bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian cancer progression is controlled by phenotypic changes in dendritic cells
Authors: Scarlett Uciane K. , Rutkowski Melanie R. , Rauwerdink Adam M. , Fields Jennifer , Escovar-Fadul Ximena , Baird Jason , Cubillos-Ruiz Juan R. , Jacobs Ana C. , Gonzalez Jorge L. , Weaver John , Fiering Steven , Conejo-Garcia Jose R.
Published: February 2012

We characterized the initiation and evolution of the immune response against a new inducible p53-dependent model of aggressive ovarian carcinoma that recapitulates the leukocyte infiltrates and cytokine milieu of advanced human tumors. Unlike other models that initiate tumors before the development of a mature immune system, we detect measurable anti-tumor immunity from very early stages, which is driven by infiltrating dendritic cells (DCs) and prevents steady tumor growth for prolonged periods. Coinciding with a phenotypic switch in expanding DC infiltrates, tumors aggressively progress to terminal disease in a comparatively short time. Notably, tumor cells remain immunogenic at advanced stages, but anti-tumor T cells become less responsive, whereas their enduring activity is abrogated by different microenvironmental immunosuppressive DCs. Correspondingly, depleting DCs early in the disease course accelerates tumor expansion, but DC depletion at advanced stages significantly delays aggressive malignant progression. Our results indicate that phenotypically divergent DCs drive both immunosurveillance and accelerated malignant growth. We provide experimental support for the cancer immunoediting hypothesis, but we also show that aggressive cancer progression after a comparatively long latency period is primarily driven by the mobilization of immunosuppressive microenvironmental leukocytes, rather than loss of tumor immunogenicity.
Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma
Authors: Cook Natalie , Frese Kristopher K. , Bapiro Tashinga E. , Jacobetz Michael A. , Gopinathan Aarthi , Miller Jodi L. , Rao Sudhir S. , Demuth Tim , Howat William J. , Jodrell Duncan I. , Tuveson David A.
Published: February 2012

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation.
Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K
Authors: Conley Mary Ellen , Dobbs A. Kerry , Quintana Anita M. , Bosompem Amma , Wang Yong-Dong , Coustan-Smith Elaine , Smith Amber M. , Perez Elena E. , Murray Peter J.
Published: February 2012

Whole exome sequencing was used to determine the causative gene in patients with B cell defects of unknown etiology. A homozygous premature stop codon in exon 6 of PIK3R1 was identified in a young woman with colitis and absent B cells. The mutation results in the absence of p85α but normal expression of the p50α and p55α regulatory subunits of PI3K. Bone marrow aspirates from the patient showed <0.1% CD19+ B cells with normal percentages of TdT+VpreB+CD19− B cell precursors. This developmental block is earlier than that seen in patients with defects in the B cell receptor signaling pathway or in a strain of engineered mice with a similar defect in p85α. The number and function of the patient’s T cells were normal. However, Western blot showed markedly decreased p110δ, as well as absent p85α, in patient T cells, neutrophils, and dendritic cells. The patient had normal growth and development and normal fasting glucose and insulin. Mice with p85α deficiency have insulin hypersensitivity, defective platelet function, and abnormal mast cell development. In contrast, the absence of p85α in the patient results in an early and severe defect in B cell development but minimal findings in other organ systems.
Spectroscopy and electron microscopy imaging of a single metal nano-object
Authors: Baida H , Berthelot A , Crut A , Maioli P , Del Fatti N , Vallée F
Published: February 2012

The optical extinction spectra of single metal nano-objects measured by the spatial modulation spectroscopy technique were correlated with their image obtained by scanning electron microscopy. The results show a large influence of both the object shape and the presence of the substrate on the measured optical spectra.
Portable cholesterol detection with polyaniline-carbon nanotube film based interdigitated electrodes
Authors: Nguyen Le Huy , Nguyen Hai Binh , Nguyen Ngoc Thinh , Nguyen Tuan Dung , Tran Dai Lam
Published: February 2012

Polyaniline-carboxylic multiwalled carbon nanotubes composite film (PANi-MWCNT) has been polymerized on the surface of interdigitated platinum electrode (fabricated by MEMS technology) which was compatibly connected to Autolab interface via universal serial bus (USB). An amperometric biosensor based on covalent immobilization of cholesterol oxidase (ChOx) on PANi–MWCNT film with potassium ferricyanide (FeCN) as the redox mediator was developed. The mediator helps to shuttle the electrons between the immobilized ChOx and the PANi-MWCNT electrode, therefore operating at a low potential of −0.3 Vcompared to the saturated calomel electrode (SCE). This potential precludes the interfering compounds from oxidization. The bio-electrode exhibits good linearity from 0.02 to 1.2 mM cholesterol concentration with a correlation coefficient of 0.9985.
Manipulating single atoms and photons using optical nanofibers
Authors: Hakuta Kohzo , Nayak Kali Prasanna
Published: February 2012

