bluuebunny/crossref_metadata_2025 huggingface dataset:
The β-Subunit of the SnRK1 Complex Is Phosphorylated by the Plant Cell Death Suppressor Adi3
Authors: Avila Julian , Gregory Oliver G. , Su Dongyin , Deeter Taunya A. , Chen Sixue , Silva-Sanchez Cecilia , Xu Shouling , Martin Gregory B. , Devarenne Timothy P.
Published: May 2012

The protein kinase AvrPto-dependent Pto-interacting protein3 (Adi3) is a known suppressor of cell death, and loss of its function has been correlated with cell death induction during the tomato (Solanum  lycopersicum) resistance response to its pathogen Pseudomonas syringae pv tomato. However, Adi3 downstream interactors that may play a role in cell death regulation have not been identified. We used a yeast two-hybrid screen to identify the plant SnRK1 (for Sucrose non-Fermenting-1-Related Protein Kinase1) protein as an Adi3-interacting protein. SnRK1 functions as a regulator of carbon metabolism and responses to biotic and abiotic stresses. SnRK1 exists in a heterotrimeric complex with a catalytic α-subunit (SnRK1), a substrate-interacting β-subunit, and a regulatory γ-subunit. Here, we show that Adi3 interacts with, but does not phosphorylate, the SnRK1 α-subunit. The ability of Adi3 to phosphorylate the four identified tomato β-subunits was also examined, and it was found that only the Galactose Metabolism83 (Gal83) β-subunit was phosphorylated by Adi3. This phosphorylation site on Gal83 was identified as serine-26 using a mutational approach and mass spectrometry. In vivo expression of Gal83 indicates that it contains multiple phosphorylation sites, one of which is serine-26. An active SnRK1 complex containing Gal83 as the β-subunit and sucrose nonfermenting4 as the γ-subunit was constructed to examine functional aspects of the Adi3 interaction with SnRK1 and Gal83. These assays revealed that Adi3 is capable of suppressing the kinase activity of the SnRK1 complex through Gal83 phosphorylation plus the interaction with SnRK1 and suggested that this function may be related to the cell death suppression activity of Adi3.
Lymph node‐induced immune tolerance in chronic lymphocytic leukaemia: a role for caveolin‐1
Authors: Gilling Christine E. , Mittal Amit K. , Chaturvedi Nagendra K. , Iqbal Javeed , Aoun Patricia , Bierman Philip J. , Bociek Robert G. , Weisenburger Dennis D. , Joshi Shantaram S.
Published: May 2012

Emerging evidence indicates that the tumour microenvironment (TME) regulates the behaviour of chronic lymphocytic leukaemia (CLL). However, the precise mechanism and molecules involved in this process remain unknown. Gene expression profiles of CLL cells from lymph node (LN), bone marrow (BM) and peripheral blood (PB) indicate overexpression of a tolerogenic signature in CLL cells in lymph nodes (LN‐CLL). Based on their role in B cell biology, the progression of CLL, or immune regulation, a few genes of this 83‐gene signature were selected for further analyses. We observed a significant correlation between the clinical outcomes and the expression of CAV1 (P = 0·041), FGFR1 isoform 8 (P = 0·032), PTPN6 (P = 0·031) and ZWINT (P < 0·001). CAV1, a molecule involved in the regulation of tumour progression in other cancers, was seven‐fold higher in LN‐CLL cells compared to BM‐ and PB‐CLL cells. Knockdown of CAV1 expression in CLL cells resulted in significantly decreased migration (P = 0·016) and proliferation (P = 0·04). When CAV1 was knocked down in B and T cell lines, we observed an inability to form immune synapses. Furthermore, CAV1 knockdown in CLL cells impaired their ability to form immune synapses with autologous T lymphocytes and allogeneic, healthy T cells. Subsequent analyses of microarray data showed differential expression of cytoskeletal genes, specifically those involved in actin polymerization. Therefore, we report a novel role for CAV1 in tumour‐induced immunosuppression during the progression of CLL.
Study of the D‐‐ phenotype reveals erythrocyte membrane alterations in the absence of RHCE
Authors: Flatt Joanna F. , Musa Rozi H. , Ayob Yasmin , Hassan Afifah , Asidin Norhanim , Yahya Nurul M. , Mathlouthi Rosalind , Thornton Nicole , Anstee David J. , Bruce Lesley J.
Published: May 2012

Red cells with the D‐‐ phenotype do not express the RHCE protein because of mutations in both alleles of the RHCE gene. At present, little is known of the effect this has on the normal function of erythrocytes. In this study a group of five families belonging to a nomadic tribe in Malaysia were identified as carriers of the D‐‐ haplotype. Analysis of homozygous individuals' genomic DNA showed two separate novel mutations. In four of the families, RHCE exons 1, 9 and 10 were present, while the 5th family possessed RHCE exons 1–3 and 10. Analysis of cDNA revealed hybrid transcripts, suggesting a gene conversion event with RHD, consistent with previously reported D‐‐ mutations. Immunoblotting analysis of D‐‐ erythrocyte membrane proteins found that Rh‐associated glycoprotein (RHAG) migrates with altered electrophoretic mobility on sodium dodecyl sulphate polyacrylamide gel electrophoresis, consistent with increased glycosylation. Total amounts of Rh polypeptide in D‐‐ membranes were comparable with controls, indicating that the exalted D antigen displayed by D‐‐ red cells may be associated with altered surface epitope presentation. The adhesion molecules CD44 and CD47 are significantly reduced in D‐‐. Together these results suggest that absence of RHCE polypeptide alters the structure and packing of the band 3/Rh macrocomplex.
Polymorphisms in VKORC1 have more impact than CYP2C9 polymorphisms on early warfarin International Normalized Ratio control and bleeding rates
Authors: Lund Kirstin , Gaffney Dairena , Spooner Richard , Etherington Anne Marie , Tansey Patrick , Tait Robert Campbell
Published: May 2012

