bluuebunny/crossref_metadata_2025 huggingface dataset:
Semi-automatic ESOL error annotation
Authors: Andersen Øistein E.
Published: September 2011

Manual error annotation of learner corpora is time-consuming and error-prone, whereas existing automatic techniques cannot reliably detect and correct all types of error. This paper shows that the two methods can successfully complement each other: automatic detection and partial correction of trivial errors relieves the human annotator from the laborious task of incessantly marking up oft-committed mistakes and enables him or her to focus on errors which cannot or cannot yet be handled mechanically, thus enabling more consistent annotation with considerably less manual time and effort expended.
Hierarchical Model Composition updates
Authors: Smith Lucian
Published: September 2011

A summary of the status of the hierarchical model composition package for SBML Level 3, and of its current implementation.
Targeted polyubiquitylation of RASSF1C by the Mule and SCFβ-TrCP ligases in response to DNA damage
Authors: Zhou Xin , Li Ting-Ting , Feng Xu , Hsiang Esther , Xiong Yue , Guan Kun-Liang , Lei Qun-Ying
Published: September 2011

RASSF1A [Ras association (RalGDS/AF-6) domain family member 1A] and RASSF1C are two ubiquitously expressed isoforms of the RASSF1 gene. The promoter of RASSF1A is frequently hypermethylated, resulting in inactivation in various human cancers. RASSF1A is implicated in the regulation of apoptosis, microtubule stability and cell cycle arrest. However, little is known about the regulation and function of RASSF1C. In the present study we show that exogenously expressed RASSF1C is a very unstable protein that is highly polyubiquitylated and degraded via the proteasome. Furthermore, RASSF1C degradation is enhanced when cells are exposed to stress signals, such as UV irradiation. Mule, a HECT (homologous with E6-associated protein C-terminus) family E3 ligase, but not SCFβ-TrCP [where SCF is Skp1 (S-phase kinase-associated protein 1)/cullin/F-box and β-TrCP is β-bransducin repeat-containing protein] or CUL4 (cullin 4)-DDB1 (damage-specific DNA-binding protein 1), is the E3 ligase for RASSF1C under normal conditions, whereas both Mule and SCFβ-TrCP target RASSF1C degradation in response to UV irradiation. GSK3 (glycogen synthase kinase 3) phosphorylates RASSF1C to promote RASSF1C degradation subsequently, which is negatively regulated by the PI3K (phosphoinositide 3-kinase)/Akt pathway. Thus the present study reveals a novel regulation of RASSF1C and the potentially important role of RASSF1C in DNA damage responses.
Minimizing quasiparticle generation from stray infrared light in superconducting quantum circuits
Authors: Barends R. , Wenner J. , Lenander M. , Chen Y. , Bialczak R. C. , Kelly J. , Lucero E. , O’Malley P. , Mariantoni M. , Sank D. , Wang H. , White T. C. , Yin Y. , Zhao J. , Cleland A. N. , Martinis John M. , Baselmans J. J. A.
Published: September 2011

We find that quasiparticle generation from stray infrared light creates a significant loss mechanism in superconducting resonators and qubits. We show that resonator quality factors and qubit energy relaxation times are limited by a quasiparticle density of approximately 200 μm−3, induced by 4 K blackbody radiation from the environment. We demonstrate how this influence can be fully removed by isolating the devices from the radiative environment using multistage shielding.
Structural and optical properties of m-plane GaN/AlGaN quantum wires grown by metalorganic chemical vapor deposition
Authors: Yang Xuelin , Arita Munetaka , Kako Satoshi , Arakawa Yasuhiko
Published: September 2011

We have investigated the structural and optical properties of GaN quantum wires grown by metalorganic chemical vapor deposition on m-plane AlGaN templates. The quantum wire formation can be attributed to the surface morphology of the AlGaN buffer layer and to the anisotropic lattice mismatch between wires and template. The quantum wires exhibit a triangular cross-sectional geometry with width and height fluctuations. The appearance of individual spectrally narrow emission lines in the micro-photoluminescence spectra clearly demonstrates the localizations in the quantum wires. We correlate the narrow emission lines with the structural fluctuations in the cross-sectional geometry of the quantum wires.
Effect of nitrogen fertilisation on diurnal phenolic concentration and foam strength in forage of hard red wheat (Triticum aestivum L.) cv. Cutter
Authors: Malinowski D. P. , Pitta D. W. , Pinchak W. E. , Min B. R. , Emendack Y. Y.
Published: September 2011

Frothy bloat is a serious digestive disorder in cattle (Bos taurus L.) grazing winter wheat (Triticum aestivum L.) forage in the southern Great Plains of the USA. Wheat plant metabolism is one of the factors involved in bloat. We determined diurnal and seasonal patterns of total phenolic accumulation and foam strength (a measure of bloat potential) in forage of winter wheat cv. Cutter in response to nitrogen (N) fertilisation when grown at Vernon, Texas, during two growing seasons (November–March) in 2006–07 and 2007–08. The diurnal pattern of phenolic accumulation followed the diurnal pattern of solar radiation, with lower values in the morning and the evening, and maximum values around midday. The range of phenolic concentrations measured was 1.9–6.6 mg/g dry matter (tannic acid equivalent). The diurnal pattern of foam strength was opposite to that of phenolic accumulation and ranged from 15.5 to 21.8 min/cm. Nitrogen fertilisation (33, 67, and 134 kg/ha) had inconsistent effects on diurnal patterns of phenolic accumulation and foam strength. With increased N fertilisation rate, concentrations of total, soluble, and insoluble protein fractions increased, whereas soluble carbohydrate concentrations declined. Phenolic concentrations were higher in January–February 2007 and November–December 2007 than in other months and declined in March of each growing season. Foam strength was higher in late autumn than spring in both growing seasons. The results suggest that diurnal patterns of phenolic accumulation in wheat forage respond to diurnal pattern of solar radiation and are inversely correlated with diurnal patterns of foam strength. Breeding wheat cultivars with enhanced phenolic content in forage may be one approach to reduce bloat incidence in grazing cattle.
Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity
Authors: Fawcett Tim W. , Kuijper Bram , Weissing Franz J. , Pen Ido
Published: September 2011

