bluuebunny/crossref_metadata_2025 huggingface dataset:
A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits
Authors: Maywood Elizabeth S. , Chesham Johanna E. , O'Brien John A. , Hastings Michael H.
Published: July 2011

The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of mammals, coordinating daily rhythms of behavior and metabolism. Circadian timekeeping in SCN neurons revolves around transcriptional/posttranslational feedback loops, in whichPeriod(Per) andCryptochrome(Cry) genes are negatively regulated by their protein products. Recent studies have revealed, however, that these “core loops” also rely upon cytosolic and circuit-level properties for sustained oscillation. To characterize interneuronal signals responsible for robust pacemaking in SCN cells and circuits, we have developed a unique coculture technique using wild-type (WT) “graft” SCN to drive pacemaking (reported by PER2::LUCIFERASE bioluminescence) in “host” SCN deficient either in elements of neuropeptidergic signaling or in elements of the core feedback loop. We demonstrate that paracrine signaling is sufficient to restore cellular synchrony and amplitude of pacemaking in SCN circuits lacking vasoactive intestinal peptide (VIP). By using grafts with mutant circadian periods we show that pacemaking in the host SCN is specified by the genotype of the graft, confirming graft-derived factors as determinants of the host rhythm. By combining pharmacological with genetic manipulations, we show that a hierarchy of neuropeptidergic signals underpins this paracrine regulation, with a preeminent role for VIP augmented by contributions from arginine vasopressin (AVP) and gastrin-releasing peptide (GRP). Finally, we show that interneuronal signaling is sufficiently powerful to maintain circadian pacemaking in arrhythmic Cry-null SCN, deficient in essential elements of the transcriptional negative feedback loops. Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN.
Ineffective erythropoiesis with reduced red blood cell survival in serotonin-deficient mice
Authors: Amireault Pascal , Hatia Sarah , Bayard Elisa , Bernex Florence , Collet Corinne , Callebert Jacques , Launay Jean-Marie , Hermine Olivier , Schneider Elke , Mallet Jacques , Dy Michel , Côté Francine
Published: July 2011

Serotonin (5-HT) has long been recognized as a neurotransmitter in the central nervous system, where it modulates a variety of behavioral functions. Availability of 5-HT depends on the expression of the enzyme tryptophan hydroxylase (TPH), and the recent discovery of a dual system for 5-HT synthesis in the brain (TPH2) and periphery (TPH1) has renewed interest in studying the potential functions played by 5-HT in nonnervous tissues. Moreover, characterization of the TPH1 knockout mouse model (TPH1
−/−
) led to the identification of unsuspected roles for peripheral 5-HT, revealing the importance of this monoamine in regulating key physiological functions outside the brain. Here, we present in vivo data showing that mice deficient in peripheral 5-HT display morphological and cellular features of ineffective erythropoiesis. The central event occurs in the bone marrow where the absence of 5-HT hampers progression of erythroid precursors expressing 5-HT
2A
and 5-HT
2B
receptors toward terminal differentiation. In addition, red blood cells from 5-HT–deficient mice are more sensitive to macrophage phagocytosis and have a shortened in vivo half-life. The combination of these two defects causes TPH1
−/−
animals to develop a phenotype of macrocytic anemia. Direct evidence for a 5-HT effect on erythroid precursors is provided by supplementation of the culture medium with 5-HT that increases the proliferative capacity of both 5-HT–deficient and normal cells. Our thorough analysis of TPH1
−/−
mice provides a unique model of morphological and functional aberrations of erythropoiesis and identifies 5-HT as a key factor for red blood cell production and survival.
Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2–mediated heparin-binding EGF signaling in endothelial cells
Authors: Svensson Katrin J. , Kucharzewska Paulina , Christianson Helena C. , Sköld Stefan , Löfstedt Tobias , Johansson Maria C. , Mörgelin Matthias , Bengzon Johan , Ruf Wolfram , Belting Mattias
Published: July 2011

Highly malignant tumors, such as glioblastomas, are characterized by hypoxia, endothelial cell (EC) hyperplasia, and hypercoagulation. However, how these phenomena of the tumor microenvironment may be linked at the molecular level during tumor development remains ill-defined. Here, we provide evidence that hypoxia up-regulates protease-activated receptor 2 (PAR-2), i.e., a G-protein–coupled receptor of coagulation-dependent signaling, in ECs. Hypoxic induction of PAR-2 was found to elicit an angiogenic EC phenotype and to specifically up-regulate heparin-binding EGF-like growth factor (HB-EGF). Inhibition of HB-EGF by antibody neutralization or heparin treatment efficiently counteracted PAR-2–mediated activation of hypoxic ECs. We show that PAR-2–dependent HB-EGF induction was associated with increased phosphorylation of ERK1/2, and inhibition of ERK1/2 phosphorylation attenuated PAR-2–dependent HB-EGF induction as well as EC activation. Tissue factor (TF), i.e., the major initiator of coagulation-dependent PAR signaling, was substantially induced by hypoxia in several types of cancer cells, including glioblastoma; however, TF was undetectable in ECs even at prolonged hypoxia, which precludes cell-autonomous PAR-2 activation through TF. Interestingly, hypoxic cancer cells were shown to release substantial amounts of TF that was mainly associated with secreted microvesicles with exosome-like characteristics. Vesicles derived from glioblastoma cells were found to trigger TF/VIIa–dependent activation of hypoxic ECs in a paracrine manner. We provide evidence of a hypoxia-induced signaling axis that links coagulation activation in cancer cells to PAR-2–mediated activation of ECs. The identified pathway may constitute an interesting target for the development of additional strategies to treat aggressive brain tumors.
Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing
Authors: Billon-Galés Audrey , Krust Andrée , Fontaine Coralie , Abot Anne , Flouriot Gilles , Toutain Céline , Berges Hortense , Gadeau Alain-Pierre , Lenfant Françoise , Gourdy Pierre , Chambon Pierre , Arnal Jean-François
Published: July 2011

