bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bifunctional role of aconitase in Streptomyces viridochromogenesTü494
Authors: Michta Ewelina , Schad Klaus , Blin Kai , Ort‐Winklbauer Regina , Röttig Marc , Kohlbacher Oliver , Wohlleben Wolfgang , Schinko Eva , Mast Yvonne 
Published: October 2012

SummaryIn many organisms, aconitases have dual functions; they serve as enzymes in the tricarboxylic acid cycle and as regulators of iron metabolism. In this study we defined the role of the aconitase AcnA in Streptomyces viridochromogenes Tü494, the producer of the herbicide phosphinothricyl‐alanyl‐alanine, also known as phosphinothricin tripeptide or bialaphos. A mutant in which the aconitase gene acnA was disrupted showed severe defects in morphology and physiology, as it was unable to form any aerial mycelium, spores nor phosphinothricin tripeptide. AcnA belongs to the iron regulatory proteins (IRPs). In addition to its catalytic function, AcnA plays a regulatory role by binding to iron responsive elements (IREs) located on the untranslated region of certain mRNAs. A mutation preventing the formation of the [4Fe‐4S] cluster of AcnA eliminated its catalytic activity, but did not inhibit RNA‐binding ability. In silico analysis of the S. viridochromogenes genome revealed several IRE‐like structures. One structure is located upstream of recA, which is involved in the bacterial SOS response, and another one was identified upstream of ftsZ, which is required for the onset of sporulation in streptomycetes. The functionality of different IRE structures was proven with gel shift assays and specific IRE consensus sequences were defined. Furthermore, RecA was shown to be upregulated on post‐transcriptional level under oxidative stress conditions in the wild‐type strain but not in the acnA mutant, suggesting a regulatory role of AcnA in oxidative stress response.
Microarray evaluation of specific IgE to allergen components in elite athletes
Authors: Bonini M. , Marcomini L. , Gramiccioni C. , Tranquilli C. , Melioli G. , Canonica G. W. , Bonini S. ,   on behalf of the ISAC Study Group
Published: October 2012

AbstractBackgroundAllergic sensitization and diseases have been reported to have a very high and increasing prevalence in elite athletes. Over 80% of allergic athletes are poly‐sensitized.ObjectiveThis study aims at evaluating the potential diagnostic added value of a microarray technology (ImmunoCAP ISAC, Phadia AB [at present Thermo Fisher Scientific] Uppsala, Sweden which detects IgE antibodies to specific or cross‐reacting allergen components.MethodsSeventy‐two poly‐sensitized athletes according to skin prick test (SPT) with different allergic phenotypes (asthma n = 19; rhino‐conjunctivitis n = 20; food allergy and/or oral allergy syndrome n = 13; no clinical symptoms n = 20) and two different control populations (20 poly‐sensitized sedentary subjects with respiratory allergy and 20 healthy athletes with negative SPT) were studied for detecting specific IgE (sIgE) both to allergen extracts (ImmunoCAPsIgE) and to allergen components (ImmunoCAP ISAC).ResultsImmunoCAP ISAC detected the presence of sIgE in 90% of poly‐sensitized athletes – in 96% with symptoms and in 75% without symptoms – and in 100% of allergic controls. The pattern of positivity towards the 103 components tested differed from subject to subject, even in those with the same sensitization to allergen extract SPT or sIgE. Based on the ISAC results, poly‐sensitized athletes were classified into the following prototypical patterns, differently represented in the clinical phenotypes studied (P = 0.03): (1) One single predominant specific allergen positivity; (2) sIgE to two or more non‐cross‐reacting allergens; (3) sIgE to cross‐reacting allergens; and (4) sIgE to components potentially responsible for severe allergic reactions.ConclusionsThe ImmunoCAP ISAC represents a useful additional tool for diagnosis and management of poly‐sensitized athletes.
Challenges of alloimmunization in patients with haemoglobinopathies
Authors: Chou Stella T. , Liem Robert I. , Thompson Alexis A. 
Published: October 2012

