bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment
Authors: Nora Gerald J. , Harun Rashed , Fine David F. , Hutchison Daniel , Grobart Adam C. , Stezoski Jason P. , Munoz Miranda J. , Kochanek Patrick M. , Leak Rehana K. , Drabek Tomas , Wagner Amy K. 
Published: April 2017

AbstractCardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic‐ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF‐CA). Fast‐scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D‐Str) and nucleus accumbens 14 days after a 5‐min VF‐CA when compared to Sham or Naïve. VF‐CA increased D‐Str‐evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (Vmax). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF‐CA and Shams after establishing a baseline, pre‐drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more‐so in VF‐CA versus Sham and reduced D‐Str Vmax in VF‐CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF‐CA versus Sham. Our work demonstrates that 5‐min VF‐CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF‐CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions.
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CB1 receptors down‐regulate a cAMP/Epac2/PLC pathway to silence the nerve terminals of cerebellar granule cells
Authors: Alonso Beatris , Bartolomé‐Martín David , Ferrero José Javier , Ramírez‐Franco Jorge , Torres Magdalena , Sánchez‐Prieto José 
Published: April 2017

AbstractCannabinoid receptors mediate short‐term retrograde inhibition of neurotransmitter release, as well as long‐term depression of synaptic transmission at excitatory synapses. The responses of individual nerve terminals in VGLUT1‐pHluorin transfected cerebellar granule cells to cannabinoids have shown that prolonged activation of cannabinoid type 1 receptors (CB1Rs) silences a subpopulation of previously active synaptic boutons. Adopting a combined pharmacological and genetic approach to study the molecular mechanisms of CB1R‐induced silencing, we found that adenylyl cyclase inhibition decreases cAMP levels while it increases the number of silent synaptic boutons and occludes the induction of further silencing by the cannabinoid agonist HU‐210. Guanine nucleotide exchange proteins directly activated by cAMP (Epac proteins) mediate some of the presynaptic effects of cAMP in the potentiation of synaptic transmission. ESI05, a selective Epac2 inhibitor, and U‐73122, the specific inhibitor of phospholipase C (PLC), both augment the number of silent synaptic boutons. Moreover, they abolish the capacity of the Epac activator, 8‐(4‐chlorophenylthio)‐2′‐O‐methyladenosine 3′,5′‐cyclic monophosphate monosodium hydrate, to prevent HU‐210‐induced silencing consistent with PLC signaling lying downstream of Epac2 proteins. Furthermore, Rab3‐interacting molecule (RIM)1α KO cells have many more basally silent synaptic boutons (12.9 ± 3.5%) than wild‐type cells (1.1 ± 0.5%). HU‐210 induced further silencing in these mutant cells, although 8‐(4‐chlorophenylthio)‐2′‐O‐methyladenosine 3′,5′‐cyclic monophosphate monosodium hydrate only awoke the HU‐210‐induced silence and not the basally silent synaptic boutons. This behavior can be rescued by expressing RIM1α in RIM1α KO cells, these cells behaving very much like wild‐type cells. These findings support the hypothesis that a cAMP/Epac/PLC signaling pathway targeting the release machinery appears to mediate cannabinoid‐induced presynaptic silencing.
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An ecological approach to discover new bioactive extracts and products: the case of extremophile plants
Authors: Sahli Ramla , Rivière Céline , Neut Christel , Bero Joanne , Sahuc Marie-Emmanuelle , Smaoui Abderrazak , Beaufay Claire , Roumy Vincent , Hennebelle Thierry , Rouillé Yves , Quetin-Leclercq Joëlle , Séron Karin , Ksouri Riadh , Sahpaz Sevser 
Published: April 2017

Abstract

Objectives
Eight extremophile plants from Tunisia were screened to find natural products with benefits in human health.

Methods
These plants were collected in different areas in Tunisia. Their methanolic extracts were evaluated for their total phenolic content and for their antiradical (DPPH), antimicrobial (on 35 bacteria and one yeast), antiviral (hepatitis C virus, HCV) and cytotoxic activity (against WI38 and J774 cell lines). The most active species were subjected to a bioguided fractionation.

