bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis
Authors: Takata M , Tanaka H , Kimura M , Nagahara Y , Tanaka K , Kawasaki K , Seto M , Tsuruma K , Shimazawa M , Hara H 
Published: June 2013

Background and PurposeAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no effective treatment. Fasudil hydrochloride (fasudil), a potent rho kinase (ROCK) inhibitor, is useful for the treatment of ischaemic diseases. In previous reports, fasudil improved pathology in mouse models of Alzheimer's disease and spinal muscular atrophy, but there is no evidence in that it can affect ALS. We therefore investigated its effects on experimental models of ALS.Experimental ApproachIn mice motor neuron (NSC34) cells, the neuroprotective effect of hydroxyfasudil (M3), an active metabolite of fasudil, and its mechanism were evaluated. Moreover, the effects of fasudil, 30 and 100 mg·kg−1, administered via drinking water to mutant superoxide dismutase 1 (SOD1G93A) mice were tested by measuring motor performance, survival time and histological changes, and its mechanism investigated.Key ResultsM3 prevented motor neuron cell death induced by SOD1G93A. Furthermore, M3 suppressed both the increase in ROCK activity and phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and the reduction in phosphorylated Akt induced by SOD1G93A. These effects of M3 were attenuated by treatment with a PI3K inhibitor (LY294002). Moreover, fasudil slowed disease progression, increased survival time and reduced motor neuron loss, in SOD1G93A mice. Fasudil also attenuated the increase in ROCK activity and PTEN, and the reduction in Akt in SOD1G93A mice.Conclusions and ImplicationsThese findings indicate that fasudil may be effective at suppressing motor neuron degeneration and symptom progression in ALS. Hence, fasudil may have potential as a therapeutic agent for ALS treatment.
Istaroxime stimulates SERCA2a and accelerates calcium cycling in heart failure by relieving phospholamban inhibition
Authors: Ferrandi Mara , Barassi Paolo , Tadini‐Buoninsegni Francesco , Bartolommei Gianluca , Molinari Isabella , Tripodi Maria Grazia , Reina Cristina , Moncelli Maria Rosa , Bianchi Giuseppe , Ferrari Patrizia 
Published: June 2013

Background and PurposeCalcium handling is known to be deranged in heart failure. Interventions aimed at improving cell Ca2+ cycling may represent a promising approach to heart failure therapy. Istaroxime is a new luso‐inotropic compound that stimulates cardiac contractility and relaxation in healthy and failing animal models and in patients with acute heart failure (AHF) syndrome. Istaroxime is a Na‐K ATPase inhibitor with the unique property of increasing sarcoplasmic reticulum (SR) SERCA2a activity as shown in heart microsomes from humans and guinea pigs. The present study addressed the molecular mechanism by which istaroxime increases SERCA2a activity.Experimental ApproachTo study the effect of istaroxime on SERCA2a‐phospholamban (PLB) complex, we applied different methodologies in native dog healthy and failing heart preparations and heterologous canine SERCA2a/PLB co‐expressed in Spodoptera frugiperda (Sf21) insect cells.Key ResultsWe showed that istaroxime enhances SERCA2a activity, Ca2+ uptake and the Ca2+‐dependent charge movements into dog healthy and failing cardiac SR vesicles. Although not directly demonstrated, the most probable explanation of these activities is the displacement of PLB from SERCA2a.E2 conformation, independently from cAMP/PKA. We propose that this displacement may favour the SERCA2a conformational transition from E2 to E1, thus resulting in the acceleration of Ca2+ cycling.Conclusions and ImplicationsIstaroxime represents the first example of a small molecule that exerts a luso‐inotropic effect in the failing human heart through the stimulation of SERCA2a ATPase activity and the enhancement of Ca2+ uptake into the SR by relieving the PLB inhibitory effect on SERCA2a in a cAMP/PKA independent way.Linked ArticlesThis article is commented on by Huang, pp. 486–488 of volume 170 issue 3. To view this commentary visit http://dx.doi.org/10.1111/bph.12288.
Effects of biological sex on the pathophysiology of the heart
Authors: Fazal Loubina , Azibani Feriel , Vodovar Nicolas , Cohen Solal Alain , Delcayre Claude , Samuel Jane‐Lise 
Published: June 2013

Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex‐specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex‐based differences in cardiac structure and function in adult mammals, and the sex‐based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex‐based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches.Linked ArticlesThis article is part of a themed section on Biological Sex and Cardiovascular Pharmacology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐3
Association between body mass index and caries among children and adolescents
Authors: Lempert Susanne M. , Froberg Karsten , Christensen Lisa B. , Kristensen Peter L. , Heitmann Berit L. 
Published: June 2013

AbstractObjectiveThe aim of this article was to examine the relationship between childhood caries, body mass index (BMI) and subsequent changes in BMI over 6 years, and to investigate whether these associations were modified by social class.MethodsData were from the European Youth Heart Study (EYHS) merged with data on caries experience from the Danish National Board of Health, (SCOR register).ResultsAt baseline, 26.2% of the children/adolescents were caries free and 39% at follow‐up. A larger percentage of normal weight children/adolescents were caries free, compared with the overweight/obese group of children/adolescents. The linear regression analysis showed that childhood caries was generally not associated with either BMI or subsequent changes in BMI. However, among children whose mothers were well educated, there was an inverse association between caries at baseline and subsequent changes in BMI over a period of 6 years, for example, a high caries experience was associated with a smaller increment in BMI, compared with the group of children with a low caries experience. No association was found for those with lower SES.ConclusionAn inverse association between caries and subsequent changes in BMI was found, but only among children with well‐educated mothers, suggesting that high caries experience may be a marker for low future risk of overweight among the more advantaged. Associations did not appear to be significant among the less advantaged; however, numbers in this group were low, and an association may have been overlooked. Hence, more studies are needed to confirm these findings.
Effects of Exurban Development and Temperature on Bird Species in the Southern Appalachians
Authors: LUMPKIN HEATHER A. , PEARSON SCOTT M. 
Published: June 2013

AbstractLand‐use dynamics and climatic gradients have large effects on many terrestrial systems. Exurban development, one of the fastest growing forms of land use in the United States, may affect wildlife through habitat fragmentation and building presence may alter habitat quality. We studied the effects of residential development and temperature gradients on bird species occurrence at 140 study sites in the southern Appalachian Mountains (North Carolina, U.S.A.) that varied with respect to building density and elevation. We used occupancy models to determine 36 bird species’ associations with building density, forest canopy cover, average daily mean temperature, and an interaction between building density and mean temperature. Responses varied with habitat requirement, breeding range, and migration distance. Building density and mean temperature were both included in the top occupancy models for 19 of 36 species and a building density by temperature interaction was included in models for 8 bird species. As exurban development expands in the southern Appalachians, interior forest species and Neotropical migrants are likely to decline, but shrubland or edge species are not likely to benefit. Overall, effects of building density were greater than those of forest canopy cover. Exurban development had a greater effect on birds at high elevations due to a greater abundance of sensitive forest‐interior species and Neotropical migrants. A warming climate may exacerbate these negative effects.Efectos del Desarrollo Exurbano y de la Temperatura sobre Especies de Aves en las Apalaches del Sur
Climate Change, Multiple Stressors, and the Decline of Ectotherms
Authors: ROHR JASON R. , PALMER BRENT D. 
Published: June 2013

