bluuebunny/crossref_metadata_2025_split huggingface dataset:
The A-chain of insulin is a hot-spot for CD4+ T cell epitopes in human type 1 diabetes
Authors: Mannering S I , Pang S H , Williamson N A , Naselli G , Reynolds E C , O'Brien-Simpson N M , Purcell A W , Harrison L C 
Published: February 2009

Summary
Type 1 diabetes (T1D) is caused by T cell-mediated destruction of the pancreatic insulin-producing β cells. While the role of CD4+ T cells in the pathogenesis of T1D is accepted widely, the epitopes recognized by pathogenic human CD4+ T cells remain poorly defined. None the less, responses to the N-terminal region of the insulin A-chain have been described. Human CD4+ T cells from the pancreatic lymph nodes of subjects with T1D respond to the first 15 amino acids of the insulin A-chain. We identified a human leucocyte antigen-DR4-restricted epitope comprising the first 13 amino acids of the insulin A-chain (A1-13), dependent upon generation of a vicinal disulphide bond between adjacent cysteines (A6–A7). Here we describe the analysis of a CD4+ T cell clone, isolated from a subject with T1D, which recognizes a new HLR-DR4-restricted epitope (KRGIVEQCCTSICS) that overlaps the insulin A1-13 epitope. This is a novel epitope, because the clone responds to proinsulin but not to insulin, T cell recognition requires the last two residues of the C-peptide (Lys, Arg) and recognition does not depend upon a vicinal disulphide bond between the A6 and A7 cysteines. The finding of a further CD4+ T cell epitope in the N-terminal A-chain region of human insulin underscores the importance of this region as a target of CD4+ T cell responses in human T1D.
Alteration of soil organic matter pools and aggregation in semi‐arid steppe topsoils as driven by organic matter input
Authors: Steffens M. , Kölbl A. , Kögel‐Knabner I. 
Published: February 2009

SummaryGrazing is one of the most important factors that may reduce soil organic carbon (SOC) stocks and subsequently aggregate stability in grassland soils. The central aim of this study was to analyse the quality and quantity of SOC fractions and their contribution to aggregate formation, stability and carbon sequestration, as affected by increased inputs of organic matter after grazing exclusion. We applied a combined aggregate size, density and particle size fractionation procedure and aggregate stability measurements to sandy steppe topsoils with different organic matter inputs from different grazing intensities (continuously grazed = Cg, winter grazing = Wg, ungrazed since 1999 = Ug99, ungrazed since 1979 = Ug79). Greater inputs of organic matter led to larger amounts of OC in coarse aggregate size classes (ASC) and especially in light fractions (LF). We found no grazing‐induced changes of soil organic matter (SOM) quantity in fine ASC and mineral fractions. SOM quality (13C solid‐state NMR spectroscopy, neutral sugar analysis) was comparable between different grazing intensities, but ungrazed plots had slightly more decomposed SOM across all fractions. We found generally greater radiocarbon concentrations in Ug79 compared with Cg. Aggregate stability, analysed as resistance to sonication, was greater in Ug79 compared with Cg. Larger litter inputs in grazing exclosures increased LF quantity, led to faster SOM turnover and resulted in the formation and stabilization of coarse aggregates. Organo‐mineral associations turned over faster as indicated by increased radiocarbon concentrations, but the OC content of this pool did not change. To summarize, additional litter inputs were sequestered in the intermediate LF pool and the long‐term pool of organo‐mineral associations appears to be close to saturation. We conclude that management changes in steppe ecosystems do not necessarily increase carbon sequestration and their assumed potential to act as carbon sinks has to be questioned.
The cardiac patient: a gender comparison via illness narratives
Authors: Rassin Michal 
Published: February 2009

