bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific protein homeostatic functions of small heat‐shock proteins increase lifespan
Authors: Vos Michel J. , Carra Serena , Kanon Bart , Bosveld Floris , Klauke Karin , Sibon Ody C. M. , Kampinga Harm H. 
Published: December 2015

SummaryDuring aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat‐shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress‐denatured substrates and/or to prevent aggregation of disease‐associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70‐dependent refolding of stress‐denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70‐independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.
Longitudinal evaluation of functional connectivity variation in the monkey sensorimotor network induced by spinal cord injury
Authors: Rao J.S. , Liu Z. , Zhao C. , Wei R.H. , Zhao W. , Yang Z.Y. , Li X.G. 
Published: December 2015

AbstractAimGiven the unclear pattern of cerebral function reorganization induced by spinal cord injury (SCI), this study aimed to longitudinally evaluate the changes in resting‐state functional connectivity (FC) in the sensorimotor network after SCI and explore their relationship with gait performance.MethodsFour adult female rhesus monkeys were examined using resting‐state functional magnetic resonance imaging during their healthy stage and after hemitransected SCI (4, 8 and 12 weeks after SCI), and the gait characteristics of their hindlimbs were recorded (except 4 weeks after SCI). Twenty sensorimotor‐related cortical areas were adopted in the FC analysis to evaluate the functional network reorganization. Correlation analyses were then used to explore the relationship between functional network variations and gait characteristic changes.ResultsCompared with that during the healthy stage, the FC strength during post‐SCI period was significantly increased in multiple areas of the motor control network, including the primary sensorimotor cortex, supplementary motor area (SMA) and putamen (Pu). However, the FC strength was remarkably reduced in the thalamus and parieto‐occipital association cortex of the sensory network 8 weeks after SCI. Most FC intensities gradually approached the normal level 12 weeks after the SCI. Correlation analyses revealed that the enhanced FC strength between Pu and SMA in the left hemisphere, which regulates motor functions of the right side, was negatively correlated with the gait height of the right hindlimb.ConclusionThe cerebral functional network presents an adjust–recover pattern after SCI, which may help us further understand the cerebral function reorganization after SCI.
Mechanisms Involved in Thromboxane A2‐induced Vasoconstriction of Rat Intracavernous Small Penile Arteries
Authors: Grann Martin , Comerma‐Steffensen Simon , Arcanjo Daniel D. R. , Simonsen Ulf 
Published: December 2015

AbstractDiabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+]i) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619 by activation of thromboxane receptors concentration dependently increased calcium and contraction. U46619‐induced calcium influx was blocked by nifedipine, a blocker of L‐type calcium channels, and by 2‐aminoethoxydiphenyl borate, a blocker of transient receptor potential (TRP) channels. Inhibitors of ROCK, Y27632 and glycyl‐H1152P, concentration dependently reduced U46619‐induced contraction, but only Y27632 reduced [Ca2+]i levels in the penile arteries activated with either high extracellular potassium or U46619. MYPT‐Thr850 phosphorylation in corpus cavernous strips was increased in response to U46619 through activation of TP receptors and was found to be a direct result of phosphorylation by ROCK. Y27632 induced less relaxation in mesenteric arteries, H1152P induced equipotent relaxations, and a protein kinase C inhibitor, Ro‐318220, failed to relax intracavernous penile arteries, but induced full relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L‐type and TRP channels, and ROCK‐dependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated with hypertension and diabetes.
Sydnone 1: A Mesoionic Compound with Antitumoral and Haematological Effects In Vivo
Authors: Galuppo Larissa Favaretto , dos Reis Lívero Francislaine Aparecida , Martins Gracianny Gomes , Cardoso Cibele Campos , Beltrame Olair Carlos , Klassen Liliane Maria Bacaro , Canuto André Vinicius dos Santos , Echevarria Aurea , Telles José Ederaldo Queiroz , Klassen Giseli , Acco Alexandra 
Published: December 2015

AbstractThis study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd‐1) against Walker‐256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd‐1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro‐apoptotic protein expression (Bax and p53), while the expression of the anti‐apoptotic protein Bcl‐2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd‐1 treatment. However, significant splenomegaly was evident in animals that received Syd‐1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd‐1 against Walker‐256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.
Physiology and Pharmacology of Ejaculation
Authors: Clement Pierre , Giuliano François 
Published: December 2015

