bluuebunny/crossref_metadata_2025 huggingface dataset:
A genome-wide association study using international breeding-evaluation data identifies major loci affecting production traits and stature in the Brown Swiss cattle breed
Authors: Guo Jiazhong , Jorjani Hossein , Carlborg Örjan
Published: October 2012

Background

The genome-wide association study (GWAS) is a useful approach to identify genes affecting economically important traits in dairy cattle. Here, we report the results from a GWAS based on high-density SNP genotype data and estimated breeding values for nine production, fertility, body conformation, udder health and workability traits in the Brown Swiss cattle population that is part of the international genomic evaluation program.

Result

GWASs were performed using 50 k SNP chip data and deregressed estimated breeding values (DEBVs) for nine traits from between 2061 and 5043 bulls that were part of the international genomic evaluation program coordinated by Interbull Center. The nine traits were milk yield (MY), fat yield (FY), protein yield (PY), lactating cow’s ability to recycle after calving (CRC), angularity (ANG), body depth (BDE), stature (STA), milk somatic cell score (SCS) and milk speed (MSP). Analyses were performed using a linear mixed model correcting for population confounding. A total of 74 SNPs were detected to be genome-wide significantly associated with one or several of the nine analyzed traits. The strongest signal was identified on chromosome 25 for milk production traits, stature and body depth. Other signals were on chromosome 11 for angularity, chromosome 24 for somatic cell score, and chromosome 6 for milking speed. Some signals overlapped with earlier reported QTL for similar traits in other cattle populations and were located close to interesting candidate genes worthy of further investigations.

Conclusions

Our study shows that international genetic evaluation data is a useful resource for identifying genetic factors influencing complex traits in livestock. Several genome wide significant association signals could be identified in the Brown Swiss population, including a major signal on BTA25. Our findings report several associations and plausible candidate genes that deserve further exploration in other populations and molecular dissection to explore the potential economic impact and the genetic mechanisms underlying these production traits in cattle.
The complete mitochondrial genomes of two ghost moths, Thitarodes renzhiensis and Thitarodes yunnanensis: the ancestral gene arrangement in Lepidoptera
Authors: Cao Yong-Qiang , Ma Chuan , Chen Ji-Yue , Yang Da-Rong
Published: October 2012

Background

Lepidoptera encompasses more than 160,000 described species that have been classified into 45–48 superfamilies. The previously determined Lepidoptera mitochondrial genomes (mitogenomes) are limited to six superfamilies of the lineage Ditrysia. Compared with the ancestral insect gene order, these mitogenomes all contain a tRNA rearrangement. To gain new insights into Lepidoptera mitogenome evolution, we sequenced the mitogenomes of two ghost moths that belong to the non-ditrysian lineage Hepialoidea and conducted a comparative mitogenomic analysis across Lepidoptera.

Results

The mitogenomes ofThitarodes renzhiensisandT.yunnanensisare 16,173 bp and 15,816 bp long with an A + T content of 81.28 % and 82.34 %, respectively. Both mitogenomes include 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and the A + T-rich region. Different tandem repeats in the A + T-rich region mainly account for the size difference between the two mitogenomes. All the protein-coding genes start with typical mitochondrial initiation codons, except forcox1(CGA) andnad1(TTG) in both mitogenomes. The anticodon oftrnS(AGN)inT. renzhiensisandT. yunnanensisis UCU instead of the mostly used GCU in other sequenced Lepidoptera mitogenomes. The 1,584-bp sequence fromrrnStonad2was also determined for an unspecified ghost moth (Thitarodessp.), which has no repetitive sequence in the A + T-rich region. All threeThitarodesspecies possess the ancestral gene order withtrnI-trnQ-trnMlocated between the A + T-rich region andnad2, which is different from the gene ordertrnM-trnI-trnQin all previously sequenced Lepidoptera species. The formerly identified conserved elements of Lepidoptera mitogenomes (i.e. the motif ‘ATAGA’ and poly-T stretch in the A + T-rich region and the long intergenic spacer upstream ofnad2) are absent in theThitarodesmitogenomes.

Conclusion

The mitogenomes ofT. renzhiensisandT. yunnanensisexhibit unusual features compared with the previously determined Lepidoptera mitogenomes. Their ancestral gene order indicates that the tRNA rearrangement event(s) likely occurred after Hepialoidea diverged from other lepidopteran lineages. Characterization of the two ghost moth mitogenomes has enriched our knowledge of Lepidoptera mitogenomes and contributed to our understanding of the mechanisms underlying mitogenome evolution, especially gene rearrangements.
A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells
Authors: Polman J Annelies E , Welten Jennifer E , Bosch Danny S , de Jonge Robert T , Balog Judit , van der Maarel Silvère M , de Kloet E Ronald , Datson Nicole A
Published: October 2012

Background

Glucocorticoids, secreted by the adrenals in response to stress, profoundly affect structure and plasticity of neurons. Glucocorticoid action in neurons is mediated by glucocorticoid receptors (GR) that operate as transcription factors in the regulation of gene expression and either bind directly to genomic glucocorticoid response elements (GREs) or indirectly to the genome via interactions with bound transcription factors. These two modes of action, respectively called transactivation and transrepression, result in the regulation of a wide variety of genes important for neuronal function. The objective of the present study was to identify genome-wide glucocorticoid receptor binding sites in neuronal PC12 cells using Chromatin ImmunoPrecipitation combined with next generation sequencing (ChIP-Seq).

