bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for modular evolution in a long-tailed pterosaur with a pterodactyloid skull
Authors: Lü Junchang , Unwin David M. , Jin Xingsheng , Liu Yongqing , Ji Qiang
Published: October 2009

The fossil record is a unique source of evidence for important evolutionary phenomena such as transitions between major clades. Frustratingly, relevant fossils are still comparatively rare, most transitions have yet to be documented in detail and the mechanisms that underpin such events, typified by rapid large scale changes and for which microevolutionary processes seem insufficient, are still unclear. A new pterosaur (Mesozoic flying reptile) from the Middle Jurassic of China,Darwinopterus modularisgen. et sp. nov., provides the first insights into a prominent, but poorly understood transition between basal, predominantly long-tailed pterosaurs and the more derived, exclusively short-tailed pterodactyloids.Darwinopterusexhibits a remarkable ‘modular’ combination of characters: the skull and neck are typically pterodactyloid, exhibiting numerous derived character states, while the remainder of the skeleton is almost completely plesiomorphic and identical to that of basal pterosaurs. This pattern supports the idea that modules, tightly integrated complexes of characters with discrete, semi-independent and temporally persistent histories, were the principal focus of natural selection and played a leading role in evolutionary transitions.
Epigenetic responses to environmental change and their evolutionary implications
Authors: Turner Bryan M.
Published: October 2009

Chromatin is a complex of DNA, RNA, histones and non-histone proteins and provides the platform on which the transcriptional machinery operates in eukaryotes. The structure and configuration of chromatin are manipulated by families of enzymes, some catalysing the dynamic addition and removal of chemical ligands to selected protein amino acids and some directly altering or displacing the basic structural units. The activities of many of these enzymes are sensitive to environmental and metabolic agents and can thereby serve as sensors through which environmental agents can alter gene expression. Such changes can, in turn, precipitate either local or cell-wide changes as the initial effect spreads through multiple interactive networks. This review discusses the increasingly well-understood mechanisms through which these enzymes alter chromatin function. In some cases at least, it seems that the effects on gene expression may persist even after the removal of the inducing agent, and can be passed on, through mitosis, to subsequent cell generations, constituting a heritable, epigenetic change. If such changes occur in germ cells or their precursors, then they may be passed on to subsequent generations. Mechanisms are now known to exist through which an epigenetic change might give rise to a localized change in DNA sequence exerting the same functional effect, thereby converting an epigenetic to a genetic change. If the induced genetic change has phenotypic effects on which selection can act, then this hypothetical chain of events constitutes a potential route through which the environment might directly influence evolution.
The endocrine control of reproduction in Nereidae: a new multi-hormonal model with implications for their functional role in a changing environment
Authors: Lawrence A. J. , Soame J. M.
Published: October 2009

Nereidae are vital to the functioning of estuarine ecosystems and are major components in the diets of over-wintering birds and commercial fish. They use environmental cues to synchronize reproduction. Photoperiod is the proximate cue, initiating vitellogenesis in a temperature-compensated process. The prevailing paradigm in Nereidae is of a single ‘juvenile’ hormone controlling growth and reproduction. However, a new multi-hormone model is presented here that integrates the environmental and endocrine control of reproduction. This is supported by evidence from
in vitro
bioassays. The juvenile hormone is shown to be heat stable and cross reactive between species. In addition, a second neuro-hormone, identified here as a gonadotrophic hormone, is shown to be present in mature females and is found to promote oocyte growth. Furthermore, dopamine and melatonin appear to switch off the juvenile hormone while serotonin and oxytocin promote oocyte growth. Global warming is likely to uncouple the phase relationship between temperature and photoperiod, with significant consequences for Nereidae that use photoperiod to cue reproduction during the winter in northern latitudes. Genotypic adaptation of the photoperiodic response may be possible, but significant impacts on fecundity, spawning success and recruitment are likely in response to short-term extreme events. Endocrine-disrupting chemicals may also impact on putative steroid hormone pathways in Nereidae with similar consequences. These impacts may have significant implications for the functional role of Nereidae and highlight the importance of comparative endocrinology studies in these and other invertebrates.
miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb–E2F1 activity through a feedback loop by targeting CDK6 and CDC25A
Authors: Yang Xiaojing , Feng Min , Jiang Xia , Wu Zhenlong , Li Zhimei , Aau Meiyee , Yu Qiang
Published: October 2009

The Rb–E2F pathway drives cell cycle progression and cell proliferation, and the molecular strategies safeguarding its activity are not fully understood. Here we report that E2F1 directly transactivates miR-449a/b. miR-449a/b targets and inhibits oncogenic CDK6 and CDC25A, resulting in pRb dephosphorylation and cell cycle arrest at G1 phase, revealing a negative feedback regulation of the pRb–E2F1 pathway. Moreover, miR-449a/b expression in cancer cells is epigenetically repressed through histone H3 Lys27 trimethylation, and epigenetic drug treatment targeting histone methylation results in strong induction of miR-449a/b. Our study reveals a tumor suppressor function of miR-449a/b through regulating Rb/E2F1 activity, and suggests that escape from this regulation through an aberrant epigenetic event contributes to E2F1 deregulation and unrestricted proliferation in human cancer.
Development of mammary luminal progenitor cells is controlled by the transcription factor STAT5A
Authors: Yamaji Daisuke , Na Risu , Feuermann Yonatan , Pechhold Susanne , Chen Weiping , Robinson Gertraud W. , Hennighausen Lothar
Published: October 2009