AbstractEjaculation is the final stage of coitus in mammalian male and is mandatory for natural procreation. Two synchronized phases, emission and expulsion, form the ejaculatory response and involve specific organs and anatomical structures. The peripheral events leading to ejaculation are commanded by autonomic (sympathetic and parasympathetic) and somatic divisions of the nervous system. The autonomic and somatic motor efferents originate in spinal nuclei located in thoracolumbar and lumbosacral segments. Co‐ordinated activation of autonomic and somatic spinal nuclei is orchestrated by a group of lumbar spinal interneurons defined as the spinal generator of ejaculation. The generator of ejaculation together with the autonomic and somatic spinal nuclei constitutes a spinal network that is under the strong influence of stimulating or inhibiting genital sensory and supraspinal inputs. A brain circuitry dedicated to ejaculation has been delineated that is part of a more global network controlling other aspects of the sexual response. This circuitry includes discrete neuronal populations distributed in all divisions of the brain. The corollary to the expanded CNS network is the variety of neurotransmitter systems participating in the ejaculatory process. Among them, serotonin neurotransmission plays a key role and its targeting led to the development of the first registered pharmacological treatment of premature ejaculation in human beings. Critical gaps remain in the understanding of neurophysiopharmacology of ejaculation and management of ejaculatory disorders in human beings needs improvement. Because the ejaculatory response in laboratory animals and in human beings shares many similarities, the use of animal models will certainly provide further advances in the field.
Systematic Review and Meta‐Analysis: Macrolides‐ and Amoxicillin/Clavulanate‐induced Acute Liver Injury
Authors: Ferrer Pili , Amelio Justyna , Ballarín Elena , Sabaté Mònica , Vidal Xavi , Rottenkolber Marietta , Schmiedl Sven , Laporte Joan‐Ramon , Ibáñez Luisa ,   the PROTECT Work Package 2
Published: December 2015

AbstractAntibacterials are frequently associated with idiosyncratic drug‐induced liver injury (DILI). The objective of this study was to estimate the risk of macrolides and amoxicillin/clavulanate (AMC) on DILI. We conducted a systematic review (SR) and meta‐analysis (MA) with studies retrieved from PubMed, Cochrane Library Plus, Web of Knowledge, clinicaltrials.gov, Livertox and Toxline (1980–2014). We searched for macrolides, AMC and MeSH and synonym terms for DILI. We included all study designs except case reports/series, all population ages and studies with a placebo/non‐user comparator. We summarized the evidence with a random‐effects MA. Quality of the studies was appraised with a checklist developed for SR of adverse effects. Heterogeneity and publication bias were assessed with different exploratory tools. We finally included 10 (two randomized clinical trials, six case–control, one cohort and one case–population studies) and 9 (case–population excluded) articles in the SR and MA, respectively. The overall summary relative risk of DILI for macrolides was 2.85 [95% confidence interval (CI) 1.81–4.47], p < 0.0001, I2 = 57%. Three studies were perceived to be missing in the area of low statistical significance. Year of study and selected exposure window partly explained the variability between studies. For AMC, the risk of DILI was 9.38 (95% CI 0.65–135.41) p = 0.3, I2 = 95%. In conclusion, although spontaneous reports and case series have long established an association between macrolides and AMC with acute liver injury, these SR and MA have assessed the magnitude of this association. The low incidence of DILI and the therapeutic place of these antibiotics might tilt the balance in favour of their benefits.
BERTRAND Vs. COURNOT COMPETITION WITH UPSTREAM FIRM INVESTMENT
Authors: Lee DongJoon , Choi Kangsik 
Published: December 2015

ABSTRACTThis paper compares Bertrand and Cournot competition in a vertical structure in which the upstream firm sets the input price and makes R&D investments. We show that from the downstream firms’ point of view, Cournot competition has the advantage of a more monopolistic effect, leading to the setting of a higher price, but has the disadvantage of inducing a lower incentive for the upstream firm to invest. On the other hand, Bertrand competition has the advantage of providing a greater incentive for the upstream firm to invest but has the disadvantage of a more competitive effect, leading to the setting of a lower price. Our main findings are as follows. First, R&D investment level is greater under Bertrand competition than under Cournot competition. Second, from the standpoint of the upstream firm and industry, Bertrand competition is more efficient than Cournot competition. Third, from the standpoint of the downstream firms, Bertrand competition is more efficient than Cournot when investment is sufficiently efficient and products are sufficiently differentiated.
COGNITIVE SKILLS AND CONFIDENCE: INTERRELATIONS WITH OVERESTIMATION, OVERPLACEMENT AND OVERPRECISION
Authors: Duttle Kai 
Published: December 2015