Poor warfarin control with resultant high International Normalized Ratios (INRs) and bleeding events is most common during the first months of treatment. The effects of genetic polymorphisms at the vitamin K epoxide reductase [VKORC1] and cytochrome P450 2C9 [CYP2C9] loci have been increasingly acknowledged as contributory factors of enhanced warfarin sensitivity. In our prospective, blinded study, 557 patients (49·1% male, mean age 65·4 years, range 18–91 years) commencing warfarin (target INR 2·5) were genotyped and monitored through the first 3 months of anticoagulation. Homozygosity for the −1639 G>A single nucleotide functional promoter polymorphism of the VKORC1 gene (genotype AA; 14·5% of cases) was associated with a significantly shortened time to therapeutic INR ≥ 2 (P < 0·01), reduced stable warfarin dose (P < 0·01), and an increased number of INRs > 5 (P < 0·001) and occurrence of bleeding events (P < 0·01) during the first month, as compared to the GG genotype. CYP2C9 genetic variations *2 and *3 were not associated with significant effect on these factors. Neither VKORC1 nor CYP2C9 polymorphisms influenced these parameters beyond the first month of treatment. These findings imply possible benefits of assessing VKORC1 polymorphisms prior to anticoagulation, particularly as a low dose induction regime in VKORC1 AA individuals appears to reduce the incidence of high INRs.
How I manage priapism in chronic myeloid leukaemia patients
Authors: Rodgers Ryan , Latif Zak , Copland Mhairi
Published: May 2012

Priapism is a rare presenting feature of chronic myeloid leukaemia (CML). It is a urological emergency requiring urgent treatment to prevent long‐term complications, in particular erectile dysfunction. In males with CML, ischaemic priapism is believed to result from hyperleucocytosis and associated leucostasis or hyperviscosity, and is seen in patients presenting with a high white cell count. Increasingly, a combined modality approach is being used to treat CML patients presenting with priapism. This includes systemic therapy with chemotherapy (hydroxycarbamide or tyrosine kinase inhibitors) and therapeutic leukapheresis to reduce the white cell count as well as local intracavernous therapy. This review will examine the literature and discuss the presenting features, investigations and management of priapism in CML.
Neridronate improves bone mineral density and reduces back pain in β‐thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel‐arm, open‐label study
Authors: Forni Gian Luca , Perrotta Silverio , Giusti Andrea , Quarta Giovanni , Pitrolo Lorella , Cappellini Maria Domenica , D'Ascola Domenico Giuseppe , Borgna Pignatti Caterina , Rigano Paolo , Filosa Aldo , Iolascon Giovanni , Nobili Bruno , Baldini Marina , Rosa Alessandra , Pinto Valeria , Palummeri Ernesto
Published: May 2012

Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open‐label study, 118 adults with β‐thalassaemia and bone mineral density (BMD) Z scores ≤−2·0 were randomized 1:1–500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P < 0·001), and values were significantly higher than the control group at both time intervals. Neridronate also significantly decreased serum bone alkaline phosphatase and C‐telopeptide of collagen type 1 levels from as early as 3 months (P = 0·04 and P < 0·001, respectively), reaching significantly lower values at 12 months compared with the control group (P < 0·05). Reductions in back pain and analgesic use were also evident, starting 3 months from commencing treatment. Treatment was well tolerated by all patients. In this largest randomized trial in thalassaemia‐induced osteoporosis to date, neridronate was safe and effective in reducing bone resorption and increasing BMD. The associated reduction in back pain and improved quality of life will encourage adherence to therapy. (Clinicaltrials.gov identifier NCT01140321.)
A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy‐induced febrile neutropenia in children
Authors: Caselli Désirée , Cesaro Simone , Ziino Ottavio , Ragusa Pietro , Pontillo Alfredo , Pegoraro Anna , Santoro Nicola , Zanazzo Giulio , Poggi Vincenzo , Giacchino Mareva , Livadiotti Susanna , Melchionda Fraia , Chiodi Marcello , Aricò Maurizio
Published: May 2012

