bluuebunny/crossref_metadata_2025_split huggingface dataset:
The trans‐envelope Tol–Pal complex is part of the cell division machinery and required for proper outer‐membrane invagination during cell constriction in E. coli
Authors: Gerding Matthew A. , Ogata Yasuyuki , Pecora Nicole D. , Niki Hironori , De Boer Piet A. J. 
Published: January 2007

SummaryFission of bacterial cells involves the co‐ordinated invagination of the envelope layers. Invagination of the cytoplasmic membrane (IM) and peptidoglycan (PG) layer is likely driven by the septal ring organelle. Invagination of the outer membrane (OM) in Gram‐negative species is thought to occur passively via its tethering to the underlying PG layer with generally distributed PG‐binding OM (lipo)proteins. The Tol–Pal system is energized by proton motive force and is well conserved in Gram‐negative bacteria. It consists of five proteins that can connect the OM to both the PG and IM layers via protein–PG and protein–protein interactions. Although the system is needed to maintain full OM integrity, and for class A colicins and filamentous phages to enter cells, its precise role has remained unclear. We show that all five components accumulate at constriction sites in Escherichia coli and that mutants lacking an intact system suffer delayed OM invagination and contain large OM blebs at constriction sites and cell poles. We propose that Tol–Pal constitutes a dynamic subcomplex of the division apparatus in Gram‐negative bacteria that consumes energy to establish transient trans‐envelope connections at/near the septal ring to draw the OM onto the invaginating PG and IM layers during constriction.
Novel nickel transport mechanism across the bacterial outer membrane energized by the TonB/ExbB/ExbD machinery
Authors: Schauer Kristine , Gouget Barbara , Carrière Marie , Labigne Agnès , De Reuse Hilde 
Published: January 2007

SummaryNickel is a cofactor for various microbial enzymes, yet as a trace element, its scavenging is challenging. In the case of the pathogen Helicobacter pylori, nickel is essential for the survival in the human stomach, because it is the cofactor of the important virulence factor urease. While nickel transport across the cytoplasmic membrane is accomplished by the nickel permease NixA, the mechanism by which nickel traverses the outer membrane (OM) of this Gram‐negative bacterium is unknown. Import of iron‐siderophores and cobalamin through the bacterial OM is carried out by specific receptors energized by the TonB/ExbB/ExbD machinery. In this study, we show for the first time that H. pylori utilizes TonB/ExbB/ExbD for nickel uptake in addition to iron acquisition. We have identified the nickel‐regulated protein FrpB4, homologous to TonB‐dependent proteins, as an OM receptor involved in nickel uptake. We demonstrate that ExbB/ExbD/TonB and FrpB4 deficient bacteria are unable to efficiently scavenge nickel at low pH. This condition mimics those encountered by H. pylori during stomach colonization, under which nickel supply and full urease activity are essential to combat acidity. We anticipate that this nickel scavenging system is not restricted to H. pylori, but will be represented more largely among Gram‐negative bacteria.
Efficient degradation of misfolded mutant Pma1 by endoplasmic reticulum‐associated degradation requires Atg19 and the Cvt/autophagy pathway
Authors: Mazón María J. , Eraso Pilar , Portillo Francisco 
Published: January 2007

SummaryMisfolded proteins are usually arrested in the endoplasmic reticulum (ER) and degraded by the ER‐associated degradation (ERAD) machinery. Several mutant alleles of PMA1, the gene coding for the plasma membrane H+‐ATPase, render misfolded proteins that are retained in the ER and degraded by ERAD. A subset of misfolded PMA1 mutants exhibit a dominant negative effect on yeast growth since, when coexpressed with the wild‐type allele, both proteins are retained in the ER. We have used a pma1‐D378T dominant negative mutant to identify new genes involved in ERAD. A genetic screen was performed for isolation of multicopy suppressors of a GAL1‐pma1‐D378T allele. ATG19, a member of the cytoplasm to vacuole targeting (Cvt) pathway, was found to suppress the growth arrest phenotype caused by the expression of pma1‐D378T. ATG19 accelerates the degradation of pma1‐D378T thus allowing the co‐retained wild‐type Pma1 to reach the plasma membrane. ATG19 was also able to suppress other dominant lethal PMA1 mutations. The degradation of the mutant ATPase occurs in the proteasome and requires intact both ERAD and Cvt/autophagy pathways. We propose the cooperation of both pathways for an efficient degradation of misfolded Pma1.
How do antibiotic‐producing bacteria ensure their self‐resistance before antibiotic biosynthesis incapacitates them?
Authors: Hopwood David A. 
Published: January 2007

SummaryAcquired antibiotic resistance among dangerous bacterial pathogens is an increasing medical problem. While inMycobacterium tuberculosisthis occurs by mutation in the genes encoding the targets for antibiotic action, other pathogens have generally gained their resistance genes by horizontal gene transfer from non‐pathogenic bacteria. The ultimate source of many of these genes is almost certainly the actinomycetes that make the antibiotics and therefore need self‐protective mechanisms to avoid suicide. How do they ensure that they are resistant at the time when intracellular antibiotic concentrations reach potentially lethal levels? In this issue ofMolecular Microbiology, Tahlanet al. describe a solution to this problem in which an antibiotically inactive precursor of aStreptomyces coelicolorantibiotic induces resistance – in this example by means of atrans‐membrane export pump – so that the organism is already primed for resistance at the time when it is needed. The authors generalize their interpretation to other cases where antibiotic resistance depends on export, but it will be interesting to find out whether it could in fact apply more widely, to include the other major mechanisms of resistance: target modification and the synthesis of antibiotics via a series of chemically modified intermediates, with removal of the protective group at the time of secretion into the outside medium.
Transcriptional regulation of the sil locus by the SilCR signalling peptide and its implications on group A streptococcus virulence
Authors: Eran Yoni , Getter Yoav , Baruch Moshe , Belotserkovsky Ilia , Padalon Gilly , Mishalian Inbal , Podbielski Andreas , Kreikemeyer Bernd , Hanski Emanuel 
Published: January 2007

SummaryIn the last two decades an increasing number of local outbreaks of invasive group A streptococcus (GAS) infections including necrotizing fasciitis (NF) have been reported. We identified the streptococcal invasion locus (sil) which is essential for virulence of the M14 strain JS95 isolated from an NF patient. This locus contains six genes: silA/B and silD/E encoding two‐component system (TCS) and ABC transporter, respectively, homologous to the corresponding entities in the regulon of Streptococcus pneumoniae involved in genetic competence. Situated between these two units are silC and silCR, which highly overlap and are transcribed from the complementing strand at opposite directions. SilCR is a putative competence stimulating peptide, but in the M14 strain it has a start codon mutation. Deletion of silC or addition of synthetic SilCR attenuates virulence of the M14 strain. Here we found that silC and silCR form a novel regulatory circuit that controls the sil locus transcription. Under non‐inducing conditions silC represses the silCR promoter. Externally added SilCR peptide activates the TCS, which in turn stimulates silCR transcription. Ongoing silCR transcription mediates the repression of the converging and overlapping silC transcript. Transcription of bacteriocin‐like peptide (blp) operon mirrors the inverse relationships between the silC and silCR transcripts. It is upregulated by either addition of SilCR or deletion of silC. Moreover, expression of silC from a plasmid in a silC deleted‐mutant significantly represses blp transcription. Finally, we show that 18% of clinically relevant GAS isolates possess sil and produce SilCR. Based on these results we propose a working model for regulation gene expression and virulence in GAS by the SilCR signalling peptide.
Mesocarp localization of a bi‐functional resveratrol/hydroxycinnamic acid glucosyltransferase of Concord grape (Vitis labrusca)
Authors: Hall Dawn , De Luca Vincenzo 
Published: January 2007