Results

In total we identified 1183 genomic binding sites of GR, the majority of which were novel and not identified in other ChIP-Seq studies on GR binding. More than half (58%) of the binding sites contained a GRE. The remaining 42% of the GBS did not harbour a GRE and therefore likely bind GR via an intermediate transcription factor tethering GR to the DNA. While the GRE-containing binding sites were more often located nearby genes involved in general cell functions and processes such as apoptosis, cell motion, protein dimerization activity and vasculature development, the binding sites without a GRE were located nearby genes with a clear role in neuronal processes such as neuron projection morphogenesis, neuron projection regeneration, synaptic transmission and catecholamine biosynthetic process. A closer look at the sequence of the GR binding sites revealed the presence of several motifs for transcription factors that are highly divergent from those previously linked to GR-signaling, including Gabpa, Prrx2, Zfp281, Gata1 and Zbtb3. These transcription factors may represent novel crosstalk partners of GR in a neuronal context.

Conclusions

Here we present the first genome-wide inventory of GR-binding sites in a neuronal context. These results provide an exciting first global view into neuronal GR targets and the neuron-specific modes of GR action and potentially contributes to our understanding of glucocorticoid action in the brain.
In Vitro efficacy of antimicrobial extracts against the atypical ruminant pathogen Mycoplasma mycoides subsp. capri
Authors: Arjoon Amanda V , Saylor Charlotte V , May Meghan
Published: October 2012

Background

Mycoplasmosis is a common infection in human and veterinary medicine, and is associated with chronic inflammation and high morbidity. Mycoplasma species are often intrinsically resistant to many conventional antimicrobial therapies, and the resistance patterns of pathogenic mycoplasmas to commonly used medicinal (antimicrobial) plant extracts are currently unknown.

Methods

Aqueous extracts, ethanol extracts, or oils of the targeted plant species and colloidal silver were prepared or purchased. Activity against the wall-less bacterial pathogen Mycoplasma mycoides subsp. capri was determined and compared to activities measured against Escherichia coli and Bacillus subtilis. Antimicrobial susceptibility testing was performed by broth microdilution assays. The lethal or inhibitory nature of each extract was determined by subculture into neat growth medium.

Results

Growth of M. mycoides capri, E. coli, and B. subtilis was inhibited by elderberry extract, oregano oil, ethanol extract of oregano leaves, and ethanol extract of goldenseal root. No inhibition was seen with aqueous extract of astragalus or calendula oil. Growth of M. mycoides capri and B. subtilis was inhibited by ethanol extract of astragalus, whereas growth of E. coli was not. Similarly, M. mycoides capri and E. coli were inhibited by aqueous extract of thyme, but B. subtilis was unaffected. Only B. subtilis was inhibited by colloidal silver. Measured MICs ranged from 0.0003 mg/mL to 3.8 mg/mL. Bacteriostatic and bactericidal effects differed by species and extract.

Conclusions

The atypical pathogen M. mycoides capri was sensitive to extracts from many medicinal plants commonly used as antimicrobials in states of preparation and concentrations currently available for purchase in the United States and Europe. Variation in bacteriostatic and bactericidal activities between species and extracts indicates that multiple effecter compounds are present in these plant species.
Anti-inflammatory effect of ethanolic extract from Myagropsis myagroides on murine macrophages and mouse ear edema
Authors: Joung Eun-Ji , Lee Min-Sup , Choi Ji-Woong , Kim Jong-Soon , Shin Taisun , Jung Bok-Mi , Yoon Na Young , Lim Chi-Won , Kim Jae-Il , Kim Hyeung-Rak
Published: October 2012

Background

This study aims to investigate anti-inflammatory effect of ethanolic extract ofMyagropsis myagroides(EMM) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and the phorbol 12-myristate 13-acetate (PMA)-induced ear edema in mice, and to clarify its underlying molecular mechanisms.

Methods

The levels of nitric oxide (NO), prostaglandin E2(PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blotting. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunocytochemistry and reporter gene assay, respectively. PMA-induced mouse ear edema was used as the animal model of inflammation. Anti-inflammatory compounds in EMM were isolated using high-performance liquid chromatography and identified by nuclear magnetic resonance.

Results

EMM significantly inhibited the production of NO, PGE2, and pro-inflammatory cytokines in a dose-dependent manner and suppressed the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. EMM strongly suppressed nuclear translocation of NF-κB by preventing degradation of inhibitor of κB-α as well as by inhibiting phosphorylation of Akt and MAPKs. EMM reduced ear edema in PMA-induced mice. One of the anti-inflammatory compounds in EMM was identified as 6,6’-bieckol.

