bluuebunny/crossref_metadata_2025 huggingface dataset:
Pivotal roles of shear stress in the microenvironmental changes that occur within sentinel lymph nodes
Authors: Kawai Yoshiko , Kaidoh Maki , Yokoyama Yumiko , Ohhashi Toshio
Published: April 2012

A sentinel lymph node (SLN) is the first lymph node that receives drainage from a primary tumor. According to their physiological and biomechanical characteristics, we hypothesized that SLN contains lymphatic endothelial cells (LEC) that are constantly loaded with high levels of shear stress, which might contribute to the production of a suitable environment for micrometastasis within them. To test this hypothesis, we investigated the effects of shear stress stimulation on the expression of adhesion molecules on human LEC isolated from the lymph vessels nearest the SLN of breast cancers, and on the release of ATP from human LEC. The study clarified that the shear stress stimulation produced a significant increase of ICAM‐1 expression at protein and mRNA levels in human LEC. Next, we examined whether the shear stress‐mediated increase of ICAM‐1 expression accelerates the attachment of carcinoma cells to human LEC. Finally, in in vivo experiments, we evaluated whether exogenous ATP facilitates the expression of carcinoma cell‐ligated adhesion molecules in rat SLN. In conclusion, shear stress stimulation induces ICAM‐1 expression on human LEC by activating cell surface F1/FO ATP synthase, which might contribute to the development of a premetastatic environment within SLN. (Cancer Sci 2012; 103: 1245–1252)
Preliminary bonobo and chimpanzee nesting by habitat type in the northernLacTumbaLandscape,DemocraticRepublic ofCongo
Authors: Inogwabini Bila‐Isia , Abokome Mbenzo , Kamenge Tokate , Mbende Longwango , Mboka Lomboto
Published: April 2012

Knowing how habitat determines the distribution of great apes is essential for understanding their ecology and conservation requirements. Habitats in the northernLacTumbaLandscape where this study was conducted are mostly swamp and flooded forests, which types have been overlooked in many great ape surveys. This study describes and discusses patterns of bonobo and chimpanzee nesting sites across these habitat types in the general scope of habitat use by great apes. Considerable efforts were deployed to survey forests of theNgiriTriangle (186 km),Bomongo‐Lubengo (126 km) and Bolombo‐Losombo (112 km). Great ape nesting site encounter rates (r) were calculated forBonobos (r = 0.21 nesting sites km−1;Bolombo‐Losombo), chimpanzees (r = 0.11 nesting sites km−1; Ngiri Triangle) and (r= 0.02 nesting sites km−1;Bomongo‐Lubengo). Swamps and flooded forests dominated the three zones. Nesting sites were at the highest encounter rates in flooded forests; both great ape species were significantly associated with swampy and flood forests. Human signs did not influence the occurrence of nesting sites in these forests. These results confirm findings from other sites where great apes were observed using swamps; they suggest that future surveys include these types of habitat to avoid under‐estimating population sizes.
The pharmacokinetics of peginterferon alfa‐2a and ribavirin in African American, Hispanic and Caucasian patients with chronic hepatitis C
Authors: Brennan B. J. , Morcos P. N. , Wang K. , Blotner S. D. , Morrison R. , Hagedorn C. H. , Marbury T. C. , Sulkowski M. , Grippo J. F.
Published: April 2012

Background

Amongst Caucasian, Hispanic and African Americans with genotype 1 hepatitis C virus (HCV), there is a wide variation in response to treatment with peginterferon alfa‐2a (PEG‐IFN alfa‐2a) and ribavirin.

Aim

To evaluate the pharmacokinetics (PK) of PEG‐IFN alfa‐2a and ribavirin among these three groups.

Methods

Forty‐seven patients with genotype 1 CHC (17 African Americans, 14 Hispanics and 16 Caucasians) received 8 weeks of PEG‐IFN alfa‐2a (180 &g/week) and ribavirin (1000 or 1200 mg/day). PEG‐IFN alfa‐2a serum concentrations and ribavirin plasma concentrations were measured following the first dose and at week 8. Pharmacokinetic parameters (Cmax, Tmax, AUC, CL/F) were estimated using noncompartmental methods.

Results

There was no difference in the pharmacokinetic parameters for PEG‐IFN alfa‐2a following single‐dose or steady‐state administration between African American or Hispanic patients compared with Caucasian patients. Ribavirin pharmacokinetic parameters were similar between Hispanic and Caucasian patients for single‐dose and steady‐state administration. The single‐dose Cmax was 33% lower (P < 0.05) in African American compared with Caucasian patients. Other ribavirin single‐dose and steady‐state pharmacokinetic parameters were slightly decreased (approximately 20% lower) in African American patients, but were not considered clinically meaningful.

Conclusions

No differences were observed in PEG‐IFN alfa‐2a pharmacokinetic parameters between African American or Hispanic patients compared with Caucasian patients. For ribavirin, no differences were observed in pharmacokinetic parameters between Hispanic and Caucasian patients. While a trend towards increased ribavirin clearance and decreased exposure was observed in African American patients vs. Caucasian patients, the differences were small and not considered clinically meaningful (Clinical Trial Number: NP17354).
Methotrexate for psoriasiform lesions associated with anti‐tumour necrosis factor therapy in inflammatory bowel disease
Authors: Buisson A. , Cuny J.‐F. , Barbaud A. , Schmutz J.‐L. , Bigard M.‐A. , Guéant J.‐L. , Peyrin‐Biroulet L.
Published: April 2012

Background

Psoriasiform lesions associated with anti‐tumour necrosis factor (TNF) therapy are frequent in patients with inflammatory bowel disease (IBD). While methotrexate is the most frequently used systemic treatment for psoriasis, its efficacy for psoriasiform lesions related to anti‐TNF therapy remains unknown.