SummaryResveratrol is a stilbene with well‐known health‐promoting effects in humans that is produced constitutively or accumulates as a phytoalexin in several plant species including grape (Vitis sp.). Grape berries accumulate stilbenes in the exocarp as cis‐ and trans‐isomers of resveratrol, together with their respective 3‐O‐monoglucosides. An enzyme glucosylating cis‐ and trans‐resveratrol was purified to apparent homogeneity from Concord (Vitis labrusca) grape berries, and peptide sequencing associated it to an uncharacterized Vitis vinifera full‐length clone (TC38971, tigr database). A corresponding gene from Vitis labrusca (VLRSgt) had 98% sequence identity to clone TC38971 and 92% sequence identity to a Vitis viniferap‐hydroxybenzoic acid glucosyltransferase that produces glucose esters. The recombinant enzyme was active over a broad pH range (5.5–10), producing glucosides of stilbenes, flavonoids and coumarins at higher pH and glucose esters of several hydroxybenzoic and hydroxycinnamic acids at low pH. Vitis labrusca grape berries accumulated both stilbene glucosides and hydroxycinnamic acid glucose esters, consistent with the bi‐functional role of VLRSgt in stilbene and hydroxycinnamic acid modification. While phylogenetic analysis of VLRSgt and other functionally characterized glucosyltransferases places it with other glucose ester‐producing enzymes, the present results indicate broader biochemical activities for this class of enzymes.
Asthma score: predictive ability and risk factors
Authors: Sunyer J. , Pekkanen J. , Garcia‐Esteban R. , Svanes C. , Künzli N. , Janson C. , De Marco R. , Antó J. M. , Burney P. 
Published: January 2007

Background: Definition of asthma as a continuous score is a promising tool for population studies that has not yet been fully evaluated.Objective: We assessed (i) the predictive ability of an asthma score against the occurrence of different asthma‐related outcomes and (ii) the risk factors identified when using an asthma score.Methods: The European Community Respiratory Health Study II included subjects from the general population randomly studied during 1991–1993 who were followed up in the years 1998–2001, from 29 centres in 14 countries. A total of 8956 subjects were included. The asthma score consisted of a simple sum of the positive answers to five respiratory symptoms.Results: Asthma score at baseline showed a linear relationship with incidence of asthma, the occurrence of asthma attacks, use of asthma medication and bronchial reactivity at the end of the follow‐up. Asthma score at the end of follow‐up was associated with known risk factors at baseline such as IgE to grass, rhinitis or body mass index, in addition to passive smoking in men [average score ratio (RR) = 1.30; 95% confidence interval (CI) 1.09–1.50] or changes in body mass index (RR = 1.27; 95% CI 1.05–1.27, per each kg/m2).Conclusion: The asthma score had good predictive ability against outcomes related with asthma and also good ability to detect risk factors. This encourages the use of the score as a measure of asthma in epidemiological studies on aetiology of asthma.
Efficacy and safety of methylprednisolone aceponate ointment 0.1% compared to tacrolimus 0.03% in children and adolescents with an acute flare of severe atopic dermatitis
Authors: Bieber T. , Vick K. , Fölster‐Holst R. , Belloni‐Fortina A. , Städtler G. , Worm M. , Arcangeli F. 
Published: January 2007

Background:  Topical glucocorticosteroids are the gold standard in treatment of atopic dermatitis (AD). Recently, topical calcineurin inhibitors have been developed for treatment of this condition. This study compared efficacy and safety of 0.1% methylprednisolone aceponate (MPA) ointment with 0.03% tacrolimus ointment for 3 weeks, in children and adolescents with severe to very severe flare of AD.Methods:  The primary end point was treatment success, defined as a score of ‘clear’ or ‘almost clear’ in the static Investigator's Global Assessment (IGA) score. Secondary end points were the percentage change in the Eczema Area and Severity Index (EASI) and patients’ assessment of itch and sleep, Children's Dermatology Life Quality Index, patient's assessment of global response, affected Body Surface Area and medication costs.Results:  265 patients were randomized to either MPA (n = 129) or tacrolimus (n = 136) treatment, 257 patients completed the study. Methylprednisolone aceponate 0.1% ointment once daily provided rapid and relevant clinical benefit. Tacrolimus 0.03% ointment twice daily was equally effective with regard to success rate. Methylprednisolone aceponate was superior to tacrolimus for EASI, itch and sleep. Both treatments were well tolerated. Drug‐related adverse events were only observed in the tacrolimus group. Medication costs were significantly lower for MPA.Conclusions:  While both treatment groups showed similar efficacy results regarding treatment success (IGA), significant advantages were observed for EASI, itch and sleep with MPA 0.1%. These advantages and the significantly lower treatment costs highlight the benefits of MPA treatment, underlining its first‐line role in treatment of children and adolescents with severe AD.
T‐cell activation in occupational asthma and rhinitis
Authors: Mamessier E. , Milhe F. , Guillot C. , Birnbaum J. , Dupuy P. , Lorec A.‐M. , Vervloet D. , Magnan A. 
Published: January 2007

