bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effects of some statins on epileptogenesis and depressive‐like behavior in WAG/Rij rats, a genetic animal model of absence epilepsy
Authors: Citraro Rita , Chimirri Serafina , Aiello Rossana , Gallelli Luca , Trimboli Francesca , Britti Domenico , De Sarro Giovambattista , Russo Emilio 
Published: June 2014

SummaryObjectiveStatins (3‐hydroxy‐3‐methylglutaryl‐coenzyme A [HMG‐CoA] reductase inhibitors) exert cholesterol‐independent pleiotropic effects that include antithrombotic, antiinflammatory, and antioxidative properties. Moreover, both in vitro and in vivo studies have shown neuroprotective, antiseizure, and antiexcitotoxic effects of statins, suggesting their potential role in the treatment of neurologic diseases. Only a few studies have investigated whether statins modulate absence seizure activity and epileptogenesis.MethodsWe investigated the effects of atorvastatin (5 and 10 mg/kg/day), simvastatin (10 mg/kg/day), and pravastatin (10 and 30 mg/kg/day), given orally for 17 consecutive weeks (starting at 45 days of age), on the development of absence seizures (electroencephalography [EEG] recordings), depressive‐like behavior (forced swimming test [FST]), and anxiety levels (open field test [OF]) in Wistar Albino Glaxo/Rijswijk rats (WAG/Rij) rats at the age of 6 months (1 month after suspension). WAG/Rij rats are a genetic animal model of absence epilepsy, epileptogenesis, and mild‐depression comorbidity. The effects of statins were also studied after acute intraperitoneal injection for 4 h after administration of various doses in 6‐months‐old rats. Plasma cholesterol levels were measured throughout drug treatment.ResultsWe found that early long‐term statin treatment possesses antiepileptogenic properties, reduced immobility time in the FST, and reduced anxiety in the OF, whereas they were not effective against established absence seizures when acutely administered. The observed effects were not related to changes in plasma cholesterol levels, which remained unchanged during drug treatment.SignificanceOur results suggest that statins administration might be a possible intervention and promising strategy for preventing the epileptogenesis and/or behavioral comorbidity.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Adjunctive use of controlled‐release pregabalin in adults with treatment‐resistant partial seizures: A double‐blind, randomized, placebo‐controlled trial
Authors: French Jacqueline , Brandt Christian , Friedman Daniel , Biton Victor , Knapp Lloyd , Pitman Verne , Chew Marci , Dubrava Sarah , Posner Holly B. 
Published: June 2014

SummaryObjectivesTo assess the efficacy and tolerability of add‐on pregabalin controlled‐release formulation (PGB‐CR) (doses of 165 or 330 mg/day) in patients with partial‐onset seizures (POS).MethodsThis was a randomized, double‐blind (DB), parallel‐group study of PGB‐CR once‐daily as adjunctive treatment in adults with treatment‐resistant partial seizures. After an 8‐week baseline period, eligible patients were randomized (1:1:1) to placebo, PGB‐CR 165 mg, or PGB‐CR 330 mg for 14 weeks, including a 2‐week dose escalation. Primary endpoint was the loge‐transformed 28‐day seizure rate for all POS with observable component during the full 14‐week double‐blind treatment phase. Secondary endpoints included the 50% responder rate and percent change from baseline in 28‐day POS rate.ResultsThree hundred twenty‐three patients were randomized and received treatment; placebo (n = 110), PGB‐CR 330 mg (n = 100), PGB‐CR 165 mg (n = 113); and 287 (88.9%) completed the trial. The primary efficacy analysis result, expressed as percent reduction from placebo, was 13.1% and 1.0% for PGB‐CR 330 mg and PGB‐CR 165 mg, respectively, and was not statistically significant (p = 0.091, 0.908). The proportion of 50% responders was similar for placebo (35.8%) and 165 mg PGB‐CR (37.8%) and nominally higher for 330 mg PGB‐CR (45.9%, p = 0.125 compared to placebo). The LS mean estimates of the percent change from baseline for placebo (−5.7%) was nominally smaller than 165 mg PGB‐CR (−15.0%, p = 0.540) and 330 mg PGB‐CR (−31.5%, p = 0.079); however, the median percent changes from baseline were not as well differentiated (placebo, −35.4%; 165 mg PGB‐CR, −38.0%; 330 mg PGB‐CR −43.4%). Rates of adverse events (AEs) were low for placebo and study drug; the most frequent reported AEs were dizziness, somnolence, and fatigue, consistent with the immediate‐release formulation.SignificanceResults from this trial did not demonstrate that PGB‐CR is effective in reducing seizure frequency below that of placebo. Both doses of PGB‐CR were shown to be safe and well‐tolerated.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Memory impairment is not necessarily related to seizure frequency in mesial temporal lobe epilepsy with hippocampal sclerosis
Authors: Pacagnella Denise , Lopes Tatila M. , Morita Marcia E. , Yasuda Clarissa L. , Cappabianco Fabio A. M. , Bergo Felipe , Balthazar Marcio L. F. , Coan Ana C. , Cendes Fernando 
Published: June 2014