Female choice is a powerful selective force, driving the elaboration of conspicuous male ornaments. This process of sexual selection has profound implications for many life-history decisions, including sex allocation. For example, females with attractive partners should produce more sons, because these sons will inherit their father's attractiveness and enjoy high mating success, thereby yielding greater fitness returns than daughters. However, previous research has overlooked the fact that there is a reciprocal feedback from life-history strategies to sexual selection. Here, using a simple mathematical model, we show that if mothers adaptively control offspring sex in relation to their partner's attractiveness, sexual selection is weakened and male ornamentation declines. This weakening occurs because the ability to determine offspring sex reduces the fitness difference between females with attractive and unattractive partners. We use individual-based, evolutionary simulations to show that this result holds under more biologically realistic conditions. Sexual selection and sex allocation thus interact in a dynamic fashion: The evolution of conspicuous male ornaments favors sex-ratio adjustment, but this conditional strategy then undermines the very same process that generated it, eroding sexual selection. We predict that, all else being equal, the most elaborate sexual displays should be seen in species with little or no control over offspring sex. The feedback process we have described points to a more general evolutionary principle, in which a conditional strategy weakens directional selection on another trait by reducing fitness differences.
Mass extinction of birds at the Cretaceous–Paleogene (K–Pg) boundary
Authors: Longrich Nicholas R. , Tokaryk Tim , Field Daniel J.
Published: September 2011

The effect of the Cretaceous-Paleogene (K-Pg) (formerly Cretaceous–Tertiary, K–T) mass extinction on avian evolution is debated, primarily because of the poor fossil record of Late Cretaceous birds. In particular, it remains unclear whether archaic birds became extinct gradually over the course of the Cretaceous or whether they remained diverse up to the end of the Cretaceous and perished in the K–Pg mass extinction. Here, we describe a diverse avifauna from the latest Maastrichtian of western North America, which provides definitive evidence for the persistence of a range of archaic birds to within 300,000 y of the K–Pg boundary. A total of 17 species are identified, including 7 species of archaic bird, representing Enantiornithes, Ichthyornithes, Hesperornithes, and an
Apsaravis
-like bird. None of these groups are known to survive into the Paleogene, and their persistence into the latest Maastrichtian therefore provides strong evidence for a mass extinction of archaic birds coinciding with the Chicxulub asteroid impact. Most of the birds described here represent advanced ornithurines, showing that a major radiation of Ornithurae preceded the end of the Cretaceous, but none can be definitively referred to the Neornithes. This avifauna is the most diverse known from the Late Cretaceous, and although size disparity is lower than in modern birds, the assemblage includes both smaller forms and some of the largest volant birds known from the Mesozoic, emphasizing the degree to which avian diversification had proceeded by the end of the age of dinosaurs.
Circadian cycles are the dominant transcriptional rhythm in the intertidal musselMytilus californianus
Authors: Connor Kwasi M. , Gracey Andrew Y.
Published: September 2011

Residents in the marine intertidal, the zone where terrestrial and marine habitats converge, inhabit an environment that is subject to both the 24-h day and night daily rhythm of the terrestrial earth and also the 12.4-h ebb and flow of the tidal cycle. Here, we investigate the relative contribution of the daily and tidal cycle on the physiology of intertidal mussels,Mytilus californianus, by monitoring rhythms of gene expression in both simulated and natural tidal environments. We report that >40% of the transcriptome exhibits rhythmic gene expression, and that depending on the specific tidal conditions, between 80% and 90% of the rhythmic transcripts follow a circadian expression pattern with a period of 24 to 26 h. Consistent with the dominant effect of the circadian cycle we show that the expression of clock genes oscillates with a 24-h period. Our data indicate that the circadian 24-h cycle is the dominant driver of rhythmic gene expression in this intertidal inhabitant despite the profound environmental and physiological changes associated with aerial exposure during tidal emergence.
Structure and dynamics of a conformationally constrained nitroxide side chain and applications in EPR spectroscopy
Authors: Fleissner Mark R. , Bridges Michael D. , Brooks Evan K. , Cascio Duilio , Kálai Tamás , Hideg Kálmán , Hubbell Wayne L.
Published: September 2011

