MicroRNAs (miRNA), small noncoding RNA molecules, may regulate protein synthesis, while resistance exercise training (RT) is an efficient strategy for stimulating muscle protein synthesis in vivo. ...However, RT increases muscle mass, with a very wide range of effectiveness in humans. We therefore determined the expression level of 21 abundant miRNAs to determine whether variation in these miRNAs was able to explain the variation in RT-induced gains in muscle mass. Vastus lateralis biopsies were obtained from the top and bottom ∼20% of responders from 56 young men who undertook a 5 day/wk RT program for 12 wk. Training-induced muscle mass gain was determined by dual-energy X-ray absorptiometry, and fiber size was evaluated by histochemistry. The expression level of each miRNA was quantified using TaqMan-based quantitative PCR, with the analysis carried out in a blinded manner. Gene ontology and target gene profiling were used to predict the potential biological implications. Of the 21 mature miRNAs examined, 17 were stable during RT in both groups. However, miR-378, miR-29a, miR-26a, and miR-451 were differentially expressed between low and high responders. miR-378, miR-29a, and miR-26a were downregulated in low responders and unchanged in high responders, while miR-451 was upregulated only in low responders. Interestingly, the training-induced change in miR-378 abundance was positively correlated with muscle mass gains in vivo. Gene ontology analysis of the target gene list of miR-378, miR-29a, miR-26a, and miR-451, from the weighted cumulative context ranking methodology, indicated that miRNA changes in the low responders may be compensatory, reflecting a failure to "activate" growth and remodeling genes. We report, for the first time, that RT-induced hypertrophy in human skeletal muscle is associated with selected changes in miRNA abundance. Our analysis indicates that miRNAs may play a role in the phenotypic change and pronounced intergroup variation in the RT response.
The MINOS experiment took data from 2005 up until 2012. The MINOS experiment took data from 2005 up until 2012, continuing beyond that as the MINOS+ experiment. The experiment is a two-detector, ...on-axis, long-baseline experiment, sending neutrinos from Fermilab to the Soudan Underground Laboratory in northern Minnesota. By searching for the deficit of muon neutrinos at the Far Detector, MINOS/MINOS+ is sensitive to the atmospheric neutrino oscillation parameters Δm322 and θ23. By using the full MINOS data set looking at both νμ disappearance and νe appearance in both neutrino and antineutrino configurations at the NuMI beam along with atmospheric neutrino data recorded at the FD, MINOS has made the most precise measurement of Δm322. Using a full three-flavour framework and searching for νe appearance, MINOS/MINOS+ gains sensitivity to θ13, the mass hierarchy, and the octant of θ23. Exotic phenomenon is also explored with the MINOS detectors looking for nonstandard interactions and sterile neutrinos. The current MINOS+ era goals are to build on the previous MINOS results improving the precision on the three-flavour oscillation parameter measurements and strengthening the constraints placed on the sterile neutrino parameter space.
A low maximal oxygen consumption (VO2max) is a strong risk factor for premature mortality. Supervised endurance exercise training increases VO2max with a very wide range of effectiveness in humans. ...Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts VO2max training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous VO2max response. Two independent preintervention RNA expression data sets were generated (n=41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in VO2max ("predictor" genes). The HERITAGE Family Study (n=473) was used for genotyping. We discovered a 29-RNA signature that predicted VO2max training response on a continuous scale; these genes contained approximately 6 new single-nucleotide polymorphisms associated with gains in VO2max in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., "reciprocal" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in VO2max, corresponding to approximately 50% of the estimated genetic variance for VO2max. In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. VO2max responses to endurance training can be predicted by measuring a approximately 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
Even though the production of 3D printed foams has already been widely studied, the main focus of the reports has been on their mechanical properties or their cushion behavior. In the present work a ...preliminary approach is made concerning the potential application of 3D printed PU foams for thermal applications with enhanced mechanical properties. For that propose, cork was used to enhance the properties of the resulting 3D printed composite foams. From the results obtained, it was observed that the addition of cork decreased the density and thermal conductivity of the ensuing foams. The stiffness of the ensuing composites was also reduced. Yet, the use of cork did not affect the thermal stability of the composites. Finally, the layer-to-layer bonding was evaluated and the results suggest that the addition of cork may not jeopardize the performance of the 3D printed PU foams. Besides their thermal insulation properties, the elastomeric behavior of the 3D printed foams produced may find applications that combine thermal insulation with damping properties. Furthermore, advances in the 3D printing technology may increase the range of applications of these foams.
