bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative model for cyclin-dependent kinase control of the cell cycle: revisited
Authors: Uhlmann Frank , Bouchoux Céline , López-Avilés Sandra
Published: November 2011

The eukaryotic cell division cycle encompasses an ordered series of events. Chromosomal DNA is replicated during S phase of the cell cycle before being distributed to daughter cells in mitosis. Both S phase and mitosis in turn consist of an intricately ordered sequence of molecular events. How cell cycle ordering is achieved, to promote healthy cell proliferation and avert insults on genomic integrity, has been a theme of Paul Nurse's research. To explain a key aspect of cell cycle ordering, sequential S phase and mitosis, Stern & Nurse proposed ‘A quantitative model for cdc2 control of S phase and mitosis in fission yeast’. In this model, S phase and mitosis are ordered by their dependence on increasing levels of cyclin-dependent kinase (Cdk) activity. Alternative mechanisms for ordering have been proposed that rely on checkpoint controls or on sequential waves of cyclins with distinct substrate specificities. Here, we review these ideas in the light of experimental evidence that has meanwhile accumulated. Quantitative Cdk control emerges as the basis for cell cycle ordering, fine-tuned by cyclin specificity and checkpoints. We propose a molecular explanation for quantitative Cdk control, based on thresholds imposed by Cdk-counteracting phosphatases, and discuss its implications.
A furnace and environmental cell for thein situinvestigation of molten salt electrolysis using high-energy X-ray diffraction
Authors: Styles Mark J. , Rowles Matthew R. , Madsen Ian C. , McGregor Katherine , Urban Andrew J. , Snook Graeme A. , Scarlett Nicola V. Y. , Riley Daniel P.
Published: November 2011

This paper describes the design, construction and implementation of a relatively large controlled-atmosphere cell and furnace arrangement. The purpose of this equipment is to facilitate thein situcharacterization of materials used in molten salt electrowinning cells, using high-energy X-ray scattering techniques such as synchrotron-based energy-dispersive X-ray diffraction. The applicability of this equipment is demonstrated by quantitative measurements of the phase composition of a model inert anode material, which were taken during anin situstudy of an operational Fray–Farthing–Chen Cambridge electrowinning cell, featuring molten CaCl2as the electrolyte. The feasibility of adapting the cell design to investigate materials in other high-temperature environments is also discussed.
Mechanism for enhancing dispersion of Co3O4nanoparticles in Co/SiO2Fischer–Tropsch synthesis catalyst by adding glycol to impregnating solution: a quick-XAFS study
Authors: Koizumi Naoto , Suzuki Shigenobu , Ibi Yukiya , Hayasaka Yasuhiko , Hamabe Yusuke , Shindo Takayoshi , Yamada Muneyoshi
Published: November 2011

In situCoK-edge quick-EXAFS (QEXAFS) coupled with temperature-programmed oxidation as well asex situXAFS was applied to investigating the mechanism for enhancing the dispersion of Co3O4nanoparticles in a calcined Co/SiO2Fischer–Tropsch synthesis catalyst prepared by adding triethylene glycol (TEG) to a Co(NO3)2.6H2O impregnating solution.Ex situCoK-edge XAFS indicated that, regardless of whether the catalysts were prepared with or without using TEG, the hexaaqua Co (II) complex was formed in impregnated samples which then underwent the dehydration process to some extent during the subsequent drying step at 393 K.In situQEXAFS andex situEXAFS results also indicated that small oxide clusters were formed in the TEG-modified catalyst calcined at ∼400–470 K which interacted with polymer species derived from TEG. Since the Fischer–Tropsch synthesis activity of the TEG-modified catalyst increased with an increase in the calcination temperature in a similar temperature range [Koizumiet al.(2011),Appl. Catal. A,395, 138–145], it was suggested that such an interaction enables the clusters to be distributed over the support surface uniformly, resulting in enhancing their dispersion. After combustion of polymer species, Co3O4-like species were formed, and agglomeration of the Co3O4-like species at high calcination temperatures was suppressed by the addition of TEG to the impregnating solution. It was speculated that the addition of TEG induced the formation of some surface silicate which worked as an anchoring site for Co3O4and Co0nanoparticles during calcination and H2reduction, respectively.
Status of the hard X-ray microprobe beamline ID22 of the European Synchrotron Radiation Facility
Authors: Martínez-Criado Gema , Tucoulou Rémi , Cloetens Peter , Bleuet Pierre , Bohic Sylvain , Cauzid Jean , Kieffer Isabelle , Kosior Ewelina , Labouré Sylvain , Petitgirard Sylvain , Rack Alexander , Sans Juan Angel , Segura-Ruiz Jaime , Suhonen Heikki , Susini Jean , Villanova Julie
Published: November 2011

The ESRF synchrotron beamline ID22, dedicated to hard X-ray microanalysis and consisting of the combination of X-ray fluorescence, X-ray absorption spectroscopy, diffraction and 2D/3D X-ray imaging techniques, is one of the most versatile instruments in hard X-ray microscopy science. This paper describes the present beamline characteristics, recent technical developments, as well as a few scientific examples from recent years of the beamline operation. The upgrade plans to adapt the beamline to the growing needs of the user community are briefly discussed.
X-ray absorption measurements on an ultrasonic spray aerosol
Authors: Schlaf R. , Höpfner B. , Figueroa J. , Tridas E. , Welter E. , Köhler T. , Lauermann I. , Fischer Ch.-H.
Published: November 2011