Given that the rationale for empirical antifungal therapy in neutropenic children is limited and based on adult patient data, we performed a prospective, randomized, controlled trial that evaluated 110 neutropenic children with persistent fever. Those at high risk for invasive fungal infections (IFI) received caspofungin (Arm C) or liposomal amphotericinB (Arm B); those with a lower risk were randomized to receive Arm B, C, or no antifungal treatment (Arm A). Complete response to empirical antifungal therapy was achieved in 90/104 patients (86·5%): 48/56 at high risk (85·7%) [88·0% in Arm B; 83·9% in Arm C (P = 0·72)], and 42/48 at low risk (87·5%) [87·5% in control Arm A, 80·0% Arm B, 94·1% Arm C; (P = 0·41)]. None of the variables tested by multiple logistic regression analysis showed a significant effect on the probability to achieve complete response. IFI was diagnosed in nine patients (8·2%, 95% confidence interval, 3·8–15·0). This randomized controlled study showed that empirical antifungal therapy was of no advantage in terms of survival without fever and IFI in patients aged <18 years and defined with low risk of IFI. Higher risk patients, including those with relapsed cancer, appear to be the target for empirical antifungal therapy during protracted febrile neutropenia.
Secreted factors from adipose tissue increase adipogenic differentiation of mesenchymal stem cells
Authors: Wu L. , Wang T. , Ge Y. , Cai X. , Wang J. , Lin Y.
Published: May 2012

Objectives

Adipose tissue engineering is one of the hottest topics in the field of regenerative medicine. Fat tissue has been considered as an abundant and accessible source of adult stem cells by tissue engineers, since it gives rise to adipose stem cells. However, recent reports have pointed out that adipose tissue, as a secretory and endocrine organ, might secrete cytokines that regulate body functions such as metabolism, infammation and more. In this study, we aim to investigate the adipogenic‐inducing factors secreted by fat tissue.

Materials and methods

Conditioned medium were collected by culturing fat tissue fragments in plastic flasks. Mesenchymal stem cells (MSCs) cultured in conditioned medium (CM) to test the adipogenic‐inducing factors. Oil red O staining, reverse transcription/polymerase chain reaction and immunocytofluorescent staining were performed to examine the differentiation of MSCs in CM.

Results

MSCs cultured in CM of adipose tissue spontaneously differentiated into adipocytes. Furthermore, supplementation of insulin or dexamethasone to CM accelerated the process of lipid accumulation of differentiated MSCs.

Discussion

Results from this study demonstrated that fat tissues secrete small molecules, which induce adipogenic differentiation of MSCs.

Conclusions

Our study provides clues for improving adipose tissue engineering by using fragmented adipose tissue as sources of fat‐inducing factors.
The social networks of young people in Ireland with experience of long‐term foster care: some lessons for policy and practice
Authors: Mc Mahon Conor , Curtin Chris
Published: May 2012

This paper presents findings from the first study of the social networks of a group of young people in Ireland who have experienced long‐term foster care. The study group was composed of two groups of young people, a group who were currently in care and a group who had left the care system. The central focus was to examine the impact of foster care on the social network experience of the young people. Findings indicated that foster care impacts on the young people's social network experience in the following ways: losing contact with extended family; a greater challenge in making and sustaining friendships; an impact on education; and an inability to maintain contact with groups and activities that are of significance. This paper also presents recommendations in relation to policy and practice, including the raising of awareness of the importance of a social network approach in working with young people with care experience.
The science of attracting foster carers
Authors: Randle Melanie , Miller Leonie , Dolnicar Sara , Ciarrochi Joseph
Published: May 2012

Across the world the number of children needing a foster home is increasing; however, the number of individuals willing to foster a child is decreasing. It is therefore critical to gain insight into the barriers preventing people from fostering a child. Using data from a 2009 survey of 756 Australians, combinations of barriers are investigated by conducting a posteriori segmentation analysis within the market of potential foster carers. Four segments are identified and profiled to determined significant differences in terms of psychological and socio‐demographic characteristics. Findings, including the fact that almost one‐third of respondents indicated that they had not considered foster caring before because no one had ever asked them to, have practical implications. Improved marketing strategies tailored to the characteristics of each segment are required to harvest the full potential of individuals willing to foster a child and thus contribute to solving one of the most difficult social challenges facing developed nations.
Down syndrome, autoimmunity and T regulatory cells
Authors: Pellegrini F P , Marinoni M , Frangione V , Tedeschi A , Gandini V , Ciglia F , Mortara L , Accolla R S , Nespoli L
Published: May 2012

Autoimmune diseases are more represented in Down syndrome (DS) individuals compared to chromosomally normal people. Natural T regulatory cells (nTreg) have been considered to be primary in the role of controlling the intensity and targets of the immune response. We have investigated the phenotypical and functional alteration of nTreg in a group of DS people. The phenotypical characteristic of Treg cells of 29 DS was analysed and compared with an age-matched healthy control group. The inhibitory potential of CD4+CD25highCD127low T regulatory cells was evaluated on autologous CD4+CD25– T cell proliferation in response to activation with a mytogenic pan-stimulus (anti-CD2, anti-CD3 and anti-CD28 antibodies). The CD4+CD25high cells in the DS and control groups were 2·692 ± 0·3808%, n = 29 and 1·246 ± 0·119, n = 29%, respectively (P = 0.0007), with a percentage of forkhead box protein 3 (FoxP3)-expressing cells of 79·21 ± 3·376%, n = 29 and 59·75 ± 4·496%, respectively (P = 0.0015). CD4+CD25+FoxP3+ cells were increased in peripheral blood from DS subjects (DS mean 5·231 ± 0·6065% n = 29, control mean 3·076 ± 0·3140% n = 29). The majority of CD4+CD25high were CD127low and expressed a high percentage of FoxP3 (natural Treg phenotype). While the proliferative capacity of DS T cells was not altered significantly compared to normal individuals, a reduced inhibitory potential of Treg compared to healthy controls was clearly observed (mean healthy control inhibition in Teff : Treg 1:1 co-culture: 58·9% ± 4·157%, n = 10 versus mean DS inhibition in Teff : Treg 1:1 co-culture: 39·8 ± 4·788%, n = 10, P = 0.0075; mean healthy control inhibition in Teff : Treg 1:0·5 co-culture: 45·10 ± 5·858%, n = 10 versus DS inhibition in Teff : Treg 1:0·5 co-culture: 24·10 ± 5·517%, n = 10, P = 0.0177). DS people present an over-expressed peripheral nTreg population with a defective inhibitory activity that may partially explain the increased frequency of autoimmune disease.
Low‐grade systemic inflammation and suboptimal bone mineral density throughout adolescence: a prospective study in girls
Authors: Lucas Raquel , Ramos Elisabete , Oliveira Andreia , Monjardino Teresa , Barros Henrique
Published: May 2012