Conclusions

These results suggest that the anti-inflammatory properties of EMM are associated with the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the inhibition of NF-κB pathway in LPS-stimulated macrophages.
Isolated Crohn’s disease of the esophagus with esophago-mediastinal fistula formation
Authors: Wang Wuping , Ni Yunfeng , Ke Changkang , Cheng Qingshu , Lu Qiang , Li Xiaofei
Published: October 2012

Isolated Crohn’s disease of the esophagus is rare, and accurate diagnosis and treatment in its early course are difficult. Most cases are often found very late, when severe strictures or other complications have occurred. We report the case of a male 60-year-old patient with complaints of progressive dysphagia for more than two months and the sudden appearance of heartburn for seven consecutive days. Clinical examination revealed severe esophageal stricture with a suspected fistula and mediastinitis. The patient received a successful esophagectomy. The resected specimen and pathological results confirmed a deep linear ulcer, chronic and noncaseating granulomatous inflammation, as well as a circular stricture of the esophagus with fistula into the mediastinum due to isolated esophageal Crohn’s disease.
Comparison and analysis of point target reference spectrum of FMCW synthetic aperture imaging sensor
Authors: Liu Yue , Deng Yun-Kai , Wang Robert , Jia Xiao-Xue , Han Xiao-Dong
Published: October 2012

Frequency-modulated continuous-wave (FMCW) synthetic aperture imaging sensor (SAIS) combines FMCW technology and SAIS techniques which makes a lightweight, high-resolution, and cost-effective imaging sensor. FMCW SAIS systems are going to play an important role in airborne and spaceborne earth observation fields. However, the stop-and-go approximation used in conventional pulsed SAIR (e.g., synthetic aperture radar—SAR) is no longer valid due to the long signal duration time or low wave propagation speed. To exploit the potentialities of an accurate signal model under FMCW SAIS circumstances, this article presents the relationship and remarkable differences between the analytical FMCW SAIS point target reference spectrum model and the traditional ones in pulsed SAR and Synthetic Aperture Acoustic imaging system, and validates the significance of the additional range–azimuth coupling term and range walk term in FMCW SAIS spectrum introduced by the variation of slant range during the long pulse durations, and highlight the limitations of other two spectra. Finally, the simulation experiments are carried out to compare the performance of the aforementioned spectrum formulations.
Host predilection and transmissibility of vesicular stomatitis New Jersey virus strains in domestic cattle (Bos taurus) and swine (Sus scrofa)
Authors: Smith Paul F , Howerth Elizabeth W , Carter Deborah , Gray Elmer W , Noblet Raymond , Berghaus Roy D , Stallknecht David E , Mead Daniel G
Published: October 2012

Background

Epidemiologic data collected during epidemics in the western United States combined with limited experimental studies involving swine and cattle suggest that host predilection of epidemic vesicular stomatitis New Jersey virus (VSNJV) strains results in variations in clinical response, extent and duration of virus shedding and transmissibility following infection in different hosts. Laboratory challenge of livestock with heterologous VSNJV strains to investigate potential viral predilections for these hosts has not been thoroughly investigated. In separate trials, homologous VSNJV strains (NJ82COB and NJ82AZB), and heterologous strains (NJ06WYE and NJOSF [Ossabaw Island, sand fly]) were inoculated into cattle via infected black fly bite. NJ82AZB and NJ06WYE were similarly inoculated into swine.

Results

Clinical scores among viruses infecting cattle were significantly different and indicated that infection with a homologous virus resulted in more severe clinical presentation and greater extent and duration of viral shedding. No differences in clinical severity or extent and duration of viral shedding were detected in swine.

Conclusions

Differences in clinical presentation and extent and duration of viral shedding may have direct impacts on viral spread during epidemics. Viral transmission via animal-to-animal contact and insect vectored transmission are likely to occur at higher rates when affected animals are presenting severe clinical signs and shedding high concentrations of virus. More virulent viral strains resulting in more severe disease in livestock hosts are expected to spread more rapidly and greater distances during epidemics than those causing mild or inapparent signs.
A WUSCHEL-like homeobox gene, OsWOX3B responses to NUDA/GL-1 locus in rice
Authors: Zhang Honglei , Wu Kun , Wang Yufeng , Peng Yu , Hu Fengyi , Wen Lu , Han Bin , Qian Qian , Teng Sheng
Published: October 2012

Background

Most of the rice varieties are pubescent. However, the presence of trichomes is an undesirable characteristic in rice production because trichomes can cause atmospheric pollution. The use of glabrous rice varieties represents a solution to this problem. Yunnan Nuda Rice, a glabrous cultivar that constitutes approximately 20% of rice germplasms in Yunnan can provide important recourse for breeding of glabrous rice varieties.