SummaryRed blood cell (RBC) transfusions can be life‐sustaining in chronic inherited anaemias, such as thalassaemia, and the indications for blood transfusions in patients with sickle cell disease continue to expand. Complications of transfusions, such as allosensitization, can create significant medical challenges in the management of patients with haemoglobinopathies. This review summarizes key findings from the medical literature related to alloimmunization in haemoglobinopathies and examines potential measures to mitigate these risks. Areas where future studies are needed are also addressed.
Representing Spatial Structure Through Maps and Language: Lord of the Rings Encodes the Spatial Structure of Middle Earth
Authors: Louwerse Max M. , Benesh Nick 
Published: October 2012

AbstractSpatial mental representations can be derived from linguistic and non‐linguistic sources of information. This study tested whether these representations could be formed from statistical linguistic frequencies of city names, and to what extent participants differed in their performance when they estimated spatial locations from language or maps. In a computational linguistic study, we demonstrated that co‐occurrences of cities in Tolkien’sLord of the Ringstrilogy andThe Hobbitpredicted the authentic longitude and latitude of those cities in Middle Earth. In a human study, we showed that human spatial estimates of the location of cities were very similar regardless of whether participants read Tolkien’s texts or memorized a map of Middle Earth. However, text‐based location estimates obtained from statistical linguistic frequencies better predicted the human text‐based estimates than the human map‐based estimates. These findings suggest that language encodes spatial structure of cities, and that human cognitive map representations can come from implicit statistical linguistic patterns, from explicit non‐linguistic perceptual information, or from both.
Practice‐related reduction of electromyographic mirroring activity depends on basal levels of interhemispheric inhibition
Authors: Bologna Matteo , Caronni Antonio , Berardelli Alfredo , Rothwell John C. 
Published: October 2012

AbstractPaired‐pulse transcranial magnetic stimulation (TMS) is used to measure the excitability of interhemispheric inhibition (IHI) between the hand areas of the two motor cortices. It varies from person to person, and is highly predictive of individual differences in callosal anatomy (fractional anisotropy) and even motor behaviour, e.g. the amount of involuntary electromyographic (EMG) ‘mirroring’ in one hand during rapid contraction of the other. The present experiments tested whether it also predicts how well individuals can improve motor performance in a task involving the two hands. Healthy participants were given 100 trials to maximize the initial acceleration of a ballistic finger movement made with one hand while trying to maintain a tonic low level of EMG activity in the other hand. Initially, each movement was accompanied by additional unwanted EMG mirroring in the other hand. However, after practice, participants had on average increased acceleration by approximately one‐third without changing the amount of EMG mirroring in the contralateral hand; indeed, in some individuals EMG mirroring activity declined. TMS measures showed that there was an increase in corticospinal excitability in the trained hemisphere, but there was no change in the excitability of short‐ or long‐latency IHI from the trained to non‐trained hemisphere. Nevertheless, in each individual, the baseline (pre‐practice) excitability of short‐latency IHI was highly predictive (r = 0.65; P = 0.0019) of the change in EMG mirroring. The implication is that a physiological measure of brain excitability at rest can predict behaviour in response to training.
Positive Relationship Between a Polymorphism in Helicobacter pylori Neutrophil‐Activating Protein A Gene and Iron‐Deficiency Anemia
Authors: Yokota Shin‐ichi , Toita Nariaki , Yamamoto Soh , Fujii Nobuhiro , Konno Mutsuko 
Published: October 2012