17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF2
0
)
. Our results prove four points. (
i
) Compared with WT ERα, the ability of ERαAF2
0
to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (
ii
) The uterotrophic action of E2 was totally absent in

ERαAF2
0

mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (
iii
) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of

ERαAF2
0

in vivo. (
iv
) Finally, the atheroprotective effect of E2 was abrogated in

ERαAF2
0
LDL-r
−/−

mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect.
Unique structure of iC3b resolved at a resolution of 24 Å by 3D-electron microscopy
Authors: Alcorlo Martin , Martínez-Barricarte Ruben , Fernández Francisco J. , Rodríguez-Gallego César , Round Adam , Vega M. Cristina , Harris Claire L. , de Cordoba Santiago Rodríguez , Llorca Oscar
Published: July 2011

Activation of C3, deposition of C3b on the target surface, and subsequent amplification by formation of a C3-cleaving enzyme (C3-convertase; C3bBb) triggers the effector functions of complement that result in inflammation and cell lysis. Concurrently, surface-bound C3b is proteolyzed to iC3b by factor I and appropriate cofactors. iC3b then interacts with the complement receptors (CR) of the Ig superfamily, CR2 (CD21), CR3 (CD11b/CD18), and CR4 (CD11c/CD18) on leukocytes, down-modulating inflammation, enhancing B cell-mediated immunity, and targeting pathogens for clearance by phagocytosis. Using EM and small-angle X-ray scattering, we now present a medium-resolution structure of iC3b (24 Å). iC3b displays a unique conformation with structural features distinct from any other C3 fragment. The macroglobulin ring in iC3b is similar to that in C3b, whereas the TED (thioester-containing domain) domain and the remnants of the CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain have moved to locations more similar to where they were in native C3. A consequence of this large conformational change is the disruption of the factor B binding site, which renders iC3b unable to assemble a C3-convertase. This structural model also justifies the decreased interaction between iC3b and complement regulators and the recognition of iC3b by the CR of the Ig superfamily, CR2, CR3, and CR4. These data further illustrate the extraordinary conformational versatility of C3 to accommodate a great diversity of functional activities.
Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc−/−mice improves engraftment of human hematopoietic cells in humanized mice
Authors: Strowig Till , Rongvaux Anthony , Rathinam Chozhavendan , Takizawa Hitoshi , Borsotti Chiara , Philbrick William , Eynon Elizabeth E. , Manz Markus G. , Flavell Richard A.
Published: July 2011

Transplantation of human hematopoietic stem cells into severely immunocompromised newborn mice allows the development of a human hematopoietic and immune system in vivo. NOD/scid/γc−/−(NSG) and BALB/c Rag2−/−γc−/−mice are the most commonly used mouse strains for this purpose and a number of studies have demonstrated the high value of these model systems in areas spanning from basic to translational research. However, limited cross-reactivity of many murine cytokines on human cells and residual host immune function against the xenogeneic grafts results in defective development and maintenance of human cells in vivo. Whereas NSG mice have higher levels of absolute human engraftment than similar mice on a BALB/c background, they have a shorter lifespan and NOD ES cells are unsuitable for the complex genetic engineering that is required to improve human hematopoiesis and immune responses by transgenesis or knockin of human genes. We have generated mice that faithfully express a transgene of human signal regulatory protein alpha (SIRPa), a receptor that negatively regulates phagocytosis, in Rag2−/−γc−/−mice on a mixed 129/BALB/c background, which can easily be genetically engineered. These mice allow significantly increased engraftment and maintenance of human hematopoietic cells reaching levels comparable to NSG mice. Furthermore, we found improved functionality of the human immune system in these mice. In summary, hSIRPa-transgenic Rag2−/−γc−/−mice represent a unique mouse strain supporting high levels of human cell engraftment, which can easily be genetically manipulated.
Wolf–Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage
Authors: Hajdu Ildiko , Ciccia Alberto , Lewis Susanna M. , Elledge Stephen J.
Published: July 2011

