Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man

Evaluation of intra- and interspecific divergence of satellite DNA sequences by nucleotide frequency calculation and pairwise sequence comparison

Satellite DNA sequences are known to be highly variable and to have been subjected to concerted evolution that homogenizes member sequences within species. We have analyzed the mode of evolution of satellite DNA sequences in four fishes from the genus Diplodus by calculating the nucleotide frequency of the sequence array and the phylogenetic distances between member sequences. Calculation of nucleotide frequency and pairwise sequence comparison enabled us to characterize the divergence among member sequences in this satellite DNA family. The results suggest that the evolutionary rate of satellite DNA in D. bellottii is about two-fold greater than the average of the other three fishes, and that the sequence homogenization event occurred in D. puntazzo more recently than in the others. The procedures described here are effective to characterize mode of evolution of satellite DNA

Ca2+ monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor

Calcium (Ca2+)-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (300?nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca2+ level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca2+ signaling in P. falciparum and is applicable for drug screening.We are grateful to Japanese Red Cross Blood Society for providing human RBC and plasma. We also thank Tanaka R, Ogoshi (Sakura) M and Matsumoto N for technical assistance and Templeton TJ for critical reading. This study was conducted at the Joint Usage / Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan. KP was a Tokyo Biochemical Research Foundation (TBRF, http://www.tokyobrf.or.jp) post-doctoral fellow and PEF was a Japanese Society of Promotion Sciences (JSPS) post-doctoral fellow. This work was supported in part by the TBRF (K.P.), JSPS (P.E.F.), Takeda Science Foundation (K.Y.), Grants-in-Aids for Scientific Research 24590509 (K.Y.), 22390079 (O.K.), and for Scientific Research on Innovative Areas 23117008 (O.K.), MEXT, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Nutritional behavior of cyclists during a 24-hour team relay race: a field study report

Background Information about behavior of energy intake in ultra-endurance cyclists during a 24-hour team relay race is scarce. The nutritional strategy during such an event is an important factor which athletes should plan carefully before the race. The purpose of this study was to examine and compare the nutritional intake of ultra-endurance cyclists during a 24-hour team relay race with the current nutritional guidelines for endurance events. Additionally, we analyzed the relationship among the nutritional and performance variables. Methods Using a observational design, nutritional intake of eight males (mean ± SD: 36.7 ± 4.7 years; 71.6 ± 4.9 kg; 174.6 ± 7.3 cm; BMI 23.5 ± 0.5 kg/m2) participating in a 24-hour team relay cycling race was assessed. All food and fluid intake by athletes were weighed and recorded. Additionally, distance and speed performed by each rider were also recorded. Furthermore, before to the race, all subjects carried out an incremental exercise test to determine two heart rate-VO2 regression equations which were used to estimate the energy expenditure. Results The mean ingestion of macronutrients during the event was 943 ± 245 g (13.1 ± 4.0 g/kg) of carbohydrates, 174 ± 146 g (2.4 ± 1.9 g/kg) of proteins and 107 ± 56 g (1.5 ± 0.7 g/kg) of lipids, respectively. This amount of nutrients reported an average nutrient intake of 22.8 ± 8.9 MJ which were significantly lower compared with energy expenditure 42.9 ± 6.8 MJ (P = 0.012). Average fluid consumption corresponded to 10497 ± 2654 mL. Mean caffeine ingestion was 142 ± 76 mg. Additionally, there was no relationship between the main nutritional variables (i.e. energy intake, carbohydrates, proteins, fluids and caffeine ingestion) and the main performance variables (i.e. distance and speed). Conclusions A 24-hour hours cycling competition in a team relay format elicited high energy demands which were not compensated by energy intake of the athletes despite that dietary consumption of macronutrients did not differ to the nutritional guidelines for longer events

Generalized Dynamic Analysis of Structural Single Rocking Walls (SRWs)

The investigation of structural single rocking walls (SRWs) continues to gain interest as they produce self-centering lateral load responses with reduced structural damage. The Simple Rocking Model (SRM) with modifications has been shown to capture these responses accurately if the SRW and its underlying base are infinitely rigid. This paper advances previous rocking models by accounting for: 1) the inelastic actions at or near the base of the SRW; and 2) the flexural responses within the wall. Included in the proposed advancements are hysteretic and inherent viscous damping associated with these two deformation components so that the total dynamic responses of SRWs can be captured with good accuracy. A system of nonlinear equations of motion is developed, in which the rocking base is discretized into fibers using a zero-length element to locate the associated compressive deformations and damage. The flexural deformations of the rocking body are captured using an elastic term, while the impact events are modeled using impulse-momentum equations. Comparisons with experiments of structural precast concrete and masonry SRWs show that the proposed approach accurately estimates the dynamic responses of different SRWs with and without unbonded posttensioning, for various dynamic excitations and degrees of hysteretic action. Using the proposed approach, a numerical investigation employs different configurations of structural SRWs to quantify the various sources of energy loss, including hysteretic action and impact damping, during various horizontal ground motions

Comparison of Bone and Renal Effects In HIV-infected Adults Switching to Abacavir or Tenofovir Based Therapy in a Randomized Trial

Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Clinicaltrials.gov NCT00647244

Regulation of Pacing Strategy during Athletic Competition

Background: Athletic competition has been a source of interest to the scientific community for many years, as a surrogate of the limits of human ambulatory ability. One of the remarkable things about athletic competition is the observation that some athletes suddenly reduce their pace in the mid-portion of the race and drop back from their competitors. Alternatively, other athletes will perform great accelerations in mid-race (surges) or during the closing stages of the race (the endspurt). This observation fits well with recent evidence that muscular power output is regulated in an anticipatory way, designed to prevent unreasonably large homeostatic disturbances. Principal Findings: Here we demonstrate that a simple index, the product of the momentary Rating of Perceived Exertion (RPE) and the fraction of race distance remaining, the Hazard Score, defines the likelihood that athletes will change their velocity during simulated competitions; and may effectively represent the language used to allow anticipatory regulation of muscle power output. Conclusions: These data support the concept that the muscular power output during high intensity exercise performance is actively regulated in an anticipatory manner that accounts for both the momentary sensations the athlete is experiencing as well as the relative amount of a competition to be completed

Dynamic response and impact energy loss in controlled rocking members

Unbonded posttensioning anchors a rocking structural member to its foundation and produces its controlled rocking response when the member undergoes seismic action. Unlike rocking of free‐standing bodies, little attention has been given to the dynamic behavior of these controlled rocking members. This paper utilizes experiments of concrete structural members with unbonded posttensioning, varying member geometries, and levels of initial posttensioning force to (a) characterize the associated impact energy loss and (b) improve modeling of controlled rocking motions. Experimental results show that impact energy loss in controlled rocking members can be captured accurately using the coefficient of restitution (r) approach of the modified simple rocking model (MSRM). Based on the MSRM, a controlled rocking model (CRM) is developed that additionally accounts for the variations in contact length at the member‐to‐foundation (rocking) interface. The CRM reproduces the experimental responses of controlled rocking members with good accuracy and is used to investigate controlled rocking motions under horizontal base excitations