AbstractBackgroundNumerous studies have suggested a link between iron‐deficiency anemia (IDA) and Helicobacter pylori infection. Previously, we found that strains isolated from IDA patients showed higher levels of Fe ion uptake and Fe‐ion‐dependent rapid proliferation than those of strains derived from patients without IDA.Materials and MethodsTwenty‐four H. pylori strains from IDA patients (IDA strains) and 25 strains from patients who had H. pylori gastritis without anemia (non‐IDA strains) were examined. Their nucleotide sequences of napA, fur, and feoB, which contribute to Fe ion uptake, were determined.ResultsNumerous polymorphisms of the three genes were found in both strains. Frequency of neutrophil‐activating protein A (NapA), which encoded by napA, with threonine at amino acid residue No. 70 (Thr70‐type NapA) was significantly higher in IDA strains than in non‐IDA strains. Strains with Thr70‐type NapA showed significantly higher levels of Fe3+ and Fe2+ uptake than did strains with other types, Ser70‐type of NapA, which is found in standard strains. Other significantly different occurrences of polymorphisms between IDA and non‐IDA groups were not observed in these genes.ConclusionThe results suggest that H. pylori strains with Thr70‐type NapA have enhanced Fe ion uptake ability and are associated with the pathogenesis of IDA.
A design process for using normative models in shared decision making: a case study in the context of prenatal testing
Authors: Rapaport Sivan , Leshno Moshe , Fink Lior 
Published: October 2012

AbstractBackgroundShared decision making (SDM) encourages the patient to play a more active role in the process of medical consultation and its primary objective is to find the best treatment for a specific patient. Recent findings, however, show that patient preferences cannot be easily or accurately judged on the basis of communicative exchange during routine office visits, even for patients who seek to expand their role in medical decision making (MDM).ObjectiveThe objective of this study is to improve the quality of patient–physician communication by developing a novel design process for SDM and then demonstrating, through a case study, the applicability of this process in enabling the use of a normative model for a specific medical situation.DesignOur design process goes through the following stages: definition of medical situation and decision problem, development/identification of normative model, adaptation of normative model, empirical analysis and development of decision support systems (DSS) tools that facilitate the SDM process in the specific medical situation.Case studyThis study demonstrates the applicability of the process through the implementation of the general normative theory of MDM under uncertainty for the medical–financial dilemma of choosing a physician to perform amniocentesis.DiscussionThe use of normative models in SDM raises several issues, such as the goal of the normative model, the relation between the goals of prediction and recommendation, and the general question of whether it is valid to use a normative model for people who do not behave according to the model's assumptions.
Patients’ engagement in primary care: powerlessness and compounding jeopardy. A qualitative study
Authors: Sheridan Nicolette F , Kenealy Timothy W , Kidd Jacquie D , Schmidt‐Busby Jacqueline I G , Hand Jennifer E , Raphael Deborah L , McKillop Ann M , Rea Harold H 
Published: October 2012

AbstractBackgroundPrimary health care does not adequately respond to populations known to have high needs such as those with compounding jeopardy from chronic conditions, poverty, minority status and age; as such populations report powerlessness.ObjectiveTo explore what poor older adults with chronic conditions who mostly belong to ethnic minority groups say they want from clinicians.Setting and ParticipantsParticipants were older adults whose chronic conditions were severe enough to require hospital admission more than twice in the previous 12 months. All participants lived in poor localities inAuckland,NewZealand's largest city.MethodsForty‐two in‐depth interviews were conducted and analysed using qualitative description.ResultsAn outward acceptance of health care belied an underlying dissatisfaction with low engagement. Participants did not feel heard and wanted information conveyed in a way that indicated clinicians understood them in the context of their lives. Powerlessness, anger, frustration and non‐concordance were frequent responses.Discussion and ConclusionsDespite socio‐cultural and disease‐related complexity, patients pursue the (unrealised) ideal of an engaged therapeutic relationship with an understanding clinician. Powerlessness means that the onus is upon the health system and the clinician to engage. Engagement means building a relationship on the basis of social, cultural and clinical knowledge and demonstrating a shift in the way clinicians choose to think and interact in patient care. Respectful listening and questioning can deepen clinicians' awareness of patients' most important concerns. Enabling patients to direct the consultation is a way to integrate clinician expertise with what patients need and value.
Treatment of non‐alcoholic steatohepatitis with Phyllanthus urinaria: A randomized trial
Authors: Wong Vincent Wai‐Sun , Wong Grace Lai‐Hung , Chan Anthony Wing‐Hung , Chu Winnie Chiu‐Wing , Choi Paul Cheung‐Lung , Chim Angel Mei‐Ling , Yiu Karen Kar‐Lum , Yu Jun , Chan Francis Ka‐Leung , Chan Henry Lik‐Yuen 
Published: October 2012