Wolf–Hirschhorn syndrome (WHS) is a malformation syndrome associated with growth retardation, mental retardation, and immunodeficiency resulting from a hemizygous deletion of the short arm of chromosome 4, called the WHS critical region (WHSC). The WHSC1 gene is located in this region, and its loss is believed to be responsible for a number of WHS characteristics. We identified WHSC1 in a genetic screen for genes involved in responding to replication stress, linking Wolf–Hirschhorn syndrome to the DNA damage response (DDR). Here, we report that the WHSC1 protein is a member of the DDR pathway. WHSC1 localizes to sites of DNA damage and replication stress and is required for resistance to many DNA-damaging and replication stress-inducing agents. Through its SET domain, WHSC1 regulates the methylation status of the histone H4 K20 residue and is required for the recruitment of 53BP1 to sites of DNA damage. We propose that Wolf–Hirschhorn syndrome results from a defect in the DDR.
Identification of the thiazolyl peptide GE37468 gene cluster from
Streptomyces
ATCC 55365 and heterologous expression in
Streptomyces lividans
Authors: Young Travis S. , Walsh Christopher T.
Published: July 2011

Thiazolyl peptides are bacterial secondary metabolites that potently inhibit protein synthesis in Gram-positive bacteria and malarial parasites. Recently, our laboratory and others reported that this class of trithiazolyl pyridine-containing natural products is derived from ribosomally synthesized preproteins that undergo a cascade of posttranslational modifications to produce architecturally complex macrocyclic scaffolds. Here, we report the gene cluster responsible for production of the elongation factor Tu (EF-Tu)-targeting 29-member thiazolyl peptide GE37468 from
Streptomyces
ATCC 55365 and its heterologous expression in the model host
Streptomyces lividans
. GE37468 harbors an unusual
β
-methyl-
δ
-hydroxy-proline residue that may increase conformational rigidity of the macrocycle and impart reduced entropic costs of target binding. Isotope feeding and gene knockout were employed in the engineered
S. lividans
strain to identify the P450 monooxygenase GetJ as the enzyme involved in posttranslational transformation of isoleucine 8 to
β
-methyl-
δ
-hydroxy-proline through a predicted tandem double hydroxylation/cyclization mechanism. Loss of Ile8 oxygenative cyclization or mutation of Ile8 to alanine via preprotein gene replacement resulted in a 4-fold and 2-fold drop in antibiotic activity, respectively. This report of genetic manipulation of a 29-member thiazolyl peptide sets the stage for further genetic examination of structure activity relationships in the EF-Tu targeting class of thiazolyl peptides.
Diamond-shaped electromagnetic transparent devices with homogeneous material parameters
Authors: Li Tinghua , Huang Ming , Yang Jingjing , Yu Jiang , Lan Yaozhong
Published: July 2011

Based on the linear coordinate transformation method, two-dimensional and three-dimensional electromagnetic transparent devices with diamond shape composed of homogeneous and non-singular materials are proposed in this paper. The permittivity and permeability tensors of the transparent devices are derived. The performance and scattering properties of the transparent devices are confirmed by a full-wave simulation. It can physically protect electric devices such as an antenna and a radar station inside, without sacrificing their performance. This work represents important progress towards the practical realization of metamaterial-assisted transparent devices and expands the application of transformation optics.
Manipulation of palladium nanoparticles in a 20 nm gap between electrodes for hydrogen sensor application
Authors: Le Huy Binh , Kumar Sanjeev , Kim Gil-Ho
Published: July 2011

This study reports a promising, cost-effective nanoscale hydrogen sensor fabricated using the dielectrophoresis (DEP) process. Palladium nanoparticles (NPs) of diameter in the range 2–4 nm were assembled in a 20 nm gap between electrodes under optimized DEP parameters of frequency, voltage and assembling time of 1 M Hz, 1.5 V and 90 s, respectively. The fabricated nanoscale device was powered by applying a dc voltage of 10 mV across nanogap electrodes and temporal change in resistance at an operating temperature of 160 °C was recorded in the presence of 3000 ppm of hydrogen gas. A rise and recovery times of 100 s and 300 s, respectively, in the temporal hydrogen gas response characteristic were observed which could be attributed to the hydride formation due to the strong affinity of assembled palladium NPs towards hydrogen. The nanoscale device was sensitive enough to respond to hydrogen presence even at 30 °C. Preliminary results show the potential of DEP in fabricating cost-effective nanoscale hydrogen sensor.
Are beta2‐agonists responsible for increased mortality in heart failure?
Authors: Bermingham Margaret , O'Callaghan Eleanor , Dawkins Ian , Miwa Saki , Samsudin Shazzarina , McDonald Kenneth , Ledwidge Mark
Published: July 2011

Aims

Previous large‐scale, retrospective studies have shown increased mortality in heart failure (HF) patients using β2‐agonists (B2As). We further examined the relationship between B2A use and mortality in a well‐characterized population by adjusting for natriuretic peptide levels as a measure of HF severity.

Methods and results

This was a retrospective cohort study of patients attending an HF Disease Management Programme with mean follow‐up of 2.9 ± 2.4 years. Chart review confirmed B2A use, dose and duration of use, and documented pulmonary function evaluation. The primary endpoint was the effect of B2A use compared with no B2A use on mortality using unadjusted and adjusted Kaplan−Meier survival curves. Data were available for 1294 patients (age 70.6 ± 11.5 years) of whom 64% were male and 22.2% were taking B2As. β2‐Agonist users were older, more likely to be male, to have smoked, to have chronic obstructive pulmonary disease (COPD) and asthma, and less likely to take beta‐blockers. Multivariable associates of mortality included: B‐type natriuretic peptide (BNP), coronary artery disease, age, and beta‐blocker use. Unadjusted mortality rates for B2A users were found to be significantly higher than non‐B2A users [hazard ratio (HR) 1.304, 95% confidence interval (CI) 1.030–1.652, P= 0.028]. However, when adjusted for age, sex, medication, co‐morbidity, smoking, COPD, and BNP differences, overall mortality rates were similar [HR 1.043, 95% CI (0.771–1.412), P= 0.783].