ABSTRACTThis experimental study measures the three major types of judgmental overconfidence in a within‐subjects design. Performance‐based overestimation and overplacement are elicited in a Raven Progressive Matrices test for general intelligence. Calibration‐based overprecision is evaluated in a forecasting by confidence intervals task. This study takes a closer look at the interrelations of these different types. Moreover, as the main focus, it considers the effect of cognitive abilities on overconfidence. These are quantified in a cognitive reflection test. I find that cognitive skills are substantially interrelated with subjects’ confidence levels. Although overconfidence in absolute terms (overestimation) is not affected by cognitive abilities, the effect on overconfidence in relative terms (overplacement) is positive and significant. Overprecision, the calibration‐based type of overconfidence, is found to be significantly affected by cognitive capacity as well. Interval forecasts of cognitively more able subjects were much better calibrated than those of their peers who displayed substantial overconfidence in the precision of their forecasts.
The Ties That Bind: Social Capital, Families, and Children's Well‐Being
Authors: Parcel Toby L. , Bixby Monica S. 
Published: December 2015

AbstractSocial bonds between parents and their children, an important form of social capital, promote children's cognition and their social adjustment. Both bonding and bridging social capital are consequential, as are parental norms and values, which vary by social class. Parents' working conditions, including occupational complexity and work schedules, influence children's home environments as well as their children's development. Family social capital is more important than school social capital in influencing both cognitive and social child outcomes. Recent studies show how fathers' roles are changing, with implications for social capital in families, and point to bonding with fathers as a possible mechanism for building social capital. We know relatively little about how different forms of capital, including financial, human, cultural, and social capital, combine to influence families and children. We need further analyses regarding how to build social capital, particularly for at‐risk children.
Survival analysis of wide dental implant: systematic review and meta‐analysis
Authors: Lee Chun‐Teh , Chen Ya‐Wei , Starr Jacqueline R. , Chuang Sung‐Kiang 
Published: December 2015

AbstractObjectiveWide‐diameter implants are frequently placed in molar sites to obtain appropriate restoration profiles, to rescue implants that lack stability, and to engage bone in extraction sites. However, studies of wide‐diameter implant placement have provided conflicting evidence regarding clinical outcomes. This systematic review aims to analyze survival rates of wide‐diameter implants (platform diameter ≥5 mm) and assess clinical variables potentially affecting failure rates.Material and methodsElectronic search was conducted using MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE from January 1980 to October 2014. Publication screening, data extraction, and quality assessment were performed. Failure rate per implant‐year was analyzed using mix‐effects Poisson regression model to obtain summary estimates of the 5‐year survival rate. Relative risk (RR) was calculated to evaluate the association of different clinical variables with estimated failure rates.ResultsEleven retrospective studies and eight prospective studies having at least 1‐year follow‐up period were included in the analysis. The estimated 5‐year survival rate was 92.67% (95% confidence interval: [79.60, 97.50]) in the retrospective studies and 97.76% (Confidence interval: [93.25, 99.27]) in the prospective studies. Implant surface and implant diameter were significantly associated with the failure events in the retrospective studies.ConclusionsPlacement of wide‐diameter implants demonstrated a promising survival rate during 5‐year follow‐up. Further controlled trials with the control group and longer follow‐up period are needed to provide the direct evidence comparing survival rates of wide implants with survival rates of narrower implants.
Can We Forget What We Know in a False‐Belief Task? An Investigation of the True‐Belief Default
Authors: Rubio‐Fernández Paula 
Published: December 2015

AbstractIt has been generally assumed in the Theory of Mind literature of the past 30 years that young children fail standard false‐belief tasks because they attribute their own knowledge to the protagonist (what Leslie and colleagues called a “true‐belief default”). Contrary to the traditional view, we have recently proposed that the children's bias is task induced. This alternative view was supported by studies showing that 3 year olds are able to pass a false‐belief task that allows them to focus on the protagonist, without drawing their attention to the target object in the test phase. For a more accurate comparison of these two accounts, the present study tested the true‐belief default with adults. Four experiments measuring eye movements and response inhibition revealed that (a) adults do not have an automatic tendency to respond to the false‐belief question according to their own knowledge and (b) the true‐belief response need not be inhibited in order to correctly predict the protagonist's actions. The positive results observed in the control conditions confirm the accuracy of the various measures used. I conclude that the results of this study undermine the true‐belief default view and those models that posit mechanisms of response inhibition in false‐belief reasoning. Alternatively, the present study with adults and recent studies with children suggest that participants' focus of attention in false‐belief tasks may be key to their performance.
Anti‐SPAG16 antibodies in primary progressive multiple sclerosis are associated with an elevated progression index
Authors: de Bock L. , Fraussen J. , Villar L. M. , Álvarez‐Cermeño J. C. , Van Wijmeersch B. , van Pesch V. , Stinissen P. , Somers V. 
Published: December 2015