A disulfide-linked nitroxide side chain (R1) is the most widely used spin label for determining protein topology, mapping structural changes, and characterizing nanosecond backbone motions by site-directed spin labeling. Although the internal motion of R1 and the number of preferred rotamers are limited, translating interspin distance measurements and spatial orientation information into structural constraints is challenging. Here, we introduce a highly constrained nitroxide side chain designated RX as an alternative to R1 for these applications. RX is formed by a facile cross-linking reaction of a bifunctional methanethiosulfonate reagent with pairs of cysteine residues at
i
and
i
 + 3 or
i
and
i
 + 4 in an α-helix, at
i
and
i
 + 2 in a β-strand, or with cysteine residues in adjacent strands in a β-sheet. Analysis of EPR spectra, a crystal structure of RX in T4 lysozyme, and pulsed electron-electron double resonance (ELDOR) spectroscopy on an immobilized protein containing RX all reveal a highly constrained internal motion of the side chain. Consistent with the constrained geometry, interspin distance distributions between pairs of RX side chains are narrower than those from analogous R1 pairs. As an important consequence of the constrained internal motion of RX, spectral diffusion detected with ELDOR reveals microsecond internal motions of the protein. Collectively, the data suggest that the RX side chain will be useful for distance mapping by EPR spectroscopy, determining spatial orientation of helical segments in oriented specimens, and measuring structural fluctuations on the microsecond time scale.
Crystal structure of QscR, aPseudomonas aeruginosaquorum sensing signal receptor
Authors: Lintz Mario J. , Oinuma Ken-Ichi , Wysoczynski Christina L. , Greenberg Everett Peter , Churchill Mair E. A.
Published: September 2011

Acyl-homoserine lactone (AHL) quorum sensing controls gene expression in hundreds of Proteobacteria including a number of plant and animal pathogens. Generally, the AHL receptors are members of a family of related transcription factors, and although they have been targets for development of antivirulence therapeutics there is very little structural information about this class of bacterial receptors. We have determined the structure of the transcription factor, QscR, bound to N-3-oxo-dodecanoyl-homoserine lactone from the opportunistic human pathogenPseudomonas aeruginosaat a resolution of 2.55 Å. The ligand-bound QscR is a dimer with a unique symmetric “cross-subunit” arrangement containing multiple dimerization interfaces involving both domains of each subunit. The QscR dimer appears poised to bind DNA. Predictions about signal binding and dimerization contacts were supported by studies of mutant QscR proteins in vivo. The acyl chain of the AHL is in close proximity to the dimerization interfaces. Our data are consistent with an allosteric mechanism of signal transmission in the regulation of DNA binding and thus virulence gene expression.
Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation
Authors: Wong Carmen Chak-Lui , Gilkes Daniele M. , Zhang Huafeng , Chen Jasper , Wei Hong , Chaturvedi Pallavi , Fraley Stephanie I. , Wong Chun-Ming , Khoo Ui-Soon , Ng Irene Oi-Lin , Wirtz Denis , Semenza Gregg L.
Published: September 2011

Primary tumors facilitate metastasis by directing bone marrow-derived cells (BMDCs) to colonize the lungs before the arrival of cancer cells. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of breast cancer metastatic niche formation through induction of multiple members of the lysyl oxidase (LOX) family, including LOX, LOX-like 2, and LOX-like 4, which catalyze collagen cross-linking in the lungs before BMDC recruitment. Only a subset of LOX family members was expressed in any individual breast cancer, but HIF-1 was required for expression in each case. Knockdown of HIF-1 or hypoxia-induced LOX family members reduced collagen cross-linking, CD11b
+
BMDC recruitment, and metastasis formation in the lungs of mice after orthotopic transplantation of human breast cancer cells. Metastatic niche formation is an HIF-1–dependent event during breast cancer progression.
Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity
Authors: Guo Yiqi , Audry Magali , Ciancanelli Michael , Alsina Laia , Azevedo Joana , Herman Melina , Anguiano Esperanza , Sancho-Shimizu Vanessa , Lorenzo Lazaro , Pauwels Elodie , Philippe Paul Bastard , Pérez de Diego Rebeca , Cardon Annabelle , Vogt Guillaume , Picard Capucine , Andrianirina Zafitsara Zo , Rozenberg Flore , Lebon Pierre , Plancoulaine Sabine , Tardieu Marc , Doireau Valérie , Jouanguy Emmanuelle , Chaussabel Damien , Geissmann Frederic , Abel Laurent , Casanova Jean-Laurent , Zhang Shen-Ying
Published: September 2011

Autosomal dominant TLR3 deficiency has been identified as a genetic etiology of childhood herpes simplex virus 1 (HSV-1) encephalitis (HSE). This defect is partial, as it results in impaired, but not abolished induction of IFN-β and -λ in fibroblasts in response to TLR3 stimulation. The apparently normal resistance of these patients to other infections, viral illnesses in particular, may thus result from residual TLR3 responses. We report here an autosomal recessive form of complete TLR3 deficiency in a young man who developed HSE in childhood but remained normally resistant to other infections. This patient is compound heterozygous for two loss-of-function TLR3 alleles, resulting in an absence of response to TLR3 activation by polyinosinic-polycytidylic acid (poly(I:C)) and related agonists in his fibroblasts. Moreover, upon infection of the patient’s fibroblasts with HSV-1, the impairment of IFN-β and -λ production resulted in high levels of viral replication and cell death. In contrast, the patient’s peripheral blood mononuclear cells responded normally to poly(I:C) and to all viruses tested, including HSV-1. Consistently, various TLR3-deficient leukocytes from the patient, including CD14+ and/or CD16+ monocytes, plasmacytoid dendritic cells, and in vitro derived monocyte-derived macrophages, responded normally to both poly(I:C) and HSV-1, with the induction of antiviral IFN production. These findings identify a new genetic etiology for childhood HSE, indicating that TLR3-mediated immunity is essential for protective immunity to HSV-1 in the central nervous system (CNS) during primary infection in childhood, in at least some patients. They also indicate that human TLR3 is largely redundant for responses to double-stranded RNA and HSV-1 in various leukocytes, probably accounting for the redundancy of TLR3 for host defense against viruses, including HSV-1, outside the CNS.
Genetic Diversity of Sheep Breeds from Albania, Greece, and Italy Assessed by Mitochondrial DNA and Nuclear Polymorphisms (SNPs)
Authors: Pariset Lorraine , Mariotti Marco , Gargani Maria , Joost Stephane , Negrini Riccardo , Perez Trinidad , Bruford Michael , Ajmone Marsan Paolo , Valentini Alessio
Published: September 2011