Objective

We aimed at quantifying the associations between high‐sensitivity C‐reactive protein (hs‐CRP) and forearm bone mineral density (BMD) throughout adolescence in overweight and normal‐weight girls.

Design

Prospective cohort study.

Patients

346 girls born in 1990 and attending schools in Porto, Portugal.

Measurements

Adolescents were evaluated at 13 and 17 years of age using a standard protocol. Forearm BMD was measured by dual‐energy X‐ray absorptiometry. Anthropometric assessment included weight, height, body fat percentage and waist circumference. Girls were categorized according to age‐ and sex‐specific body mass index (BMI) percentiles as normal weight in both evaluations or overweight in at least one assessment. Pubertal development was estimated using menarche age. Serum hs‐CRP was determined using particle‐enhanced immunonephelometry. Hs‐CRP was log‐transformed, and associations were quantified using linear regression coefficients and 95% confidence intervals (95%CI).

Results

An inverse association between hs‐CRP and BMD was observed from 13 years of age in overweight girls [−11·26 mg/cm2 (−21·99, −0·52)]. Among normal‐weight adolescents, 13‐year‐old hs‐CRP was negatively associated with prospective BMD variation between 13 and 17 years of age [−1·90 mg/cm2 year (−3·35, −0·45)]. Overweight girls who maintained higher levels of hs‐CRP throughout adolescence had lower 17‐year‐old BMD (adjusted mean 0·441 vs 0·483 g/cm2 in those who remained with lower levels of hs‐CRP). At 17 years of age, significant inverse associations were found between hs‐CRP and BMD among normal‐weight and overweight girls.

Conclusions

Obesity‐related early systemic inflammation might be involved in suboptimal bone accrual, particularly in overweight girls.
Vitamin D in the aetiology and management of polycystic ovary syndrome
Authors: Thomson Rebecca L. , Spedding Simon , Buckley Jonathan D.
Published: May 2012

Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS), with the 67–85% of women with PCOS having serum concentrations of 25‐hydroxy vitamin D (25OHD) <20 ng/ml. Vitamin D deficiency may exacerbate symptoms of PCOS, with observational studies showing lower 25OHD levels were associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity and elevated cardiovascular disease risk factors. There is some, but limited, evidence for beneficial effects of vitamin D supplementation on menstrual dysfunction and insulin resistance in women with PCOS. Vitamin D deficiency may play a role in exacerbating PCOS, and there may be a place for vitamin D supplementation in the management of this syndrome, but current evidence is limited and additional randomized controlled trials are required to confirm the potential benefits of vitamin D supplementation in this population.
Growth hormone reduces growth in free‐living Atlantic salmon fry
Authors: Sundt‐Hansen Line , Einum Sigurd , Neregård Lena , Björnsson Björn Thrandur , Johnsson Jörgen I. , Fleming Ian A. , Devlin Robert H. , Hindar Kjetil
Published: May 2012

1. Although life‐history theory predicts that juvenile growth rates should be high, there is substantial evidence that most juveniles grow below their physiological maximum. The endocrine system plays an important role in the determination of fundamental life‐history traits, and hormones often serve as a link between an organism’s environment and the expression of a trait. Particularly, growth is a life‐history trait, which is strongly associated with growth hormone (GH) in fish, as well as most vertebrates.

2. To elucidate trade‐offs related to elevated GH in fish in a natural environment, we experimentally administrated GH exogenously to juvenile Atlantic salmon using sustained‐release GH implants, at an earlier ontogenetic stage than previously achieved (1·5 months). We assessed the effects on growth, dispersal and survival in contrasting environments.

3. Exogenous GH treatment increased the growth rate when fish were fedad libitumin captivity. However, in a natural stream, GH treatment had a significant negative effect on growth and no apparent effect on survival or dispersal. This contrasts with previous studies conducted at later developmental stages, which show either a positive growth effect or no effect of elevated GH levels.

