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91.
Autophagy is a key degradative pathway coordinated by external cues, including starvation, oxidative stress, or pathogen detection. Rare are the molecules known to contribute mechanistically to the regulation of autophagy and expressed specifically in particular environmental contexts or in distinct cell types. Here, we unravel the role of RUN and FYVE domain–containing protein 4 (RUFY4) as a positive molecular regulator of macroautophagy in primary dendritic cells (DCs). We show that exposure to interleukin-4 (IL-4) during DC differentiation enhances autophagy flux through mTORC1 regulation and RUFY4 induction, which in turn actively promote LC3 degradation, Syntaxin 17–positive autophagosome formation, and lysosome tethering. Enhanced autophagy boosts endogenous antigen presentation by MHC II and allows host control of Brucella abortus replication in IL-4–treated DCs and in RUFY4-expressing cells. RUFY4 is therefore the first molecule characterized to date that promotes autophagy and influences endosome dynamics in a subset of immune cells.  相似文献   
92.
A thrombin-like enzyme from Bothrops leucurus venom, named leucurobin (leuc), was purified by gel filtration, affinity and ion exchange chromatographies. Physicochemical studies indicated that the purified enzyme is a 35 kDa monomeric glycoprotein on SDS-PAGE under reducing conditions, which decreased to 29 kDa after deglycosylation with N-glycosidase F (PNGase F). The amino acid sequence of leuc was determined by automated sequencing of the intact native protein and peptides produced by digestion of the S-pyridyl-ethylated protein with trypsin. The protein sequence exhibits significant similarities with other serine proteases reported from snake venoms, and contains two potential sites of N-linked glycosylation. The proteinase split off fibrinopeptide A (FPA) rapidly from human fibrinogen; however, only negligible traces of fibrinopeptide B (FPB) were observed. In addition, the enzyme released the N-terminal peptide (Mr=4572) containing the first 42 residues from the Bbeta-chain. Leuc could neither activate factor XIII nor release kinins from heat-treated bovine plasma. Its specific clotting activity was equivalent to 198 NIH thrombin U/mg on human fibrinogen. Kinetic properties of leuc were determined using representative chromogenic substrates. The enzyme evoked the gyroxin syndrome when injected into the tail veins of mice at levels of 0.143 microg/g mouse. The inhibitory effects of PMSF and benzamidine on the amidolytic activity suggest that leuc is a serine proteinase, and inhibition by beta-mercaptoethanol revealed the important role of the disulfide bonds in the stabilization of the native structure. Antibothropic serum, SBTI and EDTA had little or no effect on its amidolytic activity. However, the clotting effect of the enzyme was strongly inhibited by antibothropic serum. A Dixon plot showed that the hydrolysis of Bz-L-Arg-pNA by leuc was competitively inhibited by benzamidine (Ki=1.61+/-0.25 mM).  相似文献   
93.
    
Transmissible spongiform encephalopathies are neurodegenerative diseases caused by prions in mammals. An aberrantly folded protein (PrPSc) is the main component of these proteinaceous infectious particles. Prions exhibit strong resistance to protease digestion, which is typically exploited for biochemical discrimination from its native cellular form (PrPC). This classical feature has been partially challenged by the isolation of sizeable amounts of protease-sensitive PrPSc isoforms that self-propagate in vivo. Here, we report that the degree of PrPSc protease resistance is highly dependent on the concentration of salt in the solution. Similar changes were observed in PrPSc obtained from different strains and species. Strikingly, the effect of salt is reversible and is associated with changes on the size of PrPSc particles, but surprisingly, the more protease-sensitive species consists of a larger size. These findings shed light on the mechanistic aspects of prion proteolysis and should be considered when assessing samples of biomedical relevance.  相似文献   
94.
    
We reconstructed the genetic patterns and identified the main genetic breaks of several taxa across California and Baja California coast. Additionally, we evaluated the contribution of different variables to the level of structure.  相似文献   
95.
96.
    
Size at maturity in ectotherms commonly declines with warming. This near‐universal phenomenon, formalised as the temperature–size rule, has been observed in over 80% of tested species, from bacteria to fish. The proximate cause has been attributed to the greater temperature dependence of development rate than growth rate, causing individuals to develop earlier but mature smaller in the warm. However, few studies have examined the ontogenetic progression of the temperature–size response at high resolution. Using marine planktonic copepods, we experimentally determined the progression of the temperature–size response over ontogeny. Temperature–size responses were not generated gradually from egg to adult, contrary to the predictions of a naïve model in which development rate was assumed to be more temperature‐dependent than growth rate, and the difference in the temperature dependence of these two rates remained constant over ontogeny. Instead, the ontogenetic progression of the temperature–size response in experimental animals was highly episodic, indicating rapid changes in the extent to which growth and development rates are thermally decoupled. The strongest temperature–size responses occurred temporally mid‐way through ontogeny, corresponding with the point at which individuals reached between ~5 and 25% of their adult mass. Using the copepod Oithona nana, we show that the temperature‐dependence of growth rate varied substantially throughout ontogeny, whereas the temperature dependence of development rate remained constant. The temperature‐dependence of growth rate even exceeded that of development rate in some life stages, leading to a weakening of the temperature–size response. Our analyses of arthropod temperature–size responses from the literature, including crustaceans and insects, support these conclusions more broadly. Overall, our findings provide a better understanding of how the temperature–size rule is produced over ontogeny. Whereas we find support for the generality of developmental rate isomorphy in arthropods (shared temperature dependence of development rate across life stages), this concept appears not to apply to growth rates.  相似文献   
97.
    