Aims.  To compare responses to heart disease between women and men, aged 30–50 years, and to identify the factors influencing them in health and illness.Background.  The quality of life and prognosis for women with heart disease are worse than for men.Methods.  Participants were 30 men and 30 women who had coronary heart disease. The study was conducted using a qualitative method based on narrative investigation. Narratives were gathered using in‐depth interviews and were analyzed by thematic analysis. Data were collected in 2006.Results.  Women often delayed seeking treatment. When they did seek treatment they were often not initially diagnosed as having heart disease. The recovery period for women was characterised by their quick return to daily home making before their physical condition permitted it. Conversely, men extended their recovery period and received family support. Men were strict in following the instructions of the health regimen, whereas most women ignored it. The women, compared to the men, received less support from their spouses and families, and they noted that social expectations concerning their role were high.Conclusions.  The role of the cardiac patient is socially formed based on male characteristics and, as a result, men are legitimised and receive social support in all that relates to the disease. Consequently, men adhere to the health regimen, whereas women are less inclined to.Relevance to clinical practice.  Improved disease models for women with heart disease are needed, as are specifically design rehabilitation programmes to meet the needs of women with heart disease.
Nurses as family learning brokers: shared management in childhood chronic kidney disease
Authors: Swallow Veronica , Clarke Charlotte , Campbell Steve , Lambert Heather 
Published: February 2009

Aim. To explore the contribution of nurses to families’ learning in shared management of childhood chronic kidney disease.Background. From early in the disease course, nurses are involved in teaching families to share management. The failure of family members to share management can negatively influence children’s clinical outcomes. Earlier studies discussed the value of nurses’ involvement in chronic disease management and described learning by novices in organisations as a social activity involving communication brokers; however, little is known about the contribution of nurses to family learning in chronic kidney disease management.Design. A longitudinal qualitative study conducted in a regional kidney unit for children.Method. Data were obtained between September 2003–September 2005 from five families of children referred for management of conditions needing moderate/high levels of intervention and the four renal nurse‐specialists involved in their management. Data sources were 30 semi‐structured interviews, 19 postinterview case‐note reviews and four mother/child learning diaries; analysis followed the principles of grounded theory.Results. In promoting family competence, nurses acted as learning brokers, demonstrating five distinct yet overlapping teaching activities: assessing learning needs, creating learning opportunities, implementing teaching strategies, acting as interpreters and ambassadors and assessing learning progress. Families highlighted the contribution of nurses as learning brokers in the process of shared disease management.Conclusion. Nurses’ teaching activities in shared disease management are more important than previously reported. A clear distinction needs to be made between their contribution to management and to the promotion of family competence in shared management.Relevance to clinical practice. Recognition of nurses’ distinct teaching activities can inform professionals’ practice when caring for children with chronic disease and inform strategies to educate nurses and other professionals about the role of family learning broker.
Identification of a transcription factor in the mosquito‐invasive stage of malaria parasites
Authors: Yuda Masao , Iwanaga Shiroh , Shigenobu Shuji , Mair Gunnar R. , Janse Chris J. , Waters Andrew P. , Kato Tomomi , Kaneko Izumi 
Published: February 2009

SummaryGene expression in Plasmodium parasites undergoes significant changes in each developmental stage, but the transcription factors (TFs) regulating these changes have not been identified. We report here a Plasmodium TF (AP2‐O) that activates gene expression in ookinetes, the mosquito‐invasive form, and has a DNA‐binding domain structurally related to that of a plant TF, Apetala2 (AP2). AP2‐O mRNA is pre‐synthesized by intraerythrocytic female gametocytes and translated later during ookinete development in the mosquito. The Plasmodium TF activates a set of genes, including all genes reported to be required for midgut invasion, by binding to specific six‐base sequences on the proximal promoter. These results indicate that AP2 family TFs have important roles in stage‐specific gene regulation in Plasmodium parasites.
Natural‐host animal models indicate functional interchangeability between the filamentous haemagglutinins of Bordetella pertussis and Bordetella bronchiseptica and reveal a role for the mature C‐terminal domain, but not the RGD motif, during infection
Authors: Julio Steven M. , Inatsuka Carol S. , Mazar Joseph , Dieterich Christine , Relman David A. , Cotter Peggy A. 
Published: February 2009