Key findings
The screening revealed promising activity for four plants, but two species have both antiradical and antimicrobial activity: Juncus maritimus and Limonium virgatum. The rhizomes extract of J. maritimus showed the highest activity against HCV, a selective antibacterial activity against Streptococcus dysgalactiae, and a moderate antiradical activity which is due to luteolin isolated in one step by centrifugal partition chromatography. The stems’ and leaves’ extracts of L. virgatum were rich in polyphenols responsible for the antiradical activity. Also, Limonium extracts showed an antibacterial activity with a broad spectrum.

Conclusions
Extremophile plants have proven to be a promising source for bioactive metabolites. They have a powerful antioxidant system highly influenced by biotic and abiotic factors and the ability to produce secondary metabolites with antimicrobial activity.
Dietary mannoheptulose does not alter glucose or lipid metabolism in adult Labrador Retrievers
Authors: McKnight L. L. , France J. , Wright D. , Davenport G. , Shoveller A. K. 
Published: April 2017

SummaryMannoheptulose (MH), a glycolytic inhibitor, has been preliminarily investigated as a novel functional food ingredient for dogs. This study aimed to determine the effects of dietary MH, delivered as an extract of un‐ripened avocados, on fatty acid and glucose kinetics in healthy adult Labrador Retriever dogs (n = 12 dogs). The study was a double‐blindcrossover with each dog receiving both dietary treatments, control (CON) and MH (400 mg/kg of diet), in random order. Glucose and glycerol plasma turnover (Ra) and oxidation (Ox) were measured in fasting and in response to repeated meal feeding (“fed”) with stable isotope tracers (U‐13C‐glucose, 1,1,2,3,3‐D5‐glycerol) and indirect calorimetry. Palmitate Ra and Ox were examined during repeated meal feeding only using an oral bolus of U‐13C‐K2‐palmitate and indirect calorimetry. MH had no discernible effect on fasting glucose Ra (677, 722 SEM 36 μmol/min, CON, MH) or Ox (107, 109 μmol/min, CON, MH SEM 10 μmol/min) or fed glucose Ra (2913, 3626 SEM 644 μmol/min, CON, MH) or Ox (951, 936 SEM 174 μmol/min, CON, MH). Glycerol Ra, an index of the rate of lipolysis, was not different between dietary treatments (Fast 162, 113 SEM 35 μmol/min CON, MH; Fed 172, 135 SEM 21 μmol/min, CON, MH). Similarly, palmitate oxidation was not impacted by MH feeding (1966, 2276 SEM 79 μmol/min, CON, MH). Together, these findings do not support MH as a novel functional food ingredient at least at the dietary dose tested.
Protection of protein from ruminal degradation by alkali‐induced oxidation of chlorogenic acid in sunflower meal
Authors: Bongartz V. , Böttger C. , Wilhelmy N. , Schulze‐Kaysers N. , Südekum K.‐H. , Schieber A. 
Published: April 2017

