bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of catalytically active orthologues of the Parkinson's disease kinase PINK1: analysis of substrate specificity and impact of mutations
Authors: Woodroof Helen I. , Pogson Joe H. , Begley Mike , Cantley Lewis C. , Deak Maria , Campbell David G. , van Aalten Daan M. F. , Whitworth Alexander J. , Alessi Dario R. , Muqit Miratul M. K.
Published: November 2011

Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is known about the intrinsic catalytic properties of PINK1 since the human enzyme displays such low kinase activity
in vitro
. We have discovered that, in contrast to mammalian PINK1, insect orthologues of PINK1 we have investigated—namely
Drosophila melanogaster
(dPINK1)
, Tribolium castaneum
(TcPINK1) and
Pediculus humanus corporis
(PhcPINK1)—are active as judged by their ability to phosphorylate the generic substrate myelin basic protein. We have exploited the most active orthologue, TcPINK1, to assess its substrate specificity and elaborated a peptide substrate (PINKtide, KKWIpYRRSPRRR) that can be employed to quantify PINK1 kinase activity. Analysis of PINKtide variants reveal that PINK1 phosphorylates serine or threonine, but not tyrosine, and we show that PINK1 exhibits a preference for a proline at the +1 position relative to the phosphorylation site. We have also, for the first time, been able to investigate the effect of Parkinson's disease-associated PINK1 missense mutations, and found that nearly all those located within the kinase domain, as well as the C-terminal non-catalytic region, markedly suppress kinase activity. This emphasizes the crucial importance of PINK1 kinase activity in preventing the development of Parkinson's disease. Our findings will aid future studies aimed at understanding how the activity of PINK1 is regulated and the identification of physiological substrates.
Reintroduction of H5N1 highly pathogenic avian influenza virus by migratory water birds, causing poultry outbreaks in the 2010–2011 winter season in Japan
Authors: Sakoda Yoshihiro , Ito Hiroshi , Uchida Yuko , Okamatsu Masatoshi , Yamamoto Naoki , Soda Kosuke , Nomura Naoki , Kuribayashi Saya , Shichinohe Shintaro , Sunden Yuji , Umemura Takashi , Usui Tatsufumi , Ozaki Hiroichi , Yamaguchi Tsuyoshi , Murase Toshiyuki , Ito Toshihiro , Saito Takehiko , Takada Ayato , Kida Hiroshi
Published: November 2011

H5N1 highly pathogenic avian influenza virus (HPAIV) was reintroduced and caused outbreaks in chickens in the 2010–2011 winter season in Japan, which had been free from highly pathogenic avian influenza (HPAI) since 2007 when HPAI outbreaks occurred and were controlled. On 14 October 2010 at Lake Ohnuma, Wakkanai, the northernmost part of Hokkaido, Japan, H5N1 HPAIVs were isolated from faecal samples of ducks flying from their nesting lakes in Siberia. Since then, in Japan, H5N1 HPAIVs have been isolated from 63 wild birds in 17 prefectures and caused HPAI outbreaks in 24 chicken farms in nine prefectures by the end of March in 2011. Each of these isolates was genetically closely related to the HPAIV isolates at Lake Ohnuma, and those in China, Mongolia, Russia and Korea, belonging to genetic clade 2.3.2.1. In addition, these isolates were genetically classified into three groups, suggesting that the viruses were transmitted by migratory water birds through at least three different routes from their northern territory to Japan. These isolates were antigenic variants, which is consistent with selection in poultry under the immunological pressure induced by vaccination. To prevent the perpetuation of viruses in the lakes where water birds nest in summer in Siberia, prompt eradication of HPAIVs in poultry is urgently needed in Asian countries where HPAI has not been controlled.
Human T-cell leukemia viruses are highly unstable over a wide range of temperatures
Authors: Shinagawa Masahiko , Jinno-Oue Atsushi , Shimizu Nobuaki , Roy Bibhuti Bhusan , Shimizu Akira , Hoque Sk. Ariful , Hoshino Hiroo
Published: November 2011

The biological properties of human T-cell leukemia virus type I (HTLV-I) and HTLV type II (HTLV-II) are not well elucidated as cell-free viruses. We established new assay systems to detect the infectivity of cell-free HTLVs and examined the stability of cell-free HTLVs at different temperatures. HTLVs lost infectivity more rapidly than did bovine leukemia virus (BLV), which is genetically related to HTLVs. The half-lives of three HTLV-I strains (two cosmopolitan strains and one Melanesian strain) at 37 °C were approximately 0.6 h, whereas the half-life of a BLV strain was 8.5 h. HTLV-I rapidly lost infectivity unexpectedly at 0 and 4 °C. We examined the stability of vesicular stomatitis virus pseudotypes with HTLV-I, HTLV-II or BLV Env proteins, and the Env proteins of HTLVs were found to be more unstable at 4 and 25 °C than the Env proteins of the BLV. Over the course of the viral life cycle, heat treatment inhibited HTLV-I infection at the phase of attachment to the host cells, and inhibition was more marked upon entry into the cells. The HTLV-I Env surface (SU) protein (gp46) was easily released from virions during incubation at 37 °C. However, this release was inhibited by pre-treatment of the virions with N-ethylmaleimide, suggesting that the inter-subunit bond between gp46 SU and gp21 transmembrane (TM) proteins is rearranged by disulfide bond isomerization. HTLVs are highly unstable over a wide range of temperatures because the disulfide bonds between the SU and TM proteins are labile.
Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis)
Authors: Saito Akatsuki , Kono Ken , Nomaguchi Masako , Yasutomi Yasuhiro , Adachi Akio , Shioda Tatsuo , Akari Hirofumi , Nakayama Emi E.
Published: November 2011