SummaryBacteria of the Bordetella genus cause respiratory tract infections. Both broad host range (e.g. Bordetella bronchiseptica) and human‐adapted (e.g. Bordetella pertussis) strains produce a surface‐exposed and secreted protein called filamentous haemagglutinin (FHA) that functions in adherence and immunomodulation. Previous studies using B. pertussis and cultured mammalian cells identified several FHA domains with potential roles in host cell interactions, including an Arg‐Gly‐Asp (RGD) triplet that was reported to bind integrins on epithelial cells and monocytes to activate host signalling pathways. We show here that, in contrast to our previous report, the fhaB genes of B. pertussis and B. bronchiseptica are functionally interchangeable, at least with regard to the various in vitro and in vivo assays investigated. This result is significant because it indicates that information obtained studying FHA using B. bronchiseptica and natural‐host animal models should apply to B. pertussis FHA as well. We also show that the C‐terminus of mature FHA, which we name the MCD, mediates adherence to epithelial and macrophage‐like cells and is required for colonization of the rat respiratory tract and modulation of the inflammatory response in mouse lungs. We could not, however, detect a role for the RGD in any of these processes.
Menaquinone synthesis is critical for maintaining mycobacterial viability during exponential growth and recovery from non‐replicating persistence
Authors: Dhiman Rakesh K. , Mahapatra Sebabrata , Slayden Richard A. , Boyne Melissa E. , Lenaerts Anne , Hinshaw Jerald C. , Angala Shiva K. , Chatterjee Delphi , Biswas Kallolmay , Narayanasamy Prabagaran , Kurosu Michio , Crick Dean C. 
Published: February 2009

SummaryUnderstanding the basis of bacterial persistence in latent infections is critical for eradication of tuberculosis. Analysis of Mycobacterium tuberculosis mRNA expression in an in vitro model of non‐replicating persistence indicated that the bacilli require electron transport chain components and ATP synthesis for survival. Additionally, low μM concentrations of aminoalkoxydiphenylmethane derivatives inhibited both the aerobic growth and survival of non‐replicating, persistent M. tuberculosis. Metabolic labelling studies and quantification of cellular menaquinone levels suggested that menaquinone synthesis, and consequently electron transport, is the target of the aminoalkoxydiphenylmethane derivatives. This hypothesis is strongly supported by the observations that treatment with these compounds inhibits oxygen consumption and that supplementation of growth medium with exogenous menaquinone rescued both growth and oxygen consumption of treated bacilli. In vitro assays indicate that the aminoalkoxydiphenylmethane derivatives specifically inhibit MenA, an enzyme involved in the synthesis of menaquinone. Thus, the results provide insight into the physiology of mycobacterial persistence and a basis for the development of novel drugs that enhance eradication of persistent bacilli and latent tuberculosis.
The Aspergillus fumigatus transcription factor Ace2 governs pigment production, conidiation and virulence
Authors: Ejzykowicz Daniele E. , Cunha Marcel M. , Rozental Sonia , Solis Norma V. , Gravelat Fabrice N. , Sheppard Donald C. , Filler Scott G. 
Published: February 2009

Summary Aspergillus fumigatus causes serious and frequently fatal infections in immunocompromised patients. To investigate the regulation of virulence of this fungus, we constructed and analysed an A. fumigatus mutant that lacked the transcription factor Ace2, which influences virulence in other fungi. The Δace2 mutant had dysmorphic conidiophores, reduced conidia production and abnormal conidial cell wall architecture. This mutant produced an orange pigment when grown on solid media, although its conidia had normal pigmentation. Conidia of the Δace2 mutant were larger and had accelerated germination. The resulting germlings were resistant to hydrogen peroxide, but not other stressors. Non‐neutropenic mice that were immunosuppressed with cortisone acetate and infected with the Δace2 mutant had accelerated mortality, greater pulmonary fungal burden, and increased pulmonary inflammatory responses compared with mice infected with the wild‐type or Δace2::ace2‐complemented strains. The Δace2 mutant had reduced ppoC, ecm33 and ags3 mRNA expression. It is known that A. fumigatus mutants with absent or reduced expression of these genes have increased virulence in mice, as well as other phenotypic similarities to the Δace2 mutant. Therefore, reduced expression of these genes likely contributes to the increased virulence of the Δace2 mutant.
Assembly of the MreB‐associated cytoskeletal ring of Escherichia coli
Authors: Vats Purva , Shih Yu‐Ling , Rothfield Lawrence 
Published: February 2009