We employed mtDNA and nuclear SNPs to investigate the genetic diversity of sheep breeds of three countries of the Mediterranean basin: Albania, Greece, and Italy. In total, 154 unique mtDNA haplotypes were detected by means of D-loop sequence analysis. The major nucleotide diversity was observed in Albania. We identified haplogroups, A, B, and C in Albanian and Greek samples, while Italian individuals clustered in groups A and B. In general, the data show a pattern reflecting old migrations that occurred in postneolithic and historical times. PCA analysis on SNP data differentiated breeds with good correspondence to geographical locations. This could reflect geographical isolation, selection operated by local sheep farmers, and different flock management and breed admixture that occurred in the last centuries.
Emission Rates of Volatile Organic Compounds Released from Newly Produced Household Furniture Products Using a Large-Scale Chamber Testing Method
Authors: Ho Duy Xuan , Kim Ki-Hyun , Ryeul Sohn Jong , Hee Oh Youn , Ahn Ji-Won
Published: September 2011

The emission rates of volatile organic compounds (VOCs) were measured to investigate the emission characteristics of five types of common furniture products using a 5 m3size chamber at 25°C and 50% humidity. The results indicated that toluene andα-pinene are the most dominant components. The emission rates of individual components decreased constantly through time, approaching the equilibrium emission level. The relative ordering of their emission rates, if assessed in terms of total VOC (TVOC), can be arranged as follows: dining table > sofa > desk chair > bedside table > cabinet. If the emission rates of VOCs are examined between different chemical groups, they can also be arranged in the following order: aromatic (AR) > terpenes (TER) > carbonyl (CBN) > others > paraffin (PR) > olefin (HOL) > halogenated paraffin (HPR). In addition, if emission strengths are compared between coated and uncoated furniture, there is no significant difference in terms of emission magnitude. Our results indicate that the emission characteristics of VOC are greatly distinguished between different furniture products in terms of relative dominance between different chemicals.
On the calculation of the gauge volume size for energy-dispersive X-ray diffraction
Authors: Rowles Matthew R.
Published: September 2011

Equations for the calculation of the dimensions of a gauge volume, also known as the active volume or diffraction lozenge, in an energy-dispersive diffraction experiment where the detector is collimated by two ideal slits have been developed. Equations are given for equatorially divergent and parallel incident X-ray beams, assuming negligible axial divergence.
Pre‐emptive rituximab based on viraemia and T cell reconstitution: a highly effective strategy for the prevention of Epstein–Barr virus‐associated lymphoproliferative disease following stem cell transplantation
Authors: Worth Austen , Conyers Rachel , Cohen Jonathon , Jagani Mamta , Chiesa Robert , Rao Kanchana , Goulden Nicholas , Veys Paul , Amrolia Persis J.
Published: September 2011

This study investigated the efficacy of a pre‐emptive strategy based on the combination of Epstein–Barr virus (EBV) viraemia and poor T cell reconstitution in preventing post‐transplant lymphoproliferative disease (PTLD) following T cell depleted stem cell transplant (SCT). EBV viral load and immune reconstitution were prospectively monitored in 70 consecutive children undergoing SCT following reduced intensity conditioning with alemtuzumab. Patients who developed significant EBV viraemia (>40 000 copies/ml blood) were treated pre‐emptively with rituximab if they were within 3 months of SCT or their CD3 count was <0·3 × 109/l. Of 20/70 patients who developed significant EBV viraemia, 13 received pre‐emptive rituximab. The incidence of PTLD was significantly reduced in the pre‐emptive cohort compared to historical controls (1·4% vs. 21·7%, P = 0·003). This difference was more marked among viraemic patients (2·7% vs. 62·5%P < 0·0001). Patients treated with rituximab demonstrated significantly delayed B cell reconstitution at 1 year post‐SCT but this was not associated with an increase in infectious mortality. In 6/6 patients >3 months post‐SCT who had a CD3 count >0·3 × 109/l, reduced immunosuppression only resulted in successful resolution of EBV viraemia without PTLD. This strategy is safe and highly effective in preventing PTLD following T cell depleted SCT, and directs rituximab therapy to patients at highest risk of this complication.
The effect of azithromycin on the maturation and function of murine bone marrow-derived dendritic cells
Authors: Iwamoto S , Kumamoto T , Azuma E , Hirayama M , Ito M , Amano K , Ido M , Komada Y
Published: September 2011