The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses.
Assembly of the Light-Harvesting Chlorophyll Antenna in the Green Alga Chlamydomonas reinhardtii Requires Expression of the TLA2-CpFTSY Gene
Authors: Kirst Henning , García-Cerdán Jose Gines , Zurbriggen Andreas , Melis Anastasios
Published: November 2011

The truncated light-harvesting antenna2 (tla2) mutant of Chlamydomonas reinhardtii showed a lighter-green phenotype, had a lower chlorophyll (Chl) per-cell content, and higher Chl a/b ratio than corresponding wild-type strains. Physiological analyses revealed a higher intensity for the saturation of photosynthesis and greater P  max values in the tla2 mutant than in the wild type. Biochemical analyses showed that the tla2 strain was deficient in the Chl a-b light-harvesting complex, and had a Chl antenna size of the photosystems that was only about 65% of that in the wild type. Molecular and genetic analyses showed a single plasmid insertion in the tla2 strain, causing a chromosomal DNA rearrangement and deletion/disruption of five nuclear genes. The TLA2 gene, causing the tla2 phenotype, was cloned by mapping the insertion site and upon complementation with each of the genes that were deleted. Successful complementation was achieved with the C. reinhardtii TLA2-CpFTSY gene, whose occurrence and function in green microalgae has not hitherto been investigated. Functional analysis showed that the nuclear-encoded and chloroplast-localized CrCpFTSY protein specifically operates in the assembly of the peripheral components of the Chl a-b light-harvesting antenna. In higher plants, a cpftsy null mutation inhibits assembly of both the light-harvesting complex and photosystem complexes, thus resulting in a seedling-lethal phenotype. The work shows that cpftsy deletion in green algae, but not in higher plants, can be employed to generate tla mutants. The latter exhibit improved solar energy conversion efficiency and photosynthetic productivity under mass culture and bright sunlight conditions.
RNA‐Seq reveals infection‐related global gene changes in Phytophthora phaseoli, the causal agent of lima bean downy mildew
Authors: KUNJETI SRIDHARA G. , EVANS THOMAS A. , MARSH ADAM G. , GREGORY NANCY F. , KUNJETI SARITHA , MEYERS BLAKE C. , KALAVACHARLA VENUGOPAL S. , DONOFRIO NICOLE M.
Published: November 2011

Lima bean is an important vegetable processing crop to the mid‐Atlantic USA and is highly susceptible to the oomycete pathogen Phytophthora phaseoli, which causes downy mildew. Genetic resistance and fungicides are used to manage P. phaseoli and often fail. Currently, the molecular basis of the interaction between this host and pathogen is unknown. To begin to rectify this situation, we used Illumina RNA‐Seq to perform a global transcriptome analysis comparing P. phaseoli growing in culture with P. phaseoli infecting its host. Sequence reads from a total of six libraries mapped to gene models from the closely related late blight pathogen, Phytophthora infestans, resulting in 10 427 P. phaseoli genes with homology to P. infestans and expression in at least one library. Of these, 318 P. phaseoli homologues matched known or putative virulence genes in P. infestans. Two well‐studied classes, RxLRs and elicitins, were up‐regulated in planta, whereas the reverse was true for another class, called crinklers. These results are discussed with respect to the differences and similarities in the pathogenicity mechanisms of P. phaseoli and P. infestans.
The long‐term outcome of patients with polycystic liver disease treated with lanreotide
Authors: Chrispijn M. , Nevens F. , Gevers T. J. G. , Vanslembrouck R. , van Oijen M. G. H. , Coudyzer W. , Hoffmann A. L. , Dekker H. M. , de Man R. A. , van Keimpema L. , Drenth J. P. H.
Published: November 2011

Aliment Pharmacol Ther 2012; 35: 266–274

Background  Polycystic liver disease (PLD) is a phenotypical expression of autosomal dominant polycystic kidney disease and isolated polycystic liver disease. Somatostatin analogues, such as lanreotide, reduce polycystic liver volume.

Aim  To establish long‐term outcome and safety of lanreotide.

Methods  This was an open‐label, observational extension study of a 6‐month, randomised, placebo‐controlled trial with lanreotide (120 mg/month) in PLD. The length of total treatment was 12 months. Primary endpoint was relative change in liver volume, as determined by CT‐volumetry after 12 months of treatment. We offered patients a CT scan 6 months after stopping lanreotide.

Results  A total of 41/54 (76%) patients participated in the extension study. Liver volume decreased by 4% (IQR −8% to −1%) after 12 months of treatment. The greatest effect was observed during the first 6 months of treatment (decrease of 4% (IQR −6% to −1%)). Liver volume remained unchanged during the following 6 months. We found that liver volume increased by 4% (IQR 0–6%) 6 months after end of treatment (n = 22).

