addressed. Thus, the effects of EPA supplementation (36 g/kg EPA) in high-fat diet (HFD) (45% fat, 20% protein, 35% carbohydrate) were studied in mice with focus on muscle lipid metabolism and apelin/APJ expression. Compared with HFD mice, HFD+EPA mice had significantly less weight gain, fat mass, lower blood glucose, insulinemia and hepatic steatosis after 10 weeks of diet. In addition, EPA prevented muscle metabolism alterations since intramuscular triglycerides were decreased and β-oxidation increased. In soleus muscles of HFD+EPA mice, apelin and APJ expression were significantly increased compared to HFD mice. However, plasma apelin concentrations in HFD and HFD+EPA mice were similar. EPA-induced apelin expression was confirmed in differentiated C2C12 myocytes but in this model, apelin secretion was also increased in response to EPA treatment. In conclusion, EPA supplementation in HFD prevents obesity and metabolic alterations in mice, especially in skeletal muscle. Since EPA increases apelin/APJ expression in muscle, apelin may act in a paracrine/autocrine manner to contribute to these benefical effects.  相似文献   
103.
Several species of Culicoides (Diptera: Ceratopogonidae) biting midges serve as biological vectors for the bluetongue virus (BTV) and the recently described Schmallenberg virus (SBV) in northern Europe. Since their recent emergence in this part of the continent, these diseases have caused considerable economic losses to the sheep and cattle industries. Much data is now available that describe the distribution, population dynamics, and feeding habits of these insects. However, little is known regarding the presence of Culicoides in unusual habitats such as peaty marshes, nor their potential vector capacity. This study evaluated Culicoides biting midges present in the bogs of a Belgian nature reserve compared to those residing at a nearby cattle farm. Culicoides were trapped in 2011 at four different sites (broadleaved and coniferous forested areas, open environments, and at a scientific station) located in the Hautes Fagnes Nature Reserve (Belgium). An additional light trap was operated on a nearby cattle farm. Very high numbers of biting midges were captured in the marshy area and most of them (70 to 95%) were Culicoides impunctatus, a potential vector of BTV and other pathogens. In addition, fewer numbers of C. obsoletus/C. scoticus species, C. chiopterus, and C. dewulfi were observed in the bogs compared to the farm. The wet environment and oligotrophic nature of the soil were probably responsible for these changes in the respective populations. A total of 297,808 Culicoides midges belonging to 27 species were identified during this study and 3 of these species (C. sphagnumensis, C. clintoni and C. comosioculatus) were described in Belgium for the first time.  相似文献   
104.
Length-weight relationship parameters were calculated for twelve mesopelagic fish species from the western Tropical Atlantic: Diretmus argenteus, Melamphaes polylepis, Bolinichthys distofax, Diaphus lucidus, Diaphus splendidus, Electrona risso, Hygophum taaningi, Taaningichthys bathyphilus, Melanolagus bericoides, Winteria telescopa, Diplophos taenia, Astronesthes similus. Data was collected off northeastern Brazil from April 9th to May 6th, 2017. Hauls were conducted during day and night at 47 stations by using a micronekton trawl (body mesh: 40 mm, cod-end mesh: 10 mm) from 10 to 1,113 m depth. The material was fixed in a 4% formalin solution for 1 month and then preserved in a 70% alcohol solution for proximally 6 months before processing for length (nearest 0.1 cm of standard length) and weight (nearest 0.01 g of total weight). A new maximum standard length for Winteria telescopa is also provided.  相似文献   
105.

Background

Albumin constitutes the most abundant circulating antioxidant and prevents oxidative damages. However, in diabetes, this plasmatic protein is exposed to several oxidative modifications, which impact on albumin antioxidant properties.

Methods

Most studies dealing on albumin antioxidant activities were conducted on in vitro modified protein. Here we tried to decipher whether reduced antioxidant properties of albumin could be evidenced in vivo. For this, we compared the antioxidant properties of albumin purified from diabetic patients to in vitro models of glycated albumin.

Results

Both in vivo and in vitro glycated albumins displayed impaired antioxidant activities in the free radical-induced hemolysis test. Surprisingly, the ORAC method (Oxygen Radical Antioxidant Capacity) showed an enhanced antioxidant activity for glycated albumin. Faced with this paradox, we investigated antioxidant and anti-inflammatory activities of our albumin preparations on cultured cells (macrophages and adipocytes). Reduced cellular metabolism and enhanced intracellular oxidative stress were measured in cells treated with albumin from diabetics. NF-kB –mediated gene induction was higher in macrophages treated with both type of glycated albumin compared with cells treated with native albumin. Anti inflammatory activity of native albumin is significantly impaired after in vitro glycation and albumin purified from diabetics significantly enhanced IL6 secretion by adipocytes. Expression of receptor for advanced glycation products is significantly enhanced in glycated albumin-treated cells.

