bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hfq affects the expression of the LEE pathogenicity island in enterohaemorrhagic Escherichia coli
Authors: Hansen Anne‐Marie , Kaper James B. 
Published: June 2009

SummaryColonization of the intestinal epithelium by enterohaemorrhagic Escherichia coli (EHEC) is characterized by an attaching and effacing (A/E) histopathology. The locus of enterocyte effacement (LEE) pathogenicity island encodes many genes required for the A/E phenotype including the global regulator of EHEC virulence gene expression, Ler. The LEE is subject to a complex regulatory network primarily targeting ler transcription. The RNA chaperone Hfq, implicated in post‐transcriptional regulation, is an important virulence factor in many bacterial pathogens. Although post‐transcriptional regulation of EHEC virulence genes is known to occur, a regulatory role of Hfq in EHEC virulence gene expression has yet to be defined. Here, we show that an hfq mutant expresses increased levels of LEE‐encoded proteins prematurely, leading to earlier A/E lesion formation relative to wild type. Hfq indirectly affects LEE expression in exponential phase independent of Ler by negatively controlling levels of the regulators GrlA and GrlR through post‐transcriptional regulation of the grlRA messenger. Moreover, Hfq negatively affects LEE expression in stationary phase independent of GrlA and GrlR. Altogether, Hfq plays an important role in co‐ordinating the temporal expression of the LEE by controlling grlRA expression at the post‐transcriptional level.
Major role for CD8+ T cells in the protection against Toxoplasma gondii following dendritic cell vaccination
Authors: GUITON R. , ZAGANI R. , DIMIER‐POISSON I. 
Published: June 2009

Summary Toxoplasma gondii is the causative agent of toxoplasmosis, a worldwide zoonosis for which an effective vaccine is needed. Vaccination with pulsed dendritic cells is very efficient but their use in a vaccination protocol is unconceivable. Nevertheless, unravelling the induced effector mechanisms is crucial to design new vaccine strategies. We vaccinated CBA/J mice with parasite extract‐pulsed dendritic cells, challenged them with T. gondii cysts and carried out in vivo depletion of CD4+ or CD8+ T lymphocytes to study the subsequent cellular immune response and protective mechanisms. CD4+ lymphocytes were poorly implicated either in spleen and mesenteric lymph node (MLN) cytokine secretion or in mice protection. By contrast, the increasing number of intracerebral cysts and depletion of CD8+ cells were strongly correlated, revealing a prominent role for CD8+ lymphocytes in the protection of mice. Splenic CD8+ lymphocytes induce a strong Th1 response controlled by a Th2 response whereas CD8+ cells from MLNs inhibit both Th1 and Th2 responses. CD8+ cells are the main effectors following dendritic cell vaccination and Toxoplasma infection while CD4+ T cells only play a minor role. This contrasts with T. gondii infection which elicits the generation of CD4+ and CD8+ T cells that provide protective immunity.
Heterogeneity of Arabidopsis core promoters revealed by high‐density TSS analysis
Authors: Yamamoto Yoshiharu Y. , Yoshitsugu Tomoaki , Sakurai Tetsuya , Seki Motoaki , Shinozaki Kazuo , Obokata Junichi 
Published: June 2009

SummaryOur limited understanding of plant promoters does not allow us to recognize any core promoter elements for the majority of plant promoters. To understand the promoter architecture of Arabidopsis, we used the combined approach of in silico detection of novel core promoter elements and large‐scale determination of transcription start sites (TSSs). To this end, we developed a novel methodology for TSS identification, using a combination of the cap‐trapper and massively parallel signature sequencing methods. This technique, CT–MPSS, allowed us to identify 158 237 Arabidopsis TSS tags corresponding to 38 311 TSS loci, which provides an opportunity for quantitative analysis of plant promoters. The expression characteristics of these promoters were analyzed with respect to core promoter elements detected by our in silico analyses, revealing that Arabidopsis promoters contain two main types of elements with exclusive characteristics, the TATA type and the GA type. The TATA‐type promoters tend to be associated with the Y Patch and the Inr motif, and cause high expression with sharp‐peak TSS clusters. By contrast, the GA type produces broad‐type TSS clusters. Unlike mammalian promoters, plant promoters are not associated with CpG islands. However, plant‐specific GA‐type promoters share some characteristics with mammalian CpG‐type promoters.
Uracil salvage is necessary for early Arabidopsis development
Authors: Mainguet Samuel E. , Gakière Bertrand , Majira Amel , Pelletier Sandra , Bringel Françoise , Guérard Florence , Caboche Michel , Berthomé Richard , Renou Jean Pierre 
Published: June 2009