SummaryObjectiveTo investigate the effect of seizure frequency on memory, we performed a cross sectional study comparing mesial temporal lobe epilepsy (MTLE) patients with frequent and infrequent seizures.MethodsWe performed magnetic resonance imaging (MRI) hippocampal volume (HV) measurements and neuropsychological assessment in 22 patients with frequent seizures (at least one dyscognitive seizure [DS] per month) that were refractory to antiepileptic drugs and 20 patients with infrequent seizures (three or less DS per year and no event evolving to a bilateral convulsive seizure), all with MRI signs of hippocampal sclerosis (HS) on visual analysis. We also included 29 controls for comparison of volumetric data.ResultsThere was no difference in memory performance between patients with frequent seizures and infrequent seizures. We observed a significant bilateral reduction of HV in patients with MTLE when compared to controls (p < 0.001). The degree of hippocampal atrophy (HA) between patients with frequent and infrequent seizures was not different. There was a negative correlation between seizure frequency and HV, with r = −0.3 for the HV ipsilateral to the HS and r = −0.55 for the contralateral side, thus, explaining only 9% and 30% of the HV loss. There was a positive correlation between age of onset and degree of HA (r = 0.37).SignificanceOur data suggest that seizure frequency does not explain most of the HV loss or memory impairment in MTLE. Memory impairment appears to be more influenced by hippocampal damage than by seizure frequency. Further studies are necessary to identify the factors that influence memory decline in patients with MTLE.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
A field guide to whole‐genome sequencing, assembly and annotation
Authors: Ekblom Robert , Wolf Jochen B. W. 
Published: June 2014

AbstractGenome sequencing projects were long confined to biomedical model organisms and required the concerted effort of large consortia. Rapid progress in high‐throughput sequencing technology and the simultaneous development of bioinformatic tools have democratized the field. It is now within reach for individual research groups in the eco‐evolutionary and conservation community to generate de novo draft genome sequences for any organism of choice. Because of the cost and considerable effort involved in such an endeavour, the important first step is to thoroughly consider whether a genome sequence is necessary for addressing the biological question at hand. Once this decision is taken, a genome project requires careful planning with respect to the organism involved and the intended quality of the genome draft. Here, we briefly review the state of the art within this field and provide a step‐by‐step introduction to the workflow involved in genome sequencing, assembly and annotation with particular reference to large and complex genomes. This tutorial is targeted at scientists with a background in conservation genetics, but more generally, provides useful practical guidance for researchers engaging in whole‐genome sequencing projects.
State of the art: Stem cells in equine regenerative medicine
Authors: Lopez M. J. , Jarazo J. 
Published: June 2014