Conclusions  Lanreotide reduces liver volume within the first 6 months of treatment and the beneficial effect is maintained in the following 6 months. Stopping results in recurrence of polycystic liver growth. This suggests that continuous use of lanreotide is needed to maintain its effect.
Efficacy and tolerability of methotrexate therapy for refractory Crohn’s disease: a large single‐centre experience
Authors: Suares N. C. , Hamlin P. J. , Greer D. P. , Warren L. , Clark T. , Ford A. C.
Published: November 2011

Aliment Pharmacol Ther 2012; 35: 284–291

Background  Randomised controlled trials demonstrate that methotrexate is effective in inducing remission and preventing relapse of Crohn’s disease (CD) as a first‐line immunosuppressant, but efficacy data after failure with, or intolerance to, thiopurines are limited.

Aims  To report efficacy of methotrexate in a cohort of refractory CD patients, most of whom had not responded to, or were intolerant of, thiopurines.

Methods  Data were collected for patients receiving methotrexate for active CD. Response to methotrexate induction therapy at 4 months, and sustained clinical benefit at last point of follow‐up with maintenance therapy, were assessed via physician’s global assessment. Demographic and disease factors predicting response, or sustained clinical benefit, were examined by univariate and multivariate analysis.

Results  Sixty‐six [38 (54%) female patients, mean age at diagnosis 29.4 years] patients received methotrexate between 2001 and 2010, 61 (92%) of whom received the drug parenterally. Sixty patients had failed, or were intolerant of, thiopurines. Response to therapy at 4 months occurred in 54 (82%) patients. However, sustained clinical benefit occurred in only 19 (29%) patients at last point of follow‐up, including six patients who discontinued the drug for family planning reasons. No predictors of response or sustained clinical benefit were identified. Adverse events occurred in 20 (30%) patients.

Conclusions  These data suggest that methotrexate is effective in terms of initial response in Crohn’s disease patients who have failed, or are intolerant of, thiopurines. However, efficacy is not sustained in the long term.
Meta‐analysis: the relative efficacy of oral bowel preparations for colonoscopy 1985–2010
Authors: Belsey J. , Crosta C. , Epstein O. , Fischbach W. , Layer P. , Parente F. , Halphen M.
Published: November 2011

Aliment Pharmacol Ther 2012; 35: 222–237

Background  Previous reviews of bowel preparation for colonoscopy have given contradictory answers.

Aim  To provide a definitive insight, using PRISMA‐compliant methodology.

Methods  A comprehensive literature review identified randomised controlled trials comparing bowel preparation regimens. Data for quality of bowel preparation were pooled in multiple meta‐analyses exploring a range of inclusion criteria.

Results  A total of 104 qualifying studies were identified, the majority of which involved comparisons of sodium phosphate (NaP) or polyethylene glycol (PEG). There was no significant difference demonstrated between NaP and PEG overall (OR = 0.82; 95% CI = 0.56–1.21; P = 0.36). Cumulative meta‐analysis demonstrated that this conclusion has been qualitatively similar since the mid 1990s, with little quantitative change for the past 10 years. Amongst studies with previous day dosing in both study arms there was a significant advantage in favour of PEG (OR = 1.78; 95% CI = 1.13–2.81; P = 0.006). Studies focussing on results in the proximal colon also favoured PEG (OR = 2.36; 95% CI = 1.16–4.77; P = 0.012). PEG was also significantly more effective than non‐NaP bowel preparation regimens (OR = 2.02; 95% CI = 1.08–3.78; P = 0.03). Other comparisons showed no significant difference between regimens.

Conclusions  Although there is no compelling evidence favouring either of the two most commonly used bowel preparation regimens, this may reflect shortcomings in study design. Where studies have ensured comparable dosage, or the clinically relevant outcome of proximal bowel clearance is considered, PEG‐based regimens offer the most effective option.
The pharmacokinetics and pharmacodynamics of cisatracurium in critically ill patients with severe sepsis
Authors: Liu Xin , Kruger Peter S. , Weiss Michael , Roberts Michael S.
Published: November 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Cisatracurium is a non‐depolarizing neuromuscular blocking drug used in anaesthesia and intensive care.

• Cisatracurium degrades at physiological pH via Hofmann elimination. Therefore, the elimination of cisatracurium may be from both plasma and tissues.

• Critically ill patients may have or develop resistance to non‐depolarizing neuromuscular blocking drugs.

• Pathophysiological changes in critically ill patients with sepsis can cause changes in both pharmacokinetics (PK) and pharmacodynamics (PD).

WHAT THIS STUDY ADDS

• This is the first study to characterize PK and PD of cisatracurium in intensive care patients with severe sepsis following a single bolus dose.

• This study suggests that standard dosing of cisatracurium in patients with severe sepsis results in a slower patient response with a reduced effect.

• The resistance to cisatracurium in these patients is more attributed to altered PD as pharmacokinetic parameters were similar to those described in other patient populations.

AIM To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in critically ill patients with severe sepsis.

METHODS

Blood samples were collected before and over 8 h after a single bolus dose of cisatracurium 0.1 mg kg−1. Neuromuscular block was assessed by accelerometric peripheral nerve stimulation (TOF Watch). Plasma concentration and neuromuscular block data were fitted using population analysis.

