The defining DNA methylation signature of Floating-Harbor Syndrome

Floating-Harbor syndrome (FHS) is an autosomal dominant genetic condition characterized by short stature, delayed osseous maturation, expressive language impairment, and unique facial dysmorphology. We previously identified mutations in the chromatin remodeling protein SRCAP (SNF2-related CBP Activator Protein) as the cause of FHS. SRCAP has multiple roles in chromatin and transcriptional regulation; however, specific epigenetic consequences of SRCAP mutations remain to be described. Using high resolution genome-wide DNA methylation analysis, we identified a unique and highly specific DNA methylation epi-signature in the peripheral blood of individuals with FHS. Both hyper and hypomethylated loci are distributed across the genome, preferentially occurring in CpG islands. Clonal bisulfite sequencing of two hypermethylated (FIGN and STPG2) and two hypomethylated (MYO1F and RASIP1) genes confirmed these findings. The identification of a unique methylation signature in FHS provides further insight into the biological function of SRCAP and provides a unique biomarker for this disorder

Expenditure, Coping, and Academic Behaviors Among Food-Insecure College Students at 10 Higher Education Institutes in the Appalachian and Southeastern Regions

Background A number of studies have measured college student food insecurity prevalence higher than the national average; however, no multicampus regional study among students at 4-y institutions has been undertaken in the Appalachian and Southeast regions of the United States. Objectives The aims of this study were to determine the prevalence of food insecurity among college students in the Appalachian and Southeastern regions of the United States, and to determine the association between food-insecurity status and money expenditures, coping strategies, and academic performance among a regional sample of college students. Methods This regional, cross-sectional, online survey study included 13,642 college students at 10 public universities. Food-insecurity status was measured through the use of the USDA Adult Food Security Survey. The outcomes were associations between food insecurity and behaviors determined with the use of the money expenditure scale (MES), the coping strategy scale (CSS), and the academic progress scale (APS). A forward-selection logistic regression model was used with all variables significant from individual Pearson chi-square and Wilcoxon analyses. The significance criterion α for all tests was 0.05. Results The prevalence of food insecurity at the universities ranged from 22.4% to 51.8% with an average prevalence of 30.5% for the full sample. From the forward-selection logistic regression model, MES (OR: 1.47; 95% CI: 1.40, 1.55), CSS (OR: 1.19; 95% CI: 1.18, 1.21), and APS (OR: 0.95; 95% CI: 0.91, 0.99) scores remained significant predictors of food insecurity. Grade point average, academic year, health, race/ethnicity, financial aid, cooking frequency, and health insurance also remained significant predictors of food security status. Conclusions Food insecurity prevalence was higher than the national average. Food-insecure college students were more likely to display high money expenditures and exhibit coping behaviors, and to have poor academic performance

Expenditure, Coping, and Academic Behaviors Among Food-Insecure College Students at 10 Higher Education Institutes in the Appalachian and Southeastern Regions

Background A number of studies have measured college student food insecurity prevalence higher than the national average; however, no multicampus regional study among students at 4-y institutions has been undertaken in the Appalachian and Southeast regions of the United States. Objectives The aims of this study were to determine the prevalence of food insecurity among college students in the Appalachian and Southeastern regions of the United States, and to determine the association between food-insecurity status and money expenditures, coping strategies, and academic performance among a regional sample of college students. Methods This regional, cross-sectional, online survey study included 13,642 college students at 10 public universities. Food-insecurity status was measured through the use of the USDA Adult Food Security Survey. The outcomes were associations between food insecurity and behaviors determined with the use of the money expenditure scale (MES), the coping strategy scale (CSS), and the academic progress scale (APS). A forward-selection logistic regression model was used with all variables significant from individual Pearson chi-square and Wilcoxon analyses. The significance criterion α for all tests was 0.05. Results The prevalence of food insecurity at the universities ranged from 22.4% to 51.8% with an average prevalence of 30.5% for the full sample. From the forward-selection logistic regression model, MES (OR: 1.47; 95% CI: 1.40, 1.55), CSS (OR: 1.19; 95% CI: 1.18, 1.21), and APS (OR: 0.95; 95% CI: 0.91, 0.99) scores remained significant predictors of food insecurity. Grade point average, academic year, health, race/ethnicity, financial aid, cooking frequency, and health insurance also remained significant predictors of food security status. Conclusions Food insecurity prevalence was higher than the national average. Food-insecure college students were more likely to display high money expenditures and exhibit coping behaviors, and to have poor academic performance

College student sleep quality and mental and physical health are associated with food insecurity in a multi-campus study

Objective: To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students. Design: An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health. Setting: Twenty-two higher education institutions. Participants: College students (n 17 686) enrolled at one of twenty-two participating universities. Results: Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P \u3c 0·0001) and reported more days with poor mental (P \u3c 0·0001) and physical (P \u3c 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P \u3c 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04). Conclusions: College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes

Trans European decomposition index study in arable soils with different crop species diversity using 13C-labelled litter

Póster presentado en la Sessión 8 en el Joint European Stable Isotope Users group Meeting JESIUM 2022 Kuopio, Finland Online 10–14 October 2022.Mixed species systems are currently increasing in area in Europe providing opportunities for sustainable intensification of agriculture. The agroforestry systems cover about 9% of the utilized agricultural area and integrated crop livestock systems occupy a major place in the European agricultural area including perennial forage grasses and grasslands sown with varying degrees of duration. Intercropping and other mixed cash crop systems are currently less developed in the EU. The EU EJP-SOIL funded MIXROOT-C project (2021-2024) is gaining a management-oriented understanding of the effect of mixed-species root systems on carbon flow and organic matter accumulation in European agricultural soils.N

BAFopathies\u27 DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin-Siris and Nicolaides-Baraitser syndromes.