SummaryUridine nucleotides can be formed by energy‐consuming de novo synthesis or by the energy‐saving recycling of nucleobases resulting from nucleotide catabolism. Uracil phosphoribosyltransferases (UPRTs; EC 2.4.2.9) are involved in the salvage of pyrimidines by catalyzing the formation of uridine monophosphate (UMP) from uracil and phosphoribosylpyrophosphate. To date, UPRTs are described as non‐essential, energy‐saving enzymes. In the present work, the six genes annotated as UPRTs in the Arabidopsis genome are examined through phylogenetic and functional complementation approaches and the available T‐DNA insertion mutants are characterized. We show that a single nuclear gene encoding a protein targeted to plastids, UPP, is responsible for almost all UPRT activity in Arabidopsis. The inability to salvage uracil caused a light‐dependent dramatic pale‐green to albino phenotype, dwarfism and the inability to produce viable progeny in loss‐of‐function mutants. Plastid biogenesis and starch accumulation were affected in all analysed tissues, with the exception of stomata. Therefore we propose that uracil salvage is of major importance for plant development.
Phosphorylation at S384 regulates the activity of the TaALMT1 malate transporter that underlies aluminum resistance in wheat
Authors: Ligaba Ayalew , Kochian Leon , Piñeros Miguel 
Published: June 2009

SummaryIn this study we examined the role of protein phosphorylation/dephosphorylation in the transport properties of the wheat (Triticum aestivum) root malate efflux transporter underlying Al resistance, TaALMT1. Pre‐incubation of Xenopus laevis oocytes expressing TaALMT1 with protein kinase inhibitors (K252a and staurosporine) strongly inhibited both basal and Al3+‐enhanced TaALMT1‐mediated inward currents (malate efflux). Pre‐incubation with phosphatase inhibitors (okadaic acid and cyclosporine A) resulted in a modest inhibition of the TaALMT1‐mediated currents. Exposure to the protein kinase C (PKC) activator, phorbol 12‐myristate 13‐acetate (PMA), enhanced TaALMT1‐mediated inward currents. Since these observations suggest that TaALMT1 transport activity is regulated by PKC‐mediated phosphorylation, we proceeded to modify candidate amino acids in the TaALMT1 protein in an effort to identify structural motifs underlying the process regulating phosphorylation. The transport properties of eight single point mutations (S56A, S183A, S324A, S337A, S351‐352A, S384A, T323A and Y184F) generated in amino acid residues predicted to be phosphorylation sites and examined electrophysiologically. The basic transport properties of mutants S56A, S183A, S324A, S337A, S351‐352A, T323A and Y184F were not altered relative to the wild‐type TaALMT1. Likewise the sensitivity of these mutants to staurosporine resembled that observed for the wild‐type transporter. However, the mutation S384A was noticeable, as in oocytes expressing this mutant protein TaALMT1‐mediated basal and Al‐enhanced currents were significantly inhibited, and the currents were insensitive to staurosporine or PMA. These findings indicate that S384 is an essential residue regulating TaALMT1 activity via direct protein phosphorylation, which precedes Al3+ enhancement of transport activity.
A mutation in the Arabidopsis mTERF‐related plastid protein SOLDAT10 activates retrograde signaling and suppresses 1O2‐induced cell death
Authors: Meskauskiene Rasa , Würsch Marco , Laloi Christophe , Vidi Pierre‐Alexandre , Coll Núria S. , Kessler Felix , Baruah Aiswarya , Kim Chanhong , Apel Klaus 
Published: June 2009

SummaryThe conditional flu mutant of Arabidopsis thaliana generates singlet oxygen (1O2) in plastids during a dark‐to‐light shift. Seedlings of flu bleach and die, whereas mature plants stop growing and develop macroscopic necrotic lesions. Several suppressor mutants, dubbed singlet oxygen‐linked death activator (soldat), were identified that abrogate 1O2‐mediated cell death of flu seedlings. One of the soldat mutations, soldat10, affects a gene encoding a plastid‐localized protein related to the human mitochondrial transcription termination factor mTERF. As a consequence of this mutation, plastid‐specific rRNA levels decrease and protein synthesis in plastids of soldat10 is attenuated. This disruption of chloroplast homeostasis in soldat10 seedlings affects communication between chloroplasts and the nucleus and leads to changes in the steady‐state concentration of nuclear gene transcripts. The soldat10 seedlings suffer from mild photo‐oxidative stress, as indicated by the constitutive up‐regulation of stress‐related genes. Even though soldat10/flu seedlings overaccumulate the photosensitizer protochlorophyllide in the dark and activate the expression of 1O2‐responsive genes after a dark‐to‐light shift they do not show a 1O2‐dependent cell death response. Disturbance of chloroplast homeostasis in emerging soldat10/flu seedlings seems to antagonize a subsequent 1O2‐mediated cell death response without suppressing 1O2‐dependent retrograde signaling. The results of this work reveal the unexpected complexity of what is commonly referred to as ‘plastid signaling’.
Evaluation of cluster‐randomized trials on maternal and child health research in developing countries
Authors: Handlos Line Neerup , Chakraborty Hrishikesh , Sen Pranab Kumar 
Published: June 2009

SummaryObjective  To summarize and evaluate all publications including cluster‐randomized trials used for maternal and child health research in developing countries during the last 10 years.Methods  All cluster‐randomized trials published between 1998 and 2008 were reviewed, and those that met our criteria for inclusion were evaluated further. The criteria for inclusion were that the trial should have been conducted in maternal and child health care in a developing country and that the conclusions should have been made on an individual level. Methods of accounting for clustering in design and analysis were evaluated in the eligible trials.Results  Thirty‐five eligible trials were identified. The majority of them were conducted in Asia, used community as randomization unit, and had less than 10 000 participants. To minimize confounding, 23 of the 35 trials had stratified, blocked, or paired the clusters before they were randomized, while 17 had adjusted for confounding in the analysis. Ten of the 35 trials did not account for clustering in sample size calculations, and seven did not account for the cluster‐randomized design in the analysis. The number of cluster‐randomized trials increased over time, and the trials generally improved in quality.Conclusions  Shortcomings exist in the sample‐size calculations and in the analysis of cluster‐randomized trials conducted during maternal and child health research in developing countries. Even though there has been improvement over time, further progress in the way that researchers utilize and analyse cluster‐randomized trials in this field is needed.
Predictors for mortality and loss to follow‐up among children receiving anti‐retroviral therapy in Lilongwe, Malawi
Authors: Fetzer Bradley C. , Hosseinipour Mina C. , Kamthuzi Portia , Hyde Lisa , Bramson Brian , Jobarteh Kebba , Torjesen Kristine , Miller William C. , Hoffman Irving , Kazembe Peter , Mwansambo Charles 
Published: June 2009

SummaryObjectives  To determine predictors of mortality in children on anti‐retroviral therapy (ART) who attended the Paediatric HIV Clinic at Kamuzu Central Hospital in Lilongwe, Malawi.Methods  Retrospective case cohort study by chart review of children who had started ART between October 2004 and May 2006. Bivariable and multivariable analysis were performed with and without defaulters to evaluate associations according to vital status and to identify independent predictors of mortality.Results  Forty‐one of 258 children (15.9%) were deceased, 185 (71.7%) were alive, and 32 (12.4%) had defaulted: 51% were female, 7% were under 18 months, 26% were 18 months to 5 years, and 54% were >5 years of age. Most were WHO stage III or IV (56% and 37%, respectively). On multivariate analysis, factors most strongly associated with mortality and defaulting were age <18 months [hazards ratio (HR) 2.11 (95% CI 1.0–4.51)] and WHO stage IV [HR 2.00 (95% CI 1.07–3.76)].Conclusions  To improve outcomes of HIV‐positive children, they must be identified and treated early, specifically children under 18 months of age. Access to infant diagnostic procedures must be improved to allow effective initiation of ART in infants at higher risk of death.
Spatial distribution and risk factors of dengue and Japanese encephalitis virus infection in urban settings: the case of Vientiane, Lao PDR
Authors: Vallée Julie , Dubot‐Pérès Audrey , Ounaphom Phonepaseuth , Sayavong Chantalay , Bryant Juliet E. , Gonzalez Jean‐Paul 
Published: June 2009