RESULTS

Steady‐state volume of distribution was determined to be 111 ± 71 ml kg−1 and plasma clearance was 5.2 ± 1.8 ml min−1 kg−1 in these patients with greater inter‐patient variability compared with other populations. The time to maximum block (8.3 ± 2.9 min) and delay time of transferring from central to effect compartment (17.2 min) was much longer, while the maximum block (95.0 ± 6.3%) was less compared with those in other patient populations. The effect compartment concentration resulting in 50% of maximum effect (128 ± 58 ng ml−1) was larger than previously described.

CONCLUSIONS

This study suggests that standard dosing of cisatracurium in patients with severe sepsis results in a slower patient response with a reduced effect. Use of a larger dose may overcome this reduced delayed response.
Moving beyond safe sex to women‐controlled safe sex: a concept analysis
Authors: Alexander Kamila A. , Coleman Christopher L. , Deatrick Janet A. , Jemmott Loretta S.
Published: November 2011

alexander k.a., coleman c.l., deatrick j.a. & jemmott l.s. (2011) Moving beyond safe sex to women‐controlled safe sex: a concept analysis. Journal of Advanced Nursing68(6), 1858–1869.

Aim.  This paper is a report of a conceptual analysis of women‐controlled safe sex.

Background.  Women bear disproportionate burdens from sexually related health compromising outcomes. Imbalanced societal gender and power positions contribute to high morbidities. The expression, women‐controlled safe sex, aims to empower women to gain control of their sexual lives. Few researchers focus on contextualized socio‐cultural definitions of sexual safety among women.

Data sources.  The sample included scientific literature from Scopus, CINAHL, PubMed, PsychINFO and Sociological Abstracts. Papers were published 2000–2010.

Review methods.  Critical analyses of literature about women‐controlled safe sex were performed in May 2011 using Rodgers’ evolutionary concept analysis methods. The search focused on social and cultural influences on sexual practices aimed at increasing women’s control over their sexual safety.

Results.  The analysis uncovered five attributes of women‐controlled safe sex: technology; access to choices; women at‐risk; ‘condom migration’ panic; and communication. Three antecedents included: male partner influence; body awareness; and self‐efficacy. Consequences were categorized as positive or negative. Nine surrogate terms included: empowerment; gender power; female‐controlled sexual barrier method; microbicides; diaphragm; sexual negotiation and communication; female condom; women‐initiated disease transmission prevention; and spermicides. Finally, a consensus definition was identified: a socio‐culturally influenced multi‐level process for initiating sexual safety by women deemed at‐risk for sexually related dangers, usually sexually transmitted infections and/or HIV/AIDS.

Conclusion.  This concept analysis described current significance, uses, and applications of women‐controlled safe sex in the scientific literature. The authors clarified its limited nature and conclude that additional conceptual refinement in nursing is necessary to influence women’s health.
Quality of nursing doctoral education in Korea: towards policy development
Authors: Ja Kim Mi , Gi Park Chang , Kim Minju , Lee Hyeonkyeong , Ahn Yang‐Heui , Kim Euisook , Yun Soon‐Nyoung , Lee Kwang‐Ja
Published: November 2011

kim m.j., park c.g., kim m., lee h., ahn y‐h., kim e., yun s‐n. & lee k‐j. (2012) Quality of nursing doctoral education in Korea: towards policy development. Journal of Advanced Nursing68(7), 1494–1503.

Aims.  This article is a report on an international study of the quality of nursing doctoral education; herein, we report findings for Korea. Specific aims were to: examine the validity and reliability of the quality of nursing doctoral education questionnaire; and identify contributing factors and domain(s) for improvement.

Background.  The quality of nursing doctoral education has been a worldwide concern with the recent rapid increase in number of nursing doctoral programmes around the world, and comprehensive evaluation is needed for policy recommendations.

Methods.  A cross‐sectional descriptive study, conducted from October 2006 to January 2007, used an online questionnaire evaluating four domains: programme, faculty, resources and evaluation. Seven deans, 48 faculty, 52 graduates and 87 students from 14 nursing schools participated.

Results.  Content and construct validity, and construct reliability of the questionnaire were established. Overall, participants reported that the perceived quality of private universities/schools was significantly higher than that of public/national universities. A higher ratio of doctoral to non‐doctoral students was significantly associated with higher quality. The domains of programme, faculty and resources were highly correlated. The programme was the most important domain; availability of sufficient materials and information for students most needed improvement. Overall, faculty perceived the quality of the programme, faculty and resources as more positively than did the graduates and students.

Conclusion.  This study provides useful policy guidance for nurse educators worldwide for improving doctoral programmes and faculty’s role in educating students. Further study is recommended that examines contributing factors to quality doctoral education.
Gaining confidence and perspective: a phenomenological study of mothers’ lived experiences caring for infants at home after neonatal unit discharge
Authors: Murdoch Marlies R. , Franck Linda S.
Published: November 2011

Murdoch M.R. & Franck L.S. (2012) Gaining confidence and perspective: a phenomenological study of mothers’ lived experiences caring for infants at home after neonatal unit discharge. Journal of Advanced Nursing68(9), 2008–2020.

Aim.  This paper is a report of a descriptive study of mothers’ experiences in caring for preterm or term infants following discharge from a neonatal unit, including how they manage infant pain/discomfort.

Background.  Few studies have focused on the transition that parents experience after infants are discharged home and little is known about parents’ caregiving experiences when their infant has pain/discomfort. Greater knowledge about these issues will help healthcare professionals to better support parents.