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening

New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes.

Notch signaling is an evolutionary conserved pathway that is mediated by cell-cell contact. It is involved in a variety of developmental processes and has an essential role in vascular development and angiogenesis. Delta-like 4 (Dll4) is a Notch ligand that is up-regulated during angiogenesis. It is expressed in endothelial cells and regulates the differentiation between tip cells and stalk cells of neovasculature. Here, we present evidence that Dll4 is incorporated into endothelial exosomes. It can also be incorporated into the exosomes of tumor cells that overexpress Dll4. These exosomes can transfer the Dll4 protein to other endothelial cells and incorporate it into their cell membrane, which results in an inhibition of Notch signaling and a loss of Notch receptor. Transfer of Dll4 was also shown in vivo from tumor cells to host endothelium. Addition of Dll4 exosomes confers a tip cell phenotype on the endothelial cell, which results in a high Dll4/Notch-receptor ratio, low Notch signaling, and filopodia formation. This was further evidenced by increased branching in a tube-formation assay and in vivo. This reversal in phenotype appears to enhance vessel formation and is a new form of signaling for Notch ligands that expands their signaling potential beyond cell-cell contact

Hybrid Models Identified a 12-Gene Signature for Lung Cancer Prognosis and Chemoresponse Prediction

Lung cancer remains the leading cause of cancer-related deaths worldwide. The recurrence rate ranges from 35-50% among early stage non-small cell lung cancer patients. To date, there is no fully-validated and clinically applied prognostic gene signature for personalized treatment.From genome-wide mRNA expression profiles generated on 256 lung adenocarcinoma patients, a 12-gene signature was identified using combinatorial gene selection methods, and a risk score algorithm was developed with Naïve Bayes. The 12-gene model generates significant patient stratification in the training cohort HLM & UM (n = 256; log-rank P = 6.96e-7) and two independent validation sets, MSK (n = 104; log-rank P = 9.88e-4) and DFCI (n = 82; log-rank P = 2.57e-4), using Kaplan-Meier analyses. This gene signature also stratifies stage I and IB lung adenocarcinoma patients into two distinct survival groups (log-rank P<0.04). The 12-gene risk score is more significant (hazard ratio = 4.19, 95% CI: [2.08, 8.46]) than other commonly used clinical factors except tumor stage (III vs. I) in multivariate Cox analyses. The 12-gene model is more accurate than previously published lung cancer gene signatures on the same datasets. Furthermore, this signature accurately predicts chemoresistance/chemosensitivity to Cisplatin, Carboplatin, Paclitaxel, Etoposide, Erlotinib, and Gefitinib in NCI-60 cancer cell lines (P<0.017). The identified 12 genes exhibit curated interactions with major lung cancer signaling hallmarks in functional pathway analysis. The expression patterns of the signature genes have been confirmed in RT-PCR analyses of independent tumor samples.The results demonstrate the clinical utility of the identified gene signature in prognostic categorization. With this 12-gene risk score algorithm, early stage patients at high risk for tumor recurrence could be identified for adjuvant chemotherapy; whereas stage I and II patients at low risk could be spared the toxic side effects of chemotherapeutic drugs

The Stakes in Bayh-Dole: Public Values Beyond the Pace of Innovation

Evaluation studies of the Bayh-Dole Act are generally concerned with the pace of innovation or the transgressions to the independence of research. While these concerns are important, I propose here to expand the range of public values considered in assessing Bayh-Dole and formulating future reforms. To this end, I first examine the changes in the terms of the Bayh-Dole debate and the drift in its design. Neoliberal ideas have had a definitive influence on U.S. innovation policy for the last thirty years, including legislation to strengthen patent protection. Moreover, the neoliberal policy agenda is articulated and justified in the interest of “competitiveness.” Rhetorically, this agenda equates competitiveness with economic growth and this with the public interest. Against that backdrop, I use Public Value Failure criteria to show that values such as political equality, transparency, and fairness in the distribution of the benefits of innovation, are worth considering to counter the “policy drift” of Bayh-Dole

The developmental trajectory of attentional orienting to socio-biological cues.

It has been proposed that the orienting of attention in the same direction as another’s point of gaze relies on innate brain mechanisms which are present from birth, but direct evidence relating to the influence of eye gaze cues on attentional orienting in young children is limited. In two experiments, 137 children aged 3–10 years old performed an adapted pro-saccade task with centrally presented uninformative eye gaze, finger pointing and arrow pre-cues which were either congruent or incongruent with the direction of target presentations. When the central cue overlapped with presentation of the peripheral target (Experiment 1), children up to 5 years old had difficulty disengaging fixation from central fixation in order to saccade to the target. This effect was found to be particularly marked for eye gaze cues. When central cues were extinguished simultaneously with peripheral target onset (Experiment 2), this effect was greatly reduced. In both experiments finger pointing cues (image of pointing index finger presented at fixation) exerted a strong influence on saccade reaction time to the peripheral stimulus for the youngest group of children (<5 years). Overall the results suggest that although young children are strongly engaged by centrally presented eye gaze cues, the directional influence of such cues on overt attentional orienting is only present in older children, meaning that the effect is unlikely to be dependent upon an innate brain module. Instead, the results are consistent with the existence of stimulus–response associations which develop with age and environmental experience