Aims

To assess the efficacy of methotrexate for psoriasiform lesions associated with anti‐TNF therapy refractory to topical therapy in IBD patients.

Methods

The charts of eight patients from the Nancy IBD cohort who developed psoriasiform lesions on anti‐TNF therapy were reviewed. Clinical response was defined as a decrease of more than 50% in the lesions covering surface. All patients were followed up by the same experienced dermatologist.

Results

Eight women (seven Crohn's disease) were followed up for a median duration of 29 months (range, 20–45). Of the eight patients receiving methotrexate, three were primary responders without discontinuation of anti‐TNF agents. Only one patient had a sustained response at final follow‐up and was able to continue both methotrexate and anti‐TNF therapy. Of the two other primary responders, one patient had to discontinue anti‐TNF because of severe psoriasiform lesions, whereas the other one continued anti‐TNF therapy despite persistent skin lesions at final follow‐up. Among the five primary nonresponders, four patients had to stop anti‐TNF treatment due to disabling skin lesions.

Conclusion

Methotrexate does not appear effective in treating psoriasiform lesions associated with anti‐TNF therapy refractory to topical therapy in IBD.
Inhaled LPS challenges in smokers: a study of pulmonary and systemic effects
Authors: Aul Raminder , Armstrong Jane , Duvoix Annelyse , Lomas David , Hayes Brian , Miller Bruce E. , Jagger Chris , Singh Dave
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Neutrophilic airway inflammation is a feature of chronic obstructive pulmonary disease (COPD). Inhaled lipopolysaccharide (LPS) challenge in healthy non‐smokers has been used to assess the anti‐inflammatory effects of novel drugs on neutrophilic airway inflammation.

WHAT THIS STUDY ADDS

• We performed inhaled LPS challenge in smokers to study an inflammatory response in subjects who more closely resemble COPD patients. Inhaled LPS caused reproducible pulmonary inflammation in smokers, associated with changes in systemic biomarkers. Inhaled LPS appears to be a suitable model for studying exacerbations of COPD.

AIMS Lipopolysaccharide (LPS) is a TLR4 agonist which activates NFκB dependent cytokine production. We investigated LPS inhalation in healthy smokers as a model of COPD bacterial exacerbations. We studied safety, reproducibility, the translocation of the NFκB subunit p65 in sputum cells and changes in systemic biomarkers of inflammation.

METHODS Twelve smokers inhaled 5 and 30 µg LPS and safety was monitored over 24 h. IL‐6, CRP, CCl‐18, SP‐D, CC‐16 and β‐defensin 2 were measured in serum samples collected at baseline, 4, 8 and 24 h. Sputum was induced at baseline, 6 and 24 h for cell counts and p65 expression. Repeated challenges were performed after a 2 week interval in 10 smokers.

RESULTS LPS inhalation was well tolerated. Significant increases occurred in sputum neutrophil counts with both doses, with a maximum increase of 21.5% at 6 h after 30 µg which was reproducible, ri (intraclass correlation coefficient) = 0.88. LPS increased sputum cell nuclear p65 translocation and phospho‐p65 expression. All of the serum biomarkers increased following challenge but with different temporal patterns.

DISCUSSION Inhaled LPS challenge in smokers causes pulmonary and systemic inflammation that involves NFκB activation. This appears to be a suitable model for studying bacterial exacerbations of COPD.
Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE)
Authors: Styles Lori , Wager Carrie G. , Labotka Richard J. , Smith‐Whitley Kim , Thompson Alexis A. , Lane Peter A. , McMahon Lillian E. C. , Miller Robin , Roseff Susan D. , Iyer Rathi V. , Hsu Lewis L. , Castro Oswaldo L. , Ataga Kenneth I. , Onyekwere Onyinye , Okam Maureen , Bellevue Rita , Miller Scott T. ,   for the Sickle Cell Disease Clinical Research Network (SCDCRN)
Published: April 2012

Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre‐emptive therapy in high‐risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain who developed fever and elevated sPLA2 were eligible for randomization to transfusion or observation; all others were enrolled in an observational arm. Of 237 enrolled, only 10 were randomized; one of the four to receive transfusion had delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A threshold level of sPLA2 ≥ 48 ng/ml gave optimal sensitivity (73%), specificity (71%) and accuracy (71%), but a positive predictive value of only 24%. The predictive value of sPLA2 was improved in adults and patients with chest or back pain, lower haemoglobin concentration and higher white blood cell counts, and in those receiving less than two‐thirds maintenance fluids. The hurdles identified in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized controlled trial.
‘I think I do have strategies’: lawyers' approaches to parent engagement in care proceedings
Authors: Masson Judith
Published: April 2012

