Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial

Aims/hypothesis: Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction, which has important implications for the progression of disease. Thus, in the present study, we designed a randomised double-blind, placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus. Methods: All data were collected from hospitalised diabetic patients. The electron paramagnetic resonance spectroscopic detection of spin-trapped a-phenyl-tert-butylnitrone (PBN) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes (HbA1c 7.9±1%, n=12) and healthy controls (HbA1c 4.6±0.5%, n=14). Following participant randomisation using numbers in a sealed envelope, venous blood samples were obtained at rest, after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo. Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments. Primary outcome was the difference in changes in free radicals following ascorbate ingestion. Resuts: Six diabetic patients and seven healthy control participants were randomised to each of the placebo and ascorbate groups. Diabetic patients (n=12) exhibited an elevated concentration of PBN adducts (p<0.05 vs healthy, n=14), which were confirmed as secondary, lipid-derived oxygen-centred alkoxyl (RO•) radicals (a nitrogen=1.37 mT and aßhydrogen=0.18 mT). Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene (p<0.05 vs healthy). Vitamin C supplementation increased plasma vitamin C concentration to a similar degree in both groups (p<0.05 vs pre-supplementation) and attenuated the exercise-induced oxidative stress response (p<0.05 vs healthy). There were no selective treatment differences between groups in the primary outcome variable. Conclusions/ interpretation: These findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood.

Role of creatine supplementation on exercise-induced cardiovascular function and oxidative stress

Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabdities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2) separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr) or a placebo (P) for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise), at the end of exercise (postexercise), and the day following exercise (post24 h). Serum hypdroperoxide concentrations were elevated at postexercise by 17 +/- 5% above preexercise values (p = 0.030). However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations), resistance of low density lipoprotein to oxidative stress (t(1/2max) LDL oxidation) and plasma concentrations of non-enzymatic antioxidants (retinol, alpha-carotene, beta-carotene, alpha-tocopherol, gamma-tocopherol, lycopene and vitamin Q. Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males.

Reliability of blood pressure determination with the Finapres with altered physiological states or pharmacodynamic conditions

The blood pressure waveform is modified on distal propagation by phenomena such as dispersion, reflection and the state of the arterial compliance. The consequent effects are amplification and narrowing of the wave, with an increased systolic, reduced diastolic and essentially unaltered mean blood pressure. The Finapres measures the peripheral pressure using the volume clamp principle; it has not been validated under altered physiological conditions and during pharmacodynamic interventions. We studied simultaneous Finapres and brachial blood pressures (using a conventional oscillometric sphygmomanometer—Vitalmap) in ten normal volunteers at rest, and during dynamic exercise and a cold pressor test. The effects of pharmacodynamic intervention were examined following beta-adrenoceptor blockade with propranolol (160 mg) or beta-adrenoceptor modulation with the beta-adrenoceptor partial agonist celiprolol (400 mg). The Finapres systolic pressure was significantly higher than the brachial value during all three test states. The difference between the systolic pressures measured by the two devices was shown to increase significantly during the cold pressor test, but not during dynamic (supine bicycle) exercise. The Finapres diastolic pressure was significantly higher than the Vitalmap value during exercise and the cold pressor test. The differences between the two methods increased significantly over time. Beta-adrenergic blockade with propranolol or modulation with celiprolol had no significant interaction with the pressure differences between the Finapres and Vitalmap techniques. The results would support the view that the Finapres can provide blood pressure information which is robust under most circumstances. Although this pharmacodynamic intervention did not alter the relationship between the peripheral and central blood pressure, it is important to note that this dynamic relationship is sensitive to circulatory loading conditions and wave transmission characteristics; it is possible that the Finapres could be less reliable in clinical settings where potent vasoactive agents were being administered.

