bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regionally different immunoreactivity for Smurf2 and pSmad2/3 in TDP‐43‐positive inclusions of amyotrophic lateral sclerosis
Authors: Nakamura M. , Kaneko S. , Wate R. , Asayama S. , Nakamura Y. , Fujita K. , Ito H. , Kusaka H. 
Published: March 2012

M. Nakamura, S. Kaneko, R. Wate, S. Asayama, Y. Nakamura, K. Fujita, H. Ito and H. Kusaka (2013) Neuropathology and Applied Neurobiology39, 144–156Regionally different immunoreactivity for Smurf2 and pSmad2/3 in TDP‐43‐positive inclusions of amyotrophic lateral sclerosisAims: Smad ubiquitination regulatory factor‐2 (Smurf2), an E3 ubiquitin ligase, can interact with Smad proteins and promote their ubiquitin‐dependent degradation, thereby controlling the cellular levels of these signalling mediators. We previously reported that phosphorylated Smad2/3 (pSmad2/3) was sequestered in transactive response DNA‐binding protein‐43 (TDP‐43) inclusions in the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Recent biochemical and immunohistochemical studies on spinal cord and brain of ALS patients demonstrated that the composition of the TDP‐43 inclusions is regionally distinct, suggesting different underlying pathogenic processes. We aimed to elucidate regional differences in pathomechanisms and composition of TDP‐43 inclusions in relation to pSmad2/3 and Smurf2. Methods: The spinal cord and brain tissues of 13 sporadic ALS (SALS) patients were investigated using immunohistochemical analysis. Results: TDP‐43‐positive inclusions in lower motor neurones of SALS patients were immunopositive for Smurf2 and pSmad2/3. Multiple immunofluorescence staining for Smurf2, pSmad2/3, TDP‐43 and ubiquitin revealed co‐localization of these four proteins within the inclusions in lower motor neurones of SALS patients. Furthermore, the loss of nuclear pSmad2/3 immunoreactivity was observed in cells bearing TDP‐43 inclusions. In contrast, TDP‐43‐positive inclusions in the extramotor neurones in the brain of SALS patients were noticeably negative for Smurf2 and pSmad2/3. In addition, pSmad2/3 immunoreactivity was preserved in the nuclei of inclusion‐bearing cells. Conclusions: This regional difference in the expression of Smurf2 and pSmad2/3 within TDP‐43‐positive inclusions might be one of the pathomechanisms underlying the loss of lower motor neurones and comparatively spared cortical neurones seen in ALS.
Environmental tobacco smoke and male sex modify the influence of IL‐13 genetic variants on cord blood IgE levels
Authors: Chen Chien‐Han , Lee Yungling Leo , Wu Ming‐Hsun , Chen Pao‐Jen , Wei Tien‐Shan , Wu Che‐Tsung , Tung Kuan‐Yen , Chen Wei J. 
Published: March 2012

To cite this article: Chen C‐H, Lee YL, Wu M‐H, Chen P‐J, Wei T‐S, Wu C‐T, Tung K‐Y, Chen WJ. Environmental tobacco smoke and male sex modify the influence of IL‐13 genetic variants on cord blood IgE levels. Pediatric Allergy Immunology 2012: 23: 456–463.AbstractElevated cord blood IgE (cIgE) levels enhance the risk of childhood atopic diseases. However, genetic determinants of cIgE elevation and their potential modifiers remain inconclusive. We aimed to investigate the associations of single‐nucleotide polymorphisms (SNPs) in the IL‐13 gene (IL‐13) with cIgE elevation and their interactions with prenatal environmental tobacco smoke (ETS) and neonatal sex. A structured questionnaire regarding prenatal environmental exposures was completed during pregnancy. Birth information was extracted from the medical records. Cord blood from 794 term neonates was genotyped for three SNPs (rs1800925, rs20541, and rs848) of IL‐13 and measured for cIgE levels. SNP rs20541 and a 3‐SNP haplotype containing rs1800925, rs20541, and rs848 (denoted as h011) were significantly associated with cIgE elevation (p = 0.04 and 0.003, respectively). Two‐way interaction analysis revealed that the associations of IL‐13 rs20541 and h011 with cIgE elevation were synergistically enhanced by prenatal ETS (p for interaction = 0.03 and 0.03, respectively), but not by male sex. If the association analyses were stratified by prenatal ETS and neonatal sex simultaneously, IL‐13 rs20541 and h011 had the highest risks for cIgE elevation in male babies prenatally exposed to ETS, with adjusted odds ratios (95% confidence interval) being 3.03 (1.56–5.88) and 2.81 (1.54–5.15), respectively. When three‐way interactions were examined, both IL‐13 rs20541 and h011 exhibited significant interactions with male sex and ETS (p for interaction = 0.03 and 0.007, respectively). In conclusion, the influence of IL‐13 genetic variants on cIgE elevation was modified by male sex and prenatal ETS.
Comparative analysis of encephalization in mammals reveals relaxed constraints on anthropoid primate and cetacean brain scaling
Authors: BODDY A. M. , McGOWEN M. R. , SHERWOOD C. C. , GROSSMAN L. I. , GOODMAN M. , WILDMAN D. E. 
Published: March 2012

AbstractThere is a well‐established allometric relationship between brain and body mass in mammals. Deviation of relatively increased brain size from this pattern appears to coincide with enhanced cognitive abilities. To examine whether there is a phylogenetic structure to such episodes of changes in encephalization across mammals, we used phylogenetic techniques to analyse brain mass, body mass and encephalization quotient (EQ) among 630 extant mammalian species. Among all mammals, anthropoid primates and odontocete cetaceans have significantly greater variance in EQ, suggesting that evolutionary constraints that result in a strict correlation between brain and body mass have independently become relaxed. Moreover, ancestral state reconstructions of absolute brain mass, body mass and EQ revealed patterns of increase and decrease in EQ within anthropoid primates and cetaceans. We propose both neutral drift and selective factors may have played a role in the evolution of brain–body allometry.
Non‐high‐density lipoprotein cholesterol: An important predictor of stroke and diabetes‐related mortality in Japanese elderly diabetic patients
Authors: Araki Atsushi , Iimuro Satoshi , Sakurai Takashi , Umegaki Hiroyuki , Iijima Katsuya , Nakano Hiroshi , Oba Kenzo , Yokono Koichi , Sone Hirohito , Yamada Nobuhiro , Ako Junya , Kozaki Koichi , Miura Hisayuki , Kashiwagi Atsunori , Kikkawa Ryuichi , Yoshimura Yukio , Nakano Tadasumi , Ohashi Yasuo , Ito Hideki ,   the Japanese Elderly Intervention Trial Research Group
Published: March 2012

Aims:  To evaluate the association of low‐density lipoprotein, high‐density lipoprotein and non‐high‐density lipoprotein cholesterol with the risk of stroke, diabetes‐related vascular events and mortality in elderly diabetes patients.Methods:  This study was carried out as a post‐hoc landmark analysis of a randomized, controlled, multicenter, prospective intervention trial. We included 1173 elderly type 2 diabetes patients (aged ≥65 years) from 39 Japanese institutions who were enrolled in the Japanese elderly diabetes intervention trial study and who could be followed up for 1 year. A landmark survival analysis was carried out in which follow up was set to start 1 year after the initial time of entry.Results:  During 6 years of follow up, there were 38 cardiovascular events, 50 strokes, 21 diabetes‐related deaths and 113 diabetes‐related events. High low‐density lipoprotein cholesterol was associated with incident cardiovascular events, and high glycated hemoglobin was associated with strokes. After adjustment for possible covariables, non‐high‐density lipoprotein cholesterol showed a significant association with increased risk of stroke, diabetes‐related mortality and total events. The adjusted hazard ratios (95% confidence intervals) of non‐high‐density lipoprotein cholesterol were 1.010 (1.001–1.018, P = 0.029) for stroke, 1.019 (1.007–1.031, P < 0.001) for diabetes‐related death and 1.008 (1.002–1.014; P < 0.001) for total diabetes‐related events.Conclusions:  Higher non‐high‐density lipoprotein cholesterol was associated with an increased risk of stroke, diabetes‐related mortality and total events in elderly diabetes patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 18–28.
Institutions Are What Actors Make of Them — The Changing Construction of Firm‐Level Employment Relations in Spain
Authors: Hauptmeier Marco 
Published: March 2012

AbstractThis article analyses the variation and change in firm‐level employment relations in Spain between the transition to democracy and the global financial crisis. Using three auto companies as case studies, I address a crucial puzzle in the institutional literature on comparative employment relations: How do employment relations change and vary, even when national employment relations institutions do not? This article argues that differences in actor ideologies shape the construction of national institutions at the firm level, which explains change and variation of employment relations over time and across cases. The study identifies four drivers of ideological change — generational change, leadership change, identity work and diffusion — that impact the variation and change in employment relations at the firm level.
Reduced urinary glutamate levels are associated with the frequency of migraine attacks in females
Authors: Ragginer C. , Lechner A. , Bernecker C. , Horejsi R. , Möller R. , Wallner‐Blazek M. , Weiss S. , Fazekas F. , Schmidt R. , Truschnig‐Wilders M. , Gruber H.‐J. 
Published: March 2012

Background and purpose:  Recent evidences indicate that glutamatergic homeostasis disorders are implicated in the pathogenesis of migraine. In particular, plasma and cerebrospinal fluid glutamate levels seem to be altered in migraine patients. However, the impacts of glutamate on migraine and especially on aura symptoms, alterations in the frequency of migraine attacks as well as investigations on glutamate on migraine‐related metabolic dysfunctions, like hyperinsulinaemia, and an atherogenic lipid profile remain elusive to date. The aim of the present study was to investigate the impact of glutamate on migraine and related metabolic dysfunctions.Methods:  We investigated the urinary glutamate levels of female migraineurs (n = 48) in the interictal phase and healthy controls (n = 48). Parameters of the insulin‐ and lipid metabolism, inflammatory parameters and anthropometric parameters were additionally determined.Results:  Urinary glutamate levels of female migraineurs were significantly decreased with respect to the control group. Logistic regression revealed an odds ratio of 4.04 for migraine. We found a significant correlation with the time‐period of patients’ last attack and a significant inverse correlation with the annual frequency of migraine attacks. Other parameters of the insulin‐ and lipid metabolism, anthropometric and inflammatory parameters showed no significant correlation with glutamate levels.Conclusion:  We show here that female migraineurs exhibit decreased urinary glutamate levels which are associated with a 4.04‐fold higher risk for migraine and correlated with patients' frequency of migraine attacks.
Plasma exchange and rituximab treatment for lenalidomide‐associated cold agglutinin disease
Authors: Brauer David L. , Edelman Bennett , Rapoport Aaron P. , Hess John R. , Akpek Görgün 
Published: March 2012

BACKGROUND: Lenalidomide is an amino‐substituted analog of thalidomide with potent immunomodulatory properties. The drug has been widely used for treatment of multiple myeloma and myelodysplastic syndrome (MDS) associated with 5q‐abnormality. The most common side effects are cytopenias, infections, and deep venous thrombosis.CASE STUDY: We report a clinical observation of severe autoimmune hemolytic anemia (AIHA) due to cold agglutinin disease (CAD) that developed 11 days after initiation of lenalidomide treatment in a patient with MDS who relapsed after allogeneic bone marrow transplantation.RESULTS: CAD was diagnosed by the presence of hemolytic variables and cold agglutinin detected in patient's plasma. The antibody screen, which was performed at 37°C, was negative throughout. The direct antiglobulin test was positive only for complement (C3d). These findings supported the diagnosis of CAD associated with lenalidomide administration. Other causes of hemolysis including ABO incompatibility and infectious etiologies were ruled out. Rituximab therapy in conjunction with daily plasma exchange decreased the rate of hemolysis and transfusion requirement in our case.CONCLUSION: In addition to warm AIHA, lenalidomide use can also be associated with development of CAD. Rituximab given in conjunction with plasma exchange can be effective in treating CAD in this setting.
Cardiac protein changes in ischaemic and dilated cardiomyopathy: a proteomic study of human left ventricular tissue
Authors: Roselló‐Lletí Esther , Alonso Jana , Cortés Raquel , Almenar Luis , Martínez‐Dolz Luis , Sánchez‐Lázaro Ignacio , Lago Francisca , Azorín Inmaculada , Juanatey Jose R González , Portolés Manuel , Rivera Miguel 
Published: March 2012

AbstractThe development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM). Twenty‐four explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and six non‐diseased donor hearts (CNT) were analysed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. We encountered 35 differentially regulated spots in the comparison CNT versus ICM, 33 in CNT versus DCM, and 34 in ICM versus DCM. We identified glyceraldehyde 3‐phophate dehydrogenase up‐regulation in both ICM and DCM, and alpha‐crystallin B down‐regulation in both ICM and DCM. Heat shock 70 protein 1 was up‐regulated only in ICM. Ten of the eleven differentially regulated proteins common to both aetiologies are interconnected as a part of a same network. In summary, we have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of eleven proteins common to both ischaemic and dilated aetiology, we also observed different proteins altered in both groups. Furthermore, we obtained that seven of these eleven proteins are involved in cell death and apoptosis processes, and therefore in HF progression.
E.A.O. guidelines for the use of diagnostic imaging in implant dentistry 2011. A consensus workshop organized by the European Association for Osseointegration at the Medical University of Warsaw
Authors: Harris David , Horner Keith , Gröndahl Kerstin , Jacobs Reinhilde , Helmrot Ebba , Benic Goran I. , Bornstein Michael M. , Dawood Andrew , Quirynen Marc 
Published: March 2012

AbstractDiagnostics imaging is an essential component of patient selection and treatment planning in oral rehabilitation by means of osseointegrated implants. In 2002, the EAO produced and published guidelines on the use of diagnostic imaging in implant dentistry. Since that time, there have been significant developments in both the application of cone beam computed tomography as well as in the range of surgical and prosthetic applications that can potentially benefit from its use. However, medical exposure to ionizing radiation must always be justified and result in a net benefit to the patient. The as low a dose as is reasonably achievable principle must also be applied taking into account any alternative techniques that might achieve the same objectives. This paper reports on current EAO recommendations arising from a consensus meeting held at the Medical University of Warsaw (2011) to update these guidelines. Radiological considerations are detailed, including justification and optimization, with a special emphasis on the obligations that arise for those who prescribe or undertake such investigations. The paper pays special attention to clinical indications and radiographic diagnostic considerations as well as to future developments and trends.
Brachial‐Ankle Pulse Wave Velocity and the Cardio‐Ankle Vascular Index as a Predictor of Cardiovascular Outcomes in Patients on Regular Hemodialysis
Authors: Kato Akihiko , Takita Takako , Furuhashi Mitsuyoshi , Maruyama Yukitaka , Miyajima Hiroaki , Kumagai Hiromichi 
Published: March 2012

AbstractBrachial‐ankle pulse wave velocity (baPWV) and the cardio‐ankle vascular index (CAVI) are both used to evaluate arterial stiffness. The aim of the present study is to determine whether baPWV or CAVI is superior as a marker of arterial stiffness in hemodialysis (HD) patients. Of 194 patients, 59 patients had been excluded from the study due to advanced age over 76 years old (n = 29), or abnormal ankle‐brachial pressure index (ABI) (<0.90 or ≥1.30) (n = 30). We then followed the 135 patients (age: 60 ± 11 years, time on HD: 110 ± 93 months) for the 63 ± 4 (55–70) months. Thirty‐two (23.7%) patients had expired, 22 of them of cardiovascular (CV) causes. There were 37 fatal and non‐fatal CV events. Kaplan–Meier analysis revealed that the patients with the highest tertile of baPWV (≥16.6 m/s) had a significantly lower survival rate (P < 0.01) when compared with the second (13.4 ≤ baPWV < 16.6 m/s) and the lowest tertiles (<13.4 m/s). Cox hazards analysis after adjustment for comorbid risk factors revealed that the top tertile of baPWV was a determinant of CV death (hazards ratio [HR]: 16.9 [1.1–251.8], P < 0.05) In contrast, CAVI did not associate with CV mortality or events. These findings suggest that baPWV is superior to CAVI as a predictor of CV outcomes in patients on regular HD.
Drugs that target pathogen public goods are robust against evolved drug resistance
Authors: Pepper John W. 
Published: March 2012

