Extensive microbial and functional diversity within the chicken cecal microbiome

Chickens are major source of food and protein worldwide. Feed conversion and the health of chickens relies on the largely unexplored complex microbial community that inhabits the chicken gut, including the ceca. We have carried out deep microbial community profiling of the microbiota in twenty cecal samples via 16S rRNA gene sequences and an in-depth metagenomics analysis of a single cecal microbiota. We recovered 699 phylotypes, over half of which appear to represent previously unknown species. We obtained 648,251 environmental gene tags (EGTs), the majority of which represent new species. These were binned into over two-dozen draft genomes, which included Campylobacter jejuni and Helicobacter pullorum. We found numerous polysaccharide- and oligosaccharide-degrading enzymes encoding within the metagenome, some of which appeared to be part of polysaccharide utilization systems with genetic evidence for the co-ordination of polysaccharide degradation with sugar transport and utilization. The cecal metagenome encodes several fermentation pathways leading to the production of short-chain fatty acids, including some with novel features. We found a dozen uptake hydrogenases encoded in the metagenome and speculate that these provide major hydrogen sinks within this microbial community and might explain the high abundance of several genera within this microbiome, including Campylobacter, Helicobacter and Megamonas

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

Neighbourhood ethnic density effects on behavioural and cognitive problems among young racial/ethnic minority children in the US and England: a cross-national comparison

Studies on adult racial/ethnic minority populations show that the increased concentration of racial/ethnic minorities in a neighbourhood—a so-called ethnic density effect—is associated with improved health of racial/ethnic minority residents when adjusting for area deprivation. However, this literature has focused mainly on adult populations, individual racial/ethnic groups, and single countries, with no studies focusing on children of different racial/ethnic groups or comparing across nations. This study aims to compare neighbourhood ethnic density effects on young children’s cognitive and behavioural outcomes in the US and in England. We used data from two nationally representative birth cohort studies, the US Early Childhood Longitudinal Study-Birth Cohort and the UK Millennium Cohort Study, to estimate the association between own ethnic density and behavioural and cognitive development at 5 years of age. Findings show substantial heterogeneity in ethnic density effects on child outcomes within and between the two countries, suggesting that ethnic density effects may reflect the wider social and economic context. We argue that researchers should take area deprivation into account when estimating ethnic density effects and when developing policy initiatives targeted at strengthening and improving the health and development of racial and ethnic minority children

The association between levels of alcohol consumption and mental health problems and academic performance among young university students

Purpose: Mental health problems and harmful alcohol consumption have been found to be high among young university students compared to the general population in Australia. This research aimed to investigate the association between levels of drinking and mental health problems and academic performance among university students aged 18 to 24 years. Methods: This study used a quantitative cross-sectional design using data that were collected in 2014 as part of the Youth Alcohol Project (YAP). Participants were randomly drawn from a cross sectional sample of 6000 undergraduate students. Included in the study were only students who were within the age of 18-24, undergraduate, and internally enrolled at the main campus. A total of 2518 undergraduate students aged 18 to 24 years who were enrolled internally at Curtin University Bentley campus were randomly recruited. Data were collected through an online survey. Students were invited to participate in the study through their student email address. The email invitations coincided with the release of semester results to increase the likelihood of students accessing their emails. A further 628 students were randomly recruited through face to face intercept survey during the campus market days. Data were collected by trained research assistants. Validated instruments were used to collected data on levels of alcohol consumption, mental health, and academic performance. Results: A considerable proportion of participants (44%) reported consuming alcohol at hazardous or harmful levels. Multiple logistic regression analysis showed that students who were consuming alcohol at hazardous levels were 1.2 times more likely to report psychological distress than those with lower levels of alcohol consumption (aOR 1.2, 95% CI: 1.1-1.5). In addition, being late for class (aOR 1.7, 95% CI:1.1-2.4), missing classes (aOR = 2.6, 95% CI: 1.9-2.6), inability to concentrate in class (aOR = 2.6, 95% CI: 1.9-3.4), and inability to complete assignments (aOR = 3.5, 95% CI 2.0-6.0) independently predicted for moderate or hazardous alcohol consumption. Conclusion: The study shows that a considerable proportion of undergraduate students at university consume alcohol at hazardous or harmful levels. In addition, high levels of alcohol consumption are associated with poor academic performance and mental health outcomes among students. The results of the study warrant multi-strategy interventions that focus on policy, organisational, educational, environmental and economic strategies that will help to reduce alcohol related harms among university students

