Simultaneous Nasal Carriage by Methicillin-Resistant and Methicillin Susceptible Staphylococcus aureus of Lineage ST398 in a Live Pig Transporter.

Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST)398 is a livestock associated (LA) lineage with zoonotic potential, especially in humans with live pig contact. The objective of this study was to characterize two S. aureus strains of lineage ST398 (one methicillin-resistant (MRSA), one methicillin-susceptible (MSSA)) isolated from the same nasal sample of a patient admitted in the Intensive-Care Unit of a Spanish Hospital, and with previous occupational exposure to live pigs, by whole-genome-sequencing (WGS). The sample was obtained during routine surveillance for MRSA colonization. Purified genomic DNA was sequenced using Illumina HiSeq 2000 and processed using conventional bioinformatics software. The two isolates recovered were both S. aureus t011/ST398 and showed similar resistance-phenotypes, other than methicillin susceptibility. The possession of antibiotic resistance genes was the same, except for the mecA-gene located in SCCmecV in the MRSA isolate. The MSSA isolate harbored remnants of a SCCmec following the deletion of 17342bp from a recombination between two putative primases. Both isolates belonged to the livestock-associated clade as defined by three canonical single-nucleotide-polymorphisms, and neither possessed the human immune evasion cluster genes, chp, scn, or sak. The core genome alignment showed a similarity of 99.6%, and both isolates harbored the same mobile genetic elements. The two nasal ST398 isolates recovered from the patient with previous occupational exposure to pigs appeared to have a livestock origin and could represent different evolutionary steps of animal-human interface lineage. The MSSA strain was formed as a result of the loss of the mecA gene from the livestock-associated-MRSA lineage

Absolute properties of the low-mass eclipsing binary CM Draconis

Spectroscopic and eclipsing binary systems offer the best means for determining accurate physical properties of stars, including their masses and radii. The data available for low-mass stars have yielded firm evidence that stellar structure models predict smaller radii and higher effective temperatures than observed, but the number of systems with detailed analyses is still small. In this paper we present a complete reanalysis of one of such eclipsing systems, CM Dra, composed of two dM4.5 stars. New and existing light curves as well as a radial velocity curve are modeled to measure the physical properties of both components. The masses and radii determined for the components of CM Dra are M1=0.2310+/-0.0009 Msun, M2=0.2141+/-0.0010 Msun, R1=0.2534+/-0.0019 Rsun, and R2=0.2396+/-0.0015 Rsun. With relative uncertainties well below the 1% level, these values constitute the most accurate properties to date for fully convective stars. This makes CM Dra a valuable benchmark for testing theoretical models. In comparing our measurements with theory, we confirm the discrepancies reported previously for other low-mass eclipsing binaries. These discrepancies seem likely to be due to the effects of magnetic activity. We find that the orbit of this system is slightly eccentric, and we have made use of eclipse timings spanning three decades to infer the apsidal motion and other related properties.Comment: 19 pages, 9 figures. Accepted for publication in Ap

A Comparative Genomic Analysis of Putative Pathogenicity Genes in the Host-Specific Sibling Species \u3cem\u3eColletotrichum graminicola\u3c/em\u3e and \u3cem\u3eColletotrichum sublineola\u3c/em\u3e

Background: Colletotrichum graminicola and C. sublineola cause anthracnose leaf and stalk diseases of maize and sorghum, respectively. In spite of their close evolutionary relationship, the two species are completely host-specific. Host specificity is often attributed to pathogen virulence factors, including specialized secondary metabolites (SSM), and small-secreted protein (SSP) effectors. Genes relevant to these categories were manually annotated in two co-occurring, contemporaneous strains of C. graminicola and C. sublineola. A comparative genomic and phylogenetic analysis was performed to address the evolutionary relationships among these and other divergent gene families in the two strains. Results: Inoculation of maize with C. sublineola, or of sorghum with C. graminicola, resulted in rapid plant cell death at, or just after, the point of penetration. The two fungal genomes were very similar. More than 50% of the assemblies could be directly aligned, and more than 80% of the gene models were syntenous. More than 90% of the predicted proteins had orthologs in both species. Genes lacking orthologs in the other species (non-conserved genes) included many predicted to encode SSM-associated proteins and SSPs. Other common groups of non-conserved proteins included transporters, transcription factors, and CAZymes. Only 32 SSP genes appeared to be specific to C. graminicola, and 21 to C. sublineola. None of the SSM-associated genes were lineage-specific. Two different strains of C. graminicola, and three strains of C. sublineola, differed in no more than 1% percent of gene sequences from one another. Conclusions: Efficient non-host recognition of C. sublineola by maize, and of C. graminicola by sorghum, was observed in epidermal cells as a rapid deployment of visible resistance responses and plant cell death. Numerous non-conserved SSP and SSM-associated predicted proteins that could play a role in this non-host recognition were identified. Additional categories of genes that were also highly divergent suggested an important role for co-evolutionary adaptation to specific host environmental factors, in addition to aspects of initial recognition, in host specificity. This work provides a foundation for future functional studies aimed at clarifying the roles of these proteins, and the possibility of manipulating them to improve management of these two economically important diseases