SummaryAccording to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano‐ and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no ‘one‐size‐fits‐all’ regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine.
Toll‐like receptor 2 mediates a cutaneous reaction induced by repetitive ultraviolet B irradiation in C57/BL6 mice in vivo
Authors: Park Hyun Sun , Jin Seon Pil , Lee Youngae , Oh In Gyung , Lee Serah , Kim Jung Ho , Cho Kwang Hyun , Chung Jin Ho 
Published: June 2014

AbstractToll‐like receptors (TLRs) mediate not only innate immunity against infection and but also sterile inflammation triggered by endogenous molecules. We conducted a comparative study of the different inflammatory responses induced by repetitive ultraviolet (UV) B irradiation in wild‐type (WT) and TLR2 knockout (KO) mice, to provide in vivo evidence of the role of TLRs in mediating UVB‐induced responses. UVB‐induced inflammatory responses were less severe in TLR2 KO mice than in WT mice after 6 weeks of repeated UVB irradiation. UVB‐treated TLR2 KO mice displayed less prominent erythema and scaling, and histopathology showed significantly thinner skin and less inflammatory cell infiltration than that in WT mice. UVB‐induced expression of heat‐shock protein 70 (an endogenous ligand of TLR2) was lower in TLR2 KO mice. Quantitative RT‐PCR revealed significantly lower gene expression levels of UVB‐induced interleukin (IL)‐1β, IL‐6 and matrix metalloproteinase (MMP)‐13 in TLR2 KO mice. TLR2 KO mice also showed significantly lower protein level expression of UVB‐induced IL‐1β in ELISA and MMP‐13 in Western blots. Our study demonstrated that TLR2 was associated with inflammatory responses to repetitive UVB irradiation in C57/BL6 mice. Moreover, it suggests that the role of TLR2 in the cutaneous response of UV irradiation and in developing new agents for modulating the effects of UV irradiation should be considered.
Magnesium‐dependent folding of a picornavirus IRES element modulates RNA conformation and eIF4G interaction
Authors: Lozano Gloria , Fernandez Noemi , Martinez‐Salas Encarnacion 
Published: June 2014

Internal ribosome entry site (IRES) elements are high‐order RNA structures that promote internal initiation of translation to allow protein synthesis under situations that compromise the general cap‐dependent translation mechanism. Picornavirus IRES elements are highly efficient elements with a modular RNA structure organization. Here we investigated the effect of Mg2+ concentration on the local flexibility and solvent accessibility of the foot‐and‐mouth disease virus (FMDV) IRES element measured on the basis of selective 2′‐hydroxyl acylation analyzed by primer extension (SHAPE) reactivity and hydroxyl radical cleavage. We have found that Mg2+ concentration affects the organization of discrete IRES regions, mainly the apical region of domain 3, the 10 nt loop of domain 4, and the pyrimidine tract of domain 5. In support of the effect of RNA structure on IRES activity, substitution or deletion mutants of the 10 nt loop of domain 4 impair internal initiation. In addition, divalent cations affect the binding of eIF4G, a eukaryotic initiation factor that is essential for IRES‐dependent translation that interacts with domain 4. Binding of eIF4G is favored by the local RNA flexibility adopted at low Mg2+ concentration, while eIF4B interacts with the IRES independently of the compactness of the RNA structure. Our study shows that the IRES element adopts a near‐native structure in the absence of proteins, shedding light on the influence of Mg2+ ions on the local flexibility and binding of eIF4G in a model IRES element.
A review of equivalent pre‐crack sizes in aluminium alloy 7050‐T7451
Authors: Molent L. 
Published: June 2014

