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21.
Arbuscular mycorrhizal fungi (AMF) represent an ecologically relevant and evolutionarily intriguing group of land plant symbionts, which produce multinucleated spores and hyphae that are currently thought to have propagated clonally for over 500 million years. This long-term absence of sex in AMF is a puzzling evolutionary feature that has sparked scientific interest for some time, but a provoking explanation for their successful evolutionary history in the absence of an obvious sexual cycle is that these organisms may have cryptic sex, or a parasexual life cycle, allowing them to recombine alleles and compensate for deleterious mutations. Interestingly, the recent acquisition of large sequence data from many AMF species can finally allow this hypothesis to be tested more extensively. In this perspective, we highlight emerging evidence based on sequence data for the potential of AMF to have sexual reproduction, and propose a number of routes that could be taken to further explore the presence (or absence thereof) of sex in this poorly studied, yet highly relevant, fungal group.  相似文献   
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Observation of short-term temporal variation in bacterial and viral communities is important for understanding patterns of aquatic microbial diversity. We collected surface seawater once daily for 38 consecutive days with seven more samples interspersed over 40 more days at one location ∼2 km from Santa Catalina Island, California. Bacterial communities were analyzed by automated ribosomal intergenic spacer analysis (ARISA) and viral communities were analyzed by terminal restriction fragment length polymorphism (TRFLP) of the conserved T4-like myoviral gene encoding the major capsid protein (g23). Common bacterial and viral taxa were consistently dominant, and relatively few displayed dramatic increases/decreases or ‘boom/bust'' patterns that might be expected from dynamic predator-prey interactions. Association network analysis showed most significant covariations (associations) occurred among bacterial taxa or among viral taxa and there were several modular (highly-interconnected) associations (P⩽0.005). Associations observed between bacteria and viruses (P⩽0.005) occurred with a median time lag of 2 days. Regression of all pairwise Bray-Curtis similarities between samples indicated a rate of bacterial community change that slows from 2.1%–0.18% per day over a week to 2 months; the rate stays around 0.4% per day for viruses. Our interpretation is that, over the scale of days, individual bacterial and viral OTUs can be dynamic and patterned; resulting in statistical associations regarded as potential ecological interactions. However, over the scale of weeks, average bacterial community variation is slower, suggesting that there is strong community-level ecological resilience, that is, a tendency to converge towards a ‘mean'' microbial community set by longer-term controlling factors.  相似文献   
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Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.  相似文献   
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Kidney transplantation is the treatment of choice for patients suffering from end-stage renal disease. It offers better life expectancy and higher quality of life when compared to dialysis. Although the last few decades have seen major improvements in patient outcomes following kidney transplantation, the increasing shortage of available organs represents a severe problem worldwide. To expand the donor pool, marginal kidney grafts recovered from extended criteria donors (ECD) or donated after circulatory death (DCD) are now accepted for transplantation. To further improve the postoperative outcome of these marginal grafts, research must focus on new therapeutic approaches such as alternative preservation techniques, immunomodulation, gene transfer, and stem cell administration.Experimental studies in animal models are the final step before newly developed techniques can be translated into clinical practice. Porcine kidney transplantation is an excellent model of human transplantation and allows investigation of novel approaches. The major advantage of the porcine model is its anatomical and physiological similarity to the human body, which facilitates the rapid translation of new findings to clinical trials. This article offers a surgical step-by-step protocol for an autotransplantation model and highlights key factors to ensure experimental success. Adequate pre- and postoperative housing, attentive anesthesia, and consistent surgical techniques result in favorable postoperative outcomes. Resection of the contralateral native kidney provides the opportunity to assess post-transplant graft function. The placement of venous and urinary catheters and the use of metabolic cages allow further detailed evaluation. For long-term follow-up studies and investigation of alternative graft preservation techniques, autotransplantation models are superior to allotransplantation models, as they avoid the confounding bias posed by rejection and immunosuppressive medication.  相似文献   
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Conceptual design and modification of urea moiety in chemotype PF-3845/04457845, the bench marking irreversible inhibitor of fatty acid amide hydrolase (FAAH), led to discovery of a novel nicotinamide-based lead 12a having reversible mechanism of action. Focused SAR around the pyridine heterocycle (Ar) in 12a (Tables 1 and 2) resulted into four shortlisted compounds, (?)-12a, (?)-12i, (?)-12lm. The required (?)-enantiomers were obtained via diastereomeric resolution of a novel chiral dissymmetric intermediate 15. Based on comparative profile of FAAH potency, metabolic stability in liver microsome, liability of inhibiting major hCYP450 isoforms, rat PK, and brain penetration ability, two SAR optimized compounds, (?)-12l and (?)-12m, were selected for efficacy study in rat model of chemotherapy-induced peripheral neuropathy (CIPN). Both the compounds exhibited dose related antihyperalgesic effects, when treated with 3–30?mg/kg po for 7?days. The effects at 30?mg/kg are comparable to that of PF-04457845 (10?mg/kg) and Tramadol (40?mg/kg).  相似文献   
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GCC88 is a golgin coiled‐coil protein at the trans‐Golgi (TGN) that functions as a tethering factor for the endosome‐derived retrograde transport vesicles. Here, we demonstrate that GCC88 is required for the endosome‐to‐TGN retrograde transport of the cation‐independent mannose 6‐phosphate receptor (CI‐M6PR). The knockout of GCC88 perturbs the retrieval of CI‐M6PR and decreases its cellular level at the steady state, which causes the improper processing of newly synthesized cathepsin‐D, a lysosomal hydrolase dependent on CI‐M6PR for its delivery to lysosomes. At the whole cell level, the knockout of GCC88 reduces the lysosomal proteolytic capacity but does not impair of the efficiency of autophagy within these cells.  相似文献   
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Mutualisms are important ecological interactions that underpin much of the world's biodiversity. Predation risk has been shown to regulate mutualism dynamics in species‐specific case studies; however, we lack studies which investigate whether predation can also explain broader patterns of mutualism evolution. We report that fish‐anemone mutualisms have evolved on at least 55 occasions across 16 fish families over the past 60 million years and that adult body size is associated with the ontogenetic stage of anemone mutualisms: larger‐bodied species partner with anemones as juveniles, while smaller‐bodied species partner with anemones throughout their lives. Field and laboratory studies show that predators target smaller prey, that smaller fishes associate more with anemones, and that these relationships confer protection to small fishes. Our results indicate that predation is likely driving the recurrent convergent evolution of fish‐anemone mutualisms and suggest that similar ecological processes may have selected convergence in interspecies interactions in other animal clades.  相似文献   
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