4. This study shows that environmental conditions strongly affect the response to GH and that under some natural conditions, it may also reduce growth. We suggest that the endogenous plasma GH levels may be maximizing growth during early, but not later, juvenile stages in nature.
Influence of cold chain interruptions on the shelf life of fresh pork and poultry
Authors: Bruckner Stefanie , Albrecht Antonia , Petersen Brigitte , Kreyenschmidt Judith
Published: May 2012

In this study, the influence of fluctuations of the cold chain on the growth of Pseudomonas spp. on fresh pork and poultry and, therefore, their shelf life was evaluated. Thus, four storage trials were examined. In each trial, shelf life at the control scenario (4 °C, constant) was compared with shelf life at two dynamic scenarios including temperature shifts from 4 to 7 and to 15 °C, respectively. Overall, fresh pork and fresh poultry showed similar spoilage patterns at dynamic temperature conditions with remarkable reductions in the shelf life when short temperature upshifts occurred at the beginning of the storage. Reductions were up to 2 days (up to over 30%), although the storage time with an abusive temperature was <5% of the total storage time. As expected, scenarios with shifts to 15 °C led to higher shelf life reductions than scenarios with shifts to 7 °C for both meat types.
Analysis of odour‐active compounds of black mangrove (Avicennia germinans L.) honey by solid‐phase microextraction combined with gas chromatography–mass spectrometry and gas chromatography–olfactometry
Authors: Pino Jorge A.
Published: May 2012

The volatile compounds of Cuban black mangrove (Avicennia germinans L.) honey were analysed by solid‐phase microextraction (SPME) followed by gas chromatography–mass spectrometry and gas chromatography–olfactometry. A total of 66 compounds were positively identified in this product for the first time. Application of the aroma extract dilution analysis in a novel approach, which consisted of carrying out successively dilutions of the honey sample with a synthetic honey before the SPME, revealed 17 odour‐active areas in the flavour dilution factor range of 32–1024. On the basis of the quantitative data and odour thresholds, odour activity values (OAV; ratio of concentration to odour threshold) were calculated. Sixteen compounds showed OAVs >1, among which dimethyl sulphide, 3‐methyl butanal, 2‐methylbutanal, heptanal, octanal, phenylacetaldehyde, (Z)‐linalool oxide, (E)‐linalool oxide, nonanal, hotrienol, isophorone, lilac aldehyde A, 1‐nonanol, decanal, 4‐vinyl‐2‐methoxyphenol and (E)‐β‐damascenone showed the highest values and should be considered as the most odour‐active compounds, particularly (E)‐β‐damascenone, nonanal and decanal.
Gender and abiotic stress affect community‐scale intensity of facilitation and its costs
Authors: Cranston Brittany H. , Callaway Ragan M. , Monks Adrian , Dickinson Katharine J. M.
Published: May 2012

1. Facilitation allows some plant species to occupy environments that they are otherwise unable to inhabit, potentially leading to greater fitness, greater productivity or abundance, and range expansions. However, we know little about the costs incurred by facilitators or how variation in resource allocation by facilitators influences effects and costs.

2. Gynodioecy provides an opportunity to explore the effects of facilitation and potential costs because females and hermaphrodites differ in resource allocation patterns. We explored whether environmental stress and gender‐specific facilitation influence species interactions in an alpine plant community. We investigated the degree of facilitation and correlative associated costs for the gynodioecious alpine plant,Silene acaulis, at two elevations (2317 and 2560 m) in the northern Rocky Mountains of Montana, USA.

3. Hermaphroditic Silene individuals supported a greater number of plant species and individual plants than female Silene (hermaphrodites = 4.2 ± 0.3, females = 3.5 ± 0.2; hermaphrodites = 11.5 ± 1.0, females = 9.1 ± 1.1). Facilitative effects on species richness significantly increased with elevation (2.1 ± 1.6 species at the low site vs. 3.2 ± 1.8 species at the high site), but abundance and percentage cover did not.

4. Silene fitness at the high elevation site (2560 m) was reduced compared to the lower site (2317 m) as measured by flower and seed production. Female flower production decreased by 40%, the number of seeds per fruit by 11.6% and leaf size by 24%.

5. Increases in the percentage cover of beneficiaries reduced the number of flowers per Silene plant, indicating a cost of facilitating other species, and this cost was slightly greater for females. However, seed size for hermaphrodites and leaf length for females increased with the percentage cover of beneficiaries, suggesting a mutual benefit of harbouring other species.

6. Synthesis.Our results show that gender can affect the balance between competitive and facilitative interactions. Stronger facilitation by hermaphroditicSilene acaulis, coupled with a lower cost of harbouring beneficiaries, suggests that life‐history traits and related patterns of resource allocation can influence the facilitative effects of a species.
Development of a multiplex polymerase chain reaction to detect five common Gram‐negative bacteria of aquatic animals
Authors: Tsai M‐A , Ho P‐Y , Wang P‐C , E Y‐J , Liaw L‐L , Chen S‐C
Published: May 2012