Mammary alveologenesis is abrogated in the absence of the transcription factors STAT5A/5B, which mediate cytokine signaling. To reveal the underlying causes for this developmental block, we studied mammary stem and progenitor cells. While loss of STAT5A/5B did not affect the stem cell population and its ability to form mammary ducts, luminal progenitors were greatly reduced and unable to form alveoli during pregnancy. Temporally controlled expression of transgenic STAT5A in mammary epithelium lacking STAT5A/5B restored the luminal progenitor population and rescued alveologenesis in a reversible fashion in vivo. Thus, STAT5A is necessary and sufficient for the establishment of luminal progenitor cells.
Reduced capacity of alternative σs to melt promoters ensures stringent promoter recognition
Authors: Koo Byoung-Mo , Rhodius Virgil A. , Nonaka Gen , deHaseth Pieter L. , Gross Carol A.
Published: October 2009

In bacteria, multiple σs direct RNA polymerase to distinct sets of promoters. Housekeeping σs direct transcription from thousands of promoters, whereas most alternative σs are more selective, recognizing more highly conserved promoter motifs. For σ32 and σ28, two Escherichia coli Group 3 σs, altering a few residues in Region 2.3, the portion of σ implicated in promoter melting, to those universally conserved in housekeeping σs relaxed their stringent promoter requirements and significantly enhanced melting of suboptimal promoters. All Group 3 σs and the more divergent Group 4 σs have nonconserved amino acids at these positions and rarely transcribe >100 promoters. We suggest that the balance of “melting” and “recognition” functions of σs is critical to setting the stringency of promoter recognition. Divergent σs may generally use a nonoptimal Region 2.3 to increase promoter stringency, enabling them to mount a focused response to altered conditions.
Allelic inactivation of rDNA loci
Authors: Schlesinger Sharon , Selig Sara , Bergman Yehudit , Cedar Howard
Published: October 2009

Human cells contain several hundred ribosomal genes (rDNA) that are clustered into nucleolar organizer regions (NORs) on the short arms of five different acrocentric chromosomes. Only ∼50% of the gene copies are actually expressed in somatic cells. Here, we used a new cytological technique to demonstrate that rDNA is regulated allelically in a regional manner, with one parental copy of each NOR being repressed in any individual cell. This process is similar to that of X-chromosome inactivation in females. Early in development, one copy of each NOR becomes late-replicating, thus probably marking it for inactivation and subsequent targeted de novo methylation at rDNA promoter regions. Once established, this multichromosomal allelic pattern is then maintained clonally in somatic cells. This pathway may serve as an epigenetic mechanism for controlling the number of available rDNA copies during development.
Histological type of Thorotrast‐induced liver tumors associated with the translocation of deposited radionuclides
Authors: Yamamoto Yoichiro , Chikawa Junichi , Uegaki Yoshinobu , Usuda Nobuteru , Kuwahara Yoshikazu , Fukumoto Manabu
Published: October 2009

Exposure to internally deposited radionuclides is known to induce malignant tumors of various histological types. Thorotrast, a colloidal suspension of radioactive Thorium dioxide (232ThO2) that emits alpha‐particles, was used as a radiographic contrast during World War II. Thorotrast is known to induce liver tumors, particularly intrahepatic cholangiocarcinoma (ICC) and angiosarcoma (AS), decades after injection. Therefore, patients injected with Thorotrast comprise a suitable study group to understand biological effects of internal ionizing radiation injury. Autoradiography and X‐ray fluorescence spectrometry (XRF) were carried out on non‐tumorous liver sections from Thorotrast‐induced ICC (T‐ICC) and Thorotrast‐induced AS (T‐AS). Autoradiography revealed that the slope of the regression line of the number of alpha tracks for the amount of deposited Thorium (232Th) was higher in non‐tumorous parts of the liver with T‐ICC than those with T‐AS. XRF showed that the intensity ratio of Radium (Ra) to Thorium (Th) in non‐tumorous liver tissue with T‐ICC was significantly higher than that with T‐AS. Furthermore, the mean 228Ra/232Th radioactivity ratio at the time of death calculated was also significantly higher in T‐ICC cases than in T‐AS cases. These suggest that the metabolic behavior of radionuclides such as relocation and excretion, as well as the content of deposited radionuclides, is a major factor in determining the histological type of Thorotrast‐induced liver tumors. (Cancer Sci 2009)
Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells
Authors: Pérez‐Persona Ernesto , Mateo Gema , García‐Sanz Ramón , Mateos María‐Victoria , De Las Heras Natalia , De Coca Alfonso García , Hernández José M. , Galende Josefina , Martín‐Nuñez Guillermo , Bárez Abelardo , Alonso José M. , Martín Alejandro , López‐Berges Consuelo , Orfao Alberto , San Miguel Jesús F. , Vidriales María‐Belén
Published: October 2009

