Coxiella burnetii: turning hostility into a home

Coxiella burnetii, the causative agent of the human disease Q fever, is a unique intracellular bacterial pathogen. Coxiella replicates to high numbers within a pathogen‐derived lysosome‐like vacuole, thriving within a low pH, highly proteolytic and oxidative environment. In 2009, researchers developed means to axenically culture Coxiella paving the way for the development of tools to genetically manipulate the organism. These advances have revolutionized our capacity to examine the pathogenesis of Coxiella. In recent years, targeted and random mutant strains have been used to demonstrate that the Dot/Icm type IV secretion system is essential for intracellular replication of Coxiella. Current research is focused towards understanding the unique cohort of over 130 effector proteins that are translocated into the host cell. Mutagenesis screens have been employed to identify effectors that play important roles for the biogenesis of the Coxiella‐containing vacuole and intracellular replication of Coxiella. A surprisingly high number of effector mutants demonstrate significant intracellular growth defects, and future studies on the molecular function of these effectors will provide great insight into the pathogenesis of Coxiella. Already, this expanse of new data implicates many eukaryotic processes that are targeted by the arsenal of Coxiella effectors including autophagy, apoptosis and vesicular trafficking.     

Human and mouse mutations in WDR35 cause short-rib polydactyly syndromes due to abnormal ciliogenesis

Defects in cilia formation and function result in a range of human skeletal and visceral abnormalities. Mutations in several genes have been identified to cause a proportion of these disorders, some of which display genetic (locus) heterogeneity. Mouse models are valuable for dissecting the function of these genes, as well as for more detailed analysis of the underlying developmental defects. The short-rib polydactyly (SRP) group of disorders are among the most severe human phenotypes caused by cilia dysfunction. We mapped the disease locus from two siblings affected by a severe form of SRP to 2p24, where we identified an in-frame homozygous deletion of exon 5 in WDR35. We subsequently found compound heterozygous missense and nonsense mutations in WDR35 in an independent second case with a similar, severe SRP phenotype. In a mouse mutation screen for developmental phenotypes, we identified a mutation in Wdr35 as the cause of midgestation lethality, with abnormalities characteristic of defects in the Hedgehog signaling pathway. We show that endogenous WDR35 localizes to cilia and centrosomes throughout the developing embryo and that human and mouse fibroblasts lacking the protein fail to produce cilia. Through structural modeling, we show that WDR35 has strong homology to the COPI coatamers involved in vesicular trafficking and that human SRP mutations affect key structural elements in WDR35. Our report expands, and sheds new light on, the pathogenesis of the SRP spectrum of ciliopathies.     

Soil Carbon and Nitrogen Storage in Upper Montane Riparian Meadows

Though typically limited in aerial extent, soils of high-elevation riparian wetlands have among the highest density of soil carbon (C) and nitrogen (N) of terrestrial ecosystems and therefore contribute disproportionally to ecosystem services such as water retention, forage production, wildlife habitat, and reactive N removal. Because much soil C and N is stored in labile forms in anaerobic conditions, management activities or environmental changes that lead to drying cause mineralization of labile soil organic matter, and loss of C and N. Meadows are focal points of human activities in mountain regions, often with incised stream channels from historically heavy grazing exacerbated by extreme runoff events. To quantify soil C and N stores in montane riparian meadows across hydrologic conditions, 17 meadows between 1950- and 2675-m elevation were selected in the central Sierra Nevada Range, California, that were classified using the proper functioning condition (PFC) system. Results indicate that C and N density in whole-solum soil cores were equivalent at forest edge positions of properly functioning, functioning at-risk, and nonfunctioning condition. Soils under more moist meadow positions in properly functioning meadows have at least twice the C, N, dissolved organic C, and dissolved organic N (DON) than those under nonfunctioning meadows. Densities of total N and DON, but not C, of functioning at-risk meadows are significantly lower (P < 0.05) than those of properly functioning meadows at mid-slope and stream-bank positions, suggesting accelerated loss of N early in degradation processes. Though variable, the soil attributes measured correspond well to the PFC riparian wetland classification system.     

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand

The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer.     

Vision-Related Quality of Life and Appearance Concerns Are Associated with Anxiety and Depression after Eye Enucleation: A Cross-Sectional Study

Aims

To investigate the association of demographic, clinical and psychosocial variables with levels of anxiety and depression in participants wearing an ocular prosthesis after eye enucleation.