AbstractBackground and AimsNon‐alcoholic steatohepatitis (NASH) is a common liver disease that may progress to cirrhosis and hepatocellular carcinoma. There is currently no approved pharmacological treatment for NASH. Phyllanthus urinaria is a commonly used hepatoprotective herb that ameliorates NASH in animal studies. We aimed to test the hypothesis that Phyllanthus was superior to placebo in improving histological non‐alcoholic fatty liver disease (NAFLD) activity score.MethodsThis was a placebo‐controlled parallel‐group double‐blind randomized controlled trial. Patients with histology‐proven NASH were randomized to receive Phyllanthus or placebo for 24 weeks. The primary endpoint was change in NAFLD activity score from baseline to week 24. Secondary endpoints included changes in individual histological parameters, liver biochemistry and metabolic profile.ResultsWe enrolled 60 patients (40 received Phyllanthus and 20 received placebo). The change in NAFLD activity score was −0.8 ± 1.4 in the Phyllanthus group and −0.3 ± 1.3 in the placebo group (P = 0.24). The change in steatosis, lobular inflammation, ballooning and fibrosis was also similar between the two groups. Within the Phyllanthus group, although there was reduction in hepatic steatosis (−0.2 ± 0.7; P = 0.039) and ballooning grades (−0.4 ± 0.5; P < 0.001), the change was small and of limited clinical significance. Furthermore, there was no significant difference in the changes in alanine aminotransferase, aspartate aminotransferase, fasting glucose and lipid profile between the two groups.ConclusionsPhyllanthus is not superior to placebo in improving NAFLD activity score in NASH patients.
Novel splice‐site mutation in ATP8B1 results in atypical Progressive Familial Intrahepatic Cholestasis Type 1
Authors: Copeland Emily , Renault Nisa , Renault Marc , Dyack Sarah , Bulman Dennis E , Bedard Karen , Otley Anthony , Magee Fergall , Acott Philip , Greer Wenda L 
Published: October 2012

AbstractBackground and AimOur objective was to identify the molecular genetic basis of an Alagille‐like condition not linked to JAG1 or NOTCH2 in two related sibships.MethodsBecause of common ancestry, and an autosomal recessive mode of inheritance, it was hypothesized that all affected and no unaffected individuals would be homozygous for the same haplotype in the region of the causative gene. Single nucleotide polymorphism arrays were therefore used to genotype 3 affected individuals from two sibships, their mothers and four unaffected siblings, to identify regions of homozygosity. Genes within the largest regions were prioritized and sequenced for mutations. Mutant RNA transcripts were also sequenced.ResultsA novel splice acceptor site mutation in the ATP8B1 gene was identified (a G–C preceding exon 16 resulting in a 4 bp deletion and frameshift from the 5′ end of exon 16). This result was unexpected because ATP8B1 mutations are associated with Progressive Familial Intrahepatic Cholestasis Type 1 (PFIC1). Intrahepatic bile duct paucity, cardiac anomalies, renal tubular acidosis and hypothyroidism led to an initial diagnosis of Alagille Syndrome. However, in retrospect, abnormal sweat chloride, normal gamma‐glutamyl transferase, normal to low cholesterol, and an autosomal recessive mode of inheritance were consistent with PFIC1. Renal tubular acidosis, hypothyroidism and cardiac anomalies have not previously been associated with PFIC1.ConclusionThis work expands the phenotypic spectrum of PFIC1, and highlights the overlap in clinical phenotype between Alagille Syndrome and PFIC1. Knowledge of the causative mutation allows for carrier testing and prenatal diagnosis in this community.
High grade prostatic intraepithelial neoplasia does not display loss of heterozygosity at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer
Authors: Willems‐Jones Amber , Kavanagh Liam , Clouston David , Bolton Damien ,   kConFab Investigators, Fox Stephen , Thorne Heather 
Published: October 2012