Results

The “Nuda” phenotype in Yunnan Nuda Rice was found to be controlled by a single recessive allelic gene within the well-characterizedGL-1locus. A high-resolution genetic and physical map was constructed using 1,192 Nuda individuals from the F2population that was delivered from the cross between the Yunnan Nuda variety HMK and the pubescent TN1 variety. TheNUDA/GL-1gene was mapped to a 28.5 kb region containing six annotated genes based on the Nipponbare genomic sequence. By comparing the sequences and expression patterns of different pubescent and glabrous varieties,LOC_Os05g02730, aWUSCHEL-like homeobox gene (OsWOX3B) was identified as the candidate gene. This hypothesis was confirmed by RNA interference (RNAi) and transgenic complementation. Trichome deficiency in RNAi lines was associated with increased efficiency of grain packaging but did not affect the main agronomic traits.

Conclusion

NUDA/GL-1locus encodesOsWOX3Bgene.
Expression of human papillomavirus 6b L1 protein in silkworm larvae and enhanced green fluorescent protein displaying on its virus-like particles
Authors: Palaniyandi Muthukutty , Kato Tatsuya , Park Enoch Y
Published: October 2012

Human papillomavirus (HPV) 6b L1 capsid protein was expressed using the Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid expression system in silkworm larvae. Two constructs, full-length L1 (500 a.a) and C-terminal-deleted short L1 (479 a.a), and three PCR-manipulated antigenic loops at amino acids 55–56, 174–175, and 348–349 regions were incorporated with whole enhanced green fluorescent protein (EGFP). Expressed in full, short L1 proteins and variants were purified in heparin affinity column chromatography and confirmed by SDS-PAGE and western blot. The presence of self-assembled virus-like particles (VLPs) and EGFP incorporation on the surface of VLPs were confirmed by the observation of transmission electron and immunoelectron microscopies, respectively. HPV 6b L1 major capsid protein was successfully expressed in silkworm, and effective manipulation on the antigenic regions showed the path to versatile vaccine development based on HPV L1-VLPs.
An analytic algorithm of Lane-Emden-type equations arising in astrophysics - a hybrid approach
Authors: Baranwal Vipul K , Pandey Ram K , Tripathi Manoj P , Singh Om P
Published: October 2012

A new analytic algorithm for Lane-Emden equations is proposed in this paper. The proposed algorithm is obtained by using a new iterative method. The new iterative method is a hybrid of variational iteration method and the Adomian decomposition method and further refined by introducing a new correction functional. This new correction functional is obtained from the standard correction functional of variational iteration method by introducing an auxiliary parameter γ in it. Further, a sequence

G
n

x

, with suitably chosen support, is also introduced in the new correction functional. The algorithm is easy to implement and gives fairly accurate solutions. Several test examples are given establishing the accuracy and the efficiency of the algorithm.
Dendritic cells provide a potential link between smoking and inflammation in rheumatoid arthritis
Authors: Kazantseva Marina G , Highton John , Stamp Lisa K , Hessian Paul A
Published: October 2012

Introduction

Smoking increases the risk of developing rheumatoid arthritis (RA) and affects the severity of established RA. Smoking can impact on Th17 lymphocyte differentiation and function through activation of the aryl hydrocarbon receptor (AHR), a process with implications for the pathogenic mechanisms in RA that involve the cytokine, interleukin (IL)-17A. The objective of this study was to establish any effect of smoking on the inflammatory tissue lesions of rheumatoid arthritis via the AHR and IL-17A.

Methods

Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established. Expression of AHR, CYP1A1, AHRR, IL6, IL17A, IL17F, IL22, IL23, IL23R, IFNG, TBX21, IDO1 and FOXP3 genes were assessed in tissues and cultured cells using real-time PCR. Two-colour immunofluorescence was used to co-localise AHR and CYP1A1 protein in synovial tissues. The response of monocytes and monocyte-derived dendritic cells (mo-DCs) to the AHR agonist, benzo(a)pyrene (BaP) was compared in vitro.

Results

AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia. Expression was not influenced by smoking in either tissue. Evidence of AHR activation, indicated by CYP1A1 and AHRR gene expression, was found only in synovia from patients who smoked. However, IL17A gene expression was lower in synovia from smokers. TBX21 and FOXP3 expression was not affected by smoking. Within the synovial tissues of smokers the principal cell type with evidence of AHR activation was a subset of synovial DCs. This observation was consistent with the sensitivity of human mo-DCs to BaP stimulation demonstrated in vitro. Exposure to BaP affected mo-DC function as demonstrated by decreased IL6 expression induced by PolyI:C, without affecting indoleamine 2,3 dioxygenase (IDO)1 expression.

Conclusion

Our findings show that one effect of smoking on inflamed rheumatoid synovial tissue involves activation of the AHR pathway. A subset of synovial DCs is important in the response to cigarette smoke. The potential for smoking to affect DC behaviour in joint tissues has relevance to both early and late phases of RA pathogenesis and warrants further investigation.
Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes
Authors: Peck Amy R , Witkiewicz Agnieszka K , Liu Chengbao , Klimowicz Alexander C , Stringer Ginger A , Pequignot Edward , Freydin Boris , Yang Ning , Ertel Adam , Tran Thai H , Girondo Melanie A , Rosenberg Anne L , Hooke Jeffrey A , Kovatich Albert J , Shriver Craig D , Rimm David L , Magliocco Anthony M , Hyslop Terry , Rui Hallgeir
Published: October 2012

Introduction

Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome.