We discuss how optical nanofibers, subwavelength-diameter fibers, can open new perspectives in quantum optical technologies theoretically and experimentally. Discussions are mainly focused on the manipulation of spontaneous emission for atoms around the nanofiber. We show that photons from single quantum emitters can be efficiently channeled into guided modes of the nanofiber. Especially by fabricating a cavity structure of the nanofiber, the channeling efficiency can be improved to exceed 80% although the cavity finesse is moderate. We discuss also how to realize such a nanofiber cavity experimentally.
Recurrent acute pulmonary oedema and cardiac arrest secondary to intermittent electrical dyssynchrony: a role for cardiac resynchronization despite preserved left ventricular function
Authors: Duncan Edward , Rao Kamini , Sporton Simon
Published: February 2012

Recurrent pulmonary oedema with no obvious precipitant can prove difficult to treat in patients with preserved left ventricular (LV) systolic function. This report describes the novel use of cardiac resynchronization therapy (CRT) in the prevention of acute pulmonary oedema precipitated by intermittent electrical dyssynchrony in a patient with preserved LV systolic function.
Evaluation of White Salted Noodles Enriched with Oat Flour
Authors: Mitra Sabori , Cato Larisa , James Anthony Paul , Solah Vicky Ann
Published: February 2012

Oat consumption is regarded as having significant health benefits. The enrichment of white salted noodles with oat flour would provide a potential health benefit but may affect the texture and sensory quality. Oat cultivars grown in Western Australia (Yallara, Kojonup, Mitika, Carrolup, and new line SV97181‐8) and a commercial oat variety were milled into flour and added to wheat flour at 10, 20, and 30% to produce oat‐enriched white salted noodles. The purpose of the study was to determine the quality characteristics of the oat flours and to assess the influence the oat flour blends had on noodle texture, color, and sensory characteristics. In addition, another goal was to determine whether the different oat cultivars had similar potential to provide health benefits by measuring the β‐glucan content before and after processing. The results indicated that protein, ash content, and noodle firmness increased with the increased percentage of oat flour in the noodle formulations, whereas the pasting properties of the noodle wheat–oat flour blends did not differ significantly. The color of raw noodle sheets and boiled noodles changed significantly with oat incorporation and resulted in lower lightness/brightness, higher redness, lower yellowness, and lower color stability in comparison to standard wheat white salted noodles. Noodles made with the lowest oat percentage (10%) scored highest for all sensory parameters and were significantly different in appearance, color, and overall acceptability compared with noodles made with 20 and 30% oat flour. The β‐glucan content of the flour blends increased with the increase in the level of oat incorporation but subsequently decreased during processing into noodles. The decrease in the β‐glucan content varied across the different oat cultivars and levels of incorporation into the noodles. A new oat cultivar, SV97181‐8, exhibited the least β‐glucan loss during processing. In this study, the quality characteristics of white salted noodles enriched with oat flour from Western Australian cultivars were determined to provide essential information for the commercial development of healthier noodles.
Effects of Selected Harvest Moistures and Frozen Storage Times on Selected Yellow Dent Corn: Wet‐Milling Yields and Starch Pasting Properties
Authors: Huang Haibo , Xu Li , Eckhoff Steven R.
Published: February 2012

The effects of harvest moistures and frozen storage times on corn wet‐milling yields and the pasting properties of the resulting starch were studied. Pioneer hybrid P‐0916‐XR harvested at three moisture contents (49, 35, and 21% wb) were stored frozen for three days or for five months, followed by wet‐milling. The pasting properties of the resulting starch were evaluated with a Rapid Visco Analyzer. The yields of starch and germ increased by 1.2 and 1.9 percentage points, respectively, when harvest moisture decreased from 49 to 21% wb, whereas the yields of steep water solids, total fiber, and gluten decreased by 2.1, 0.7, and 0.6 percentage points, respectively. The frozen corn had lower coarse fiber yields but higher cellular fiber yields. The starch pasting properties showed that peak and breakdown viscosities decreased by 8% (3,824 ± 36 versus 3,520 ± 38 cP) and 13% (2,336 ± 47 versus 2,029 ± 60 cP), respectively, when harvest moisture decreased from 49 to 21% wb, whereas peak time increased by 5% (6.32 ± 0.06 versus 6.62 ± 0.07 min). The setback and final viscosities of starch from long‐term frozen storage (five months) were 14% (1,574 ± 65 versus 1,828 ± 79 cP) and 8% (3,063 ± 27 versus 3,317 ± 101 cP) lower, respectively, than that from control (unfrozen) corn.
Effects of Bacterial ACC Deaminase onBrassica napusGene Expression
Authors: Stearns Jennifer C. , Woody Owen Z. , McConkey Brendan J. , Glick Bernard R.
Published: February 2012