Urban-rural disparities in smoking behaviour in Germany

BACKGROUND: It is currently not clear whether individuals living in metropolitan areas differ from individuals living in rural and urban areas with respect to smoking behaviours. Therefore, we sought to explore the relation between residential area and smoking behaviours in Germany. METHODS: We used a nationwide German census representative for the general population of Germany. A number of 181,324 subjects aged 10 years or older were included. Information on the average daily usage of cigarettes that have or had been smoked formerly or currently was available in subjects who have ever smoked. A daily consumption of more than 20 cigarettes was considered heavy smoking. Logistic regression analyses were performed sex-stratified and adjusted for relevant confounders. RESULTS: Analyses revealed inhabitants of metropolitan areas to be more likely current smokers than inhabitants of rural areas (odds ratio 1.56, 95%-confidence interval 1.51; 1.62). Among current and former smokers those who lived in urban communities had also increased odds for being heavy smokers than those who lived in rural communities. CONCLUSION: We conclude that living in an urban and particularly living in a metropolitan area is a determinant of both smoking and severity of current smoking. Tobacco control programs should recognize the difference in living conditions between rural and urban areas

Surgical clipping is still a good choice for the treatment of paraclinoid aneurysms

ABSTRACT Paraclinoid aneurysms are lesions located adjacent to the clinoid and ophthalmic segments of the internal carotid artery. In recent years, flow diverter stents have been introduced as a better endovascular technique for treatment of these aneurysms. Method From 2009 to 2014, a total of 43 paraclinoid aneurysms in 43 patients were surgically clipped. We retrospectively reviewed the records of these patients to analyze clinical outcomes. Results Twenty-six aneurysms (60.5%) were ophthalmic artery aneurysms, while 17 were superior hypophyseal artery aneurysms (39.5%). The extradural approach to the clinoid process was used to clip these aneurysms. One hundred percent of aneurysms were clipped (complete exclusion in 100% on follow-up angiography). The length of follow-up ranged from 1 to 60 months (mean, 29.82 months). Conclusion Surgical clipping continues to be a good option for the treatment of paraclinoid aneurysms

Inter-Allelic Prion Propagation Reveals Conformational Relationships among a Multitude of [PSI] Strains

Immense diversity of prion strains is observed, but its underlying mechanism is less clear. Three [PSI] prion strains—named VH, VK, and VL—were previously isolated in the wild-type yeast genetic background. Here we report the generation and characterization of eight new [PSI] isolates, obtained by propagating the wild-type strains with Sup35 proteins containing single amino-acid alterations. The VH strain splits into two distinct strains when propagated in each of the three genetic backgrounds, harboring respectively single mutations of N21L, R28P, and Gi47 (i.e. insertion of a glycine residue at position 47) on the Sup35 N-terminal prion-forming segment. The six new strains exhibit complex inter-conversion patterns, and one of them continuously mutates into another. However, when they are introduced back into the wild-type background, all 6 strains revert to the VH strain. We obtain two more [PSI] isolates by propagating VK and VL with the Gi47 and N21L backgrounds, respectively. The two isolates do not transmit to other mutant backgrounds but revert to their parental strains in the wild-type background. Our data indicate that a large number of [PSI] strains can be built on three basic Sup35 amyloid structures. It is proposed that the three basic structures differ by chain folding topologies, and sub-strains with the same topology differ in distinct ways by local structural adjustments. This “large number of variations on a small number of basic themes” may also be operative in generating strain diversities in other prion elements. It thus suggests a possible general scheme to classify a multitude of prion strains

Enhanced Immunogenicity, Mortality Protection, and Reduced Viral Brain Invasion by Alum Adjuvant with an H5N1 Split-Virion Vaccine in the Ferret