This paper examines the issue of parental engagement where children's services have brought court proceedings to protect children, from the perspective of specialist lawyers who represent parents. It draws on an in‐depth, qualitative study of parents' representation conducted between 2008 and 2010. Parental non‐co‐operation with children's services is a common feature in these cases. Lawyers are partisans with duties to follow clients' instructions. They seek to build a trusting relationship and keep clients engaged in the process by giving advice, taking instructions and providing emotional support. Lawyers accept that parents have an absolute right to contest but use their power and authority to encourage their most vulnerable clients to concede. They are largely successful in keeping clients engaged in proceedings but parents rarely make the necessary changes in parenting.
Making the developmental system work better for children: lessons learned implementing an innovative programme
Authors: Branch Sara , Homel Ross , Freiberg Kate
Published: April 2012

Pathways to Prevention is an early prevention project founded on developmental systems theory operating through a schools‐community agency‐university partnership in a socially disadvantaged area of Brisbane. Circles of Care is a Pathways programme also implemented on a small scale by the same agency in a regional city. The Circles programme is designed to strengthen connections between schools, families and community services, and harmonize activities in these settings by surrounding children with identified needs with a supportive group of adults. A Circle, which includes at least the child, parent(s), teacher and agency staff, sets goals, mobilizes resources for the child, family and school, and monitors progress. The client is conceptualized not as the child but as a dysfunctional developmental system, with better outcomes for children as the ultimate goal. Qualitative evaluation at the two sites showed that while Circles worked well at the level of practical support and relationship building and did achieve good child outcomes, its capacity to achieve collaborative practice and strengthen system relations was limited by entrenched organizational structures and cultures. However, one site, with more support for collaboration across organizational boundaries, suggested that system alignment is achievable on a larger scale with vision and leadership for organizational reform.
Resettlement challenges faced by refugee claimant families in Montreal: lack of access to child care
Authors: Morantz Gillian , Rousseau Cécile , Banerji Anna , Martin Carolina , Heymann Jody
Published: April 2012

Adult refugee claimants experience several well‐documented post‐migratory challenges. Little is known about the resettlement process for refugee claimant families with children. This study reports on 75 open‐ended, in‐depth interviews with refugee claimant families in Montreal about their resettlement challenges and their proposed solutions to them. These interviews were conducted with 33 dyads and triads of children and parents attending a paediatric hospital. Experiences accessing formal and informal child care in Montreal were addressed. Subsequently, a comparative policy analysis was conducted on residency eligibility criteria for child care subsidization. Twenty‐eight out of 39 parents (73%) report a lack of informal or formal child care and 15 out of 33 families (39%) propose improving access to formal child care services. They describe a lack of informal child care as a result of reduced social networks, and affordability as a barrier to formal child care services. Refugee claimants are not eligible for subsidized child care in Quebec. A comparative policy analysis within Canada and comparable countries reveals that this situation is not unique to Quebec. However, most provinces and European countries offer child care subsidies to refugee claimants. Refugee claimants should qualify for child care subsidies. Social workers and community organizations should consider their clients' child care needs in designing programmes and services.
Resting egg banks can facilitate recovery of zooplankton communities after extended exposure to saline conditions
Authors: NIELSEN DARYL L. , SMITH DANIELLE , PETRIE ROCHELLE
Published: April 2012

1. Salinisation has had a major effect on the diversity of biota associated with freshwater wetlands. However, there is no information available about whether elements of the biotic communities would be able to recover if the concentration of salts within secondarily salinised wetlands was lowered to levels more typical of freshwater wetlands.

2. We tested the hypothesis that dormant eggs of zooplankton are able to persist in wetlands with elevated salinities for extended periods of time by using zooplankton communities that had developed in mesocosms exposed to either salt concentrations of 13 500 mg L−1 or freshwater (<300 mg L−1) for a period of 22 months. We measured the response of the zooplankton community as concentration was reduced along a gradient of decreasing salinity from 13 500 mg L−1 to freshwater.

3. In the freshwater mesocosms, the zooplankton community was abundant and taxon rich. In comparison at the start of the experiment in the high salinity mesocosms, the zooplankton community had low abundances and very few taxa. Numbers remained low in these mesocosms until salinity was reduced to <2500 mg L−1. Below this, there was a rapid increase in the abundance, and richness of zooplankton and communities became similar to the communities in the freshwater mesocosms.

4. These results indicate that dormant eggs of zooplankton are able to persist in wetlands exposed to high salinity levels for up to 22 months and provide a means for zooplankton communities to rapidly respond once a wetland returns to freshwater.

5. It is likely that if the underlying causes of secondary salinisation in wetlands are addressed, it will be possible to undertake restoration activities that allow the rapid return of some components of their biotic communities.
Chlorhexidine, ethanol, lipopolysaccharide and nicotine do not enhance the cytotoxicity of a calcium hydroxide pulp capping material
Authors: Wheater M. A. , Falvo J. , Ruiz F. , Byars M.
Published: April 2012

Wheater MA, Falvo J, Ruiz F, Byars M. Chlorhexidine, ethanol, lipopolysaccharide and nicotine do not enhance the cytotoxicity of a calcium hydroxide pulp capping material. International Endodontic Journal, 45, 989–995, 2012.

Aim  To determine whether cells pre‐stressed by known cytotoxic or inflammatory agents are more susceptible to the deleterious effects of a calcium hydroxide formulation used in pulp capping.

Methodology  Adult human dermal fibroblasts were treated for 48 h with 0.001% chlorhexidine, 0.2% ethanol, 5 μg mL−1Escherichia coli lipopolysaccharide (LPS) or 0.05 mmol L−1 nicotine. Cells were subsequently treated with the soluble materials extracted from Dycal pellets for an additional 24 h. Controls included cells cultured in medium only and cells exposed to Dycal only. Cytotoxicity was measured using colorimetric MTT, WST and secreted lactate dehydrogenase assays. In addition, mitotic activity was evaluated using a colorimetric histone H3 phosphorylation assay. Data were statistically analysed using anova with Tukey’s multiple comparison post‐test and significance at P ≤ 0.05.

Results  For all assays, measured values for cells treated with chlorhexidine, ethanol, LPS or nicotine plus the soluble materials extracted from Dycal pellets were significantly lower compared to control (P < 0.05) for all comparisons between experimental conditions. However, between treatments and for comparisons of treatments with Dycal, there were no differences observed for any assay.

Conclusions  Calcium hydroxide in a formulation used in dental clinical procedures is highly cytotoxic to cultured cells, as evidenced by several cellular assays. However, other known toxic agents, including chlorhexidine, ethanol, bacterial LPS and nicotine, do not appear to function synergistically to increase the deleterious cellular effects of the calcium hydroxide in an in vitro model of cytotoxicity.
Rapid environmental degradation in a subarctic ecosystem influences resource use of a keystone avian herbivore
Authors: Winiarski Kristopher J. , McWilliams Scott R. , Rockwell Robert F.
Published: April 2012

1. Environmental degradation can change resource use strategies of animals and thereby affect survival and fitness. Arctic herbivores may be especially susceptible to the effects of such environmental change because their rapid growth rates demand high‐quality forage, which may be limited as environmental conditions deteriorate. We studied the consequences of a trophic cascade, driven by Lesser Snow Goose (Chen caerulescens caerulescens) overgrazing on the south‐west coast of Hudson Bay, Canada, which has caused tidal marsh (TM) degradation and the reduction in high‐quality forage plants, on gosling growth and resource use.

2. We compared resource use and body size of goslings that inhabited tidal and freshwater marsh (FM) to determine how current foraging strategies influence growth and to test the hypothesis that during early growth goslings require and so consume high‐quality TM plants, but that during later growth they may switch to foraging in lower‐quality FM.

3. To investigate gosling resource use throughout growth, we measured once a week for 28 days the body size of goslings as well as stable isotope ratios (δ34S, δ15N and δ13C) in multiple tissues of goslings that were collected from both TM and nearby FM. We also measured the stable isotope ratios in forage plants sampled along transects and from gosling foreguts. We used an isotope‐mixing model to determine the contribution of FM plants to gosling tissues.

4. Contrary to the proposed hypothesis, goslings inhabiting FM or TM primarily consumed FM plants during early growth. Furthermore, goslings that foraged extensively in FM had similar growth rates and grew to a similar size and body mass, as goslings that foraged in the degraded TM. However, goslings that currently inhabit freshwater or TM were significantly smaller than goslings that inhabited TM in the 1980s prior to habitat degradation.

5. Consequences of smaller overall body size include decreased survival and fecundity for arctic‐nesting geese. The ability of phenotypically plastic responses to sustain persistence is limited by reaction norms and the extent of environmental change. Current research is assessing whether those limits have been reached in this system.
Impact of landscape alteration and invasions on pollinators: a meta‐analysis
Authors: Montero‐Castaño Ana , Vilà Montserrat
Published: April 2012

1. Alterations in land use and biological invasions are two major components of global change that threaten biodiversity. There is high concern about their impact on pollinators and the pollination services they provide. However, the growing literature shows different, even contradictory results.

2. We present a global meta‐analysis of 58 publications reporting 143 studies (37 on landscape alteration and 21 on biological invasions) to assess the extent to which these components affect pollinators, and whether taxonomic and ecosystem‐type differences in pollinator responses occur. We also quantified which component of landscape alteration had the largest effect on pollinators and assessed whether animal invasions differ from plant invasions in their effect on native pollinators.

3. Habitat alteration and invasions affected pollinators to the same magnitude by decreasing visitation rates. Vertebrates in altered landscapes and insects (excluding bees) in invaded areas were the most affected pollinator taxa.

4. Pollinator abundance was more reduced in altered forest ecosystems than in altered grasslands; while the reverse pattern was found for pollinator richness. However, the response of pollinators to invasions was independent of ecosystem type.

5. Disturbance of the surrounding matrix was more important in decreasing pollinator visitation rates than fragment size.