Plants in association with plant growth-promoting rhizobacteria can benefit from lower plant ethylene levels through the action of the bacterial enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. This enzyme cleaves the immediate biosynthetic precursor of ethylene, ACC. Ethylene is responsible for many aspects of plant growth and development but, under stressful conditions, it exacerbates stress symptoms. The ACC deaminase-containing bacterium Pseudomonas putida UW4 is a potent plant growth-promoting strain and, as such, was used to elaborate the detailed role of bacterial ACC deaminase in Brassica napus (canola) plant growth promotion. Transcriptional changes in bacterially treated canola plants were investigated with the use of an Arabidopsis thaliana oligonucleotide microarray. A heterologous approach was necessary because there are few tools available at present to measure global expression changes in nonmodel organisms, specifically with the sensitivity of microarrays. The results indicate that the transcription of genes involved in plant hormone regulation, secondary metabolism, and stress response was altered in plants by the presence of the bacterium, whereas the upregulation of genes for auxin response factors and the downregulation of stress response genes was observed only in the presence of bacterial ACC deaminase. These results support the suggestion that there is a direct link between ethylene and the auxin response, which has been suggested from physiological studies, and provide more evidence for the stress-reducing benefits of ACC deaminase-expressing plant growth-promoting bacteria.
TaMCA4, a Novel Wheat Metacaspase Gene Functions in Programmed Cell Death Induced by the Fungal Pathogen Puccinia striiformis f. sp. tritici
Authors: Wang Xiaodong , Wang Xiaojie , Feng Hao , Tang Chunlei , Bai Pengfei , Wei Guorong , Huang Lili , Kang Zhensheng
Published: February 2012

Programmed cell death (PCD) is a physiological process to remove redundant or harmful cells, for the development of multicellular organisms, or for restricting the spread of pathogens (hypersensitive response). Metacaspases are cysteine-dependent proteases which play an essential role in PCD. Triticum aestivum metacaspase 4 (TaMCA4) is a type II metacaspase gene cloned from ‘Suwon11’ wheat, with typical structural features such as peptidase C14 caspase domain and a long linker sequence between the two subunits. Transient expression of TaMCA4 in tobacco leaves failed to induce PCD directly but enhanced cell death triggered by a mouse Bax gene or a candidate effector gene from Puccinia striiformis f. sp. tritici. Enhancement of PCD was also observed in wheat leaves co-bombarded with TaMCA4. When challenged with the avirulent race of P. striiformis f. sp. tritici, the expression level of TaMCA4 in wheat leaves was sharply upregulated, whereas the transcript level was not significantly induced by the virulent race. Moreover, knocking down TaMCA4 expression by virus-induced gene silencing enhanced the susceptibility of Suwon11 to the avirulent race of P. striiformis f. sp. tritici and reduced the necrotic area at infection sites.
Opprimo ergo sum—Evasion and Suppression in the Root Endophytic Fungus Piriformospora indica
Authors: Lahrmann Urs , Zuccaro Alga
Published: February 2012

The genetically tractable endophytic fungus Piriformospora indica is able to colonize the root cortex of a great variety of different plant species with beneficial effects to its hosts, and it represents a suitable model system to study symbiotic interactions. Recent cytological studies in barley and Arabidopsis showed that, upon penetration of the root, P. indica establishes a biotrophic interaction during which fungal cells are encased by the host plasma membrane. Large-scale transcriptional analyses of fungal and plant responses have shown that perturbance of plant hormone homeostasis and secretion of fungal lectins and other small proteins (effectors) may be involved in the evasion and suppression of host defenses at these early colonization steps. At later stages, P. indica is found more often in moribund host cells where it secretes a large variety of hydrolytic enzymes that degrade proteins. This strategy of colonizing plants is reminiscent of that of hemibiotrophic fungi, although a defined shift to necrotrophy with massive host cell death is missing. Instead, the association with the plant root leads to beneficial effects for the host such as growth promotion, increased resistance to root as well as leaf pathogens, and increased tolerance to abiotic stresses. This review describes current advances in understanding the components of the P. indica endophytic lifestyle from molecular and genomic analyses.
Phytophthora hedraiandra Detected from Irrigation Water at a Perennial Ornamental Plant Nursery in Virginia
Authors: Yang X. , Richardson P. A. , Ghimire S. R. , Kong P. , Hong C. X.
Published: February 2012

