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排序方式: 共有508条查询结果,搜索用时 62 毫秒
61.
Kirsty J. MacLeod Kevin D. Kohl Brian K. Trevelline Tracy Langkilde 《Molecular ecology》2022,31(1):185-196
The vertebrate gut microbiota (bacterial, archaeal and fungal communities of the gastrointestinal tract) can have profound effects on the physiological processes of their hosts. Although relatively stable, changes in microbiome structure and composition occur due to changes in the environment, including exposure to stressors and associated increases in glucocorticoid hormones. Although a growing number of studies have linked stressor exposure to microbiome changes, few studies have experimentally explored the specific influence of glucocorticoids on the microbiome in wild animals, or across ecologically important processes (e.g., reproductive stages). Here we tested the response of the gut microbiota of adult female Sceloporus undulatus across gestation to ecologically relevant elevations of a stress-relevant glucocorticoid hormone (CORT) in order to determine (i) how experimentally elevated CORT influenced microbiome characteristics, and (ii) whether this relationship was dependent on reproductive context (i.e., whether females were gravid or not, and, in those that were gravid, gestational stage). We show that the effects of CORT on gut microbiota are complex and depend on both gestational state and stage. CORT treatment altered microbial community membership and resulted in an increase in microbiome diversity in late-gestation females, and microbial community membership varied according to treatment. In nongravid females, CORT treatment decreased interindividual variation in microbial communities, but this effect was not observed in late-gestation females. Our results highlight the need for a more holistic understanding of the downstream physiological effects of glucocorticoids, as well as the importance of context (here, gestational state and stage) in interpreting stress effects in ecology. 相似文献
62.
C. ALBUQUERQUE F. MORINHA J. MAGALHÃES J. REQUICHA I. DIAS H. GUEDES-PINTO E. BASTOS C. VIEGAS 《Journal of genetics》2015,94(4):651-659
Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria. In humans, polymorphisms in the IL1A and IL1B genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case–control study was conducted in which a molecular analysis of dog IL1A and IL1B genes was performed. Of the eight genetic variants identified, seven in IL1A gene and one in IL1B gene, IL1A/1_g.388A >C and IL1A/1_g.521T >A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03–0.76), P= 0.022; 5.76 (1.03–32.1), P= 0.046, respectively). It suggests that in the studied population the IL1A/1_g.388C allele is associated with a decreased PD risk, whereas the IL1A/1_g.521A allele can confer an increased risk. Additionally, the IL1A/2_g.515G >T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that IL1 genetic variants may be important in PD susceptibility in canines. 相似文献
63.
Stieler JT Bullmann T Kohl F Tøien Ø Brückner MK Härtig W Barnes BM Arendt T 《PloS one》2011,6(1):e14530
Abnormal phosphorylation and aggregation of tau protein are hallmarks of a variety of neurological disorders, including Alzheimer's disease (AD). Increased tau phosphorylation is assumed to represent an early event in pathogenesis and a pivotal aspect for aggregation and formation of neurofibrillary tangles. However, the regulation of tau phosphorylation in vivo and the causes for its increased stage of phosphorylation in AD are still not well understood, a fact that is primarily based on the lack of adequate animal models. Recently we described the reversible formation of highly phosphorylated tau protein in hibernating European ground squirrels. Hence, mammalian hibernation represents a model system very well suited to study molecular mechanisms of both tau phosphorylation and dephosphorylation under in vivo physiological conditions. Here, we analysed the extent and kinetics of hibernation-state dependent tau phosphorylation in various brain regions of three species of hibernating mammals: arctic ground squirrels, Syrian hamsters and black bears. Overall, tau protein was highly phosphorylated in torpor states and phosphorylation levels decreased after arousal in all species. Differences between brain regions, hibernation-states and phosphosites were observed with respect to degree and kinetics of tau phosphorylation. Furthermore, we tested the phosphate net turnover of tau protein to analyse potential alterations in kinase and/or phosphatase activities during hibernation. Our results demonstrate that the hibernation-state dependent phosphorylation of tau protein is specifically regulated but involves, in addition, passive, temperature driven regulatory mechanisms. By determining the activity-state profile for key enzymes of tau phosphorylation we could identify kinases potentially involved in the differentially regulated, reversible tau phosphorylation that occurs during hibernation. We show that in black bears hibernation is associated with conformational changes of highly phosphorylated tau protein that are typically related to neuropathological alterations. The particular hibernation characteristics of black bears with a continuous torpor period and an only slightly decreased body temperature, therefore, potentially reflects the limitations of this adaptive reaction pattern and, thus, might indicate a transitional state of a physiological process. 相似文献
64.
K(V)10.1 is a mammalian brain voltage-gated potassium channel whose ectopic expression outside of the brain has been proven relevant for tumor biology. Promotion of cancer cell proliferation by K(V)10.1 depends largely on ion flow, but some oncogenic properties remain in the absence of ion permeation. Additionally, K(V)10.1 surface populations are small compared to large intracellular pools. Control of protein turnover within cells is key to both cellular plasticity and homeostasis, and therefore we set out to analyze how endocytic trafficking participates in controlling K(V)10.1 intracellular distribution and life cycle. To follow plasma membrane K(V)10.1 selectively, we generated a modified channel of displaying an extracellular affinity tag for surface labeling by α-bungarotoxin. This modification only minimally affected K(V)10.1 electrophysiological properties. Using a combination of microscopy and biochemistry techniques, we show that K(V)10.1 is constitutively internalized involving at least two distinct pathways of endocytosis and mainly sorted to lysosomes. This occurs at a relatively fast rate. Simultaneously, recycling seems to contribute to maintain basal K(V)10.1 surface levels. Brief K(V)10.1 surface half-life and rapid lysosomal targeting is a relevant factor to be taken into account for potential drug delivery and targeting strategies directed against K(V)10.1 on tumor cells. 相似文献
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68.