6. Invasive animals seemed to have a more consistent negative effect on visitation rates than invasive plants.

7. Synthesis. Our study highlights that different components of global change have similar negative outcomes on pollination patterns, but that responses of pollinators vary among taxa and ecosystem types, as well as the attributes of landscape alteration considered and whether the invader is an animal or a plant.
Interferon therapy of acute hepatitis C in dialysis patients: meta‐analysis
Authors: Fabrizi F. , Dixit V. , Messa P. , Martin P.
Published: April 2012

Summary.  The efficacy and safety of antiviral therapy in patients with acute hepatitis C on long‐term dialysis remains unclear, although a number of small clinical studies have been published addressing this issue. We evaluated the efficacy and safety of interferon therapy in chronic dialysis patients with acute hepatitis C by performing a systematic review of the literature with a meta‐analysis of clinical studies. The primary outcome was sustained virological response (SVR, as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eight clinical studies (173 unique patients), three (37.5%) being controlled clinical trials (CCTs). Among CCTs, the viral response was much more common in study (patients on antiviral therapy) than control (patients who did not receive therapy) groups; the pooled odds ratio of SVR being 27.06, 95% Confidence Intervals (95% CI), 9.26; 79.1 (P =0.00001). No difference in the dropout rate between study and control patients was shown, odds ratio = 0.920 (95% CI, 0.367; 1.92), NS. Pooling all study results (n = 8 studies) demonstrated that the summary estimate for SVR and dropout rate was 58% (95% CI, 38; 77) and 9% (95% CI, 4; 14), respectively. The most frequent side‐effects requiring interruption of the treatment were flu‐like symptoms (n = 4, 18%), followed by haematological changes and loss to follow‐up. A strong relationship between increasing age and reported dropout rate was recognized (P = 0.001). The studies were heterogeneous with regard to SVR but not to dropout rate. Our meta‐analysis of CCTs showed that the viral response after antiviral therapy was more common than the spontaneous viral clearance in dialysis patients with acute hepatitis C. Pooled analysis demonstrated that IFN‐based therapy of acute hepatitis C in dialysis populations gives SVR in around one half of patients. These results support IFN‐based therapy for acute hepatitis C in patients on maintenance dialysis.
Forest fragmentation genetics in a formerly widespread island endemic tree: Vateriopsis seychellarum (Dipterocarpaceae)
Authors: FINGER A. , KETTLE C. J. , KAISER‐BUNBURY C. N. , VALENTIN T. , MOUGAL J. , GHAZOUL J.
Published: April 2012

Habitat fragmentation and changed land use have seriously reduced population size in many tropical forest tree species. Formerly widespread species with limited gene flow may be particularly vulnerable to the negative genetic effects of forest fragmentation and small population size. Vateriopsis seychellarum (Dipterocarpaceae) is a formerly widespread canopy tree of the Seychelles, but is now reduced to 132 adult individuals distributed in eleven sites. Using ten microsatellite loci, a genetic inventory of all adult trees and a sample of 317 progeny, we demonstrate that despite its restricted range, overall genetic diversity was relatively high (HE: 0.56). The juvenile cohort, however, had significantly lower allelic richness (adults RS: 3.91; juveniles RS: 2.83) and observed heterozygosity than adult trees (adults HO: 0.62; juveniles HO: 0.48). Rare alleles were fewer and kinship between individuals was stronger in juveniles. Significant fine‐scale spatial genetic structure was observed in remnant adults, and parentage analysis indicated that more than 90% of sampled progeny disperse <25 m and pollen dispersed <50 m. The molecular data confirmed that two populations were derived entirely from self‐fertilized offspring from a single surviving mother tree. These populations produce viable offspring. Despite this extreme genetic bottleneck, self‐compatibility may provide V. seychellarum with some resistance to the genetic consequences of habitat fragmentation, at least in the short term. We discuss our findings in the context of other rare and threatened dipterocarp species which are vulnerable to miss‐management of genetic resources and population fragmentation.
Small proteins link coat and cortex assembly during sporulation in Bacillus subtilis
Authors: Ebmeier Sarah E. , Tan Irene S. , Clapham Katie Rose , Ramamurthi Kumaran S.
Published: April 2012

Mature spores of the bacterium Bacillus subtilis are encased by two concentric shells: an inner shell (the ‘cortex’), made of peptidoglycan; and an outer proteinaceous shell (the ‘coat’), whose basement layer is anchored to the surface of the developing spore via a 26‐amino‐acid‐long protein called SpoVM. During sporulation, initiation of cortex assembly depends on the successful initiation of coat assembly, but the mechanisms that co‐ordinate the morphogenesis of both structures are largely unknown. Here, we describe a sporulation pathway involving SpoVM and a 37‐amino‐acid‐long protein named ‘CmpA’ that is encoded by a previously un‐annotated gene and is expressed under control of two sporulation‐specific transcription factors (σE and SpoIIID). CmpA localized to the surface of the developing spore and deletion of cmpA resulted in cells progressing through the sporulation programme more quickly. Overproduction of CmpA did not affect normal growth or cell division, but delayed entry into sporulation and abrogated cortex assembly. In those cells that had successfully initiated coat assembly, CmpA was removed by a post‐translational mechanism, presumably in order to overcome the sporulation inhibition it imposed. We propose a model in which CmpA participates in a developmental checkpoint that ensures the proper orchestration of coat and cortex morphogenesis by repressing cortex assembly until coat assembly successfully initiates.
Physical map and dynamics of the chaperone network in Escherichia coli
Authors: Kumar Mohit , Sourjik Victor
Published: April 2012