Methods

Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models.

Results

Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naïve, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome.

Conclusions

Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.
Hypertonic saline reduces lipopolysaccharide-induced mouse brain edema through inhibiting aquaporin 4 expression
Authors: C Cao , X Yu , Z Liao , N Zhu , H Huo , M Wang , G Ji , H She , Z Luo , S Yue
Published: October 2012

Introduction

Three percent sodium chloride (NaCl) treatment has been shown to reduce brain edema and inhibited brain aquaporin 4 (AQP4) expression in bacterial meningitis induced by Escherichia coli. Lipopolysaccharide (LPS) is the main pathogenic component of E. coli. We aimed to explore the effect of 3% NaCl in mouse brain edema induced by LPS, as well as to elucidate the potential mechanisms of action.

Methods

Three percent NaCl was used to treat cerebral edema induced by LPS in mice in vivo. Brain water content, IL-1β, TNFα, immunoglobulin G (IgG), AQP4 mRNA and protein were measured in brain tissues. IL-1β, 3% NaCl and calphostin C (a specific inhibitor of protein kinase C) were used to treat the primary astrocytes in vitro. AQP4 mRNA and protein were measured in astrocytes. Differences in various groups were determined by one-way analysis of variance.

Results

Three percent NaCl attenuated the increase of brain water content, IL-1β, TNFα, IgG, AQP4 mRNA and protein in brain tissues induced by LPS. Three percent NaCl inhibited the increase of AQP4 mRNA and protein in astrocytes induced by IL-1β in vitro. Calphostin C blocked the decrease of AQP4 mRNA and protein in astrocytes induced by 3% NaCl in vitro.

Conclusions

Osmotherapy with 3% NaCl ameliorated LPS-induced cerebral edema in vivo. In addition to its osmotic force, 3% NaCl exerted anti-edema effects possibly through down-regulating the expression of proinflammatory cytokines (IL-1β and TNFα) and inhibiting the expression of AQP4 induced by proinflammatory cytokines. Three percent NaCl attenuated the expression of AQP4 through activation of protein kinase C in astrocytes.
Blood levels of copeptin on admission predict outcomes in out-of-hospital cardiac arrest survivors treated with therapeutic hypothermia
Authors: Ostadal Petr , Kruger Andreas , Zdrahalova Vladimira , Janotka Marek , Vondrakova Dagmar , Neuzil Petr , Prucha Miroslav
Published: October 2012

Introduction

Prognostic stratification of cardiac arrest survivors is essential for the selection of the most appropriate therapeutic strategy. However, accurate early outcome predictions for this patient population remain challenging. At present, there is a lack of data examining the prognostic value of C-terminal provasopressin (copeptin) in cardiac arrest survivors.

Methods

A group of 40 out-of-hospital cardiac arrest survivors who were treated with endovascular hypothermia was analyzed. Copeptin levels were measured in blood samples taken at admission using a commercially available immunoassay. Neurological outcome was assessed at 30 days post admission according to the Cerebral Performance Category (CPC): CPC 1, no neurological deficit; CPC 2, mild to moderate dysfunction; CPC 3, severe dysfunction; CPC 4, coma; and CPC 5, death.

Results

Copeptin levels were significantly lower in patients with CPC 1 compared with CPC 2 or CPC 3 to CPC 5 (74.3 ± 14.4 pmol/l, 219.8 ± 33.9 pmol/l and 302.7 ± 52.1 pmol/l, respectively; P < 0.0001). Using an optimal cutoff value ≤ 217.9 pmol/l calculated from the receiver operating characteristic curve (area under curve = 0.801, 95% confidence interval = 0.644 to 0.910; P = 0.0001), the sensitivity of predicting survival with good neurological outcome was 78.6% and the specificity was 75.0%. Multiple logistic regression analysis revealed that a copeptin level > 217.9 pmol/l was an independent predictor of severe neurological dysfunction or death, with an adjusted odds ratio of 27.00 (95% confidence interval = 2.27 to 321.68; P = 0.009).

Conclusion

The present study found that copeptin levels have a significant prognostic value at the time of hospital admission, and are a promising diagnostic tool for predicting outcomes in out-of-hospital cardiac arrest survivors.
Suppression of Food Intake by Glucagon-Like Peptide-1 Receptor Agonists: Relative Potencies and Role of Dipeptidyl Peptidase-4
Authors: Jessen Lene , Aulinger Benedikt A. , Hassel Jonathan L. , Roy Kyle J. , Smith Eric P. , Greer Todd M. , Woods Stephen C. , Seeley Randy J. , D'Alessio David A.
Published: October 2012