Water survey for Phytophthora spp. by baiting with rhododendron leaves in April 2006 at a perennial ornamental plant nursery in Virginia detected five isolates showing a unique, previously unknown single-strand conformation polymorphism (SSCP) fingerprint (1). These cultures were isolated from two reservoirs at different depths of water column from surface to 2 m. They were homothallic and produced smooth-surfaced spherical oogonia with an average diameter of 27 μm on 10% V8 agar. Oospores were aplerotic. The paragynous antheridia were averaging 12 μm in diameter. Sporangia were papillate, spherical to ovoid, averaging 39 by 28 μm (length by width). They were caducous with short (<4 μm) pedicels. Chlamydospores and hyphal swellings were not observed. Two isolates were sequenced for rDNA internal transcribed spacer (ITS) 1 and 2 regions and cytochrome oxidase subunit 1 (Cox 1) gene. ITS sequences of both isolates (GenBank Accession Nos. JN376065 and JN376066) were identical to that of Phytophthora hedraiandra type culture (GenBank Accession No. AY707987). Also, the Cox 1 sequence of an isolate (Accession No. JN376067) had 99% homology with that of the type culture (GenBank Accession No. AY69115). Pathogenicity of both isolates was tested on Rhododendron catawbiense and Viburnum tinus, two known hosts of P. hedraiandra (2). For each isolate and host, five leaves and stems on potted plants were wounded by needles and then inoculated by placing over each wound a 5-mm2 mycelial plug from a 7-day-old culture and securing with Parafilm. V8 agar was used instead of mycelial plugs on control plants. After inoculation, each plant was enclosed in a plastic bag for 1 day and then incubated at 22°C with a 12-h photoperiod. Distilled water was sprayed daily for 5 days postinoculation (dpi) until disease symptoms were observed. At 15 dpi, 3 of the 10 inoculated rhododendron leaves and 6 of the 10 stems showed leaf lesions, wilting, dieback, and cankers, eventually leading to rhododendron death. Two of the 10 viburnum leaves and 4 of the 10 stems showed similar symptoms. Leaf lesions were approximately 3 to 5 cm in diameter. P. hedraiandra was recovered from diseased tissues and all resulting cultures showed an identical SSCP fingerprint to tested isolates as well as a P. hedraiandra isolate from Minnesota (3). No symptom developed on control plants. To our knowledge, this is the first report of P. hedraiandra in Virginia. Considering neither host plant has been grown or bought for resale by this nursery, this study indicates that P. hedraiandra may have a wider host range than is currently known. This possibility and the importance of water dispersal for P. hedraiandra in disease epidemiology warrant further investigation.

References: (1) P. Kong et al. Fungal Genet. Biol. 39:238, 2003. (2) W. A. Man in't Veld et al. Eur. J. Plant Pathol. 117:25, 2007. (3) B. W. Schwingle et al. Plant Dis. 90:109, 2006.
New Insights into Esca of Grapevine: The Development of Foliar Symptoms and Their Association with Xylem Discoloration
Authors: Lecomte P. , Darrieutort G. , Liminana J.-M. , Comont G. , Muruamendiaraz A. , Legorburu F.-J. , Choueiri E. , Jreijiri F. , El Amil Roula , Fermaud Marc
Published: February 2012

A new study on the development of foliar symptoms of esca was carried out from 2004 to 2006 in five mature vineyards in Aquitaine, France. Symptoms were monitored for severity and changes over time. Initial foliar symptoms were characterized by the presence of drying zones or discolorations (reddening or yellowing), which are symptoms that have also been attributed to Black Dead Arm (BDA). Then, the less-severely affected leaves persisted throughout the summer and developed into typical “tiger-stripe” symptoms of esca. The most severely symptomatic leaves fell soon after symptoms appeared. Severely diseased vines showed typical apoplectic or acute forms of esca that did not differ from the severe BDA forms. The appearance of leafsymptomatic vines increased uniformly over time, reaching a maximum incidence by the end of July. A second survey in 41 European and Lebanese vineyards showed that longitudinal discolorations were visible under the bark of 95% of the vines showing foliar esca symptoms. These wood symptoms, also previously attributed to BDA, appeared as xylem orange-brown stripes. Thus, foliar symptoms of esca showed transitory phases which overlapped with some BDA descriptions. Most of these symptoms, in the west-palearctic regions that were investigated, were commonly associated with the presence of one or several xylem discolorations.
Occurrence of Lily mottle virus on Lilium in Italy
Authors: Rizzo D. , Stefani L. , Paoli M. , Lazzereschi S. , Nesi B. , Pecchioli S. , Bartola M. Della , Materazzi A. , Grassotti A.
Published: February 2012

