Web-Based Randomized Controlled Trial

Background: Patients often seek other patients’ experiences with the disease. The Internet provides a wide range of opportunities to share and learn about other people’s health and illness experiences via blogs or patient-initiated online discussion groups. There also exists a range of medical information devices that include experiential patient information. However, there are serious concerns about the use of such experiential information because narratives of others may be powerful and pervasive tools that may hinder informed decision making. The international research network DIPEx (Database of Individual Patients’ Experiences) aims to provide scientifically based online information on people’s experiences with health and illness to fulfill patients’ needs for experiential information, while ensuring that the presented information includes a wide variety of possible experiences. Objective: The aim is to evaluate the colorectal cancer module of the German DIPEx website krankheitserfahrungen.de with regard to self-efficacy for coping with cancer and patient competence. Methods: In 2015, a Web-based randomized controlled trial was conducted using a two-group between-subjects design and repeated measures. The study sample consisted of individuals who had been diagnosed with colorectal cancer within the past 3 years or who had metastasis or recurrent disease. Outcome measures included self-efficacy for coping with cancer and patient competence. Participants were randomly assigned to either an intervention group that had immediate access to the colorectal cancer module for 2 weeks or to a waiting list control group. Outcome criteria were measured at baseline before randomization and at 2 weeks and 6 weeks Results: The study randomized 212 persons. On average, participants were 54 (SD 11.1) years old, 58.8% (124/211) were female, and 73.6% (156/212) had read or heard stories of other patients online before entering the study, thus excluding any influence of the colorectal cancer module on krankheitserfahrungen.de. No intervention effects were found at 2 and 6 weeks after baseline. Conclusions: The results of this study do not support the hypothesis that the website studied may increase self-efficacy for coping with cancer or patient competencies such as self-regulation or managing emotional distress. Possible explanations may involve characteristics of the website itself, its use by participants, or methodological reasons. Future studies aimed at evaluating potential effects of websites providing patient experiences on the basis of methodological principles such as those of DIPEx might profit from extending the range of outcome measures, from including additional measures of website usage behavior and users’ motivation, and from expanding concepts, such as patient competency to include items that more directly reflect patients’ perceived effects of using such a website. Trial Registration: Clinicaltrials.gov NCT02157454; https://clinicaltrials.gov/ct2/show/NCT02157454 (Archived by WebCite at http://www.webcitation.org/6syrvwXxi

High glucose disrupts oligosaccharide recognition function via competitive inhibition : a potential mechanism for immune dysregulation in diabetes mellitus

Diabetic complications include infection and cardiovascular disease. Within the immune system, host-pathogen and regulatory host-host interactions operate through binding of oligosaccharides by C-type lectin. A number of C-type lectins recognise oligosaccharides rich in mannose and fucose – sugars with similar structures to glucose. This raises the possibility that high glucose conditions in diabetes affect protein-oligosaccharide interactions via competitive inhibition. Mannose binding lectin, soluble DC-SIGN & DC-SIGNR, and surfactant protein D, were tested for carbohydrate binding in the presence of glucose concentrations typical of diabetes, via surface plasmon resonance and affinity chromatography. Complement activation assays were performed in high glucose. DC-SIGN and DC-SIGNR expression in adipose tissues was examined via immunohistochemistry. High glucose inhibited C-type lectin binding to high-mannose glycoprotein and binding of DC-SIGN to fucosylated ligand (blood group B) was abrogated in high glucose. Complement activation via the lectin pathway was inhibited in high glucose and also in high trehalose - a nonreducing sugar with glucoside stereochemistry. DC-SIGN staining was seen on cells with DC morphology within omental and subcutaneous adipose tissues. We conclude that high glucose disrupts C-type lectin function, potentially illuminating new perspectives on susceptibility to infectious and inflammatory disease in diabetes. Mechanisms involve competitive inhibition of carbohydrate-binding within sets of defined proteins, in contrast to broadly indiscriminate, irreversible glycation of proteins