Spray deposition of thin films and coatings is a widely used manufacturing process owing to its low cost, versatility and simple implementation. The objective of the presented experiments was to investigate whether X-ray absorption measurements on solutes carried by aerosols are possible, and what count rates can be achieved depending on solution flow through and the resulting mass density in the interrogation volume. The investigated prototypical spray aerosol was InCl3dissolved in water or ethanol dispersedviaan ultrasonic nebulizer. InCl3spray is essential for the ion layer gas reaction process used for the deposition of In2S3buffer layers for highly efficient chalcopyrite solar cells. The discussed experiments demonstrate that measurements are possible, but that the achievement of good signal-to-noise ratios requires extended sampling times and concentrated solutions.
Interactions between killer immunoglobulin‐like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm
Authors: Littera Roberto , Orrù Nicola , Caocci Giovanni , Sanna Marco , Mulargia Marina , Piras Eugenia , Vacca Adriana , Giardini Claudio , Orofino Maria G. , Visani Giuseppe , Bertaina Alice , Giorgiani Giovanna , Locatelli Franco , Carcassi Carlo , La Nasa Giorgio
Published: November 2011

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin‐like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft‐versus‐host disease (GvHD) [hazard risk (HR) 4·2, 95% confidence interval (CI) 1·7–10·1, P = 0·002] and transplantation‐related mortality (HR 4·7, 95% CI 1·6–14·2, P = 0·01). The risk of GvHD furthermore increased when recipients heterozygous for HLA‐C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6·1, 95% CI 1·9–19·2, P = 0·002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA‐KIR ligand group and the donor carried two or more activating KIRs (HR 6·8, 95% CI 1·9–24·4, P = 0·005). By interpolating the number of donor activating KIRs with recipient HLA‐C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision‐making.
Inflammation and remodelling patterns in early stage chronic rhinosinusitis
Authors: Van Bruaene N. , C. Perez‐Novo , Van Crombruggen K. , De Ruyck N. , Holtappels G. , Van Cauwenberge P. , Gevaert P. , Bachert C.
Published: November 2011

Background

A distinct set of inflammatory and remodelling factors have been found elevated in chronic rhinosinusitis.

Objective

The investigation of their expression in early stage disease may reveal early events in this common disease.

Methods

Sinonasal mucosal samples from nine patients with early stage CRSsNP were taken from the inferior and middle turbinates, the uncinate process, maxillary sinus, anterior ethmoid, bulla ethmoidalis and the posterior ethmoid and measured for TGF‐beta 1 and it's receptors, MPO protein as well as pro‐inflammatory cytokines (TNF‐alpha and IL‐1beta) and the Th1 cell signature (IFN‐gamma and T‐bet). As outcome parameter for TGF‐beta signalling collagen deposition was analysed. Inferior turbinates from patients undergoing (rhino‐) septoplasty were collected as controls.

Results

TGF‐beta 1 protein concentrations were significantly increased in the maxillary sinuses (P = 0.006), the uncinate process (P = 0.01), the anterior ethmoid including the bulla ethmoidalis (P = 0.005) and the posterior ethmoid (P = 0.037) when compared to the inferior and middle turbinates. Collagen deposition was significantly increased in the maxillary sinus when compared to the inferior turbinates (P = 0.008). In contrast, mRNA for TGF‐beta receptors, Th1 related markers (IFN‐gamma and T‐bet), pro‐inflammatory cytokines (IL‐1 beta and TNF‐alpha), and MPO protein as neutrophil marker were expressed at all locations but showed no significant differences between the various locations. TGF‐beta 1 mRNA expression in inferior turbinates of CRSsNP was significantly higher when compared to inferior turbinates of controls (P = 0.017). The pro‐inflammatory cytokines and Th1‐related cytokines did not show an upregulation in inferior turbinates of CRSsNP when compared to controls.

Conclusions

In early stage chronic sinus disease, TGF‐beta protein is expressed in significantly higher concentrations within the paranasal sinuses when compared to turbinates, whereas pro‐inflammatory, neutrophilic and Th1 markers did not show any difference. These findings suggest that TGF‐beta plays a central role in the initiation of CRSsNP, and represents a major target for further research and future intervention.
Evaluation of the child with atopic dermatitis
Authors: de Bruin Weller M. S. , Knulst A. C. , Meijer Y. , Bruijnzeel‐Koomen C. A. F. M. , Pasmans S. G. M.
Published: November 2011