SummaryLactating ruminants require an adequate supply of absorbable amino acids for the synthesis of milk protein from two sources, that is crude protein (CP) synthesized microbially in the rumen and ruminally undegraded CP (RUP) from feed which can both be digested in the small intestine. Several chemical and physical methods have been identified as being effective in increasing the proportion of RUP of total CP of a feedstuff, yet there is a continuing need for developing and establishing methods which protect feed protein from ruminal degradation with acceptable expenditure of labour and other costs. The objective of this study was to identify and quantify effects of and interactions between chlorogenic acid and protein in solvent‐extracted sunflower meal (SFM) as induced by alkali treatment. Response surface methodology was employed to investigate the influence of pH, reaction time and drying temperature on the resulting SFM and, subsequently, its protein value for ruminants estimated from laboratory values. For this purpose, alkali‐treated SFM was subjected to a fractionation of feed CP according to the Cornell net carbohydrate and protein system as a basis for estimating RUP at different assumed ruminal passage rates (Kp). To estimate the intestinal digestibility of the treated SFM and its RUP, a three‐step enzymatic in vitro procedure was applied. Alkaline treatment of SFM increased RUP values with factors ranging from approximately 3 (Kp=.08/hr) to 12 (Kp=.02/hr). Furthermore, the intestinal digestibility of the alkali‐treated SFM was enhanced by approximately 10% compared to untreated SFM. Increasing pH and reaction time led to both increasing RUP values and intestinal digestibility. In conclusion, a targeted alkaline treatment of naturally occurring compounds in feedstuffs might be a promising approach to provide high‐RUP feeds for ruminants which, at the same time, have improved intestinal digestibility values.
Soils and rainfall drive landscape‐scale changes in the diversity and functional composition of tree communities in premontane tropical forest
Authors: Prada Cecilia M. , Morris Arturo , Andersen Kelly M. , Turner Benjamin L. , Caballero Pedro , Dalling James W. 
Published: April 2017

AbstractQuestionsPremontane tropical forests harbour exceptionally high plant species diversity; understanding which factors influence their species composition is critical to conserving them, and to predicting how global environmental change will affect them. We asked: (1) how do α‐ and β‐diversity vary at the landscape scale; (2) how important is environmental filtering in structuring these communities; and (3) which soil and climate variables account for the most compositional variation?LocationOld‐growth premontane forest, Fortuna Forest Reserve, western Panama.MethodsAll trees ≥5‐cmDBHwere censused in 12 1‐ha plots up to 13 km apart. For each plot, we measured soil properties (0–10 cm depth) at 13 locations, and estimated or measured monthly rainfall. To evaluate how the environmental and spatial variables are associated with community composition, we used ordination and Mantel tests.ResultsDiversity varied nearly three‐fold among plots (68–184 species·ha−1). β‐Diversity was also high, with only one of 364 species present in all plots. Turnover reflected distinct forest community types that have developed on different parent materials: forests on rhyolite had an abundance of either ectomycorrhizal‐associated trees or canopy palms, while forests on the other rock types (andesite, dacite and basalt) were dominated by trees that form arbuscular mycorrhizal associations. WhileNMDSordination showed that species turnover was significantly correlated with rainfall seasonality, and also co‐varied with geographic distance. Nonetheless, large compositional differences were apparent among sites <2 km apart with similar rainfall but differing soils. Partial Mantel tests controlling for geographic distance highlighted the relationship between total phosphorus and species composition.ConclusionsSoil nutrient availability and rainfall seasonality in premontane forests at Fortuna are associated with striking variation in the taxonomic and functional composition of nearby tree communities, and with plot differences in species richness comparable in magnitude to those reported over >1000 m a.s.l. in previous studies. Accounting for how local edaphic conditions structure premontane and montane tropical forests will be critical to predicting how tree communities will respond to climate change.
New insights into neurogenic cyclic motor activity in the isolated guinea‐pig colon
Authors: Costa M. , Wiklendt L. , Keightley L. , Brookes S. J. H. , Dinning P. G. , Spencer N. J. 
Published: April 2017