Methods

This cross-sectional study included 195 participants with an enucleated eye who were attending an ophthalmic clinic for prosthetic rehabilitation between July and November 2014. Demographic and clinical data, and self-reported feelings of shame, sadness and anger were collected. Participants also completed the National Eye Institute Visual Function Questionnaire, the Facial Appearance subscale of the Negative Physical Self Scale, and the Hospital Anxiety and Depression Scale. Regression models were used to identify the factors associated with anxiety and depression.

Results

The proportion of participants with clinical anxiety was 11.8% and clinical depression 13.8%. More anxiety and depression were associated with poorer vision-related quality of life and greater levels of appearance concerns. Younger age was related to greater levels of anxiety. Less educated participants and those feeling more angry about losing an eye are more prone to experience depression. Clinical variables were unrelated to anxiety or depression.

Conclusions

Anxiety and depression are more prevalent in eye-enucleated patients than the general population, which brings up the issues of psychiatric support in these patients. Psychosocial rather than clinical characteristics were associated with anxiety and depression. Longitudinal studies need to be conducted to further elucidate the direction of causality before interventions to improve mood states are developed.     

The synthesis of novel chromogenic enzyme substrates for detection of bacterial glycosidases and their applications in diagnostic microbiology

The preparation and evaluation of chromogenic substrates for detecting bacterial glycosidase enzymes is reported. These substrates are monoglycoside derivatives of the metal chelators catechol, 2,3-dihydroxynaphthalene (DHN) and 6,7-dibromo-2,3-dihydroxynaphthalene (6,7-dibromo-DHN). When hydrolysed by appropriate bacterial enzymes these substrates produced coloured chelates in the presence of ammonium iron(III) citrate, thus enabling bacterial detection. A β-d-riboside of DHN and a β-d-glucuronide derivative of 6,7-dibromo-DHN were particularly effective for the detection of S. aureus and E. coli respectively.     

Introduced cats Felis catus eating a continental fauna: inventory and traits of Australian mammal species killed

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Mitogen-activated Protein Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7

Cbx7 is one of five mammalian orthologs of the Drosophila Polycomb. Cbx7 recognizes methylated lysine residues on the histone H3 tail and contributes to gene silencing in the context of the Polycomb repressive complex 1 (PRC1). However, our knowledge of Cbx7 post-translational modifications remains limited. Through combined biochemical and mass spectrometry approaches, we report a novel phosphorylation site on mouse Cbx7 at residue Thr-118 (Cbx7T118ph), near the highly conserved Polycomb box. The generation of a site-specific antibody to Cbx7T118ph demonstrates that Cbx7 is phosphorylated via MAPK signaling. Furthermore, we find Cbx7T118 phosphorylation in murine mammary carcinoma cells, which can be blocked by MEK inhibitors. Upon EGF stimulation, Cbx7 interacts robustly with other members of PRC1. To test the role of Cbx7T118 phosphorylation in gene silencing, we employed a RAS-induced senescence model system. We demonstrate that Cbx7T118 phosphorylation moderately enhances repression of its target gene p16. In summary, we have identified and characterized a novel MAPK-mediated phosphorylation site on Cbx7 and propose that mitogen signaling to the chromatin template regulates PRC1 function.     

High mitochondrial and nuclear genetic diversity in one of the world’s most endangered seabirds,the Chatham Island Taiko (<Emphasis Type="Italic">Pterodroma magentae</Emphasis>)

Interpreting the levels of genetic diversity in organisms with diverse life and population histories can be difficult. The processes and mechanisms regulating this diversity are complex and still poorly understood. However, endangered species typically have low genetic variation as a consequence of the effects of genetic drift in small populations. In this study we examine genetic variation in the critically endangered Chatham Island Taiko (Tchaik, Pterodroma magentae), one of the world’s rarest seabirds. The Taiko has a very small population size of between 120 and 150 individuals, including just 8–15 breeding pairs. We report surprisingly high mitochondrial and nuclear genetic diversity in this critically endangered long-lived species. We hypothesise that the present Taiko population has retained a significant proportion of its past genetic diversity. However, it is also possible that undiscovered birds are breeding in unknown areas, which could increase the population size estimate. Importantly, from a conservation perspective, we show that the high level of variation is unlikely to be maintained in the future since chicks currently being born have only a limited number of the mitochondrial DNA haplotypes found in adults. Reduced genetic variation will mean that our ability to infer past events and the population history of Taiko using genetics could soon be lost and the power to determine, for example, parentage and other close order relationships will be diminished. Therefore, the maintenance of genetic diversity in future generations is an important consideration for conservation management of the Taiko.