Diverse families of molecular chaperones cooperate to effect protein homeostasis, but the extent and dynamics of direct interactions among chaperone systems within cells remain little studied. Here we used fluorescence resonance energy transfer to systematically map the network of pairwise interactions among the major Escherichia coli chaperones. We demonstrate that in most cases functional cooperation between chaperones within and across families involves physical complex formation, which pre‐exists even in the absence of folding substrates. The observed connectivity of the overall chaperone network confirms its partitioning into sub‐networks that are responsible for de novo protein folding and maturation and for refolding/disaggregation of misfolded proteins, respectively, and are linked by the Hsp70 system. We further followed heat‐induced changes in the cellular chaperone network, revealing two distinct pathways that process heat‐denatured substrates. Our data suggest that protein folding within cells relies on highly ordered and direct channelling of substrates between chaperone systems and provide a comprehensive view of the underlying interactions and of their dynamics.
Anticipation of public speaking and sleep and the hypothalamic‐pituitary‐adrenal axis in women with irritable bowel syndrome
Authors: Heitkemper M. M. , Cain K. C. , Deechakawan W. , Poppe A. , Jun S‐E. , Burr R. L. , Jarrett M. E.
Published: April 2012

Background  Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper‐responsive to a variety of laboratory stress conditions.

Methods  This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS‐constipation and 21 IBS‐diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 min from 08:00 PM until awakening. As the subjects had different sleep onsets, each subject’s results were synchronized to the first onset of stage 2 sleep.

Key Results  Compared the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS.

Conclusions & Inferences  This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS.
CD4‐ and CD3‐T Lymphocyte Reference Values of Immunocompetent Urban and Rural Subjects in an African Nation
Authors: Adoga M. P. , Pennap G. R. , John P. A. , Shawulu P. T. , Kaba S. V. , Forbi J. C. , Agwale S. M.
Published: April 2012

Studies on the reference values of CD4 and CD3 T cells in healthy individuals have continued to gain significance because of the importance of these immunological markers in the initiation of combination antiretroviral therapy (cART). The aim of the present study was to determine and compare the reference values of CD4 and CD3 T cells in urban and rural Nigerians who were human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) negative. After ethical clearance and informed consent, 1123 subjects who met the inclusion criteria [mean age = 24.4 (± 11.2) years] were recruited in this study. Blood samples were analysed using the BD FACScount cytometer according to the manufacturer’s instructions. Of the overall 1123 subjects, reference means of CD4, CD3 and CD4/CD3 ratio were 1030 ± 367, 1757 ± 609 cells/μl and 0.59 ± 0.08, respectively. Five hundred and fifty‐one (49.1%) were an urban population with the mean CD4, CD3 and CD4/CD3 T cell ratio of 1032 ± 369, 1761 ± 612 cells/μl and 0.59 (±0.08), respectively. The remaining 572 (50.9%) were of a rural population with the mean CD4, CD3 and CD4/CD3 T cell ratio of 1028 ± 459, 1753 ± 958 cells/μl and 0.59 ± 0.13, respectively. Subjects with higher CD4 and CD3 T cells were more likely to be female than male (P < 0.05). There was no significant difference between the T cell values of the two populations (P > 0.05). Our findings provide new insight in the CD4 and CD3 T cell reference values of Nigerians.
Effect of nitrogen, phosphorus and potassium availability on mother plant size, seed production and germination ability of Rumex crispus
Authors: HEJCMAN M , KŘIŠŤÁLOVÁ V , ČERVENÁ K , HRDLIČKOVÁ J , PAVLŮ V
Published: April 2012

Hejcman M, Křišťálová V, Červená K, Hrdličková J & Pavlů V (2012). Effect of nitrogen, phosphorus and potassium availability on mother plant size, seed production and germination ability of Rumex crispus. Weed Research52, 260–268.

Rumex crispus is believed to be a highly nutrient‐demanding weedy species that spreads mainly by seeds. However, the effects of nutrient availability on its performance and seed production have never been fully investigated. In this study, we investigated how plant size, seed production and germination were affected by the supply of N, P and K. In May 2008, a pot N, P and K fertiliser experiment was established in Prague (Czech Republic). During 2009, plant growth data were collected, and fully ripe seeds were tested for germination and N, P and K concentrations. Rumex crispus showed high phenotypic plasticity in plant height, number of leaves, leaf length and number of stems per plant in relation to N, P and K supply. Seed production per plant ranged from <2000 in the control and low P treatment up to almost 25 000 in the high NPK treatment. More than 16 000 seeds were produced per plant in all treatments where N and P were applied together. To produce a high quantity of rapidly germinating seeds, R. crispus requires a balanced N, P and K supply, as a deficiency of P and K together with a high N supply can result in the production of P‐ and K‐deficient seeds (P and K <3 g kg−1) with lower germination ability. In central Europe, at least some populations of R. crispus do not flower in the seeding year and are strictly monocarpic. Given the short lifespan and monocarpic character of the species, control is probably most effective if applied at the rosette stage, prior to the production of viable seeds.
Exome sequencing in a family with an X‐linked lethal malformation syndrome: clinical consequences of hemizygous truncating OFD1 mutations in male patients
Authors: Tsurusaki Y , Kosho T , Hatasaki K , Narumi Y , Wakui K , Fukushima Y , Doi H , Saitsu H , Miyake N , Matsumoto N
Published: April 2012

Tsurusaki Y, Kosho T, Hatasaki K, Narumi Y, Wakui K, Fukushima Y, Doi H, Saitsu H, Miyake N, Matsumoto N. Exome sequencing in a family with an X‐linked lethal malformation syndrome: clinical consequences of hemizygous truncating OFD1 mutations in male patients.