AbstractBackgroundThe contents of the guinea pig distal colon consist of multiple pellets that move anally in a coordinated manner. This row of pellets results in continued distention of the colon. In this study, we have investigated quantitatively the features of the neurally dependent colonic motor patterns that are evoked by constant distension of the full length of guinea‐pig colon.MethodsConstant distension was applied to the excised guinea‐pig by high‐resolution manometry catheters or by a series of hooks.Key ResultsConstant distension elicited regular Cyclic Motor Complexes (CMCs) that originated at multiple different sites along the colon and propagated in an oral or anal direction extending distances of 18.3±10.3 cm. CMCs were blocked by tetrodotoxin (TTX; 0.6 μ mol L−1), hexamethonium (100 μ mol L−1) or hyoscine (1 μ mol L−1). Application of TTX in a localized compartment or cutting the gut circumferentially disrupted the spatial continuity of CMCs. Localized smooth muscle contraction was not required for CMC propagation. Shortening the length of the preparations or disruption of circumferential pathways reduced the integrity and continuity of CMCs.Conclusions & InferencesCMCs are a distinctive neurally dependent cyclic motor pattern, that emerge with distension over long lengths of the distal colon. They do not require changes in muscle tension or contractility to entrain the neural activity underlying CMC propagation. CMCs are likely to play an important role interacting with the neuromechanical processes that time the propulsion of multiple natural pellets and may be particularly relevant in conditions of impaction or obstruction, where long segments of colon are simultaneously distended.
Equivalence of complex drug products: advances in and challenges for current regulatory frameworks
Authors: Hussaarts Leonie , Mühlebach Stefan , Shah Vinod P. , McNeil Scott , Borchard Gerrit , Flühmann Beat , Weinstein Vera , Neervannan Sesha , Griffiths Elwyn , Jiang Wenlei , Wolff‐Holz Elena , Crommelin Daan J.A. , de Vlieger Jon S.B. 
Published: April 2017

AbstractBiotechnology and nanotechnology provide a growing number of innovator‐driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron–carbohydrate complexes, drug‐carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1‐day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow‐on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow‐on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow‐up were identified: (1) assessment of critical attributes to establish equivalence for follow‐on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified.
Luminosity Guaranteed
Authors: Barz Wolfgang 
Published: April 2017

AbstractThis article aims to show that Williamson's anti‐luminosity argument does not succeed if we presuppose a constitutive connection between the phenomenal and the doxastic. In contrast to other luminists, however, my strategy is not to critically focus on the refined safety condition in terms of degrees of confidence that anti‐luminists typically use in this context. Instead, I will argue that, given a certain conception of what Chalmers calls ‘direct phenomenal concepts,’ luminosity is guaranteed even if the refined safety condition in terms of degrees of confidence is taken for granted.
The influence of frontal alpha‐asymmetry on the processing of approach‐ and withdrawal‐related stimuli—A multichannel psychophysiology study
Authors: Adolph Dirk , von Glischinski Michael , Wannemüller André , Margraf Jürgen 
Published: April 2017

AbstractThe approach‐withdrawal model of hemispheric activation suggests that left frontal cortical areas mediate approach, while right frontal cortical areas mediate withdrawal motivation. Within this framework, the present study investigates the association of frontal cortical asymmetry with attentional and emotional responses toward approach‐ and withdrawal‐related emotional stimuli. Resting frontal asymmetry was measured from 43 students before they passively viewed negative, neutral, and positive emotional pictures. The startle reflex, skin conductance response, and subjective ratings of valence and arousal were assessed to quantify emotional responding, while attention was assessed with ERPs. We also assessed frontal asymmetry in response to the pictures. Results indicated that relatively stronger right frontal cortical activation was associated with increased N1 amplitudes and more negative subjective emotional evaluation of all stimuli. Furthermore, enhanced right frontal asymmetry (state and trait) was associated with diminished emotional modulation of the late positive potential. In contrast, no association of frontal asymmetry with defensive reflex physiology or activation of sympathetic nervous system activity was found. The current data suggest dissociable influence of resting frontal brain asymmetry on attentional and physiological processing of withdrawal‐ and approach‐related stimuli. That is, asymmetrical frontal cortical brain activation might not modulate approach‐/withdrawal‐related motor responses and sympathetic arousal directly, but instead enhances allocation of attentional resources to subjectively significant stimuli. The results are discussed in terms of their potential importance for emotion perception in anxiety disorders and their contribution to the understanding of frontal asymmetry.
Little‐v0Agreement and Templatic Morphology in Ch'ol
Authors: Coon Jessica 
Published: April 2017