Experimental observations of the stress regime in unsaturated compacted clay when laterally confined

Construction processes often involve reformation of the landscape, which will inevitably encompass compaction of artificially placed soils. A common application of fill materials is their use as backfill in many engineering applications, for example behind a retaining wall. The post-construction behaviour of clay fills is complex with respect to stresses and deformation when the fills become saturated over time. Heavily compacted fills swells significantly more than the lightly compacted fills. This will produce enhanced lateral stresses if the fill is laterally restrained. The work presented in this paper examines how the stress regime in unsaturated clay fills changes with wetting under laterally restrained conditions. Specimens of compacted kaolin, with different initial conditions, were wetted to various values of suction under zero lateral strain at constant net overburden pressure which allowed the concept of K _{0 (the ratio between the net horizontal stress and the net vertical stress) to be examined. Tests were also carried out to examine the traditional concept of the earth pressure coefficient ‘at rest' under loading and unloading and its likely effects on the stress–strain properties. The results have shown that the stress regime (i.e. the lateral stress) changes significantly during wetting under laterally restrained conditions. The magnitude of the change is affected by the initial condition of the soil. The results have also indicated that the earth pressure coefficient ‘at rest' during loading (under the normally consolidated condition) is unaffected by suction and such loading conditions inevitably lead to the development of anisotropic stress–strain properties}

Sedentary aging increases resting and exercise-induced intramuscular free radical formation

Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 ± 6 yr) and six aged (71 ± 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 ± 62%) and during exercise (+143 ± 40%), and this was further complemented by a greater increase in a-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 ± 96% and +298 ± 120%). Lipid hydroperoxides were also elevated at rest (0.190 ± 0.169 vs. 0.148 ± 0.071 nmol/mg total protein) and during exercise (0.567 ± 0.259 vs. 0.320 ± 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of a/ß-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans.

Mammals and agri-environment schemes: hare haven or pest paradise?

1. Agri-environment schemes (AESs) are designed to create landscape-scale improvements in biodiversity. While the specific aims of AESs do not always include the enhancement of species of conservation concern, associated conservation strategies, such as the UK Biodiversity Action Plan, often rest on the assumption that AESs enhance environmental conditions and thereby improve the conservation status of target species. However, there is little evidence for the general efficacy of AESs in this respect. 2. To evaluate the effects of the Environmentally Sensitive Area (ESA) scheme, a widespread AES in Northern Ireland, a spotlight survey of the relative abundance of three mammal species, Irish hare Lepus timidus hibernicus, European rabbit Oryctolagus cuniculus and red fox Vulpes vulpes, was conducted. Of these, the Irish hare is a priority species for conservation action and the focus of a species action plan, while rabbit and fox are commonly considered agricultural pests. The effects of ESA designation and habitat on each species were assessed at 150 ESA and 50 non-ESA sites, matched for landscape characteristics. 3. The ESA scheme had no demonstrable effect on the abundance of Irish hares, and this agri-environment scheme did not target the landscape and habitat variables associated with hares. 4. In contrast, the abundance of rabbits and foxes was significantly greater within ESAs than the wider countryside. Agricultural factors such as reduced livestock stocking density, reduced overgrazing and field boundary enhancements may create more favourable conditions for both species. Aside from the implications for farm economics, the proliferation of rabbit populations within conservation areas may raise issues concerning the grazing of important plant communities, while increases in fox populations may adversely affect ground-nesting birds and other animal species of conservation concern. 5. Synthesis and applications: The abundance of rabbits and foxes corroborates recent work that suggests AESs may benefit common species but can not be relied upon to encourage rarer species. The Irish hare species action plan relies on agri-environment schemes to enhance the species’ status and realize the target of increasing the hare population by 2010 by promoting suitable habitat. However, the ESA scheme is unlikely to help in achieving these objectives. Targeted and evidence-based agri-environment prescriptions are clearly required in order to ensure the realization of species-specific conservation targets.