Atopic dermatis (AD) is a very common inflammatory skin disease in childhood. Various doctors such as paediatricians, general practitioners, allergologists and dermatologists are regularly consulted by these children and their parents, but there is no clear consensus on the diagnostic work‐up that should be performed when evaluating a child with eczema. A careful history, clinical examination and adequate documentation of disease severity are essential in all children with eczema, irrespective of their disease severity. AD is a clinical diagnosis; diagnostic criteria, such as the UK diagnostic criteria, can be helpful for an accurate definition of the disease. A careful history, including alarm symptoms, respiratory symptoms and the impact of the disease on psychosocial functioning is important. Clinical scoring lists such as SCORAD and EASI are well validated for clinical studies; they are, however, not very suitable tools in clinical practice. More simple scoring systems, such as Three Item Severity Score (TIS) and Investigator Global Assessment (IGA), are more easy to use for clinical record keeping in daily practice. Allergen testing in children with AD without a history of acute non‐eczematous reactions after allergen exposure is not necessary. In very young children with eczema, not yet exposed to foods, routine allergen testing is not necessary. If in individual cases, the decision is made to perform allergen tests, oral challenges should performed to confirm the diagnoses of food allergy.
Temporal and spatial variation in ecosystem metabolism and food web carbon transfer in a wet‐dry tropical river
Authors: HUNT RICHARD J. , JARDINE TIMOTHY D. , HAMILTON STEPHEN K. , BUNN STUART E. ,   TROPICAL RIVERS and COASTAL KNOWLEDGE RESEARCH HUB
Published: November 2011

1. High light availability and stable base flow during the dry season promote primary production in perennial rivers of the wet–dry tropics, in contrast to production during the wet season which is often limited by turbidity and scouring. The Mitchell River of northern Queensland (Australia) was studied to understand controls on aquatic production and respiration in the dry season in relation to spatial and temporal gradients of light and temperature.

2. At three sites along the river, whole‐ecosystem gross primary production (GPP) and respiration (ER) were measured from diel changes of dissolved oxygen using the open‐channel single station method. Using stable carbon and nitrogen isotope analysis, aquatic consumers and their potential basal food resources were also assessed to determine food web relationships at the beginning and end of the dry season.

3. Nutrient limitation of aquatic net primary production was implied from the oligotrophic conditions and high algal C:N ratios. Rates of GPP were comparable with other tropical and temperate rivers and were regulated by light availability.

4. Respiration rates were high and similar to other tropical and subtropical rivers. Up to 52% of temporal variation of ER was explained by temperature, while P/R was lowest at the downstream site.

5. Benthic algae were the major carbon source for primary and secondary benthic consumers (insects) in the dry season but not for higher consumers (fish and crustaceans). Despite high rates of ER, which were probably supported by decaying terrestrial C3 plant material, this carbon source was not identified as contributing to animal consumer biomass.

6. While benthic algal production in the dry season sustained benthic invertebrates, the importance of external subsidies of carbon along the river, probably from the floodplain, was emphasised for fish and large invertebrates, which evidently were feeding on carbon sources not present in channel waterholes during the dry season.
Evaluation of online miRNA resources for biomedical applications
Authors: Tan Gana Neil H. , Victoriano Ann F. B. , Okamoto Takashi
Published: November 2011

MicroRNAs (miRNAs) are endogenous single‐stranded, 22‐nt (nucleotide) RNAs which complement mRNA to initiate post‐transcriptional regulation. This review presents updates and evaluations of the public domain resources available for miRNA identification and target prediction toward their utilization in the biomedical research approach. This study discusses the basic principles of miRNA computational studies based on the nature and mechanism of action of miRNAs. Furthermore, we have explored fifty‐nine current online miRNA tools that can be categorized into three classes in this paper: (i) miRNA identification; (ii) miRNA target prediction; and (iii) specialized miRNA tools.
Pregnancy in type 2B VWD: a case series
Authors: RANGER A. , MANNING R. A. , LYALL H. , LAFFAN M. A. , MILLAR C. M.
Published: November 2011

Summary.  Type 2B von Willebrand disease (VWD) is a rare, inherited bleeding disorder resulting from a qualitative defect in von Willebrand factor (VWF). There is very little published information on how to quantify bleeding risk and manage haemostasis in type 2B VWD patients during pregnancy. This article presents the changes in VWF parameters and details of patient management and delivery outcomes for four pregnancies in three women with two different mutations causing type 2B VWD. We report an unexpected rise in the VWF:Ag at 37 weeks gestation in two sisters with R1306W associated with significant thrombocytopenia. These patients were supported with platelet transfusions as well as intermediate purity VWF‐FVIII plasma concentrates during the peri‐ and postpartum periods. No thrombocytopenia was observed in our third case with a mutation encoding an R1308C substitution; haemostatic support was with intermediate purity VWF‐FVIII plasma concentrates alone. No adverse bleeding events occurred and in all cases a live healthy infant was delivered. One patient was readmitted post partum with bleeding symptoms due to retained placenta; no further haemostatic support was given at this time. This case series is the first to detail the progression of laboratory parameters, management and outcomes of pregnancy in patients with type 2B VWD. The cases illustrate some of the challenges posed by the increased production of a VWF variant with a gain‐of‐function effect. The rapid coagulation changes observed in this series illustrate the need for continual monitoring of VWF parameters and platelet count throughout pregnancy in women with type 2B VWD.
Second‐generation platelet concentrate (PRF) as a pulpotomy medicament in a permanent molar with pulpitis: a case report
Authors: Hiremath H. , Saikalyan S. , Kulkarni S. S. , Hiremath V.
Published: November 2011

Hiremath H, Saikalyan S, Kulkarni SS, Hiremath V. Second‐generation platelet concentrate (PRF) as a pulpotomy medicament in a permanent molar with pulpitis: A case report. International Endodontic Journal, 45, 105–112, 2012.