Genome-wide analysis demonstrates conserved localization of messenger RNAs to mitotic microtubules

RNA localization is of critical importance in many fundamental cell biological and developmental processes by regulating the spatial control of gene expression. To investigate how spindle-localized RNAs might influence mitosis, we comprehensively surveyed all messenger RNAs (mRNAs) that bound to microtubules during metaphase in both Xenopus laevis egg extracts and mitotic human cell extracts. We identify conserved classes of mRNAs that are enriched on microtubules in both human and X. laevis. Active mitotic translation occurs on X. laevis meiotic spindles, and a subset of microtubule-bound mRNAs (MT-mRNAs) associate with polyribosomes. Although many MT-mRNAs associate with polyribosomes, we find that active translation is not required for mRNA localization to mitotic microtubules. Our results represent the first genome-wide survey of mRNAs localized to a specific cytoskeletal component and suggest that microtubule localization of specific mRNAs is likely to function in mitotic regulation and mRNA segregation during cell division

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation.United States. National Institutes of Health (R00HL112962)United States. National Institutes of Health (R01 HL57900)Oregon Health & Science University. Knight Cancer Institute (2015-Dive-Knight-01

Anatomy and phylogenetic relationships of Temnodontosaurus zetlandicus (Reptilia: Ichthyosauria)

peer reviewedParvipelvia is a major clade of ichthyosaurians that diversified during the Triassic-Jurassic transition. The interrelationships of early parvipelvians remain unclear and many genera are loosely diagnosed, such as Temnodontosaurus, an ecologically important genus from the Early Jurassic of Western Europe. One taxon concentrates many taxonomic issues: ‘Ichthyosaurus’ acutirostris was previously assigned to Temnodontosaurus and for which ‘Ichthyosaurus’ zetlandicus represents a junior synonym. We redescribe the holotype of ‘Ichthyosaurus’ zetlandicus (CAMSM J35176) and a new specimen probably attributable to this taxon (MNHNL TU885) from the Toarcian of Luxembourg. We find that Temnodontosaurus zetlandicus comb. nov. is a valid species that should be referred to the genus Temnodontosaurus, sharing a number of traits with Temnodontosaurus nuertingensis and Temnodontosaurus trigonodon, despite having a distinct cranial architecture. Our phylogenetic analyses under both implied weighting maximum parsimony and Bayesian inference recover T. zetlandicus as closely related to several species currently assigned to Temnodontosaurus. Species included in Temnodontosaurus form a polyphyletic yet well-clustered group among basal neoichthyosaurians, demonstrating that the monophyly of this genus needs to be thoroughly investigated

A Review of the Scientific Rigor, Reproducibility, and Transparency Studies Conducted by the ABRF Research Groups.

Shared research resource facilities, also known as core laboratories (Cores), are responsible for generating a significant and growing portion of the research data in academic biomedical research institutions. Cores represent a central repository for institutional knowledge management, with deep expertise in the strengths and limitations of technology and its applications. They inherently support transparency and scientific reproducibility by protecting against cognitive bias in research design and data analysis, and thedy have institutional responsibility for the conduct of research (research ethics, regulatory compliance, and financial accountability) performed in their Cores. The Association of Biomolecular Resource Facilities (ABRF) is a FASEB-member scientific society whose members are scientists and administrators that manage or support Cores. The ABRF Research Groups (RGs), representing expertise for an array of cutting-edge and established technology platforms, perform multicenter research studies to determine and communicate best practices and community-based standards. This review provides a summary of the contributions of the ABRF RGs to promote scientific rigor and reproducibility in Cores from the published literature, ABRF meetings, and ABRF RGs communications

Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 Å resolution and two structures of HP HA at 2.95 and 3.10 Å resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species

FoxO and Stress Responses in the Cnidarian Hydra vulgaris

Background: In the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms. Methods/Principal Findings: We have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases. Conclusions: These findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians an