bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coagulation activation in autoimmune bullous diseases
Authors: Marzano A V , Tedeschi A , Spinelli D , Fanoni D , Crosti C , Cugno M 
Published: June 2009

SummaryThe main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0·001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0·0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view.
Multi-nucleated giant cell formation from human cord blood monocytesin vitro, in comparison with adult peripheral blood monocytes
Authors: Kondo Y , Yasui K , Yashiro M , Tsuge M , Kotani N , Morishima T 
Published: June 2009

SummaryMulti-nucleated giant cells (MGCs; Langhans-type cell), formed from macrophage fusion, are recognized as a hallmark histological feature in chronic inflammation. However, their precise pathological role is still poorly understood, especially for microorganism pathogens in the neonatal immune system, which are capable of surviving intracellularly in phagocytes. To conduct a partial evaluation of the monocyte function of neonates, we investigated the ability of human cord blood monocytes to form MGCs in vitro by stimulating various cytokines and comparing them with adult peripheral blood monocytes. Monocytes from cord blood and adult peripheral blood were isolated and cultured for 14 days with cytokines known to induce MGC in vitro. The fusion index in experiments with a combination of interleukin (IL)-4 and macrophage colony-stimulating factor (M-CSF) and a combination of IL-4 and granulocyte–macrophage colony-stimulating factor (GM-CSF) was significantly lower in cord blood than in adult blood monocytes (P = 0·0018 and P = 0·0141, respectively). The number of nuclei per MGC was significantly lower in cord blood than in adult blood monocytes in experiments with IL-4 alone, the combination of IL-4 and M-CSF, and the combination of IL-4 and GM-CSF (P &lt; 0·0001). These results suggest the possibility that the susceptibility of newborns to mycobacterium infection is due partly to impaired MGC formation.
Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2
Authors: Chung Teng‐Teng L. L. , Chan Li F. , Metherell Louise A. , Clark Adrian J. L. 
Published: June 2009

SummaryContext  Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder as a result of mutation in genes encoding either the ACTH receptor [melanocortin 2 receptor (MC2R)] or its accessory protein [melanocortin 2 receptor accessory protein (MRAP)]. The disorder is known as FGD type 1 and 2, respectively.Objective  The aim of the study was to compare the phenotype/genotype relationships between FGD 1 and 2.Design and patients  Forty patients with missense MC2R mutations and 22 patients with MRAP mutations were included. Forty‐four of these patients had been referred for genetic screening and 18 were patients published by other authors.Results  The median age at presentation for FGD type 1 was variable at 2·0 years; range 0·02–16 years, and this was associated with unusually tall stature, mean height SDS + 1·75 ± 1·53 (mean ± SD). In contrast, FGD type 2 presented at a much earlier median age (0·08 years; range at birth to 1·6 years) (P < 0·01) and patients were of normal height SDS + 0·12 ± 1·35 (P < 0·001). No differences in baseline cortisol or ACTH levels were seen between FGD types 1 and 2.Conclusion  FGD type 2 appears to present earlier. This may reflect the functional significance of the underlying mutations in that all MRAP mutations are nonsense or splice site mutations that result in abolition of a functional protein, whereas most of the MC2R mutations are missense mutations and give rise to proteins with some residual function. Tall stature is associated with mutations in MC2R but not in MRAP. There were no other significant clinical distinctions between the two.
Suppression of constitutive SOS expression by recA4162 (I298V) and recA4164 (L126V) requires UvrD and RecX in Escherichia coli K‐12
Authors: Long Jarukit E. , Renzette Nicholas , Sandler Steven J. 
Published: June 2009

SummarySensing DNA damage and initiation of genetic responses to repair DNA damage are critical to cell survival. In Escherichia coli, RecA polymerizes on ssDNA produced by DNA damage creating a RecA–DNA filament that interacts with the LexA repressor inducing the SOS response. RecA filament stability is negatively modulated by RecX and UvrD. recA730 (E38K) and recA4142 (F217Y) constitutively express the SOS response. recA4162 (I298V) and recA4164 (L126V) are intragenic suppressors of the constitutive SOS phenotype of recA730. Herein, it is shown that these suppressors are not allele specific and can suppress SOSC expression of recA730 and recA4142 in cis and in trans. recA4162 and recA4164 single mutants (and the recA730 and recA4142 derivatives) are Rec+, UVR and are able to induce the SOS response after UV treatment like wild‐type. UvrD and RecX are required for the suppression in two (recA730,4164 and recA4142,4162) of the four double mutants tested. To explain the data, one model suggests that recAC alleles promote SOSC expression by mimicking RecA filament structures that induce SOS and the suppressor alleles mimic RecA filament at end of SOS. UvrD and RecX are attracted to these latter structures to help dismantle or destabilize the RecA filament.
Heterogeneity in quorum sensing‐regulated bioluminescence of Vibrio harveyi
Authors: Anetzberger Claudia , Pirch Torsten , Jung Kirsten 
Published: June 2009

SummaryQuorum sensing (QS) refers to the ability of bacterial populations to read out the local environment for cell density and to collectively activate gene expression. Vibrio harveyi, one of the best characterized model organisms in QS, was used to address the question how single cells behave within a QS‐activated community in a homogeneous environment. Analysis of the QS‐regulated bioluminescence of a wild type strain revealed that even at high cell densities only 69% of the cells of the population produced bioluminescence, 25% remained dark and 6% were dead. Moreover, light intensities greatly varied from cell to cell at high population density. Addition of autoinducer to a bright liquid culture of V. harveyi increased the percentage of luminescent cells up to 98%, suggesting that V. harveyi produces and/or keeps the autoinducers at non‐saturating concentrations. In contrast, all living cells of a constitutive QS‐active mutant (ΔluxO) produced light. We also found that QS affects biofilm formation in V. harveyi. Our data provide first evidence that a heterogeneous population produces more biofilm than a homogeneous one. It is suggested that even a QS‐committed population of V. harveyi takes advantage of heterogeneity, which extends the current view of QS‐regulated uniformity.
The PhyR‐σEcfG signalling cascade is involved in stress response and symbiotic efficiency in Bradyrhizobium japonicum
Authors: Gourion Benjamin , Sulser Sandra , Frunzke Julia , Francez‐Charlot Anne , Stiefel Philipp , Pessi Gabriella , Vorholt Julia A. , Fischer Hans‐Martin 
Published: June 2009

SummaryPhyR is an unusual type of response regulator consisting of a receiver domain and an extracytoplasmic function (ECF) sigma factor‐like domain. It was recently described as a master regulator of general stress response in Methylobacterium extorquens. Orthologues of this regulator are present in essentially all free‐living Alphaproteobacteria. In most of them, phyR is genetically closely linked to a gene encoding an ECF σ factor. Here, we investigate the role of these two regulators in the soybean symbiont Bradyrhizobium japonicum USDA110. Using deletion mutants and phenotypic assays, we showed that PhyR and the ECF σ factor σEcfG are involved in heat shock and desiccation resistance upon carbon starvation. Both mutants had symbiotic defects on the plant hosts Glycine max (soybean) and Vigna radiata (mungbean). They induced fewer nodules than the wild type and these nodules were smaller, less pigmented, and their specific nitrogenase activity was drastically reduced 2 or 3 weeks after inoculation. Four weeks after infection, soybean nodule development caught up to a large extent whereas most mungbean nodules remained defective even 5 weeks after infection. Remarkably, both mutants triggered aberrant nodules on the different host plants with ectopically emerging roots. Microarray analysis revealed that PhyR and σEcfG control congruent regulons suggesting both regulators are part of the same signalling cascade. This finding was further substantiated by in vitro protein–protein interaction studies which are in line with a partner‐switching mechanism controlling gene regulation triggered by phosphorylation of PhyR. The large number of genes of unknown function present in the PhyR/σEcfG regulon and the conspicuous symbiotic phenotype suggest that these regulators are involved in the Bradyrhizobium–legume interaction via yet undisclosed mechanisms.
Transcriptional loops meet chromatin: a dual‐layer network controls white–opaque switching in Candida albicans
Authors: Hnisz Denes , Schwarzmüller Tobias , Kuchler Karl 
Published: June 2009