Kohl A Amstutz P Parizek P Binz HK Briand C Capitani G Forrer P Plückthun A Grütter MG 《Structure (London, England : 1993)》2005,13(8):1131-1141
Aminoglycoside phosphotransferase (3')-IIIa (APH) is a bacterial kinase that confers antibiotic resistance to many pathogenic bacteria and shares structural homology with eukaryotic protein kinases. We report here the crystal structure of APH, trapped in an inactive conformation by a tailor-made inhibitory ankyrin repeat (AR) protein, at 2.15 A resolution. The inhibitor was selected from a combinatorial library of designed AR proteins. The AR protein binds the C-terminal lobe of APH and thereby stabilizes three alpha helices, which are necessary for substrate binding, in a significantly displaced conformation. BIAcore analysis and kinetic enzyme inhibition experiments are consistent with the proposed allosteric inhibition mechanism. In contrast to most small-molecule kinase inhibitors, the AR proteins are not restricted to active site binding, allowing for higher specificity. Inactive conformations of pharmaceutically relevant enzymes, as can be elucidated with the approach presented here, represent powerful starting points for rational drug design. 相似文献
69.
The infection pattern of Kroeyerina elongata (Kroyeriidae, Copepoda) in the olfactory sacs of the blue shark, Prionace glauca, was investigated using 4,722 copepods from 54 olfactory sacs. Copepod prevalence and mean intensity of infection per olfactory sac were 94.0 and 91.1%, respectively, and the most intensely infected olfactory sac and shark hosted 218 and 409 copepods, respectively. There were significant linear relationships between the number of female and total copepods per left olfactory sac and shark fork length as well as between the numbers of female, male, and total copepods per shark and mean olfactory sac width and cumulative olfactory sac width. Female copepods typically outnumbered males within olfactory sacs (mean intensity = 65.7 and 26.3, respectively), and no statistical differences were detected between the numbers of copepods inhabiting the left and right olfactory sacs. Copepods were not evenly distributed within olfactory sacs. Typically, female copepods occupied olfactory chambers located centrally along the length of the olfactory sac, while males infected lateral olfactory chambers nearest the naris. The orientation of most copepods (84.6%) suggested positive rheotaxis relative to the path of water through the olfactory sac. Within olfactory chambers, most mature females (68.2%) infected the first third of the peripheral excurrent channel and the adjacent fringe of olfactory lamellae, while most males (91.7%) infected the olfactory lamellae, and the 4 larval females collected were attached within the lamellar field and grasped by males. Based on the observed infection patterns and the pattern of water flow throughout the olfactory sac, a hypothesis regarding the life cycle of K. elongata is advanced wherein infective copepodids are swept into the olfactory sac from the surrounding sea and initially colonize the olfactory lamellae. Copepodids feed and mature among the olfactory lamellae, and adult males search for mates and copulate with young females among the olfactory lamellae. Inseminated females move to the peripheral excurrent channels to mature and produce ovisacs. Hatching ovisacs release free-swimming nauplii into the excurrent water flow to be swept into the milieu, where they can molt into infective copepodids that may infect new hosts. 相似文献
70.
Krüger M Kohl T Linke WA 《American journal of physiology. Heart and circulatory physiology》2006,291(2):H496-H506
The giant protein titin, a major contributor to myocardial mechanics, is expressed in two main cardiac isoforms: stiff N2B (3.0 MDa) and more compliant N2BA (>3.2 MDa). Fetal hearts of mice, rats, and pigs express a unique N2BA isoform ( approximately 3.7 MDa) but no N2B. Around birth the fetal N2BA titin is replaced by smaller-size N2BA isoforms and N2B, which predominates in adult hearts, stiffening their sarcomeres. Here we show that perinatal titin-isoform switching and corresponding passive stiffness (STp) changes do not occur in the hearts of guinea pig and sheep. In these species the shift toward "adult" proportions of N2B isoform is almost completed by midgestation. The relative contributions of titin and collagen to STp were estimated in force measurements on skinned cardiac muscle strips by selective titin proteolysis, leaving the collagen matrix unaffected. Titin-based STp contributed between 42% and 58% to total STp in late-fetal and adult sheep/guinea pigs and adult rats. However, only approximately 20% of total STp was titin based in late-fetal rat. Titin-borne passive tension and the proportion of titin-based STp generally scaled with the N2B isoform percentage. The titin isoform transitions were correlated to a switch in troponin-I (TnI) isoform expression. In rats, fetal slow skeletal TnI (ssTnI) was replaced by adult carciac TnI (cTnI) shortly after birth, thereby reducing the Ca2+ sensitivity of force development. In contrast, guinea pig and sheep coexpressed ssTnI and cTnI in fetal hearts, and skinned fibers from guinea pig showed almost no perinatal shift in Ca2+ sensitivity. We conclude that TnI-isoform and titin-isoform switching and corresponding functional changes during heart development are not initiated by birth but are genetically programmed, species-specific regulated events. 相似文献