Aim  To discuss the clinical and radiographic success of a pulpotomy with second‐generation platelet concentrate (PRF), in a human mature permanent molar tooth.

Summary  A 19‐year‐old female patient reported to the Department of Conservative Dentistry and Endodontics with established pulpitis in tooth 36. The tooth had a carious pulp exposure, with a history of lingering pain. After isolation, caries removal and pulp exposure, pulpotomy with PRF was performed and a permanent restoration was placed immediately. At the first recall (+1 day), no postoperative pain was reported. At 6, 12, 18 and 22 months recall, the tooth responded positively to pulp sensibility tests, and radiographic examination revealed a normal periodontal ligament space. Positive results of this case imply the need for more studies with larger sample sizes and a longer recall period to justify the use of this novel material for the treatment of pulpitis in human permanent molar teeth.

Key learning points 

 Pulpotomy with PRF could be an alternate treatment to mineral trioxide aggregate or other materials in mature permanent teeth with pulpitis.
Vegetation dynamics and avian seasonal migration: clues from remotely sensed vegetation indices and ecological niche modelling
Authors: Papeş M. , Peterson A. T. , Powell G. V. N.
Published: November 2011

Aim  Regional movements of tropical birds are among the least understood patterns of migration, generally assumed to be related to seasonality of vegetation and food resources. We used readily available remotely sensed data to analyse this relationship in the three‐wattled bellbird (Procnias tricarunculatus), an IUCN Vulnerable canopy frugivorous bird that undergoes localized altitudinal and latitudinal movements between several non‐breeding and breeding ranges.

Location  Central America.

Methods  We generated ecological niche models (GARP and Maxent) based on remotely sensed vegetation indices (enhanced vegetation index, EVI; red index, RI; and normalized difference water index, NDWI) that were used as proxies for canopy characteristics and phenological changes between seasons. The variation in EVI was also analysed in relation to known bellbird seasonal migration patterns.

Results  Remotely sensed summaries of intra‐annual vegetation variation could not explain known movement patterns of bellbirds breeding in Monteverde Cloud Forest Reserve, Costa Rica. The ecological niche modelling (ENM) framework used for exploring potential movement patterns of another population of bellbirds, observed in March 2004 in Corcovado National Park, Costa Rica, showed that the Atlantic and Pacific lowlands are suitable for the bellbirds year‐round, while middle elevations, where breeding may occur, have limited suitability.

Main conclusions  Our findings suggest that: (1) the Corcovado population tracks similar environmental conditions during the non‐breeding season; (2) migration to middle elevation breeding sites might be related to factors other than vegetation seasonality or breeding might not be restricted to these elevation ranges; and (3) the lowlands comprising most of the suitable areas for bellbirds are where anthropogenic pressure is highest, so conservation status should consider this threat, and conservation planning should emphasize these areas.
Furfural reduction mechanism of a zinc‐dependent alcohol dehydrogenase from Cupriavidus necator JMP134
Authors: Kang ChulHee , Hayes Robert , Sanchez Emiliano J. , Webb Brian N. , Li Qunrui , Hooper Travis , Nissen Mark S. , Xun Luying
Published: November 2011

FurX is a tetrameric Zn‐dependent alcohol dehydrogenase (ADH) from Cupriavidus necator JMP134. The enzyme rapidly reduces furfural with NADH as the reducing power. For the first time among characterized ADHs, the high‐resolution structures of all reaction steps were obtained in a time‐resolved manner, thereby illustrating the complete catalytic events of NADH‐dependent reduction of furfural and the dynamic Zn2+ coordination among Glu66, water, substrate and product. In the fully closed conformation of the NADH complex, the catalytic turnover proved faster than observed for the partially closed conformation due to an effective proton transfer network. The domain motion triggered by NAD(H) association/dissociation appeared to facilitate dynamic interchanges in Zn2+ coordination with substrate and product molecules, ultimately increasing the enzymatic turnover rate. NAD+ dissociation appeared to be a slow process, involving multiple steps in concert with a domain opening and reconfiguration of Glu66. This agrees with the report that the cofactor is not dissociated from FurX during ethanol‐dependent reduction of furfural, in which ethanol reduces NAD+ to NADH that is subsequently used for furfural reduction.
Molecular analysis of the crenarchaeal flagellum
Authors: Lassak Kerstin , Neiner Tomasz , Ghosh Abhrajyoti , Klingl Andreas , Wirth Reinhard , Albers Sonja‐Verena
Published: November 2011

