bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adolescent female rats exhibiting activity‐based anorexia express elevated levels of GABAA receptor α4 and δ subunits at the plasma membrane of hippocampal CA1 spines
Authors: Aoki Chiye , Sabaliauskas Nicole , Chowdhury Tara , Min Jung‐Yun , Colacino Anna Rita , Laurino Kevin , Barbarich‐Marsteller Nicole C. 
Published: December 2011

AbstractActivity‐based anorexia (ABA) is an animal model for anorexia nervosa that has revealed genetic links to anxiety traits and neurochemical characteristics within the hypothalamus. However, few studies have used this animal model to investigate the biological basis for vulnerability of pubertal and adolescent females to ABA, even though the great majority of the anorexia nervosa cases are females exhibiting the first symptoms during puberty. GABAergic inhibition of the hippocampus strongly regulates anxiety as well as plasticity throughout life. We recently showed that the hippocampal CA1 of female mice undergo a dramatic change at puberty onset—from expressing virtually none of the nonsynaptic α4βδ GABAA receptors (GABARs) prepubertally to expressing these GABARs at ∼7% of the CA1 dendritic spine membranes at puberty onset. Furthermore, we showed that this change underlies the enhanced modulation of anxiety, neuronal excitability, and NMDA receptor‐dependent synaptic plasticity in the hippocampus by the stress neurosteroid, THP (3α‐OH‐5α[β]‐pregnan‐20‐one or [allo]pregnanolone). Here, we used quantitative electron microscopy to determine whether ABA induction in female rats during adolescence also elevates the expression of α4 and δ subunits of α4βδ GABARs, as was observed at puberty onset for mice. Our analysis revealed that rats also exhibit a rise of α4 and δ subunits of α4βδ GABARs at puberty onset, in that these subunits are detectable at ∼6% of the dendritic spine membranes of CA1 pyramidal cells at puberty onset (postnatal day 32–36; P32–36) but this drops to about 2% by P40–P44. The levels of α4 and δ subunits at the CA1 spines remained low following exposure of females to either of the two environmental factors needed to generate ABA—food restriction and access to a running wheel for 4 days—from P40 to P44. This pattern contrasted greatly from those of ABA animals, for which the two environmental factors were combined. Within the hippocampus of ABA animals, 12% of the spine profiles were labeled for α4, reflecting a sixfold increase, relative to hippocampi of age‐matched (P44) control females (p < 0.005). Concurrently, 7% of the spine profiles were labeled for δ, reflecting a 130% increase from the control values of 3% (p = 0.01). No measurable change was detected for spine size. The observed magnitude of increase in the α4 and δ subunits at spines is sufficient to increase both tonic inhibition of hippocampus and anxiety during stress, thereby likely to exacerbate hyperactivity and weight loss. Synapse, 2012. © 2011 Wiley Periodicals, Inc.
Effect of transient blockade of N‐methyl‐D‐aspartate receptors at neonatal stage on stress‐induced lactate metabolism in the medial prefrontal cortex of adult rats: Role of 5‐HT1A receptor agonism
Authors: Uehara Takashi , Itoh Hiroko , Matsuoka Tadasu , Rujescu Dan , Genius Just , Seo Tomonori , Sumiyoshi Tomiki 
Published: December 2011