Lily mottle virus (LMoV), a member of the genus Potyvirus, is one of the main viruses infecting lily. Symptoms on lily differ according to the susceptibility and sensitivity of different cultivars and hybrids. They range from leaf mottle or mosaic, vein clearing, chlorotic and yellow streaking, leaf curling, and necrotic spots, to milder forms of leaf symptoms. Plants may even be symptomless at some stages of growth. A varietal collection of Lilium from the early 1990s is held in Pistoia Province (Tuscany, Italy) and is composed of Asian hybrids obtained from intraspecific breeding of commercial cultivars. During a survey conducted from May to June 2010, several plants showing vein clearing, leaf mottle, leaf mosaic, and reddish brownish necrotic spots were observed. Leaf samples from 60 symptomatic or symptomless lily plants, belonging to 20 cultivars, were collected and tested for the presence of LMoV. Samples were assayed by double-antibody sandwich (DAS)-ELISA and eight of them, belonging to four different cultivars, tested positive. Total RNA was extracted from 2 g of leaf tissue of every collected sample according to the protocol described earlier (3) and cDNA synthesis was performed with an iScript cDNA Synthesis Kit (Bio-Rad, Hercules, CA). Samples were tested by reverse transcription (RT)-PCR and real-time PCR assays using primers LMoV1 (5′-GCAAATGAGACACTCAATGCTG-3′) and LMoV2 (5′-CGTGCGTGAAGTAACTTCATAG-3′) designed to amplify 651 bp of the coat protein (CP) gene of LMoV (1). Results obtained with RT-PCR and real-time PCR exactly matched those achieved with ELISA assay, and the eight positive samples showed amplicons of the expected size. PCR products from five infected samples were directly sequenced from both directions and submitted in GenBank (Accessions Nos. JQ655106 to JQ655110). Our isolates share more than 99% nucleotide identity among each other. Comparison with other LMoV-CP gene sequences present in GenBank showed nucleotide identities ranging from 93 to 94% with LMoV isolates from South Korea (GenBank Accession Nos. GQ150683 to GQ150686), China (GenBank Accession Nos. EU348826, AJ748256, AJ564636, and AJ564637), Australia (GenBank Accession No. JN127341), and Japan (GenBank Accession No. AB570195). To our knowledge, this is the first report of LMoV on Lilium in Italy where this virus was already reported to infect escarole (2). Considering the economic importance of Lilium production as a flowering plant in Pistoia Province, and in several other areas of Italy, the report of LMoV present on lilies suggests the use of healthy propagation material and the adoption of preventive measures to avoid its diffusion.

References: (1) J.-H. Lim et al. Korean J. Microbiol. 45:251, 2009. (2) V. Lisa et al. Plant Dis. 86:329, 2002. (3) D. J. MacKenzie et al. Plant Dis. 81:222, 1997.
Microbial-Induced Carbon Competition in the Spermosphere Leads to Pathogen and Disease Suppression in a Municipal Biosolids Compost
Authors: Chen Mei-Hsing , Nelson Eric B.
Published: February 2012

The aim of this study was to understand whether competition for fatty acids in plant seed exudates by compost-derived seed-colonizing microbial communities could explain the suppression of plant infections initiated by sporangia of Pythium ultimum. The germination behavior of P. ultimum sporangia in response to cucumber seeds was measured to determine the impact of seed-colonizing microbes on pathogen suppression. Seed-colonizing microbial communities from municipal biosolids compost utilized cucumber seed exudates and linoleic acid in vitro, reducing the respective stimulatory activity of these elicitors to P. ultimum sporangial germination. However, when sporangia were observed directly in the spermosphere of seeds sown in the compost medium, levels of germination and sporangial emptying did not differ from the responses in sand. The percentage of aborted germ tubes was greater after incubating sporangia in compost medium for 12-h than the level of germ tube abortion when sporangia were incubated in sand. Abortion did not occur if previously germinated sporangia were supplemented with cucumber seed exudate. Furthermore, removal of cucumber seed exudate after various stages of germ tube emergence resulted in an increase in aborted germ tubes over time. Adding increasing levels of glucose directly to the compost medium alleviated germ tube abortion in the spermosphere and also eliminated disease suppression. These data fail to support a role for linoleic acid competition in Pythium seedling disease suppression but provide evidence for general carbon competition mediated by seed-colonizing microbial communities as a mechanism for the suppression of Pythium seed infections in municipal biosolids compost.
Species, sex, size and male maturity composition of previously unreported elasmobranch landings in Kuwait, Qatar and Abu Dhabi Emirate
Authors: Moore A. B. M. , McCarthy I. D. , Carvalho G. R. , Peirce R.
Published: February 2012