Method.  Nine mothers were interviewed in 2007–2008 about their caregiving experiences in the months following neonatal unit discharge. Interviews were conducted using a descriptive phenomenological approach and analysed using Giorgi’s framework.

Findings.  Six themes formed mothers’ experiences: apprehension, confidence, responsibility, awareness, normalcy and perspective. Mothers had apprehension about their infants’ fragile health, losing support of the neonatal team, and performing medical procedures. They developed confidence as infant health improved. Responsibility for performing infant medical care often dominated mothers’ experiences. Awareness of infant needs was described as a learning process utilizing external resources, trial‐and‐error, and an internal intuitive sense; particularly in identifying and dealing with infant pain/discomfort. During the transition to prior social environments, concerns about normalcy arose. Over time, mothers’ gained a philosophical perspective and saw their experiences in a positive light.

Conclusion.  The apprehension‐confidence continuum model provides a framework for nursing assessment of mothers’ needs following their infants’ discharge from a neonatal unit. Factors such as infant health, medical procedures, and family or health professional support may influence the degree of apprehension or confidence.
Assessment of respiration‐related quality of life of Chinese patients with silicosis and its influencing factors using the St. George’s Respiratory Questionnaire (SGRQ)
Authors: Liu Hongbo , Yan Bo , Han Bing , Sun Jinkai , Yang Yang , Chen Jie
Published: November 2011

Aims and objectives.  The aims are to assess respiration‐related quality of life using the St. George Respiratory Questionnaire and determine its influencing factors among patients with silicosis in China.

Background.  The incidence of silicosis had an increasing trend in recent years in developing countries. Although the majority of patients with silicosis are in therapy routinely, the patients’ quality of life has been impaired because silicosis cannot be cured. The study on quality of life of patients with silicosis is few, and clinical physicians have difficulty in planning to promote quality of life of patients with silicosis according to the current health situation.

Design.  A cross‐sectional design was used for this study.

Methods.  A survey was performed on patients with silicosis by face‐to‐face interview in the Shenyang No. 9 Hospital in China. The St. George Respiratory Questionnaire was used to assess respiration‐related quality of life.

Results.  In all 208 enrolled patients with silicosis, symptoms, activity and impacts scores were 56·02, 56·46 and 52·33, respectively. Lower impacts scores were found comparing with symptoms and activity ones. Patient age was associated with an expected decrease in respiration‐related quality of life. Patients with longer duration of exposure had higher total scores of the St. George Respiratory Questionnaire, indicating worse quality of life. Patients with more co‐morbidities reported worse quality of life.

Conclusion.  Patients with silicosis were found relatively moderate respiration‐related quality of life. Shortening dust exposure, decreasing the number of co‐morbidity and controlling the occurrence of pulmonary tuberculosis could improve respiration‐related quality of life.

Relevance to clinical practice.  As indicated by the results of this study, the number of co‐morbidity negatively impact the quality of life of patients with silicosis. Clinical physicians and nurses should pay close attention to the co‐morbidity to promote quality of life of patients with silicosis according to the current health situation.
Reversal of nonstructural protein 3‐specific CD4+ T cell dysfunction in patients with persistent hepatitis C virus infection
Authors: Bes M. , Sauleda S. , Casamitjana N. , Piron M. , Campos‐Varela I. , Quer J. , Cubero M. , Puig L. , Guardia J. , Esteban J. I.
Published: November 2011

Summary.  Hepatitis C virus (HCV)‐specific T cell responses are essential for HCV control, and chronic infection is characterized by functionally altered antigen‐specific T cells. It has been proposed that the early inactivation of specific CD4+ T cell responses may be involved in establishment of HCV persistence. We have investigated whether HCV‐specific CD4+ T cells dysfunction can be reversed in vitro. Nonstructural protein 3 (NS3) and core‐specific CD4+ T cells from eight chronically infected and eight spontaneously resolved HCV individuals were selected through transient CD154 (CD40 ligand) expression, and their functional profile (IFN‐γ, IL‐2, TNF‐α, IL‐10 and IL‐4 production by enzyme‐linked immunospot assay, cytometric bead array and intracellular cytokine staining, and proliferation by carboxy‐fluorescein diacetate succinimidyl ester dilution assay) was determined both ex vivo and after in vitro expansion of sorted CD154‐expressing cells in the absence of specific antigen in IL‐7/IL‐15‐supplemented medium. Ex vivo bulk CD4+ T cells from chronic patients expressed CD154 in most cases, albeit at lower frequencies than those of resolved patients (0.11%vs 0.41%; P = 0.01), when stimulated with NS3, but not core, although they had a markedly impaired capacity to produce IL‐2 and IFN‐γ. Antigen‐free in vitro expansion of NS3‐specific CD154+ cells from chronic patients restored IFN‐γ and IL‐2 production and proliferation to levels similar to those of patients with spontaneously resolved infection. Hence, NS3‐specific CD4+ T cell response can be rescued in most chronic HCV patients by in vitro expansion in the absence of HCV‐specific antigen. These results might provide a rationale for adoptive immunotherapy.
Larval nutritional stress affects vector immune traits in adult yellow fever mosquito Aedes aegypti (Stegomyia aegypti)
Authors: TELANG A. , QAYUM A. A. , PARKER A. , SACCHETTA B. R. , BYRNES G. R.
Published: November 2011

