Gene regulation knowledge commons: community action takes care of DNA binding transcription factors

A large gap remains between the amount of knowledge in scientific literature and the fraction that gets curated into standardized databases, despite many curation initiatives. Yet the availability of comprehensive knowledge in databases is crucial for exploiting existing background knowledge, both for designing follow-up experiments and for interpreting new experimental data. Structured resources also underpin the computational integration and modeling of regulatory pathways, which further aids our understanding of regulatory dynamics. We argue how cooperation between the scientific community and professional curators can increase the capacity of capturing precise knowledge from literature. We demonstrate this with a project in which we mobilize biological domain experts who curate large amounts of DNA binding transcription factors, and show that they, although new to the field of curation, can make valuable contributions by harvesting reported knowledge from scientific papers. Such community curation can enhance the scientific epistemic process.Database URL: http://www.tfcheckpoint.org

Idiotypic DNA vaccination for the treatment of multiple myeloma: safety and immunogenicity in a phase I clinical study

We report on the safety and immunogenicity of idiotypic DNA vaccination in a phase I, non-randomised, open-label study in patients with multiple myeloma. The study used DNA fusion gene vaccines encoding patient-specific single chain variable fragment, or idiotype (Id), linked to fragment C (FrC) of tetanus toxin. Patients in complete or partial response following high-dose chemotherapy and autologous stem cell transplant were vaccinated intramuscularly with 1 mg DNA on six occasions, beginning at least 6 months post-transplant; follow-up was to week 52. Fourteen patients were enrolled on study and completed vaccinations. Idiotypic DNA vaccines were well tolerated with vaccine-related adverse events limited to low-grade constitutional symptoms. FrC- and Id-specific T-cell responses were detected by ex vivo ELISPOT in 9/14 and 3/14 patients, respectively. A boost of pre-existing anti-FrC antibody (Ab) was detected by ELISA in 8/14 patients, whilst anti-Id Ab was generated in 1/13 patients. Overall, four patients (29 %) made an immune response to FrC and Id, with six patients (43 %) responding to FrC alone. Over the 52-week study period, serum paraprotein was undetectable, decreased or remained stable for ten patients (71 %), whilst ongoing CR/PR was maintained for 11 patients (79 %). The median time to progression was 38.0 months for 13/14 patients. Overall survival was 64 % after a median follow-up of 85.6 months

Urinary MicroRNA Profiling in the Nephropathy of Type 1 Diabetes

Background: Patients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease. Methods and Findings: We studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease. Conclusions: Urinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes. © 2013 Argyropoulos et al

Low back pain status in elite and semi-elite Australian football codes: a cross-sectional survey of football (soccer), Australian rules, rugby league, rugby union and non-athletic controls

<p>Abstract</p> <p>Background</p> <p>Our understanding of the effects of football code participation on low back pain (LBP) is limited. It is unclear whether LBP is more prevalent in athletic populations or differs between levels of competition. Thus it was the aim of this study to document and compare the prevalence, intensity, quality and frequency of LBP between elite and semi-elite male Australian football code participants and a non-athletic group.</p> <p>Methods</p> <p>A cross-sectional survey of elite and semi-elite male Australian football code participants and a non-athletic group was performed. Participants completed a self-reported questionnaire incorporating the Quadruple Visual Analogue Scale (QVAS) and McGill Pain Questionnaire (short form) (MPQ-SF), along with additional questions adapted from an Australian epidemiological study. Respondents were 271 elite players (mean age 23.3, range 17–39), 360 semi-elite players (mean age 23.8, range 16–46) and 148 non-athletic controls (mean age 23.9, range 18–39).</p> <p>Results</p> <p>Groups were matched for age (p = 0.42) and experienced the same age of first onset LBP (p = 0.40). A significant linear increase in LBP from the non-athletic group, to the semi-elite and elite groups for the QVAS and the MPQ-SF was evident (p < 0.001). Elite subjects were more likely to experience more frequent (daily or weekly OR 1.77, 95% CI 1.29–2.42) and severe LBP (discomforting and greater OR 1.75, 95% CI 1.29–2.38).</p> <p>Conclusion</p> <p>Foolers in Australia have significantly more severe and frequent LBP than a non-athletic group and this escalates with level of competition.</p