Estimation of in situ stresses using anisotropic elasticity and suction measurements

Sampling and specimen preparation produce changes in mean effective stresses and pore water pressures, even with ‘perfect sampling’. The paper takes an existing simplified three-parameter cross-anisotropic elastic model and uses it to model these changes. The required ratio of cross-anisotropic parameters J/3G* can be obtained from standard CIU triaxial tests. If measurements are also made of suctions in unloaded specimens in the laboratory, then a combination of J/3G*, the measured suction, and the effective overburden pressure permits an estimation of the horizontal effective pressure and the K 0 ‘at rest’ coefficient. This can be helpful in numerical modelling that needs to start from in situ conditions, and in planning pressure levels for reconsolidation of clay specimens in the laboratory. Tests were done on Belfast Upper Boulder Clay from a depth of 28 m. Values of horizontal in situ effective stress estimated from these measurements compare favorably with conventional estimates of the ‘at rest’ coefficient K 0 and the overconsolidation ratio. Estimates of horizontal stress in London Clay were made using published data and the results compared with actual measurements. Again reasonable agreement was obtained.

Atmospheric parameters and rotational velocities for a sample of Galactic B-type supergiants

High-resolution optical spectra of 57 Galactic B-type supergiant stars have been analysed to determine their rotational and macroturbulent velocities. In addition, their atmospheric parameters (effective temperature, surface gravity and microturbulent velocity) and surface nitrogen abundances have been estimated using a non-local thermodynamic equilibrium grid of model atmospheres. Comparisons of the projected rotational velocities have been made with the predictions of stellar evolutionary models and in general good agreement was found. However, for a small number of targets, their observed rotational velocities were significantly larger than predicted, although their nitrogen abundances were consistent with the rest of the sample. We conclude that binarity may have played a role in generating their large rotational velocities. No correlation was found between nitrogen abundances and the current projected rotational velocities. However, a correlation was found with the inferred projected rotational velocities of the main-sequence precursors of our supergiant sample. This correlation is again in agreement with the predictions of single star evolutionary models that incorporate rotational mixing. The origin of the macroturbulence and microturbulent velocity fields is discussed and our results support previous theoretical studies that link the former to subphotospheric convection and the latter to non-radial gravity mode oscillations. In addition, we have attempted to identify differential rotation in our most rapidly rotating targets.

Neonatal control of sucking pressures

Human newborns appear to regulate sucking pressure when bottle feeding by employing, with similar precision, the same principle of control evidenced by adults in skilled behavior, such as reaching (Lee et al., 1998a). In particular, the present study of 12 full-term newborn infants indicated that the intraoral sucking pressures followed an internal dynamic prototype - an intrinsic tau-guide. The intrinsic tau-guide, a recent hypothesis of general tau theory is a time-varying quantity, tau(g), assumed to be generated within the nervous system. It corresponds to some quantity (e.g., electrical charge), chang ing with a constant second-order temporal derivative from a rest level to a goal level, in the sense that tau(g) equals tau of the gap between the quantity and its goal level at each time t. (tau of a gap is the rime-to-closure of the gap at the current closure-rate.) According to the hypoth esis, the infant senses tau(p), the tau of the gap between the current intraoral pressure and its goal level, and regulates intraoral pressure so that tau(p) and tau(g) remain coupled in a constant ratio, k; i.e., tau(p) = k tau(g). With k in the range 0-1, the tau-coupling would result in a bell-shaped rate of change pressure profile, as was, in fact, found. More specifically, the high mean r(2) values obtained when regressing tau(p) on tau(g), for both the increasing and decreasing suction periods of the infants' suck, supported a strong tau-coupling between tau(p) and tau(g). The mean k values were significantly higher In the Increasing suction period, indicating that the ending of the movement was more forceful, a finding which makes sense given the different functions of the two periods of the suck.