We report key physiological traits that link larval nutritional experience to adult immune status in the yellow fever mosquito Aedes aegypti L. (Stegomyia aegypti) (Diptera: Culicidae). Many lines of defence make up the innate immune system of mosquitoes. Among defences, the epithelium‐lined midgut is the first barrier, circulating haemocytes are cellular components of innate immunity and, when triggered, the Toll and Imd pathways signal production of antimicrobial peptides (AMP) as part of humoral defences. We quantified three lines of defence in Ae. aegypti in response to larval nutritional stress, and our data show that important female immune functions are modified by the larval rearing environment. Adult midgut basal lamina thickness was not affected by larval nutrient stress as has been observed in another Aedes sp. However, nutrient stresses experienced by larvae lead to a reduced number of haemocytes in females. Transcripts of Spaetzle (upstream regulator of Toll pathway that leads to induction of AMPs) and some immune‐related genes were less abundant in stressed larvae but showed increased expression in females derived from stressed larvae. Results indicate a potential for compensation by the humoral branch for a reduced cellular branch of innate immunity in adults in response to larval nutrient stress.
FtsA mutants impaired for self‐interaction bypass ZipA suggesting a model in which FtsA's self‐interaction competes with its ability to recruit downstream division proteins
Authors: Pichoff Sebastien , Shen Bang , Sullivan Bradley , Lutkenhaus Joe
Published: November 2011

Z‐ring assembly requires polymers of the tubulin homologue FtsZ to be tethered to the membrane. Although either ZipA or FtsA is sufficient to do this, both of these are required for recruitment of downstream proteins to form a functional cytokinetic ring. Gain of function mutations in ftsA, such as ftsA* (ftsA‐R286W), bypass the requirement for ZipA suggesting that this atypical, well‐conserved, actin homologue has a more critical role in Z‐ring function. FtsA forms multimers both in vitro and in vivo, but little is known about the role of FtsA polymerization. In this study we identify FtsA mutants impaired for self‐interaction. Such mutants are able to support Z‐ring assembly and are also able to bypass the requirement for ZipA. These mutants, including FtsA*, have reduced ability to self‐interact but interact normally with FtsZ and are less toxic if overexpressed. These results do not support a model in which FtsA monomers antagonize FtsZ polymers. Instead, we propose a new model in which FtsA self‐interaction competes with its ability to recruit downstream proteins. In this model FtsA self‐interaction at the Z ring is antagonized by ZipA, allowing unpolymerized FtsA to recruit downstream proteins such as FtsN.
Identification of a novel prophage regulator in Escherichia coli controlling the expression of type III secretion
Authors: Flockhart Allen F. , Tree Jai J. , Xu Xuefang , Karpiyevich Maryia , McAteer Sean P. , Rosenblum Ronen , Shaw Darren J. , Low Christopher J. , Best Angus , Gannon Victor , Laing Chad , Murphy Kenan C. , Leong John M. , Schneiders Thamarai , La Ragione Roberto , Gally David L.
Published: November 2011

This study has identified horizontally acquired genomic regions of enterohaemorrhagic Escherichia coli O157:H7 that regulate expression of the type III secretion (T3S) system encoded by the locus of enterocyte effacement (LEE). Deletion of O‐island 51, a 14.93 kb cryptic prophage (CP‐933C), resulted in a reduction in LEE expression and T3S. The deletion also had a reduced capacity to attach to epithelial cells and significantly reduced E. coli O157 excretion levels from sheep. Further characterization of O‐island 51 identified a novel positive regulator of the LEE, encoded by ecs1581 in the E. coli O157:H7 strain Sakai genome and present but not annotated in the E. coli strain EDL933 sequence. Functionally important residues of ECs1581 were identified based on phenotypic variants present in sequenced E. coli strains and the regulator was termed RgdR based on a motif demonstrated to be important for stimulation of gene expression. While RgdR activated expression from the LEE1 promoter in the presence or absence of the LEE‐encoded regulator (Ler), RgdR stimulation of T3S required ler and Ler autoregulation. RgdR also controlled the expression of other phenotypes, including motility, indicating that this new family of regulators may have a more global role in E. coli gene expression.
Correlations between cortical and subcortical tau pathology
Authors: Attems J. , Thomas A. , Jellinger K.
Published: November 2011

