High intensity interval training in a real world setting: A randomized controlled feasibility study in overweight inactive adults, measuring change in maximal oxygen uptake

Background In research clinic settings, overweight adults undertaking HIIT (high intensity interval training) improve their fitness as effectively as those undertaking conventional walking programs but can do so within a shorter time spent exercising. We undertook a randomized controlled feasibility (pilot) study aimed at extending HIIT into a real world setting by recruiting overweight/obese, inactive adults into a group based activity program, held in a community park. Methods Participants were allocated into one of three groups. The two interventions, aerobic interval training and maximal volitional interval training, were compared with an active control group undertaking walking based exercise. Supervised group sessions (36 per intervention) were held outdoors. Cardiorespiratory fitness was measured using VO2max (maximal oxygen uptake, results expressed in ml/min/kg), before and after the 12 week interventions. Results On ITT (intention to treat) analyses, baseline (N = 49) and exit (N = 39) O2 was 25.3±4.5 and 25.3±3.9, respectively. Participant allocation and baseline/exit VO2max by group was as follows: Aerobic interval training N =  16, 24.2±4.8/25.6±4.8; maximal volitional interval training N = 16, 25.0±2.8/25.2±3.4; walking N = 17, 26.5±5.3/25.2±3.6. The post intervention change in VO2max was +1.01 in the aerobic interval training, −0.06 in the maximal volitional interval training and −1.03 in the walking subgroups. The aerobic interval training subgroup increased VO2max compared to walking (p = 0.03). The actual (observed, rather than prescribed) time spent exercising (minutes per week, ITT analysis) was 74 for aerobic interval training, 45 for maximal volitional interval training and 116 for walking (p =  0.001). On descriptive analysis, the walking subgroup had the fewest adverse events. Conclusions In contrast to earlier studies, the improvement in cardiorespiratory fitness in a cohort of overweight/obese participants undertaking aerobic interval training in a real world setting was modest. The most likely reason for this finding relates to reduced adherence to the exercise program, when moving beyond the research clinic setting

Comparison of observed and model-computed low frequency circulation and hydrography on the New England Shelf

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): C09015, doi:10.1029/2007JC004394.The finite volume coastal ocean model (FVCOM) is configured to study the interannual variability of circulation in the Gulf of Maine (GoM) and Georges Bank. The FVCOM-GoM system incorporates realistic time-dependent surface forcing derived from a high-resolution mesoscale meteorological model (MM5) and assimilation of observed quantities including sea surface temperature and salinity and temperature fields on the open boundary. An evaluation of FVCOM-GoM model skill on the New England shelf is made by comparison of computed fields and data collected during the Coastal Mixing and Optics (CMO) Program (August 1996–June 1997). Model mean currents for the full CMO period compare well in both magnitude and direction in fall and winter but overpredict the westward flow in spring. The direction and ellipticity of the subtidal variability correspond but computed magnitudes are around 20% below observed, partially due to underprediction of the variability by MM5. Response of subtidal currents to wind-forcing shows the model captures the directional dependence, as well as seasonal variability of the lag. Hydrographic results show that FVCOM-GoM resolves the spatial and temporal evolution of the temperature and salinity fields. The model-computed surface salinity field compares well, except in May when there is no indication of the fresh surface layer from the Connecticut River discharge noted in the observations. Analysis of model-computed results indicates that the plume was unable to extend to the mooring location due to the presence of a westward mean model-computed flow during that time that was stronger than observed. Overall FVCOM-GoM captures well the dynamics of the mean and subtidal flow on the New England shelf.G. Cowles was supported by the Massachusetts Marine Fisheries Institute (MFI) through NOAA grants DOC/NOAA/ NA04NMF4720332 and DOC/NOAA/NA05NMF4721131, S. Lentz by the NSF Ocean Sciences Division through grants OCE-841292 and OCE- 848961, C. Chen and Q. Xu through the NSF/NOAA GLOBEC/Northwest Atlantic/Georges Bank Program under NSF grants OCE-0234545 and OCE-0227679 and NOAA grants NA-16OP2323, and R. Beardsley through NOAA grant NA-17RJ1223

