bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis
Authors: Zheng Huiyuan , Rinaman Linda 
Published: February 2013

AbstractThe α2 adrenergic receptor antagonist yohimbine (YO) increases transmitter release from noradrenergic (NA) terminals in cortical and subcortical brain regions, including the bed nucleus of the stria terminalis (BST). YO activates the hypothalamic–pituitary–adrenal (HPA) stress axis and is potently anxiogenic in rats and humans. We previously reported that hindbrain NA neurons within the caudal nucleus of the solitary tract (NST‐A2/C2) and ventrolateral medulla (VLM‐A1/C1) that innervate the anterior ventrolateral (vl)BST contribute to the ability of YO to activate the HPA stress axis in rats. To determine whether the same NA pathway also contributes to YO‐induced anxiogenesis in the elevated plus maze (EPMZ), a selective saporin ribotoxin conjugate (dopamine beta hydroxylase conjugated to saporin toxin, DSAP) was microinjected bilaterally into the anterior vlBST to destroy its NA inputs. Sham‐lesioned controls were microinjected with vehicle. Two experiments were conducted to determine DSAP lesion effects on EPMZ behavior. DSAP lesions did not alter maze behavior in rats after intraperitoneal saline, and did not alter the significant effect of prior maze experience to reduce exploratory and open arm maze activities. However, in maze‐naïve rats, DSAP lesions abolished YO anxiogenesis in the EPMZ. Post‐mortem immunocytochemical analyses confirmed that DSAP consistently ablated caudal NST‐A2/C2 and VLM‐A1/C1 neurons that innervate the anterior vlBST. DSAP lesions did not destroy non‐NA inputs to the anterior vlBST, and produced inconsistent cell loss within the pontine locus coeruleus (A6 cell group) that was unrelated to YO anxiogenesis. Thus, the ability of YO to increase anxiety‐like behavior in the EPMZ depends on hindbrain NA neurons that target the anterior vlBST.
Interobserver agreement of the old and the newly proposed ILAE epilepsy classification in children
Authors: van Campen Jolien S. , Jansen Floor E. , Brouwer Oebele F. , Nicolai Joost , Braun Kees P. J. 
Published: February 2013

SummaryPurposeAccurate classification of epileptic seizures, epilepsies, and epilepsy syndromes is mandatory in both clinical practice and epilepsy research. In 2010, the International League Against Epilepsy (ILAE) proposed a new classification scheme. The aim of this study is to determine whether application of this new classification for epileptic seizures and epilepsies has improved interobserver agreement compared to the classification schemes used previously.MethodsThree pediatric neurologists working in different university hospitals retrospectively classified seizures and epilepsies of 80 children (165 seizures) referred to the University Center Utrecht, based on anonymized data, according to the newly proposed (2010) as well as the old (1981/1989) ILAE classification schemes. We determined interobserver agreement of the application of both ILAE classifications with kappa statistics.Key FindingsInterobserver agreement of the new classification for seizures and epilepsies is comparable to that of previous classifications. There is substantial agreement on the newly introduced etiologic axis.SignificanceIntroduction of the new epilepsy classification has not substantially improved interobserver agreement. This study shows which items cause considerable interobserver disagreement and therefore need specification.
Border Children: Interpreting Autism Spectrum Disorder in South Korea
Authors: Grinker Roy Richard , Cho Kyungjin 
Published: February 2013

AbstractIn this article, we describe reluctant mothers on the brink of accepting autism spectrum disorder (ASD) as a diagnosis for their children, but caught in a web of social meanings that push them to resist it. We argue that several tensions underlie this resistance: (1) an opposition between homogeneity and heterogeneity, in which mothers aim to define their child as “normal”; (2) a distinction between social and intellectual domains of child development, in which mothers localize their children's problems as deficits in a discrete area of development, rather than as a global or pervasive impairment; and (3) an opposition between chronicity and recovery, in which mothers reject a label they fear will index a permanent condition. These oppositions help to define the interaction between a diagnosis new to Koreans (ASD) and a particular condition (the child who has the symptoms of ASD but is academically successful) to form a new kind of child that mothers and teachers increasingly call “border children” (gyonggye‐seon aideul). This specific ethnographic inquiry informs debates over the ontological bases for psychiatric diagnoses in children, and the processes through which local institutions, classificatory schemes, expertise, and child behavior shape conceptions of child development. [autism, Korea, child development, child psychiatry, border children]
“We Want to See Our King”: Apparitions in Messianic Habad
Authors: Bilu Yoram 
Published: February 2013