Conclusion

Unlike previous reports, this retrospective evaluation of B2A therapy in HF patients shows no relationship with long‐term mortality when adjusted for population differences including BNP.  Large, prospective studies are required to define the risk/benefit ratio of B2As in patients with heart failure.
The burden of proof in co-management and results-based management: the elephant on the deck!
Authors: Fitzpatrick Mike , Graham Norman , Rihan Dominic J. , Reid Dave G.
Published: July 2011

Fitzpatrick, M., Graham, N., Rihan, D. J., and Reid, D. G. 2011. The burden of proof in co-management and results-based management: the elephant on the deck! – ICES Journal of Marine Science, 68: 1656–1662. Results-based management requires that outcomes can be demonstrated by industry and verified by managers on behalf of society. The core questions are: what outcomes, and how can they be proved? Existing fishery approaches to reversing the burden of proof are examined with focus on how proof is demonstrated. Outcomes can be measured in situ (on the vessel) or ex situ (at the stock or ecosystem level). In situ measures are preferable because they give direct measurements, although they can be invasive and costly. Ex situ results are only observable on scales that make it difficult to attribute them to specific management measures, or they may be influenced by external factors. Three main environmental impacts caused by fishing are assessed with respect to how industry can assume the burden of proof. The combined use of vessel-monitoring systems and benthic-impact models may offer a practical solution to the problem of managing fishery impacts on the benthos. Three Irish fisheries are assessed in terms of the feasibility of reversing the burden of proof. There are limits to the extent to which industry can assume the burden of proof, and the concept of sharing the burden of proof could be more realistic.
First Report of Rust on Osmorhiza Longistylis Caused by Puccinia Pimpinellae in India
Authors: Singh B. , Kalha C. S. , Razdan V. K. , Maheswari C. Uma
Published: July 2011

Osmorhiza longistylis (Torr.) DC., commonly known as sweet cicely, is a dominant plant species in the wastelands of the Bhaderwah Valley of District Doda in the states of Jammu and Kashmir (India). The plant is a perennial herb found abundantly near water streams and irrigation channels. The herb has medicinal value and is being used to treat digestive disorders and used as an antiseptic wash. During a disease survey in July 2010, leaf samples collected from Bhaderwah (Gwari Research Farm of Regional Horticulture Research Substation-Bhaderwah (Doda), SKUAST-Jammu) had symptoms of a rust disease. Rust symptoms appeared as small, cream colored flecks on the lower surfaces of leaves. Numerous hypophyllous, narrow, linear lesions were observed. These lesions slowly enlarged and formed light brown, erumpent, and seriately arranged sori surrounded by yellow haloes. Sori originated beneath the epidermis but ruptured through the host epidermis on sporulation. In later stages, infection extended to the stem, flowering buds, inflorescence, and fruit seeds (1,3). Teliospores were uniformly two celled, reticulate with a yellowish brown wall, obovoid-ellipsoid or oblong-ellipsoid, and 30 to 40 × 20 to 27 μm. Aeciospores were subglobose and verrucose. Urediniospores were subglobose with a yellowish brown color and 23 to 30 × 21 to 27 μm. Uredia, telia, and aecia were observed on infected leaves (2). Infected plant material has been deposited and identified at the Herbarium Crytogamae Indiae Orientalis (HCIO 50095), New Delhi. To our knowledge, this is the first report of rust on O. longistylis caused by Puccinia pimpinellae from India.

References: (1) K. M. Ghoneem et al. Plant Pathol. J. (Faisalabad) 8:165, 2009. (2) W. E. I. A. Saber et al. Afr. J. Microbiol. Res. 3:153, 2009. (3) W. I. A. Saber et al. Plant Pathol. J. (Faisalabad) 8:32, 2009.
Enterococcus ureasiticus sp. nov. and Enterococcus quebecensis sp. nov., isolated from water
Authors: Sistek Viridiana , Maheux Andrée F. , Boissinot Maurice , Bernard Kathryn A. , Cantin Philippe , Cleenwerck Ilse , De Vos Paul , Bergeron Michel G.
Published: July 2011

Three enterococcal isolates, CCRI-16620, CCRI-16986T and CCRI-16985T, originating from water were characterized using morphological, biochemical and molecular taxonomic methods. 16S rRNA gene sequence analysis classified all three strains in the

Enterococcus faecalis

species group. The phylogenetic tree of 16S rRNA gene sequences showed that the three isolates form two separate branches. The first branch is represented by strains CCRI-16620 and CCRI-16986T and the second branch by strain CCRI-16985T. Further sequence analysis of the housekeeping genes rpoA (encoding RNA polymerase α subunit), pheS (phenylalanyl-tRNA synthase), tufA (elongation factor Tu) and atpD (ATP synthase β-subunit) as well as the results of amplified fragment length polymorphism (AFLP) DNA fingerprinting and DNA–DNA hybridization experiments confirmed the distinct status of these strains. Moreover, biochemical tests allowed phenotypic differentiation of the strains from the other species of the