A multiplex polymerase chain reaction (m‐PCR) technique was developed as a rapid and accurate diagnostic tool for identifying five major Gram‐negative bacilli –Vibrio vulnificus, V. parahaemolyticus, Aeromonas hydrophila, Chryseobacterium meningosepticum and Edwardsiella tarda– that cause major diseases in cultured aquatic animals in Taiwan. The expected amplicons for V. vulnificus, V. parahaemolyticus, A. hydrophila, C. meningosepticum and E. tarda were 410, 368, 685, 180 and 230 bp, respectively. The assay was shown to be specific for the target pathogens. The sensitivities of detection were estimated to be 20.5 fg∼200 pg of genomic DNA or 102∼104 colony‐forming units (cfu) of bacterial isolates when adopted as PCR templates. The m‐PCR was capable of simultaneously amplifying target fragments from bacterial genome DNA mixed with the DNA extracted from viscera and tissues taken from fish without affecting the performance of the method.
Clinical performance of long‐span zirconia frameworks for fixed dental prostheses: 5‐year results
Authors: SCHMITTER M. , MUSSOTTER K. , RAMMELSBERG P. , GABBERT O. , OHLMANN B.
Published: May 2012

Summary  The purpose of this prospective cohort study was to assess the performance of tooth‐supported, long‐span, zirconia fixed dental prostheses (FDPs). Thirty FDPs with span lengths from 36 to 46 mm (mean 40·33 mm), with 4–7 units and with connector dimensions ∼9 mm2 were inserted (19 in the posterior region, 11 including anterior teeth) using glass–ionomer cement. The performance of the FDPs was assessed (aesthetic evaluation, failures, hypersensitivity/tooth vitality, secondary caries, pocket depth, decementation, and chipping) at baseline and after 5 years. Cox regression analysis was performed to identify risk factors. There were 16 failures after 5 years. Framework fracture occurred for two FDPs, four FDPs had to be re‐cemented, one abutment tooth had to be treated endodontically, one abutment tooth fractured and cohesive failure of the veneer occurred for eight. Four FDPs had to be replaced, so survival was 82%. The aesthetics were rated as excellent by the patients at baseline and good at the 5‐year recall. Cox regression analysis showed that both length [P = 0·05, exp(B) = 1·22] and location [P = 0·019, exp(B) = 4·09] of the FDP were risk factors for failure. Compared with the previously published 2‐year results, the incidence of complications increased dramatically. Additionally, it was shown that long‐span FDPs in the molar region are at greater risk of failure than FDPs in the anterior region.
Factors associated with access to antiviral treatment in a multicentre cross‐sectional study of patients with chronic hepatitis B in Italy
Authors: Antonucci G. , Mazzotta F. , Puoti M. , Angeletti C. , Girardi E. , Santantonio T. , Ambu S. , Gaeta G. B. , Colucci M. , Angarano G. , Marino N. , Rinaldi R. , Bellissima P. , Armignacco O. , Carosi G. , Sagnelli E. ,   on behalf of the Coorte Epatiti B SIMIT (COESI‐B) Group
Published: May 2012

Summary.  A multicentre cross‐sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg‐positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1–1.3, P < 0.001), HBeAg positivity (aOR 1.8, 95% CI 1.1–2.8, P < 0.001), cirrhosis (aOR 3.6, 95% CI 2–6.3, P = 0.012), HDV (aOR 1.6, 95% CI 1.02–2.5, P = 0.042) and HIV positivity (aOR 6.5, 95% CI 4–10.8, P < 0.001). Conversely, a decreased chance was associated with female gender (aOR 0.6, 95% CI 0.5–0.7, P < 0.001), immigration (aOR 0.6, 95% CI 0.5–0.9, P = 0.009), alcohol consumption (aOR 0.7, 95% CI 0.5–0.98, P = 0.04) and HCV positivity (aOR 0.5, 95% CI 0.3–0.8, P = 0.005). Our study shows that Italian IDCs treat a high percentage of patients with CHB. Nevertheless, disparities exist which are not related to the severity of disease limiting access to antiviral therapy of CHB, even in a country with a universal healthcare system.
Prevalence of hepatitis B virus infection among persons with diagnosed diabetes mellitus in the United States, 1999–2010*
Authors: Schillie S. F. , Xing J. , Murphy T. V. , Hu D. J.
Published: May 2012

Summary.  The prevalence of hepatitis B virus (HBV) infection among persons with diabetes has not been assessed among the US population, despite increasing reports of HBV transmission in institutional care settings. Using national survey data, we found a 60% higher prevalence of HBV infection among persons with (vs without) diagnosed diabetes.
The impact and implications of climate change for bats
Authors: Sherwin Hayley A. , Montgomery W. Ian , Lundy Mathieu G.
Published: May 2012

Climate influences the biogeography of bats, their access to food, timing of hibernation, reproduction and development, frequency and duration of torpor and rate of energy expenditure.

Empirical data on the impact of climate change on bats are a cause for concern as current increases in global temperature are one fifth, or less, of those expected over the next century.

We review observed impacts of climate change on bats and identify risk factors allowing species‐specific predictions.

The impact on species is reviewed in relation to six aspects, namely foraging, roosting, reproduction, biogeography, extreme weather events and indirect effects of climate change. For some aspects of species' ecology, there are insufficient data available to make accurate assessment of impacts.

We identify seven risk factors encompassing three broad aspects: biogeography – small range size, high latitude or high altitude range and a range occupying a geographic area likely to become water stressed; foraging niche – frugivory and species restricted to aerial hawking; dispersal ability – species with restricted dispersal behaviour.

We use the European and north‐west African bats as a case study to assess the relative risk of climate change to individual species. Risk scores are compared with existing International Union for Conservation of Nature conservation assessments providing further insight into the conservation outlook for individual species.

