Project description:Tuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared, at two timepoints, the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. The immune response was assessed using the TruCulture system with a Null stimulation. samples were tested by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC MS/MS) for a total of 696 metabolites.
Project description:We report for the first time movement of Correia Repeat Enclosed Elements, through inversion of the element at its chromosomal location. Analysis of Ion Torrent generated genome sequence data from Neisseria gonorrhoeae strain NCCP11945 passaged for 8 weeks in the laboratory under standard conditions and stress conditions revealed a total of 37 inversions: 24 were exclusively seen in the stressed sample; 7 in the control sample; and the remaining 3 were seen in both samples. These inversions have the capability to alter gene expression in N. gonorrhoeae through the previously determined activities of the sequence features of these elements. In addition, the locations of predicted non-coding RNAs were investigated to identify potential associations with CREE. Associations varied between strains, as did the number of each element identified. The analysis indicates a role for CREE in disrupting ancestral regulatory networks, including non-coding RNAs. RNA-Seq was used to examine expression changes related to Correia repeats in the strain
Project description:We describe a novel experiment that we conducted with the Drug Interaction Knowledge-base (DIKB) to determine which combinations of evidence enable a rule-based theory of metabolic drug-drug interactions to make the most optimal set of predictions. The focus of the experiment was a group of 16 drugs including six members of the HMG-CoA-reductase inhibitor family (statins). The experiment helped identify evidence-use strategies that enabled the DIKB to predict significantly more interactions present in a validation set than the most rigorous strategy developed by drug experts with no loss of accuracy. The best-performing strategies included evidence types that would normally be of lesser predictive value but that are often more accessible than more rigorous types. Our experimental methods represent a new approach to leveraging the available scientific evidence within a domain where important evidence is often missing or of questionable value for supporting important assertions.
Project description:BACKGROUND:Nordic walking is an attractive method of endurance training. Nevertheless, the biomechanic response due to the additional contribution of using poles in relation to free walking training has been less explored in the elderly. PURPOSE:This randomized parallel controlled trial aimed to assess the effects of 8 weeks of Nordic walking and free walking training on the walking economy, mechanical work, metabolically optimal speed, and electromyographic activation in elderly. METHODS:Thirty-three sedentary elderly were randomized into Nordic walking (n = 16) and free walking group (n = 17) with equalized loads. Submaximal walking tests were performed from 1 to 5 km h-1 on the treadmill. RESULTS:Walking economy was improved in both free and Nordic walking groups (x2 4.91, p = 0.014) and the metabolically optimal speed was increased by approximately 0.5 km h-1 changing the speed-cost profile. The electromyographic activation in lower and upper limbs, pendular recovery, and total, external, and internal mechanical work remained unchanged (p > 0.05). Interestingly, the internal mechanical work associated with arm movement was higher in the Nordic walking group than in the free walking group after training, while the co-contraction from upper limb muscles was reduced similarly to both groups. CONCLUSIONS:Eight weeks of Nordic walking training effectively improved the walking economy and functionality as well as maintained the gait mechanics, similar to free walking training in elderly people. This enhancement in the metabolic economy may have been mediated by a reduction in the co-contraction from upper limb muscles. TRIAL REGISTRATION:ClinicalTrails.gov NCT03096964.
Project description:External secretions play a vital role in external immune defense. However, the functions and components of these exudates are largely unknown in the red palm weevil, Rhynchophorus ferrugineus (Olivier) (Coleoptera: Curculionidae). In order to determine their role in external immunity, the immunosuppressive efficacy of the secretions in vitro against microbes, including bacteria and fungi, was clarified. In the present study, we found that these secretions had antimicrobial activity in vitro, implying external immunizing potency against pathogens. Surprisingly, all liquid phases of secretions could not significantly inhibit the growth of microbes in vitro compared to solid phases. To explain this phenomenon, the composition and emission differentia of secretions from the exocrine glands associated with different developmental stages, secretory regions, and phases were identified and analyzed based on metabonomics techniques. A total of more than 200 compounds, including quinines, phenols, aldehydes, acids, alcohols, saccharides, ketones, esters, amines, salts, ureas, and heterocycles, were identified in the secretions of larvae and adults. The liquid phase shared a number of metabolites with the solid phase, but the emission types and amounts were significantly different in the two phases, resulting in differences in external immunological activity. Tyrosine and p-benzoquinone were the dominant metabolites in all of the secretions, accounting for approximately 11.29% of emissions, with the portion in the solid phase being generally higher than that in the liquid phase. Moreover, only p-benzoquinone was entirely significantly upregulated in the solid phase compared to the liquid phase. Therefore, metabolome analysis suggested that p-benzoquinone, which may potentially be developed to be a valuable marker for determining external immunity, was considered to be the main substance responsible for external immune functions. This hypothesis was further demonstrated by the antimicrobial activity of p-benzoquinone.
Project description:Changes in cellular metabolism contribute to the development and progression of tumors, and can render tumors vulnerable to interventions. However, studies of human cancer metabolism remain limited due to technical challenges of detecting and quantifying small molecules, the highly interconnected nature of metabolic pathways, and the lack of designated tools to analyze and integrate metabolomics with other âomics data. Our study generates the largest comprehensive metabolomics dataset on a single cancer type, and provides a significant advance in integration of metabolomics with sequencing data. Our results highlight the massive re-organization of cellular metabolism as tumors progress and acquire more aggressive features. The results of our work are made available through an interactive public data portal for cancer research community. 10 RNA samples from human ccRCC tumors analyzed from the high glutathione cluster
Project description:Cardiovascular mortality has remained high in patients on peritoneal dialysis (PD) due to the high prevalence of various cardiovascular complications including coronary artery disease, left ventricular hypertrophy and dysfunction, heart failure, arrhythmia (especially atrial fibrillation), cerebrovascular disease, and peripheral arterial disease. In addition, nearly a quarter of PD patients develop sudden cardiac death as the terminal life event. Thus, it is essential to identify effective treatment that may lower cardiovascular mortality and improve survival of PD patients. The International Society for Peritoneal Dialysis (ISPD) commissioned a global workgroup in 2012 to formulate a series of recommendation statements regarding lifestyle modification, assessment and management of various cardiovascular risk factors, and management of the various cardiovascular complications to be published in 2 guideline documents. This publication forms the second part of the guideline documents and includes recommendation statements on the management of various cardiovascular complications in adult chronic PD patients. The documents are intended to serve as a global clinical practice guideline for clinicians who look after PD patients. We also define areas where evidence is clearly deficient and make suggestions for future research in each specific area.