The introduction of Iberian cattle in the Americas after Columbus’ arrival imposed high selection pressures on a limited number of animals over a brief period of time. Knowledge of the genomic regions selected during this process may help in enhancing climatic resilience and sustainable animal production. We first determined taurine and indicine contributions to the genomic structure of modern Creole cattle. Second, we inferred their demographic history using approximate Bayesian computation (ABC), linkage disequilibrium (LD) and Ne Slope (NeS) analysis. Third, we performed whole genome scans for selection signatures based on cross‐population extended haplotype homozygosity (XP‐EHH) and population differentiation (FST) to disentangle the genetic mechanisms involved in adaptation and phenotypic change by a rapid and major environmental transition. To tackle these questions, we combined SNP array data (~54,000 SNPs) in Creole breeds with their modern putative Iberian ancestors. Reconstruction of the population history of Creoles from the end of the 15th century indicated a major demographic expansion until the introduction of zebu and commercial breeds into the Americas ~180 years ago, coinciding with a drastic Ne contraction. NeS analysis provided insights into short‐term complexity in population change and depicted a decrease/expansion episode at the end of the ABC‐inferred expansion, as well as several additional fluctuations in Ne with the attainment of the current small Ne only towards the end of the 20th century. Selection signatures for tropical adaptation pinpointed the thermoregulatory slick hair coat region, identifying a new candidate gene (GDNF), as well as novel candidate regions involved in immune function, behavioural processes, iron metabolism and adaptation to new feeding conditions. The outcomes from this study will help in future‐proofing farm animal genetic resources (FAnGR) by providing molecular tools that allow selection for improved cattle performance, resilience and welfare under climate change.  相似文献   
98.
    
Plyometric jump training (PJT) can be used for improving balance through bilateral and unilateral jump-landing drills. Since the increased number of articles testing the effects of PJT on dynamic and static balance, it is relevant to summarize the evidence and determine the effects across different original articles. This systematic review with meta-analysis was conducted to assess the effects of PJT programs on dynamic and static balance in soccer players. The data sources utilized were Cochrane, Medline (PubMed), SPORTDiscus, and Web of Science. (i) Soccer players of any age or sex without injury, illness, or other clinical conditions; (ii) PJT-based programs restricted to a minimum of three weeks (duration); (iii) passive or active control groups; (iv) pre-post interventions values of dynamic and/or static balance; (v) randomized-controlled trials; and (vi) peerreviewed original full-text studies written in English, Portuguese, and/or Spanish. The database search initially identified 803 titles. From those, eight articles were eligible for the systematic review and meta-analysis. The results showed no significant differences between PJT and active controls in dynamic anterior, postero-medial, or postero-lateral balance for both left and right legs (p > 0.05). Additionally, no significant differences were found between PJT and active controls in terms of static balance (p = 0.495). The current evidence suggests that PJT has no significant advantage over active control groups in terms of dynamic or static balance.  相似文献   
99.
Cancer cachexia is a syndrome characterised by a marked weight loss, anorexia, asthenia and anaemia. In fact, many patients who die with advanced cancer suffer from cancer cachexia. The cachectic state is invariably associated with the presence and growth of the tumour and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumour and the host leads to an accelerated starvation state which promotes severe metabolic disturbances in the host, including hypermetabolism which leads to an increased energetic inefficiency. Although, the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. The main aim of the present review is to summarise and evaluate the different catabolic mediators (both humoural and tumoural) involved in cancer cachexia since they may represent targets for future promising clinical investigations.  相似文献   
100.
We explore the dynamic properties of multiple-beam optical traps to manipulate arrays of microstructures for biosensor applications. Multiple optical traps are generated by a virtually loss-less transformation of input phase patterns into high-intensity trapping-beams. A direct image projection of the phase patterns enables an adjustable number of optical traps in addition to instantaneous control of the position, size, shape and intensity of each trapping-beam. We present experimental results showing various colloidal formations through dynamic optical manipulation of polystyrene microspheres and yeast cells in aqueous media. The experimental configurations are geared towards the use of multiple-beam optical traps for biosensor applications.  相似文献   
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