We provide a base for Chiroptera to be incorporated into future frameworks of risk assessment and identify areas that require further research.
Extending the tools of single‐molecule fluorescence imaging to problems in microbiology
Authors: Biteen Julie S.
Published: May 2012

Single‐molecule fluorescence microscopy enables non‐invasive, high‐sensitivity, high‐resolution imaging, and this direct, quantitative method has recently been extended to understanding organization, dynamics and cooperativity of macromolecules in prokaryotes. In this issue of Molecular Microbiology, Bakshi et al. (2012) examine fluorescently labelled ribosomes and RNA polymerase (RNAP) in live Escherichia coli cells. By localizing individual molecules with 30 nm scale accuracy, they resolve the spatial distribution of RNAP (and thus of the E. coli nucleoid) and of the ribosomes, measure diffusion rates, and sensitively count protein copy numbers. This work represents an exciting achievement in terms of applying biophysical methods to live cells and quantitatively answering important questions in physiologically relevant conditions. In particular, the authors directly relate the positions, dynamics, and numbers of ribosomes and RNAP to transcription and translation in E. coli. The results indicate that, since the ribosomes and the nucleoid are well segregated, translation and transcription must be predominantly uncoupled. As well, the radial extension of ribosomes and RNAP to the cytoplasmic membrane is consistent with the hypothesis of transertion (simultaneous insertion of membrane proteins upon translation).
Francisella tularensis tmRNA system mutants are vulnerable to stress, avirulent in mice, and provide effective immune protection
Authors: Svetlanov Anton , Puri Neha , Mena Patricio , Koller Antonius , Karzai A. Wali
Published: May 2012

Through targeted inactivation of the ssrA and smpB genes, we establish that the trans‐translation process is necessary for normal growth, adaptation to cellular stress and virulence by the bacterial pathogen Francisella tularensis. The mutant bacteria grow slower, have reduced resistance to heat and cold shocks, and are more sensitive to oxidative stress and sublethal concentrations of antibiotics. Modifications of the tmRNA tag and use of higher‐resolution mass spectrometry approaches enabled the identification of a large number of native tmRNA substrates. Of particular significance to understanding the mechanism of trans‐translation, we report the discovery of an extended tmRNA tag and extensive ladder‐like pattern of endogenous protein‐tagging events in F. tularensis that are likely to be a universal feature of tmRNA activity in eubacteria. Furthermore, the structural integrity and the proteolytic function of the tmRNA tag are both crucial for normal growth and virulence of F. tularensis. Significantly, trans‐translation mutants of F. tularensis are impaired in replication within macrophages and are avirulent in mouse models of tularemia. By exploiting these attenuated phenotypes, we find that the mutant strains provide effective immune protection in mice against lethal intradermal, intraperitoneal and intranasal challenges with the fully virulent parental strain.
BslA(YuaB) forms a hydrophobic layer on the surface of Bacillus subtilis biofilms
Authors: Kobayashi Kazuo , Iwano Megumi
Published: May 2012

Biofilms are surface‐associated bacterial aggregates, in which bacteria are enveloped by polymeric substances known as the biofilm matrix. Bacillus subtilis biofilms display persistent resistance to liquid wetting and gas penetration, which probably explains the broad‐spectrum resistance of the bacteria in these biofilms to antimicrobial agents. In this study, BslA (formerly YuaB) was identified as a major contributor to the surface repellency of B. subtilis biofilms. Disruption of bslA resulted in the loss of surface repellency and altered the biofilm surface microstructure. BslA localized to the biofilm matrix in an exopolysaccharide‐dependent manner. Purified BslA exhibited amphiphilic properties and formed polymers in response to increases in the area of the air–water interface in vitro. Genetic and biochemical analyses showed that the self‐polymerization activity of BslA was essential for its ability to localize to the biofilm matrix. Confocal laser scanning microscopy showed that BslA formed a layer on the biofilm surface. Taken together, we propose that BslA, standing for biofilm‐surface layer protein, is responsible for the hydrophobic layer on the surface of biofilms.
Developmental origins of neural tumours: old idea, new approaches
Authors: Phoenix T. N. , Currle D. S. , Robinson G. , Gilbertson R. J.
Published: May 2012

T. N. Phoenix, D. S. Currle, G. Robinson and R. J. Gilbertson (2012) Neuropathology and Applied Neurobiology38, 222–227

Developmental origins of neural tumours: old idea, new approaches

The recent convergence of pathology, cancer research and basic neurobiology disciplines is providing unprecedented insights to the origins of brain tumours. This new knowledge holds great promise for patients, transforming the way we view and develop new treatments for these devastating diseases.
An inhibitory effect of the sequence‐conserved upstream open‐reading frame on the translation of the main open‐reading frame of HsfB1 transcripts in Arabidopsis
Authors: ZHU XUJUN , THALOR SUNIL KUMAR , TAKAHASHI YOSHIHIRO , BERBERICH THOMAS , KUSANO TOMONOBU
Published: May 2012