The present study explored the impact of two novel criteria; having >95% abnormal plasma cells by flow cytometry at diagnosis and the evolving subtype of the disease, as predictors of progression in 61 smouldering multiple myeloma (SMM) and 311 monoclonal gammopathy of unknown significance (MGUS) patients. Although both criteria were of prognostic value, the risk of progression was better identified by immunophenotyping [Hazard Ratio (HR) 6·2 and 17·2 for SMM and MGUS, respectively] than evolving subtype, which had independent prognostic value only in MGUS (HR 3·6). Immunophenotyping discriminated the different risk of progression within the evolving and non‐evolving subgroups of SMM (P = 0·01) and MGUS (P < 0·001).
Immunotoxin BL22 induces apoptosis in mantle cell lymphoma (MCL) cells dependent on Bcl‐2 expression
Authors: Bogner Christian , Dechow Tobias , Ringshausen Ingo , Wagner Michaela , Oelsner Madlen , Lutzny Gloria , Licht Thomas , Peschel Christian , Pastan Ira , Kreitman Robert J , Decker Thomas
Published: October 2009

Mantle cell lymphoma (MCL) is an incurable mature B cell proliferation, combining the unfavourable clinical features of aggressive and indolent lymphomas. The blastic variant of MCL has an even worse prognosis and new treatment options are clearly needed. We analysed the effects of BL22, an immunotoxin composed of the Fv portion of an anti‐ CD22 antibody fused to a 38‐kDa Pseudomonas exotoxin‐A fragment on four MCL cell lines as well as on primary cells of four MCL patients. Apoptosis induction by BL22 was much more pronounced in MCL cell lines with low Bcl‐2 expression (NCEB‐1, JeKo‐1 and JVM‐2) compared to Granta‐519 cells with high Bcl‐2 expression. While the expression of the antiapoptotic protein Mcl‐1 declined (NCEB‐1, Granta‐519), Bcl‐2 levels remained unchanged in Granta‐519 cells. However transfection of BCL2 cDNA into NCEB‐1, JeKo‐1 and JVM‐2 cells significantly reduced BL22‐mediated toxicity. Accordingly we examined the effects of Bcl‐2 inactivation in Granta‐519 cells using siRNA. Indeed, apoptosis induction was strongly enhanced in Granta‐519 cells with silenced Bcl‐2. Our results were confirmed in freshly isolated MCL‐cells from patients with leukaemic MCL. We conclude that Bcl‐2 expression is important for mediating resistance against the immunotoxin BL22 in MCL cells.
Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R‐CHOP)
Authors: Gratzinger Dita , Advani Ranjana , Zhao Shuchun , Talreja Neha , Tibshirani Robert J. , Shyam Ragini , Horning Sandra , Sehn Laurie H. , Farinha Pedro , Briones Javier , Lossos Izidore S. , Gascoyne Randy D. , Natkunam Yasodha
Published: October 2009

Diffuse large B cell lymphoma (DLBCL) is clinically and biologically heterogeneous. In most cases of DLBCL, lymphoma cells co‐express vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, suggesting autocrine in addition to angiogenic effects. We enumerated microvessel density and scored lymphoma cell expression of VEGF, VEGFR1, VEGFR2 and phosphorylated VEGFR2 in 162 de novo DLBCL patients treated with R‐CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone)‐like regimens. VEGFR2 expression correlated with shorter overall survival (OS) independent of International Prognostic Index (IPI) (P = 0·0028). Phosphorylated VEGFR2 (detected in 13% of cases) correlated with shorter progression‐free survival (PFS, P = 0·044) and trended toward shorter OS on univariate analysis. VEGFR1 was not predictive of survival on univariate analysis, but it did correlate with better OS on multivariate analysis with VEGF, VEGFR2 and IPI (P = 0·036); in patients with weak VEGFR2, lack of VEGFR1 coexpression was significantly correlated with poor OS independent of IPI (P = 0·01). These results are concordant with our prior finding of an association of VEGFR1 with longer OS in DLBCL treated with chemotherapy alone. We postulate that VEGFR1 may oppose autocrine VEGFR2 signalling in DLBCL by competing for VEGF binding. In contrast to our prior results with chemotherapy alone, microvessel density was not prognostic of PFS or OS with R‐CHOP‐like therapy.
A high normal TSH is associated with the metabolic syndrome
Authors: Ruhla Stephan , Weickert Martin O. , Arafat Ayman M. , Osterhoff Martin , Isken Frank , Spranger Joachim , Schöfl Christof , Pfeiffer Andreas F. H. , Möhlig Matthias
Published: October 2009

Objective  Obesity and insulin resistance are key features of the metabolic syndrome. In euthyroidism, the relationships between TSH and insulin resistance or the metabolic syndrome are less clear. We investigated the associations between TSH and the features and prevalence of the metabolic syndrome in euthyroid German subjects.

Methods  In a cross‐sectional study, glucose metabolism was defined by an oral glucose tolerance test (oGTT) (except for those with evident diabetes) in 1333 subjects with TSH values between 0·3 and 4·5 mU/l who did not take any thyroid medication. Lipid parameters were measured, blood pressure and anthromopmetric parameters were taken, and insulin resistance was quantified as HOMA%S.