J. Attems, A. Thomas and K. Jellinger (2012) Neuropathology and Applied Neurobiology38, 582–590

Correlations between cortical and subcortical tau pathology

Aim: Recent studies indicate that tau pathology in Alzheimer's disease (AD) does not initially manifest in the cerebral cortex but in selected subcortical nuclei, in particular the locus ceruleus (LC). In this study we correlate both olfactory and brainstem tau pathology with neuritic Braak stages. Methods: We examined 239 unselected autopsy cases (57.3% female, 42.7% male; aged 55–102, mean 82.8 ± 9.7 SD years; AD, 44.8%; non‐demented controls, 31.8%; Parkinson's disease, 5.0%; dementia with Lewy bodies, 2.5%; AD + Lewy body disease, 15.9%). Neuropathological examination according to standardized methods included immunohistochemistry and semiquantitative assessment of tau lesions in LC, substantia nigra (SN), dorsal motor nucleus of nervus vagus (dmX), and olfactory bulb (OB). Results: In Braak stage 0, tau pathology (usually very sparse pretangle material) was seen in the OB in 52.9% and in the SN/LC in 44%. The prevalence of OB and subcortical tau pathology increased with increasing Braak stages and reached 100% in OB, SN and LC and 95.2% in dmX in Braak stage VI, respectively. The severity of tau pathology in OB and subcortical nuclei significantly (P < 0.001) correlated with Braak stages and these correlations remained statistically significant when controlling for concomitant α‐synuclein pathology in the respective regions. Conclusions: Our finding of an increase in both prevalence and severity of OB, LC, SN and dmX tau pathology in AD with increasing Braak stages suggests that these regions become increasingly involved during AD progression rather than representing sites initially affected by AD‐associated tau pathology.
Local glucocorticoid production in the mouse lung is induced by immune cell stimulation
Authors: Hostettler N. , Bianchi P. , Gennari‐Moser C. , Kassahn D. , Schoonjans K. , Corazza N. , Brunner T.
Published: November 2011

To cite this article: Hostettler N, Bianchi P, Gennari‐Moser C, Kassahn D, Schoonjans K, Corazza N, Brunner T. Local glucocorticoid production in the mouse lung is induced by immune cell stimulation. Allergy 2012; 67: 227–234.

Background:  Glucocorticoids (GC) are potent anti‐inflammatory and immunosuppressive steroid hormones, mainly produced by the adrenal glands. However, increasing evidence supports the idea of additional extra‐adrenal sources of bioactive GC. The lung epithelium is constantly exposed to a plethora of antigenic stimuli, and local GC synthesis could contribute to limit uncontrolled immune reactions and tissue damage.

Methods:  Expression of steroidogenic enzymes and GC synthesis in ex vivo organ cultures was studied in mouse lung tissue after in vivo stimulation of immune cells.

Results:  Mouse lung tissue was found to express steroidogenic enzymes required for the synthesis of corticosterone from cholesterol and to synthesize corticosterone in large quantities after immune cell activation by anti‐CD3 antibody, lipopolysaccharide, or TNFα. In marked contrast, ovalbumin‐induced allergic airway inflammation failed to promote lung GC synthesis. Although the lung expresses all steroidogenic enzymes necessary for de novo synthesis of corticosterone from cholesterol, functional data indicated that inactive serum‐derived dehydrocorticosterone is converted to active corticosterone by 11β‐hydroxysteroid dehydrogenase 1.

Conclusion:  Our results support the notion that local GC synthesis represents a novel immunoregulatory mechanism to limit uncontrolled immune responses in the lung and indicate that defective local steroidogenesis may contribute to the pathogenesis of allergic airway inflammation.
Niche divergence and lineage diversification among closely related Sistrurus rattlesnakes
Authors: WOOTEN J. A. , GIBBS H. L.
Published: November 2011

Comparing niche divergence among closely related taxa can yield important insights into the ecological distinctiveness of genetically similar forms, and identify the processes that are responsible for diversification in such organisms. Here, we apply newly developed techniques for analysing niche divergence to assess how ecologically distinct a group of closely related rattlesnakes (Sistrurus sp.) are and to explore the role that niche divergence may have played in their diversification. We find that all taxa even the most recently evolved subspecies (approximately 100 000 years old) are now ecologically distinct, implying a role for ecology in the diversification process. Statistical analysis based on comparisons with null models show that niche divergence between forms is more common than niche conservation. Finally, there is nonlinear relationship between phylogenetic and niche divergence in this group whereby niche divergence develops more rapidly between recently diverged subspecies than more distantly related forms. Overall, our results argue that ecology may play an important role in the diversification process in these snakes.
The evolution of cranial form and function in theropod dinosaurs: insights from geometric morphometrics
Authors: BRUSATTE S. L. , SAKAMOTO M. , MONTANARI S. , HARCOURT SMITH W. E. H.
Published: November 2011

Abstract Theropod dinosaurs, an iconic clade of fossil species including Tyrannosaurus and Velociraptor, developed a great diversity of body size, skull form and feeding habits over their 160+ million year evolutionary history. Here, we utilize geometric morphometrics to study broad patterns in theropod skull shape variation and compare the distribution of taxa in cranial morphospace (form) to both phylogeny and quantitative metrics of biting behaviour (function). We find that theropod skulls primarily differ in relative anteroposterior length and snout depth and to a lesser extent in orbit size and depth of the cheek region, and oviraptorosaurs deviate most strongly from the “typical” and ancestral theropod morphologies. Noncarnivorous taxa generally fall out in distinct regions of morphospace and exhibit greater overall disparity than carnivorous taxa, whereas large‐bodied carnivores independently converge on the same region of morphospace. The distribution of taxa in morphospace is strongly correlated with phylogeny but only weakly correlated with functional biting behaviour. These results imply that phylogeny, not biting function, was the major determinant of theropod skull shape.
Role of renin‐angiotensin system in gastric oncogenesis
Authors: Sugimoto Mitsushige , Yamaoka Yoshio , Shirai Naohito , Furuta Takahisa
Published: November 2011