Plants have as many as 20 heat shock factors (Hsfs) grouped into three classes, A, B and C, based on sequence similarity and modular structures. Through screening for cell death‐inducing factor(s) in Nicotiana benthamiana, we identified Arabidopsis HsfB2b and thus subjected all other members of Arabidopsis Hsf class B (HsfB1, HsfB2a, HsfB2b, HsfB3 and HsfB4) to the same cell death assay. When expressed in N. benthamiana leaves, only HsfB1 and HsfB2b elicited mild cell death. Simultaneously we found that HsfB1 has a post‐transcriptional control mechanism, in which a sequence‐conserved upstream open‐reading frame (sc‐uORF) is involved. The known repressor function of the respective HsfBs was confirmed and the difference in cell death‐inducing activity of HsfBs was explained by the fact that HsfB1 and HsfB2b are transcriptional repressors but the others are not. Indeed, the cell death symptom by HsfB1 and HsfB2b required not only their repression activity but also their nuclear localization activity. HsfB1 expression was drastically and transiently induced by heat shock (HS) and the intactness of sc‐uORF was required for its HS response. Based on the results, the physiological significance of cell death‐inducing activity of HsfB1 and HsfB2b and the sc‐uORF in the HsfB1 transcript during HS response is discussed.
Diagnosis of asthma – a new approach
Authors: Löwhagen O.
Published: May 2012

Current definition of asthma involves four cornerstones: inflammation, hyperresponsiveness, bronchoconstriction, and symptoms. In research, the symptoms have had the slightest attention. According to international guidelines, the asthma symptoms are episodic breathlessness, wheeze, cough, tightness of the chest, and shortness of breath. As there are several symptoms, a primary question is how they are related to bronchoconstriction, the main clinical feature of asthma. Symptoms and lung function tests are regularly used for the evaluation of clinical health status and effect of treatment. However, there is no or poor correlation between these two variables, which means that they represent different mechanisms. Reduced lung function, such as a low FEV1, represents bronchial constriction, what do the symptoms represent? Some symptoms such as breathlessness and shortness of breath seem not to be evidence‐based asthma symptoms. Focusing on bronchial obstruction is important in view of the potential risk of asthma attacks, but nonobstructive symptoms occur frequently and may also cause severe discomfort and poor quality of life. Interpreting all symptoms as signs of bronchoconstriction (asthma) may lead to misinterpretation when assessing health status and effect of treatment. Although a ‘soft’ variable, the strength of symptoms is that they are representing various mechanisms. The physiological preconditions for control and defense of respiration must be considered in the diagnostic process, regardless of inflammation, allergy, psychology, or other etiological factors. Based on studies on dyspnea in cardiopulmonary diseases, including asthma and asthma‐like disorders, there seems to be a continuous spectrum of symptoms and mechanisms integrated in a single asthma syndrome.
SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V
Authors: Sánchez‐Ferrero E , Coto E , Beetz C , Gámez J , Corao AI , Díaz M , Esteban J , del Castillo E , Moris G , Infante J , Menéndez M , Pascual‐Pascual SI , López de Munaín A , Garcia‐Barcina MJ , Alvarez V
Published: May 2012

Sánchez‐Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual‐Pascual SI, López de Munaín A, Garcia‐Barcina MJ, Alvarez V on behalf of the Genetics of Spastic Paraplegia study group. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.

Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.
Interleukin‐6 promoter polymorphism and plasma levels in patients with schizophrenia
Authors: Zakharyan R. , Petrek M. , Arakelyan A. , Mrazek F. , Atshemyan S. , Boyajyan A.
Published: May 2012

Schizophrenia is a severe psychiatric disease with inflammatory component. Several studies indicated the increased blood levels of proinflammatory interleukin‐6 cytokine in schizophrenia. However, only limited studies explored the relationship between excess production and genetic variations of this cytokine in schizophrenia, and the results were controversial. Here, we investigated possible association of the interleukin‐6 gene (IL6) rs1800795 (–174G/C) polymorphism with schizophrenia and relationship between this polymorphism and interleukin‐6 protein (IL‐6) blood levels. This polymorphism was found by other researchers to associate with different transcription rates and different plasma levels of IL‐6. A total of 208 unrelated Armenians were genotyped by polymerase chain reaction with sequence‐specific primers, and IL‐6 levels were assessed by enzyme‐linked immunosorbent assay. The IL6 rs1800795 alleles and genotypes in both groups were in Hardy–Weinberg (H–W) equilibrium. We found that rs1800795*C allele [38% vs 24%, P = 0.002, odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.18–2.14] and its carriers (62% vs 42%, P = 0.003, OR = 2.28, 95% CI: 1.13–1.94) were more frequent in patients than in controls. IL‐6 in patients was 1.5‐fold higher than in controls (mean ± SD: 6.41 ± 2.47 pg/ml vs 4.15 ± 1.42 pg/ml, P = 1.9E–19). In both groups, higher IL‐6 in rs1800795 GG compared to rs1800795*C allele carriers was observed (GG vs GC + CC, patients: 7.02 ± 2.83 pg/ml vs 5.39 ± 1.2 pg/ml, P = 0.0006; controls: 5.21 ± 1.17 pg/ml vs 3.38 ± 1.03 pg/ml, P = 1.6E–15). In conclusion, we report an association of IL6 rs1800795 and higher IL‐6 with schizophrenia. We also conclude that IL6 rs1800795*C allele is linked to increased IL‐6 blood levels and may be a risk factor for schizophrenia development at least in Armenian population.