Results  TSH was weakly correlated with BMI (R = 0·061, P = 0·025). This association remained significant after adjustment for sex, age, and impaired glucose metabolism (P = 0·002). Subjects with a TSH in the upper normal range (2·5–4·5 mU/l, n = 119) had a significantly higher BMI (30·47 ± 0·57 vs. 28·74 ± 0·18 kg/m2, P = 0·001) and higher fasting triglycerides (1·583 ± 0·082 vs. 1·422 ± 0·024 mmol/l, P = 0·023), and their likeliness for fulfilling the ATP III criteria of the metabolic syndrome was 1·7‐fold increased (95% CI: 1·11– 2·60).

Conclusion  In euthyroidism, subjects with a TSH in the upper normal range (2·5–4·5 mU/l) were more obese, had higher triglycerides, and had an increased likeliness for the metabolic syndrome. Therefore, a TSH below 2·5 mU/l is associated with a favourable metabolic profile. Whether lowering TSH to levels below 2·5 mU/l improves metabolism needs to be investigated in intervention trials.
Larval cannibalism during the late developmental stages of a facultatively gregarious encyrtid endoparasitoid
Authors: TENA ALEJANDRO , KAPRANAS APOSTOLOS , GARCIA‐MARÍ FERRAN , LUCK ROBERT F.
Published: October 2009

The larvae of many gregarious parasitoid species are usually non‐aggressive when they develop in or on a host, but those of Metaphycus flavus are one of the few exceptions known. Herein we describe their aggressive behaviour and the conditions under which it occurs, using observations in which larval development and physical conflict within parasitised and superparasitised hosts were mapped daily.

Metaphycus flavus larvae often engaged in physical conflict that resulted in consumption of the losing larvae (= cannibalism ) in superparasitised hosts, whereas such conflict and consumption occurred rarely when a single brood developed in a host.

Cannibalism among M. flavus larvae only occurred after the host resources had become scarce. Typically it occurred after the sixth day of development (fourth‐instar larvae) when the larvae in a clutch had separated from their aeroscopic plate and were freed of their attachment to the host's cuticle.

Female larvae in the initial clutch appeared more aggressive than male larvae when a second clutch was allocated 4 h after the first clutch. The probability of a larva being attacked and consumed by a brood mate increased as the number of larvae increased in the host. This partial tolerance might allow the members of the initial brood to defend themselves from offspring of a superparasitising female (= competitors ). Such post‐ovipositional regulation of brood size might be interpreted as high‐density intolerance among female offspring.
Wetland isolation facilitates larval mosquito density through the reduction of predators
Authors: CHASE JONATHAN M. , SHULMAN RACHEL S.
Published: October 2009

Wetlands harbour high biodiversity and offer important ecosystem services, but they are also a habitat for mosquito larvae (Diptera: Culicidae), which are important disease vectors.

Isolation among remnant, or newly created wetlands and ponds, and their consequent density in the landscape, is a key factor that can influence a variety of food web processes, including effects on mosquitoes which are important prey to many predators.

We assess the impact of habitat isolation on the density of pond‐breeding mosquitoes (several Anopheles and Culex species) both directly and indirectly through the food web.

Results from structural equation modelling of survey data shows that larval mosquitoes are denser in ponds that are more isolated from one another, and that this result was primarily driven indirectly by a reduction of larval mosquito predators (e.g. predaceous insects and amphibians). Furthermore, results from a long‐term mesocosm experiment factorially manipulating isolation and predator reduction show that the effect of isolation on mosquito density was eliminated when predators were experimentally reduced.

It is concluded that metacommunity processes, both directly and indirectly mediated through predators, can play an important role in the local abundance of wetland breeding mosquitoes and possibly the diseases they spread.
Attitudes of nursing students towards caring for people with HIV/AIDS: thematic literature review
Authors: Pickles David , King Lindy , Belan Ingrid
Published: October 2009

Title.  Attitudes of nursing students towards caring for people with HIV/AIDS: thematic literature review.

Aim. This paper is a report of a literature review conducted to examine current research studies into attitudes of nursing students towards caring for people with HIV/AIDS and to identify factors that influenced those attitudes to inform current nursing practice and to develop nursing education regarding care provided to people with HIV/AIDS.

Background. Attitudes of nurses towards people living with HIV/AIDS have long been scrutinized. Studies show that some nurses have negative attitudes and are reluctant to provide care to people with HIV/AIDS, resulting in poorer quality nursing support being provided. Attitudes of nursing students towards caring for people with HIV/AIDS is thus of vital importance since they become the future practising nurses.

Data sources.  Eight electronic data bases were searched from 1996–2008.

Review methods.  Criteria used for study selection were: attitudes of nursing students towards caring for people with HIV/AIDS, primary research studies, published in English language in peer reviewed journals from 1996 to June 2008. Sixteen studies were identified for inclusion in this thematic review.

Results.  The following themes were identified: education and knowledge of HIV/AIDS; fear of contracting HIV/AIDS; reluctance to care for people with HIV/AIDS; homophobia; and stigma associated with HIV/AIDS.