AbstractDecreased activity of the medial prefrontal cortex (mPFC) has been considered a basis for core symptoms of schizophrenia, an illness associated with a neurodevelopmental origin. Evidence from preclinical and clinical studies indicates that serotonin (5‐HT)1A receptors play a crucial role in the energy metabolism of the mPFC. This study was undertaken to determine (1) if transient blockade of N‐methyl‐D‐aspartate receptors during the neonatal stage inhibit energy demands in response to stress, as measured by extracellular lactate concentrations, in the mPFC at the young adult stage, and (2) if tandospirone, a 5‐HT1A partial agonist, reverses the effect of the neonatal insult on energy metabolism. Male pups received MK‐801 (0.20 mg/kg) on postnatal days (PDs) 7–10. On PD 63, footshock stress‐induced lactate levels were measured using in vivo microdialysis technique. Tandospirone (0.1, 1.0, and 5.0 mg/kg) was administered once daily for 14 days before the measurement of lactate levels. Neonatal MK‐801 treatment suppressed footshock stress‐induced lactate production in the mPFC, but not caudate‐putamen, whereas basal lactate levels were not significantly changed in either brain region. The MK‐801‐induced suppression of footshock stress‐induced lactate production in the mPFC was attenuated by tandospirone at 1.0mg/kg/day, but not 0.1 or 5.0 mg/kg/day, which is an effect antagonized by coadministration of WAY‐100635, a selective 5‐HT1A antagonist. These results suggest a role for impaired lactate metabolism in some of the core symptoms of schizophrenia, for example, negative symptoms and cognitive deficits. The implications for the ability of 5‐HT1A agonism to ameliorate impaired lactate production in the mPFC of this animal model are discussed. Synapse, 2012. © 2011 Wiley Periodicals, Inc.
Impact of Clinical and Pathohistological Characteristics on the Incidence of Recurrence and Survival in Elderly Patients with Gastric Cancer
Authors: Dittmar Yves , Rauchfuss Falk , Götz Max , Scheuerlein Hubert , Jandt Karin , Settmacher Utz 
Published: December 2011

AbstractBackgroundGastric cancer is one of the most frequent malignant tumors worldwide. Despite improvements in diagnostic procedures, as well as the introduction of multimodal treatment strategies, the overall prognosis remains poor. The role of gastric resection in elderly patients with gastric cancer has not been clearly defined as yet. The goal of the present study was to assess whether specific pathohistological features result in different outcomes for younger patients and elderly patients.MethodsA total of 272 patients with advanced gastric cancer treated surgically in our hospital between 1998 and 2009 were included in the study. Data were analyzed from a prospectively maintained database.ResultsMedian overall survival was 84 months in the younger subgroup and 37 months in the elderly subgroup (P = 0.038), whereas local recurrence occurred more frequently in younger patients (33% vs. 23%). We identified positive lymph nodes at the contralateral curvature, perilymphonodular tumor cells, and positive lymph node conglomerates as strong negative prognostic factors. There were few pathohistological characteristics that affected survival and the incidence of tumor recurrence differently in elderly and younger patients. Although only a few elderly patients underwent chemotherapy plus gastric resection (7% vs. 28% of the younger patients), there was a trend toward longer survival for those who received multimodal treatment.ConclusionsOur results suggest that there is no tumor‐related prognostic difference between young and elderly patients that would preclude radical surgery in elderly patients, as long as they are generally fit for surgery.
Mineral, Virginia, earthquake illustrates seismicity of a passive‐aggressive margin
Authors: Wolin Emily , Stein Seth , Pazzaglia Frank , Meltzer Anne , Kafka Alan , Berti Claudio 
Published: December 2011

The August 2011 M 5.8 Mineral, Virginia, earthquake that shook much of the northeastern U.S. dramatically demonstrated that passive continental margins sometimes have large earthquakes. We illustrate some general aspects of such earthquakes and outline some of the many unresolved questions about them. They occur both offshore and onshore, reaching magnitude 7, and are thought to reflect reactivation of favorably‐oriented, generally margin‐parallel, faults created during one or more Wilson cycles by the modern stress field. They pose both tsunami and shaking hazards. However, their specific geologic setting and causes are unclear because large magnitude events occur infrequently, microseismicity is not well recorded, and there is little, if any, surface expression of repeated ruptures. Thus presently active seismic zones may be areas associated with higher seismicity over the long term, the present loci of activity that migrates, or aftershock zones of large prehistoric earthquakes. The stresses causing the earthquakes may result from platewide driving forces, glacial isostatic adjustment, localized margin stresses, and/or dynamic topography. The resulting uncertainties make developing cost‐effective mitigation strategies a major challenge. Progress on these issues requires integrating seismic, geodetic, and geological techniques.
High-resolution dose–response screening using droplet-based microfluidics
Authors: Miller Oliver J. , Harrak Abdeslam El , Mangeat Thomas , Baret Jean-Christophe , Frenz Lucas , Debs Bachir El , Mayot Estelle , Samuels Michael L. , Rooney Eamonn K. , Dieu Pierre , Galvan Martin , Link Darren R. , Griffiths Andrew D. 
Published: December 2011