AbstractReports of apparitions of the late Rabbi Menachem Mendel Schneerson, the last leader of the Habad Hasidic movement, have been spreading among the radically messianic Hasidim (meshichistim) in Israel, who maintain that the Rabbi, the designated Messiah, has not died. Expanding on the cognitive model of source misattribution, I seek to account for the apparitions by unpacking the messianic ecology cultivated by the meshichistim to make the absent Rabbi present. Habad's dialectical mysticism and anguish over the Rabbi's disappearance are likely to provide the mindset and motivation for sightings, but it is the rich array of icons and traces of the Rabbi, and mimetic practices in which they are embedded, that constitute the perceptual field where he can be seen. This cultural décor is particularly evident for apparitions in ritual arenas, while apparitions in mundane settings are often triggered by acute distress. Comparing the apparitions to visions in Christianity, I account for the lingering ambivalence toward apparitions in messianic Habad by highlighting the epistemological constraints imposed on them by the denial of the Rabbi's death. [apparitions, Habad Hasidism, signal detection theory, messianic ecology, Rabbi Menachem Mendel Schneeerson]
Respiratory diseases and their effects on respiratory function and exercise capacity
Authors: Van Erck‐Westergren E. , Franklin S. H. , Bayly W. M. 
Published: February 2013

SummaryGiven that aerobic metabolism is the predominant energy pathway for most sports, the respiratory system can be a rate‐limiting factor in the exercise capacity of fit and healthy horses. Consequently, respiratory diseases, even in mild forms, are potentially deleterious to any athletic performance. The functional impairment associated with a respiratory condition depends on the degree of severity of the disease and the equestrian discipline involved. Respiratory abnormalities generally result in an increase in respiratory impedance and work of breathing and a reduced level of ventilation that can be detected objectively by deterioration in breathing mechanics and arterial blood gas tensions and/or lactataemia. The overall prevalence of airway diseases is comparatively high in equine athletes and may affect the upper airways, lower airways or both. Diseases of the airways have been associated with a wide variety of anatomical and/or inflammatory conditions. In some instances, the diagnosis is challenging because conditions can be subclinical in horses at rest and become clinically relevant only during exercise. In such cases, an exercise test may be warranted in the evaluation of the patient. The design of the exercise test is critical to inducing the clinical signs of the problem and establishing an accurate diagnosis. Additional diagnostic techniques, such as airway sampling, can be valuable in the diagnosis of subclinical lower airway problems that have the capacity to impair performance. As all these techniques become more widely used in practice, they should inevitably enhance veterinarians' diagnostic capabilities and improve their assessment of treatment effectiveness and the long‐term management of equine athletes.
Synstatin: a selective inhibitor of the syndecan‐1‐coupled IGF1R–αvβ3 integrin complex in tumorigenesis and angiogenesis
Authors: Rapraeger Alan C. 
Published: February 2013

The syndecans are a family of heparan sulfate‐decorated cell‐surface proteoglycans: matrix receptors with roles in cell adhesion and growth factor signaling. Their heparan sulfate chains recognize ‘heparin‐binding’ motifs that are ubiquitously present in the extracellular matrix, providing the means for syndecans to constitutively bind and cluster to sites of cell–matrix adhesion. Emerging evidence suggests that specialized docking sites in the syndecan extracellular domains may serve to localize other receptors to these sites as well, including integrins and growth factor receptor tyrosine kinases. A prototype of this mechanism is capture of the αvβ3 integrin and insulin‐like growth factor 1 receptor (IGF1R) by syndecan‐1 (Sdc1), forming a ternary receptor complex in which signaling downstream of IGF1R activates the integrin. This Sdc1‐coupled ternary receptor complex is especially prevalent on tumor cells and activated endothelial cells undergoing angiogenesis, reflecting the up‐regulated expression of αvβ3 integrin in such cells. As such, much effort has focused on developing therapeutic agents that target this integrin in various cancers. Along these lines, the site in the Sdc1 ectodomain that is responsible for capture and activation of the αvβ3 or αvβ5 integrins by IGF1R can be mimicked by a short peptide called ‘synstatin’, which competitively displaces the integrin and IGF1R kinase from the syndecan and inactivates the complex. This review summarizes our current knowledge of the Sdc1‐coupled ternary receptor complex and the efficacy of synstatin as an emerging therapeutic agent to target this signaling mechanism.
Endorepellin laminin‐like globular 1/2 domains bind Ig3–5 of vascular endothelial growth factor (VEGF) receptor 2 and block pro‐angiogenic signaling by VEGFA in endothelial cells
Authors: Willis Chris D. , Poluzzi Chiara , Mongiat Maurizio , Iozzo Renato V. 
Published: February 2013