E. faecalis

species group. On the basis of the results obtained, the names Enterococcus ureasiticus sp. nov. (type strain CCRI-16986T = CCUG 59304T = DSM 23328T = LMG 26304T) and Enterococcus quebecensis sp. nov. (type strain CCRI-16985T = CCUG 59306T = DSM 23327T = LMG 26306T) are proposed for the two hitherto undescribed species.
Herbaspirillum
canariense sp. nov., Herbaspirillum
aurantiacum sp. nov. and Herbaspirillum
soli sp. nov., isolated from volcanic mountain soil, and emended description of the genus

Herbaspirillum
Authors: Carro Lorena , Rivas Raúl , León-Barrios Milagros , González-Tirante María , Velázquez Encarna , Valverde Angel
Published: July 2011

Three Gram-negative, motile and slightly curved rod-shaped bacteria, strains SUEMI03T, SUEMI08T and SUEMI10T, were isolated from an old volcanic mountain soil on Tenerife (Canary Islands). The three strains were related phylogenetically to

Herbaspirillum seropedicae

. 16S rRNA gene sequence similarity was 99.2–99.6 % among strains SUEMI03T, SUEMI08T and SUEMI10T, which presented 97.5, 97.8 and 97.7 % identity, respectively, with respect to

H. seropedicae

DSM 6445T. The three strains grew optimally in TSB at 28 °C and contained summed features 3 (C16 : 1ω6c and/or C16 : 1ω7c) and 8 (C18 : 1ω6c and/or C18 : 1ω7c) and C16 : 0 as major cellular fatty acids. The DNA G+C contents of strains SUEMI03T, SUEMI08T and SUEMI10T were 61.6, 60.4 and 61.9 mol%, respectively. Strains SUEMI03T, SUEMI08T and SUEMI10T presented less than 60 % interstrain DNA relatedness and less than 30 % relatedness with respect to

H. seropedicae

DSM 6445T. In spite of their common geographical origin, the three strains isolated in this study presented several phenotypic differences, presenting phenotypic profiles highly divergent from that of

H. seropedicae

. Therefore, we propose that the strains isolated in this study represent three novel species of the genus

Herbaspirillum

, named Herbaspirillum canariense sp. nov. (type strain SUEMI03T  = LMG 26151T  = CECT 7838T), Herbaspirillum aurantiacum sp. nov. (type strain SUEMI08T  = LMG 26150T  = CECT 7839T) and Herbaspirillum soli sp. nov. (type strain SUEMI10T  = LMG 26149T  = CECT 7840T).
Guidelines for the laboratory investigation of heritable disorders of platelet function
Authors: Harrison Paul , Mackie Ian , Mumford Andrew , Briggs Carol , Liesner Ri , Winter Mark , Machin Sam ,   British Committee for Standards in Haematology
Published: July 2011

The guideline writing group was selected to be representative of UK‐based medical experts. MEDLINE was systematically searched for publications in English up to the Summer of 2010 using key words platelet, platelet function testing and platelet aggregometry. Relevant references generated from initial papers and published guidelines/reviews were also examined. Meeting abstracts were not included. The writing group produced the draft guideline, which was subsequently revised and agreed by consensus. Further comment was made by members of the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 40 UK haematologists, the British Committee for Standards in Haematology (BCSH) and the British Society for Haematology Committee and comments incorporated where appropriate. Criteria used to quote levels and grades of evidence are as outlined in appendix 7 of the Procedure for Guidelines Commissioned by the BCSH [http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html]. The objective of this guideline is to provide healthcare professionals with clear guidance on platelet function testing in patients with suspected bleeding disorders. The guidance may not be appropriate to patients receiving antiplatelet therapy and in all cases individual patient circumstances may dictate an alternative approach.
The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept
Authors: Kanelleas A. , Liapi C. , Katoulis A. , Stavropoulos P. , Avgerinou G. , Georgala S. , Economopoulos T. , Stavrianeas N. G. , Katsambas A.
Published: July 2011

Background. Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)-α, which plays a central role in the psoriatic inflammation process.

Aim. To reveal any possible association between disease severity [measured by Psoriasis Area and Severity Index (PASI)] and the inflammatory burden (measured by a group of inflammatory markers), before and after etanercept treatment.

Methods. In total, 41 patients with psoriasis vulgaris, eligible for biological treatment with etanercept, were enrolled in the study. A set of inflammatory markers was measured, including levels of white blood cells and neutrophils, fibrinogen, ferritin, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), haptoglobin, ceruloplasmin and α1-antitrypsin, before and after 12 weeks of etanercept 50 mg twice weekly.

Results. All markers were reduced after treatment (P < 0.001). PASI correlated with fibrinogen and hs-CRP. Of the 41 patients, 19 (46.3%) achieved reduction of 75% in PASI (PASI75). An increase in hs-CRP and ESR difference (values before minus values after treatment) was related to higher likelihood of achieving PASI75.