The ability to move towards favourable conditions provides fundamental advantages to organisms. Interestingly, flagella as motility structures evolved independently in the bacterial and the archaeal kingdom. Whereas bacterial flagella have been intensively studied, our knowledge regarding the archaeal counterpart is mostly restricted to Euryarchaeota rather than crenarchaeal flagella. We therefore investigated the flagellar assembly system of the crenarchaeal model organism Sulfolobus acidocaldarius in vivo. Promoter studies and qRT‐PCR analyses of the flagella gene cluster provided evidence that the expression of the fla genes was induced by tryptone starvation. Moreover, we confirmed presence of a secondary fla promoter within the flaB gene that regulates the transcription of downstream genes flaX‐J. Markerless in‐frame deletions for all fla genes encoded in the fla gene cluster were constructed. Western blot analysis of all fla deletion strains suggested hierarchical protein interactions during the archaeal flagella assembly. Moreover, functional analysis by thermomicroscopy revealed non‐motile cells for each of the mutant strains. Electron micrographs demonstrated that lack of motility coincided with the loss of flagellar assembly. Thus we demonstrated that all seven fla genes are essential for crenarchaeal flagellum assembly and function.
Epigenetic modifications in cancer
Authors: Kanwal R , Gupta S
Published: November 2011

Kanwal R, Gupta S. Epigenetic modifications in cancer.

Cancer initiation and progression is controlled by both genetic and epigenetic events. The complexity of carcinogenesis cannot be accounted for by genetic alterations alone but also involves epigenetic changes. Epigenetics refers to the study of mechanisms that alter gene expression without altering the primary DNA sequence. Epigenetic mechanisms are heritable and reversible, and include changes in DNA methylation, histone modifications and small noncoding microRNAs (miRNA). Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Aberrant epigenetic modifications probably occur at a very early stage in neoplastic development, and they are widely described as essential players in cancer progression. Recent advances in epigenetics offer a better understanding of the underlying mechanism(s) of carcinogenesis and provide insight into the discovery of putative cancer biomarkers for early detection, disease monitoring, prognosis, and risk assessment. In this review, we summarize the current literature on epigenetic changes causing genetic alterations that are thought to contribute to cancer, and discuss the potential impact of epigenetics future research.
A CD40 single‐nucleotide polymorphism affects the lymphocyte profiles in the bronchoalveolar lavage of Japanese patients with sarcoidosis
Authors: Tanizawa K. , Handa T. , Nagai S. , Ito I. , Kubo T. , Ito Y. , Watanabe K. , Aihara K. , Mishima M. , Izumi T.
Published: November 2011

CD40 plays a critical role in adaptive immunity, and alveolar macrophages in patients with sarcoidosis express higher levels of CD40. This study investigated the association of rs1883832, a functional single‐nucleotide polymorphism in the CD40 gene with susceptibility to sarcoidosis and phenotypes of sarcoidosis. Genotyping of rs1883832 in 175 Japanese patients with sarcoidosis and 150 age‐ and sex‐matched controls revealed no significant difference between the genotypes of the patient and control groups (CC/CT/TT, 32.8/52.0/14.7% in the patients; 37.3/48.0/14.7% in the controls, P = 0.66; allele C, 59.1% in the patients, 61.3% in the controls, P = 0.57). T‐cell and CD4+ cell counts in the bronchoalveolar lavage fluid were significantly higher in the TT genotype group than in the CC and CT genotype group.
Genome‐wide analysis of extended pedigrees confirms IL2–IL21 linkage and shows additional regions of interest potentially influencing coeliac disease risk
Authors: Einarsdottir E. , Koskinen L. L. E. , de Kauwe A. L. , Dukes E. , Mustalahti K. , Balogh M. , Korponay‐Szabo I. R. , Kaukinen K. , Kurppa K. , Ádány R. , Pocsai Z. , Széles G. , Mäki M. , Kere J. , Saavalainen P.
Published: November 2011

Coeliac disease is a chronic inflammatory condition of the small intestine, triggered by dietary exposure to gluten in genetically susceptible individuals. Risk alleles at HLA‐DQA1 and HLA‐DQB1 are necessary for disease development, but are alone not sufficient for disease onset. We aimed to identify novel loci underlying susceptibility to coeliac disease through the use of extended Finnish and Hungarian families with multiple affected individuals. An initial whole‐genome linkage approach yielded several loci that were followed up further using the Immunochip custom array. Loci with a parametric logarithm of odds (LOD) score of >1.3 were identified at 4q, 6p [human leukocyte antigen (HLA) region], 6q, 7p, 17p, 17q and at 22p. The 4q and 6q loci have been identified previously in coeliac disease risk, whereas follow‐up analyses indicate that the 17p and 22p loci may be novel risk loci for coeliac disease. These loci harbour previously described risk variants for other autoimmune diseases, but their segregation patterns do not explain the linkage to coeliac disease. We followed up the linkage to the 4q region, containing the previously described interleukin (IL)2 and IL21 genes. The risk variants at 4q in the studied pedigrees are most likely distinct from previously described risk variants, indicating that the observed linkage may be due to rare high‐risk variants of still unknown nature. The importance of this locus to coeliac disease risk was further shown by the finding that serum levels of IL21 were elevated in both untreated and treated coeliac patients compared to controls.
Natural killer cell engineering for cellular therapy of cancer
Authors: Shook D. R. , Campana D.
Published: November 2011