This paper presents data from the first major survey of the diversity, biology and fisheries of elasmobranchs in the Persian (Arabian) Gulf. Substantial landings of elasmobranchs, usually as gillnet by‐catch, were recorded in Kuwait, Qatar and the Emirate of Abu Dhabi (part of the United Arab Emirates), although larger elasmobranchs from targeted line fisheries were landed in Abu Dhabi. The elasmobranch fauna recorded was distinctive and included species that are undescribed, rare and have a highly restricted known distribution. Numerical abundance was dominated by sharks (c. 80%), of which carcharhinids were by far the most important. The milk shark Rhizoprionodon acutus and whitecheek shark Carcharhinus dussumieri together comprised just under half of all recorded individuals. Around 90% of recorded sharks were small (50–90 cm total length, LT) individuals, most of which were mature individuals of species with a small maximum size (<100 cm LT), although immature individuals of larger species (e.g. Carcharhinus sorrah and other Carcharhinus spp.) were also important. The most frequently recorded batoid taxa were cownose rays Rhinoptera spp., an undescribed whipray, and the granulated guitarfish Rhinobatos granulatus. The first size, sex and maturity data for a wide range of Gulf elasmobranch species are presented (including LT at 50% maturity for males of four shark species) and include some notable differences from other locations in the Indo‐West Pacific Ocean. A number of concerns regarding the sustainability of the fishery were highlighted by this study, notably that most of the batoid species recorded are classed by the IUCN Red List as vulnerable, endangered, data deficient or not evaluated. Despite their considerable elasmobranch landings, none of the three countries sampled have developed a ‘Shark Plan’ as encouraged to do so under the FAO International Plan of Action: Sharks. Furthermore, Kuwait and Qatar currently report zero or no elasmobranch landings to the FAO.
Evidence of stability in a chondrichthyan population: case study of the spotted ratfish Hydrolagus colliei (Chondrichthyes: Chimaeridae)
Authors: Barnett L. A. K. , Ebert D. A. , Cailliet G. M.
Published: February 2012

Results presented here provide evidence of an exception to the generalization that all chondrichthyan populations are especially vulnerable to exploitation to the extent that they remain at low abundance for a protracted or indefinite duration even after exploitation rates are reduced. Delta log‐normal generalized linear models (GLM) and cluster analysis of fishery‐independent catch‐per‐unit‐effort (CPUE) data from 1977 to 2006 indicated the presence of at least two distinct stocks of spotted ratfish Hydrolagus colliei off the U.S. West Coast. CPUE of the continental slope and northern continental shelf and upper slope populations did not vary between 1977 and 1995 and increased from 1995 to 2006. On the basis of the timing of these changes, it is likely that both fishing and climate influenced these trends. Sex and size‐specific differences in bathymetric distribution, along with the identification of nursery sites, indicate that fishery by‐catch could have a significant effect on population growth. These aggregative behaviours, combined with low fecundity, indicate that H. colliei may be vulnerable to irreversible population depletion by fisheries mortality. Temporal abundance trends indicated, however, that their population size has increased significantly within the last decade, a demonstration of population stability. A literature review indicated that there is also evidence for population stability in other chondrichthyans. The paradigm that all chondrichthyan populations fail to rebuild in response to exploitation, therefore, may not be as broadly applicable as previously thought. Thus, it is not necessarily sufficient to make generalizations regarding the vulnerability of chondrichthyans across higher taxonomic scales.
Modified‐orientation log to assess hepatic encephalopathy
Authors: Salam M. , Matherly S. , Farooq I. S. , Stravitz R. T. , Sterling R. K. , Sanyal A. J. , Gibson D. P. , Wade J. B. , Thacker L. R. , Heuman D. M. , Fuchs M. , Puri P. , Luketic V. , Bickston S. J. , Bajaj J. S.
Published: February 2012

Background

The subjectivity of the West‐Haven criteria (WHC) hinders hepatic encephalopathy (HE) evaluation. The new HE classification has emphasised assessment of orientation. The modified‐orientation log (MO‐log, eight questions, scores 0–24; 24 normal) is adapted from a validated brain injury measure.

Aim

To validate MO‐log for HE assessment in cirrhosis.

Methods

Cirrhotics admitted with/without HE were administered MO‐log. We collected cirrhosis/HE details, admission/daily MO‐logs and WHC (performed by different examiners), time to reach normal mentation (MO‐log ≥23) and MO‐log/WHC change (Δ) over day 1. Outcomes were in‐hospital mortality, duration to normal mentation and length‐of‐stay (LOS). Regressions were performed for each outcome. MO‐log inter‐rater reliability was measured.

