bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subchondral Bone Remodelling Is More Active in Resting Than Training Thoroughbred Racehorses
Authors: Holmes J , Mirams M , Mackie E , Whitton C 
Published: June 2014

IntroductionSubchondral bone fatigue is an important cause of poor performance, morbidity and mortality in racehorses. Fatigued bone is repaired by remodelling, a process that is attenuated under high cyclical loads, yet the effects of training on remodelling activity in Thoroughbred racehorses is unknown. We hypothesised that remodelling rates are lower in training horses than those that are resting from training.MethodsSections of the palmar metacarpal condyles from Thoroughbred horses that were in race training (n = 24) or resting from training (n = 24) at the time of death were examined with light microscopy and back scattered electron microscopy (BSEM). Bone area fraction (B.Ar/T.Ar), and eroded bone surface (E.Pm/T.Ar) were measured within two regions of interest; (1) the lateral parasagittal groove (PS); and (2) the lateral condylar subchondral bone (LC). BSEM variables were analysed for the effect of group (independent samples t‐test), region (paired t‐test) and interaction with time since change in training status (general linear model). Mean ± SE are reported.ResultsFor both regions of interest E.Pm/T.Ar was lower in the training horses (PS: 0.39 ± 0.06 mm−1, LC: 0.24 ± 0.04 mm−1) than in the resting group (PS: 0.65 ± 0.07 mm−1, P = 0.010, LC: 0.85 ± 0.10 mm−1, P<0.001). Lower subchondral bone porosity was observed, reflected by higher B.Ar/T.Ar in the LC of training horses (90.8 ± 0.6%) than resting horses (85.3 ± 1.4%, P = 0.0010). E.Pm/T.Ar was higher with increased duration of a training period in the lateral condyle (r2 = 0.26, P = 0.011).ConclusionsRace training inhibits remodelling in the subchondral bone of highly loaded areas of the distal metacarpus. Therefore periods of less intense loading are important for allowing repair of subchondral bone fatigue in Thoroughbred racehorses.Ethical Animal ResearchThe study was performed on material collected during post‐mortem examination. Sources of funding: Rural Industries Research and Development Corporation of the Australian Commonwealth Government and Racing Victoria Limited. Competing interests: none.
Factors Affecting Owners' Choice of Nutritional Supplements in Dressage and Eventing Horses
Authors: Gemmill R , Agar C , Freeman S , Hollands T 
Published: June 2014

IntroductionHorse owners are faced with a vast range of supplements and different sources of information. The aim of this study was to evaluate sources of information used by owners/riders when choosing supplements for competition horses, their opinions on different sources of information and evaluation of factors that affect their decisions.MethodsA mixed methods (open and closed questions) online questionnaire was distributed through British Eventing and Dressage websites to owners/riders of dressage and/or event horses, to collect data on the demographics of the owner/rider and their horses, sources of information used when choosing nutritional supplements, and their opinion on these different sources. Data was evaluated using descriptive analysis and Chi‐squared tests for quantitative data, and thematic analysis for qualitative data.Results757 responses met the inclusion criteria, and owners/riders competed at dressage and eventing from unaffiliated novice to affiliated advanced level. Veterinary surgeons were considered the most reliable source of information, followed by nutritionists, research studies, coach/trainer and other horse owners. ‘Other horse owners’ were the top source (18% of participants) for the participants' most recent choice of supplement. Respondents with a higher education qualification were significantly more likely to use research papers as a source of information (P<0.005). Owners/riders under 34 years of age were significantly more likely to use a coach / trainer as a source of information (P<0.005).ConclusionsHorse owners identified veterinary surgeons, nutritionists and research papers as reliable sources of information, but ultimately most chose their supplement based on recommendations of other owners or coaches/trainers.Ethical Animal ResearchThe study was reviewed and approved by the School of Veterinary Medicine and Science Ethics Committee at the University of Nottingham. Sources of funding: School of Veterinary Medicine and Science at the University of Nottingham. Competing interests: Teresa Hollands is employed by Dodson and Horrell Ltd.
Energy Expenditure During a 160 km Endurance Race
Authors: Goachet A , Loriers A , Le Floch E , Julliand V 
Published: June 2014