Endorepellin, a processed fragment of perlecan protein core, possesses anti‐angiogenic activity by antagonizing endothelial cells. Endorepellin contains three laminin G‐like (LG) domains and binds simultaneously to vascular endothelial growth factor receptor 2 (VEGFR2) and α2β1 integrin, resulting in dual receptor antagonism. Treatment of endothelial cells with endorepellin inhibits transcription of VEGFA, the natural ligand for VEGFR2, attenuating the pro‐survival and migratory activities of VEGFA/VEGFR2 signaling cascade. Here, we investigated the specific binding site of endorepellin within the ectodomain of VEGFR2. Full‐length endorepellin was not capable of displacing VEGFA binding from VEGFR2 and LG3 domain alone did not bind VEGFR2. This suggested different binding mechanisms of the extracellular Ig domains of VEGFR2. Therefore, we hypothesized that endorepellin would bind through its proximal LG1/2 domains to VEGFR2 in a different region than VEGFA. Indeed, we found that LG1/2 did not bind Ig1–3, but did bind with high affinity to Ig3–5, distal to the known VEGFA binding site, i.e. Ig2–3. These results support a role for endorepellin as an allosteric inhibitor of VEGFR2. Moreover, we found that LG1/2 blocked the rapid VEGFA activation of VEGFR2 at Tyr1175 in endothelial cells. In contrast, LG1/2 did not result in actin cytoskeletal disassembly in endothelial cells whereas LG3 alone did induce cytoskeletal collapse. However, LG1/2 did inhibit VEGFA‐dependent endothelial migration through fibrillar collagen I. These studies provide a mechanistic understanding of how the different LG domains of endorepellin signal in endothelial cells while serving as a template for protein design of receptor tyrosine kinase antagonists.Structured digital abstract

Ig1-3 of VEGFR2 binds to VEGFA by filter binding (View interaction)

Ig3-5 of VEGFR2 binds to Endorepellin LG1/2 by enzyme linked immunosorbent assay (View interaction)

Ig1-3 of VEGFR2 binds to Endorepellin LG1/2 by filter binding (View Interaction: 1, 2)

Endorepellin LG1/2 binds to Ig3-5 of VEGFR2 by anti bait coimmunoprecipitation (View interaction)

[Structured digital abstract was added on 3 May 2013 after original online publication]
Interannual variability of net ecosystem productivity in forests is explained by carbon flux phenology in autumn
Authors: Wu Chaoyang , Chen Jing M. , Black T. Andrew , Price David T. , Kurz Werner A. , Desai Ankur R. , Gonsamo Alemu , Jassal Rachhpal S. , Gough Christopher M. , Bohrer Gil , Dragoni Danilo , Herbst Mathias , Gielen Bert , Berninger Frank , Vesala Timo , Mammarella Ivan , Pilegaard Kim , Blanken Peter D. 
Published: February 2013