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•Polyurethane foams were produced using 3D printing technology.•Cork was used to enhance the properties of the 3D printed composite foams.•The 3D printed foams have potential to be used in applications beyond thermal insulation.
Coercive control is defined as the systematic use of demands, threats, and surveillance behaviors to gain control over an individual. Content validity appears to be an issue for existing measures of ...coercive control tactics, as they do not assess all of these behaviors. This study investigated the validity and reliability of the Demand, Threat, Surveillance, and Response to Demands subscales of the Coercion in Intimate Partner Relationships (CIPR) scale. Participants (N = 541) completed online measures of coercive control, physical intimate partner violence, depression, and posttraumatic stress disorder symptomatology. Confirmatory factor analyses, linear regressions, and correlational analyses investigated the construct (i.e., concurrent, convergent, and discriminant) validity of the CIPR subscales. Internal consistency of the subscales and test–retest reliability were also examined. Results provided support for the validity and reliability of the CIPR. Implications and usage of the CIPR in research and practice are discussed. We report how we determined our sample size, all data exclusions, all manipulations, and all measures in the study.
Electrical pulses have been used to enhance uptake of molecules into living cells for decades. This technique, often referred to as electroporation, has become an increasingly popular method to ...enhance in vivo DNA delivery for both gene therapy applications as well as for delivery of vaccines against both infectious diseases and cancer. In vivo electrovaccination (gene delivery followed by electroporation) is currently being investigated in several clinical trials, including DNA delivery to healthy volunteers. However, the mode of action at molecular level is not yet fully understood.
This study investigates intradermal DNA electrovaccination in detail and describes the effects on expression of the vaccine antigen, plasmid persistence and the local tissue environment. Gene profiling of the vaccination site showed that the combination of DNA and electroporation induced a significant up-regulation of pro-inflammatory genes. In vivo imaging of luciferase activity after electrovaccination demonstrated a rapid onset (minutes) and a long duration (months) of transgene expression. However, when the more immunogenic prostate specific antigen (PSA) was co-administered, PSA-specific T cells were induced and concurrently the luciferase expression became undetectable. Electroporation did not affect the long-term persistence of the PSA-expressing plasmid.
This study provides important insights to how DNA delivery by intradermal electrovaccination affects the local immunological responses of the skin, transgene expression and clearance of the plasmid. As the described vaccination approach is currently being evaluated in clinical trials, the data provided will be of high significance.
The circadian cycle allows organisms to track external time of day and predict/respond to changes in the external environment. In higher order organisms, circadian rhythmicity is a central feature of ...innate and adaptive immunity. We focus on the role of the molecular clock and circadian rhythmicity specifically in monocytes and macrophages of the innate immune system. These cells display rhythmicity in their internal functions, such as metabolism and inflammatory mediator production as well as their external functions in pathogen sensing, phagocytosis, and migration. These inflammatory mediators are of clinical interest as many are therapeutic targets in inflammatory disease such as cardiovascular disease, diabetes, and rheumatoid arthritis. Moreover, circadian rhythm disruption is closely linked with increased prevalence of these conditions. Therefore, understanding the mechanisms by which circadian disruption affects monocyte/macrophage function will provide insights into novel therapeutic opportunities for these chronic inflammatory diseases.