Conclusions. Inflammatory markers, particularly hs-CRP and to a lesser extent, fibrinogen and ESR, can be used to assist in assessing disease severity and response to treatment in patients with psoriasis. A combination of selected inflammatory factors (which we term the Index of Psoriasis Inflammation) in combination with PASI might reflect inflammatory status in psoriasis more accurately than each one separately.
Inhibitory effect of sericin on polyphenol oxidase and its application as edible coating
Authors: Thongsook Tipawan , Tiyaboonchai Waree
Published: July 2011

Sericin, a water‐soluble globular protein derived from silk industry wastewater, was investigated for food industrial applications. The results proved that sericin retarded polyphenol oxidase (PPO) activity. However, the degree of inhibition varied depending on the enzyme origins, the types of substrate, sericin content and sericin molecular size. Using catechol as a substrate, under the conditions studied, sericin lowered purified mushroom PPO and apple extract PPO activity by 40% and mango extract PPO by 75%. Kinetic studies on purified mushroom PPO indicated that the type of inhibition of sericin was dependent on the substrates used. Inhibitory effects of sericin increased as the sericin content increased. The reduction in sericin molecular size by enzymatic hydrolysis produced sericin hydrolysate with ability to decrease PPO activity approximately three times greater than that of sericin. Fresh‐cut Red Delicious apples coated with sericin showed significant reduction in weight loss and improvement in the colour and texture.
Spray‐drying encapsulation of citral in sucrose or trehalose matrices: physicochemical and sensory characteristics
Authors: Sosa Natalia , Zamora María C. , Chirife Jorge , Schebor Carolina
Published: July 2011

The potential of the disaccharide trehalose as carrier for producing spray‐dried citral was examined. Some physical and sensory characteristics of citral encapsulated in matrices containing either trehalose or sucrose and maltodextrin (MD) were analysed. They included water sorption, glass transition temperatures (Tg), nuclear magnetic resonance (NMR) relaxation and citral retention during spray‐drying. The glassy state at room temperature (25 °C) was maintained as far as 33% relative humidities (RH) for the spray‐dried trehalose formulation and 43% RH for trehalose–MD; however, for sucrose–MD and for sucrose formulations, the glassy state was limited to RHs lower than 33% and 22%, respectively. Sensory evaluation and gas chromatographic analysis indicated that citral retention after spray‐drying was similar for matrices containing either trehalose or sucrose. However, trehalose formulations had improved physical stability as compared to sucrose.
Investigation into the interaction between resveratrol and whey proteins using fluorescence spectroscopy
Authors: Hemar Yacine , Gerbeaud Marie , Oliver Christine M. , Augustin Mary Ann
Published: July 2011

Fluorescence spectroscopy was used to investigate the interaction between resveratrol and whey proteins. The whey proteins examined were lactoferrin, holo‐lactoferrin, apo‐lactoferrin, whey protein isolate (WPI) and the β‐lactoglobulin‐ and α‐lactalbumin‐rich fractions of WPI. Both an analytical‐grade and food‐grade resveratrol were examined. In all the systems studied, it was found that resveratrol interacted with the whey proteins to form a 1:1 complex. The binding constant, Ks, for the protein–resveratrol complex for all the proteins examined varied from 1.7 × 104 to 1.2 × 105 m−1. Furthermore, the interaction between the whey proteins and resveratrol did not affect the secondary structure of the proteins.
The effects of weirs on structural stream habitat and biological communities
Authors: Mueller Melanie , Pander Joachim , Geist Juergen
Published: July 2011

1. Most of the world’s rivers are affected by dams and weirs. Information on the quantitative and qualitative effects of weirs across biological communities is crucial for successful management and restoration of stream ecosystems. Yet, there is a lack of comprehensive studies that have analysed the serial discontinuity in direct proximity of weirs including diverse taxonomic groups from algae to fish.

2. This study compared the abiotic stream habitat characteristics upstream and downstream of weirs as well as their effects on the community structure of periphyton, aquatic macrophytes, macroinvertebrates and fish at five different study rivers.

3. Physicochemical habitat characteristics discriminated strongly between upstream and downstream sides of weirs in terms of water depth, current speed, substratum composition and the transition between free‐flowing water and interstitial zone. Accordingly, abundance, diversity, community structure and functional ecological traits of all major taxonomic groups were indicative of serial discontinuity, but the discriminative power of individual taxonomic groups strongly differed between rivers.

4. The simultaneous inclusion of abiotic habitat variables, taxonomic diversity and biological traits in multivariate non‐metric multidimensional scaling was most comprehensive and powerful for the quantification of weir effects. In some cases, the intrastream discrimination induced by weirs exceeded the variation between geographically distant rivers of different geological origin and drainage systems. Community effects were generally detectable on high levels of taxonomic resolution such as family or order level.

5.
Synthesis and applications. River sections in spatial proximity to weirs are affected seriously and should be included in the ecological assessments of the European Water Framework Directive. Multivariate models that include several taxonomic groups and physicochemical habitat variables provide a universally applicable tool for the ecological assessment of impacts on serial discontinuity and other stressors on stream ecosystem health.
The housing and support needs of people with an intellectual disability into older age
Authors: Shaw K. , Cartwright C. , Craig J.
Published: July 2011

Background  People with intellectual disabilities (IDs) are growing older as a population cohort. Many live at home with family members who are their carers but who are also becoming older and less able to provide care. The housing and support preferences of people with IDs and their carers into older age are poorly characterised in the literature.