A critical early step in drug discovery is the screening of a chemical library. Typically, promising compounds are identified in a primary screen and then more fully characterized in a dose–response analysis with 7–10 data points per compound. Here, we describe a robust microfluidic approach that increases the number of data points to approximately 10,000 per compound. The system exploits Taylor–Aris dispersion to create concentration gradients, which are then segmented into picoliter microreactors by droplet-based microfluidics. The large number of data points results in IC50values that are highly precise (± 2.40% at 95% confidence) and highly reproducible (CV = 2.45%,n = 16). In addition, the high resolution of the data reveals complex dose–response relationships unambiguously. We used this system to screen a chemical library of 704 compounds against protein tyrosine phosphatase 1B, a diabetes, obesity, and cancer target. We identified a number of novel inhibitors, the most potent being sodium cefsulodine, which has an IC50of 27 ± 0.83 μM.
Identification of PlantRAD52Homologs and Characterization of theArabidopsis thaliana RAD52-Like Genes
Authors: Samach Aviva , Melamed-Bessudo Cathy , Avivi-Ragolski Naomi , Pietrokovski Shmuel , Levy Avraham A. 
Published: December 2011

AbstractRADiation sensitive52 (RAD52) mediates RAD51 loading onto single-stranded DNA ends, thereby initiating homologous recombination and catalyzing DNA annealing. RAD52 is highly conserved among eukaryotes, including animals and fungi. This article reports that RAD52 homologs are present in all plants whose genomes have undergone extensive sequencing. Computational analyses suggest a very early RAD52 gene duplication, followed by later lineage-specific duplications, during the evolution of higher plants. Plant RAD52 proteins have high sequence similarity to the oligomerization and DNA binding N-terminal domain of RAD52 proteins. Remarkably, the two identified Arabidopsis thaliana RAD52 genes encode four open reading frames (ORFs) through differential splicing, each of which specifically localized to the nucleus, mitochondria, or chloroplast. The A. thaliana RAD52-1A ORF provided partial complementation to the yeast rad52 mutant. A. thaliana mutants and RNA interference lines defective in the expression of RAD52-1 or RAD52-2 showed reduced fertility, sensitivity to mitomycin C, and decreased levels of intrachromosomal recombination compared with the wild type. In summary, computational and experimental analyses provide clear evidence for the presence of functional RAD52 DNA-repair homologs in plants.
Increased exhaled nitric oxide predicts new‐onset rhinitis and persistent rhinitis in adolescents without allergic symptoms
Authors: Malinovschi A. , Alving K. , Kalm‐Stephens P. , Janson C. , Nordvall L. 
Published: December 2011