Conclusion. There is reluctance on the part of some nursing students in specific regions of the world to provide care for people with HIV/AIDS. Educational programmes based on research evidence must play a leading role in developing strategies to help nursing students understand and overcome such attitudes.
Feeding strategies used by primary school meal staff and their impact on children’s eating
Authors: Moore S. N. , Tapper K. , Murphy S.
Published: October 2009

Background:  In parent–child interactions, feeding strategies including pressure, restriction, modelling, rewards, encouragement and repeated taste exposure have been reliably shown to influence children’s eating. Because there is no evidence that the psychosocial interactions inherent in the strategies are context‐dependent, the present study investigated their utilisation during primary school meal supervision.

Methods:  A case study of one Local Authority in Wales was conducted involving eleven primary schools stratified into socio‐economic quartiles. Focussed observations were carried out over two to three lunchtimes per school to explore the feeding strategies, outcomes and behaviours inherent in the dining hall context. These were supplemented by semi‐structured interviews with catering staff and midday supervisors, which were carried out after the observation session.

Results:  Most feeding strategies used by school meal staff reflected those reported in the literature (e.g. pressure, encouragement and rewards), although purposeful modelling of eating behaviours was not found and the imposition of food norms, such as eating dessert last, was common. Dining hall staff readily, if not consistently, used these strategies, although the constraints and opportunities of each dining hall context influenced their selection and implementation. However, even if children left the service point with nutritionally balanced meals, they often failed to eat them.

Conclusions:  Because repeated taste exposure is known to increase liking for foods, further studies are recommended to investigate how the naturally occurring feeding strategies evident in primary school dining halls could be harnessed to encourage children to taste the nutritionally balanced schools meals that school meal transformation programmes will expose them to.
The disposition of hepatitis C antibody‐positive patients in an urban hospital
Authors: Putka B. , Mullen K. , Birdi S. , Merheb M.
Published: October 2009

Summary.  Previous studies have indicated that only 26–61% of hepatitis C virus (HCV) antibody‐positive patients are referred to specialists who treat HCV. However, these studies were conducted in homogeneous populations and before pegylated interferon and ribavirin became the standard of care for chronic HCV infection. The aims of this study were: (i) to determine the percentage of HCV antibody‐positive patients who were referred to specialists for further management in an urban, racially diverse population, (ii) to determine the percentage of referred patients who attend specialty clinics, and (iii) to identify factors that predict referral and follow‐up. All patients with a positive HCV antibody test in 2005 were identified by an inquiry of EpicTM, our electronic medical record system. All medical records were reviewed for demographics, location where the test was ordered (inpatient vs outpatient), specialty ordering the test, referral, clinic attendance, detectability of HCV RNA and liver function tests. Univariate and multivariate logistic regression were used to evaluate each variable’s effect on referral and clinic attendance. Overall, 251 of 375 (67%) antibody positive patients were referred to HCV specialists. Of the 251 referrals, 166 (66%) attended at least one specialty clinic appointment. Patients were more likely to be referred if their HCV antibody was ordered in the outpatient setting (77% outpatient vs 38% inpatient, P < 0.001) ordered by a family practitioner (79% FP vs 64% for internal medicine doctor vs 58% for all other specialties, P = 0.01) had detectable RNA (88% detectable vs 65% not detectable vs 23% RNA status not available, P < 0.001) or elevation of alanine aminotransferase (75% elevated vs 56% not elevated, P < 0.001). Location, HCV RNA status and ALT elevation remained significant in a multivariate logistic regression model. These data confirm that up to one‐third of HCV antibody‐positive patients are not referred to HCV specialists, despite the availability of improved treatment regimens. Additional patients are lost to follow‐up after being referred. The reasons for suboptimal referral and specialty clinic attendance rates are probably multifactorial. Institution of reflexive RNA testing for positive antibody tests and additional education of those physicians who encounter HCV‐positive individuals may improve both rates.
Uncovering the tracks of a recent and rapid invasion: the case of the fruit fly pest Bactrocera invadens (Diptera: Tephritidae) in Africa
Authors: KHAMIS F. M. , KARAM N. , EKESI S. , DE MEYER M. , BONOMI A. , GOMULSKI L. M. , SCOLARI F. , GABRIELI P. , SICILIANO P. , MASIGA D. , KENYA E. U. , GASPERI G. , MALACRIDA A. R. , GUGLIELMINO C. R.
Published: October 2009

Phytophagous insects of the genus Bactrocera are among the most economically important invasive fruit fly pests. In 2003, an unknown Bactrocera species was found in Kenya. First identified as an ‘aberrant form’ of the Asian B. dorsalis complex, it was later recognized as a new species, Bactrocera invadens. Within 2 years of its discovery, the species was recorded in several African countries, becoming an important quarantine pest. As this invasive fly was discovered only recently, no data are available on its invasion pattern in Africa. This pilot study attempts to infer from genetic data the dynamic aspects of the African invasion of this pest. Using microsatellite markers, we evaluated the level of genetic diversity and the extent of common ancestry among several African populations collected across the invaded areas. A sample from the Asian Sri Lankan population was analysed to confirm the Asian origin of this pest. Genetic data cast no doubt that Sri Lanka belongs to the native range, but only a small percentage of its genotypes can be found in Africa. African populations display relatively high levels of genetic diversity associated with limited geographical structure and no genetic footprints of bottlenecks. These features are indicative of processes of rapid population growth and expansion with possible multiple introductions. In the span of relatively few years, the African invasion registered the presence of at least two uncorrelated outbreaks, both starting from the East. The results of the analyses support that invasion started in East Africa, where B. invadens was initially isolated.
Activation of σ28‐dependent transcription in Escherichia coli by the cyclic AMP receptor protein requires an unusual promoter organization
Authors: Hollands Kerry , Lee David J. , Lloyd Georgina S. , Busby Stephen J. W.
Published: October 2009