Dendritic cells (DCs) are professional antigen-presenting cells capable of initiating primary/adaptive immune responses and tolerance. DC functions are regulated by their state of maturation. However, the molecular pathways leading to DC development and maturation remain poorly understood. We attempted to determine whether inhibition of nuclear factor kappa B (NF-κB), which is one of the pivotal pathways underlying these processes, could induce immunophenotypic and functional changes in lipopolysaccharide-induced mature DCs derived from murine bone marrow. A comparative in vitro study of five clinically used drugs that are known to inhibit NF-κB demonstrated that azithromycin, a macrolide antibiotic, significantly inhibited expression of co-stimulatory molecules (CD40 and CD86) and major histocompatibility complex (MHC) class II by DCs. It also reduced Toll-like receptor 4 expression, interleukin-12 production and the allostimulatory capacity of DCs. These data suggest that azithromycin, as not only an NF-κB inhibitor but also an antibiotic, has potential as a novel drug for manipulation of allogeneic responses.
Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL
Authors: Kappelle Paul J. W. H. , de Boer Jan Freark , Perton Frank G. , Annema Wijtske , de Vries Rindert , Dullaart Robin P. F. , Tietge Uwe J. F.
Published: September 2011

Eur J Clin Invest 2012; 42 (5): 487–495

Background  Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes mellitus and aimed to identify potential determinants of this parameter.

Materials and methods  In a cross‐sectional study, we investigated 74 patients with type 2 diabetes and 75 control subjects. Antioxidative properties of HDL were measured and expressed as either (i) HDL antioxidative capacity or (ii) HDL antioxidation index after multiplying HDL antioxidative capacity results with individual plasma HDL cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) and paraoxonase‐1 (PON‐1) activities were determined.

Results  HDL antioxidative capacity was similar in patients with diabetes and controls, while the HDL antioxidation index was decreased in patients with diabetes (P = 0·005) owing to lower plasma HDL cholesterol (P < 0·001). LCAT activity was higher and PON‐1 activity lower in type 2 diabetes mellitus (each P < 0·001). In the combined subjects, HDL antioxidative capacity was inversely related to LCAT activity (P < 0·01). The HDL antioxidation index correlated negatively with blood glucose (P < 0·001), HbA1c and LCAT activity (each P < 0·01), and positively with PON‐1 activity (P < 0·01). Multiple linear regression analysis demonstrated that high LCAT activity was associated with both decreased HDL antioxidation capacity (P < 0·05) and index (P < 0·001) independent of diabetes status, glycaemic control and PON‐1.

Conclusions  Overall, the antioxidative functionality of HDL is impaired in type 2 diabetes mellitus mostly because of lower HDL cholesterol. Hyperglycaemia, increased LCAT activity and lower PON‐1 activity likely contribute to impaired antioxidative functionality of HDL.
The status of carrier and prenatal diagnosis of haemophilia in China
Authors: DAI J. , LU Y. , DING Q. , WANG H. , XI X. , WANG X.
Published: September 2011

Summary.  Haemophilia A (HA) and haemophilia B (HB) are the most common X‐linked inherited bleeding disorders. It is important to detect the carrier women in families with HA/HB and subsequent antenatal diagnosis of confirmed carriers. This study consists of 102 HA families which include 68 mothers for prenatal diagnosis and 107 female relatives for carrier diagnosis, and 29 HB families which include 16 mothers and 31 female relatives respectively. The rapid fluorescent PCR with two groups of different combined polymorphism markers was applied for linkage analysis in HA and HB families respectively. The Amelogenin gene was added to help the detection of gender diagnosis. Gene sequencing was also used to detect the mutations directly. There were 37 causative F8C mutations (23 novel) and 24 causative F9C mutations (eight novel) found in this cohort of patients. Few of the women could not be diagnosed due to homologous recombination and/or inability to locate the mutation. Complicated cases have been found in some families. With regard to carrier and prenatal diagnosis, it was considered that genetic diagnosis by linkage analysis and direct sequencing was successful. Some special families might require combination of the linkage analysis and gene sequence for a successful diagnosis. New intragenic SNP and STR sites special to Chinese population need to be discovered.
A review of chronic hepatitis B epidemiology and management issues in selected countries in the Middle East
Authors:   Specialist Panel on Chronic Hepatitis B in the Middle East
Published: September 2011

Summary. Experts from seven countries convened as a Specialist Panel for the Middle East to share information on practical issues relating to the epidemiology, diagnosis and management of chronic hepatitis B (CHB) infection. The Middle East is regarded as a region of high‐to‐intermediate epidemicity; however, infant vaccination programmes have successfully lowered the prevalence of hepatitis B infection in most countries to that of low‐to‐intermediate endemicity. Vaccine issues still to be addressed included improving coverage in some rural/poor communities, instituting hepatitis B vaccine at birth and providing vaccines for high‐risk population groups. Hepatitis B infection in the Middle East primarily occurs as a result of perinatal infection, horizontal transmission between family members and transmission from injections. Blood transfusion services have broadly efficient screening programmes, but immunocompromised and haemodialysis patients are at risk. The cost of screening, monitoring and treating CHB influences practice in a number of Middle East countries, and there is a need for information on the most cost‐effective options.
Pinniped taxonomy: review of currently recognized species and subspecies, and evidence used for their description
Authors: BERTA Annalisa , CHURCHILL Morgan
Published: September 2011

Pinnipeds are charismatic but difficult to study, and taxonomy is poorly understood. An accurate taxonomic framework is essential for studies of biogeography, ecology and conservation.

