A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci

Crohn''s disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2–4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10⁻⁶). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10⁻⁸; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10⁻⁹; OR = 1.16), 8q21.11 (rs12677663, p = 2×10⁻⁸; OR = 1.15), 10q26.3 (rs10734105, p = 3×10⁻⁸; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10⁻⁹; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.     

Brief intervention to prevent hazardous drinking in young people aged 14--15 in a high school setting (SIPS JR-HIGH): study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Whilst the overall proportion of young people drinking alcohol in the United Kingdom has decreased in recent years, those who do drink appear to drink a larger amount, and more frequently. Early and heavy drinking by younger adolescents is a significant public health problem linked to intellectual impairment, increased risk of injuries, mental health issues, unprotected or regretted sexual experience, violence, and sometimes accidental death, which leads to high social and economic costs. This feasibility pilot trial aims to explore the feasibility of delivering brief alcohol intervention in a school setting with adolescents aged 14 and 15 and to examine the acceptability of study measures to school staff, young people and parents.Methods and designSeven schools across one geographical area in the North East of England will be recruited. Schools will be randomly allocated to one of three conditions: provision of an advice leaflet (control condition, n = 2 schools); a 30-minute brief interactive session, which combines structured advice and motivational interviewing techniques delivered by the school learning mentor (level 1 condition, n = 2 schools); and a 60-minute session involving family members delivered by the school learning mentor (level 2 condition, n = 3 schools). Participants will be year 10 school pupils (aged 14 and 15) who screen positively on a single alcohol screening question and who consent to take part in the trial. Year 10 pupils in all seven schools will be followed up at 6 and 12 months. Secondary outcome measures include the ten-question Alcohol-Use Disorders Identification Test. The EQ-5D-Y and a modified short service use questionnaire will inform the health and social resource costs for any future economic evaluation.Young people recruited into the trial will also complete a 28-day timeline follow back questionnaire at 12-month follow-up. A qualitative evaluation (with young people, school staff, learning mentors, and parents) will examine facilitators and barriers to the use of screening and brief intervention approaches in the school setting in this age group.Trial registrationTrial reference number ISRCTN07073105.     

A New Noninvasive Method for Detecting Mammals From Birds' Nests

Abstract: Certain birds use mammal hair for the lining or structural strengthening of their nest. As a result, many bird nests can be regarded as natural hair snares. Preliminary studies indicate that analyses of hairs found in birds' nests are an effective method for detecting and identifying mammals that live in or migrate through an area and could be a useful tool to gain information about rare or hard to detect mammals. I documented 27 mammal taxa that were identified from hair collected from >3,000 nests. This study summarizes the results of 4 projects that represent application of this technique. This noninvasive method appears to be a useful tool for easily accessing basic faunistical data about mammal fauna of the given area.     

Extracellular release of photosynthetic products by freshwater phytoplankton populations, with special reference to the algal species involved

SUMMARY. Over three successive years, depth profiles of C-fixation and excretion, chlorophyll- a concentrations, phytoplankton species composition and bacterial numbers were determined in Lake Vechten, a slightly eutrophic lake in The Netherlands. Special attention was given to the method used to measure extracellular release.
Excretion of dissolved organic ¹⁴C depended largely upon the photo-synthetic activity of the phytoplankton, ranging from 0–2.5 mg m^-1 h^-1, representing a percentage extracellular release (PER) of 0–25%.
During a period in August, however, a subsurface chlorophyll- a maximum at 5–7 m depth coincided with high excretion rates of up to 10 mg Cm^-3 h^-1 (PER = 55%). Phytoplankton analysis revealed a stratification in numbers of Mallomonas caudata with a maximum at 5–7 m depth.
The results suggest that in these water layers bacterial populations grew at the expense of the dissolved organic carbon compounds excreted by Mallomonas caudata. This means that extracellular release can temporarily function as an important nutrient source for the heterotrophie community in addition to the more or less constant dissolved organic carbon pool.     

Studies on Fusarium-Gladiolus Interactions

Using standardized conditions, 65 genotypes of Gladiolus were screened for Fusarium resistance. High levels were found in 'large-flowered" types, Primulinus hybrids, G. callianthus, G. garnierii , and G. dalenii. Some accessions of G. dalenii exhibited no disease symptoms when inoculated with two standard test isolates. No resistance was found in 'small-flowered' types. To estimate race-specifity of the resistance, eight highly resistant Gladiolus genotypes were tested in an in vitro test against 43 isolates of F. oxysporum f.sp. gladioli. Two isolates were able to partially infect the G. dalenii accessions and this was confirmed using whole plants. Implications for resistance breeding are discussed.     

Intersection of endocytic and exocytic systems in Toxoplasma gondii

Host cytosolic proteins are endocytosed by Toxoplasma gondii and degraded in its lysosome‐like compartment, the vacuolar compartment (VAC), but the dynamics and route of endocytic trafficking remain undefined. Conserved endocytic components and plant‐like features suggest T. gondii endocytic trafficking involves transit through early and late endosome‐like compartments (ELCs) and potentially the trans‐Golgi network (TGN) as in plants. However, exocytic trafficking to regulated secretory organelles, micronemes and rhoptries, also proceeds through ELCs and requires classical endocytic components, including a dynamin‐related protein, DrpB. Here, we show that host cytosolic proteins are endocytosed within 7 minutes post‐invasion, trafficked through ELCs en route to the VAC, and degraded within 30 minutes. We could not definitively interpret if ingested protein is trafficked through the TGN. We also found that parasites ingest material from the host cytosol throughout the parasite cell cycle. Ingested host proteins colocalize with immature microneme proteins, proM2AP and proMIC5, in transit to the micronemes, but not with the immature rhoptry protein proRON4, indicating that endocytic trafficking of ingested protein intersects with exocytic trafficking of microneme proteins. Finally, we show that conditional expression of a DrpB dominant negative mutant increases T. gondii ingestion of host‐derived proteins, suggesting that DrpB is not required for parasite endocytosis.