Functional network changes and cognitive control in schizophrenia

Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task. We characterized general and cognitive control-specific effects of schizophrenia on functional connectivity within an expanded frontal parietal network (FPN) and quantified network topology properties using graph analysis. Using the network based statistic (NBS), we observed greater network functional connectivity in cognitive control demanding conditions during both tasks in both groups in the FPN, and demonstrated cognitive control FPN specificity against a task independent auditory network. NBS analyses also revealed widespread connectivity deficits in schizophrenia patients across all tasks. Furthermore, quantitative changes in network topology associated with diagnostic status and task demand were observed. The present findings, in an analysis that was limited to correct trials only, ensuring that subjects are on task, provide critical insights into network connections crucial for cognitive control and the manner in which brain networks reorganize to support such control. Impairments in this mechanism are present in schizophrenia and these results highlight how cognitive control deficits contribute to the pathophysiology of this illness

Impact of a sketch-based tutoring system at multiple universities

Large class sizes in engineering programs often prevent instructors from providing detailed and meaningful feedback to students on their homework problems. While the literature shows that frequent and immediate formative feedback has several benefits in terms of knowledge gain and academic motivation, several instructors struggle to provide any feedback. Motivated by this inability, a sketch-based virtual tutoring system, named Mechanix, has been developed and implemented. Mechanix lets the students to sketch their freebody diagram on a virtual interface and the process involved is very close to using a pencil and paper. The system provides real-time feedback on the accuracy of their Freebody diagrams and the solution to the problem. This paper reports the implementation of Mechanix at two large public universities in the United States - Georgia Institute of Technology and Texas State University. Mechanix is used to solve specific assignments from each school that involve the use of freebody diagrams. Pre- and post- concept inventories are used to measure the improvements in the conceptual understanding of the students. The results show that students who solve their homework using Mechanix outperform their peers who do not in one school, whereas the results are similar across the two groups in the second school. The evaluation of the concept inventories shows that the students who used Mechanix has the same level of improvement in their conceptual knowledge compared to the control group

Genetic structure and admixture in sheep from terminal breeds in the United States

Selection for performance in diverse production settings has resulted in variation across sheep breeds worldwide. Although sheep are an important species to the United States, the current genetic relationship among many terminal sire breeds is not well characterized. Suffolk, Hampshire, Shropshire and Oxford (terminal) and Rambouillet (dual purpose) sheep (n = 248) sampled from different flocks were genotyped using the Applied Biosystems Axiom Ovine Genotyping Array (50K), and additional Shropshire sheep (n = 26) using the Illumina Ovine SNP50 BeadChip. Relationships were investigated by calculating observed heterozygosity, inbreeding coefficients, eigenvalues, pairwise Wright’s FST estimates and an identity by state matrix. The mean observed heterozygosity for each breed ranged from 0.30 to 0.35 and was consistent with data reported in other US and Australian sheep. Suffolk from two different regions of the United States (Midwest and West) clustered separately in eigenvalue plots and the rectangular cladogram. Further, divergence was detected between Suffolk from different regions with Wright’s FST estimate. Shropshire animals showed the greatest divergence from other terminal breeds in this study. Admixture between breeds was examined using ADMIXTURE, and based on cross-validation estimates, the best fit number of populations (clusters) was K = 6. The greatest admixture was observed within Hampshire, Suffolk, and Shropshire breeds. When plotting eigenvalues, US terminal breeds clustered separately in comparison with sheep from other locations of the world. Understanding the genetic relationships between terminal sire breeds in sheep will inform us about the potential applicability of markers derived in one breed to other breeds based on relatedness

Compositional and Mineralogical Effects on Ice Nucleation Activity of Volcanic Ash

Volcanic ash produced during explosive eruptions may serve as ice nuclei in the atmosphere, contributing to the occurrence of volcanic lightning due to tribocharging from ice&ndash;ice or ice&ndash;ash collisions. Here, different ash samples were tested using deposition-mode and immersion-mode ice nucleation experiments. Results show that bulk composition and mineral abundance have no measurable effect on depositional freezing at the temperatures tested, as all samples have similar ice saturation ratios. In the immersion mode, there is a strong positive correlation between K₂O content and ice nucleation site density at &minus;25 &deg;C and a strong negative correlation between MnO and TiO₂ content at temperatures from &minus;35 to &minus;30 &deg;C. The most efficient sample in the immersion mode has the highest surface area, smallest average grain size, highest K₂O content, and lowest MnO content. These results indicate that although ash abundance&mdash;which creates more available surface area for nucleation&mdash;has a significant effect on immersion-mode freezing, composition may also contribute. Consequently, highly explosive eruptions of compositionally evolved magmas create the necessary parameters to promote ice nucleation on grain surfaces, which permits tribocharging due to ice&ndash;ice or ice&ndash;ash collisions, and contribute to the frequent occurrence of volcanic lightning within the eruptive column and plume during these events.</p

TLR2 expression is increased in rosacea and stimulates enhanced serine protease production by keratinocytes.