Natural killer (NK) cells can kill transformed cells and represent a promising tool for the treatment of cancer. Their function is governed by a balance of stimulatory and inhibitory signals triggered by surface receptors. Advances in NK cell therapy require the development of dependable methods for obtaining an adequate number of effector cells; additional activation or genetic modification may further increase their anticancer capacity. A method for NK cell expansion used in our laboratory relies on a genetically modified form of the K562 myeloid leukemia cell line, engineered to express a membrane‐bound form of interleukin‐15 and the ligand for the costimulatory molecule 4‐1BB (CD137). Expanded NK cells can be transduced with genes encoding chimeric antigen receptors that stimulate tumor cell‐specific cytotoxicity. These methods for NK cell expansion and genetic modification have been adapted to large‐scale, clinical‐grade, Current Good Manufacturing Practice conditions and support two active clinical trials. Summarized are current efforts for NK cell immunotherapy for cancer and future perspectives.
Maternal effects and heritability of annual productivity
Authors: SCHROEDER J. , BURKE T. , MANNARELLI M.‐E. , DAWSON D. A. , NAKAGAWA S.
Published: November 2011

Within‐individual consistency and among‐individual heterogeneity in fitness are prerequisites for selection to take place. Within‐individual variation in productivity between years, however, can vary considerably, especially when organisms become older and more experienced. We examine individual consistency in annual productivity, the covariation between survival and annual productivity, and the sources of variation in annual productivity, while accounting for advancing age, to test the individual‐quality and resource‐allocation life‐history theory hypotheses. We use long‐term data from a pedigreed, wild population of house sparrows. Within‐individual annual productivity first increased and later decreased with age, but there were no selective mortality due to individual quality and no correlation between lifespan and productivity. Individuals were consistent in their annual productivity (C = 0.49). Narrow‐sense heritability was low (h2 = 0.09), but maternal effects explained much of the variation (M = 0.33). Such effects can influence evolutionary processes and are of major importance for our understanding of how variation in fitness can be maintained.
Development and verification of a diagnostic assay based on EF‐1 α for the identification ofArmillariaspecies in Northern Europe
Authors: Mulholland V. , MacAskill G. A. , Laue B. E. , Steele H. , Kenyon D. , Green S.
Published: November 2011

The overall aim of this study was to develop a new, reliable and rapid diagnostic assay for differentiating six EuropeanArmillariaspecies based on variation in their elongation factor‐1 alpha (EF‐1 α) gene sequences and to verify a set of species‐specific primers on 61Armillariaisolates from Europe. Partial sequences of the EF‐1 α gene obtained inArmillaria borealis,Armillaria cepistipes,Armillaria gallica,Armillaria mellea,Armillaria ostoyaeandArmillaria tabescensrevealed sufficient interspecific variation to distinguish among species using nested primers. These primers gave unambiguous bands when tested on representative isolates of five of these species. However, the EF‐1 α sequences of EuropeanA. borealisisolates clustered into two distinct clades, termed hereAbX andAbY. Specific primers were subsequently designed and tested successfully on bothAbX‐type andAbY‐typeA. borealisisolates. The taxonomy ofA. borealisneeds to be elucidated to determine whether a new, as yet unnamedArmillariataxon exists in Europe. ThreeA. borealisisolates were also found to have heterozygous sites in their EF‐1 α sequences, which suggests that the gene could exist in more than one copy or that these isolates contain hybrid sequences. A pyrosequencing method was also developed, targeting a small region of EF‐1 α intron 4, which was able to differentiate EuropeanArmillariaisolates to the species level and additionally could distinguishAbX‐type andAbY‐typeA. borealisisolates.
Severe neonatal jaundice: Is it a rare event in Australia?
Authors: McGillivray Angela , Evans Nick
Published: November 2011

Hyperbilirubinaemia is common in the newborn period, and while the vast majority of babies are unaffected, significant neurological impairment remains a risk associated with extremely high levels of bilirubin. There is concern internationally that the number of babies affected by severe neonatal hyperbilirubinaemia may be increasing. This review describes the most current published data pertaining to the incidence and causes of severe neonatal hyperbilirubinaemia in order to determine whether concern regarding the possible re‐emergence of kernicterus in Australia is warranted. Seven incidence studies conducted internationally between 1988 and 2005 identify an estimated incidence of severe neonatal jaundice of between 7.1 and 45 per 100 000 births and of kernicterus at 0.4–2.7. Major pathophysiological causes or associations include ABO and other blood group incompatibility, glucose‐6‐phoshate‐dehydrogenase deficiency, infection and haemolysis of other causes including spherocytosis. Other factors associated with poor outcomes include prematurity, male gender, ethnicity, breastfeeding and early hospital discharge. The management of severe neonatal jaundice requires multifaceted risk quantification in addition to the availability of adequate surveillance, particularly in the context of early hospital discharge. It is of concern that currently there is a paucity of incidence data in Australia relating to this potentially devastating yet generally preventable condition. Therefore, a surveillance study has been initiated through the Australian Paediatric Surveillance Unit. It is anticipated that these data will accurately define the incidence in Australia and hopefully guide strategies to prevent a condition that we may have prematurely considered to be of historical interest only.
Bony presentations of childhood haematological malignancy to the emergency room
Authors: Teo Wan‐Yee , Chan Mei‐Yoke , Ng Kee‐Chong , Tan Ah‐Moy
Published: November 2011

Aim:  Bony complaints are well‐recognised symptoms of childhood haematological malignancy. However, this elusive symptom complex of haematological malignancy is not easily recognised in the emergency room (ER) where musculoskeletal problems are frequent. This study reviews bony complaints of childhood haematological malignancy in the ER.