Results

Ninety‐six HE (55 ± 8 years, MELD 21) and 20 non‐HE (54 ± 5 years, MELD 19) in‐patients were included. In HE patients, median admission WHC was 3 (range 1–4). Mean MO‐log was 12 ± 8 (range 0–22). Their LOS was 6 ± 5 days and 13% died. Time to reach normal mentation was 2.4 ± 1.7 days. Concurrent validity: there was a significant negative correlation between admission MO‐log and WHC (r = −0.79, P < 0.0001). Discriminant validity: admission MO‐logs were significantly lower in those who died (7 vs. 12, P = 0.03) and higher in those admitted without HE (23.6 vs. 12, P < 0.0001). MO‐log improved in 69% on day 1 (ΔMO‐log 4 ± 8) which was associated with lower duration to normal mentation (2 vs. 3.5 days, P = 0.03) and mortality (3% vs.43%, P < 0.0001), not ΔWHC. Regression models for all outcomes included admission/ΔMO‐log but not WHC as a predictor. Inter‐rater reliability: ICC for MO‐log inter‐rater observations was 0.991.

Conclusions

Modified‐orientation log is a valid tool for assessing severity and is better than West‐Haven criteria in predicting outcomes in hospitalised hepatic encephalopathy patients.
Lipopolysaccharide interference in erythropoiesis in mice
Authors: Brendt P. , Rehfeld I. , Kamphausen A. , Kreissig C. , Peters J.
Published: February 2012

Anaemia is a common problem in septic patients. We tested whether lipopolysaccharide suppressed erythropoiesis and interfered with erythropoietin. Male mice (strain C57BL/6, n = 76) were injected Escherichia coli lipopolysaccharide (serotype O127:B8; 20 mg.kg−1 intraperitoneally) or vehicle, followed by either erythropoietin (5000 IU.kg−1 intraperitoneally) or vehicle, and killed after 24 or 72 h. Femur bone marrow cells were stained for Ter‐119, CD71 and C‐Kit antigen using specific flow cytometry gates for proerythroblasts, basophilic, polychromatic and orthochromatic erythroblasts, and peripheral blood reticulocytes were counted. Erythropoietin stimulated erythropoiesis, as evidenced by increased reticulocytes after 72 h by 197% and proerythroblasts by 50% (p < 0.05). Lipopolysaccharide alone decreased proerythroblasts by 53% and basophilic erythroblasts by 75% (p < 0.05). Orthochromatic erythroblasts doubled after lipopolysaccharide exposure (p < 0.05) without any increase in reticulocytes. Lipopolysaccharide completely suppressed erythropoietin’s stimulatory effects and evoked a maturation block at the late stage of erythropoiesis. Lipopolysaccharide could cause anaemia in sepsis.
Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans
Authors: Litonius E. , Tarkkila P. , Neuvonen P. J. , Rosenberg P. H.
Published: February 2012

Intravenous lipid emulsion is the recommended treatment for severe local anaesthetic intoxication. Lipid emulsion may entrap lipid soluble drugs by functioning as a ‘lipid sink’, but its effect on bupivacaine pharmacokinetics remains unknown. In this randomised, double‐blind, crossover study, eight healthy male volunteers were infused bupivacaine 0.5 mg.kg−1 intravenously over 20 min, followed by an infusion of either intravenous lipid emulsion or Hartmann’s solution for 30 min. At 20 and 30 min after the start of the infusion, the total plasma bupivacaine concentration was lower while receiving lipid emulsion than Hartmann’s solution (mean difference 111 (95% CI 55–167) μg.l−1 and 75 (95% CI 26–124 μg.l−1 at 20 and 30 min, respectively; p < 0.02). However, there were no differences in un‐entrapped (non‐lipid bound) or free (non‐protein bound) bupivacaine plasma concentrations during the infusion. Intravenous lipid emulsion infusion reduced the context‐sensitive half‐life of total plasma bupivacaine from 45 (95% CI 32–76) min to 25 (95% CI 20–33) min; p = 0.01. We observed no significant adverse effects of lipid emulsion. In conclusion, lipid emulsion may slightly increase the rate of bupivacaine tissue distribution. No ‘lipid sink’ effect was observed with the non‐toxic dose of bupivacaine used.
Exacerbations of severe asthma
Authors: McDonald V. M. , Gibson P. G.
Published: February 2012

Exacerbations occur frequently in severe asthma. They result in significant morbidity and can lead to hospitalization and death. Severe exacerbations can also lead to an accelerated decline in lung function. Phenotyping severe asthma can aid with both prognostication of exacerbation risk and maintenance treatment selection to minimize future risks of exacerbations in severe asthma. The rate of exacerbations differs by phenotype, and is most frequent in refractory eosinophilic asthma and early onset allergic asthma. Phenotype specific therapy can reduce exacerbations in both these forms of severe asthma. Exacerbations are multi‐component events. Each exacerbation represents an opportunity to assess and target treatment to the domains of airway pharmacotherapy, self‐management behaviour, risk factors, and relevant co‐morbidities.
Cysteinyl leukotriene receptors, old and new; implications for asthma
Authors: Laidlaw T. M. , Boyce J. A.
Published: February 2012