SummaryThe human pathogen Candida albicans is able to undergo a reversible switch between two distinct cell types called white and opaque, which are considered different transcriptional states of cells harbouring identical genomes. The present model of switching regulation includes the bistable expression of a master switch gene that is controlled by multiple transcriptional feedback loops. Here, we show that chromatin‐modifying enzymes constitute an additional important regulatory layer of morphogenetic switching. We identify eight chromatin modifiers as switching modulators. Extensive epistasis analysis maps them into at least two independent signalling pathways overlaying the known transcriptional network. Interestingly, we identify the conserved Set3/Hos2 histone deacetylase complex as a key regulator relying on the methylation status of histone H3 lysine 4 for switching modulation. Furthermore, we demonstrate that opaque to white switching is facilitated by the presence of adenine in vitro, but adenine has no effect on switching once the Set3/Hos2 complex is disrupted. Our observations postulate that chromatin modifications may serve as a means to integrate environmental or host stimuli through the underlying transcriptional circuits to determine cell fate in C. albicans.
The Role of Extracellular DNA in Autoimmunity in SLE
Authors: Su K.‐Y. , Pisetsky D. S. 
Published: June 2009

AbstractSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the expression of antibodies to DNA. These antibodies form immune complexes that can stimulate cytokine production as well as deposit in the tissues to incite inflammation and damage. For the formation of immune complexes, the availability of extracellular DNA in an immunologically relevant form is essential. While apoptosis has been implicated as the source of this nuclear material in SLE, as shown with in vitro or in vivo systems, extracellular DNA can originate from apoptotic as well as necrotic cells. In experimental models, the release of DNA occurs with the administration of cells induced to die, in vitro as well as the administration of agents to induce cell death in situ. This release can be influenced by the presence of inflammatory cells such as macrophages that can interact with dead and dying cells to modulate the translocation of DNA from the inside to the outside of cells. In vivo, both glucocorticoids and oestrogens can modify the extent of DNA release from the administration of dead and dying cells. Together, these findings indicate that the generation of extracellular DNA in SLE can result from cell death and that steps in this process represent potential targets for new therapies.
Post‐consolidation Immunotherapy with Histamine Dihydrochloride and Interleukin‐2 in AML
Authors: Romero A. I. , Thorén F. B. , Aurelius J. , Askarieh G. , Brune M. , Hellstrand K. 
Published: June 2009

AbstractThe initial chemotherapy in acute myeloid leukaemia (AML) comprises a first phase of induction and a second phase of consolidation. In the majority of patients, the induction treatment leads to complete remission (CR), defined as microscopic disappearance of leukaemic disease along with the return of normal haematopoiesis. However, despite the introduction of more efficacious consolidation regimens, a worryingly large proportion of AML patients in CR will subsequently experience relapses with poor prospects of long‐term survival. A relapse is assumed to be the result of expansion of residual leukaemic cells that have escaped the initial chemotherapy. The anti‐leukaemic functions of T cells and natural killer (NK) cells has formed the background to the use of interleukin‐2 (IL‐2), a T‐ and NK cell‐activating cytokine, with the aim to eliminate residual leukaemia and hence reduce the relapse rate in AML, but the clinical trials using IL‐2 monotherapy have yielded disappointment. A recent phase III study has demonstrated that post‐consolidation treatment with the combination of histamine dihydrochloride (HDC) and IL‐2 significantly prevents relapse in AML patients. Here we account for the preclinical background to the use of HDC/IL‐2 in AML along with a review of clinical results.
Feasibility, acceptability and cost of home‐based HIV testing in rural Kenya
Authors: Negin Joel , Wariero James , Mutuo Patrick , Jan Stephen , Pronyk Paul 
Published: June 2009

SummaryObjective  To demonstrate the feasibility, acceptability and cost of home‐based HIV testing and to examine the applicability of the model to high HIV prevalence settings.Methods  Quantitative, qualitative and cost data were collected during a home‐based HIV testing program in a high‐prevalence rural area of Kenya; data on age, gender and marital status along with HIV test results were collected. This was complemented with qualitative research including key informant interviews with counselors and program managers to highlight experiences and challenges. Direct costs of the interventions were estimated through the review of budgets and monthly expenditure sheets.Results  Of 3180 15–49‐year olds exposed to a community awareness campaign, 2033 (63.9%) agreed to be visited by counselors, of whom 1984 (97.6%) agreed to be tested and receive the results. Adult HIV prevalence was 8.2% and married women were 4.8 times more likely to be HIV‐positive than those never married. Counselors reported feeling welcomed and noted the enthusiasm of the community towards testing. The total cost of the exercise was $17 569. The program cost was $2.60 for each of the 6750 community members, $5.88 for each person tested, and $84 per positive case detected.Conclusion  This study suggests that home‐based HIV testing is feasible with high uptake, and has the potential to substantially expand access to HIV testing services. There is a strong economic case for the extension of such a screening program to other communities.
Risk factors for in‐hospital mortality of visceral leishmaniasis patients in eastern Uganda
Authors: Mueller Yolanda , Mbulamberi Dawson B. , Odermatt Peter , Hoffmann Axel , Loutan Louis , Chappuis François 
Published: June 2009

SummaryObjective  To identify risk factors for in‐hospital mortality in patients treated for visceral leishmaniasis (VL) in Uganda.Methods  Retrospective analysis of VL patients’ clinical data collected for project monitoring by Médecins Sans Frontières in Amudat, eastern Uganda.Results  Between 2000 and 2005, of 3483 clinically suspect patients, 53% were confirmed with primary VL. Sixty‐two per cent were children <16 years of age with a male/female ratio of 2.2. The overall case‐fatality rate during pentavalent antimonial (n = 1641) or conventional amphotericin B treatment (n = 217) was 3.7%. There was no difference in the case‐fatality rate between treatment groups (P > 0.20). The main risk factors for in‐hospital death identified by a multivariate analysis were age <6 years and >15 years, concomitant tuberculosis or hepatopathy, and drug‐related adverse events. The case‐fatality rate among patients >45 years of age was strikingly high (29.0%).Conclusion  Subgroups of VL patients at higher risk of death during treatment with drugs currently available in Uganda were identified. Less toxic drugs should be evaluated and used in these patients.
Recessive, sex‐I inked, progressive, oculocerebral degeneration
Authors: Jancar J. 
Published: June 2009

Norrie's disease is a rare condition with a recessive sex‐linked mode of inheritance, blindness with progressive ocular degeneration, and mental retardation of varying severity. Deafness and epilepsy may occasionally occur.The findings in a 42‐year‐old, male, mentally retarded patient suffering from Norrie's disease are reported. His family tree is noted and the differential diagnosis of this condition is discussed.
Ancestral state reconstruction analysis of hymenopteran sex determination mechanisms
Authors: ASPLEN M. K. , WHITFIELD J. B. , DE BOER J. G. , HEIMPEL G. E. 
Published: June 2009