Methods:  This was a retrospective study of 148 children diagnosed with haematological malignancy between March 2002 and February 2007.

Results:  Twenty‐one cases (14.2%) presented with bony complaints to the ER within 3 months prior diagnosis of malignancy. The median age was 5.1 years, and majority (90.5%) had acute lymphoblastic leukaemia. Fifteen cases were undiagnosed for malignancy at first visit; diagnoses included pulled elbow, lower limb sprain and septic arthritis, with 21 days median time to correct diagnosis. In this undiagnosed group, history of trauma, fever, multiple bony site involvement, normal radiography and blood counts were common. Undiagnosed cases were referred to orthopaedics, paediatrics, rheumatology or the general practitioner, hospitalised or discharged without follow‐up.

Conclusion:  The diagnosis of childhood haematological malignancy with first bony presentation to the ER was challenging, with a high prevalence of 71.4% undiagnosed cases at first visit. We highlight the common misdiagnoses because failure to correctly diagnose could delay timely institution of treatment. Trauma or normal investigations do not exclude an underlying haematological malignancy. This rare diagnosis in the ER should always be considered when challenged with recurrent bony complaints.
Opportunities taken: The need for and effectiveness of secondary care opportunistic immunisation
Authors: Shingler Simon , Hunter Kim , Romano Andrina , Graham David
Published: November 2011

Aim:  To evaluate the effectiveness of a formalised opportunistic immunisation (OI) system in a hospital setting.

Methods:  Pre–post implementation audit of missed immunisation opportunities.

Results:  Of 5583 children in the National Immunisation Register cohort seen in a hospital setting, 1641 (29.4%) were under‐immunised, compared with the concurrent regional cohort of 15%. Māori children were less likely to be age‐appropriately immunised (36.9% under‐immunised, P < 0.0005, χ2= 41.4). Of the 1641 under‐immunised children, 337 (20.5%) were deemed to have current medical reasons not to be immunised acutely, and of the remaining 1304, 244 (18.7%) declined immunisations. This left 1060 for whom immunisation was possible, and we immunised 880 (83.0%) of these. All children were re‐engaged with primary care services.

Conclusions:  Children in contact with secondary care services have low immunisation rates with ethnic disparity. Appropriately resourced formalised OI is effective, with potential for further improvement. The system we have implemented enhances primary care involvement.
Serial developmental assessments in infants with deformational plagiocephaly
Authors: Hutchison B Lynne , Stewart Alistair W , de Chalain Tristan , Mitchell Edwin A
Published: November 2011

Aim:  An association between positional plagiocephaly and developmental problems has previously been noted, but whether delays persist over time has not been established. This study aimed to determine developmental outcomes for children with deformational plagiocephaly over 1 year of follow up.

Methods:  This was a longitudinal cohort study of 126 infants with deformational plagiocephaly recruited at an outpatient clinic. Development was assessed with the parent‐completed Ages and Stages Questionnaires at recruitment and repeated at follow‐up assessments in the home 3, 6 and 12 months later. Questionnaires were scored according to cut‐off scores from the Ages and Stages Questionnaires, Third Edition.

Results:  Ninety‐six percent of children were followed up for the full 12 months. The existence of one or more delays initially was 30%; this rose to 42% at the 3‐month follow up then dropped back to 23% by the 12‐month follow up. Delays were predominantly in the gross motor domain. Ten percent had >4 delays in total over the four assessments. Mothers with tertiary education were more likely to have infants showing delays that persisted over time.

Conclusions:  Infants with deformational plagiocephaly exhibited marked delays especially in early infancy. These delays were largely gross motor in type but had reduced to approach the expected level by the time of the 12‐month follow up, at a mean age of 17 months.
Corticomotor representation to a human forearm muscle changes following cervical spinal cord injury
Authors: Freund Patrick , Rothwell John , Craggs Michael , Thompson Alan J. , Bestmann Sven
Published: November 2011

Functional imaging studies, using blood oxygen level‐dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging‐navigated transcranial magnetic stimulation (TMS) to non‐invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1‐weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma‐related anatomical changes and TMS parameters. SCI participants had increased AMTs (P = 0.01) and increased CSP duration (P = 0.01). The CoG of the EDC motor‐evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (P = 0.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r2 ≥ 0.26, P < 0.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI.
Elevation of serum high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension: association with arterial stiffness and hypercoagulability
Authors: Aso Y. , Wakabayashi S. , Terasawa T. , Naruse R. , Hara K. , Takebayashi K. , Inukai T.
Published: November 2011

Diabet. Med. 29, 80–87 (2012)

Aim  Orthostatic hypotension is a hallmark of diabetic autonomic neuropathy and is associated with increased mortality. The serum level of adiponectin is elevated in patients with heart failure or renal failure. In the present study, we measured serum levels of total and high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension. We also investigated the relationship between the presence of orthostatic hypotension and various clinical variables in patients with Type 2 diabetes.

