Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)

High prevalence of the arginine catabolic mobile element in carriage isolates of methicillin-resistant Staphylococcus epidermidis

Background The arginine catabolic mobile element (ACME) associated with staphylococcal cassette chromosome mec (SCCmec) in the USA300 clone of community-acquired methicillin-resistant Staphylococcus aureus enhances its fitness and ability to colonize the host. Staphylococcus epidermidis may act as a reservoir of ACME for S. aureus. We assessed the diffusion of ACME in methicillin-resistant S. epidermidis (MRSE) isolates colonizing outpatients. Methods Seventy-eight MRSE strains isolated in outpatients from five countries were characterized by multilocus sequence typing (MLST) and SCCmec typing and screened for the arcA and opp3AB markers of ACME. ACME-arcA and ACME-opp3AB were sequenced. ACME type I from MRSE and USA300 were compared by long-range PCR (LR-PCR). Results Fifty-three (67.9%) MRSE strains carried an ACME element, including 19 (24.4%), 32 (41.0%) and 2 (2.6%) with ACME type I (arcA+/opp3AB+), II (arcA+/opp3AB−) and III (arcA−/opp3AB+), respectively. The prevalence of ACME did not differ between clonal complex 2 (42/60 strains) and other sequence types (11/18 strains, P = 0.7), with MLST data suggesting frequent intraspecies acquisition. ACME-arcA sequences were highly conserved, whereas ACME-opp3AB displayed 11 distinct allotypes. ACME was found in 14/29, 9/11 and 30/37 strains with type IV, type V and non-typeable SCCmec, respectively (P = 0.01). ACME was more frequently associated with ccrC than with ccrAB2 (82.4% versus 60.0%, P = 0.048). LR-PCR indicated structural homologies of ACME I between MRSE and USA300. Conclusions ACME is widely disseminated in MRSE strains colonizing outpatients and may contribute to their spread in a community environment with low antibiotic exposure, as suggested for USA30

“Think horizontally, act vertically” : the centenary (1916–2016) of pollen analysis and the legacy of Lennart von Post

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Methicillin-Resistant Coagulase-Negative Staphylococci in the Community: High Homology of SCCmec IVa between Staphylococcus epidermidis and Major Clones of Methicillin-Resistant Staphylococcus aureus

Background. Data on community spread of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) are scarce. We assessed their potential role as a reservoir of staphylococcal cassette chromosome mec (SCCmec) IVa, the leading SCCmec subtype in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Methods. Nasal carriage of MR-CoNS was prospectively investigated in 291 adults at hospital admission. MR-CoNS were characterized by SCCmec typing, long-range polymerase chain reaction (PCR) for SCCmec IV, and multiple-locus variable-number tandem repeat analysis (MLVA) for Staphylococcus epidermidis (MRSE) strains. Three SCCmec IVa elements were fully sequenced. Results. The carriage rate of MR-CoNS was 19.2% (25.9% and 16.5% in patients with and patients without previous exposure to the health care system, respectively; P = .09). MR-CoNS strains (n=83, including 58 MRSE strains with highly heterogeneous MLVA patterns) carried SCCmec type IVa (n=9, all MRSE), other SCCmec IV subtypes (n=9, including 7 MRSE), other SCCmec types (n=15), and nontypeable SCCmec (n=50). Long-range PCR indicated structural homology between SCCmec IV in MRSE and that in MRSA. Complete sequences of SCCmec IVa from 3 MRSE strains were highly homologous to those available for CA-MRSA, including major clones USA300 and USA400. Conclusions. MR-CoNS are probably disseminated in the community, notably in subjects without previous exposure to the health care system. MRSE, the most prevalent species, may act as a reservoir of SCCmec IVa for CA-MRS

Holocene changes in vegetation composition in northern Europe: why quantitative pollen-based vegetation reconstructions matter

International audienceWe present pollen-based reconstructions of the spatio-temporal dynamics of northern European regional vegetation abundance through the Holocene. We apply the Regional Estimates of VEgetation Abundance from Large Sites (REVEALS) model using fossil pollen records from eighteen sites within five modern biomes in the region. The eighteen sites are classified into four time-trajectory types on the basis of principal components analysis of both the REVEALS-based vegetation estimates (RVs) and the pollen percentage (PPs). The four trajectory types are more clearly separated for RVs than PPs. Further, the timing of major Holocene shifts, rates of compositional change, and diversity indices (turnover and evenness) differ between RVs and PPs. The differences are due to the reduction by REVEALS of biases in fossil pollen assemblages caused by different basin size, and inter-taxonomic differences in pollen productivity and dispersal properties. For example, in comparison to the PPs, the RVs show an earlier increase in Corylus and Ulmus in the early-Holocene and a more pronounced increase in grassland and deforested areas since the mid-Holocene. The results suggest that the influence of deforestation and agricultural activities on plant composition and abundance from Neolithic times was stronger than previously inferred from PPs. Relative to PPs, RVs show a more rapid compositional change, a largest decrease in turnover, and less variable evenness in most of northern Europe since 5200 cal yr BP. All these changes are primarily related to the strong impact of human activities on the vegetation. This study demonstrates that RV-based estimates of diversity indices, timing of shifts, and rates of change in reconstructed vegetation provide new insights into the timing and magnitude of major humandisturbance on Holocene regional vegetation, features that are critical in the assessment of humanimpact on vegetation, land-cover, biodiversity, and climate in the past

Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the \u27pediatric Status Epilepticus Research Group\u27 (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. CONCLUSION: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE

Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

International audienc

Moving forwards? Palynology and the human dimension

For the greater part of the last century, anthropogenic palynology has made a sustained contribution to archaeology and to Quaternary science in general, and pollen-analytical papers have appeared in Journal of Archaeological Science since its inception. The present paper focuses selectively upon three areas of anthropogenic palynology, enabling some assessment as to whether the field is advancing: land-use studies, archaeological site study, and modelling. The Discussion also highlights related areas including palynomorph identification and associated proxies. There is little doubt that anthropogenic palynology has contributed to the vitality of pollen analysis in general, and although published research can be replicative or incremental, site- and landscape-based studies offer fresh data for further analysis and modelling. The latter allows the testing of both palynological concepts and inferences and can inform archaeological discovery and imagination. Archaeological site studies are often difficult, but palynology can still offer much to the understanding of occupation sites and the discernment of human behaviour patterns within sites

Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells

Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10−13, 10−11, 10−9, 10−7 or 10−5 M) of 1,25(OH)2D3 for up to 6 days and markers of muscle and fat development measured. Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10−13 and 10−11 M) of 1,25(OH)2D3 increased fat droplet accumulation, whereas high physiological (10−9 M) and supraphysiological concentrations (≥10−7 M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10−13 and 10−11 M) was associated with a sequential up-regulation of PPARγ2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10−9 M) reduced all these effects, and the highest concentration (10−5 M) appeared to have toxic effects. This is the first study to demonstrate dose-dependent effects of 1,25(OH)2D3 on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect