bluuebunny/crossref_metadata_2025_split huggingface dataset:
A genetic variant of the anti-apoptotic protein Akt predicts natalizumab-induced lymphocytosis and post-natalizumab multiple sclerosis reactivation
Authors: Rossi Silvia , Motta Caterina , Studer Valeria , Monteleone Fabrizia , De Chiara Valentina , Buttari Fabio , Barbieri Francesca , Bernardi Giorgio , Battistini Luca , Cutter Gary , Stüve Olaf , Salvetti Marco , Centonze Diego 
Published: May 2012

Background: Multiple sclerosis (MS) patients discontinuing natalizumab treatment are at risk of disease reactivation. No clinical or surrogate parameters exist to identify patients at risk of post-natalizumab MS reactivation. Objective: To determine the role of natalizumab-induced lymphocytosis and of Akt polymorphisms in disease reactivation after natalizumab discontinuation. Methods: Peripheral leukocyte count and composition were monitored in 93 MS patients during natalizumab treatment, and in 56 of these subjects who discontinued the treatment. Genetic variants of the anti-apoptotic protein Akt were determined in all subjects because natalizumab modulates the apoptotic pathway and lymphocyte survival is regulated by the apoptotic cascade. Results: Natalizumab-induced peripheral lymphocytosis protected from post-natalizumab MS reactivation. Subjects who relapsed or had magnetic resonance imaging (MRI) worsening after treatment cessation, in fact, had milder peripheral lymphocyte increases during the treatment, largely caused by less marked T cell increase. Furthermore, subjects carrying a variant of the gene coding for Akt associated with reduced anti-apoptotic efficiency (rs2498804T) had lower lymphocytosis and higher risk of disease reactivation. Conclusion: This study identified one functionally meaningful genetic variant within the Akt signaling pathway that is associated with both lymphocyte count and composition alterations during natalizumab treatment, and with the risk of disease reactivation after natalizumab discontinuation.
Wavelet Coherence Model for Diagnosis of Alzheimer Disease
Authors: Sankari Ziad , Adeli Hojjat , Adeli Anahita 
Published: May 2012

This article presents a wavelet coherence investigation of electroencephalograph (EEG) readings acquired from patients with Alzheimer disease (AD) and healthy controls. Pairwise electrode wavelet coherence is calculated over each frequency band (delta, theta, alpha, and beta). For comparing the synchronization fraction of 2 EEG signals, a wavelet coherence fraction is proposed which is defined as the fraction of the signal time during which the wavelet coherence value is above a certain threshold. A one-way analysis of variance test shows a set of statistically significant differences in wavelet coherence between AD and controls. The wavelet coherence method is effective for studying cortical connectivity at a high temporal resolution. Compared with other conventional AD coherence studies, this study takes into account the time–frequency changes in coherence of EEG signals and thus provides more correlational details. A set of statistically significant differences was found in the wavelet coherence among AD and controls. In particular, temporocentral regions show a significant decrease in wavelet coherence in AD in the delta band, and the parietal and central regions show significant declines in cortical connectivity with most of their neighbors in the theta and alpha bands. This research shows that wavelet coherence can be used as a powerful tool to differentiate between healthy elderly individuals and probable AD patients.
CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair
Authors: Willenborg Sebastian , Lucas Tina , van Loo Geert , Knipper Johanna A. , Krieg Thomas , Haase Ingo , Brachvogel Bent , Hammerschmidt Matthias , Nagy Andras , Ferrara Napoleone , Pasparakis Manolis , Eming Sabine A. 
Published: May 2012

AbstractMonocytes/macrophages are critical in orchestrating the tissue-repair response. However, the mechanisms that govern macrophage regenerative activities during the sequential phases of repair are largely unknown. In the present study, we examined the dynamics and functions of diverse monocyte/macrophage phenotypes during the sequential stages of skin repair. By combining the analysis of a new CCR2-eGFP reporter mouse model with conditional mouse mutants defective in myeloid cell–restricted CCR2 signaling or VEGF-A synthesis, we show herein that among the large number of inflammatory CCR2+Ly6C+ macrophages that dominate the early stage of repair, only a small fraction strongly expresses VEGF-A that has nonredundant functions for the induction of vascular sprouts. The switch of macrophage-derived VEGF-A during the early stage of tissue growth toward epidermal-derived VEGF-A during the late stage of tissue maturation was critical to achieving physiologic tissue vascularization and healing progression. The results of the present study provide new mechanistic insights into CCR2-mediated recruitment of blood monocyte subsets into damaged tissue, the dynamics and functional consequences of macrophage plasticity during the sequential repair phases, and the complementary role of macrophage-derived VEGF-A in coordinating effective tissue growth and vascularization in the context of tissue-resident wound cells. Our findings may be relevant for novel monocyte-based therapies to promote tissue vascularization.
Genome wide response to dietary tetradecylthioacetic acid supplementation in the heart of Atlantic Salmon (Salmo salar L)
Authors: Grammes Fabian , Rørvik Kjell-Arne , Thomassen Magny S , Berge Rolf K , Takle Harald 
Published: May 2012

AbstractBackgroundUnder-dimensioned hearts causing functional problems are associated with higher mortality rates in intensive Atlantic salmon aquaculture. Previous studies have indicated that tetradecylthioacetic acid (TTA) induces cardiac growth and also stimulates transcription of peroxisome proliferator activated receptors (PPAR)αandβin the Atlantic salmon heart. Since cardiac and transcriptional responses to feed are of high interest in aquaculture, the objective of this study was to characterize the transcriptional mechanisms induced by TTA in the heart of Atlantic salmon.ResultsAtlantic salmon were kept at sea for 17 weeks. During the first 8 weeks the fish received a TTA supplemented diet. Using microarrays, profound transcriptional effects were observed in the heart at the end of the experiment, 9 weeks after the feeding of TTA stopped. Approximately 90% of the significant genes were expressed higher in the TTA group. Hypergeometric testing revealed the over-representation of 35 gene ontology terms in the TTA fed group. The GO terms were generally categorized into cardiac performance, lipid catabolism, glycolysis and TCA cycle.ConclusionsOur results indicate that TTA has profound effects on cardiac performance based on results from microarray and qRT-PCR analysis. The gene expression profile favors a scenario of ”physiological”lright hypertrophy recognized by increased oxidative fatty acid metabolism, glycolysis and TCA cycle activity as well as cardiac growth and contractility in the heart ventricle. Increased cardiac efficiency may offer significant benefits in the demanding Aquaculture situations.
Toll-like receptor 9polymorphisms are associated with severity variables in a cohort of meningococcal meningitis survivors
Authors: Sanders Marieke S , van Well Gijs TJ , Ouburg Sander , Morré Servaas A , van Furth A Marceline 
Published: May 2012

AbstractBackgroundGenetic variation in immune response genes is associated with susceptibility and severity of infectious diseases. Toll-like receptor (TLR) 9 polymorphisms are associated with susceptibility to develop meningococcal meningitis (MM). The aim of this study is to compare genotype distributions of twoTLR9polymorphisms between clinical severity variables in MM survivors.MethodsWe used DNA samples of a cohort of 390 children who survived MM. Next, we determined the genotype frequencies ofTLR9-1237 andTLR9+2848 polymorphisms and compared these between thirteen clinical variables associated with prognostic factors predicting adverse outcome of bacterial meningitis in children.ResultsTheTLR9 -1237 TC and CC genotypes were associated with a decreased incidence of a positive blood culture forNeisseria (N.) meningitidis(p = 0.014, odds ratio (OR) 0.5. 95% confidence interval (CI) 0.3 – 0.9). TheTLR9 +2848 AA mutant was associated with a decreased incidence of a positive blood culture forN. meningitidis(p = 0.017, OR 0.6, 95% CI 0.3 – 0.9). Cerebrospinal fluid (CSF) leukocytes per μL were higher in patients carrying theTLR9 -1237 TC or CC genotypes compared to carriers of the TT wild type (WT) (p = 0.024, medians: 2117, interquartile range (IQR) 4987 versus 955, IQR 3938). CSF blood/glucose ratios were lower inTLR9 -1237 TC or CC carriers than in carriers of the TT WT (p = 0.017, medians: 0.20, IQR 0.4 versus 0.35, IQR 0.5). CSF leukocytes/μL were higher in patients carrying theTLR9 +2848 AA mutant compared to carriers of GG or GA (p = 0.0067, medians: 1907, IQR 5221 versus 891, IQR 3952).ConclusionsWe identified TLR9 genotypes associated with protection against meningococcemia and enhanced local inflammatory responses inside the central nervous system, important steps in MM pathogenesis and defense.
Evolutionary engineering strategies to enhance tolerance of xylose utilizing recombinant yeast to inhibitors derived from spruce biomass
Authors: Koppram Rakesh , Albers Eva , Olsson Lisbeth 
Published: May 2012

Abstract

Background
One of the crucial factors for a sustainable and economical production of lignocellulosic based bioethanol is the availability of a robust fermenting microorganism with high tolerance to inhibitors generated during the pretreatment of lignocellulosic raw materials, since these inhibitors are known to severely hinder growth and fermentation.