SummaryBackgroundThe fraction of nitric oxide in exhaled air (FENO) is increased in rhinitis and asthma. We have previously suggested that elevated FENO levels in the absence of asthma symptoms may be a sign of ‘early asthma’. In the present study, we hypothesize that elevated exhaled NO levels may also precede rhinitis symptoms.ObjectiveTo investigate in a cohort of adolescents whether or not increased exhaled NO levels at the age of 13–14 years predicted new‐onset or persistent rhinitis within a 4‐year period.MethodsA total of 959 randomly selected adolescents (13–14 years) completed a questionnaire on respiratory symptoms at baseline and follow‐up, 4 years later. Exhaled NO was measured at baseline. After exclusion of subjects with asthma diagnosis or asthma symptoms at baseline, 657 participants were eligible for the present study.ResultsHigher FENO levels at baseline were associated with increased risk for new‐onset (P = 0.009) and persistent rhinitis (P = 0.03) within a 4‐year period. The risk of new‐onset rhinitis was 2.32 (1.23, 4.37) [OR (95% CI)] times higher if FENO > 90th percentile of the group without rhinitis at baseline. This increased risk for new‐onset rhinitis was significant [2.49 (1.24, 5.01)] after excluding subjects with allergic symptoms. The risk of persistent rhinitis was 5.11 (1.34, 19.57) times higher if FENO > 90th percentile of the group without rhinitis at baseline.ConclusionElevated exhaled nitric oxide levels predicted incident and persistent rhinitis in this population‐based study of adolescents. Moreover, these findings were consistent after excluding subjects with allergic symptoms. Thus, it appears that elevation of exhaled NO precedes airway symptoms and predicts development of rhinitis in subjects without allergic symptoms or family history of allergic disease.
Anaphylaxis and reactions to foods in children – a population‐based case study of emergency department visits
Authors: Vetander M. , Helander D. , Flodström C. , Östblom E. , Alfvén T. , Ly D. H. , Hedlin G. , Lilja G. , Nilsson C. , Wickman M. 
Published: December 2011

SummaryBackgroundInformation about acute reactions to foods among children is limited.ObjectiveTo describe the overall incidence of anaphylaxis in a paediatric emergency department (ED) setting and to describe reactions to foods in relation to sex and age, clinical characteristics and management.MethodsIn a review of medical records, children with ED visits at any of three paediatric hospitals in Stockholm County during 2007 were targeted. Inclusion criteria were any adverse reaction to foods or anaphylaxis.Results383 children fulfilled the inclusion criteria of which 371 had had reactions to foods. The incidence of anaphylaxis was 32 per 100 000 person years irrespective of cause and food was involved in 92%. Tree nuts, particular cashew, and peanut were the most common eliciting foods, and in children under 3 years, reactions to these two food allergens were as common as reactions to milk and egg. Pollen‐allergic children seemed to be admitted due to food‐induced anaphylaxis more often during the deciduous tree pollen season compared with the rest of the year (P = 0.015). Symptoms from the lower airways occurred in 49% of children with anaphylaxis but without underlying asthma compared with 72% of children with anaphylaxis and asthma, P < 0.01.Conclusions and Clinical RelevanceReactions to peanut and tree nuts are as common as reactions to milk and egg in early life. Concomitant exposure to airborne allergens seems to increase the risk of anaphylaxis to foods. Among children with anaphylaxis, wheeze is prevalent even in children without asthma diagnosis.
Immunology in the clinic review series; focus on type 1 diabetes and viruses: the enterovirus link to type 1 diabetes: critical review of human studies
Authors: Stene L C , Rewers M 
Published: December 2011

Summary
OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES
Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy.
The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans.
The association between neutrophil gelatinase‐associated lipocalin and clinical outcome in chronic heart failure: results from CORONA*
Authors: Nymo S. H. , Ueland T. , Askevold E. T. , Flo T. H. , Kjekshus J. , Hulthe J. , Wikstrand J. , McMurray J. , Van Veldhuisen D. J. , Gullestad L. , Aukrust P. , Yndestad A. 
Published: December 2011