AbstractPathogen drug resistance is a central problem in medicine and public health. It arises through somatic evolution, by mutation and selection among pathogen cells within a host. Here, we examine the hypothesis that evolution of drug resistance could be reduced by developing drugs that target the secreted metabolites produced by pathogen cells instead of directly targeting the cells themselves. Using an agent‐based computational model of an evolving population of pathogen cells, we test this hypothesis and find support for it. We also use our model to explain this effect within the framework of standard evolutionary theory. We find that in our model, the drugs most robust against evolved drug resistance are those that target the most widely shared external products, or ‘public goods’, of pathogen cells. We also show that these drugs exert a weak selective pressure for resistance because they create only a weak correlation between drug resistance and cell fitness. The same principles apply to design of vaccines that are robust against vaccine escape. Because our theoretical results have crucial practical implications, they should be tested by empirical experiments.
Genotype-Phenotype Associations in a Nonmodel Prokaryote
Authors: Enstrom Mark , Held Kiara , Ramage Beth , Brittnacher Mitchell , Gallagher Larry , Manoil Colin 
Published: March 2012

ABSTRACT

To help define the biological functions of nonessential genes of
Francisella novicida
, we measured the growth of arrayed members of a comprehensive transposon mutant library under a variety of nutrition and stress conditions. Mutant phenotypes were identified for 37% of the genes, corresponding to ten carbon source utilization pathways, nine amino acid- and nucleotide-biosynthetic pathways, ten intrinsic antibiotic resistance traits, and six other stress resistance traits. The greatest surprise of the analysis was the large number of genotype-phenotype relationships that were not predictable from studies of
Escherichia coli
and other model species. The study identified candidate genes for a missing glycolysis function (phosphofructokinase), an unusual proline-biosynthetic pathway, parallel outer membrane lipid asymmetry maintenance systems, and novel antibiotic resistance functions. The analysis provides an evaluation of annotation predictions, identifies cases in which fundamental processes differ from those in model species, and helps create an empirical foundation for understanding virulence and other complex processes.

IMPORTANCE
The value of genome sequences as foundations for analyzing complex traits in nonmodel organisms is limited by the need to rely almost exclusively on sequence similarities to predict gene functions in annotations. Many genes cannot be assigned functions, and some predictions are incorrect or incomplete. Due to these limitations, genome-scale experimental approaches that test and extend bioinformatics-based predictions are sorely needed. In this study, we describe such an approach based on phenotypic analysis of a comprehensive, sequence-defined transposon mutant library.
AMPKα Modulation in Cancer Progression: Multilayer Integrative Analysis of the Whole Transcriptome in Asian Gastric Cancer
Authors: Kim Yon Hui , Liang Han , Liu Xiuping , Lee Ju-Seog , Cho Jae Yong , Cheong Jae-Ho , Kim Hoguen , Li Min , Downey Thomas J. , Dyer Matthew D. , Sun Yongming , Sun Jingtao , Beasley Ellen M. , Chung Hyun Cheol , Noh Sung Hoon , Weinstein John N. , Liu Chang-Gong , Powis Garth 
Published: March 2012

AbstractGastric cancer is the most common cancer in Asia and most developing countries. Despite the use of multimodality therapeutics, it remains the second leading cause of cancer death in the world. To identify the molecular underpinnings of gastric cancer in the Asian population, we applied an RNA-sequencing approach to gastric tumor and noncancerous specimens, generating 680 million informative short reads to quantitatively characterize the entire transcriptome of gastric cancer (including mRNAs and miRNAs). A multilayer analysis was then developed to identify multiple types of transcriptional aberrations associated with different stages of gastric cancer, including differentially expressed mRNAs, recurrent somatic mutations, and key differentially expressed miRNAs. Through this approach, we identified the central metabolic regulator AMP-activated protein kinase (AMPK)α as a potential functional target in Asian gastric cancer. Furthermore, we experimentally showed the translational relevance of this gene as a potential therapeutic target for early-stage gastric cancer in Asian patients. Together, our findings not only provide a valuable information resource for identifying and elucidating the molecular mechanisms of Asian gastric cancer, but also represent a general integrative framework to develop more effective therapeutic targets. Cancer Res; 72(10); 2512–21. ©2012 AACR.