Oral‐facial‐digital syndrome type 1 (OFD1; OMIM #311200) is an X‐linked dominant disorder, caused by heterozygous mutations in the OFD1 gene and characterized by facial anomalies, abnormalities in oral tissues, digits, brain, and kidney; and male lethality in the first or second trimester pregnancy. We encountered a family with three affected male neonates having an ‘unclassified’ X‐linked lethal congenital malformation syndrome. Exome sequencing of entire transcripts of the whole X chromosome has identified a novel splicing mutation (c.2388+1G > C) in intron 17 of OFD1, resulting in a premature stop codon at amino acid position 796. The affected males manifested severe multisystem complications in addition to the cardinal features of OFD1 and the carrier female showed only subtle features of OFD1. The present patients and the previously reported male patients from four families (clinical OFD1; Simpson‐Golabi‐Behmel syndrome, type 2 with an OFD1 mutation; Joubert syndrome‐10 with OFD1 mutations) would belong to a single syndrome spectrum caused by truncating OFD1 mutations, presenting with craniofacial features (macrocephaly, depressed or broad nasal bridge, and lip abnormalities), postaxial polydactyly, respiratory insufficiency with recurrent respiratory tract infections in survivors, severe mental or developmental retardation, and brain malformations (hypoplasia or agenesis of corpus callosum and/or cerebellar vermis and posterior fossa abnormalities).
Transplantation for complex congenital heart disease in adults: a subanalysis of the Spanish Heart Transplant Registry
Authors: Paniagua Martín María J. , Almenar Luis , Brossa Vicenç , Crespo‐Leiro Marisa G. , Segovia Javier , Palomo Jesús , Delgado Juan , González‐Vílchez Francisco , Manito Nicolás , Lage Ernesto , García‐Guereta Luis , Rodríguez‐Lambert José L. , Albert Dimpna C.
Published: April 2012

Background

Congenital heart diseases (CHDs) have high infant mortality in their severe forms. When adulthood is reached, a heart transplant (HTx) may be required. Spanish adult population transplanted for CHD was analyzed and compared with the most frequent causes of HTx and between different subgroups of CHD.

Materials and Methods

A total of 6048 patients (HTx 1984–2009) were included. Pediatric transplants (<15 yr), combined transplants, reHTx, and HTx for heart diseases other than idiopathic dilated cardiomyopathy (IDCM) and ischemic heart disease (IHD) were excluded. Total patients included: 3166 (IHD = 1888; IDCM = 1223; CHD = 55). Subgroups were studied as follows: (1) single ventricle with pulmonary stenosis (n = 18), (2) single ventricle with tricuspid atresia and Glenn/Fontan surgery (n = 10), (3) congenitally corrected transposition of the great vessels (TGV) or with switch atrial surgery (n = 10), and (4) CHD with right ventricle overload (n = 17).

Results

Survival probability was different between groups (p = 0.0001). Post hoc analysis showed some differences between groups (CHD vs. IHD, p = 0.05; CHD vs. IDCM, p = 0.5; IHD vs. IDCM, p = 0.0001). Early mortality was different between CHD subgroups (group 1 = 19%, group 2 = 40%, group 3 = 0%, group 4 = 29%; p < 0.001); however, overall mortality did not show differences between subgroups (p = 0.5).

Conclusions

The percentage of Spanish adult HTx patients for CHD is low (1%). The survival curve is better than for other HTx causes (IHD). Nevertheless, early mortality was higher, particularly in some subgroups (Fontan).
Alternative donor HSCT in refractory acquired aplastic anemia – Prevention of graft rejection and graft versus host disease by immunoablative conditioning and graft manipulation
Authors: Urban Christian , Benesch Martin , Sovinz Petra , Sipurzynski Sabine , Lackner Herwig , Müller Ewa , Schwinger Wolfgang
Published: April 2012

Urban C, Benesch M, Sovinz P, Sipurzynski S, Lackner H, Müller E, Schwinger W. Alternative donor HSCT in refractory acquired aplastic anemia – Prevention of graft rejection and graft versus host disease by immunoablative conditioning and graft manipulation.

Abstract:  Early alternative donor HSCT is a potentially curative therapeutic option for patients with AAA not responding to IST. Seven patients (median age at diagnosis, 11 yr) with refractory AAA without a MSD underwent HSCT from matched unrelated (n = 6) or haploidentical (n = 1) donors. Conditioning regimens included CY (n = 7), muromonab‐CD3/ATG (n = 7), TT (n = 6), FLU (n = 5), and TLI (n = 2). Grafts were either CD34 purified and/or CD3/19 depleted and contained a median of 10.17 × 106/kg CD34 and 5.5 × 104/kg CD3 cells. All patients engrafted rapidly. Median time to leukocyte engraftment was 10 days. With a median follow‐up of 26 (range, 11–153) months, six patients are alive and well with complete donor hematopoiesis. One heavily pretreated patient developed GVHD grade III and died from progressive renal failure (resulting from microangiopathic hemolytic anemia) and disseminated aspergillosis. Early alternative donor HSCT can help to avoid complications from prolonged IST and presumably improve survival of patients with refractory AAA. Administration of high doses of CD34 purified and/or CD3/19 depleted stem cells following novel immunoablative conditioning may prevent graft rejection and GVHD. However, a long interval from diagnosis to HSCT seems to be associated with poor outcome.
Phytochrome A increases tolerance to high evaporative demand
Authors: Auge Gabriela Alejandra , Rugnone Matías Leandro , Cortés Leandro Emanuel , González Carina Verónica , Zarlavsky Gabriela , Boccalandro Hernán Esteban , Sánchez Rodolfo Augusto
Published: April 2012