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Advances in the Direct Study of Carbon Burning in Massive Stars

The C12+C12 fusion reaction plays a critical role in the evolution of massive stars and also strongly impacts various explosive astrophysical scenarios. The presence of resonances in this reaction at energies around and below the Coulomb barrier makes it impossible to carry out a simple extrapolation down to the Gamow window-the energy regime relevant to carbon burning in massive stars. The C12+C12 system forms a unique laboratory for challenging the contemporary picture of deep sub-barrier fusion (possible sub-barrier hindrance) and its interplay with nuclear structure (sub-barrier resonances). Here, we show that direct measurements of the C12+C12 fusion cross section may be made into the Gamow window using an advanced particle-gamma coincidence technique. The sensitivity of this technique effectively removes ambiguities in existing measurements made with gamma ray or charged-particle detection alone. The present cross-section data span over 8 orders of magnitude and support the fusion-hindrance model at deep sub-barrier energies

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

Distinct Functions of Period2 and Period3 in the Mouse Circadian System Revealed by In Vitro Analysis

The mammalian circadian system, which is composed of a master pacemaker in the suprachiasmatic nuclei (SCN) as well as other oscillators in the brain and peripheral tissues, controls daily rhythms of behavior and physiology. Lesions of the SCN abolish circadian rhythms of locomotor activity and transplants of fetal SCN tissue restore rhythmic behavior with the periodicity of the donor's genotype, suggesting that the SCN determines the period of the circadian behavioral rhythm. According to the model of timekeeping in the SCN, the Period (Per) genes are important elements of the transcriptional/translational feedback loops that generate the endogenous circadian rhythm. Previous studies have investigated the functions of the Per genes by examining locomotor activity in mice lacking functional PERIOD proteins. Variable behavioral phenotypes were observed depending on the line and genetic background of the mice. In the current study we assessed both wheel-running activity and Per1-promoter-driven luciferase expression (Per1-luc) in cultured SCN, pituitary, and lung explants from Per2−/− and Per3−/− mice congenic with the C57BL/6J strain. We found that the Per2−/− phenotype is enhanced in vitro compared to in vivo, such that the period of Per1-luc expression in Per2−/− SCN explants is 1.5 hours shorter than in Per2+/+ SCN, while the free-running period of wheel-running activity is only 11 minutes shorter in Per2−/− compared to Per2+/+ mice. In contrast, circadian rhythms in SCN explants from Per3−/− mice do not differ from Per3+/+ mice. Instead, the period and phase of Per1-luc expression are significantly altered in Per3−/− pituitary and lung explants compared to Per3+/+ mice. Taken together these data suggest that the function of each Per gene may differ between tissues. Per2 appears to be important for period determination in the SCN, while Per3 participates in timekeeping in the pituitary and lung

Substrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site

γ-Secretase generates the peptides of Alzheimer's disease, Aβ40 and Aβ42, by cleaving the amyloid precursor protein within its transmembrane domain. γ-Secretase also cleaves numerous other substrates, raising concerns about γ-secretase inhibitor off-target effects. Another important class of drugs, γ-secretase modulators, alter the cleavage site of γ-secretase on amyloid precursor protein, changing the Aβ42/Aβ40 ratio, and are thus a promising therapeutic approach for Alzheimer's disease. However, the target for γ-secretase modulators is uncertain, with some data suggesting that they function on γ-secretase, whereas others support their binding to the amyloid precursor. In this paper we address this controversy by using a fluorescence resonance energy transfer-based assay to examine whether γ-secretase modulators alter Presenilin-1/γ-secretase conformation in intact cells in the absence of its natural substrates such as amyloid precursor protein and Notch. We report that the γ-secretase allosteric site is located within the γ-secretase complex, but substrate docking is needed for γ-secretase modulators to access this site