Metabolic responses of two pioneer wood decay fungi to diurnally cycling temperature

Decomposition of lignin-rich wood by fungi drives nutrient recycling in woodland ecosystems. Fluctuating abiotic conditions are known to promote the functioning of ecological communities and ecosystems. In the context of wood decay, fluctuating temperature increases decomposition rates. Metabolomics, in tandem with other ‘omics tools, can highlight the metabolic processes affected by experimental treatments, even in the absence of genome sequences and annotations. Globally, natural wood decay communities are dominated by the phylum Basidiomycota. We examined the metabolic responses of Mucidula mucida, a dominant constituent of pioneer communities in beech branches in British woodlands, and Exidia glandulosa, a stress-selected constituent of the same communities, in response to constant and diurnally cycling temperature. We applied untargeted metabolomics and proteomics to beech wood blocks, colonised by M. mucida or E. glandulosa and exposed to either diurnally cycling (mean 15 ± 10°C) or constant (15°C) temperature, in a fully factorial design. Metabolites and proteins linked to lignin breakdown, the citric acid cycle, pentose phosphate pathway, carbohydrate metabolism, fatty acid metabolism and protein biosynthesis and turnover were under-enriched in fluctuating, compared to stable temperatures, in the generalist M. mucida. Conversely, E. glandulosa showed little differential response to the experimental treatments. Synthesis. By demonstrating temperature-dependant metabolic signatures related to nutrient acquisition in a generalist wood decay fungus, we provide new insights into how abiotic conditions can affect community-mediated decomposition and carbon turnover in forests. We show that mechanisms underpinning important biogeochemical processes can be highlighted using untargeted metabolomics and proteomics in the absence of well-annotated genomes

The Cost-Effectiveness of Early Access to HIV Services and Starting cART in the UK 1996–2008

To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI(boosted), comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI(boosted) with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685-£12,937) compared with £10,478 (95%CI £10,376-£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK

The JCMT Gould Belt Survey: A First Look at the Auriga–California Molecular Cloud with SCUBA-2

We present 850 and 450 μm observations of the dense regions within the Auriga–California molecular cloud using SCUBA-2 as part of the JCMT Gould Belt Legacy Survey to identify candidate protostellar objects, measure the masses of their circumstellar material (disk and envelope), and compare the star formation to that in the Orion A molecular cloud. We identify 59 candidate protostars based on the presence of compact submillimeter emission, complementing these observations with existing Herschel/SPIRE maps. Of our candidate protostars, 24 are associated with young stellar objects (YSOs) in the Spitzer and Herschel/PACS catalogs of 166 and 60 YSOs, respectively (177 unique), confirming their protostellar nature. The remaining 35 candidate protostars are in regions, particularly around LkHα 101, where the background cloud emission is too bright to verify or rule out the presence of the compact 70 μm emission that is expected for a protostellar source. We keep these candidate protostars in our sample but note that they may indeed be prestellar in nature. Our observations are sensitive to the high end of the mass distribution in Auriga–Cal. We find that the disparity between the richness of infrared star-forming objects in Orion A and the sparsity in Auriga–Cal extends to the submillimeter, suggesting that the relative star formation rates have not varied over the Class II lifetime and that Auriga–Cal will maintain a lower star formation efficiency

Serpin Induced Antiviral Activity of Prostaglandin Synthetase-2 against HIV-1 Replication

The serine protease inhibitors (serpins) are anti-inflammatory proteins that have various functions. By screening a diverse panel of viruses, we demonstrate that the serpin antithrombin III (ATIII) has a broad-spectrum anti-viral activity for HIV-1, HCV and HSV. To investigate the mechanism of action in more detail we investigated the HIV-1 inhibition. Using gene-expression arrays we found that multiple host cell signal transduction pathways were activated by ATIII in HIV-1 infected cells but not in uninfected controls. Moreover, the signal pathways initiated by ATIII treatment, were more than 200-fold increased by the use of heparin-activated ATIII. The most up-regulated transcript in HIV-1 infected cells was prostaglandin synthetase-2 (PTGS2). Furthermore, we found that over-expression of PTGS2 reduced levels of HIV-1 replication in human PBMC. These findings suggest a central role for serpins in the host innate anti-viral response. Host factors such as PTGS2 elicited by ATIII treatment could be exploited in the development of novel anti-viral interventions

The Oxford-Dartmouth Thirty Degree Survey I: Observations and Calibration of a Wide-Field Multi-Band Survey

