Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgEbinding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein’s digestibility is not affected by such processing

External Urethral Sphincter Pressure Measurement: An Accurate Method for the Diagnosis of Detrusor External Sphincter Dyssynergia?

Combined pelvic floor electromyography (EMG) and videocystourethrography (VCUG) during urodynamic investigation are the most acceptable and widely agreed methods for diagnosing detrusor external sphincter dyssynergia (DESD). Theoretically, external urethral sphincter pressure (EUSP) measurement would provide enough information for the diagnosis of DESD and could simplify the urodynamic investigation replacing combined pelvic floor EMG and VCUG. Thus, we evaluated the diagnostic accuracy of EUSP measurement for DESD. PATIENTS #ENTITYSTARTX00026;A consecutive series of 72 patients (36 women, 36 men) with neurogenic lower urinary tract dysfunction able to void spontaneously was prospectively evaluated at a single university spinal cord injury center. Diagnosis of DESD using EUSP measurement (index test) versus combined pelvic floor EMG and VCUG (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative.Using EUSP measurement (index test) and combined pelvic floor EMG and VCUR (reference standard), DESD was diagnosed in 10 (14%) and in 41 (57%) patients, respectively. More than half of the patients presented discordant diagnosis between the index test and the reference standard. Among 41 patients with DESD diagnosed by combined pelvic floor EMG and VCUR, EUSP measurement identified only 6 patients. EUSP measurement had a sensitivity of 15% (95% CI 5%-25%), specificity of 87% (95% CI 76%-98%), positive predictive value of 60% (95% CI 30%-90%), and negative predictive value of 56% (95% CI 44%-68%) for the diagnosis of DESD.For diagnosis of DESD, EUSP measurement is inaccurate and cannot replace combined pelvic floor EMG and VCUR

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Targeting the Akt-pathway to improve radiosensitivity in glioblastoma

Glioblastoma multiforme (GMB) is the most malignant and common type of all astrocytic tumors. Current standard of care entails maximum surgical resection of the tumor, followed by radiotherapy and chemotherapy, usually by the alkylating agent Temozolomide (TMZ). Despite this aggressive combination therapy, the survival rate of GBM patients is still low. Deregulation of the phosphatidylinositol 3-kinase (PI3K) / Akt pathway is a frequent occurrence in GBM. Activation of the PI3K-Akt pathway results in disturbance of control of cell growth and cell survival, which contributes to a competitive growth advantage, metastatic competence as well as to therapy resistance. The PI3K-Akt pathway is therefore an attractive therapeutic target in GBM, because it serves as a convergence point for malignant processes and intervention might overcome resistance to chemotherapy and radiation. The present review shows the importance of Akt in GBM and its role in the DNA damage response. Furthermore, an overview is given of specific inhibitors of Akt which are currently being tested in preclinical and in early phase clinical studies

Reliability and factorial validity of a questionnaire to assess organophosphate pesticide exposure to agricultural workers in Maule, Chile

© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. The aim was to evaluate the reliability and validity of a questionnaire to assess organophosphate pesticide (OP) exposure in agricultural workers. We then enrolled a random sample of 114 agricultural workers from the region of Maule, Chile (mean age = 50 years [SD = 12]). An internal consistency analysis (Cronbach’s alpha&gt; 0.70) and a Varimax rotational factorial analysis were applied. The instrument had a high reliability to predict likely occupational pesticide exposures: Cronbach’s alpha = 0.95, the Kaiser–Meyer–Olkin (KMO) measure was 0.90 and the Bartell sphericity test = p &lt; 0.001. Four factors explaining 68% of the variance were extracted. The factors identified were as follows: (1) labor conditions during application of OPs; (2) use of personal protective equipment; (3) workplace conditions related to OP exposure and (4) home conditions related to OP exposure. The questionnaire ha

The allosteric AKT inhibitor MK2206 shows a synergistic interaction with chemotherapy and radiotherapy in glioblastoma spheroid cultures

Glioblastoma multiforme (GBM) is the most common, invasive and deadly primary type of malignant brain tumor. The Phosphatidylinositol-3-Kinase/AKT (PI3K/AKT) pathway is highly active in GBM and has been associated with increased survival and resistance to therapy. The aim of this study is to investigate the effects of AKT inhibition in combination with the current standard of care which consists of irradiation and temozolomide (TMZ) on human malignant glioma cells growing adherent and as multicellular spheroids in vitro. The effects of the allosteric inhibitor MK2206 combined with irradiation and TMZ were assessed on glioma cells growing adherent and as multicellular 3D spheroids. The interaction was studied on proliferation, clonogenic cell survival, cell invasion, -migration and on expression of key proteins in the PI3K-AKT pathway by western blot. A differential effect was found at low- (1 μM) and high dose (10 μM) MK2206. At 1 μM, the inhibitor reduced phosphorylation of Thr308 and Ser473 residues of AKT in both adherent cells and spheroids. Low dose MK2206 delayed spheroid growth and sensitized spheroids to both irradiation and TMZ in a synergistic way (Combination index 5 μM). The data show that a 3D spheroid model show different sensitivity to irradiation when combined with AKT inhibition. Thereby we show that MK2206 has potential synergistic efficacy to the current standard of care for glioma patient