AbstractWe provide the first phylogenetic evidence supporting complementary sex determination (CSD) as the ancestral mechanism for haplodiploidy in the Hymenoptera. It is currently not possible, however, to distinguish the evolutionary polarity of single locus (sl) CSD and multiple‐locus (ml) CSD given the available data. In this light, we discuss the seemingly maladaptive hypothesis of ml‐CSD ancestry, suggesting that collapse from ml‐CSD to sl‐CSD should remain a viable evolutionary hypothesis based on (i) likely weakening of frequency‐dependent selection on sex alleles under ml‐CSD and (ii) recent findings with respect to the evolutionary novelty of the complementary sex determiner gene in honeybees. Our findings help provide a phylogenetically informed blueprint for future sampling of sex determination mechanisms in the Hymenoptera, as they yield hypotheses for many unsampled or ambiguous taxa and highlight taxa whose further sampling will influence reconstruction of the evolutionary polarity of sex determination mechanisms in major clades.
Dietary flavonoids enhance conspicuousness of a melanin‐based trait in male blackcaps but not of the female homologous trait or of sexually monochromatic traits
Authors: CATONI C. , PETERS A. , SCHAEFER H. M. 
Published: June 2009

AbstractSignalling theory predicts that signals should fulfil three fundamental requirements: high detectability, discriminability and, most importantly, reliability. Melanins are the most common pigments in animals. Correlations between genotypic and phenotypic qualities of the sender and size and morph of melanin‐based traits are known, but it is contentious whether melanin‐based colouration may signal any quality. We examined the effect of supplementing blackcaps (Sylvia atricapilla) with flavonoids, potent plant antioxidants, on plumage colouration. We demonstrate that melanin‐based colour can fulfil all requirements of signals of phenotypic condition. As predicted by sexual selection theory, flavonoid supplementation influenced only the sexually dichromatic black cap of males, whereas the female homologous trait and the sexually monochromatic back colouration remained unaffected. Using avian vision models we show that birds can estimate male flavonoid intake from colouration of males’ black cap. Because flavonoid ingestion can increase immune responsiveness in blackcaps, melanin head colouration may signal environmentally determined immune condition.
Male personality, life‐history strategies and reproductive success in a promiscuous mammal
Authors: RÉALE D. , MARTIN J. , COLTMAN D. W. , POISSANT J. , FESTA‐BIANCHET M. 
Published: June 2009

AbstractRecent theoretical work suggests that personality is a component of life history, but links between personality and either age‐dependent reproductive success or life‐history strategy are yet to be established. Using quantitative genetic analyses on a long‐term pedigree we estimated indices of boldness and docility for 105 bighorn sheep rams (Ovis canadensis), born between 1983 and 1999, and compared these indices to their reproductive history from 2 years of age until death. Docility and boldness were highly heritable and negatively genetically correlated. Docile and bold rams survived longer than indocile and shy rams. Docility and boldness had a weak negative effect on reproductive success early in life, but a strong positive effect on older rams. Our findings highlight an important role of personality on reproductive success and suggest that personality could be an important component of life‐history strategy.
Generic concept in Chlorella‐related coccoid green algae (Chlorophyta, Trebouxiophyceae)
Authors: Luo W. , Pröschold T. , Bock C. , Krienitz L. 
Published: June 2009

AbstractUsing a combined set of sequences of SSU and ITS regions of nuclear‐encoded ribosomal DNA, the concept of the experimental algal genus Chlorella was evaluated. Conventionally in the genus Chlorella, only coccoid, solitary algae with spherical morphology that do not possess any mucilaginous envelope were included. All Chlorella species reproduce asexually by autospores. However, phylogenetic analyses showed that within the clade of ‘true’Chlorella species (Chlorella vulgaris, C. lobophora, and C. sorokiniana), taxa with a mucilaginous envelope and colonial lifeform have also evolved. These algae, formerly designated as Dictyosphaerium, are considered as members of the genus Chlorella. In close relationship to Chlorella, five different genera were supported by the phylogenetic analyses: Micractinium (spherical cells, colonial, with bristles), Didymogenes (ellipsoidal cells, two‐celled coenobia, with or without two spines per cell), Actinastrum (ellipsoidal cells within star‐shaped coenobia), Meyerella (spherical cells, solitary, without pyrenoids), and Hegewaldia (spherical cells, colonial, with or without bristles, oogamous propagation). Based on the secondary structures of SSU and ITS rDNA sequences, molecular signatures are provided for each genus of the Chlorella clade.