The Escherichia coli aer regulatory region contains a single promoter that is recognized by RNA polymerase containing the flagellar sigma factor, σ28. Expression from this promoter is dependent on direct activation by the cyclic AMP receptor protein, which binds to a target centred 49.5 base pairs upstream from the transcript start. Activator‐dependent transcription from the aer promoter was reconstituted in vitro, and a tethered inorganic nuclease was used to find the position of the C‐terminal domains of the RNA polymerase α subunits in transcriptionally competent open complexes. We report that the ternary activator–RNA polymerase–aer promoter open complex is organized differently from complexes at previously characterized promoters. Among other E. coli promoters recognized by RNA polymerase containing σ28, only the trg promoter is activated directly by the cyclic AMP receptor protein. The organization of the different promoter elements and the activator binding site at the trg promoter is the same as at the aer promoter, suggesting a common activation mechanism.
Cytochrome P450 125 (CYP125) catalyses C26‐hydroxylation to initiate sterol side‐chain degradation in Rhodococcus jostii RHA1
Authors: Rosłoniec Kamila Z. , Wilbrink Maarten H. , Capyk Jenna K. , Mohn William W. , Ostendorf Martin , Van Der Geize Robert , Dijkhuizen Lubbert , Eltis Lindsay D.
Published: October 2009

The cyp125 gene of Rhodococcus jostii RHA1 was previously found to be highly upregulated during growth on cholesterol and the orthologue in Mycobacterium tuberculosis (rv3545c) has been implicated in pathogenesis. Here we show that cyp125 is essential for R. jostii RHA1 to grow on 3‐hydroxysterols such as cholesterol, but not on 3‐oxo sterol derivatives, and that CYP125 performs an obligate first step in cholesterol degradation. The involvement of cyp125 in sterol side‐chain degradation was confirmed by disrupting the homologous gene in Rhodococcus rhodochrous RG32, a strain that selectively degrades the cholesterol side‐chain. The RG32Ωcyp125 mutant failed to transform the side‐chain of cholesterol, but degraded that of 5‐cholestene‐26‐oic acid‐3β‐ol, a cholesterol catabolite. Spectral analysis revealed that while purified ferric CYP125RHA1 was < 10% in the low‐spin state, cholesterol (KDapp = 0.20 ± 0.08 μM), 5α‐cholestanol (KDapp = 0.15 ± 0.03 μM) and 4‐cholestene‐3‐one (KDapp = 0.20 ± 0.03 μM) further reduced the low spin character of the haem iron consistent with substrate binding. Our data indicate that CYP125 is involved in steroid C26‐carboxylic acid formation, catalysing the oxidation of C26 either to the corresponding carboxylic acid or to an intermediate state.
Direct activator/co‐activator interaction is essential for bacteriophage T4 middle gene expression
Authors: Yuan Andy H. , Hochschild Ann
Published: October 2009

The bacteriophage T4 AsiA protein is a bifunctional regulator that inhibits transcription from the major class of bacterial promoters and also serves as an essential co‐activator of transcription from T4 middle promoters. AsiA binds the primary σ factor in Escherichia coli, σ70, and modifies the promoter recognition properties of the σ70‐containing RNA polymerase (RNAP) holoenzyme. In its role as co‐activator, AsiA directs RNAP to T4 middle promoters in the presence of the T4‐encoded activator MotA. According to the current model for T4 middle promoter activation, AsiA plays an indirect role in stabilizing the activation complex by facilitating interaction between DNA‐bound MotA and σ70. Here we show that AsiA also plays a direct role in T4 middle promoter activation by contacting the MotA activation domain. Furthermore, we show that interaction between AsiA and the β‐flap domain of RNAP is important for co‐activation. Based on our findings, we propose a revised model for T4 middle promoter activation, with AsiA organizing the activation complex via three distinct protein–protein interactions.
Dual control by perfectly overlapping σ54‐ and σ70‐promoters adjusts small RNA GlmY expression to different environmental signals
Authors: Reichenbach Birte , Göpel Yvonne , Görke Boris
Published: October 2009