Morphologic and genetic criteria used to recognize pinniped species and subspecies are evaluated individually for all taxa in the three families: Otariidae (sea lions and fur seals), Odobenidae (walruses) and Phocidae (seals). We advocate a pragmatic approach that, in general, follows the Evolutionary Species Concept and ‘diagnosability’ criterion for subspecies delimitations.

Of the 33 species, all have at least two lines of evidence to distinguish them, and of the 29 subspecies, 24 have at least one line of evidence, but five have inadequate support. We present a composite phylogeny for pinnipeds.

We propose that the genus Arctocephalus be limited to Arctocephalus pusillus, and we resurrect the name Arctophoca for at least six species and subspecies.

We recommend large sample sizes and broad, random sampling in further research on pinniped taxonomy. Taxa should be described based on robust statistical analysis, not by arbitrary division of characters, and molecular research should include analysis of mtDNA and nuDNA.

Finally, we offer suggestions for further taxonomic research (on hybridization in otariids, and to allow consideration of life history data in sampling) in an effort to improve our understanding of pinniped diversity. Even for taxa which are already protected, better understanding of their taxonomy can only enhance their conservation status and facilitate efforts to protect their habitats.
The trafficking protein SYP121 of Arabidopsis connects programmed stomatal closure and K+ channel activity with vegetative growth
Authors: Eisenach Cornelia , Chen Zhong‐Hua , Grefen Christopher , Blatt Michael R.
Published: September 2011

The vesicle‐trafficking protein SYP121 (SYR1/PEN1) was originally identified in association with ion channel control at the plasma membrane of stomatal guard cells, although stomata of the Arabidopsis syp121 loss‐of‐function mutant close normally in ABA and high Ca2+. We have now uncovered a set of stomatal phenotypes in the syp121 mutant that reduce CO2 assimilation, slow vegetative growth and increase water use efficiency in the whole plant, conditional upon high light intensities and low relative humidity. Stomatal opening and the rise in stomatal transpiration of the mutant was delayed in the light and following Ca2+‐evoked closure, consistent with a constitutive form of so‐called programmed stomatal closure. Delayed reopening was observed in the syp121, but not in the syp122 mutant lacking the homologous gene product; the delay was rescued by complementation with wild‐type SYP121 and was phenocopied in wild‐type plants in the presence of the vesicle‐trafficking inhibitor Brefeldin A. K+ channel current that normally mediates K+ uptake for stomatal opening was suppressed in the syp121 mutant and, following closure, its recovery was slowed compared to guard cells of wild‐type plants. Evoked stomatal closure was accompanied by internalisation of GFP‐tagged KAT1 K+ channels in both wild‐type and syp121 mutant guard cells, but their subsequently recycling was slowed in the mutant. Our findings indicate that SYP121 facilitates stomatal reopening and they suggest that K+ channel traffic and recycling to the plasma membrane underpins the stress memory phenomenon of programmed closure in stomata. Additionally, they underline the significance of vesicle traffic for whole‐plant water use and biomass production, tying SYP121 function to guard cell membrane transport and stomatal control.
Subcellular localization of the Hpa RxLR effector repertoire identifies a tonoplast‐associated protein HaRxL17 that confers enhanced plant susceptibility
Authors: Caillaud Marie‐Cécile , Piquerez Sophie J. M. , Fabro Georgina , Steinbrenner Jens , Ishaque Naveed , Beynon Jim , Jones Jonathan D. G.
Published: September 2011

Filamentous phytopathogens form sophisticated intracellular feeding structures called haustoria in plant cells. Pathogen effectors are likely to play a role in the establishment and maintenance of haustoria in addition to their better‐characterized role in suppressing plant defence. However, the specific mechanisms by which these effectors promote virulence remain unclear. To address this question, we examined changes in subcellular architecture using live‐cell imaging during the compatible interaction between the oomycete Hyaloperonospora arabidopsidis (Hpa) and its host Arabidopsis. We monitored host‐cell restructuring of subcellular compartments within plant mesophyll cells during haustoria ontogenesis. Live‐cell imaging highlighted rearrangements in plant cell membranes upon infection, in particular to the tonoplast, which was located close to the extra‐haustorial membrane surrounding the haustorium. We also investigated the subcellular localization patterns of Hpa RxLR effector candidates (HaRxLs) in planta. We identified two major classes of HaRxL effector based on localization: nuclear‐localized effectors and membrane‐localized effectors. Further, we identified a single effector, HaRxL17, that associated with the tonoplast in uninfected cells and with membranes around haustoria, probably the extra‐haustorial membrane, in infected cells. Functional analysis of selected effector candidates in planta revealed that HaRxL17 enhances plant susceptibility. The roles of subcellular changes and effector localization, with specific reference to the potential role of HaRxL17 in plant cell membrane trafficking, are discussed with respect to Hpa virulence.
AtIRE1A/AtIRE1B and AGB1 independently control two essential unfolded protein response pathways in Arabidopsis
Authors: Chen Yani , Brandizzi Federica
Published: September 2011