Progression to microalbuminuria in type 1 diabetes: development and validation of a prediction rule

AIMS/HYPOTHESIS: Microalbuminuria is common in type 1 diabetes and is associated with an increased risk of renal and cardiovascular disease. We aimed to develop and validate a clinical prediction rule that estimates the absolute risk of microalbuminuria. METHODS: Data from the European Diabetes Prospective Complications Study (n = 1115) were used to develop the prediction rule (development set). Multivariable logistic regression analysis was used to assess the association between potential predictors and progression to microalbuminuria within 7 years. The performance of the prediction rule was assessed with calibration and discrimination (concordance statistic [c-statistic]) measures. The rule was validated in three other diabetes studies (Pittsburgh Epidemiology of Diabetes Complications [EDC] study, Finnish Diabetic Nephropathy [FinnDiane] study and Coronary Artery Calcification in Type 1 Diabetes [CACTI] study). RESULTS: Of patients in the development set, 13% were microalbuminuric after 7 years. Glycosylated haemoglobin, AER, WHR, BMI and ever smoking were found to be the most important predictors. A high-risk group (n = 87 [8%]) was identified with a risk of progression to microalbuminuria of 32%. Predictions showed reasonable discriminative ability, with c-statistic of 0.71. The rule showed good calibration and discrimination in EDC, FinnDiane and CACTI (c-statistic 0.71, 0.79 and 0.79, respectively). CONCLUSIONS/INTERPRETATION: We developed and validated a clinical prediction rule that uses relatively easily obtainable patient characteristics to predict microalbuminuria in patients with type 1 diabetes. This rule can help clinicians to decide on more frequent check-ups for patients at high risk of microalbuminuria in order to prevent long-term chronic complication

The IMEx coronavirus interactome: an evolving map of Coronaviridae-host molecular interactions

The current coronavirus disease of 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions can provide fine-grained resolution of the mechanisms behind the virus biology and the human organism response. We present a curated dataset of physical molecular interactions focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family that has been manually extracted by International Molecular Exchange (IMEx) Consortium curators. Currently, the dataset comprises over 4400 binarized interactions extracted from 151 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (https://www.ebi.ac.uk/intact) and will be continuously updated as research on COVID-19 progresses

Effect of different standing poses on whole body volume acquisition by three-dimensional photonic scanning

The present study compared whole body volumes obtained by three-dimensional (3D) photonic scanning of two different poses and discussed its effect on body composition estimation. Pose A with large angles of shoulder abduction and feet separated and Pose B with shoulders abducted slightly, the elbows extended and heels together. 16 male and 13 female participants were scanned twice in each pose using a 3D scanner. The mean of whole body volume and the mean of body composition obtained with Pose B was corrected by a regression equation and compared with the results obtained from Pose A. After correction, the whole body volumes acquired with these two poses were similar [limit of agreement = (-0.71 l,0.71 l)] but the body compositions obtained with Pose A and Pose B were different [limit of agreement = (-4.4%, 4.4%)]. The results indicated that scanning using either pose gives reliable estimations for whole body volume and body composition. The whole body volume obtained from different poses can be adjusted using the regression equation but small volumetric differences translate into much more substantial differences in body fat percentage. Hence, it is recommended to use the same scanning pose consistently when monitoring individuals longitudinally

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

IntAct—open source resource for molecular interaction data

IntAct is an open source database and software suite for modeling, storing and analyzing molecular interaction data. The data available in the database originates entirely from published literature and is manually annotated by expert biologists to a high level of detail, including experimental methods, conditions and interacting domains. The database features over 126 000 binary interactions extracted from over 2100 scientific publications and makes extensive use of controlled vocabularies. The web site provides tools allowing users to search, visualize and download data from the repository. IntAct supports and encourages local installations as well as direct data submission and curation collaborations. IntAct source code and data are freely available from