Understanding Intermodel Variability in Future Projections of a Sahelian Storm Proxy and Southern Saharan Warming

Projected changes in the intensity of severe rain events over the North African Sahel—falling from large mesoscale convective systems—cannot be directly assessed from global climate models due to their inadequate resolution and parameterization of convection. Instead, the large-scale atmospheric drivers of these storms must be analyzed. Here we study changes in meridional lower-tropospheric temperature gradient across the Sahel (ΔTGrad), which affect storm development via zonal vertical wind shear and Saharan air layer characteristics. Projected changes in ΔTGrad vary substantially among models, adversely affecting planning decisions that need to be resilient to adverse risks, such as increased flooding. This study seeks to understand the causes of these projection uncertainties and finds three key drivers. The first is intermodel variability in remote warming, which has strongest impact on the eastern Sahel, decaying toward the west. Second, and most important, a warming–advection–circulation feedback in a narrow band along the southern Sahara varies in strength between models. Third, variations in southern Saharan evaporative anomalies weakly affect ΔTGrad, although for an outlier model these are sufficiently substantive to reduce warming here to below that of the global mean. Together these uncertain mechanisms lead to uncertain southern Saharan/northern Sahelian warming, causing the bulk of large intermodel variations in ΔTGrad. In the southern Sahel, a local negative feedback limits the contribution to uncertainties in ΔTGrad. This new knowledge of ΔTGrad projection uncertainties provides understanding that can be used, in combination with further research, to constrain projections of severe Sahelian storm activity

Is early center-based child care associated with tantrums and unmanageable behavior over time up to school entry?

Background. Existing research suggests that there is a relationship between greater exposure to center-based child care and child behavioral problems though the mechanism for the impact is unclear. However the measure used to document child care has usually been average hours, which may be particularly unreliable in the early months when fewer children are in center care. In addition individual trajectories for behavior difficulties have not been studied. Objective. The purpose of the current study was to examine whether the extent of exposure to center-based child care before two years predicted the trajectory of children’s difficult behavior (i.e., tantrums and unmanageable behavior) from 30 to 51 months controlling for child and maternal characteristics. Method. Data were drawn from UK-based Families, Children and Child Care (FCCC) study (n=1201). Individual growth models were fitted to test the relation between early center-based child care experiences and subsequent difficult behavior. Results. Children with more exposure to center-based care before two had less difficult behavior at 30 months, but more increase over time. Initial levels were predicted by higher difficult temperament and lower verbal ability. Higher difficult temperament and lower family socio-economic status predicted its change over time. Conclusion. Findings suggest that early exposure to center-based care before two years old is a risk factor for subsequent behavior problems especially when children have a longer period of exposure. A possible explanatory process is that child coping strategies to manage frustration are less well developed in a group context, especially when they lag behind in expressive language

Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

Identification and functional characterisation of CRK12:CYC9, a novel cyclin-dependent kinase (CDK)-cyclin complex in Trypanosoma brucei

The protozoan parasite, Trypanosoma brucei, is spread by the tsetse fly and causes trypanosomiasis in humans and animals. Both the life cycle and cell cycle of the parasite are complex. Trypanosomes have eleven cdc2-related kinases (CRKs) and ten cyclins, an unusually large number for a single celled organism. To date, relatively little is known about the function of many of the CRKs and cyclins, and only CRK3 has previously been shown to be cyclin-dependent in vivo. Here we report the identification of a previously uncharacterised CRK:cyclin complex between CRK12 and the putative transcriptional cyclin, CYC9. CRK12:CYC9 interact to form an active protein kinase complex in procyclic and bloodstream T. brucei. Both CRK12 and CYC9 are essential for the proliferation of bloodstream trypanosomes in vitro, and we show that CRK12 is also essential for survival of T. brucei in a mouse model, providing genetic validation of CRK12:CYC9 as a novel drug target for trypanosomiasis. Further, functional characterisation of CRK12 and CYC9 using RNA interference reveals roles for these proteins in endocytosis and cytokinesis, respectively

Biochemical evidence for the tyrosine involvement in cationic intermediate stabilization in mouse β-carotene 15, 15'-monooxygenase

<p>Abstract</p> <p>Background</p> <p>β-carotene 15,15'-monooxygenase (BCMO1) catalyzes the crucial first step in vitamin A biosynthesis in animals. We wished to explore the possibility that a carbocation intermediate is formed during the cleavage reaction of BCMO1, as is seen for many isoprenoid biosynthesis enzymes, and to determine which residues in the substrate binding cleft are necessary for catalytic and substrate binding activity. To test this hypothesis, we replaced substrate cleft aromatic and acidic residues by site-directed mutagenesis. Enzymatic activity was measured <it>in vitro </it>using His-tag purified proteins and <it>in vivo </it>in a β-carotene-accumulating <it>E. coli </it>system.</p> <p>Results</p> <p>Our assays show that mutation of either Y235 or Y326 to leucine (no cation-π stabilization) significantly impairs the catalytic activity of the enzyme. Moreover, mutation of Y326 to glutamine (predicted to destabilize a putative carbocation) almost eliminates activity (9.3% of wt activity). However, replacement of these same tyrosines with phenylalanine or tryptophan does not significantly impair activity, indicating that aromaticity at these residues is crucial. Mutations of two other aromatic residues in the binding cleft of BCMO1, F51 and W454, to either another aromatic residue or to leucine do not influence the catalytic activity of the enzyme. Our <it>ab initio </it>model of BCMO1 with β-carotene mounted supports a mechanism involving cation-π stabilization by Y235 and Y326.</p> <p>Conclusions</p> <p>Our data are consistent with the formation of a substrate carbocation intermediate and cation-π stabilization of this intermediate by two aromatic residues in the substrate-binding cleft of BCMO1.</p

The potential of intervening on childhood adversity to reduce socioeconomic inequities in body mass index and inflammation among Australian and UK children: A causal mediation analysis.