The Oxford Dartmouth Thirty Degree Survey (ODTS) is a deep, wide, multi-band imaging survey designed to cover a total of 30 square degrees in BVRi'Z, with a subset of U and K band data, in four separate fields of 5-10 deg^2 centred at 00:18:24 +34:52, 09:09:45 +40:50, 13:40:00 +02:30 and 16:39:30 +45:24. Observations have been made using the Wide Field Camera on the 2.5-m Isaac Newton Telescope in La Palma to average limiting depths (5 sigma Vega, aperture magnitudes) of U=24.8, B=25.6, V=25.0, R=24.6, and i'=23.5, with observations taken in ideal conditions reaching the target depths of U=25.3, B=26.2, V=25.7, R=25.4, and i'=24.6. The INT Z band data was found to be severely effected by fringing and, consequently, is now being obtained at the MDM observatory in Arizona. A complementary K-band survey has also been carried out at MDM, reaching an average depth of K_{5\sigma}~18.5. At present, approximately 23 deg^2 of the ODTS have been observed, with 3.5 deg^2 of the K band survey completed. This paper details the survey goals, field selection, observation strategy and data reduction procedure, focusing on the photometric calibration and catalogue construction. Preliminary photometric redshifts have been obtained for a subsample of the objects with R <= 23. These results are presented alongside a brief description of the photometric redshift determination technique used. The median redshift of the survey is estimated to be z~0.7 from a combination of the ODTS photometric redshifts and comparison with the redshift distributions of other surveys. Finally, galaxy number counts for the ODTS are presented which are found to be in excellent agreement with previous studies.Comment: 18 pages, 21 figures, Accepted for publication in MNRA

Graded structure in sexual definitions: categorizations of having “had sex” and virginity loss among homosexual and heterosexual men and women

Definitions of sexual behavior display a robust hierarchy of agreement regarding whether or not acts should be classed as, for example, sex or virginity loss. The current research offers a theoretical explanation for this hierarchy, proposing that sexual definitions display graded categorical structure, arising from goodness of membership judgments. Moderation of this graded structure is also predicted, with the focus here on how sexual orientation identity affects sexual definitions. A total of 300 18- to 30-year-old participants completed an online survey, rating 18 behaviors for how far each constitutes having “had sex” and virginity loss. Participants fell into one of four groups: heterosexual male or female, gay male or lesbian. The predicted ratings hierarchy emerged, in which bidirectional genital acts were rated significantly higher than unidirectional or nonpenetrative contact, which was in turn rated significantly higher than acts involving no genital contact. Moderation of graded structure was also in line with predictions. Compared to the other groups, the lesbian group significantly upgraded ratings of genital contact that was either unidirectional or nonpenetrative. There was also evidence of upgrading by the gay male sample of anal intercourse ratings. These effects are theorized to reflect group-level variation in experience, contextual perspective, and identity-management. The implications of the findings in relation to previous research are discussed. It is suggested that a graded structure approach can greatly benefit future research into sexual definitions, by permitting variable definitions to be predicted and explained, rather than merely identified

Impulsivity and self-harm in adolescence: a systematic review

Research supports an association between impulsivity and self-harm, yet inconsistencies in methodology across studies have complicated understanding of this relationship. This systematic review examines the association between impulsivity and self-harm in community-based adolescents aged 11-25 years and aims to integrate findings according to differing concepts and methods. Electronic searches of EMBASE, MEDLINE, PsychINFO, CINAHL, PubMed and The Cochrane Library, and manual searches of reference lists of relevant reviews, identified 4,496 articles published up to July 2015, of which 28 met inclusion criteria. Twenty-four of the studies reported an association between broadly specified impulsivity and self-harm. However, findings varied according to the conception and measurement of impulsivity and the precision with which self-harm behaviours were specified. Specifically, lifetime non-suicidal self-injury was most consistently associated with mood-based impulsivity related traits. However, cognitive facets of impulsivity (relating to difficulties maintaining focus or acting without forethought) differentiated current self-harm from past self-harm. These facets also distinguished those with thoughts of self-harm (ideation) from those who acted on thoughts (enaction). The findings suggested that mood-based impulsivity is related to the initiation of self-harm, while cognitive facets of impulsivity are associated with the maintenance of self-harm. In addition, behavioural impulsivity is most relevant to self-harm under conditions of negative affect. Collectively, the findings indicate that distinct impulsivity facets confer unique risks across the life-course of self-harm. From a clinical perspective, the review suggests that interventions focusing on reducing rash reactivity to emotions or improving self-regulation and decision-making may offer most benefit in supporting those who self-harm

Persistent Cell-Autonomous Circadian Oscillations in Fibroblasts Revealed by Six-Week Single-Cell Imaging of PER2::LUC Bioluminescence

Biological oscillators naturally exhibit stochastic fluctuations in period and amplitude due to the random nature of molecular reactions. Accurately measuring the precision of noisy oscillators and the heterogeneity in period and strength of rhythmicity across a population of cells requires single-cell recordings of sufficient length to fully represent the variability of oscillations. We found persistent, independent circadian oscillations of clock gene expression in 6-week-long bioluminescence recordings of 80 primary fibroblast cells dissociated from PER2::LUC mice and kept in vitro for 6 months. Due to the stochastic nature of rhythmicity, the proportion of cells appearing rhythmic increases with the length of interval examined, with 100% of cells found to be rhythmic when using 3-week windows. Mean period and amplitude are remarkably stable throughout the 6-week recordings, with precision improving over time. For individual cells, precision of period and amplitude are correlated with cell size and rhythm amplitude, but not with period, and period exhibits much less cycle-to-cycle variability (CV 7.3%) than does amplitude (CV 37%). The time series are long enough to distinguish stochastic fluctuations within each cell from differences among cells, and we conclude that the cells do exhibit significant heterogeneity in period and strength of rhythmicity, which we measure using a novel statistical metric. Furthermore, stochastic modeling suggests that these single-cell clocks operate near a Hopf bifurcation, such that intrinsic noise enhances the oscillations by minimizing period variability and sustaining amplitude