The endoplasmic reticulum (ER) has the ability to maintain the balance between demand for and synthesis of secretory proteins. To ensure protein‐folding homeostasis in the ER, cells invoke signaling pathways known as the unfolded protein response (UPR). To initiate UPR, yeasts largely rely on a conserved sensor, IRE1. In metazoans, there are at least three independent UPR signalling pathways. Some UPR transducers have been identified in plants, but no genetic interaction among them has yet been examined. The Arabidopsis genome encodes two IRE1 sequence homologs, AtIRE1A and AtIRE1B. Here we provide evidence that AtIRE1A and AtIRE1B have overlapping functions that are essential for the plant UPR. A double mutant of AtIRE1A and AtIRE1B, atire1a atire1b, showed reduced ER stress tolerance and a compromised UPR activation phenotype. We have also established that Arabidopsis AGB1, a subunit of the ubiquitous heterotrimeric GTP‐binding protein family, and AtIRE1A/AtIRE1B independently control two essential plant UPR pathways. By demonstrating that atire1a atire1b has a short root phenotype that is enhanced by an agb1 loss‐of‐function mutation, we have identified a role for UPR transducers in organ growth regulation.
Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT‐II deficiency
Authors: Fanin M , Anichini A , Cassandrini D , Fiorillo C , Scapolan S , Minetti C , Cassanello M , Donati MA , Siciliano G , D'Amico A , Lilliu F , Bruno C , Angelini C
Published: September 2011

Fanin M, Anichini A, Cassandrini D, Fiorillo C, Scapolan S, Minetti C, Cassanello M, Donati MA, Siciliano G, D’Amico A, Lilliu F, Bruno C, Angelini C. Allelic and phenotypic heterogeneity in 49 Italian patients with the muscle form of CPT‐II deficiency.

As genotype–phenotype correlations require the study of large patient populations, we investigated 49 Italian patients (33 unreported) with the muscle form of carnitine‐palmitoyl‐transferase‐II (CPT‐II) deficiency and CPT2 gene mutations. CPT enzyme activity below 25% of controls would lead to the development of muscle symptoms, and CPT activity below 15% would cause a relatively severe phenotype of the muscle form. Of the 15 different mutations found, 6 are novel (40%). A functional significance of mutations could be derived only for the two homozygous missense mutations found: both the p.S113L and the p.R631C (recurring in four unrelated patients from a genetic isolate) alleles caused a severe CPT enzyme defect (15% and 7%, respectively) and a relatively severe clinical phenotype of the muscle form. We identified three genotypes (homozygous p.R631C, homozygous p.S113L, and heterozygous null mutations) usually associated with a relatively severe and often life‐threatening condition, which should be considered both in the clinical management of newly diagnosed patients (to prevent symptoms) and in their possible inclusion in therapeutic trials. We confirmed the existence of symptomatic heterozygous patient(s), through a family study, providing an important issue when offering genetic counseling and suggesting the crucial role of polymorphisms or environmental factors in determining the phenotype.
Characterization of a novel allele, HLA‐A*03:132
Authors: Endres R. O. , Hoffman A. D. , Scott I.
Published: September 2011

A*03:132 differs from A*03:01:01:01 at nucleotide 853 (codon 261) in exon 4.
Detection of Rhagoletis indifferens (Dipt., Tephritidae) larvae using brown sugar flotation and hot water methods
Authors: Yee W. L.
Published: September 2011

The brown sugar flotation and hot water methods are accepted procedures for detecting larval western cherry fruit fly, Rhagoletis indifferens Curran, in sweet cherry [Prunus avium (L.) L.] and could be included in a systems approach, a combination of all steps involved in cherry production, for showing the absence of larvae in fruit. The methods require crushing cherries and then submerging them in brown sugar solution or hot water to extract the larvae. Larvae are visually detected when they float to the surface of the brown sugar solution or sink in the hot water. The objective of this study was to test the efficacy of these two methods. Both methods detected at least one larva in all 288 moderately to heavily infested cherry samples. The brown sugar flotation and hot water methods detected 89.6–94.7% and 83.0–85.9% of total larvae, respectively, from cherry samples on each of three dates. Significantly higher percentages of 1st instars were detected using the brown sugar than hot water method on two dates, of 3rd instars on one date and of total larvae on two dates. Percent detection of 3rd instars was higher than that of 1st instars using both methods. For both methods, greater percentages of split whole cherries with seeds and non‐split cherries had larvae than split whole cherries with no seeds and halved cherries. Results show that both methods were equally efficacious in detecting the presence of R. indifferens larvae in cherry samples, but brown sugar flotation was more efficacious than the hot water method in detecting a higher percentage of total larvae present and could be integrated into a systems approach for R. indifferens.
Dermatophyte susceptibility varies towards antimicrobial textiles
Authors: Hammer Timo R. , Mucha Helmut , Hoefer Dirk
Published: September 2011

Dermatophytoses are a widespread problem worldwide. Textiles in contact with infected skin can serve as a carrier for fungus propagation. Hitherto, it is unknown, whether antifungal textiles could contribute in controlling dermatophytes e.g. by disrupting the chain of infection. Testing of antimicrobial fabrics for their antifungal activities therefore is a fundamental prerequisite to assess the putative clinical relevance of textiles for dermatophyte prevention. Fabrics finished with either didecyldimethylammonium chloride (DDAC), poly‐hexamethylenbiguanide, copper and two silver chloride concentrations were tested for their antifungal activity against Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. To prove dermatophyte susceptibility towards the textiles, swatches were subjected to DIN EN 14199 (Trichophyton sp.) or DIN EN ISO 20743 (C. albicans) respectively. In addition, samples were embedded, and semi‐thin sections were analysed microscopically. While all samples showed a clear inhibition of C. albicans, activity against Trichophyton sp. varied significantly: For example, DDAC completely inhibited T. rubrum growth, whereas T. mentagrophytes growth remained unaffected even in direct contact to the fibres. The results favour to add T. mentagrophytes as a test organism in textile dermatophyte efficacy tests. Microscopic analysis of swatches allowed detailed evaluation of additional parameters like mycelium thickness, density and hyphae penetration depth into the fabric.
Changes in nitric oxide and free radical levels in rat gastrocnemius muscle during contraction and fatigue
Authors: Ibrahim Mariam Y , Ashour Osama M
Published: September 2011