BACKGROUND: Lower maternal education is associated with higher body mass index (BMI) and higher chronic inflammation in offspring. Childhood adversity potentially mediates these associations. We examined the extent to which addressing childhood adversity could reduce socioeconomic inequities in these outcomes. METHODS: We analysed data from two early-life longitudinal cohorts: the Longitudinal Study of Australian Children (LSAC; n=1873) and the UK Avon Longitudinal Study of Parents and Children (ALSPAC; n=7085). EXPOSURE: low/medium (below university degree) versus high maternal education, as a key indicator of family socioeconomic position (0-1 year). OUTCOMES: BMI and log-transformed glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Mediator: multiple adversities (≥2/<2) indicated by family violence, mental illness, substance abuse and harsh parenting (LSAC: 2-11 years; ALSPAC: 1-12 years). A causal mediation analysis was conducted. RESULTS: Low/medium maternal education was associated with up to 1.03 kg/m2 higher BMI (95% CI: 0.95 to 1.10) and up to 1.69% higher GlycA (95% CI: 1.68 to 1.71) compared with high maternal education, adjusting for confounders. Causal mediation analysis estimated that decreasing the levels of multiple adversities in children with low/medium maternal education to be like their high maternal education peers could reduce BMI inequalities by up to 1.8% and up to 3.3% in GlycA. CONCLUSIONS: Our findings in both cohorts suggest that slight reductions in socioeconomic inequities in children's BMI and inflammation could be achieved by addressing childhood adversities. Public health and social policy efforts should help those affected by childhood adversity, but also consider underlying socioeconomic conditions that drive health inequities

Potential process 'hurdles' in the use of macroalgae as feedstock for biofuel production in the British Isles

This review examines the potential technical and energy balance hurdles in the production of seaweed biofuel, and particular for the MacroBioCrude processing pipeline for the sustainable manufacture of liquid hydrocarbon fuels from seaweed in the UK. The production of biofuel from seaweed is economically, energetically and technically challenging at scale. Any successful process appears to require both a method of preserving the seaweed for continuous feedstock availability and a method exploiting the entire biomass. Ensiling and gasification offer a potential solution to these two requirements. However there is need for more data particularly at a commercial scal

YwdL in Bacillus cereus: Its Role in Germination and Exosporium Structure

In members of the Bacillus cereus group the outermost layer of the spore is the exosporium, which interacts with hosts and the environment. Efforts have been made to identify proteins of the exosporium but only a few have so far been characterised and their role in determining spore architecture and spore function is still poorly understood. We have characterised the exosporium protein, YwdL. ΔywdL spores have a more fragile exosporium, subject to damage on repeated freeze-thawing, although there is no evidence of altered resistance properties, and coats appear intact. Immunogold labelling and Western blotting with anti-YwdL antibodies identified YwdL to be located exclusively on the inner surface of the exosporium of B. cereus and B. thuringiensis. We conclude that YwdL is important for formation of a robust exosporium but is not required to maintain the crystalline assembly within the basal layer or for attachment of the hairy nap structure. ΔywdL spores are unable to germinate in response to CaDPA, and have altered germination properties, a phenotype that confirms the expected defect in localization of the cortex lytic enzyme CwlJ in the coat

Interventions to Influence Consulting and Antibiotic Use for Acute Respiratory Tract Infections in Children: A Systematic Review and Meta-Analysis

BACKGROUND: Respiratory tract infections (RTIs) are common in children and generally self-limiting, yet often result in consultations to primary care. Frequent consultations divert resources from care for potentially more serious conditions and increase the opportunity for antibiotic overuse. Overuse of antibiotics is associated with adverse effects and antimicrobial resistance, and has been shown to influence how patients seek care in ensuing illness episodes. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a systematic review and meta-analysis to assess the effectiveness of interventions directed towards parents or caregivers which were designed to influence consulting and antibiotic use for respiratory tract infections (RTIs) in children in primary care. Main outcomes were parental consulting rate, parental knowledge, and proportion of children subsequently consuming antibiotics. Of 5,714 references, 23 studies (representing 20 interventions) met inclusion criteria. Materials designed to engage children in addition to parents were effective in modifying parental knowledge and behaviour, resulting in reductions in consulting rates ranging from 13 to 40%. Providing parents with delayed prescriptions significantly decreased reported antibiotic use (Risk Ratio (RR) 0.46 (0.40, 0.54); moreover, a delayed or no prescribing approach did not diminish parental satisfaction. CONCLUSIONS: IN ORDER TO BE MOST EFFECTIVE, INTERVENTIONS TO INFLUENCE PARENTAL CONSULTING AND ANTIBIOTIC USE SHOULD: engage children, occur prior to an illness episode, employ delayed prescribing, and provide guidance on specific symptoms. These results support the wider implementation of interventions to reduce inappropriate antibiotic use in children