Methods  Focus groups and individual interviews were conducted with 15 people with IDs who work in supported employment and with 10 family members who care for adults with IDs. Data were thematically analysed independently by two researchers.

Results  The major themes that emerged were as follows: (1) living arrangements; (2) housing preferences; (3) ageing in place; and (4) transition from informal to formal housing and support services.

Conclusions  Participants with an ID and their carers want housing and support that enable people with an ID to maintain and enhance their social networks with their peers as they grow older and require transition to formal housing and support services, and to be able to ‘age in place’. A preference was expressed for models of housing that provide the opportunity for people with an ID to live in close proximity to their peers and in large groups in the community rather than in small, dispersed community housing.
Stage‐specific requirement for Isa1 and Isa2 proteins in the mitochondrion of Trypanosoma brucei and heterologous rescue by human and Blastocystis orthologues
Authors: Long Shaojun , Changmai Piya , Tsaousis Anastasios D. , Skalický Tomáš , Verner Zdeněk , Wen Yan‐Zi , Roger Andrew J. , Lukeš Julius
Published: July 2011

IscA/Isa proteins function as alternative scaffolds for the assembly of Fe‐S clusters and/or provide iron for their assembly in prokaryotes and eukaryotes. Isa are usually non‐essential and in most organisms are confined to the mitochondrion. We have studied the function of TbIsa1 and TbIsa2 in Trypanosoma brucei, where the requirement for both of them to sustain cell growth depends on the life cycle stage. The TbIsa proteins are abundant in the procyclic form, which contains an active organelle. Both proteins are indispensable for growth, as they are required for the assembly of Fe‐S clusters in mitochondrial aconitase, fumarase and succinate dehydrogenase. Reactive oxygen species but not iron accumulate in the procyclic mitochondrion upon ablation of the TbIsa proteins, but their depletion does not influence the assembly of Fe‐S clusters in cytosolic proteins. In the bloodstream form, which has a downregulated mitochondrion, the TbIsa proteins are non‐essential. The Isa2 orthologue of the anaerobic protist Blastocystis partially rescued the growth and enzymatic activities of TbIsa1/2 knock‐down. Rescues of single knock‐downs as well as heterologous rescues with human Isa orthologues partially recovered the activities of aconitase and fumarase. These results show that the Isa1 and Isa2 proteins of diverse eukaryotes have overlapping functions.
The Isotype of Autoantibodies Influences the Phagocytosis of Antibody‐Coated Platelets in Autoimmune Thrombocytopenic Purpura
Authors: Hoemberg M. , Stahl D. , Schlenke P. , Sibrowski W. , Pachmann U. , Cassens U.
Published: July 2011

Autoimmune thrombocytopenic purpura (AITP) is an acquired autoimmune bleeding disorder, characterized by isolated thrombocytopenia because of destruction of auto‐antibody‐coated platelets by Fc‐receptor‐mediated phagocytosis. The destruction of autoantibody‐sensitized platelets by FcγR‐bearing phagocytic cells and the following antigen presentation are considered to play a key role for the pathophysiology of AITP. Although different isotypes of AITP‐mediating autoantibodies, e.g. IgG, IgM and IgA, are frequently found in AITP patients, their role in the pathophysiology of AITP remains unclear. Using a flow cytometric monocyte‐based phagocytosis assay, we investigated the impact of disease‐associated autoantibody isotype in antibody‐mediated phagocytosis of platelets. Platelets, labelled with 5‐chloromethyl fluorescein diacetate (CMFDA), were incubated with AITP patients’ serum characterized by pure IgG or IgM antiplatelet autoantibodies. Labelled platelets were incubated with monocytes. Phagocytosis was defined as the product of percentage of CMFDA‐positive monocytes and mean fluorescence intensity of CMFDA. Adherence of platelets to monocytes was quantified by anti‐CD61‐PerCp in a CMFDA+ CD14+ gate. IgG‐coated platelets showed a significantly higher phagocytic index than IgM‐coated platelets (mean 796 ± 157 versus 539 ± 78, P < 0.01). There were no significant differences regarding platelet adherence to monocytes. The isotype of autoantibodies influences the quantity of in vitro phagocytosis of autologous platelets by monocytes. Therefore, the AITP‐mediating autoantibody isotype should be considered more carefully in pathophysiologic models and furthermore in diagnostic, therapeutic and prognostic approaches in AITP.
A sedimentary facies model for stepped, fluvial tufa systems in the Iberian Range (Spain): the Quaternary Piedra and Mesa valleys
Authors: VÁZQUEZ‐URBEZ MARTA , ARENAS CONCHA , PARDO GONZALO
Published: July 2011