Background and purposeSperm‐associated antigen 16 (SPAG16), a sperm protein which is upregulated in reactive astrocytes in multiple sclerosis (MS) lesions, has recently been identified as a novel autoantibody target in MS. The aim of this study was to investigate whether anti‐SPAG16 antibody levels differ between MS subtypes (relapsing−remitting, RR; primary or secondary progressive, PP, SP) and whether antibody positivity is associated with clinical characteristics.MethodsPlasma anti‐SPAG16 antibody levels were determined by recombinant protein enzyme‐linked immunosorbent assay (ELISA) in 374 MS patients (274 RRMS, 39 SPMS and 61 PPMS) and 106 healthy controls.ResultsSignificantly elevated anti‐SPAG16 antibodies were found in 22% of MS patients with 93% specificity. Anti‐SPAG16 seropositivity was associated with an increased Expanded Disability Status Scale (EDSS) in overall MS. A higher proportion of PPMS patients showed anti‐SPAG16 antibody reactivity (34%) compared to RRMS (19%) and SPMS (26%), and presented with higher anti‐SPAG16 antibody levels. Seropositive PPMS patients had a significantly increased progression index compared to seronegative patients.ConclusionsAnti‐SPAG16 antibodies are associated with an increased EDSS in overall MS, indicating that they are linked to a worse MS disease outcome. Moreover, the presence of anti‐SPAG16 antibodies may be a biomarker for a more severe disease in PPMS patients, as indicated by an increased progression index.
Effects of prenatal antiepileptic drug exposure on newborn brain activity
Authors: Videman Mari , Tokariev Anton , Stjerna Susanna , Roivainen Reina , Gaily Eija , Vanhatalo Sampsa 
Published: December 2015

SummaryObjectivePrenatal exposure to antiepileptic drugs (AEDs) is associated with an increased risk of cognitive dysfunction at early school age. Our aim was to investigate whether signs of adverse drug effects on brain function could be detected already during the first 2 weeks of life.MethodsWe studied prospectively 56 full‐term newborns with prenatal exposure to AEDs and 67 unexposed newborns for the following characteristics: Background information, AED exposure data, pregnancy outcome, neuropsychological evaluation of the mothers, clinical neurologic status with Hammersmith Neonatal Neurological Examination and early cortical activity using electroencephalography (EEG). For EEG assessment, we developed and provide automated quantitation algorithms of several earlier described features: oscillatory bouts at theta and alpha frequencies, frequency spectra, interhemispheric synchrony, and interburst intervals (IBIs).ResultsThe AED‐exposed newborns had lower limb and axial tone and were less irritable than the unexposed newborns. EEG assessment disclosed significant differences in alpha bouts, in the frequency spectra, as well as in the spatial distributions of interhemispheric synchrony and IBIs.SignificanceThe results indicate that fetal AED exposure may affect early neonatal neurologic status and several features of early cortical activity. The findings suggest that interference of activity‐dependent network development may be a possible mechanism to explain the link from fetal AED exposure to later neurocognitive sequelae.
Antimicrobial selection and dosing in the treatment of wounds in the United Kingdom
Authors: Ross S. E. , Duz M. , Rendle D. I. 
Published: December 2015

SummaryReasons for performing studyAntimicrobial stewardship within the veterinary profession is recognised by governing and professional bodies as being important; the attitudes and behaviour of veterinary surgeons merit investigation.ObjectivesTo investigate levels of protected antimicrobial use and accuracy of antimicrobial dosing in a common clinical scenario in equine practice.Study designRetrospective cohort study.MethodsAntimicrobial use was evaluated retrospectively in 113 cases subsequently referred to a single referral hospital for the treatment of limb wounds over a 20‐month period. Antimicrobial classification (first‐line, alternative or protected) was made according to guidelines produced by the British Equine Veterinary Association. These guidelines also served as the reference for recommended dose rates.ResultsSystemic antimicrobials were administered prior to referral in 94/113 (83.2%) horses, of which 8 (8.5%) received the protected third or fourth generation cephalosporins or fluoroquinolones. Forty‐eight of 87 (55.2%) horses for which complete dosing data were available received antimicrobials at ≤90% of the recommended dose. Practitioners who held a postgraduate clinical qualification or worked in purely equine practice were no more or less likely to use protected antimicrobials (P = 0.06 and P = 0.64, respectively) or administer inadequate doses (P = 0.75 and P = 0.85, respectively). Veterinary surgeons with more experience were less likely to use protected antimicrobials (P<0.001); however, with the small case numbers, this finding should be interpreted with caution. Heavier horses were more likely to be under‐dosed (P<0.002).ConclusionsThis study highlights the administration of certain classes of antimicrobials in situations where their use is unlikely to be justified. If these findings reflect more general attitudes and behaviour then greater awareness of, and compliance with, recommendations for responsible antimicrobial use are required among equine practitioners. Bodyweight ought to be measured or estimated using validated objective techniques prior to systemic medications being administered.