AbstractClimate change is believed to be causing declines of ectothermic vertebrates, but there is little evidence that climatic conditions associated with declines have exceeded critical (i.e., acutely lethal) maxima or minima, and most relevant studies are correlative, anecdotal, or short‐term (hours). We conducted an 11‐week factorial experiment to examine the effects of temperature (22 °C or 27 °C), moisture (wet or dry), and atrazine (an herbicide; 0, 4, 40, 400 μg/L exposure as embryos and larvae) on the survival, growth, behavior, and foraging rates of postmetamorphic streamside salamanders (Ambystoma barbouri), a species of conservation concern. The tested climatic conditions were between the critical maxima and minima of streamside salamanders; thus, this experiment quantified the long‐term effects of climate change within the noncritical range of this species. Despite a suite of behavioral adaptations to warm and dry conditions (e.g., burrowing, refuge use, huddling with conspecifics, and a reduction in activity), streamside salamanders exhibited significant loss of mass and significant mortality in all but the cool and moist conditions, which were closest to the climatic conditions in which they are most active in nature. A temperature of 27 °C represented a greater mortality risk than dry conditions; death occurred rapidly at this temperature and more gradually under cool and dry conditions. Foraging decreased under dry conditions, which suggests there were opportunity costs to water conservation. Exposure to the herbicide atrazine additively decreased water‐conserving behaviors, foraging efficiency, mass, and time to death. Hence, the hypothesis that moderate climate change can cause population declines is even more plausible under scenarios with multiple stressors. These results suggest that climate change within the noncritical range of species and pollution may reduce individual performance by altering metabolic demands, hydration, and foraging effort and may facilitate population declines of amphibians and perhaps other ectothermic vertebrates.Cambio Climático, Estresantes Múltiples y la Declinación de Ectotermos
All Together Now: Concurrent Learning of Multiple Structures in an Artificial Language
Authors: Romberg Alexa R. , Saffran Jenny R. 
Published: June 2013

AbstractNatural languages contain many layers of sequential structure, from the distribution of phonemes within words to the distribution of phrases within utterances. However, most research modeling language acquisition using artificial languages has focused on only one type of distributional structure at a time. In two experiments, we investigated adult learning of an artificial language that contains dependencies between both adjacent and non‐adjacent words. We found that learners rapidly acquired both types of regularities and that the strength of the adjacent statistics influenced learning of both adjacent and non‐adjacent dependencies. Additionally, though accuracy was similar for both types of structure, participants’ knowledge of the deterministic non‐adjacent dependencies was more explicit than their knowledge of the probabilistic adjacent dependencies. The results are discussed in the context of current theories of statistical learning and language acquisition.
Dorsomedial and dorsolateral striatum exhibit distinct phasic neuronal activity during alcohol self‐administration in rats
Authors: Fanelli Rebecca R. , Klein Jeffrey T. , Reese Rebecca M. , Robinson Donita L. 
Published: June 2013

AbstractThe development of alcoholism may involve a shift from goal‐directed to habitual drinking. These action control systems are distinct in the dorsal striatum, with the dorsomedial striatum (DMS) important for goal‐directed behavior and the dorsolateral striatum (DLS) required for habit formation. Goal‐directed behavior can be modeled in rats with a fixed ratio (FR) reinforcement schedule, while a variable interval (VI) schedule promotes habitual behavior (e.g. insensitivity to contingency degradation). Using extracellular recordings from chronically implanted electrodes, we investigated how DMS and DLS neurons encoded lever‐press responses and conditioned cues during operant alcohol self‐administration in these two models. In rats self‐administering 10% alcohol on an FR schedule, the DMS neuronal population showed increased firing at the onset of start‐of‐session stimuli. During self‐administration, the most prominent phasic firing patterns in the DMS occurred at the time of reinforcement and reinforcement‐associated cues, while the most prominent phasic activity in the DLS surrounded the lever response. Neural recordings from an additional cohort of rats trained on a VI schedule revealed a similar pattern of results; however, phasic changes in firing were smaller and differences between the medial and lateral dorsal striatum were less marked. In summary, the DMS and DLS exhibited overlapping but specialized phasic firing patterns: DMS excitations were typically time‐locked to reinforcement, while DLS excitations were generally associated with lever responses. Furthermore, the regional specificities and magnitudes of phasic firing differed between reinforcement schedules, which may reflect differences in behavioral flexibility, reward expectancy and the action sequences required to procure reinforcement.
Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach
Authors: Marsot Amélie , Brevaut‐Malaty Véronique , Vialet Renaud , Boulamery Audrey , Bruguerolle Bernard , Simon Nicolas 
Published: June 2013

AbstractPhenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated. Routine clinical pharmacokinetic data were retrospectively collected from 48 neonates and infants (weight: 0.7–10 kg; patient's postnatal age: 0–206 days; GA: 27–42 weeks) treated with phenobarbital, who were administered as intravenous or suspension by oral routes and hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg (3.1–10.6 mg/kg) per day was administered by 30‐min infusion or by oral route. Pharmacokinetic analysis was performed using a nonlinear mixed‐effect population model software). Data were modelled with an allometric pharmacokinetic model, using three‐fourths scaling exponent for clearance (CL). The population typical mean [per cent relative standard error (%RSE)] values for CL, apparent volume of distribution (Vd) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg (15%) and 48.9% (22%), respectively. The interindividual variability of CL, Vd, F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and 7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in neonates and infants was estimated. The dose should be increased when switching from intravenous to oral administration.
Structural and functional importance of local and global conformational fluctuations in the RNase A superfamily
Authors: Gagné Donald , Doucet Nicolas 
Published: June 2013

Understanding the relationship between protein structure and flexibility is of utmost importance for deciphering the tremendous rates of reactions catalyzed by enzyme biocatalysts. It has been postulated that protein homologs have evolved similar dynamic fluctuations to promote catalytic function, a property that would presumably be encoded in their structural fold. Using one of the best‐characterized enzyme systems of the past century, we explore this hypothesis by comparing the numerous and diverse flexibility reports available for a number of structural and functional homologs of the pancreatic‐like RNase A superfamily. Using examples from the literature and from our own work, we cover recent and historical evidence pertaining to the highly dynamic nature of this important structural fold, as well as the presumed importance of local and global concerted motions on the ribonucleolytic function. This minireview does not pretend to cover the overwhelming RNase A literature in a comprehensive manner; rather, efforts have been made to focus on the characterization of multiple timescale motions observed in the free and/or ligand‐bound structural homologs as they proceed along the reaction coordinates. Although each characterized enzyme of this architectural fold shows unique motional features on a local scale, accumulating evidence from X‐ray crystallography, NMR spectroscopy and molecular dynamics simulations suggests that global dynamic fluctuations, such as the functionally relevant hinge‐bending motion observed in the prototypical RNase A, are shared between homologs of the pancreatic‐like RNase superfamily. These observations support the hypothesis that analogous dynamic residue clusters are evolutionarily conserved among structural and functional homologs catalyzing similar enzymatic reactions.
Ductile fracture simulation of 304 stainless steel pipes with two circumferential surface cracks
Authors: Kim J‐H. , Kim N‐H. , Kim Y‐J. , Hasegawa K. , Miyazaki K. 
Published: June 2013

ABSTRACTIn this paper, ductile fracture behaviours of 304 stainless steel pipes with two circumferential surface cracks under pure bending are simulated using finite element damage analyses. Simulations are based on the stress‐modified fracture strain model with the concept that the critical accumulated damage for progressive cracking is assumed to be dependent on an element size. The proposed method can predict not only maximum loads but also complex ductile fracture patterns observed in experiments.
Alfred Loisy's Developmental Approach to Scripture: Reading the ‘Firmin’ Articles in the Context of Nineteenth‐ and Twentieth‐Century Historical Biblical Criticism
Authors: Morrow Jeffrey L. 
Published: June 2013