Background:  Allergic asthma and rhinitis are described as associated with a Th2 activation. However, recent works indicate that a Th1 activation can also be associated with these diseases, concomitantly to a defect in regulatory T (Treg) cell activation. Occupational asthma (OA) and occupational rhinitis (OR) are peculiar cases of these diseases in which the T‐cell activation profile is largely unknown.Objective:  To characterize T‐cell activation induced after a specific inhalation test (SIT) in OA and OR.Material and methods:  A total of 21 subjects with OA, 10 subjects with OR, 10 exposed nonallergic (ENA) subjects, and 14 healthy volunteers were included. The SIT with the incriminated substance was performed in patients and ENA subjects. Blood and induced sputum were obtained before and after SIT. T cells were analysed for CD69, CD25, IL‐13, and IFN‐γ expression by flow cytometry. IL‐4 and IFN‐γ were assayed by enzyme‐linked immunosorbent assay (ELISA) in cell culture supernatants. Treg cells were identified as CD4+CD25+highCD45RO+CD69− T cells in peripheral blood.Results:  Baseline IFN‐γ production was decreased in OA and OR compared with controls. The SIT induced an increase in both Th1 and Th2 cells in blood and sputum from OA. In this group, the proportion of peripheral Treg cells decreased after SIT. Similar results were found in the CD8+ population. ELISA assays were concordant with flow cytometry. In OR, an attenuated activation profile was found, with an increase in the proportion of IL‐13‐producing T cells after SIT. By contrast, in ENA subjects, SIT induced Th2 activation, with an increase in Treg cells and a decrease in Th1 cells.Conclusions:  Our results demonstrate a gradient of T‐cell activation from a tolerating profile in ENA subjects to an inflammatory profile in OA, with an intermediate stage in OR.
Design, engineering and in vitro evaluation of MHC class‐II targeting allergy vaccines
Authors: Crameri R. , Flückiger S. , Daigle I. , Kündig T. , Rhyner C. 
Published: January 2007

Background:  The worldwide increasing incidence of allergic diseases requires the development of new, efficient vaccination strategies, the only curative treatment with a long‐lasting effect. Current allergen‐specific immunotherapy protocols suffer from limited efficacy and a long treatment time.Methods:  We engineered modular antigen translocating (MAT) molecules for intracellular targeting of allergens to the major histocompatibility class‐II (MHC‐II) presentation pathway to enhance antigen presentation. MAT‐fusions were evaluated for their ability to localize intracellularly, to induce proliferation, and for their influence on cytokine patterns in peripheral blood mononuclear cells (PBMCs) cultures.Results:  We show that MAT‐allergen fusions are able to rapidly translocate into the cytoplasm of PBMCs, whereas naked recombinant allergens are only marginally taken up. MAT vaccines accumulate intracellularly and induce strong proliferation of PBMC cultures at concentrations 10–100 times lower than the corresponding naked allergens, indicating an enhanced presentation through the MHC‐II presentation pathway. In PBMC cultures of allergic donors, MAT vaccines induce a cytokine shift from a TH2 to a TH1 profile, resulting in a stronger and earlier secretion of INF‐γ and Interleukin (IL)‐10, and a decreased secretion of IL‐4, IL‐5 and IL‐2, compared with those induced by the corresponding recombinant allergens.Conclusion:  Modular antigen translocation vaccines induce strong proliferation responses in PBMC cultures at low concentration and induce a TH1/TH2 shift in the cytokine profile, reflecting those reported to occur in successfully desensitized allergic patients. Therefore, MAT molecules represent promising lead compounds for the development of potent allergy vaccines.
Prevalence of respiratory symptoms in migrant children to Italy: the results of SIDRIA‐2 study
Authors: Migliore E. , Pearce N. , Bugiani M. , Galletti G. , Biggeri A. , Bisanti L. , Caranci N. , Dell'Orco V. , De Sario M. , Sestini P. , Piffer S. , Viegi G. , Forastiere F. , Galassi C. , Ciccone G. ,   SIDRIA‐2 Collaborative Group
Published: January 2007