IntroductionIn endurance racing, horses are required to complete distances of up to 160 km in a single day. To date, the energy expenditure (EE) of such effort has not been quantified. This study aimed to evaluate EE during a 160 km endurance race from heart rate (HR) monitoring.MethodsThree weeks before competing, two endurance horses (H1 and H2) were submitted to a field exercise test to determine their individual VO2‐HR relationship. VO2 and HR were recorded simultaneously at trot (13–14 km/h for 10 min), and at canter (18–19 km/h for 10 min, and 22–23 km/h for 5 min), using the equine K4b2, a portable metabolic measurement system. H1 was then enrolled in Monpazier CEI and H2 in Florac CEI. HR was monitored from 2 minutes before the start to the finishing line of each loop. EE of exercise was calculated from individual VO2‐HR relationship and caloric equivalent of oxygen.ResultsH1 and H2 completed the race at an average speed of 17.02 and 14.46 km/h, respectively. Mean HR was 108 ± 8 and 124 ± 24 and peak HR was 169 and 204 for H1 and H2, respectively. The proportion of time spent at HR≥180 was 0 and 2.7% for H1 and H2 respectively. EE of exercise was evaluated at 177 and 240 MJ for H1 and H2 respectively.ConclusionsA 160‐km endurance race might present a considerable energy cost, at least 5 times the EE of non‐working state.Ethical Animal ResearchThe project was conducted under license from the Department of Health and Animal Care of the French Veterinary Authority (no. A21002) and ethics committee approval n° B0710. Sources of funding: Burgundy Region and AgroSup Dijon. Competing interests: none.
Novel biosensors based on optimized glycine oxidase
Authors: Rosini Elena , Piubelli Luciano , Molla Gianluca , Frattini Luca , Valentino Mattia , Varriale Antonio , D'Auria Sabato , Pollegioni Loredano 
Published: June 2014

Glycine is involved in several physiological functions, e.g. as a neurotransmitter in the central nervous system, and sarcosine has been identified as a differential metabolite greatly enhanced during prostate cancer progression and metastasis. Glycine oxidase from Bacillus subtilis (GO) was engineered with the final aim of producing specific analytical systems to detect these small achiral amino acids. Based on in silico analysis, site‐saturation mutagenesis was independently performed at 11 positions: a total of 16 single‐point GO variants were analyzed. Significantly improved kinetic parameters were observed on glycine for the A54R, H244K‐N‐Q‐R, Y246W and M261R variants. The introduction of multiple mutations then identified the H244K/M261R variant showing a 5.4‐fold increase in maximal activity on glycine. With sarcosine as substrate, a number of single‐point variants showed increased maximal activity and/or affinity: the kinetic efficiency was increased 6‐fold for the M49L variant. Two GO variants with a high substrate specificity ratio for glycine (versus sarcosine, i.e. H244K GO) or for sarcosine (versus glycine, i.e. M49L GO) combined with high substrate affinity were used to set up a simple fluorescence‐based biosensor. This optical sensing assay represents a novel, inexpensive and fast tool to assay glycine or sarcosine concentrations in biological samples (detection limit ≤ 0.5 μm).
Enhancement of mitochondrial ATP production by the Escherichia coli cytotoxic necrotizing factor 1
Authors: Travaglione Sara , Loizzo Stefano , Rizza Teresa , Del Brocco Antonella , Ballan Giulia , Guidotti Marco , Vona Rosa , Di Nottia Michela , Torraco Alessandra , Carrozzo Rosalba , Fiorentini Carla , Fabbri Alessia 
Published: June 2014

Mitochondria are dynamic organelles that constantly change shape and structure in response to different stimuli and metabolic demands of the cell. The Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1) has recently been reported to influence mitochondrial activity in a mouse model of Rett syndrome and to increase ATP content in the brain tissue of an Alzheimer's disease mouse model. In the present work, the ability of CNF1 to influence mitochondrial activity was investigated in IEC‐6 normal intestinal crypt cells. In these cells, the toxin was able to induce an increase in cellular ATP content, probably due to an increment of the mitochondrial electron transport chain. In addition, the CNF1‐induced Rho GTPase activity also caused changes in the mitochondrial architecture that mainly consisted in the formation of a complex network of elongated mitochondria. The involvement of the cAMP‐dependent protein kinase A signaling pathway was postulated. Our results demonstrate that CNF1 positively affects mitochondria by bursting their energetic function and modifying their morphology.
The cascade of care in the Eastern European country of Georgia
Authors: Chkhartishvili N , Sharavdze L , Chokoshvili O , DeHovitz JA , del Rio C , Tsertsvadze T 
Published: June 2014