Administration of the glucagon-like peptide-1 (GLP-1) receptor agonists GLP-1 and exendin-4 (Ex-4) directly into the central nervous system decreases food intake. But although Ex-4 potently suppresses food intake after peripheral administration, the effects of parenteral GLP-1 are variable and not as strong. A plausible explanation for these effects is the rapid inactivation of circulating GLP-1 by dipeptidyl peptidase-4 (DPP-4), an enzyme that does not alter Ex-4 activity. To test this hypothesis, we assessed the relative potency of Ex-4 and GLP-1 under conditions in which DPP-4 activity was reduced. Outbred rats, wild-type mice, and mice with a targeted deletion of DPP-4 (Dpp4−/−) were treated with GLP-1 alone or in combination with the DPP-4 inhibitor vildagliptin, Ex-4, or saline, and food intake was measured. GLP-1 alone, even at high doses, did not affect feeding in wild-type mice or rats but did reduce food intake when combined with vildagliptin or given to Dpp4−/− mice. Despite plasma clearance similar to DPP-4-protected GLP-1, equimolar Ex-4 caused greater anorexia than vildagliptin plus GLP-1. To determine whether supraphysiological levels of endogenous GLP-1 would suppress food intake if protected from DPP-4, rats with Roux-en-Y gastric bypass and significantly elevated postprandial plasma GLP-1 received vildagliptin or saline. Despite 5-fold greater postprandial GLP-1 in these animals, vildagliptin did not affect food intake in Roux-en-Y gastric bypass rats. Thus, in both mice and rats, peripheral GLP-1 reduces food intake significantly less than Ex-4, even when protected from DPP-4. These findings suggest distinct potencies of GLP-1 receptor agonists on food intake that cannot be explained by plasma pharmacokinetics.
Epigenetic Changes Through DNA Methylation Contribute to Uterine Stromal Cell Decidualization
Authors: Gao Fei , Ma Xinghong , Rusie Allison , Hemingway Jennifer , Ostmann Alicia B. , Chung Daesuk , Das Sanjoy K.
Published: October 2012

Embryo-uterine interaction during early pregnancy critically depends on the coordinated expression of numerous genes at the site of implantation. The epigenetic mechanism through DNA methylation (DNM) plays a major role in the control of gene expression, although this regulatory event remains unknown in uterine implantation sites. Our analysis revealed the presence of DNA methyltransferase 1 (Dnmt1) in mouse endometrial cells on the receptive d 4 of pregnancy and early postattachment (d 5) phase, whereas Dnmt3a had lower abundant expression. Both Dnmt1 and Dnmt3a were coordinately expressed in decidual cells on d 6–8. 5-Methycytosine showed a similar expression pattern to that of Dnmt1. The preimplantation inhibition of DNM by 5-aza-2′-deoxycytodine was not antagonistic for embryonic attachment, although endometrial stromal cell proliferation at the site of implantation was down-regulated, indicating a disturbance with the postattachment decidualization event. Indeed, the peri- or postimplantation inhibition of DNM caused significant abrogation of decidualization, with concomitant loss of embryos. We next identified decidual genes undergoing alteration of DNM using methylation-sensitive restriction fingerprinting. One such gene, Chromobox homolog 4, an epigenetic regulator in the polycomb group protein family, exhibited hypomethylation in promoter DNA and increased expression with the onset of decidualization. Furthermore, inhibition of DNM resulted in enhanced expression of hypermethylated genes (Bcl3 and Slc16a3) in the decidual bed as compared with control, indicating aberration of gene expression may be associated with DNM-inhibition-induced decidual perturbation. Overall, these results suggest that uterine DNM plays a major role for successful decidualization and embryo development during early pregnancy.
Migration of cardiomyocytes is essential for heart regeneration in zebrafish
Authors: Itou Junji , Oishi Isao , Kawakami Hiroko , Glass Tiffany J. , Richter Jenna , Johnson Austin , Lund Troy C. , Kawakami Yasuhiko
Published: October 2012

Adult zebrafish possess a significant ability to regenerate injured heart tissue through proliferation of pre-existing cardiomyocytes, which contrasts with the inability of mammals to do so after the immediate postnatal period. Zebrafish therefore provide a model system in which to study how an injured heart can be repaired. However, it remains unknown what important processes cardiomyocytes are involved in other than partial de-differentiation and proliferation. Here we show that migration of cardiomyocytes to the injury site is essential for heart regeneration. Ventricular amputation induced expression of cxcl12a and cxcr4b, genes encoding a chemokine ligand and its receptor. We found that cxcl12a was expressed in the epicardial tissue and that Cxcr4 was expressed in cardiomyocytes. We show that pharmacological blocking of Cxcr4 function as well as genetic loss of cxcr4b function causes failure to regenerate the heart after ventricular resection. Cardiomyocyte proliferation was not affected but a large portion of proliferating cardiomyocytes remained localized outside the injury site. A photoconvertible fluorescent reporter-based cardiomyocyte-tracing assay demonstrates that cardiomyocytes migrated into the injury site in control hearts but that migration was inhibited in the Cxcr4-blocked hearts. By contrast, the epicardial cells and vascular endothelial cells were not affected by blocking Cxcr4 function. Our data show that the migration of cardiomyocytes into the injury site is regulated independently of proliferation, and that coordination of both processes is necessary for heart regeneration.
The Collateral Channel: How Real Estate Shocks Affect Corporate Investment
Authors: Chaney Thomas , Sraer David , Thesmar David
Published: October 2012