In Escherichia coli synthesis of glucosamine‐6‐phosphate synthase GlmS is feedback‐controlled by a regulatory cascade composed of small RNAs GlmY and GlmZ. When GlcN6P becomes limiting, GlmY accumulates and inhibits processing of GlmZ. Full‐length GlmZ base‐pairs with the glmS transcript and activates synthesis of GlmS, which re‐synthesizes GlcN6P. Here we show that glmY expression is controlled by two overlapping promoters with the same transcription start site. A σ70‐dependent promoter contributes to glmY transcription during exponential growth. Alternatively, glmY can be transcribed from a σ54‐dependent promoter, which requires the YfhK/YfhA two‐component system for activity. YfhK is a sensor kinase and YfhA is a response regulator that contains a σ54 interaction domain. YfhA binds to a DNA region located more than 100 bp upstream of glmY. Three copies of the conserved sequence TGTCN10GACA contribute to binding, and the two sites next to glmY are essential for activation of the σ54‐dependent promoter by YfhA. YfhK and YfhA upregulate GlmY when cells enter the stationary growth phase, whereas regulation by glucosamine‐6‐phosphate occurs post GlmY transcription. Target genes regulated by YfhK and YfhA were unknown so far. We propose to rename these proteins to GlrK and GlrR, for glmYregulating kinase and response regulator respectively.
Differential substrate specificity of group I and group II chaperonins in the archaeon Methanosarcina mazei
Authors: Hirtreiter Angela M. , Calloni Giulia , Forner Francesca , Scheibe Burghardt , Puype Magda , Vandekerckhove Joel , Mann Matthias , Hartl F. Ulrich , Hayer‐Hartl Manajit
Published: October 2009

Chaperonins are macromolecular machines that assist in protein folding. The archaeon Methanosarcina mazei has acquired numerous bacterial genes by horizontal gene transfer. As a result, both the bacterial group I chaperonin, GroEL, and the archaeal group II chaperonin, thermosome, coexist. A proteome‐wide analysis of chaperonin interactors was performed to determine the differential substrate specificity of GroEL and thermosome. At least 13% of soluble M. mazei proteins interact with chaperonins, with the two systems having partially overlapping substrate sets. Remarkably, chaperonin selectivity is independent of phylogenetic origin and is determined by distinct structural and biochemical features of proteins. GroEL prefers well‐conserved proteins with complex α/β domains. In contrast, thermosome substrates comprise a group of faster‐evolving proteins and contain a much wider range of different domain folds, including small all‐α and all‐β modules, and a greater number of large multidomain proteins. Thus, the group II chaperonins may have facilitated the evolution of the highly complex proteomes characteristic of eukaryotic cells.
High‐resolution architecture of the outer membrane of the Gram‐negative bacteria Roseobacter denitrificans
Authors: Jarosławski Szymon , Duquesne Katia , Sturgis James N. , Scheuring Simon
Published: October 2009

The outer membrane of Gram‐negative bacteria protects the cell against bactericidal substances. Passage of nutrients and waste is assured by outer membrane porins, beta‐barrel transmembrane channels. While atomic structures of several porins have been solved, so far little is known on the supramolecular structure of the outer membrane. Here we present the first high‐resolution view of a bacterial outer membrane gently purified maintaining remnants of peptidoglycan on the perisplasmic surface. Atomic force microscope images of outer membrane fragments of the size of ∼50% of the bacterial envelope revealed that outer membrane porins are by far more densely packed than previously assumed. Indeed the outer membrane is a molecular sieve rather than a membrane. Porins cover ∼70% of the membrane surface and form locally regular lattices. The potential role of exposed aromatic residues in the formation of the supramolecular assembly is discussed. Finally, we present first structural data of the outer membrane porin from the marine Gram‐negative bacteria Roseobacter denitrificans, and we perform a sequence alignment with porins of known structure.
Surgical management of constipation
Authors: Knowles C. H. , Dinning P. G. , Pescatori M. , Rintala R. , Rosen H.
Published: October 2009

Abstract  This review addresses the range of operations suggested to be of contemporary value in the treatment of constipation with critical evaluation of efficacy data, complications, patient selection, controversies and areas for future research.
Default during TB diagnosis: quantifying the problem
Authors: Khan Mishal S. , Khan Shoaib , Godfrey‐Faussett Peter
Published: October 2009

Objectives  To quantify default during diagnosis in TB suspects and in smear‐positive cases; to investigate sex differences in default during diagnosis, in all of Pakistan.

Methods  Data from laboratory registers were collected on 12 216 suspects in nine districts over the period July–September 2008.

Results  A total of 1573 TB suspects (12.9%, 95% CI = 12.3–13.5) dropped out of the diagnostic process after initial sputum submission. A total of 2058 smear‐positive cases were detected, and of these 107 (5.2%, 95% CI = 4.2–6.2) defaulted during diagnosis and therefore could not be started on treatment. Male suspects defaulted slightly more frequently than female suspects (P = 0.0268).

Conclusion  Default during diagnosis is a frequent occurrence in Pakistan that should be monitored and addressed by TB control programs.
Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure
Authors: Schuttelaar M. L. A. , Kerkhof M. , Jonkman M. F. , Koppelman G. H. , Brunekreef B. , De Jongste J. C. , Wijga A. , McLean W. H. I. , Postma D. S.
Published: October 2009

Background:  Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear.

Methods:  FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure.

Results:  The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4–2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8–7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early‐life cat exposure (ORs being 8.2; 95% CI: 2.6–25.9, 6.0; 95% CI: 3.2–11.3 and 5.4; 95% CI: 1.2–23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5–10.5).