Stratigraphic and sedimentological analyses of the Quaternary tufa and associated deposits in the Piedra and Mesa river valleys allowed a number of stages of their sedimentary evolution to be characterized, and a depositional sedimentary model for this north‐central sector of the Iberian Range (Spain) to be established. The proposed sedimentary facies model may explain tufa arrangements in other medium to high gradient, stepped, fluvial tufa systems with narrow transverse profiles occurring in temperate, semi‐arid areas, in both recent and past scenarios. There are several tufa deposits within the Piedra and Mesa river valleys that, over a maximum thickness of about 90 m, record one or more stages of tufa deposition produced following the fluvial incision of the bedrock or previous tufa deposits. Each depositional stage begins with coarse detrital sedimentation. Six fundamental, vertical sequences of tufa facies with small amounts of detrital material reveal the sedimentary processes that occurred in different fluvial environments: channel areas with: (i) free‐flowing water; (ii) barrages and/or cascades; and (iii) dammed water and palustrine floodplains. The proposed sedimentary model involves narrow, stepped, fluvial valleys in which tufa cascades were common. Alternating intervals of bryophyte and stromatolite facies commonly formed at some cascades. Many of these represented barrage‐cascade structures that consisted of phytoclast rudstones, thick phytoherms of mosses and associated stromatolites, and curtain‐shaped phytoherms of stems. Upstream of these structures, dammed areas with bioclastic sands and silts developed and palustrine vegetation grew. The channel stretches between barrages and/or cascades were loci for extensive stromatolite growth in fast flowing water. The palustrine floodplain was home to pools and drainage channels. The model also explains the growth of some barrages in the River Piedra that surpassed the height of the divide, with the diffluence of the main channel into a secondary course forming other tufa deposits in the area. The distribution and abundance of certain types of tufa facies in fluvial basins may be an indicator of differences in their gradients. The facies studied in this work suggest that the gradient of the ancient River Piedra was steeper than that of the ancient River Mesa. Assuming similar scenarios for climate and hydrology, the depositional settings mentioned above and their dimensions would have been determined mainly by the gradient and width of the associated river valleys. This sedimentary model may also be useful for inferring variations in other river basin slopes, as well as accounting for the presence of tufas in areas that normally have no permanent water input.
Identification of a novel HLA‐B*40 allele, B*40:162, in a Chinese individual
Authors: Jiao S.‐X. , Feng Z.‐H. , Hu B. , Chi X.‐Y. , Zhao L.
Published: July 2011

The allele was identified in a Chinese individual by sequence‐based typing. HLA‐B*40:162 differs from B*40: 06:01 by a single nucleotide at position 272 C→T in exon 2.
Factors predicting persistent thrombocytopenia after living donor liver transplantation in pediatric patients
Authors: Honda Masaki , Yamamoto Hidekazu , Hayashida Shintaro , Suda Hiroko , Ohya Yuki , Lee Kwang‐Jong , Takeichi Takayuki , Asonuma Katsuhiro , Inomata Yukihiro
Published: July 2011

Honda M, Yamamoto H, Hayashida S, Suda H, Ohya Y, Lee K‐J, Takeichi T, Asonuma K, Inomata Y. Factors predicting persistent thrombocytopenia after living donor liver transplantation in pediatric patients. Pediatr Transplantation 2011: 15: 601–605. © 2011 John Wiley & Sons A/S.

Abstract:  Thrombocytopenia is common after LT for pediatric end‐stage liver diseases. Seventy‐six pediatric patients (≤15 yr old) who underwent LDLT were evaluated for the incidence and predictive factors of post‐transplant thrombocytopenia (PLT <100 000/mm3). The prevalence of thrombocytopenia at two wk and at 12 months post‐transplant was 22/76 (28.9%) and 11/62 (17.7%), respectively. Thrombocytopenia at two wk after LDLT was significantly associated with age at transplant, preoperative PLT, GRWR, acute rejection, and CMV infection in univariate analysis. Moreover, preoperative PLT, GRWR, and acute rejection had a strong correlation in multivariate analysis. Thrombocytopenia at 12 months after LDLT was associated only with preoperative PLT. We also demonstrated that vascular complications caused thrombocytopenia and that successful treatment recovered the PLT. These results showed that, in addition to considering the preoperative PLT, post‐operative monitoring of platelets is very helpful for the early detection of adverse events related to the graft liver in pediatric liver transplant patients.
Cheats in a cooperative behaviour? Behavioural differences and breakdown of cooperative behaviour in aggregating, intertidal littorinids (Mollusca)
Authors: Stafford Richard , Davies Mark S. , Williams Gray A.
Published: July 2011

Cooperative behaviours result in the evolution of cheats: individuals that benefit from the behaviour without sharing the costs required to generate the behaviour. Normally the proportion of cheats is small, as large numbers of cheats will result in the breakdown of the behaviour. Using empirical and simulation‐derived results we demonstrate a cooperative behaviour (aggregation between two species of intertidal snails that provides a benefit by reducing desiccation stress) that shows many characteristics similar to those of a cooperative system with cheats present. In this system, the high rocky shore littorinid Echinolittorina malaccana forages for longer after high water than Echinolittorina radiata, which stops foraging and begins to form aggregations earlier. Nevertheless, E. malaccana, the ‘cheat’ in this system, still occupies an equal proportion of the most beneficial places in aggregations. Computer simulations demonstrate that up to 65% of individual snails can show the behaviour of E. malaccana before the breakdown of this aggregation behaviour begins to occur through aggregations becoming smaller, and hence less effective against desiccation. The high proportion of ‘cheats’ possible in this cooperative behaviour implies that different selective pressures may act on individuals of different species in multi‐species cooperative behaviours to those acting on individuals engaging in single species cooperative behaviours. Social symbiosis appears to be occurring between the species, but it appears that both mutualistic and parasitic symbioses are occurring.