1. The ratio of nitric oxide (NO) to free radicals is critical during skeletal muscle contraction. Changes in this ratio have been suggested to play a role in muscle fatigue.

2. The aim of the present study was to investigate the changes in NO and free radicals during tetanic and subtetanic contraction and fatigue in the gastrocnemius muscle of adult male Wistar rats.

3. Rats were subjected to either low‐ or high‐frequency stimulation (10 and 100 Hz, respectively) of the right gastrocnemius muscle. Both groups were further subdivided into untreated (0.9% NaCl solution), NG‐nitro‐l‐arginine methyl ester (l‐NAME)‐treated and reduced glutathione (GSH)‐treated groups. Rats were administered their treatments intraperitoneally 30 min prior to electrical stimulation.

4. Levels of both NO and lipid peroxides increased significantly during peak force contraction for either type of contractions, with a more significant response during subtetanic contraction. Treatment with l‐NAME significantly reduced the maximal force and this effect was more marked in the low frequency‐stimulated group. Although peroxides levels were reduced by GSH, it had no significant effect on force production. In l‐NAME‐treated rats, the onset of 50% fatigue was accelerated with a significant increase in peroxides levels, whereas the opposite effects were observed after GSH treatment.

5. Current results reflect the importance of endogenous NO, as an anti‐oxidant, in aiding muscle performance by overcoming oxidative stress during fatigue. They provide a possible explanation as to why patients with myopathies like Duchenne muscular dystrophy, in which dystrophin is lacking suffer from muscle weakness and fatigue easily.
Treating stuttering priapism
Authors: Kheirandish Pejman , Chinegwundoh Frank , Kulkarni Shailesh
Published: September 2011

What's known on the subject? and What does the study add?

Stuttering priapism is a form of ischemic priapism which mainly affects sickle cell patients. Despite recent advances in understanding the aetiology and pathophysiology of this condition, no credible evidence‐based management strategy has been produced to this date.

In this mini review we have attempted to summarize the published articles on this topic systematically. The main aim was to present the treatment options available and analyse their indications and efficacies.

Stuttering priapism is an uncommon recurrent form of ischaemic priapism consisting of episodes of unwanted, painful erections that typically last for <3 h. It occurs repeatedly with intervening periods of detumescence. If these episodes are not treated, it may evolve into a classic ischaemic priapism and eventually lead to irreversible corporal fibrosis with permanent erectile dysfunction. A comprehensive literature search was conducted in August 2010 using the PubMed database, MEDLINE and generic search engines. The search terms used to source information on this topic were, stuttering priapism (44 hits) and recurrent priapism (161 hits). Although there are numerous publications on this topic the majority of them are small trials and case reports. We identified 117 case reports, 28 reviews, 37 anecdotal reports, 22 small size clinical trials and one in vitro work. Our understanding of the underlying pathophysiology of stuttering priapism has improved in recent years. Further multicentre randomized clinical trials are required to evaluate the efficacy of different treatment options and to define safe and effective management strategies for patients with low‐flow recurrent priapism.
HbA1c 3 months after diagnosis predicts premature mortality in patients with new onset type 2 diabetes
Authors: Kerr D. , Partridge H. , Knott J. , Thomas P. W.
Published: September 2011

Diabet. Med. 28, 1520–1524 (2011)

Aims  To determine 5‐year mortality rates, following the diagnosis of Type 2 diabetes, in a large local cohort of individuals with new onset of Type 2 diabetes seen within a few weeks of diagnosis in a single, community‐based education programme.

Methods  We reviewed referrals for people with Type 2 diabetes to our service over 5 years from 1999 to 2003 and determined, via regression analysis, which factors contributed significantly to mortality rates up to the end of 2007.

Results  A total of 3781 new referrals were reviewed with an approximate doubling of referral rates over 5 years (546 in 1999–997 in 2003). Although the number of people developing the condition has increased, mortality rates over the 5 years from diagnosis has fallen from 11% in 1999–9% in 2003 (P < 0.005) Age at diagnosis was the strongest predictor of mortality (P < 0.001) but HbA1c at 3 months after diagnosis (P < 0.001), systolic (P < 0.001) and diastolic (P = 0.05) blood pressure, smoking status (P < 0.001) and gender (P = 0.04) were also significant predictors.

Conclusions  Our retrospective analysis adds weight to evidence suggesting that referral rates for people with Type 2 diabetes are increasing rapidly and that mortality rates are reducing but that the reasons for this are multifactorial. In addition to blood pressure, smoking and gender, the HbA1c achieved 3 months after the initial diagnosis also appears to predict subsequent mortality. It may be appropriate to consider early and intensive intervention for individuals with new onset type 2 diabetes.