A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea

Lower Hemoglobin Correlates with Larger Stroke Volumes in Acute Ischemic Stroke

www.karger.com/cee This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only

The Influence of Polygenic Risk Scores on Heritability of Anti-CCP Level in RA

Objective: To study genetic factors that influence quantitative anti-cyclic citrullinated peptide (anti-CCP) antibody levels in RA patients. Methods: We carried out a genome wide association study (GWAS) meta-analysis using 1,975 anti-CCP+ RA patients from 3 large cohorts, the Brigham Rheumatoid Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis Consortium (NARAC), and the Epidemiological Investigation of RA (EIRA). We also carried out a genome-wide complex trait analysis (GCTA) to estimate the heritability of anti-CCP levels. Results: GWAS-meta analysis showed that anti-CCP levels were most strongly associated with the human leukocyte antigen (HLA) region with a p-value of 2×10−11 for rs1980493. There were 112 SNPs in this region that exceeded the genome-wide significance threshold of 5×10−8, and all were in linkage disequilibrium (LD) with the HLA- DRB1*03 allele with LD r2 in the range of 0.25-0.88. Suggestive novel associations outside of the HLA region were also observed for rs8063248 (near the GP2 gene) with a p-value of 3×10−7. None of the known RA risk alleles (~52 loci) were associated with anti-CCP level. Heritability analysis estimated that 44% of anti-CCP variation was attributable to genetic factors captured by GWAS variants. Conclusions: Anti-CCP level is a heritable trait. HLA-DR3 and GP2 are associated with lower anti-CCP levels

Postoperative Intensive Care Unit Requirements After Elective Craniotomy

Objective: Commonly, patients undergoing craniotomy are admitted to an intensive care setting post-operatively to allow for close monitoring. We aim to determine the frequency with which patients who have undergone elective craniotomies require intensive care unit level interventions or experience significant complications during the post-operative period to identify a subset of patients for whom an alternative to ICU level care may be appropriate. Methods: Following Institutional Review Board approval, a prospective, consecutive cohort of adult patients undergoing elective craniotomy was established at the Massachusetts General Hospital between the dates of April 2010 and March 2011. Inclusion criteria were intradural operations requiring craniotomy performed on adults (18 years of age or greater). Exclusion criteria were cases of an urgent or emergent nature, patients who remained intubated post-operatively, and patients who had a ventriculostomy drain in place at the conclusion of the case. Results: 400 patients were analyzed. Univariate analysis revealed that diabetics (p = 0.00047), patients who required intra-operative blood product administration (p = 0.032), older patients (p < 0.0001), patients with higher intra-operative blood losses (p = 0.041), and patients who underwent longer surgical procedures (p = 0.021) were more likely to require ICU-level interventions or experience significant post-operative complications. Multivariate analysis only found diabetes (p = 0.0005) and age (p = 0.0091) to be predictive of a patient’s need for post-operative intensive care unit admission. Conclusions: Diabetes and older age predict the need for ICU-level intervention after elective craniotomy. Properly selected patients may not require post-craniotomy ICU monitoring. Further study of resource utilization is necessary to validate these preliminary findings, particularly in different hospital types

LAB/NTAL Facilitates Fungal/PAMP-induced IL-12 and IFN-γ Production by Repressing β-Catenin Activation in Dendritic Cells.

Fungal pathogens elicit cytokine responses downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled or hemiITAM-containing receptors and TLRs. The Linker for Activation of B cells/Non-T cell Activating Linker (LAB/NTAL) encoded by Lat2, is a known regulator of ITAM-coupled receptors and TLR-associated cytokine responses. Here we demonstrate that LAB is involved in anti-fungal immunity. We show that Lat2−/− mice are more susceptible to C. albicans infection than wild type (WT) mice. Dendritic cells (DCs) express LAB and we show that it is basally phosphorylated by the growth factor M-CSF or following engagement of Dectin-2, but not Dectin-1. Our data revealed a unique mechanism whereby LAB controls basal and fungal/pathogen-associated molecular patterns (PAMP)-induced nuclear β-catenin levels. This in turn is important for controlling fungal/PAMP-induced cytokine production in DCs. C. albicans- and LPS-induced IL-12 and IL-23 production was blunted inLat2−/− DCs. Accordingly, Lat2−/− DCs directed reduced Th1 polarization in vitro and Lat2−/−mice displayed reduced Natural Killer (NK) and T cell-mediated IFN-γ production in vivo/ex vivo. Thus our data define a novel link between LAB and β-catenin nuclear accumulation in DCs that facilitates IFN-γ responses during anti-fungal immunity. In addition, these findings are likely to be relevant to other infectious diseases that require IL-12 family cytokines and an IFN-γ response for pathogen clearance