ABSTRACTThis paper reviews some analyses of quantitative fractography measurements of the fatigue fracture surfaces of 7050 aluminium alloy specimens along with relevant fatigue crack information including crack initiating discontinuity size and type. These data were used to assess whether surface finish or applied stress level has any effect on the estimated effective crack initiating discontinuity size, namely the equivalent pre‐crack size (EPS). The statistical distributions for the EPSs of the following initiating discontinuity types were examined: chemically etched pits, glass bead peening damage, mechanical damage, inclusions and porosity. The EPSs at various percentile levels for these types were determined on the basis of the samples considered. Finally, the correlation between measured initiating discontinuity depth and EPS was investigated, and good correlation was found in the case of mechanical damage. The purpose of conducting these analyses was to gain a better understanding of the parameters governing the fatigue crack‐like effect of discontinuities to facilitate the better prediction of fatigue lives.
Fatigue crack tip damaging micromechanisms in pearlitic ductile cast irons
Authors: Iacoviello F. , Di Cocco V. , Rossi A. , Cavallini M. 
Published: June 2014

AbstractIn the last years, damaging micromechanisms in ductile cast irons (DCIs) were widely investigated: DCI microstructure (ranging from ferritic–pearlitic DCIs to austempered ones), graphite elements morphology (shape, dimension and distributions) and loading conditions were the main investigated parameters. Focusing on the role played by the graphite nodules, they were considered merely as voids embedded in a metal matrix. Recent analysis underlined that the nodules role in the DCIs damage evolution is more complicated and is influenced by the matrix microstructure. In this work, the crack tip damaging micromechanisms in a pearlitic DCI is investigated considering both fatigue loading conditions and the effects of overloads, focusing the interaction between the crack and the investigated DCI microstructure (pearlitic matrix and graphite nodules). On the basis of experimental results, the applicability of ASTM E399 standard on the characterization of fatigue crack propagation resistance in pearlitic DCIs is critically re‐analyzed.
Predicting potential responses to future climate in an alpine ungulate: interspecific interactions exceed climate effects
Authors: Mason Tom H.E. , Stephens Philip A. , Apollonio Marco , Willis Stephen G. 
Published: June 2014

AbstractThe altitudinal shifts of many montane populations are lagging behind climate change. Understanding habitual, daily behavioural rhythms, and their climatic and environmental influences, could shed light on the constraints on long‐term upslope range‐shifts. In addition, behavioural rhythms can be affected by interspecific interactions, which can ameliorate or exacerbate climate‐driven effects on ecology. Here, we investigate the relative influences of ambient temperature and an interaction with domestic sheep (Ovis aries) on the altitude use and activity budgets of a mountain ungulate, the Alpine chamois (Rupicapra rupicapra). Chamois moved upslope when it was hotter but this effect was modest compared to that of the presence of sheep, to which they reacted by moving 89–103 m upslope, into an entirely novel altitudinal range. Across the European Alps, a range‐shift of this magnitude corresponds to a 46% decrease in the availability of suitable foraging habitat. This highlights the importance of understanding how factors such as competition and disturbance shape a given species’ realised niche when predicting potential future responses to change. Furthermore, it exposes the potential for manipulations of species interactions to ameliorate the impacts of climate change, in this case by the careful management of livestock. Such manipulations could be particularly appropriate for species where competition or disturbance already strongly restricts their available niche. Our results also reveal the potential role of behavioural flexibility in responses to climate change. Chamois reduced their activity when it was warmer, which could explain their modest altitudinal migrations. Considering this behavioural flexibility, our model predicts a small 15–30 m upslope shift by 2100 in response to climate change, less than 4% of the altitudinal shift that would be predicted using a traditional species distribution model‐type approach (SDM), which assumes that species’ behaviour remains unchanged as climate changes. Behavioural modifications could strongly affect how species respond to a changing climate.
Joint Hypermobility and Headache: The Glue That Binds the Two Together – Part 2
Authors: Martin Vincent T. , Neilson Derek 
Published: June 2014