What is the impact of real estate prices on corporate investment? In the presence of financing frictions, firms use pledgeable assets as collateral to finance new projects. Through this collateral channel, shocks to the value of real estate can have a large impact on aggregate investment. To compute the sensitivity of investment to collateral value, we use local variations in real estate prices as shocks to the collateral value of firms that own real estate. Over the 1993–2007 period, the representative US corporation invests $0.06 out of each $1 of collateral. (JEL D22, G31, R30)
The Evolution of Brand Preferences: Evidence from Consumer Migration
Authors: Bronnenberg Bart J , Dubé Jean-Pierre H , Gentzkow Matthew
Published: October 2012

We study the long-run evolution of brand preferences, using new data on consumers' life histories and purchases of consumer packaged goods. Variation in where consumers have lived in the past allows us to isolate the causal effect of past experiences on current purchases, holding constant contemporaneous supply-side factors. We show that brand preferences form endogenously, are highly persistent, and explain 40 percent of geographic variation in market shares. Counterfactuals suggest that brand preferences create large entry barriers and durable advantages for incumbent firms and can explain the persistence of early-mover advantage over long periods. (JEL D12, L11, M31, M37)
The Rise of the Service Economy
Authors: Buera Francisco J , Kaboski Joseph P
Published: October 2012

This paper analyzes the role of specialized high-skilled labor in the disproportionate growth of the service sector. Empirically, the importance of skill-intensive services has risen during a period of increasing relative wages and quantities of high-skilled labor. We develop a theory in which demand shifts toward more skill-intensive output as productivity rises, increasing the importance of market services relative to home production. Consistent with the data, the theory predicts a rising level of skill, skill premium, and relative price of services that is linked to this skill premium. (JEL J24, L80, L90)
Maturity, Indebtedness, and Default Risk
Authors: Chatterjee Satyajit , Eyigungor Burcu
Published: October 2012

We advance quantitative-theoretic models of sovereign debt by proving the existence of a downward sloping equilibrium price function for long-term debt and implementing a novel method to accurately compute it. We show that incorporating long-term debt allows the model to match Argentina's average external debt-to-output ratio, average spread on external debt, the standard deviation of spreads, and simultaneously improve upon the model's ability to account for Argentina's other cyclical facts. We also investigated the welfare properties of maturity length and showed that if the possibility of self-fulfilling rollover crises is taken into account, long-term debt is superior to short-term debt. (JEL E23, E32, F34, O11, O19)
Disaster Risk and Business Cycles
Authors: Gourio François
Published: October 2012

Motivated by the evidence that risk premia are large and countercyclical, this paper studies a tractable real business cycle model with a small risk of economic disaster, such as the Great Depression. An increase in disaster risk leads to a decline of employment, output, investment, stock prices, and interest rates, and an increase in the expected return on risky assets. The model matches well data on quantities, asset prices, and particularly the relations between quantities and prices, suggesting that variation in aggregate risk plays a significant role in some business cycles. (JEL E13, E32, E44, G32)
But Who Will Monitor the Monitor?
Authors: Rahman David
Published: October 2012

Suppose that providing incentives for a group of individuals in a strategic context requires a monitor to detect their deviations. What about the monitor's deviations? To address this question, I propose a contract that makes the monitor responsible for monitoring, and thereby provides incentives even when the monitor's observations are not only private, but costly, too. I also characterize exactly when such a contract can provide monitors with the right incentives to perform. In doing so, I emphasize virtual enforcement and suggest its implications for the theory of repeated games. (JEL C78, D23, D82, D86)
The Strategy of Manipulating Conflict
Authors: Baliga Sandeep , Sjöström Tomas
Published: October 2012

Two players choose hawkish or dovish actions in a conflict game with incomplete information. An “extremist,” who can either be a hawk or a dove, attempts to manipulate decision making. If actions are strategic complements, a hawkish extremist increases the likelihood of conflict, and reduces welfare, by sending a public message which triggers hawkish behavior from both players. If actions are strategic substitutes, a dovish extremist instead sends a public message which causes one player to become more dovish and the other more hawkish. A hawkish (dovish) extremist is unable to manipulate decision making if actions are strategic substitutes (complements). (JEL D74, D82)
Inequality at Work: The Effect of Peer Salaries on Job Satisfaction
Authors: Card David , Mas Alexandre , Moretti Enrico , Saez Emmanuel
Published: October 2012

We study the effect of disclosing information on peers' salaries on workers' job satisfaction and job search intentions. A randomly chosen subset of University of California employees was informed about a new website listing the pay of University employees. All employees were then surveyed about their job satisfaction and job search intentions. Workers with salaries below the median for their pay unit and occupation report lower pay and job satisfaction and a significant increase in the likelihood of looking for a new job. Above-median earners are unaffected. Differences in pay rank matter more than differences in pay levels. (JEL I23, J28, J31, J64)
Credit Traps
Authors: Benmelech Efraim , Bergman Nittai K
Published: October 2012

This paper studies the limitations of monetary policy in stimulating credit and investment. We show that, under certain circumstances, unconventional monetary policies fail in that liquidity injections into the banking sector are hoarded and not lent out. We use the term “credit traps” to describe such situations and show how they can arise due to the interplay between financing frictions, liquidity, and collateral values. We show that small contractions in monetary policy can lead to a collapse in lending. Our analysis demonstrates how quantitative easing may be useful in increasing collateral prices, bank lending, and aggregate investment. (JEL E44, E52, E58, G01)
Sunitinib- and Sorafenib-lnduced Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor
Authors: Turan Nedim , Benekli Mustafa , Ozturk Selcuk Cemil , Inal Salih , Memis Leyla , Guz Galip , Cetin Bulent , Buyukberber Suleyman
Published: October 2012

Objective

TO report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy.