Background:  Epidemiological studies have documented large international variations in the prevalence of asthma, and ‘westernization’ seems to play an important role in the development of the disease. The aims of this study were to compare the prevalence of respiratory symptoms in migrant and nonmigrant children resident in Italy, and to examine the effect of length of time living in Italy.Methods:  Data were collected in a large cross‐sectional study (SIDRIA‐2) performed in 12 Italian centres, using standardized parental questionnaires. For the 29 305 subjects included in the analysis (6–7 and 13–14 years old), information about place of birth and parental nationality was available.Results:  There were 1012 children (3%) born outside of Italy, mainly in East Europe. Lifetime asthma and current wheeze were generally significantly less common among children born abroad than among children born in Italy (lifetime asthma: 5.4% and 9.7% respectively, P < 0.001; current wheeze: 5.2% and 6.9%, respectively, P = 0.04). Lower risks for lifetime asthma (prevalence odds ratio, POR = 0.39; 95% CI: 0.23–0.66) and current wheeze (POR = 0.72; 95% CI: 0.47–1.10) were found for children who had lived in Italy <5 years, while migrant children who had lived in Italy for 5 years or more had risks very similar to Italian children.Conclusions:  Migrant children have a lower prevalence of asthma symptoms than children born in Italy. Prevalence increased with the number of years of living in Italy, suggesting that exposure to environmental factors may play an important role in the development of asthma in childhood.
Localization of Hyaluronic Acid in the Seminal Vesicles of the Miniature Pig
Authors: Sakairi A. , Tsukise A. , Meyer W. 
Published: January 2007

SummaryWe studied the detailed localization of hyaluronic acid in the seminal vesicles of the miniature pig, using hyaluronic acid‐binding protein as a specific histochemical probe at the ultrastructural level. According to the results, the basolateral surface of the plasma membrane of the glandular epithelial cells, was found to contain hyaluronan. However, abundantly present was hyaluronan in the subepithelial connective tissue, in particular, in the extracellular matrix surrounding the fibroblasts, smooth muscle cells, small blood vessels and capillaries. The substance was also observed in the surface coat of the plasma membrane of the fibroblasts, but not in that of the smooth muscle cells. The findings suggest that hyaluronan in the seminal vesicles of the miniature pig is synthesized onto the surface coat of the plasma membrane of the fibroblasts, is contributed to the extracellular matrix, and consequently concentrates in the subepithelial connective tissue. The substance may particularly be involved in a variety of cellular functions to maintain morphological organization as well as to regulate physiological homeostasis in the reproductive organ of this species, rather than participate in sperm functions.
A Case of Craniothoracopagus (Monocephalus Thoracopagus Tetrabrachius) in a Dog
Authors: Nottidge H. O. , Omobowale T. O. , Olopade J. O. , Oladiran O. O. , Ajala O. O. 
Published: January 2007

SummaryThis report describes a case of craniothoracopagus (moncephalus thoracopagus tetrabrachius) twin puppies in Ibadan, Nigeria. The conjoined twins were given birth to by a 7‐year‐old bitch that was usually allowed to stray away from home in search of food. Deformities of the cardiovascular, digestive musculoskeletal, respiratory and urinary systems are reported. This is probably the first report of craniothoracopagus twinning in a dog.
The Influence of Exogenous Testosterone on the Dynamics of Nestling Provisioning in Dark‐Eyed Juncos
Authors: Clotfelter Ethan D. , Ray Chandler C. , Nolan Val , Ketterson Ellen D. 
Published: January 2007

AbstractIn many songbird species, application of exogenous testosterone (T) during the breeding season has the general effects of reducing male parental investment and increasing allocation of time and energy to mating. Most studies record the number of feeding trips made by males as a function of their hormone treatment, but few have investigated the ways in which testosterone affects the dynamics of male and female provisioning behavior or the quantity of food delivered by males. We attempt to fill these gaps in our understanding of testosterone and male parental effort by utilizing data from a long‐term study on the behavioral endocrinology of the dark‐eyed junco (Junco hyemalis). We found that male and female feeding rates covaried positively, although to different degrees, throughout the nestling period, but that this relationship was degraded in pairs in which males were given T implants. We also found that the coefficients of variation in the duration of intervals between successive feeding trips by males and females were highly positively related in broods of older nestlings. Male hormone treatment, however, had no effect on the coefficients of variation in either male or female feeding intervals. Finally, we examined the quantity of prey delivered by males and found no significant effect of hormone treatment.