AbstractThis paper addresses typological differences in subject–verb agreement and provides evidence that transitive subject agreement need not always involve a high functional head, namely T0, but may instead be the result of a local relation between the subject and a low functional head, v0. In Mayan languages, grammatical relations are head‐marked on the predicate through two series of morphemes, known as “Set A” (ergative/possessive) and “Set B” (absolutive). I argue that Set A morphemes reflect a local relationship of agreement between v0and the transitive subject in its low base position and, in an analogous structural configuration in the nominal domain, between a possessive n0head and the possessor. Crucially, I show that no higher functional projection is involved. This is important in light of proposals that ergative agreement systems are epiphenomenal, resulting from standard nominative agreement from T0which is blocked from agreeing with morphologically case‐marked ergative subjects (Woolford). In this paper, I examine the morphologically ergative Mayan language Ch'ol to show that true ergative agreement is possible even in the absence of morphological case. This paper has implications for the typology of ergative case and agreement systems and contributes to our understanding of the nature of agreement and clitic doubling.
Creutzfeldt‐Jakob disease lookback study: 21 years of surveillance for transfusion transmission risk
Authors: Crowder Lauren A. , Schonberger Lawrence B. , Dodd Roger Y. , Steele Whitney R. 
Published: April 2017

BACKGROUNDTransfusion transmission of human prion diseases has been observed for variant Creutzfeldt‐Jakob disease (vCJD), but not for the classic forms of prion disease (CJD: sporadic, genetic, and iatrogenic). Although the presence of prions or misfolded prion proteins in blood has been documented in some patients with the most common form of CJD, sporadic CJD, no transfusion‐transmitted cases of CJD have been recognized. Since 1995, the American Red Cross has conducted a lookback study of the recipients of blood products from donors who develop CJD to assess the risk of blood‐borne CJD transmission in the United States.STUDY DESIGN AND METHODSBlood donors subsequently diagnosed with confirmed or probable CJD were enrolled and the consignees were asked to identify the recipients of their blood products. These donors' transfusion recipients are traced annually with the National Death Index to see if they subsequently die of CJD.RESULTSTo date, 65 CJD donors have been enrolled along with 826 of their blood recipients. These recipients have contributed 3934 person‐years of follow‐up and no transfusion‐transmitted cases of CJD have been recognized.CONCLUSIONFrom this study, as well as other epidemiologic studies, there is no evidence of CJD transfusion transmission; this risk remains theoretical.
3 Tesla magnetic resonance imaging study of the normal canine femoral and sciatic nerves
Authors: Sievert Christine , Richter Henning , Gascho Dominic , Kircher Patrick R. , Carrera Inés 
Published: April 2017

AbstractUnderstanding the normal course and optimizing visualization of the canine peripheral nerves of the lumbar plexus, in particular the sciatic and the femoral nerves, is essential when interpreting images of patients with suspected peripheral neuropathies such as inflammatory or neoplastic conditions. The purpose of this prospective, anatomic study was to describe the magnetic resonance imaging (MRI) anatomy of the normal canine femoral and sciatic nerves and to define the sequences in which the nerves are best depicted. A preliminary postmortem cadaver study was performed to determine optimal sequences and imaging protocol. In a second step the optimized technique was implemented on 10 healthy Beagle dogs, included in the study. The applied protocol included the following sequences: T1‐weighted, T2‐weighted, T2‐Spectral Attenuated Inversion Recovery, T1‐weighted postcontrast and T1‐Spectral Presaturated Inversion Recovery postcontrast. All sequences had satisfactory signal‐to‐noise ratio and contrast resolution in all patients. The sciatic and femoral nerves were seen in all images. They were symmetric and of homogeneous signal intensity, being iso‐ to mildly hyperintense to muscle on T2‐weighted, mildly hyperintense in T2‐Spectral Attenuated Inversion Recovery, and iso‐ to mildly hypointense in T1‐weighted images. No evidence of contrast enhancement in T1‐weighted and T1‐Spectral Presaturated Inversion Recovery postcontrast sequences was observed. The anatomic landmarks helpful to identify the course of the femoral and sciatic nerves are described in detail. This study may be used as an anatomical reference, depicting the normal canine femoral and sciatic nerves at 3 Tesla MRI.