Case Summary

A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved.

Discussion

Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development.

Conclusions

The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.
Proton Pump Inhibitor Use and Association with Spontaneous Bacterial Peritonitis in Patients with Cirrhosis and Ascites
Authors: Siple Jolene F , Morey Jessica M , Gutman Tracy E , Weinberg Kathy L , Collins Peggie D
Published: October 2012

Objective:

To evaluate the literature regarding the efficacy and safety of proton pump inhibitors (PPIs) when they are used in patients with cirrhosis and ascites.

Data Sources:

A literature search was conducted using MEDLINE (1966-May 2012) and Web of Science (1990-May 2012) with the terms proton pump inhibitor, antisecretory therapy, cirrhosis, ascites, spontaneous bacterial peritonitis, and Clostridium difficile. The search was restricted to articles published in English on the use of PPIs in humans. Reference citations from identified published articles were reviewed for relevant information.

Study Selection and Data Extraction:

All articles in English identified from the data sources were evaluated for inclusion. One case series, 8 retrospective case-control trials, and 1 meta-analysis were identified.

Data Synthesis:

Cirrhosis may cause complications such as portal hypertension, esophageal varices, and ascites. Patients may be prescribed PPIs without clear indications or because of their propensity to develop upper gastrointestinal symptoms and bleeding. However, gastric acidity is a major nonspecific defense mechanism and there is insufficient evidence on the need for chronic acid suppression in patients with cirrhosis. It is postulated that the portal hypertensive environment in cirrhosis and the acid suppression from PPIs can increase the risk of spontaneous bacterial peritonitis and C. difficile infection in patients with cirrhosis with ascites. Several retrospective studies and 1 meta-analysis have confirmed this association.

Conclusions:

Patients with cirrhosis and ascites should be monitored carefully while on PPIs for a possible increased risk of infection from spontaneous bacterial peritonitis and C. difficile. Prospective randomized trials are needed to confirm this association. Clinicians should be aware of this lesser known adverse effect of PPIs.
JCAMP-DX for circular dichroism spectra and metadata (IUPAC Recommendations 2012)
Authors: Woollett Benjamin , Klose Daniel , Cammack Richard , Janes Robert W. , Wallace B. A.
Published: October 2012

Circular dichroism (CD) spectroscopy is a widely used technique for the characterisation of proteins. A number of CD instruments are currently on the market, and there are more than a dozen synchrotron radiation circular dichroism (SRCD) beamlines in operation worldwide. All produce different output formats and contents. In order for users of CD and SRCD data to be able simply to compare and contrast data and the associated recorded or unrecorded metadata, it is essential to have a common data format. For this reason, the JCAMP-DX-CD format for CD spectroscopy has been developed, based on extensive consultations with users and senior representatives of all the instrument manufacturers and beamlines, and under the auspices of IUPAC, based on the Joint Committee on Atomic and Physical Data Exchange protocols. The availability of a common format is also important for deposition to, and access from, the Protein Circular Dichroism Data Bank, the public repository for CD and SRCD data and metadata. The JCAMP-DX-CD format can be read by standard JCAMP programs such as JSpecView. We have also created a series of parsers, available at the DichroJCAMP web site (http://valispec.cryst.bbk.ac.uk/formatConverter/dichroJCAMPDX-CD.html), which will enable the conversion between instrument and beamline formats and the JCAMP-DX-CD format.
Accounting for Violence at the Victoria Industrial School
Authors: Hogeveen Bryan
Published: October 2012

Les garçons qui ont été détenus à la Victoria Industrial School (VIS) entre son ouverture en 1887 et sa fermeture en 1934 subissaient souvent des châtiments extrêmes, violents et capricieux et faisaient fait l'objet de manipulations psychologiques calculées. La violence qui leur était faite et les motifs qu'invoquaient les représentants de l'école pour justifier de telles pratiques préjudiciables sont examinés par l'entremise de dossiers de cas, d'enquêtes publiques, de reportages dans les journaux, de révélations d'anciens détenus, de déclarations défensives par les directeurs et de confessions par le personnel. L'étude de ces sources semble indiquer qu'en dépit de recommandations répétées du conseil municipal de Toronto, du public et de commissions d'enquête, les châtiments violents persistèrent. Malgré les affirmations du contraire, la VIS a été, pour bien des garçons, un établissement cruel et impitoyable.