Results
A long-term adaptation in repetitive batch cultures in shake flasks using a cocktail of 12 different inhibitors and a long-term chemostat adaptation using spruce hydrolysate were used as evolutionary engineering strategies to improve the inhibitor tolerance in the metabolically engineered xylose utilizing Saccharomyces cerevisiae strain, TMB3400. The yeast was evolved for a period of 429 and 97 generations in repetitive batch cultures and chemostat cultivation, respectively. During the evolutionary engineering in repetitive batch cultures the maximum specific growth rate increased from 0.18 h-1 to 0.33 h-1 and the time of lag phase was decreased from 48 h to 24 h. In the chemostat adaptation, after 97 generations, the specific conversion rates of HMF and furfural were found to be 3.5 and 4 folds higher respectively, compared to rates after three generations. Two evolved strains (RK60-5, RKU90-3) and one evolved strain (KE1-17) were isolated from evolutionary engineering in repetitive batches and chemostat cultivation, respectively. The strains displayed significantly improved growth performance over TMB3400 when cultivated in spruce hydrolysate under anaerobic conditions, the evolved strains exhibited 25 to 38% increase in specific consumption rate of sugars and 32 to 50% increased specific ethanol productivity compared to TMB3400. The evolved strains RK60-5 and RKU90-3 were unable to consume xylose under anaerobic conditions, whereas, KE1-17 was found to consume xylose at similar rates as TMB3400.

Conclusion
Using evolutionary engineering strategies in batch and chemostat cultivations we have generated three evolved strains that show significantly better tolerance to inhibitors in spruce hydrolysate and displayed a shorter time for overall fermentation of sugars compared to the parental strain.
Leukaemia diagnosed as a consequence of haematuria assessment: a case report
Authors: Pisipati Sailaja , Lucas Guy , Pearce Ian 
Published: May 2012

Abstract

Introduction
T-cell prolymphocytic leukaemia is a rare condition that constitutes around 2% of cases of small lymphocytic leukaemia in adults. It follows an aggressive clinical course with a poor prognosis.

Case presentation
We report a 55-year-old male who was diagnosed with T-cell prolymphocytic leukaemia following investigations for microscopic haematuria. Splenomegaly was identified on a plain abdominal radiograph and intravenous urography, thus triggering further investigations and diagnosis.

Conclusion
Our case-report serves to remind us of the need to bear in mind other possible pathologies outwith our own area of expertise when interpreting results of any kind. This is perhaps increasingly important in the current era of increasing sub-specialisation throughout medicine.
Atypical presentation of an oesophageal carcinoma with metastases to the left buttock: a case report
Authors: Smyth Sarah , O'Donnell Mark E , Kumar Susim , Hussain Atiq , Cranley Brian 
Published: May 2012

Abstract

Introduction
Oesophageal carcinomas represent 3% of all cancers in the UK accounting for 7650 new cases per annum. Oesophageal cancer may be associated with swallowing abnormalities, localised mass pressure effects, lymphatic or distant metastatic spread.

Case presentation
We report a 50-year-old man who presented with a painful, enlarging, solid, fixed lesion adjacent to the left buttock with associated dysphagia. Initial endoscopic assessment suggested severe oesophageal inflammation while the lesion in the buttock area was presumed to be a primary soft-tissue neoplasm. However, subsequent histological assessment confirmed a primary oesophageal squamous carcinoma with metastatic spread to the buttock.