Pre-pandemic development of an inactivated, split-virion avian influenza vaccine is challenged by the lack of pre-existing immunity and the reduced immunogenicity of some H5 hemagglutinins compared to that of seasonal influenza vaccines. Identification of an acceptable effective adjuvant is needed to improve immunogenicity of a split-virion avian influenza vaccine.No serum antibodies were detected after vaccination with unadjuvanted vaccine, whereas alum-adjuvanted vaccination induced a robust antibody response. Survival after unadjuvanted dose regimens of 30 µg, 7.5 µg and 1.9 µg (21-day intervals) was 64%, 43%, and 43%, respectively, yet survivors experienced weight loss, fever and thrombocytopenia. Survival after unadjuvanted dose regimen of 22.5 µg (28-day intervals) was 0%, suggesting important differences in intervals in this model. In contrast to unadjuvanted survivors, either dose of alum-adjuvanted vaccine resulted in 93% survival with minimal morbidity and without fever or weight loss. The rarity of brain inflammation in alum-adjuvanted survivors, compared to high levels in unadjuvanted vaccine survivors, suggested that improved protection associated with the alum adjuvant was due to markedly reduced early viral invasion of the ferret brain.Alum adjuvant significantly improves efficacy of an H5N1 split-virion vaccine in the ferret model as measured by immunogenicity, mortality, morbidity, and brain invasion

Bifunctional Anti-Huntingtin Proteasome-Directed Intrabodies Mediate Efficient Degradation of Mutant Huntingtin Exon 1 Protein Fragments

Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide (CAG)n repeat expansion in the coding sequence of the huntingtin gene, and an expanded polyglutamine (>37Q) tract in the protein. This results in misfolding and accumulation of huntingtin protein (htt), formation of neuronal intranuclear and cytoplasmic inclusions, and neuronal dysfunction/degeneration. Single-chain Fv antibodies (scFvs), expressed as intrabodies that bind htt and prevent aggregation, show promise as immunotherapeutics for HD. Intrastriatal delivery of anti-N-terminal htt scFv-C4 using an adeno-associated virus vector (AAV2/1) significantly reduces the size and number of aggregates in HDR6/1 transgenic mice; however, this protective effect diminishes with age and time after injection. We therefore explored enhancing intrabody efficacy via fusions to heterologous functional domains. Proteins containing a PEST motif are often targeted for proteasomal degradation and generally have a short half life. In ST14A cells, fusion of the C-terminal PEST region of mouse ornithine decarboxylase (mODC) to scFv-C4 reduces htt exon 1 protein fragments with 72 glutamine repeats (httex1-72Q) by ∼80–90% when compared to scFv-C4 alone. Proteasomal targeting was verified by either scrambling the mODC-PEST motif, or via proteasomal inhibition with epoxomicin. For these constructs, the proteasomal degradation of the scFv intrabody proteins themselves was reduced<25% by the addition of the mODC-PEST motif, with or without antigens. The remaining intrabody levels were amply sufficient to target N-terminal httex1-72Q protein fragment turnover. Critically, scFv-C4-PEST prevents aggregation and toxicity of httex1-72Q fragments at significantly lower doses than scFv-C4. Fusion of the mODC-PEST motif to intrabodies is a valuable general approach to specifically target toxic antigens to the proteasome for degradation

The Evolutionary Pathway to Obligate Scavenging in Gyps Vultures

The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group is a likely strategy for foraging Gyps vultures. Using a spatial, individual-based, optimisation model we find that the communal roost is critical for establishing the information network that enables information transfer owing to the spatial-concentration of foragers close to the roost. There is also strong selection pressure for grouping behaviour owing to the importance of maintaining network integrity and hence information transfer during foraging. We present a simple mechanism for grouping, common in many animal species, which has the added implication that it negates the requirement for roost-centric information transfer. The formation of a flotilla-like foraging group also improves foraging efficiency through the reduction of overlapping search paths. Finally, we highlight the importance of consideration of information transfer mechanisms in order to maximise the success of vulture reintroduction programmes