Stresses resulting from high transpiration demand induce adjustments in plants that lead to reductions of water loss. These adjustments, including changes in water absorption, transport and/or loss by transpiration, are crucial to normal plant development. Tomato wild type (WT) and phytochrome A (phyA)‐mutant plants, fri1‐1, were exposed to conditions of either low or high transpiration demand and several morphological and physiological changes were measured during stress conditions. Mutant plants rapidly wilted compared to WT plants after exposure to high evaporative demand. Root size and hydraulic conductivity did not show significant differences between genotypes, suggesting that water absorption and transport through this organ could not explain the observed phenotype. Moreover, stomatal density was similar between genotypes, whereas transpiration and stomatal conductance were both lower in mutant than in WT plants. This was accompanied by a lower stem‐specific hydraulic conductivity in mutant plants, which was associated to lower xylem vessel number and transversal area in fri1‐1 plants, producing a reduction in water supply to the leaves, which rapidly wilted under high evaporative demand. PhyA signaling might facilitate the adjustment to environments differing widely in water evaporative demand in part through the modulation of xylem dimensions.
Fruit‐specific overexpression of wound‐induced tap1 under E8 promoter in tomato confers resistance to fungal pathogens at ripening stage
Authors: Kesanakurti Divya , Kolattukudy Pappachan E. , Kirti Pulugurtha Bhardwaja
Published: April 2012

Based on high economic importance and nutritious value of tomato fruits and as previous studies employed E8 promoter in fruit ripening‐specific gene expression, we have developed transgenic tomato plants overexpressing tomato anionic peroxidase cDNA (tap1) under E8 promoter. Stable transgene integration was confirmed by polymerase chain reaction (PCR) and Southern analysis for nptII. Northern blotting confirmed elevated tap1 levels in the breaker‐ and red‐ripe stages of T1 transgenic fruits, whereas wild‐type (WT) plants did not show tap1 expression in these developmental stages. Further, tap1 expression levels were significantly enhanced in response to wounding in breaker‐ and red‐ripe stages of transgenic fruits, whereas wound‐induced expression of tap1 was not detected in WT fruits. Confocal microscopy revealed high accumulation of phenolic compounds at the wound site in transgenic fruits suggesting a role of tap1 in wound‐induced phenolic polymerization. Total peroxidase activity has increased remarkably in transgenic pericarp tissues in response to wounding, while very less or minimal levels were recorded in WT pericarp tissues. Transgenic fruits also displayed reduced post‐harvest decay and increased resistance toward Alternaria alternata and Fusarium solani infection with noticeable inhibition in lesion formation. Conidiospore germination and mycelial growth of F. solani were severely inhibited when treated with E8‐tap1 fruit extracts compared to WT fruits. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay showed reduced spore viability when incubated in E8‐tap1 fruit extracts. Thus, fruit‐specific expression of tap1 using E8 promoter is associated with enhanced total peroxidase activity and high phenolic accumulation in fruits with minimized post‐harvest deterioration caused by wounding and fungal attack in tomato fruits.
L‐index as a novel index to evaluate both the intensity and duration of lymphopenia after allogeneic hematopoietic stem cell transplantation
Authors: Kimura S.‐I. , Wada H. , Sakamoto K. , Ashizawa M. , Sato M. , Terasako K. , Nakasone H. , Kikuchi M. , Okuda S. , Kako S. , Yamazaki R. , Oshima K. , Tanaka Y. , Tanihara A. , Nishida J. , Kanda Y.
Published: April 2012

We retrospectively investigated L‐index, which evaluates both the intensity and duration of lymphopenia after allogeneic hematopoietic stem cell transplantation (HSCT) (n = 50). L‐index was defined as the area over the lymphocyte curve during lymphopenia (absolute lymphocyte count < 700/μL). We calculated the L‐index from the start of conditioning to day 30 – L‐index(30) – and to day 100 – L‐index(100) – after HSCT. Multivariate analysis revealed that human leukocyte antigen mismatched donor, female gender, and non‐lymphoid disease were significantly associated with high L‐index(30). Grade III–IV acute graft‐versus‐host disease, alemtuzumab‐containing regimen, and non‐lymphoid disease were identified as independent significant factors for high L‐index(100). Cytomegalovirus (CMV) antigenemia was detected > 3 cells/2 slides by C10/11 method in 30 patients (CMV‐AG ≥ 3 group) and was not detected in 20 patients (CMV‐AG < 3 group). Although no significant difference was seen in absolute lymphocyte count on day 30 between the 2 groups, the L‐index(30) was significantly higher in the CMV‐AG ≥ 3 group than in the CMV‐AG < 3 group (P = 0.050). L‐index(30) was identified as an independent factor on CMV reactivation in multivariate analysis, when it was treated as a dichotomous variable with a cut‐off value of 22,318, determined by receiver operating characteristic curve analysis. In conclusion, both the intensity and duration of lymphopenia in early phase after HSCT evaluated on the basis of L‐index(30) showed significant association with CMV reactivation.