Large Sample Size,Wide Variant Spectrum,and Advanced Machine-Learning Technique Boost Risk Prediction for Inflammatory Bowel Disease

We performed risk assessment for Crohn’s disease (CD) and ulcerative colitis (UC), the two common forms of inflammatory bowel disease (IBD), by using data from the International IBD Genetics Consortium’s Immunochip project. This data set contains ∼17,000 CD cases, ∼13,000 UC cases, and ∼22,000 controls from 15 European countries typed on the Immunochip. This custom chip provides a more comprehensive catalog of the most promising candidate variants by picking up the remaining common variants and certain rare variants that were missed in the first generation of GWAS. Given this unprecedented large sample size and wide variant spectrum, we employed the most recent machine-learning techniques to build optimal predictive models. Our final predictive models achieved areas under the curve (AUCs) of 0.86 and 0.83 for CD and UC, respectively, in an independent evaluation. To our knowledge, this is the best prediction performance ever reported for CD and UC to date.     

Soil microbial community structure and functionality changes in response to long-term metal and radionuclide pollution

Microbial communities are essential for a healthy soil ecosystem. Metals and radionuclides can exert a persistent pressure on the soil microbial community. However, little is known on the effect of long-term co-contamination of metals and radionuclides on the microbial community structure and functionality. We investigated the impact of historical discharges of the phosphate and nuclear industry on the microbial community in the Grote Nete river basin in Belgium. Eight locations were sampled along a transect to the river edge and one location further in the field. Chemical analysis demonstrated a metal and radionuclide contamination gradient and revealed a distinct clustering of the locations based on all metadata. Moreover, a relation between the chemical parameters and the bacterial community structure was demonstrated. Although no difference in biomass was observed between locations, cultivation-dependent experiments showed that communities from contaminated locations survived better on singular metals than communities from control locations. Furthermore, nitrification, a key soil ecosystem process seemed affected in contaminated locations when combining metadata with microbial profiling. These results indicate that long-term metal and radionuclide pollution impacts the microbial community structure and functionality and provides important fundamental insights into microbial community dynamics in co-metal-radionuclide contaminated sites.     

HDAC6 inhibition restores TDP‐43 pathology and axonal transport defects in human motor neurons with TARDBP mutations

TDP‐43 is the major component of pathological inclusions in most ALS patients and in up to 50% of patients with frontotemporal dementia (FTD). Heterozygous missense mutations in TARDBP, the gene encoding TDP‐43, are one of the common causes of familial ALS. In this study, we investigate TDP‐43 protein behavior in induced pluripotent stem cell (iPSC)‐derived motor neurons from three ALS patients with different TARDBP mutations, three healthy controls and an isogenic control. TARDPB mutations induce several TDP‐43 changes in spinal motor neurons, including cytoplasmic mislocalization and accumulation of insoluble TDP‐43, C‐terminal fragments, and phospho‐TDP‐43. By generating iPSC lines with allele‐specific tagging of TDP‐43, we find that mutant TDP‐43 initiates the observed disease phenotypes and has an altered interactome as indicated by mass spectrometry. Our findings also indicate that TDP‐43 proteinopathy results in a defect in mitochondrial transport. Lastly, we show that pharmacological inhibition of histone deacetylase 6 (HDAC6) restores the observed TDP‐43 pathologies and the axonal mitochondrial motility, suggesting that HDAC6 inhibition may be an interesting therapeutic target for neurodegenerative disorders linked to TDP‐43 pathology.     

Emotion Socialization and Ethnicity: An Examination of Practices and Outcomes in African American,Asian American,and Latin American Families

The current review paper summarizes the literature on parental emotion socialization in ethnically diverse families in the United States. Models of emotion socialization have been primarily developed using samples of European American parents and children. As such, current categorizations of “adaptive” and “maladaptive” emotion socialization practices may not be applicable to individuals from different ethnic backgrounds. The review examines current models of emotion socialization, with particular attention paid to the demographic breakdown of the studies used to develop these models. Additionally, the review highlights studies examining emotion socialization practices in African American, Asian American, and Latin American families. The review is synthesized with summarizing themes of similarities and differences across ethnic groups, and implications for culturally sensitive research and practice are discussed.