The renin‐angiotensin system (RAS) plays an important role not only in homeostasis but also in carcinogenesis. Recent epidemiological studies suggest that hypertensive patients with upregulated systemic RAS functions are at a significantly increased risk for the subsequent development of cancers with poor outcomes, and moreover that RAS inhibitors reduce tumor development, progression, and metastasis. Notably, Helicobacter pylori infection, one of the major predictors of gastric carcinogenesis, generally leads to RAS component overexpression, as exemplified by that of angiotensin I, angiotensin II, angiotensin I converting enzyme and angiotensin II receptor. Gastric mucosal RAS expression gradually increases with time after H. pylori infection with respect to the severity of inflammatory cell infiltration. Gastric carcinogenic potential is therefore considered to relate to RAS component expression levels and activities. This hypothesis is supported by findings that RAS genotypic variation can lead to high component expression levels (e.g. angiotensin I converting enzyme, chymase and angiotensinogen), and thereby increase the risk of development of gastric cancer. Thus, the RAS may be potently associated with the pathogenesis of H. pylori‐related gastric carcinogenesis, and RAS inhibitors may provide tools for specifically preventing this disease.
Emergency transport for Japanese children with non‐life‐threatening conditions
Authors: Ehara Akira , Yoshioka Eiji
Published: November 2011

Background:  Emergency rooms in Japan are overused by children with non‐life‐threatening conditions, and utilization of emergency transport for children in Japan should also be analyzed.

Methods:  Utilization rates of emergency transport per 1000 live births or 1000 children from 1985 to 2008 in Japan were calculated from national data of emergency transport, child population and annual live births.

Results:  Emergency transport per 1000 preschool‐age (28 days‐6 years old) and school‐age (7–17 years old) children rose, and that for newborn babies (0–27 days old) per 1000 live births grew from 1985 to 2008. The utilization rates, however, did not grow homogeneously among the different severity groups. The rates of transport for children who needed no hospitalization or those for children who needed inpatient care <3 weeks rose in each of the three age groups. The rates for patients who were dead on arrival or who needed hospitalization ≥3 weeks, however, declined in all the age groups.

Conclusions:  Emergency transport per 1000 live births or 1000 children grew from 1985 to 2008. The utilization rates, however, did not grow homogeneously among different severity groups. The rates for children with non‐life‐threatening conditions rose, while those for children dead on arrival or with severe conditions declined in the past two decades.
Fibromyalgia and chronic fatigue syndrome in children
Authors: Itoh Yasuhiko , Shigemori Tomoko , Igarashi Tohru , Fukunaga Yoshitaka
Published: November 2011

Background:  Fibromyalgia (FM) is characterized by widespread persistent pain and the presence of multiple discrete tender points. Chronic fatigue syndrome (CFS) is a syndrome characterized by debilitating fatigue associated with a variable number of non‐specific complaints. Because neither condition had necessarily been recognized in children until recently, those patients have been treated as having school refusal without being diagnosed as having either syndrome. There is a considerable overlap of clinical symptoms between these two syndromes. It is therefore controversial as to whether these syndromes have the same pathogenesis or not. The aim of the present study was to clarify the relationship between these syndromes in children.

Methods:  Fifteen patients with FM and 21 patients with CFS were investigated both clinically and immunologically. Immunological assessments included thorough analysis of autoantibodies using several techniques.

Results:  Anti‐nuclear antibody titers were higher and the prevalence of anti‐Sa antibody was far more frequent in CFS patients than in FM patients.

Conclusion:  CFS and FM are different from each other at least in childhood, from an immunological aspect, although some patients could have both conditions.
Comparing the efficacy of nebulizer recombinant human DNase and hypertonic saline as monotherapy and combined treatment in the treatment of persistent atelectasis in mechanically ventilated newborns
Authors: Altunhan Hüseyin , Annagür Ali , Pekcan Sevgi , Örs Rahmi , Koç Hasan
Published: November 2011

Background:  The purpose of the present study was to compare the cost‐effectiveness and efficacy of nebulizer recombinant human DNase (rhDNase) and hypertonic saline (HS) as monotherapy and combined treatment in neonatal atelectasis.

Methods:  Eighty‐seven newborns with persistent atelectasis who did not respond to traditional treatment were studied retrospectively. Group 1 did not receive nebulizer drugs; Group 2 received 7%HS; Group 3 received rhDNase; and Group 4 received both 7%HS and rhDNase. Subjects' chest X‐ray scores, partial pressure of CO2, respiratory rate, fraction of inspired oxygen (FiO2) peak inspiratory pressure, atelectasis healing rate, median duration of nebulizer treatment and costs were compared.

Results:  Percentages of improvement in atelectasis on Day 3 of treatment in Group 1, Group 2, Group 3 and Group 4 were 27, 70, 81 and 95%, respectively, while median duration of treatment was 8.1, 3.3, 2.9 and 2.4 days, respectively. Comparison of chest X‐ray scores, partial pressure of CO2, respiratory rate, FiO2 and peak inspiratory pressure values before and 48 h after treatment did not yield a significant difference for the control group (P > 0.05), while a marked improvement was observed in other groups for all parameters (P < 0.05). The most distinct improvement was in Group 4, followed by Group 3.

Conclusions:  Although both the combined treatment with HS and rhDNase and their monotherapies are effective in the treatment of persistent atelectasis in newborns receiving mechanical ventilation, their combined use produces higher efficacy. The efficacy of rhDNase is superior to monotherapy with HS. Use of these two treatments concomitantly reduces the cost. To the best of our knowledge, the present study is the first to use HS alone or in combination with rhDNase in newborn patients.