SummaryThe Escherichia coli actin homologue MreB is part of a helical cytoskeletal structure that winds around the cell between the two poles. It has been shown that MreB redistributes during the cell cycle to form circumferential ring structures that flank the cytokinetic FtsZ ring and appear to be associated with division and segregation of the helical cytoskeleton. We show here that the MreB cytoskeletal ring also contains the MreC, MreD, Pbp2 and RodA proteins. Assembly of MreB, MreC, MreD and Pbp2 into the ring structure required the FtsZ ring but no other known components of the cell division machinery, whereas assembly of RodA into the cytoskeletal ring required one or more additional septasomal components. Strikingly, MreB, MreC, MreD and RodA were each able to independently assemble into the cytoskeletal ring and coiled cytoskeletal structures in the absence of any of the other ring components. This excludes the possibility that one or more of these proteins acts as a scaffold for incorporation of the other proteins into these structures. In contrast, incorporation of Pbp2 required the presence of MreC, which may provide a docking site for Pbp2 entry.
Soluble vascular cell adhesion molecule‐1 induces human eosinophil migration
Authors: Ueki S. , Kihara J. , Kato H. , Ito W. , Takeda M. , Kobayashi Y. , Kayaba H. , Chihara J. 
Published: February 2009

Background:  Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2‐type immune responses including asthma. Adhesion molecules are known to play an important role in the accumulation of eosinophils in allergic inflammatory foci, and they contribute to eosinophil activation. Elevated levels of the soluble forms of adhesion molecules in the body fluid of asthmatic patients have been observed, although their pathophysiological significance remains to be fully elucidated.Methods:  Peripheral blood eosinophils were purified, and the effect of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) on eosinophil migration was investigated using in vitro systems.Results:  We found that sVCAM‐1 (1 to 10 μg/ml) induced eosinophil chemotaxis, rather than chemokinesis, in a concentration‐dependent fashion. In addition, sVCAM‐1 induced cell shape change and actin polymerization, which are necessary for cell movement. Manipulations with very late antigen (VLA)‐4‐neutralizing antibody and signal inhibitors indicated that the sVCAM‐1‐induced chemotaxis was mediated through ligand‐dependent activation of tyrosine kinase Src, p38 mitogen‐activated protein kinase (MAPK), and extracellular signal‐regulated kinase (ERK) MAPK. Rapid phosphorylation of these signaling molecules was observed using a bead‐based multiplex assay.Conclusion:  Our results raise the possibility of sVCAM‐1 in the fluid phase as a significant contributor to the heightened eosinophilic inflammatory response.
Development and validation of the Food Allergy Quality of Life Questionnaire – Adult Form
Authors: Flokstra‐de Blok B. M. J. , Van Der Meulen G. N. , DunnGalvin A. , Vlieg‐Boerstra B. J. , Oude Elberink J. N. G. , Duiverman E. J. , Hourihane J. O’B. , Dubois A. E. J. 
Published: February 2009

Background:  Health‐related quality of life (HRQL) may be affected by food allergy. Presently, no disease‐specific HRQL questionnaire exists for food allergic adults. Therefore, we developed and validated the Food Allergy Quality of Life Questionnaire – Adult Form (FAQLQ‐AF) in the Dutch language.Methods:  Twenty‐two food allergic patients (≥18 years) were interviewed and generated 180 HRQL items. The most important items were identified by 54 food allergic patients using the clinical impact method resulting in the FAQLQ‐AF containing 29 items (score range 1 ‘not troubled’ to 7 ‘extremely troubled’). The FAQLQ‐AF, the Food Allergy Independent Measure (FAIM) and a generic HRQL questionnaire (RAND‐36) were sent to 100 other food allergic adults for cross‐sectional validation of the FAQLQ‐AF.Results:  Cross‐sectional validity was assessed by the correlation between FAQLQ‐AF and FAIM (ρ = 0.76, P < 0.001). The FAQLQ‐AF had excellent internal consistency (Cronbach’s α = 0.97). The FAQLQ‐AF discriminated between patients who differ in severity of symptoms (anaphylaxis vs no anaphylaxis, total FAQLQ‐AF score 4.9 vs 4.1; P = 0.041) and number of food allergies (>3 food allergies vs≤3 food allergies, total FAQLQ‐AF score 5.2 vs 4.2; P = 0.008). The total FAQLQ‐AF score was correlated with one RAND‐36 scale (convergent/discriminant validity).Conclusions:  The FAQLQ‐AF is the first disease‐specific HRQL questionnaire for food allergic adults and reflects the most important issues that food allergic patients have to face. The questionnaire is valid, reliable and discriminates between patients with different disease characteristics. The FAQLQ‐AF is short and easy to use and may therefore be a useful tool in clinical research.
Condition dependence of developmental stability in the sexually dimorphic flyTelostylinus angusticollis(Diptera: Neriidae)
Authors: BONDURIANSKY R. 
Published: February 2009