GALEX AND PAN-STARRS1 DISCOVERY OF SN IIP 2010aq: THE FIRST FEW DAYS AFTER SHOCK BREAKOUT IN A RED SUPERGIANT STAR

We present the early UV and optical light curve of Type IIP supernova (SN) 2010aq at z = 0.0862, and compare it to analytical models for thermal emission following SN shock breakout in a red supergiant star. SN 2010aq was discovered in joint monitoring between the Galaxy Evolution Explorer (GALEX) Time Domain Survey (TDS) in the NUV and the Pan-STARRS1 Medium Deep Survey (PS1 MDS) in the g, r, i, and z bands. The GALEX and Pan-STARRS1 observations detect the SN less than 1 day after the shock breakout, measure a diluted blackbody temperature of 31,000 +/- 6000 K 1 day later, and follow the rise in the UV/optical light curve over the next 2 days caused by the expansion and cooling of the SN ejecta. The high signal-to-noise ratio of the simultaneous UV and optical photometry allows us to fit for a progenitor star radius of 700 +/- 200R(circle dot), the size of a red supergiant star. An excess in UV emission two weeks after shock breakout compared with SNe well fitted by model atmosphere-code synthetic spectra with solar metallicity is best explained by suppressed line blanketing due to a lower metallicity progenitor star in SN 2010aq. Continued monitoring of PS1 MDS fields by the GALEX TDS will increase the sample of early UV detections of Type II SNe by an order of magnitude and probe the diversity of SN progenitor star properties.

Systematics of the marine microfilamentous green algae Uronema curvatum and Urospora microscopica (Chlorophyta)

The microfilamentous green alga Uronema curvatum is widely distributed along the western and eastern coasts of the north Atlantic Ocean where it typically grows on crustose red algae and on haptera of kelps in subtidal habitats. The placement of this marine species in a genus of freshwater Chlorophyceae had been questioned. Molecular phylogenetic analysis of nuclear-encoded small and large subunit rDNA sequences reveal that U. curvatum is closely related to the ulvophycean order Cladophorales, with which it shares a number of morphological features, including a siphonocladous level of organization and zoidangial development. The divergent phylogenetic position of U. curvatum, sister to the rest of the Cladophorales, along with a combination of distinctive morphological features, such as the absence of pyrenoids, the diminutive size of the unbranched filaments and the discoid holdfast, warrants the recognition of a separate genus, Okellya, within a new family of Cladophorales, Okellyaceae. The epiphytic Urospora microscopica from Norway, which has been allied with U. curvatum, is revealed as a member of the cladophoralean genus Chaetomorpha and is herein transferred to that genus as C. norvegica nom. nov.

Tracking leatherback turtles (Dermochelys coriacea) during consecutive inter-nesting intervals: Further support for direct transmitter attachment

Over recent years there have been substantial efforts to record and interpret the post-nesting movements of leatherback turtles (Dermochelys coriacea) breeding in tropical regions. Less well documented are the movements undertaken by individual turtles during the breeding season itself, or more specifically between sequential nesting events. Such movements are of interest for two reasons: (1) gravid female leatherbacks may range extensively into the territorial waters and nesting beaches of neighbouring countries, raising questions for conservationists and population ecologists; and (2) the magnitude of movements themselves help elucidate underlying reproductive strategies (e.g. whether to rest near to the nesting or forage extensively). Here, satellite relay data loggers are used (SRDLs) to detail the movements and behaviour of two female leatherback turtles throughout three consecutive inter-nesting intervals in the Commonwealth of Dominica, West Indies. Both near-shore residence and extensive inter-nesting movements were recorded, contrasting previous studies, with movements away from the nesting beach increasing towards the end of the nesting season. Using this behavioural study as a backdrop, the suitability of attaching satellite transmitters directly to the carapace was additionally explored as an alternative approach to conventional harness deployments. Specifically, the principal aims were to (1) gather empirical data on speed of travel and (2) assess dive performance (aerobic dive limit) to enable comparisons with turtles previously fitted with harnesses elsewhere in the Caribbean (n = 6 turtles; Grenada, WI). This produced mixed results with animals bearing directly attached transmitters travelling significantly faster (55.21 km day(-1): SD 6.68) than harnessed individuals (39.80 km day(-1); SD 6.19); whilst no discernable difference in dive performance could be found between the two groups of study animals. (C) 2009 Elsevier B.V. All rights reserved.