ObjectivesIndividual and public health benefits of antiretroviral therapy (ART) rely on successful engagement of HIV‐infected patients in care. We aimed to evaluate the HIV care continuum in the Eastern European country of Georgia.MethodsThe analysis included all adult (age ≥ 18 years) HIV‐infected patients diagnosed in Georgia from January 1989 until June 2012. Data were extracted from the national HIV/AIDS database as of 1 October 2012. The following stages of the HIV care continuum were quantified: HIV infected, HIV diagnosed, linked to care, retained in care, eligible for ART and virologically suppressed.ResultsOf 3295 cumulative cases of adult HIV infection reported in Georgia, 2545 HIV‐infected patients were known to be alive as of 1 October 2012, which is 52% of the estimated 4900 persons living with HIV in the country. Of the 2545 persons diagnosed with HIV infection, 2135 (84%) were linked to care and 1847 (73%) were retained in care. Of 1446 patients eligible for ART, 1273 (88%) were on treatment and 985 (77%) of them had a viral load < 400 HIV‐1 RNA copies/mL. Overall, 39% of those diagnosed and 20% of those infected had a suppressed viral load.ConclusionsThe findings of our analysis demonstrate that the majority of patients diagnosed with HIV infection are retained in care. Loss of patients occurs at each step of the HIV care continuum, but the major gap is at the stage of HIV diagnosis. Reducing the number of persons living with undiagnosed HIV infection and simultaneously enhancing engagement in continuous care will be critical to achieve maximum individual and public health benefits of ART.
Two novel alleles HLA‐A*02:433 and HLA‐A*02:434 identified in Saudi bone marrow donors using sequence‐based typing
Authors: Fakhoury H. A. , Jawdat D. , Alaskar A. S. , Al Jumah M. , Cereb N. , Hajeer A. H. 
Published: June 2014

SummaryIn this report, we present two novel HLA‐A alleles: HLA‐A*02:433 and HLA‐A*02:434. These alleles were identified by sequence‐based typing method (SBT), in two donors for the Saudi Bone Marrow Donor Registry (SBMDR). Allele A*02:433 is identical to A*02:05:01G except for a G to A substitution at nucleotide position 449 in exon 2. This substitution results in glycine to serine substitution at position 83. Whereas, allele A*02:434 is identical to A*02:01:01G except for a C to A substitution at nucleotide position 245 in exon 2, which results in phenylalanine to threonine substitution at position 15. The generation of both alleles appears to be the result of nucleotide point mutation involving 02:01:01 and 02:05:01.
Independent and combined influence of neonatal and current body composition on academic performance in youth: The UP & DOWN Study
Authors: Esteban‐Cornejo I. , Tejero‐González C. M. , Castro‐Piñero J. , Conde‐Caveda J. , Cabanas‐Sanchez V. , Sallis J. F. , Veiga Óscar L. ,   UP & DOWN Study Group
Published: June 2014

SummaryBackgroundsUnhealthy body composition is a cause for concern across the lifespan.ObjectiveThe objective of this study was to examine the independent and combined associations between neonatal and current body composition with academic performance among youth.MethodsThis cross‐sectional study was conducted with a total of 1557 youth (745 girls) aged 10.4 ± 3.4 years. Birth weight and length at birth were self‐reported. Current body composition was assessed by body mass index (BMI), waist circumference (WC) and percentage of body fat (BF%). Academic performance was assessed through schools records.ResultsBirth weight was related to all academic variables in boys, independent of potential confounders, including BMI; whereas WC, BMI and BF% were related to all academic performance indicators in both boys and girls, independent of potential confounders, including birth weight (all P < 0.05). In addition, the combined adverse effects of low birth weight and current overweight on academic performance were observed in both boys and girls for grade point average (GPA) indicator. Boys in the group with none adverse effect had significantly higher scores in GPA (score +0.535; 95% confidence interval, 0.082–0.989) than boys in the group of both adverse effects (P < 0.007); among girls, GPA score was higher in the group with none adverse effect than in the groups with one or two adverse effects (P for trend = 0.029).ConclusionsNeonatal and current body composition, both independently and combined, may influence academic performance in youth.
Changes in immunological profile as a function of urbanization and lifestyle
Authors: Mbow Moustapha , de Jong Sanne E. , Meurs Lynn , Mboup Souleymane , Dieye Tandakha Ndiaye , Polman Katja , Yazdanbakhsh Maria 
Published: June 2014