Conclusions and general significance

Our results bring new evidences on the deleterious impairments of albumin important functions after glycation and emphasize the importance of in vivo model of glycation in studies relied to diabetes pathology.  相似文献   
106.
The effects of cavity‐creating mutations on the structural flexibility, local and global stability, and dynamics of the folded state of staphylococcal nuclease (SNase) were examined with NMR spectroscopy, MD simulations, H/D exchange, and pressure perturbation. Effects on global thermodynamic stability correlated well with the number of heavy atoms in the vicinity of the mutated residue. Variants with substitutions in the C‐terminal domain and the interface between α and β subdomains showed large amide chemical shift variations relative to the parent protein, moderate, widespread, and compensatory perturbations of the H/D protection factors and increased local dynamics on a nanosecond time scale. The pressure sensitivity of the folded states of these variants was similar to that of the parent protein. Such observations point to the capacity of the folded proteins to adjust to packing defects in these regions. In contrast, cavity creation in the β‐barrel subdomain led to minimal perturbation of the structure of the folded state, However, significant pressure dependence of the native state amide resonances, along with strong effects on native state H/D exchange are consistent with increased probability of population of excited state(s) for these variants. Such contrasted responses to the creation of cavities could not be anticipated from global thermodynamic stability or crystal structures; they depend on the local structural and energetic context of the substitutions. © 2012 Wiley Periodicals, Inc.  相似文献   
107.
108.
The chicken major histocompatibility complex (MHC) is located on the microchromosome 16 and is described as the most variable region in the genome. The genes of the MHC play a central role in the immune system. Particularly, genes encoding proteins involved in the antigen presentation to T cells. Therefore, describing the genetic polymorphism of this region is crucial in understanding host–pathogen interactions. The tandem repeat LEI0258 is located within the core area of the B region of the chicken MHC (MHC-B region) and its genotypes correlate with serology. This marker was used to provide a picture of the worldwide diversity of the chicken MHC-B region and to categorize chicken MHC haplotypes. More than 1,600 animals from 80 different populations or lines of chickens from Africa, Asia, and Europe, including wild fowl species, were genotyped at the LEI0258 locus. Fifty novel alleles were described after sequencing. The resulting 79 alleles were classified into 12 clusters, based on the SNPs and indels found within the sequences flanking the repeats. Furthermore, hypotheses were formulated on the evolutionary dynamics of the region. This study constitutes the largest variability report for the chicken MHC and establishes a framework for future diversity or association studies.  相似文献   
109.
The detection of molecular signatures of selection is one of the major concerns of modern population genetics. A widely used strategy in this context is to compare samples from several populations and to look for genomic regions with outstanding genetic differentiation between these populations. Genetic differentiation is generally based on allele frequency differences between populations, which are measured by FST or related statistics. Here we introduce a new statistic, denoted hapFLK, which focuses instead on the differences of haplotype frequencies between populations. In contrast to most existing statistics, hapFLK accounts for the hierarchical structure of the sampled populations. Using computer simulations, we show that each of these two features—the use of haplotype information and of the hierarchical structure of populations—significantly improves the detection power of selected loci and that combining them in the hapFLK statistic provides even greater power. We also show that hapFLK is robust with respect to bottlenecks and migration and improves over existing approaches in many situations. Finally, we apply hapFLK to a set of six sheep breeds from Northern Europe and identify seven regions under selection, which include already reported regions but also several new ones. We propose a method to help identifying the population(s) under selection in a detected region, which reveals that in many of these regions selection most likely occurred in more than one population. Furthermore, several of the detected regions correspond to incomplete sweeps, where the favorable haplotype is only at intermediate frequency in the population(s) under selection.  相似文献   
110.

Objective

We assessed the EDs’ characteristics associated with the offer and acceptance rates of a nontargeted HIV rapid-test screening in 29 Emergency Departments (EDs) in the metropolitan Paris region (11.7 million inhabitants), where half of France’s new HIV cases are diagnosed annually.

Methods

EDs nurses offered testing to all patients 18–64-year-old, able to provide consent, either with or without supplemental staff (hybrid staff model or indigenous staff model). The EDS’ characteristics collected included structural characteristics (location, type, size), daily workload (patients’ number and severity, length of stay in hours), staff’s participation (training, support to the intervention, leadership), type of week day (weekends vs weekdays) and time (in days). Associations between these variables and the staff model, the offer and acceptance rates were studied using multilevel modeling.

Results

Indigenous staff model was more frequent in EDs with a lower daily patient flow and a higher staff support score to the intervention. In indigenous-model EDs, the offer rate was associated with the patient flow (OR = 0.838, 95% CI = 0.773–0.908), was lower during weekends (OR = 0.623, 95% CI = 0.581–0.667) and decreased over time (OR = 0.978, 95% CI = 0.975–0.981). Similar results were found in hybrid-model EDs. Acceptance was poorly associated with EDs characteristics in indigenous-model EDs while in hybrid-model EDs it was lower during weekends (OR = 0.713, 95% CI = 0.623–0.816) and increased after the first positive test (OR = 1.526, 95% CI = 1.142–2.038).The EDs’ characteristics explained respectively 38.5% and 15% of the total variance in the offer rate across indigenous model-EDs and hybrid model-EDs vs 12% and 1% for the acceptance rate.

Conclusion

Our findings suggest the need for taking into account EDs’ characteristics while considering the implementation of an ED-based HIV screening program. Strategies allowing the optimization of human resources’ utilization such as HIV targeted screening in the EDs might be privileged.  相似文献   
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