Abstract.  Nymo SH, Ueland T, Askevold ET, Flo TH, Kjekshus J, Hulthe J, Wikstrand J, McMurray J, Van Veldhuisen DJ, Gullestad L, Aukrust P, Yndestad A (Oslo University Hospital Rikshospitalet; University of Oslo; Oslo; Norwegian University of Technology and Science, Trondheim, Norway; Gothenburg University, Gothenburg; AstraZeneca, Mölndal, Sweden; University of Glasgow, UK; and University Medical Center Groningen, University of Groningen, The Netherlands). The association between neutrophil gelatinase‐associated lipocalin and clinical outcome in chronic heart failure: results from CORONA. J Intern Med 2012; 271: 436–443.Objective.  To study the prognostic value of neutrophil gelatinase‐associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology.Background.  Neutrophil gelatinase‐associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF.Methods.  We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n = 307) and all‐cause mortality (n = 321), cardiovascular mortality (n = 259) and hospitalization (n = 647) as well as the number of hospitalizations during follow‐up for all (n = 1934) and CV causes (n = 1204) in 1415 patients with chronic HF (≥60 years, New York Heart Association class II–IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo.Results.  Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A‐1 (ApoA‐1), glomerular filtration rate (GFR), C‐reactive protein (CRP) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA‐1, but not after adjusting for CRP and NT‐proBNP. There was no interaction between rosuvastatin treatment and NGAL.Conclusion.  Neutrophil gelatinase‐associated lipocalin added no significant information to NT‐proBNP and GFR in a multivariate model for primary and secondary end‐points.
Mutational dissection of the S/T‐kinase StkP reveals crucial roles in cell division of Streptococcus pneumoniae
Authors: Fleurie Aurore , Cluzel Caroline , Guiral Sébastien , Freton Céline , Galisson Frédéric , Zanella‐Cleon Isabelle , Di Guilmi Anne‐Marie , Grangeasse Christophe 
Published: December 2011

SummaryEukaryotic‐like serine/threonine‐kinases are involved in the regulation of a variety of physiological processes in bacteria. In Streptococcus pneumoniae, deletion of the single serine/threonine‐kinase gene stkP results in an aberrant cell morphology suggesting that StkP participates in pneumococcus cell division. To understand the function of StkP, we have engineered various pneumococcus strains expressing truncated or kinase‐dead forms of StkP. We show that StkP kinase activity, but also its extracellular and cytoplasmic domains per se, are required for pneumococcus cell division. Indeed, we observe that mutant cells show round or elongated shapes with non‐functional septa and a chain phenotype, delocalized sites of peptidoglycan synthesis and diffused membrane StkP localization. To gain understanding of the underlying StkP‐mediated regulatory mechanism, we show that StkP specifically phosphorylates in vivo the cell division protein DivIVA on threonine 201. Pneumococcus cells expressing non‐phosphorylatable DivIVA‐T201A possess an elongated shape with a polar bulge and aberrant spatial organization of nascent peptidoglycan. This brings the first evidence of the importance of StkP in relationship to the phosphorylation of one of its substrates in cell division. It is concluded that StkP is a multifunctional protein that plays crucial functions in pneumococcus cell shape and division.
The GtaR protein negatively regulates transcription of the gtaRI operon and modulates gene transfer agent (RcGTA) expression in Rhodobacter capsulatus
Authors: Leung Molly M. , Brimacombe Cedric A. , Spiegelman G. B. , Beatty J. Thomas 
Published: December 2011

SummaryThe gtaI gene of Rhodobacter capsulatus encodes an N‐acyl‐homoserine lactone (acyl‐HSL) synthase. Immediately 5′ of the gtaI gene is ORF rcc00328 that encodes a potential acyl‐HSL receptor protein. A combination of genetic and biochemical approaches showed that rcc00328 (renamed gtaR) modulates the production of a genetic exchange element called the gene transfer agent (RcGTA), and regulates the transcription of gtaI. Although gtaI mutants exhibited decreased levels of RcGTA production, mutagenesis of gtaR did not, whereas a gtaR/gtaI double mutant produced wild‐type levels of RcGTA. Because mutagenesis of gtaR suppressed the effect of the gtaI mutation, we suggest that the GtaR protein is a negative transcriptional regulator of RcGTA gene expression. We discovered that the gtaR and gtaI genes are co‐transcribed, and also negatively regulated by the GtaR protein in the absence of acyl‐HSL. A His‐tagged GtaR protein was purified, and DNA‐binding experiments revealed a binding site in the promoter region of the gtaRI operon. This GtaR protein did not bind to the RcGTA promoter region, and therefore modulation of RcGTA production appears to require at least one additional factor. We found that RcGTA production was stimulated by spent media from other species, and identified exogenous acyl‐HSLs that induce RcGTA.