AbstractAlfred Loisy's ‘Firmin’ articles applied John Henry Newman's concept of development of doctrine within church history to the Bible. In doing this, Loisy was attempting to convince his Catholic audience to appropriate the historical critical method within Catholic biblical interpretation. Loisy attempted to explain the notion of development within the Bible, which had become commonplace among the Protestant historical critical scholarship of the time, in light of Newman's concept of the development of doctrine within history.
Empowered Wives and Frustrated Husbands: Nursing, Gender and Migrant Nepali in the UK
Authors: Adhikari Radha 
Published: June 2013

AbstractSince 2000, increasing numbers of Nepali nurses have crossed national borders to participate in the global healthcare market. The most common destination countries are the UK, US, Australia and New Zealand. In particular, educated middle‐class women are attracted to nursing with the full support of their families. There have been profound changes in women's position in Nepali society. As a female only profession in Nepal, nursing provides an excellent focus on how and why these changes have occurred.Based on a multi‐sited ethnography, including in‐depth interviews with nurses and their families, conducted in Nepal and the UK from 2006–2008, this article discusses the changing nursing profession within the broader context of gender dynamics. Between 2000 and 2008, around 1000 Nepali nurses migrated to the UK. International nurse migration hugely affects nurses' immediate family dynamics. This article illustrates how migrant nurses' husbands have to accept a compromised social position, from being family bread‐winners in Nepal to dependent husbands in the UK.
Policy Implications

Since the late 1990s, a new women‐migration phenomenon has emerged in Nepal. The Nepal government's current women migration policy has created a serious controversy, which requires urgent policy attention.

Because of British work permit regulations, Nepali nurses migrate to the UK on their own. Typically the UK government gives little consideration to how its international nurse recruitment practices and work permit policy affects migrants' family life. There is a need for a family‐friendly immigration policy.

Female / nurse migration has a profound impact on nurses' families' lives in the UK. This area requires further enquiry.
Associations among Pain, Non‐Medical Prescription Opioid Use, and Drug Overdose History
Authors: Bonar Erin E. , Ilgen Mark A. , Walton Maureen , Bohnert Amy S.B. 
Published: June 2013

Background and ObjectiveRecently, use of prescription opioids (POs) has increased; non‐medical PO (NMPO) use is linked to overdose. NMPO use is common among individuals prescribed opioids for pain, and those in substance use disorder (SUD) treatment with pain could be at increased risk for unintentional overdose due to NMPO use. We examined associations between pain, NMPO use, and overdose among SUD treatment patients.MethodsAmong 342 patients at a residential SUD treatment center, logistic regression examined the association of overdose with pain, adjusting for substance use, suicide attempts, and demographics.ResultsPain was positively related to NMPO use. Heroin use, suicide attempts, pain, and NMPO use were positively associated with overdose; but NMPO use attenuated the pain‐overdose relationship.ConclusionsThe relationship between pain and overdose among substance users may be, in part, explained by the association between pain and heavy NMPO use. (Am J Addict 2014;23:41–47)
One Man's Dreams, Another Man's Cosmology
Authors: Nichter Mark 
Published: June 2013

SummaryIn this article, I examine a series of conversations that I had with a South Indian Ayurvedic practitioner (vaidya) about a dream I had while in the field. The dream provided him an opportunity to engage me as cultural broker and creatively reconstruct his own cosmology. The article at once details the reasoning, diagnosis, explanation, and treatment of traditional Ayurvedic practitioners at large, and one vaidya's idiosyncratic project that has legitimacy within the larger discursive field provided by the register of Ayurveda. Further, the article also provides an example of how ongoing conversations with an anthropologist shape the knowledge produced by informants in context. In this article, I make use of a Boasian model of the elite informant as a creator of ethnographic texts that are inventive and idiosyncratic in the cultural milieu. These texts constitute a form of intellectual creativity (lila) that leads the vaidya to feel renewed in his commitment to his cosmology. As Durkheim pointed out long ago, ecstatic emotions are what generate a conviction of the presence of the transcendent. Durkheim focused on collective rituals. In this article, I provide a case in which such emotions are generated by the thrill of insight.