Ultra-bright Optical Transients are Linked with Type Ic Supernovae

Recent searches by unbiased, wide-field surveys have uncovered a group of extremely luminous optical transients. The initial discoveries of SN 2005ap by the Texas Supernova Search and SCP-06F6 in a deep Hubble pencil beam survey were followed by the Palomar Transient Factory confirmation of host redshifts for other similar transients. The transients share the common properties of high optical luminosities (peak magnitudes similar to -21 to -23), blue colors, and a lack of H or He spectral features. The physical mechanism that produces the luminosity is uncertain, with suggestions ranging from jet-driven explosion to pulsational pair instability. Here, we report the most detailed photometric and spectral coverage of an ultra-bright transient (SN 2010gx) detected in the Pan-STARRS 1 sky survey. In common with other transients in this family, early-time spectra show a blue continuum and prominent broad absorption lines of O II. However, about 25 days after discovery, the spectra developed type Ic supernova features, showing the characteristic broad Fe II and Si II absorption lines. Detailed, post-maximum follow-up may show that all SN 2005ap and SCP-06F6 type transients are linked to supernovae Ic. This poses problems in understanding the physics of the explosions: there is no indication from late-time photometry that the luminosity is powered by Ni-56, the broad light curves suggest very large ejected masses, and the slow spectral evolution is quite different from typical Ic timescales. The nature of the progenitor stars and the origin of the luminosity are intriguing and open questions.

Targets of genome copy number reduction in primary breast cancers identified by integrative genomics

The identification of specific oncogenes and tumor suppressor genes in regions of recurrent aneuploidy is a major challenge of molecular cancer research. Using both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays, we integrated genomic and transcriptional information to identify and prioritize candidate cancer genes in regions of increased and decreased chromosomal copy number in a cohort of primary breast cancers. Confirming the validity of this approach, several regions of previously-known copy number (CN) alterations in breast cancer could be successfully reidentified. Focusing on regions of decreased CN, we defined a prioritized list of eighteen candidate genes, which included ARPIN, FBNI, and LZTSI, previously shown to be associated with cancers in breast or other tissue types, and novel genes such as P29, MORF4LI, and TBCID5. One such gene, the RUNX3 transcription factor, was selected for further study. We show that RUNX3 is present at reduced CNs in proportion to the rest of the tumor genome and that RUNX3 CN reductions can also be observed in a breast cancer series from a different center. Using tissue microarrays, we demonstrate in an independent cohort of over 120 breast tissues that RUNX3 protein is expressed in normal breast epithelium but not fat and stromal tissue, and widely down-regulated in the majority of breast cancers (> 85%). In vitro, RUNX3 overexpression suppressed the invasive potential of MDA-MB-231 breast cancer cells in a matrigel assay. Our results demonstrate the utility of integrative genomic approaches to identify novel potential cancer-related genes in primary tumors. This article contains Supplementary Material available at http:// www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2006 Wiley-Liss, Inc.

Towards an Acceptable Level of Violence: Institutional Lessons from Northern Ireland

Institutional and economic development has recently returned to the forefront of economic analysis. The use of case studies (both historical and contemporary) has been important in this revival. Likewise, it has been argued recently by economic methodologists that historical context provides a kind of ‘‘laboratory’’ for the researcher interested in real world economic phenomena. Counterterrorism economics, in contrast with much of the rest of the literature on terrorism, has all too rarely drawn upon detailed contextual case studies. This article seeks to help remedy this problem. Archival evidence, including previously unpublished material on the DeLorean case, is an important feature of this article. The article examines how an inter-related strategy, which traded-off economic, security, and political considerations, operated during the Troubles. Economic repercussions of this strategy are discussed. An economic analysis of technical and organizational change within paramilitarism is also presented. A number of institutional lessons are discussed including: the optimal balance between carrot versus stick, centralization relative to decentralization, the economics of intelligence operations, and tit-for-tat violence. While existing economic models are arguably correct in identifying benefits from politico-economic decentralization, they downplay the element highlighted by institutional analysis.