Methods  We studied 105 patients with Type 2 diabetes. Orthostatic hypotension was defined as a decrease of 20 mmHg or more in systolic blood pressure and/or 10 mmHg in diastolic blood pressure when blood pressure was measured for 3 min while standing. The brachial–ankle pulse‐wave velocity was also measured as an index of arterial stiffness.

Results  Orthostatic hypotension was found in 30 patients with diabetes (28.6%). The haematocrit and estimated glomerular filtration rate were significantly lower in patients with orthostatic hypotension than in those without it. Brachial–ankle pulse‐wave velocity and serum total and high molecular weight adiponectin were significantly higher in patients with orthostatic hypotension than in those without. Furthermore, the high molecular weight/total adiponectin ratio was higher in patients with orthostatic hypotension than in those without and hypertension was more common in patients with orthostatic hypotension. Plasma prothrombin F1 + 2, a coagulation maker, was higher in patients with orthostatic hypotension than in those without, while there were no differences of fibrinolytic markers between the two groups. Multivariate analysis showed that HDL cholesterol, haematocrit, F1 + 2, brachial–ankle pulse‐wave velocity and a decline of systolic blood pressure on standing were independent determinants of high molecular weight adiponectin.

Conclusions  Patients with Type 2 diabetes and orthostatic hypotension had an elevated serum level of high molecular weight adiponectin, which was associated with the simultaneous presence of renal dysfunction, anaemia, arterial stiffness and hypercoagulability.
An Experiment Inspired by Fourier: J.B. Godin's Familistere in Guise
Authors: LALLEMENT MICHEL
Published: November 2011

Founded in 1859 by Jean‐Baptiste Godin, the Familistere in Guise (France) is one of the rare, if not the only Fourierist experiment to pass successfully the test of time. Like C. Fourier, who inspired him, Godin thought and acted above all in terms of social experimentation. What were the main social innovations to see the light within the scope of such research? In what way could they be said to have remained faithful to Fourier? And, in the end, how can we explain that Godin succeeded where so many other Fourierists had failed? In order to answer this question, a first section sketches the portrait and trajectory of Godin. The paper then mentions Godin's principal belief and analyzes a few Fourier‐inspired experiments carried out by Godin in order to promote industrial democracy. It also points to the limits of the schemes imagined by Godin to permit a community of sometimes nearly 2,000 men, women and children to exist.
Rethinking Enclosure: Space, Subjectivity and the Commons
Authors: Jeffrey Alex , McFarlane Colin , Vasudevan Alex
Published: November 2011

Abstract:  While concepts of “enclosure” and the “commons” are becoming increasingly popular in critical geography, there have been few attempts to think them together. This paper sets out a dialectic of enclosure–commons as a means for thinking through contemporary processes of exclusion, violence and alterity. We examine what is at stake through a geographical reading of enclosure, that is, the processes through which neoliberalism works through—and summons into existence—certain forms of spatiality and subjectivity. In doing so we confront the spatialities of enclosure's “other”: strategies and practices of commoning which assemble more inclusive, just and sustainable spaces. We examine the materiality of enclosure across a range of sites, from processes of walling to a more substantial assessment of the diverse assemblage of materials and subjectivities drawn into modalities of enclosure. We go on to explore the inscription of enclosure on the human body through an examination of, first, law, and second, biopolitics. In conclusion, we explore the implications of this argument for critical geographical scholarship.
Heritage Discourse and the Desexualisation of Public Space: The “Historical Restorations” of Bloomsbury's Squares
Authors: Andersson Johan
Published: November 2011

Abstract:  In recent years, the local authorities in London's historic Bloomsbury district have carried out a number of refurbishments of the area's public squares. These landscaping schemes have typically been labelled “historical restorations” in attempts to predetermine the evaluation criteria as “historic” rather than political, social and aesthetic. Focusing on Russell Square and Bloomsbury Square, this paper illustrates how the “restorations” were selective: the introduction of gates and railings and the removal of planting were not primarily designed to restore these historical gardens, but reflect a surveillance‐friendly ideal of urban space, specifically introduced to displace the men who used these squares for cruising. Through a detailed review of archival material from both mainstream and gay media, I illustrate the shifting forms of policing and landscaping in Bloomsbury's squares, while also highlighting how homonormative capital has colluded with the regulation of public space in this part of London.
Working Hours in Supply Chain Chinese and Thai Factories: Evidence from the Fair Labor Association's ‘Soccer Project’
Authors: Smyth Russell , Qian Xiaolei , Nielsen Ingrid , Kaempfer Ines
Published: November 2011

This article examines the determinants of working excessive hours, defined as working in excess of 60 hours per week or for more than six consecutive days, in Chinese and Thai supply chain factories. We use a matched employer–employee dataset collected from 15 Chinese and Thai footwear and sporting apparel supply chain factories, which supply international brands. Matched employer–employee data allow us to examine the effect of worker and firm characteristics on hours worked. We find that in addition to the demographic and human capital characteristics of workers, firm‐level characteristics and worker awareness of how to refuse overtime are important in explaining variation in hours worked.