Sleep deprivation affects the sensitivity of proactive and reactive action monitoring: A behavioural and ERP analysis

We studied the impact of sleep deprivation on action monitoring. Each participant performed a Simon task after a normal night of sleep and after 26 h of awakening. Reaction time (RT) distributions were analyzed and the sensitivity of the error negativity (Ne/Ne like) to response correctness was examined.     

Potential cross‐reactivity of monoclonal antibodies against clinically relevant mycobacteria

Tuberculosis is a disease caused by the Mycobacterium tuberculosis complex (MTb). In 2011, global mortality due to tuberculosis was 1·4 million individuals. The only available vaccine is the attenuated M. bovis [bacillus Calmette–Guérin (BCG)] strain, which confers variable protection against pulmonary tuberculosis. Some widely distributed non‐tuberculous mycobacteria (NTM), such as M. avium and M. arupense, are also potential pathogens for humans. This work aimed to produce and characterize monoclonal antibodies against the M. bovis BCG Mexico strain of the MTb, M. avium subs. hominissuis and the M. arupense strain from NTM. Hybridomas were produced from splenocytes of BALB/c female mice immunized with radiation‐inactivated mycobacteria, and the immunoglobulin (Ig)G2a antibody‐producing clones with the highest antigenic recognition were selected. The selected clones, Mbv 2A10 for M. bovis BCG Mexico, Mav 3H1 for M. avium and Mar 2D10 for M. arupense, were used in further studies. Enzyme‐linked immunosorbent assay (ELISA) and immune proteomics analyses characterized the clones as having the highest cross‐reactivity with mycobacteria. Using mass spectrometry, a number of proteins recognized by the monoclonal antibody (mAb) clones were identified. These proteins had roles in metabolic processes, hypoxia, cell cycle and dormancy. In addition, a Clustal W and Immune Epitope Database (IEDB) in‐silico analysis was performed in protein sequences that result in the conserved regions within probability epitopes that could be recognized for Mbv2A10 and Mav3H1 clones.     

Insulin-sensitizing effects on muscle and adipose tissue after dietary fiber intake in men and women with metabolic syndrome

Context: Dietary fibers have been associated with a reduced incidence of type 2 diabetes mellitus in epidemiological studies; however, the precise mechanisms are unknown. Objective: The objective of the study was to evaluate the efficacy and site of action of an insoluble dietary fiber derived from maize (HAM-RS2) in improving insulin resistance in subjects at increased risk of type 2 diabetes mellitus. Design: This study was a randomized, controlled crossover, dietary intervention study. Setting: The study was conducted at the Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Participants: Fifteen men and women with insulin resistance participated in the study. Intervention: The intervention included 40 g/d HAM-RS2 compared with a matched placebo for 8 wk. Main Outcome Measures: After each supplement, participants underwent a two-step hyperinsulinemic-euglycemic clamp study with the addition of glucose tracers; a meal tolerance test; arteriovenous sampling across forearm muscle tissue; and a sc adipose tissue biopsy for assessment of gene expression. Results: There was enhanced uptake of glucose into the forearm muscle measured by arteriovenous sampling (65 ± 15% increase after resistant starch; P < 0.001). Adipose tissue function was also affected, with enhanced fatty acid suppression after HAM-RS2 treatment and an increase in gene expression for hormone sensitive lipase (P = 0.005), perilipin (P = 0.011), lipoprotein lipase (P = 0.014), and adipose triglyceride lipase (P = 0.03) in biopsy samples. There was no effect on the insulin sensitivity of hepatic glucose production or plasma lipids after HAM-RS2. Conclusion: HAM-RS2 improved peripheral but not hepatic insulin resistance and requires further study as an intervention in patients with or at risk for type 2 diabetes.     

High-throughput molecular diagnosis of von Willebrand disease by next generation sequencing methods

Genetic analysis of von Willebrand disease by von Willebrand factor gene sequencing has not yet become routine practice. Nevertheless, the prospects for molecular diagnosis have changed dramatically in recent years with the unveiling of next-generation sequencing platforms. With the goal of applying this technology to von Willebrand disease, we designed a strategy for von Willebrand factor gene enrichment and multiplexing based on short polymerase chain reactions. Forty patients were simultaneously analyzed enabling the identification of 43 mutations, including 36 substitutions, 2 intronic splice site mutations, 2 indels, and 3 deletions. By pooling patient genomic DNA before polymerase chain reaction enrichment, indexing samples with barcode tags, and re-sequencing on the next-generation sequencing instrument, at least 350 patients and relatives per run can be simultaneously analyzed in a fast, inexpensive manner. This is one of the first reports in which this technology has been shown to be feasible for large-scale mutation screening by single gene re-sequencing.