AbstractAimTo investigate the importance of autumn phenology in controlling interannual variability of forest net ecosystem productivity (NEP) and to derive new phenological metrics to explain the interannual variability of NEP.LocationNorth America and Europe.MethodFlux data from nine deciduous broadleaf forests (DBF) and 13 evergreen needleleaf forests (ENF) across North America and Europe (212 site‐years) were used to explore the relationships between the yearly anomalies of annual NEP and several carbon flux based phenological indicators, including the onset/end of the growing season, onset/end of the carbon uptake period, the spring lag (time interval between the onset of growing season and carbon uptake period) and the autumn lag (time interval between the end of the carbon uptake period and the growing season). Meteorological variables, including global shortwave radiation, air temperature, soil temperature, soil water content and precipitation, were also used to explain the phenological variations.ResultsWe found that interannual variability of NEP can be largely explained by autumn phenology, i.e. the autumn lag. While variation in neither annual gross primary productivity (GPP) nor in annual ecosystem respiration (Re) alone could explain this variability, the negative relationship between annual NEP and autumn lag was due to a larger Re/GPP ratio in years with a prolonged autumn lag. For DBF sites, a longer autumn lag coincided with a significant decrease in annual GPP but showed no correlation with annual Re. However, annual GPP was insensitive to a longer autumn lag in ENF sites but annual Re increased significantly.Main conclusionsThese results demonstrate that autumn phenology plays a more direct role than spring phenology in regulating interannual variability of annual NEP. In particular, the importance of respiration may be potentially underestimated in deriving phenological indicators.
Comparison of near infrared reflectance spectroscopy calibration strategies for the botanical composition of grass‐clover mixtures
Authors: Cougnon M. , Van Waes C. , Dardenne P. , Baert J. , Reheul D. 
Published: February 2013

AbstractPredicting species composition in mixed swards by near infrared reflectance spectroscopy (NIRS) can save labour in grassland research, provided equations are available. This study compares calibration strategies to predict species composition in swards with tall fescue (Festuca arundinacea), perennial ryegrass (Lolium perenne) and white clover (Trifolium repens). The compared calibration strategies were based on either real or artificial samples. Real samples are samples taken from multispecies swards; the species composition is known by hand separating; after separating, the original samples are recomposed. Artificial samples are samples obtained by mixing single species grown in pure stands in known proportions. The performance of the equation based on real samples was significantly better than the performance of the equation based on artificial samples. We hypothesized that the weak performance of the equation based on artificial samples was due to a lack of environmental variation in the spectra of the artificial samples. The hypothesis was supported by the good performance of a novel calibration strategy based on the spectra of the artificial samples with added variation. According to the obtained results, a calibration strategy based on few but diverse calibration samples is discussed.
Characterization of Flow Dynamics and Vulnerability in a Coastal Aquifer System
Authors: Murgulet Dorina , Tick Geoffrey R. 
Published: February 2013

AbstractTraditional aquifer vulnerability techniques primarily rely on spatial property data for a region and are limited by their ability to directly or indirectly assess flow and transport processes occurring from the surface to depth within an aquifer system. The main objective of this study was to investigate groundwater vulnerability in terms of aquifer interconnectivity and flow dynamics. A combination of stable isotopes, groundwater age‐dating (radiocarbon), and geomorphic/geogenic spatial analyses was applied to a regional, highly developed coastal aquifer to explain the presence of nitrate at depth. The average δ13C value (−17.3 ± 2‰ VPDB, n = 27) is characteristic of groundwater originating from locally infiltrated precipitation through extensively cultivated soils. The average δ18O and δD values (−4.0 ± 0.1‰ VSMOW, n = 27; δD: −19.3 ± 1‰ VSMOW, n = 27, respectively) are similar to precipitation water derived from maritime sources feeding the region's surface water and groundwater. Stable and radioactive isotopes reveal significant mixing between shallow and deep aquifers due to high velocities, hydraulic connection, and input of local recharge water to depths. Groundwater overdevelopment enhances deeper and faster modern water downward flux, amplifying aquifer vulnerability. Therefore, aquifer vulnerability is a variable, dependent on the type and degree of stress conditions experienced by a groundwater system as well as the geospatial properties at the near surface.
Enhanced cross‐priming of naive CD8+T cells by dendritic cells treated by the IMiDs® immunomodulatory compounds lenalidomide and pomalidomide
Authors: Henry Jake Y. , Labarthe Marie‐Christine , Meyer Brendan , Dasgupta Prokar , Dalgleish Angus G. , Galustian Christine 
Published: February 2013