Glacial weathering, sulfide oxidation, and global carbon cycle feedbacks

Connections between glaciation, chemical weathering, and the global carbon cycle could steer the evolution of global climate over geologic time, but even the directionality of feedbacks in this system remain to be resolved. Here, we assemble a compilation of hydrochemical data from glacierized catchments, use this data to evaluate the dominant chemical reactions associated with glacial weathering, and explore the implications for long-term geochemical cycles. Weathering yields from catchments in our compilation are higher than the global average, which results, in part, from higher runoff in glaciated catchments. Our analysis supports the theory that glacial weathering is characterized predominantly by weathering of trace sulfide and carbonate minerals. To evaluate the effects of glacial weathering on atmospheric pCO_2, we use a solute mixing model to predict the ratio of alkalinity to dissolved inorganic carbon (DIC) generated by weathering reactions. Compared with nonglacial weathering, glacial weathering is more likely to yield alkalinity/DIC ratios less than 1, suggesting that enhanced sulfide oxidation as a result of glaciation may act as a source of CO_2 to the atmosphere. Back-of-the-envelope calculations indicate that oxidative fluxes could change ocean–atmosphere CO_2 equilibrium by 25 ppm or more over 10 ky. Over longer timescales, CO_2 release could act as a negative feedback, limiting progress of glaciation, dependent on lithology and the concentration of atmospheric O_2. Future work on glaciation–weathering–carbon cycle feedbacks should consider weathering of trace sulfide minerals in addition to silicate minerals

Secondary Infall in the Seyfert\u27s Sextet: A Plausible Way out of the Short Crossing Time Paradox

We used integral field spectroscopy from CALIFA DR3 and multiwavelength publicly available data to investigate the star formation histories of galaxies in the Seyfert\u27s Sextet (SS; HCG 79). The galaxies H79a, H79b, H79c, and H79f have low star formation rates despite showing strong signs of interaction. By exploring their individual specific star formation histories, we identified three earlier episodes of strong star formation common to these four galaxies. We use the last two episodes as markers of the epochs when the galaxies were crossing. We suggest that after the first turnaround, initially gas-rich galaxies crossed for the first time, consuming most of their gas. Hence, after the second turnaround most mergers from second crossings would be mixed or dry. The exception would be gas-rich galaxies intruding for the first time. Therefore, we suggest that SS galaxies have survived one crossing during a Hubble time. Strong Balmer absorption lines and the presence of counter-rotating disks provide independent bounds to the second and first crossing, respectively. This scenario provides a plausible way out of the short crossing time paradox

Secondary Infall in the Seyfert's Sextet:A Plausible Way Out of the Short Crossing Time Paradox

We used integral field spectroscopy from CALIFA DR3 and multiwavelength publicly-available data to investigate the star-formation histories of galaxies in the Seyfert's Sextet (SS, HCG 79). The galaxies H79a, H79b, H79c, and H79f have low star-formation rates despite showing strong signs of interaction. By exploring their individual specific star formation histories (sSFH), we identified three earlier episodes of strong star formation common to these four galaxies. We use the last two episodes as markers of the epochs when the galaxies were crossing. We suggest that after the first turn-around, initially gas-rich galaxies crossed for the first time, consuming most of their gas. Hence after the second turn-around most mergers from second crossings would be mixed or dry. The exception would be gas-rich galaxies intruding for the first time. Therefore, we suggest that SS galaxies have survived one crossing during a Hubble time. Strong Balmer absorption lines and the presence of counter-rotating disks provide independent bounds to the second and first crossing, respectively. This scenario provides a plausible way out of the short crossing time paradox.Comment: 21 pages, 5 figues, accepted for publication in ApJ Letter

Systemic Administration of Antiretrovirals Prior to Exposure Prevents Rectal and Intravenous HIV-1 Transmission in Humanized BLT Mice

Successful antiretroviral pre-exposure prophylaxis (PrEP) for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT). BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003) and intravenous (Chi square = 13, df = 1, p = 0.0003) HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics