Evaluation of next-generation sequencing software in mapping and assembly

Next-generation high-throughput DNA sequencing technologies have advanced progressively in sequence-based genomic research and novel biological applications with the promise of sequencing DNA at unprecedented speed. These new non-Sanger-based technologies feature several advantages when compared with traditional sequencing methods in terms of higher sequencing speed, lower per run cost and higher accuracy. However, reads from next-generation sequencing (NGS) platforms, such as 454/Roche, ABI/SOLiD and Illumina/Solexa, are usually short, thereby restricting the applications of NGS platforms in genome assembly and annotation. We presented an overview of the challenges that these novel technologies meet and particularly illustrated various bioinformatics attempts on mapping and assembly for problem solving. We then compared the performance of several programs in these two fields, and further provided advices on selecting suitable tools for specific biological applications.published_or_final_versio

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

<p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO_2peak), patient-reported outcomes, and the organ components that govern VO_2peakin post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO_2peakfor aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO_2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO_2peakis becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p

A fibril-specific, conformation-dependent antibody recognizes a subset of Aβ plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain

Beta-amyloid (Aβ) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Aβ have been identified that may be neurotoxic. Aβ oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Aβ deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = −0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Aβ deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Aβ pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought

Interaction between valence of empathy and familiarity: is it difficult to empathize with the positive events of a stranger?

Background: Empathy in humans is thought to have evolved via social interactions caused by the formation of social groups. Considering the role of empathy within a social group, there might be a difference between emotional empathy for strangers and familiar others belonging to the same social group. In this study, we used the global field power (GFP) index to investigate empathic brain activity during observation of a cue indicating either a negative or positive image viewed by a stranger or close friend. Methods: Sixteen healthy participants observed a partner performing an emotional gambling task displayed on a monitor. After the partner\u27s choice-response, a frowning or smiling face symbol was simultaneously presented to the participant\u27s monitor while a negative or positive emotional image was presented to the partner\u27s monitor. All participants observed a control condition (CT) showing a computer trial, a stranger-observation condition (SO) showing the trial of a stranger, and a friend-observation condition (FO) to observe the trial of a close friend. During these observations, participants\u27 event-related potentials (ERPs) were recorded to calculate GFP, and after the task, a subjective assessment of their feelings was measured. Results: Positive emotion was significantly larger under the FO compared to the CT and the SO. Significantly larger negative emotion was found under the SO and FO compared to the CT. In response to a positive cue, significantly larger GFP during 300 to 600 ms was observed under the FO compared to the CT and SO. In response to a negative cue, significantly larger GFP was observed under the FO and SO compared to the CT. A significantly larger GFP under the SO was found in response to only a negative cue. Topographic map analysis suggested that these differences were related to frontal-occipital dynamics. GFP was significantly correlated with empathic trait. Conclusion: These results revealed that familiarity with another person has different effects depending on the valence of empathy. Negative empathy, including the danger perception function, might easily occur even among strangers, whereas positive empathy related to nursing and supporting an inner group does not happen easily with strangers

Effect of Dietary and Supplemental Lycopene on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis

ABSTRACT Cardiovascular disease (CVD) is the leading cause of death globally and the presence of &ge;1 cardiovascular risk factors elevates total risk. Lycopene, a carotenoid with high antioxidant capacity, may be protective. The aim of this systematic review and meta-analyses is to determine the efficacy of consuming dietary and/or supplemental lycopene on cardiovascular risk factors. Using the PRISMA guidelines, 4 databases were systematically searched from inception: Medline, Cinahl, Proquest, and Scopus. Intervention trials assessing dietary or supplemental lycopene on CVD outcomes were included. The Cochrane Risk-of-Bias tool was used to assess the quality of the included papers. Pooled analysis was conducted using outcomes with available data. Forty-three studies were included. Lycopene interventions were highly variable (supplement with or without food, based as tomato juice/paste/raw product, or combined with olive oil), the dose ranged from 1.44 to 75 mg&nbsp;lycopene/d and was not reported in 11 of 43 included studies. Studies reported conflicting findings for the effect of lycopene on cardiovascular risk factors, This was supported by meta-analyses where there were no significant differences between lycopene intervention and control groups for blood pressure and lipids (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides). This was observed for overall groups and in subgroup analyses for individuals with elevated risk factor concentrations at baseline. Lycopene interventions for cardiovascular risk factors were highly variable across studies in both the dosage provided and the mode of delivery (supplement or food based). As such, there are conflicting findings regarding the efficacy of lycopene to improve cardiovascular risk factors. This systematic review was registered with PROSPERO as CRD42018112174.</jats:p