Conclusion
We discuss the clinical presentation, investigative modalities, and current therapeutic guidelines associated with this rare metastasis and present other atypical oesophageal musculoskeletal metastases. We emphasise the need to consider all aspects of patient symptomatology during the investigation of any atypical lesion.
Behcet's disease presenting with cerebral vasculitis: a case report
Authors: Ozturk Banu Turgut , Oltulu Refik , Kerimoglu Hurkan , Okudan Suleyman 
Published: May 2012

AbstractIntroductionBehcet's disease encompasses a group of multisystemic complications secondary to occlusive vasculitis. It presents usually with oral or genital ulcers however, other system involvements may be the first sign as well.Case presentationA 26-years-old man admitted to our clinic for his decreased visual acuity. Ophthalmologic examination revealed bilateral vitritis and optic disc swelling. However, the meticulously taken history included other complains like headache and oral ulcers. Further investigation with cranial MRI demonstrated cerebral vasculitis secondary to Behcet's disease.ConclusionBehcet's disease may be easy to diagnose when it presents with oral and genital ulcers or panuveitis, however presentation with optic disc swelling may warrant a thorough investigation.
In ovo leptin administration affects hepatic lipid metabolism and microRNA expression in newly hatched broiler chickens
Authors: Hu Yan , Zhang Rui , Zhang Yanhong , Li Jing , Grossmann Roland , Zhao Ruqian 
Published: May 2012

AbstractBackgroundA leptin-like immunoreactive substance has been found in chicken eggs and has been implicated in serving as a maternal signal to program offspring growth and metabolism. In the present study, we investigated the effects ofin ovoleptin administration on hatch weight, serum and hepatic concentrations of metabolites and hormones, as well as on the expression of genes involved in hepatic lipid metabolism and the predicted microRNAs (miRNAs) targeting the affected genes. To this end we injected fertile eggs with either 0.5 μg of recombinant murine leptin or vehicle (PBS) before incubation.ResultsPrenatally leptin-exposed chicks showed lower hatch weight, but higher liver weight relative to the body weight, compared to the control group.In ovoleptin treatment increased the hepatic content and serum concentration of leptin in newly hatched chickens. The hepatic contents of triglycerides (TG) and total cholesterol (Tch) were decreased, whereas the serum levels of TG, Tch and apolipoprotein B (ApoB) were increased. The hepatic mRNA expression ofsterol regulator element binding protein 1(SREBP-1c),SREBP-2,hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR) andcholesterol 7α-hydroxylase 1(CYP7A1) was significantly up-regulated, as was the protein content of both SREBP-1c and SREBP-2 in hepatic nuclear extracts of leptin-treated chickens. Moreover, out of 12 miRNAs targetingSREBP-1cand/orHMGCR, five were significantly up-regulated in liver of leptin-treated chicks, includinggga-miR-200bandgga-miR-429, which target bothSREBP-1candHMGCR.ConclusionsThese results suggest that leptinin ovodecreases hatch weight, and modifies hepatic leptin secretion and lipid metabolism in newly hatched broiler chickens, possibly via microRNA-mediated gene regulation.
Relaxin's induction of metalloproteinases is associated with the loss of collagen and glycosaminoglycans in synovial joint fibrocartilaginous explants
Authors: Naqvi Tabassum , Duong Trang T , Hashem Gihan , Shiga Momotoshi , Zhang Qin , Kapila Sunil 
Published: May 2012

AbstractDiseases of specific fibrocartilaginous joints are especially common in women of reproductive age, suggesting that female hormones contribute to their etiopathogenesis. Previously, we showed that relaxin dose-dependently induces matrix metalloproteinase (MMP) expression in isolated joint fibrocartilaginous cells. Here we determined the effects of relaxin with or without β-estradiol on the modulation of MMPs in joint fibrocartilaginous explants, and assessed the contribution of these proteinases to the loss of collagen and glycosaminoglycan (GAG) in this tissue. Fibrocartilaginous discs from temporomandibular joints of female rabbits were cultured in medium alone or in medium containing relaxin (0.1 ng/ml) or β-estradiol (20 ng/ml) or relaxin plus β-estradiol. Additional experiments were done in the presence of the MMP inhibitor GM6001 or its control analog. After 48 hours of culture, the medium was assayed for MMPs and the discs were analyzed for collagen and GAG concentrations. Relaxin and β-estradiol plus relaxin induced the MMPs collagenase-1 and stromelysin-1 in fibrocartilaginous explants – a finding similar to that which we observed in pubic symphysis fibrocartilage, but not in articular cartilage explants. The induction of these proteinases by relaxin or β-estradiol plus relaxin was accompanied by a loss of GAGs and collagen in joint fibrocartilage. None of the hormone treatments altered the synthesis of GAGs, suggesting that the loss of this matrix molecule probably resulted from increased matrix degradation. Indeed, fibrocartilaginous explants cultured in the presence of GM6001 showed an inhibition of relaxin-induced and β-estradiol plus relaxin-induced collagenase and stromelysin activities to control baseline levels that were accompanied by the maintenance of collagen or GAG content at control levels. These findings show for the first time that relaxin has degradative effects on non-reproductive synovial joint fibrocartilaginous tissue and provide evidence for a link between relaxin, MMPs, and matrix degradation.
Identification of arthritis-related gene clusters by microarray analysis of two independent mouse models for rheumatoid arthritis
Authors: Fujikado Noriyuki , Saijo Shinobu , Iwakura Yoichiro 
Published: May 2012

AbstractRheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population worldwide. Previously, we showed that human T-cell leukemia virus type I-transgenic mice and interleukin-1 receptor antagonist-knockout mice develop autoimmunity and joint-specific inflammation that resembles human RA. To identify genes involved in the pathogenesis of arthritis, we analyzed the gene expression profiles of these animal models by using high-density oligonucleotide arrays. We found 1,467 genes that were differentially expressed from the normal control mice by greater than threefold in one of these animal models. The gene expression profiles of the two models correlated well. We extracted 554 genes whose expression significantly changed in both models, assuming that pathogenically important genes at the effector phase would change in both models. Then, each of these commonly changed genes was mapped into the whole genome in a scale of the 1-megabase pairs. We found that the transcriptome map of these genes did not distribute evenly on the chromosome but formed clusters. These identified gene clusters include the major histocompatibility complex class I and class II genes, complement genes, and chemokine genes, which are well known to be involved in the pathogenesis of RA at the effector phase. The activation of these gene clusters suggests that antigen presentation and lymphocyte chemotaxisis are important for the development of arthritis. Moreover, by searching for such clusters, we could detect genes with marginal expression changes. These gene clusters include schlafen and membrane-spanning four-domains subfamily A genes whose function in arthritis has not yet been determined. Thus, by combining two etiologically different RA models, we succeeded in efficiently extracting genes functioning in the development of arthritis at the effector phase. Furthermore, we demonstrated that identification of gene clusters by transcriptome mapping is a useful way to find potentially pathogenic genes among genes whose expression change is only marginal.
Molecular discrimination of responders and nonresponders to anti-TNFalpha therapy in rheumatoid arthritis by etanercept
Authors: Koczan Dirk , Drynda Susanne , Hecker Michael , Drynda Andreas , Guthke Reinhard , Kekow Joern , Thiesen Hans-Juergen 
Published: May 2012

Abstract
Introduction
About 30% of rheumatoid arthritis patients fail to respond adequately to TNFα-blocking therapy. There is a medical and socioeconomic need to identify molecular markers for an early prediction of responders and nonresponders.

Methods
RNA was extracted from peripheral blood mononuclear cells of 19 rheumatoid arthritis patients before the first application of the TNFα blocker etanercept as well as after 72 hours. Clinical response was assessed over 3 months using the 28-joint-count Disease Activity Score and X-ray scans. Supervised learning methods were applied to Affymetrix Human Genome U133 microarray data analysis to determine highly selective discriminatory gene pairs or triplets with prognostic relevance for the clinical outcome evinced by a decline of the 28-joint-count Disease Activity Score by 1.2.

Results
Early downregulation of expression levels secondary to TNFα neutralization was associated with good clinical responses, as shown by a decline in overall disease activity 3 months after the start of treatment. Informative gene sets include genes (for example, NFKBIA, CCL4, IL8, IL1B, TNFAIP3, PDE4B, PPP1R15A and ADM) involved in different pathways and cellular processes such as TNFα signalling via NFκB, NFκB-independent signalling via cAMP, and the regulation of cellular and oxidative stress response. Pairs and triplets within these genes were found to have a high prognostic value, reflected by prediction accuracies of over 89% for seven selected gene pairs and of 95% for 10 specific gene triplets.

Conclusion
Our data underline that early gene expression profiling is instrumental in identifying candidate biomarkers to predict therapeutic outcomes of anti-TNFα treatment regimes.