What's known on the subject? and What does the study add?The risk of developing aggressive prostate cancer is increased for men carrying a pathogenic germline mutation in BRCA2. An earlier study by the Kathleen Cuningham Consortium for Research into Familial Breast Cancer showed that BRCA2 mutation carriers displayed a loss of heterozygosity (LOH) within their prostate cancer tissue in the majority of cases, thus implying that the prostate cancer in these men occurred as a result of LOH for BRCA2. High grade prostatic intraepithelial neoplasia (HGPIN) has been considered a precursor to prostate adenocarcinoma in some, but not all, cases of prostate adenocarcinoma.The study found that there was no LOH for BRCA2 in HGPIN. From this small cohort of BRCA2‐positive men, we suggest HGPIN is not necessarily a precursor to their prostate cancer development. The presence of HGPIN in a TRUS biopsy in these men at risk of high risk disease is not an indication for prostatectomy.OBJECTIVES
To determine if high grade prostatic intraepithelial neoplasia (HGPIN), which is considered a precursor to the development of prostate adenocarcinoma, displays the same genetic hallmarks as adenocarcinoma.
To identify, using molecular genetic techniques, if HGPIN is a precursor of tumour development and progression in men carrying a pathogenic germline mutation in BRCA2.
PATIENTS AND METHODS
Ten participants from the Kathleen Cuningham Consortium for Research into Familial Breast Cancer cohort of high‐risk breast cancer families were identified, with (i) a diagnosis of aggressive prostate cancer and presence of HGPIN, (ii) a pathogenic BRCA2 mutation, and (iii) access to archival prostate tissue specimens.
Loss of heterozygosity (LOH) at the BRCA2 gene was examined using mutation‐specific PCR and sequencing of DNA from laser microdissected HGPIN.
RESULTS
Within this cohort of 10 pathogenic BRCA2 carriers, no patient displayed LOH at the mutation locus within HGPIN, irrespective of whether or not corresponding adenocarcinoma DNA displayed LOH.
CONCLUSIONS
Although HGPIN is considered a precursor to cancer, as no LOH was observed, this assay does not provide a genetic marker that may be considered a positive predictor of tumorigenesis in BRCA2 carriers.
In this group of high‐risk men, early screening via prostate‐specific antigen testing, rectal examination and prostate biopsy may be prudent to permit the detection and the optimum clinical management of prostate cancer.
Globalization Lived Locally: Investigating Kerala's Local Labour Control Regimes
Authors: Neethi P. 
Published: October 2012

ABSTRACTThis article uses the case study of a prominent electronics manufacturer in Kerala, southern India, to illuminate an approach to labour studies which focuses on local labour control regimes. Kerala was chosen for this study because of certain unusual characteristics of its labour market. Building on the theoretical base of local labour control regimes, empirical evidence from the case study reveals that local labour markets develop their own forms of labour control and worker response patterns. These are not always clearly visible and may require something more than superficial enquiry to bring their salient features into view. In this case, the Church is shown to play an unexpected role in local labour control regimes.
Ageing and long‐term CD4 cell count trends in HIV‐positive patients with 5 years or more combination antiretroviral therapy experience
Authors: Wright ST , Petoumenos K , Boyd M , Carr A , Downing S , O'Connor CC , Grotowski M , Law MG ,   Australian HIV Observational Database study group
Published: October 2012

ObjectivesThe aim of this study was to describe the long‐term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long‐term decline in the immune system via low‐grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV‐positive patients with increasing duration of cART.MethodsRetrospective and prospective data were examined from long‐term virologically stable HIV‐positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell count changes following the completion of 5 years of cART using linear mixed models.ResultsA total of 37 916 CD4 measurements were observed for 892 patients over a combined total of 9753 patient‐years. Older patients (> 50 years old) at cART initiation had estimated mean (95% confidence interval) changes in CD4 counts by year‐5 CD4 count strata (< 500, 500–750 and > 750 cells/μL) of 14 (7 to 21), 3 (–5 to 11) and –6 (–17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long‐term declines in CD4 cell counts.ConclusionsOur results suggest that duration of cART and increasing age do not result in decreasing mean changes in CD4 cell counts for long‐term virologically suppressed patients, indicating that the level of immune recovery achieved during the first 5 years of treatment is sustained through long‐term cART.