Single-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed ...SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.
Regular physical activity (PA) can reduce the risk of developing type 2 diabetes, but adherence to time-orientated (150 min week
or more) PA guidelines is very poor. A practical and time-efficient PA ...regime that was equally efficacious at controlling risk factors for cardio-metabolic disease is one solution to this problem. Herein, we evaluate a new time-efficient and genuinely practical high-intensity interval training (HIT) protocol in men and women with pre-existing risk factors for type 2 diabetes.
One hundred eighty-nine sedentary women (
= 101) and men (
= 88) with impaired glucose tolerance and/or a body mass index >27 kg m
mean (range) age: 36 (18-53) years participated in this multi-center study. Each completed a fully supervised 6-week HIT protocol at work-loads equivalent to ~100 or ~125% Formula: see text. Change in Formula: see text was used to monitor protocol efficacy, while Actiheart™ monitors were used to determine PA during four, weeklong, periods. Mean arterial (blood) pressure (MAP) and fasting insulin resistance homeostatic model assessment (HOMA)-IR represent key health biomarker outcomes.
The higher intensity bouts (~125% Formula: see text) used during a 5-by-1 min HIT protocol resulted in a robust increase in Formula: see text (136 participants, +10.0%,
< 0.001; large size effect). 5-by-1 HIT reduced MAP (~3%;
< 0.001) and HOMA-IR (~16%;
< 0.01). Physiological responses were similar in men and women while a sizeable proportion of the training-induced changes in Formula: see text, MAP, and HOMA-IR was retained 3 weeks after cessation of training. The supervised HIT sessions accounted for the entire quantifiable increase in PA, and this equated to 400 metabolic equivalent (MET) min week
. Meta-analysis indicated that 5-by-1 HIT matched the efficacy and variability of a time-consuming 30-week PA program on Formula: see text, MAP, and HOMA-IR.
With a total time-commitment of <15 min per session and reliance on a practical ergometer protocol, 5-by-1 HIT offers a new solution to modulate cardio-metabolic risk factors in adults with pre-existing risk factors for type 2 diabetes while approximately meeting the MET min week
PA guidelines. Long-term randomized controlled studies will be required to quantify the ability for 5-by-1 HIT to reduce the incidence of type 2 diabetes, while strategies are required to harmonize the adaptations to exercise across individuals.
Traditional high volume aerobic exercise training reduces cardiovascular and metabolic disease risk but involves a substantial time commitment. Extremely low volume high-intensity interval training ...(HIT) has recently been demonstrated to produce improvements to aerobic function, but it is unknown whether HIT has the capacity to improve insulin action and hence glycemic control.
Sixteen young men (age: 21 +/- 2 y; BMI: 23.7 +/- 3.1 kg x m-2; VO2peak: 48 +/- 9 ml x kg-1 x min-1) performed 2 weeks of supervised HIT comprising of a total of 15 min of exercise (6 sessions; 4-6 x 30-s cycle sprints per session). Aerobic performance (250-kJ self-paced cycling time trial), and glucose, insulin and NEFA responses to a 75-g oral glucose load (oral glucose tolerance test; OGTT) were determined before and after training.
Following 2 weeks of HIT, the area under the plasma glucose, insulin and NEFA concentration-time curves were all reduced (12%, 37%, 26% respectively, all P < 0.001). Fasting plasma insulin and glucose concentrations remained unchanged, but there was a tendency for reduced fasting plasma NEFA concentrations post-training (pre: 350 +/- 36 v post: 290 +/- 39 micromol x l-1, P = 0.058). Insulin sensitivity, as measured by the Cederholm index, was improved by 23% (P < 0.01), while aerobic cycling performance improved by approximately 6% (P < 0.01).
The efficacy of a high intensity exercise protocol, involving only ~250 kcal of work each week, to substantially improve insulin action in young sedentary subjects is remarkable. This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes.
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