SummaryObjectives  To evaluate the prevalence of flavivirus infection in Vientiane city (Lao PDR), to describe the spatial distribution of infection within this city, and to explore the link between flavivirus seroprevalence and urbanization levels of residential neighbourhoods.Methods  A seroprevalence survey was carried out in 2006 including 1990 adults (≥35 years) and 1568 children (≥6months and <6 years) randomly selected.Results  The prevalence of individuals with previous flavivirus infection (i.e. negative for both DEN and JE IgM but positive for DEN IgG) was 57.7%, with a significantly (P < 0.001) higher prevalence among adults (84.6%; 95% confidence interval (CI) = 82.4–86.8) than children (9.4%; 95% CI = 7.2–11.6). The prevalence of individuals with recent flavivirus infection (i.e. positive for DEN and/or JE IgM) was 6.5% and also significantly (P < 0.001) higher among adults (10.0%; 95% CI = 8.3–11.7) than children (2.5%; 95% CI = 1.5–3.5). In terms of spatial distribution, IgG prevalence was significantly (P < 0.001) higher among individuals living in the central city (60.1%; 95% CI = 56.2–64.1) than among those living in the periphery (44.3%; 95% CI = 41.5–47.2). In contrast, seroprevalence of recent flavivirus infections was significantly (P < 0.001) higher among individuals living in the periphery (8.8%; 95% CI = 6.9–10.7) than in the central city (4.0%; 95% CI = 2.9–5.2). This association was also statistically consistant (P < 0.01) in multivariate logistic regression after controlling for individual risk factors.Conclusions  Our findings indicate that the level of urbanization of residential neighbourhoods influences the risk of flavivirus infection. The spatial distribution of flavivirus infection varies, even within a small city of less than 300 000 habitants such as Vientiane.
Nasopharyngeal carriage of S. pneumoniae among young children in rural Nepal
Authors: Coles Christian L. , Sherchand Jeevan B. , Khatry Subarna K. , Katz Joanne , LeClerq Steven C. , Mullany Luke C. , Tielsch James M. 
Published: June 2009

SummaryObjectives  To provide epidemiologic data on Streptococcus pneumoniae (Spn) carriage in Nepal.Methods  Prospective, population‐based study among children in Sarlahi, Nepal to estimate carriage prevalence, identify risk factors, and determine antibiotic susceptibility patterns and serotype distribution. Between December 2003 and July 2004, NP specimens were collected from 604 children aged 1–36 months with acute lower respiratory infection (ALRI) and 604 healthy, age‐ and season‐matched controls.Results  Of the 1100 specimens analysed, carriage prevalence was approximately 80% in both groups. In the multivariate analyses, significant risk factors for Spn carriage in controls were Muslim religion [adjusted odds ratio (AOR): 2.93] and no latrine in the household (AOR: 2.41). Those treated for a recent illness had lower carriage rates (AOR: 0.37). Results were similar for ALRI cases with the addition of age ≥12 months (AOR: 1.68), and symptomatic infection (AOR: 3.78) as risk factors. The antibiotics and proportions of isolates resistant to them were as follows: penicillin 4.5%, cotrimoxazole 89.2%, chloramphenicol 1.4%, erythromycin 1.5% and tetracycline 22.7%. The most prevalent serogroups/types were 6, 19, 23, 15, 9 and 10.Conclusions  Young children in rural Nepal experience high rates of Spn carriage. Most isolates were resistant to cotrimoxazole. Current conjugate Spn vaccines may substantially reduce the risk of a severe pneumonia and other Spn infections.
Clinical outcome and IL‐17, IL‐23, IL‐27 and FOXP3 expression in peripheral blood mononuclear cells of pollen‐allergic children during sublingual immunotherapy
Authors: Nieminen Kaisa , Valovirta Erkka , Savolainen Johannes 
Published: June 2009

