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1.
Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection.  相似文献   
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Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration.  相似文献   
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Silver nanoparticles (AgNPs) enter estuaries via wastewater treatment effluents, where they can inhibit microorganisms, because of their antimicrobial properties. Ammonia‐oxidising bacteria (AOB) and archaea (AOA) are involved in the first step of nitrification and are important to ecosystem function, especially where effluent discharge results in high nitrogen inputs. Here, we investigated the effect of a pulse addition of AgNPs on AOB and AOA ammonia monooxygenase (amoA) gene abundances and benthic nitrification potential rates (NPR) in low‐salinity and mesohaline estuarine sediments. Whilst exposure to 0.5 mg L?1 AgNPs had no significant effect on amoA gene abundances or NPR, 50 mg L?1 AgNPs significantly decreased AOB amoA gene abundance (up to 76% over 14 days), and significantly decreased NPR by 20‐fold in low‐salinity sediments and by twofold in mesohaline sediments, after one day. AgNP behaviour differed between sites, whereby greater aggregation occurred in mesohaline waters (possibly due to higher salinity), which may have reduced toxicity. In conclusion, AgNPs have the potential to reduce ammonia oxidation in estuarine sediments, particularly where AgNPs accumulate over time and reach high concentrations. This could lead to long‐term risks to nitrification, especially in polyhaline estuaries where ammonia‐oxidation is largely driven by AOB.  相似文献   
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Earlier work showed that the biodegradation of a commercial linear monoalkyldiphenyletherdisulfonate surfactant as a carbon source for microbial growth leads to the quantitative formation of corresponding disulfodiphenylether carboxylates (DSDPECs), which were not degraded. α-Proteobacterium strain DS-1 (DSM 13023) catalyzes these reactions. These DSDPECs have now been characterized by high-pressure liquid chromatography coupled via an electrospray interface to a mass spectrometer. DSDPECs were a complex mixture of compounds which indicated catabolism via ω-oxygenation and β-oxidation. DSDPECs were subject to quantitative desulfonation in bacterial cultures in which they served as sole sulfur sources for bacterial growth. On average, one sulfonate group per DSDPEC species was removed, and the organism responsible for this desulfonation was isolated and identified as Rhodococcus opacus ISO-5. The products were largely monosulfodiphenylether carboxylate-phenols (MSDPEC-phenols). MSDPEC-phenols were subject to extensive dissimilation by bacteria from activated sludge.  相似文献   
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The growth of Listeria monocytogenes WSLC 1364, originating from a cheese-borne outbreak, was examined in the presence and in the absence of a pediocin AcH-producing Lactobacillus plantarum strain on red smear cheese. Nearly complete inhibition was observed at 102 CFU of L. monocytogenes per ml of salt brine solution, while contamination with Listeria mutants resistant to pediocin resulted in high cell counts of the pathogen on the cheese surface. The inhibition was due to pediocin AcH added together with the L. plantarum culture to the brine solution but not to bacteriocin production in situ on cheese. Pediocin resistance developed in vitro at different but high frequencies in all 12 L. monocytogenes strains investigated, and a resistant mutant remained stable in a microbial surface ripening consortium over a 4-month production process in the absence of selection pressure. In conclusion, the addition of a L. plantarum culture is a potent measure for combating Listeria in a contaminated production line, but because of the potential development of resistance, it should not be used continuously over a long time in a production line.  相似文献   
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Abstract. The contribution of resprouts and seedling recruitment to post-fire regeneration of the South African fynbos conifer Widdringtonia nodiflora was compared eight months after wildfires in 1990. Stems on all trees were killed by fire but resprouting success was > 90 % at all but one site. A demographic study of burned skeletons revealed that prior to these fires, nearly all plants were multi-stemmed (4–9 stems/plant) and multi-aged, indicating continuous sprout production between fires. All stems were killed by these 1990 fires and at most sites > 90 % of the stems were burned to ground level. All diameter stems were susceptible to such incineration as, at most sites, there was no difference in average diameter of stems burned to ground level and those left standing. Individual genets usually had all ramets incinerated to ground level or all ramets charred, but intact, suggesting certain micro-sites burned hotter, whereas other sites were somewhat protected. Although not true of the 1990 fires, there was evidence that occasionally Widdring-tonia stems may survive fire. At one site, four of the 16 plants sampled had a burned stem twice as old as the oldest burned stem on the other 12 plants at the site, suggesting some stems had survived the previous fire (ca. 1970) and this conclusion was supported by fire-scars on these four stems that dated to ca. 1970. Based on the highly significant correlation between stem diameter and cone density left standing after the 1990 fires, we calculated that for most sites > 80 % of the initial cone crop was incinerated by fire. This is important because we observed a strong relationship between size of the canopy cone crop surviving fire and post-fire seedling recruitment. Under these conditions we hypothesize that sprouting confers a selective advantage to genets when fires cause heavy losses of seed. The infrequent occurrence of sprouting in the Cupressaceae suggests the hypothesis that resprouting is an apomorphic or derived trait in Widdringtonia. Data from this study suggests resprouting provides a selective advantage under severe fynbos fires, which are not only 'stand-replacing fires,’but also are intense enough to incinerate cone-bearing stems.  相似文献   
9.
The term “cheating” is used in the evolutionary and ecological literature to describe a wide range of exploitative or deceitful traits. Although many find this a useful short hand, others have suggested that it implies cognitive intent in a misleading way, and is used inconsistently. We provide a formal justification of the use of the term “cheat” from the perspective of an individual as a maximizing agent. We provide a definition for cheating that can be applied widely, and show that cheats can be broadly classified on the basis of four distinctions: (i) whether cooperation is an option; (ii) whether deception is involved; (iii) whether members of the same or different species are cheated; and (iv) whether the cheat is facultative or obligate. Our formal definition and classification provide a framework that allow us to resolve and clarify a number of issues, regarding the detection and evolutionary consequences of cheating, as well as illuminating common principles and similarities in the underlying selection pressures.  相似文献   
10.
For years, we have relied on population surveys to keep track of regional public health statistics, including the prevalence of non-communicable diseases. Because of the cost and limitations of such surveys, we often do not have the up-to-date data on health outcomes of a region. In this paper, we examined the feasibility of inferring regional health outcomes from socio-demographic data that are widely available and timely updated through national censuses and community surveys. Using data for 50 American states (excluding Washington DC) from 2007 to 2012, we constructed a machine-learning model to predict the prevalence of six non-communicable disease (NCD) outcomes (four NCDs and two major clinical risk factors), based on population socio-demographic characteristics from the American Community Survey. We found that regional prevalence estimates for non-communicable diseases can be reasonably predicted. The predictions were highly correlated with the observed data, in both the states included in the derivation model (median correlation 0.88) and those excluded from the development for use as a completely separated validation sample (median correlation 0.85), demonstrating that the model had sufficient external validity to make good predictions, based on demographics alone, for areas not included in the model development. This highlights both the utility of this sophisticated approach to model development, and the vital importance of simple socio-demographic characteristics as both indicators and determinants of chronic disease.  相似文献   
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