SummaryThe IMiDs® immunomodulatory compounds lenalidomide and pomalidomide are agents with anti‐inflammatory, immunomodulatory and anti‐cancer activity. An excellent success rate has been shown for multiple myeloma in phase I/II clinical trials leading to Food and Drug Administration approval of lenalidomide. One mechanism by which these drugs could enhance anti‐tumour immunity may be through enhanced dendritic cell (DC) function. Thalidomide, a compound structurally related to lenalidomide and pomalidomide, is known to enhance DC function, and we have investigated whether its analogues, pomalidomide and lenalidomide, also have functional effects on DCs. We used mouse bone marrow‐derived DCs treated with 5 or 10 μm pomalidomide, or lenalidomide from day 1 of culture. Treatment with IMiD® immunomodulatory compounds increased expression of Class I (H2‐Kb), CD86, and pomalidomide also increased Class II (I‐Ab) expression in bone marrow‐derived DCs, as measured by flow cytometry. Fluorescent bead uptake was increased by up to 45% when DCs were treated with 5 or 10 μm pomalidomide or lenalidomide compared with non‐treated DCs. Antigen presentation assays using DCs primed with ovalbumin, and syngeneic T cells from transgenic OTI and OTII mice (containing MHC restricted, ovalbumin‐specific, T cells) showed that both pomalidomide and lenalidomide effectively increased CD8+ T‐cell cross‐priming (by up to 47%) and that pomalidomide alone was effective in increasing CD4+ T‐cell priming (by 30%). Our observations suggest that pomalidomide and lenalidomide enhance tumour antigen uptake by DCs with an increased efficacy of antigen presentation, indicating a possible use of these drugs in DC vaccine therapies.
Older Methadone Patients Achieve Greater Durations of Cocaine Abstinence with Contingency Management Than Younger Patients
Authors: Weiss Lindsay , Petry Nancy M. 
Published: February 2013

Background and ObjectivesContingency management (CM) interventions are efficacious in treating cocaine abusing methadone patients, but few studies have examined the effect of age on treatment outcomes in this population. This study evaluated the impact of age on treatment outcomes in cocaine abusing methadone patients.MethodsData were analyzed from 189 patients enrolled in one of three randomized studies that evaluated the efficacy of CM versus standard care (SC) treatment.ResultsAge was associated with some demographics and drug use characteristics including racial composition, education, and methadone dose. Primary drug abuse treatment outcomes did not vary across age groups, but CM had a greater benefit for engendering longer durations of abstinence in the middle/older and older age groups compared to the younger age groups. At the 6‐month follow‐up, submission of a cocaine positive urine sample was predicted by submission of a cocaine positive sample at intake, higher methadone doses, and assignment to SC rather than CM treatment.Conclusions and Scientific SignificanceAs substance abusers are living longer, examination of the efficacy of pharmacological and psychosocial treatments specifically within older age groups may lead to a better understanding of subpopulations for whom enhanced treatments such as CM are warranted. (Am J Addict 2013;22:119‐126)
Performance‐Enhancing Drugs on the Web: A Growing Public‐Health Issue
Authors: Brennan Brian P. , Kanayama Gen , Pope Harrison G. 
Published: February 2013

Background and ObjectivesToday's Internet provides extensive “underground” guidelines for obtaining and using illicit substances, including especially anabolic‐androgenic steroids (AAS) and other appearance‐ and performance‐enhancing drugs (APEDs). We attempted to qualitatively characterize APED‐related Internet sites.MethodsWe used relevant Internet search terms (eg, “steroids bodybuilding” and “buy steroids online”) to assess (i) the numbers of site visitors; (ii) offers of drugs for sale; and (iii) the quality of online medical information. We also chose the examples of (iv) “site‐enhancing oils” and (v) “cattle implants” to illustrate the volume of available Internet information as compared with that in the medical literature.ResultsWe found thousands of sites involving AAS and other APEDs. Most sites presented an unabashedly pro‐drug position, often openly questioning the qualifications and motivations of mainstream medical practitioners. Offers of AAS and other APEDs for sale, together with medical advice of varying legitimacy, was widespread across sites. Importantly, many sites provided detailed guidelines for exotic forms of APED use, some likely associated with serious health risks, which are probably unknown to most practicing clinicians.Conclusions and Scientific SignificanceIt seems important for practitioners to be aware of the extent of this “underground literature,” which may strongly influence their patients' decisions about use and abuse of APEDs. (Am J Addict 2013;22:158‐161)