AbstractDevelopmental stability is widely regarded as a condition‐dependent trait, but its relation to genotype and environment, and extent of developmental integration, remain contentious. InTelostylinus angusticollis, the dorsocentral bristles exhibit striking variation in developmental stability, manifested as fluctuating asymmetry (FA) in bristle position (‘positional FA’) and failure to develop some bristles (‘bristle loss’), in natural and laboratory populations. To determine whether this variation reflects condition, I tested for effects of genotype and environment (larval diet quality), and examined covariation with condition‐dependent traits. Positional FA was not affected by genotype or environment. However, positional FA covaried negatively with secondary sexual trait expression in males, and with sexual dimorphism in body shape, but covaried positively with body size in females. Bristle loss reflected both genotype and larval diet. Flies reared on poor‐quality diet exhibited a similar rate of bristle loss as wild flies. Both positional FA and bristle loss were greater in males. These results suggest that the relation between developmental stability and condition is complex and sex dependent.
Diet‐dependent female evolution influences male lifespan in a nuptial feeding insect
Authors: HALL M. D. , BUSSIÈRE L. F. , BROOKS R. 
Published: February 2009

AbstractTheory predicts that lifespan will depend on the dietary intake of an individual, the allocation of resources towards reproduction and the costs imposed by the opposite sex. Although females typically bear the majority of the cost of offspring production, nuptial feeding invertebrates provide an ideal opportunity to examine the extent to which reproductive interactions through gift provisioning impose a cost on males. Here we use experimental evolution in an Australian ground cricket to assess how diet influences male lifespan and how the costs of mating evolve for males. Our findings show that males had significantly shorter lifespans in populations that adapted to a low‐quality diet and that this divergence is driven by evolutionary change in how females interact with males over reproduction. This suggests that the extent of sexual conflict over nuptial feeding may be under‐realized by focusing solely on the consequences of reproductive interactions from the female’s perspective.
Optimum allocation of test resources and relative efficiency of alternative procedures of within‐family selection in hybrid breeding
Authors: Longin C. F. H. , Maurer H. P. , Melchinger A. E. , Frisch M. 
Published: February 2009

AbstractSelection within families can be conducted as family deviation (FDS) or strict within‐family selection (WFS). Our objectives were to (i) investigate two breeding schemes combining selection among families with FDS or WFS and (ii) compare the optimum allocation of test resources for these breeding schemes. We focused on selection among S1 families and doubled haploid (DH) lines within S1 families and used Monte Carlo simulations to determine the selection gain (ΔĜ), its standard deviation (SDΔĜ), and the average coefficient of coancestry among the selected DH lines (). For breeding schemes focusing only on within‐family selection, as employed in animal breeding, the maximum ΔĜ, its SDΔĜ, and were larger for FDS than for WFS. However, for breeding schemes combining among‐ and within‐family selection, as employed commonly in plant breeding programmes, the maximum ΔĜ, SDΔĜ, and were almost equal for FDS and WFS. Furthermore, the optimum allocation of test resources was similar for FDS and WFS. We conclude that FDS and WFS are equally suited for short‐ and long‐term success in breeding schemes where among‐family selection is followed by within‐family selection.