SummaryDifferences in lifestyle and break with natural environment appear to be associated with changes in the immune system resulting in various adverse health effects. Although genetics can have a major impact on the immune system and disease susceptibility, the contribution of environmental factors is thought to be substantial. Here, we investigated the immunological profile of healthy volunteers living in a rural and an urban area of a developing African country (Senegal), and in a European country (the Netherlands). Using flow cytometry, we investigated T helper type 1 (Th1), Th2, Th17, Th22 and regulatory T cells, as well as CD4+ T‐cell and B‐cell activation markers, and subsets of memory T and B cells in the peripheral blood. Rural Senegalese had significantly higher frequencies of Th1, Th2 and Th22 cells, memory CD4+ T and B cells, as well as activated CD4+ T and B cells compared with urban Senegalese and urban Dutch people. Within the Senegalese population, rural paritcipants displayed significantly higher frequencies of Th2 and Th22 cells, as well as higher pro‐inflammatory and T‐cell activation and memory profiles compared with the urban population. The greater magnitude of immune activation and the enlarged memory pool, together with Th2 polarization, seen in rural participants from Africa, followed by urban Africans and Europeans suggest that environmental changes may define immunological footprints, which could have consequences for disease patterns in general and vaccine responses in particular.
Variable post‐zygotic isolation in Drosophila melanogaster/D. simulans hybrids
Authors: Matute D. R. , Gavin‐Smyth J. , Liu G. 
Published: June 2014

AbstractThe study of hybrid inviability reveals cryptic divergence between the genetic interactions that maintain stable phenotypes in the pure species. We characterized the effects of natural variation on the penetrance of hybrid inviability phenotypes in crosses between Drosophila melanogaster and two species of the D. simulans subcomplex, D. simulans and D. sechellia. Using a panel of wild‐caught lines, we studied the levels of genetic variance present in D. simulans and D. sechellia affecting prezygotic and post‐zygotic isolation in hybridizations with D. melanogaster females. We observed extensive variability in the viability of hybrid individuals, dependent on the genotype of the parents, suggesting that intraspecific natural variation manifests directly in hybrid phenotypes. Furthermore, we found that genetic background significantly affects the penetrance of a well‐studied determinant of hybrid inviability: the interaction between Hmrmel–Lhrsim. Our results suggest that hybrid inviability – and reproductive isolation generally – can be modified by polymorphisms at multiple loci segregating within the parental species. Just as the penetrance of most mutant phenotypes can be modified by the genetic background within the pure species, the penetrance of hybrid inviability phenotypes is highly influenced by the parental genotypes.
Tertiary montane origin of the Central Asian flora, evidence inferred from cpDNA sequences of Atraphaxis (Polygonaceae)
Authors: Zhang Ming‐Li , Sanderson Stewart C. , Sun Yan‐Xia , Byalt Vyacheslav V. , Hao Xiao‐Li 
Published: June 2014

AbstractAtraphaxis has approximately 25 species and a distribution center in Central Asia. It has been previously used to hypothesize an origin from montane forest. We sampled 18 species covering three sections within the genus and sequenced five cpDNA spacers, atpB‐rbcL, psbK‐psbI, psbA‐trnH, rbcL, and trnL‐trnF. BEAST was used to reconstruct phylogenetic relationship and time divergences, and S‐DIVA and Lagrange were used, based on distribution area and ecotype data, for reconstruction of ancestral areas and events. Our results appear compatible with designation of three taxonomic sections within the genus. The generic stem and crown ages were Eocene, approximately 47 Ma, and Oligocene 27 Ma, respectively. The origin of Atraphaxis is confirmed as montane, with an ancestral area consisting of the Junggar Basin and uplands of the Pamir‐Tianshan‐Alatau‐Altai mountain chains, and ancestral ecotype of montane forest. Two remarkable paleogeographic events, shrinkage of the inland Paratethys Sea at the boundary of the late Oligocene and early Miocene, and the time intervals of cooling and drying of global climate from 24 (22) Ma onward likely facilitated early diversification of Atraphaxis, while rapid uplift of the Tianshan Mountains during the late Miocene may have promoted later diversification.
Putative roles of Ca2+‐independent phospholipase A2 in respiratory chain‐associated ROS production in brain mitochondria: influence of docosahexaenoic acid and bromoenol lactone
Authors: Nordmann Caroline , Strokin Mikhail , Schönfeld Peter , Reiser Georg 
Published: June 2014