Conclusions:  FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.
Bee venom immunotherapy – how early is it effective?
Authors: Goldberg A. , Confino‐Cohen R.
Published: October 2009

To cite this article: Goldberg A, Confino‐Cohen R. Bee venom immunotherapy – how early is it effective? Allergy 2010; 65: 391–395.

Background:  Although the effectiveness of venom immunotherapy (VIT) in bee venom (BV) allergy has been well established over the past 30 years, no previous study has demonstrated its efficacy immediately after reaching the maintenance dose (MD). We examined the effectiveness of bee VIT within a week after the MD was achieved.

Methods:  Bee venom allergic patients underwent conventional or rush VIT. Within 1 week after reaching the 100 μg MD, patients were challenged with a live bee sting.

Results:  Seventy‐nine of 107 patients (73.8%) who reached the MD agreed to be challenged. Seventy patients (88.6%) tolerated the sting uneventfully. Four patients (5.1%) developed a very mild local transient rash and continued to receive the 100 μg MD. In five patients (6.3%), the sting resulted in a mild‐moderate systemic reaction. In four of these, the MD was increased to 200–250 μg. All four patients uneventfully tolerated a repeated sting that was performed within 1 week after achieving the increased MD in three patients and after 14 months in the fourth patient.

Conclusions:  Bee VIT is effective in most patients immediately after the conventional MD has been reached. In the minority of patients who are not protected with this dose, an increased MD will provide appropriate protection immediately after it is achieved. Thus, the dosage of the MD seems to be the major factor affecting protection from re‐stings rather than the accumulated venom dose or the duration on the MD.
Linkage between smoking and asthma
Authors: Pietinalho A. , Pelkonen A. , Rytilä P.
Published: October 2009

Smoking is one of the most important preventable public health problems. Prevalence of smoking is decreasing in the Western world but lot of work is left. We reviewed the most important papers related to smoking and asthma. Despite of decreasing smoking figures in Finland, about 15–20 per cent of pregnant women smokes. Children's exposure to harmful effects of environmental tobacco smoke (ETS) still continues. Exposure to tobacco smoke during pregnancy and in early childhood both deteriorates permanently children's lungs and increases their asthma risk. The exposure of adults to ETS also increases their asthma risk. Both passive exposure to ETS and active smoking worsen asthma. In addition, smoking asthmatics run a higher risk of developing COPD compared to non‐smokers. Smoking prevalence among the population can be regulated through legislation, but the health care personnel have a central role in encouraging smoking cessation among smoking patients.
Allergic asthma in patients with common variable immunodeficiency
Authors: Agondi R. C. , Barros M. T. , Rizzo L. V. , Kalil J. , Giavina‐Bianchi P.
Published: October 2009

To cite this article: Agondi RC, Barros MT, Rizzo LV, Kalil J, Giavina‐Bianchi P. Allergic asthma in patients with common variable immunodeficiency. Allergy 2010; 65: 510–515.

Background:  Many patients with common variable immunodeficiency (CVID) have a clinical history suggestive of allergic respiratory disease. However, in such individuals, the prevalence of asthma and the role of atopy have not been well established. The objective of this study was to evaluate pulmonary function and identify asthma in patients with CVID. We also investigated the role of IgE as a trigger of asthma in these patients.

Methods:  Sixty‐two patients diagnosed with CVID underwent spirometry, as well as skin prick testing and in vitro determination of serum‐specific IgE levels for aeroallergens, together with bronchial provocation with histamine and allergen.

Results:  The most common alteration identified through spirometry was obstructive lung disease, which was observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62 patients had a clinical history suggestive of allergic asthma. By the end of the study, asthma had been diagnosed in nine (14.5%) patients and atopy had been identified in six (9.7%). In addition, allergic asthma had been diagnosed in four patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical history suggestive of the diagnosis).

Conclusion:  In this study, CVID patients testing negative for specific IgE antibodies and suspected of having allergic asthma presented a positive response to bronchial provocation tests with allergens. To our knowledge, this is the first such study. When CVID patients with a history suggestive of allergic asthma test negative on traditional tests, additional tests designed to identify allergic asthma might be conducted.
Successful implementation of a national HLA‐B*5701 genetic testing service in Canada
Authors: Lalonde R. G. , Thomas R. , Rachlis A. , Gill M. J. , Roger M. , Angel J. B. , Smith G. , Higgins N. , Trottier B.
Published: October 2009

Abstract

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) that is used in combination antiretroviral therapy in HIV‐infected patients. It is currently recommended as a preferred or an alternative NRTI in antiretroviral‐naïve patients. The major toxicity of abacavir is a hypersensitivity reaction (HSR), which occurs in approximately 5% of treated patients. There is a strong association between the human leukocyte antigen (HLA)‐B*5701 allele and abacavir HSR, which has allowed for rapid acceptance of genetic screening for HLA‐B*5701 in clinical use. Canadian clinicians working in hospital centers with HLA typing capacity opted to launch a pilot project in 2006 to offer the screening test as standard of care to HIV‐infected patients. Currently, more than 11,000 HLA‐B*5701 tests have been performed, among which 6.3% are positive. Continued efforts have been made to ensure that testing is available to all HIV‐infected patients to widen the patients' therapeutic options. HLA‐B*5701 screening shows clinical use and preliminary data suggest cost‐effectiveness.