Nieminen K, Valovirta E, Savolainen J. Clinical outcome and IL‐17, IL‐23, IL‐27 and FOXP3 expression in peripheral blood mononuclear cells of pollen‐allergic children during sublingual immunotherapy. Pediatr Allergy Immunol 2010: 21: e174–e184. © 2009 John Wiley & Sons A/SInduction of allergen‐specific, tolerogenic, IL‐10 and/or TGF‐β‐producing T‐regulatory (Treg) cells that express transcription factor FOXP3 is considered as one of the key mechanisms of allergen‐specific immunotherapy. However, little is known of the induction of FOXP3 expression in children during sublingual immunotherapy (SLIT). Recently, also, a novel subgroup of T‐helper (Th) cells, the Th17 cells, secreting predominantly IL‐17 (IL‐17A), was identified. The expressions of IL‐17 or the Th17‐regulating cytokines IL‐23 and IL‐27 during SLIT are currently completely unexplored. This randomized, placebo‐controlled dose‐response study was performed to analyze the effects of SLIT on FOXP3, IL‐17, IL‐23, and IL‐27 expressions in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis and their associations with clinical outcome. Thirty children were included: ten received SLIT with a glycerinated mixture of birch, hazel and alder with a cumulative weekly dose of 24,000 SQ‐U, 10 with dose 200,000 SQ‐U/wk, and ten received placebo. Cytokine and FOXP3 mRNA expressions in allergen‐, purified protein derivative‐stimulated and non‐stimulated PBMC were determined at 0, 1 and 2 yr of SLIT by real‐time RT‐PCR (TaqMan®). Symptoms and medications were recorded using diary cards. Allergen‐induced IL‐17 mRNA expression was significantly increased in the study subjects with elevated combined Symptom Medication Score (SMS) after 2 yr. There was also a significant positive correlation between the allergen‐induced IL‐17 and SMS in whole study group (r = 0.38, p = 0.039) and especially the 200,000 SQ‐U dose‐treated group (r = 0.74, p = 0.027) at 2 yr. Allergen‐induced FOXP3 mRNA expression was significantly increased in the 200,000 SQ‐U dose‐treated children after two study years as compared with baseline (p = 0.016) and placebo‐treated children (p = 0.028). The changes in FOXP3 mRNA expression positively correlated with IL‐10 and TGF‐β mRNAs during SLIT in whole study population. Increased allergen‐induced IL‐17 responses during SLIT are associated with elevated SMS. Increased tolerogenic, allergen‐specific Treg responses are also observed in children during SLIT.
Suicidality among Finnish anaesthesiologists
Authors: LINDFORS P. M. , MERETOJA O. A. , LUUKKONEN R. A. , ELOVAINIO M. J. , LEINO T. J. 
Published: June 2009

Background: Suicide rates among physicians have constantly been reported to be higher than in the general population and anaesthesiologists appear to lead the suicide statistics among physicians.Methods: A cross‐sectional questionnaire study was sent to all working Finnish anaesthesiologists (n=550) investigating their suicidality (ideation and/or planning and/or attempt). The response rate was 60%.Results: One in four had at some time seriously been thinking about suicide. Respondents with poor health (crude odds ratios 11.2 and 95% confidence interval 3.8–33.0), low social support (10.5, 4.0–27.9), and family problems (6.5, 3.4–12.5) had the highest risk of suicidality. The highest risks at work were conflicts with co‐workers (4.1, 2.3–7.1) and superiors (2.1, 1.2–3.6), on‐call‐related stress symptoms (3.9, 1.9–8.3) and low organizational justice (1.9, 1.1–3.2). If a respondent had several risk factors, the risk of suicidality doubled with each cumulating factor.Conclusions: The reported level of suicidal ideation among Finnish anaesthesiologists is worth concern. It should be of utmost importance to screen the risk factors and recognize suicidal physicians in order to help them. Interpersonal relationships, decision‐making procedures, and on‐call‐burden should be focused on when aiming to prevent suicidality among physicians.
Low‐dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post‐cardiac surgery patients
Authors: BRAGADOTTIR G. , REDFORS B. , NYGREN A. , SELLGREN J. , RICKSTEN S.‐ E. 
Published: June 2009

Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine‐dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post‐cardiac surgery patients.Methods: Twelve patients were studied during sedation and mechanical ventilation after cardiac surgery. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h. At each infusion rate, systemic haemodynamics were evaluated by a pulmonary artery catheter, and RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of 51chromium–ethylenediaminetetraacetic acid, respectively. RVO2 and RO2Ex were calculated by arterial and renal vein blood samples.Results: The mean arterial pressure was not affected by vasopressin while cardiac output and heart rate decreased. RBF decreased and GFR, filtration fraction, sodium reabsorption, RVO2, RO2Ex and renal vascular resistance increased dose‐dependently with vasopressin. Vasopressin exerted direct antidiuretic and antinatriuretic effects.Conclusions: Short‐term infusion of low to moderate, non‐hypertensive doses of vasopressin induced a post‐glomerular renal vasoconstriction with a decrease in RBF and an increase in GFR in post‐cardiac surgery patients. This was accompanied by an increase in RVO2, as a consequence of the increases in the filtered tubular load of sodium. Finally, vasopressin impaired the renal oxygen demand/supply relationship.