BackgroundPast studies have reported that connective tissue disorders (CTDs) are more common in patients with specific types of headache disorders.ObjectivesThe objectives of this study are (1) to review and critique the clinical studies reporting an association between joint hypermobility, CTDs and headache and (2) to postulate mechanisms though which CTDs might predispose to headache disorders.MethodsPubMed was searched for relevant articles with search terms that included joint hypermobility, Ehlers–Danlos syndrome, Marfan syndrome, and specific headache disorders. A narrative review was performed of these articles as well as those identified from the bibliography of these articles.ResultsCase reports and case control studies confirm an association between CTDs and migraine, coat‐hanger headaches, carotid arterial dissections, intracranial hypotension, Arnold Chiari malformations‐type 1, cervical spine disorders, and temporomandibular joint disorders.ConclusionsObservational cross‐sectional studies suggest that the prevalence of CTDs is increased in patients with specific types of headache disorders. It is unknown if the CTDs directly cause these headaches disorders or are associated with them through other mechanisms.
Electrical Characterization of Pd‐Doped CMAS‐TiO2 Glass‐Ceramics
Authors: Davis Mark J. , Vullo Paula , Reich Maria‐Louisa 
Published: June 2014

Electrical characterization was performed on Pd‐bearing and Pd‐free, electrically conductive glass‐ceramics in the CMAS‐TiO2 system. AC impedance plots clearly revealed both grain‐core and grain‐boundary semicircles. Grain boundaries had a lower magnitude of conductivity but a similar activation energy to grain‐core conduction except when Pd was present, for which much lower activation energies were indicated. The lack of any frequency (f) dependence of conductivity for f < 100 Hz, while using noble metal electrodes, suggests the conduction was dominantly electronic in origin in these glass‐ceramics. Time‐dependent polarization measurements showed no change in electrical current over several days, also consistent with this conclusion. Overall, the temperature dependence of the conductivity was relatively low over a very large temperature range, but quite complex. The appearance of a sharp minimum in conduction seen near 600°C suggests some type of transition occurred with our glass‐ceramics, possibly related to semiconductor‐to‐metal transitions seen with some transition‐metal crystals. The available data suggest that Pd did have some effect on grain‐boundary conduction, but that a percolating Pd network was not formed.
Interleukin‐2‐mediated inhibition of dendritic cell development correlates with decreased CD135 expression and increased monocyte/macrophage precursors
Authors: Guerrero Alan D. , Dong Matthew B. , Zhao Yongge , Lau‐Kilby Annie , Tarbell Kristin V. 
Published: June 2014

SummaryWe have previously shown that interleukin‐2 (IL‐2) inhibits dendritic cell (DC) development from mouse bone marrow (BM) precursors stimulated with the ligand for FMS‐like tyrosine kinase 3 receptor (Flt3L), and have provided evidence that this inhibition occurs at the monocyte DC precursor stage of DC development. Here, we explored the mechanism of IL‐2‐mediated inhibition of DC development. First, we showed that these in vitro cultures accurately model DCs that develop in vivo by comparing gene and protein expression of the three main Flt3L‐induced DC subsets from the BM, CD11b+ and CD24+ conventional DCs (cDCs) and plasmacytoid DCs (pDCs) with their respective ex vivo spleen DC subsets (CD11b+, CD8+ and pDCs). Next, gene expression changes were quantified in Flt3L DC subsets that developed in the presence of IL‐2. These changes included increased expression of Bcl2l11, which encodes the apoptosis‐inducing protein Bim, and decreased expression of Flt3 (CD135), the receptor that initiates DC development. Interleukin‐2 also significantly reduced Flt3 protein expression on all three Flt3L DC subsets, and attenuated Flt3L‐induced STAT3 phosphorylation in DCs. Based on these data, we hypothesized that decreased Flt3 signalling may divert BM precursors down monocyte and macrophage lineages. Indeed, addition of IL‐2 led to increases in Flt3− cells, including cKit+ Ly6C+ CD11b− populations consistent with the recently identified committed monocyte/macrophage progenitor. Therefore, IL‐2 can inhibit DC development via decreased signalling through Flt3 and increased monocyte/macrophage development.