AbstractCa2+‐independent phospholipase A2 (iPLA2) is hypothesized to control mitochondrial reactive oxygen species (ROS) generation. Here, we modulated the influence of iPLA2‐induced liberation of non‐esterified free fatty acids on ROS generation associated with the electron transport chain. We demonstrate enzymatic activity of membrane‐associated iPLA2 in native, energized rat brain mitochondria (RBM). Theoretically, enhanced liberation of free fatty acids by iPLA2 modulates mitochondrial ROS generation, either attenuating the reversed electron transport (RET) or deregulating the forward electron transport of electron transport chain. For mimicking such conditions, we probed the effect of docosahexaenoic acid (DHA), a major iPLA2 product on ROS generation. We demonstrate that the adenine nucleotide translocase partly mediates DHA‐induced uncoupling, and that low micromolar DHA concentrations diminish RET‐dependent ROS generation. Uncoupling proteins have no effect, but the adenine nucleotide translocase inhibitor carboxyatractyloside attenuates DHA‐linked uncoupling effect on RET‐dependent ROS generation. Under physiological conditions of forward electron transport, low micromolar DHA stimulates ROS generation. Finally, exposure of RBM to the iPLA2 inhibitor bromoenol lactone (BEL) enhanced ROS generation. BEL diminished RBM glutathione content. BEL‐treated RBM exhibits reduced Ca2+ retention capacity and partial depolarization. Thus, we rebut the view that iPLA2 attenuates oxidative stress in brain mitochondria. However, the iPLA2 inhibitor BEL has detrimental activities on energy‐dependent mitochondrial functions.image
The Ca2+‐independent phospholipase A2 (iPLA2), a FFA (free fatty acids)‐generating membrane‐attached mitochondrial phospholipase, is potential to regulate ROS (reactive oxygen species) generation by mitochondria. FFA can either decrease reversed electron transport (RET)‐linked or enhance forward electron transport (FET)‐linked ROS generation. In the physiological mode of FET, iPLA2 activity increases ROS generation. The iPLA2 inhibitor BEL exerts detrimental effects on energy‐dependent mitochondrial functions.
S100B protein activates a RAGE‐dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis
Authors: Villarreal Alejandro , Seoane Rocío , González Torres Agustina , Rosciszewski Gerardo , Angelo Maria Florencia , Rossi Alicia , Barker Philip A. , Ramos Alberto Javier 
Published: June 2014

AbstractExtracellular S100B dramatically increases after brain injury. While low S100B levels are neuroprotective, micromolar S100B levels have shown in vitro to activate microglia and facilitate neuronal death. In astrocytes, S100B exposure activates nuclear factor kappa B (NF‐κB) and induces pro‐inflammatory mediators. On microglia and neurons S100B effects are essentially mediated by receptor for advanced glycation end products (RAGE)/NF‐κB, but it is not clear if these intracellular cascades are activated by different S100B levels in astrocytes and whether increased extracellular S100B is sufficient to induce reactive gliosis. A better understanding of these pathways is essential for developing successful strategies to preserve the beneficial S100B effects after brain injury. Here, we show that microglia‐depleted cultured astrocytes exposed to S100B mimicked several features of reactive gliosis by activating RAGE/Rac‐1‐Cdc42, RAGE/Erk‐Akt or RAGE/NF‐κB‐dependent pathways. S100B effects include RAGE/Rac1‐Cdc42‐dependent astroglial hypertrophy and facilitation of migration as well as increased mitosis. S100B exposure improved the astrocytic survival to oxidative stress, an effect that requires Erk/Akt. S100B also activates NF‐κB in a dose‐dependent manner; increases RAGE proximal promoter transcriptional activity and augmented endogenous RAGE expression. S100B‐exposed astrocytes showed a pro‐inflammatory phenotype with expression of Toll‐like receptor 2 (TLR 2), inducible nitric oxide synthase (iNOS) and interleukin 1‐beta (IL‐1β), and facilitated neuronal death induced by oxygen‐glucose deprivation. In vivo, intracerebral infusion of S100B was enough to induce an astroglial reactive phenotype. Together, these findings demonstrate that extracellular S100B in the micromolar level activates different RAGE‐dependent pathways that turn astrocytes into a pro‐inflammatory and neurodegenerative phenotype.
image
We propose that S100B turns astrocytes into a reactive phenotype in a RAGE‐dependent manner but engaging different intracellular pathways. While both nanomolar and micromolar S100B turn astrocytes into a reactive phenotype, micromolar S100B induces a conversion into a pro‐inflammatory‐neurodegenerative profile that facilitates neuronal death of OGD‐exposed neurons. We think that S100B/RAGE interaction is essential to expand reactive gliosis in the injured brain being a tempting target for limiting reactive gliosis to prevent the glial conversion into the neurodegenerative profile.