The 16S rRNA sequencing data and metadata generated in this study have been submitted to the NCBI Sequence Read Archive (SRA: http://www.ncbi.nlm.nih.gov/bioproject/381931).

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IntroductionType 2 diabetes (T2D) has reached epidemic proportions in North America. Recent evidence suggests that prebiotics can modulate the gut microbiome, which then plays an important role in regulating lipid metabolism, blood glucose, and insulin sensitivity. As such, prebiotics are appealing potential therapeutic strategies for prediabetes and T2D. The key objectives of this study were to determine the tolerability as well as the glucose and insulin modulating ability of MSPrebiotic® digestion resistant starch (DRS) in healthy mid-age (MID) and elderly (ELD) adults.Materials and methodsThis was a prospective, blinded, placebo-controlled study. Prediabetes and diabetes were among the exclusion factors. ELD (>70 years) and MID (30–50 years) Canadian adults were recruited and, after 2 weeks of consuming placebo, they were randomized to consume 30 g of either MSPrebiotic® or placebo per day for 12 weeks. In total, 42 ELD and 42 MID participants completed the study. Blood samples were collected over the 14-week study and analyzed for glucose, lipid profile, and CRP, lipid particles, TNF-α, IL-10, insulin, and insulin resistance (IR).ResultsAt baseline, the ELD population had a significantly higher percentage (p < 0.01) with elevated glucose and significantly higher TNF-α (p < 0.01) compared to MID adults. MSPrebiotic® DRS was well tolerated in both MID and ELD adults. There was a significant difference over time in blood glucose (p = 0.0301) and insulin levels (p = 0.009), as well as IR (HOMA-IR; p = 0.009) in ELD adults who consumed MSPrebiotic® compared to placebo. No significant changes were found in MID adults.ConclusionOur results suggest that dietary supplementation with prebiotics such as MSPrebiotic® may be part of an effective strategy to reduce IR, a major risk factor for developing T2D, in the ELD.Clinical Trial RegistrationNCT01977183 listed on NIH website: , The metadata generated in this study have been submitted to the NCBI Sequence Read Archive ().

Virtual worlds like Second Life are becoming important tools for, among other activities, socialization, social networking, entertainment, collaboration, and business development. These environments offer information systems researchers a unique opportunity to study how these environments are built and managed by operators, how they are used and misused by users, and the impact that they have on users, communities, organizations, and societies at large. This paper summarizes the discussion of this topic that was presented at the ICIS 2007 panel entitled "Second Life and other Virtual Worlds: A Roadmap for Research." The paper provides an introduction to this topic and offers a roadmap for research on virtual worlds based on insights offered by several academics and practitioners who are actively involved in building, managing, and using virtual worlds.

High-throughput (HT) in vitro methods for measuring protein-DNA binding have become invaluable for characterizing transcription factor (TF) complexes and modeling gene regulation. However, current methods do not utilize endogenous proteins and, therefore, do not quantify the impact of cell-specific post-translational modifications (PTMs) and cooperative cofactors. We introduce the HT nextPBM ( n uclear ext ract p rotein- b inding m icroarray) approach to study DNA binding of native cellular TFs that accounts for PTMs and cell-specific cofactors. We integrate immune-depletion and phosphatase treatment steps into our nextPBM pipeline to characterize the impact of cofactors and phosphorylation on TF binding. We analyze binding of PU.1/SPI1 and IRF8 from human monocytes, delineate DNA-sequence determinants for their cooperativity, and show how PU.1 affinity correlates with enhancer status and the presence of cooperative and collaborative cofactors. We describe how nextPBMs, and our accompanying computational framework, can be used to discover cell-specific cofactors, screen for synthetic cooperative DNA elements, and characterize TF cooperativity.

The type II nuclear receptors (NRs) function as heterodimeric transcription factors with the retinoid X receptor (RXR) to regulate diverse biological processes in response to endogenous ligands and therapeutic drugs. DNA-binding specificity has been proposed as a primary mechanism for NR gene regulatory specificity. Here we use protein-binding microarrays (PBMs) to comprehensively analyze the DNA binding of 12 NR:RXRα dimers. We find more promiscuous NR-DNA binding than has been reported, challenging the view that NR binding specificity is defined by half-site spacing. We show that NRs bind DNA using two distinct modes, explaining widespread NR binding to half-sites in vivo. Finally, we show that the current models of NR specificity better reflect binding-site activity rather than binding-site affinity. Our rich dataset and revised NR binding models provide a framework for understanding NR regulatory specificity and will facilitate more accurate analyses of genomic datasets.

The aim of this study was to evaluate the expression of CC chemokine receptor 7 (CCR7) in squamous cell cancer of the tonsil with respect to patterns of spread, relapse-free, overall and disease-specific survival. Eighty-four patients with squamous cell cancer of the tonsil were identified. There was a male predominance of 3 : 1 and the median age at diagnosis was 53 (range 35 -86) years. The median duration of follow-up was 33 (range 2 -124) months. There was a significant association between CCR7 immunopositivity and synchronous cervical nodal metastasis in patients with tonsillar cancer (Spearman's correlation coefficient 0.564; Po0.001). Relapse-free (P ¼ 0.0175), overall (P ¼ 0.0136) and disease-specific (P ¼ 0.0062) survival rates were significantly lower in patients whose tumours expressed high levels of CCR7. On multivariate analysis, high-level CCR7 staining predicted relapse-free (hazard ratio 3.0, 95% confidence intervals 1.1 -8.0, P ¼ 0.026) and disease-specific (hazard ratio 10.2, 95% confidence intervals 2.1 -48.6, P ¼ 0.004) survival. Fifteen percent of patients with the highest level of tumour CCR7 immunopositivity relapsed with systemic metastases. These data demonstrated that CCR7 expression was associated with cervical nodal and systemic metastases from tonsillar cancers. High levels of CCR7 expression predicted a poor prognosis.