The cysteinyl leukotrienes (cys‐LTs) are three structurally similar, but functionally distinct lipid mediators of inflammation. The parent cys‐LT, LTC4, is synthesized by and released from mast cells, eosinophils, basophils, and macrophages, and is converted to the potent constrictor LTD4 and the stable metabolite, LTE4. While only two cys‐LT‐selective receptors (CysLTRs) have been identified, cloned, and characterized, studies dating back three decades predicted the existence of at least three functional CysLTRs, each with a characteristic physiological function in airways and other tissues. The recent demonstration that mice lacking both known CysLTRs exhibit full (and in some instances, augmented) physiological responses to cys‐LTs verifies the existence of unidentified CysLTRs. Moreover, the ability to manipulate receptor expression in both whole animal and cellular systems reveals that the functions of CysLTRs are controlled at multiple levels, including receptor‐receptor interactions. Finally, studies in transgenic mice have uncovered a potentially major role for cys‐LTs in controlling the induction of Th2 responses to common allergens. This review focuses on these recent findings and their potential clinical implications.
Cyclosporin but not everolimus inhibits chemokine receptor expression on CD4+ T cell subsets circulating in the peripheral blood of renal transplant recipients
Authors: Hoerning A , Köhler S , Jun C , Lu J , Fu J , Tebbe B , Dolff S , Feldkamp T , Kribben A , Hoyer P F , Witzke O
Published: February 2012

The peripheral chemokine receptors chemokine receptor 3 (CXCR3) and CC chemokine receptor 5 (CCR5) have been reported to be associated with allograft rejection. The impact of the expression of immunosuppressive drugs on peripherally circulating CD4+ T cell subsets after renal transplantion is unknown. Expression of CXCR3 and CCR5 was investigated by flow cytometry in 20 renal allograft recipients participating in a prospective, randomized trial (NCT00514514). Initial immunosuppression consisted of basiliximab, cyclosporin A (CsA), mycophenolate sodium and corticosteroids. After 3 months, patients were treated either with CsA, mycophenolate sodium (MPA) plus corticosteroids (n = 6), CsA and everolimus plus corticosteroids (n = 8) or CsA-free (CsAfree) receiving everolimus, MPA and corticosteroids (n = 6). After initial reduction of CD4+forkhead box protein 3 (FoxP3)+ and CD4+CD25hiFoxP3+ regulatory T cells (Tregs) (P < 0·05; P < 0·01), 3-month post-transplant percentages of Tregs were reconstituted in CsAfree and CsAlo arms compared to CsAreg 12 months post transplant. Expression of CCR5 and CXCR3 on CD4+FoxP3+ and CD4+FoxP3- T cells 12 months post transplant was increased in CsAfreeversus CsAreg. Increase in CCR5+CXCR3+ co-expressing CD4+FoxP3- cells between 3 and 12 months correlated negatively with the glomerular filtration rate (GFR) slope/year [modification of diet in renal disease (MDRD); r = −0·59, P < 0·01]. CsA, but not everolimus, inhibits both Treg development and expression of CXCR3 and CCR5 on CD4+ T cell subsets. Increase in CCR5+CXCR3+ co-expressing CD4+FoxP3- T cells is associated with early loss in allograft function.
Prophylactic and therapeutic efficacies of a selective inhibitor of the immunoproteasome for Hashimoto's thyroiditis, but not for Graves' hyperthyroidism, in mice
Authors: Nagayama Y , Nakahara M , Shimamura M , Horie I , Arima K , Abiru N
Published: February 2012

Major histocompatibility complex (MHC) class I-restricted T cell epitopes are generated mainly by the immunoproteasome in antigen-presenting cells. Therefore, inhibition of activity of this proteolytic complex molecule is thought to be a potential treatment for cell-mediated autoimmune diseases. We therefore studied the efficacy of an immunoproteasome inhibitor, ONX 0914 (formerly PR-957), for the treatment of autoimmune thyroid diseases, including cell-mediated Hashimoto's thyroiditis and autoantibody-mediated Graves' hyperthyroidism using mouse models. Our data show that ONX 0914 was effective prophylactically and therapeutically at suppressing the degree of intrathyroidal lymphocyte infiltration and, to a lesser degree, the titres of anti-thyroglobulin autoantibodies in non-obese diabetic (NOD)-H2h4 mice, an iodine-induced autoimmune thyroiditis model. It also inhibited differentiation of T cells to T helper type 1 (Th1) and Th17 cells, effector T cell subsets critical for development of thyroiditis in this mouse strain. In contrast, its effect on the Graves' model was negligible. Although ONX 0914 exerts its immune-suppressive effect through not only suppression of immune proteasome but also other mechanism(s), such as inhibition of T cell differentiation, the present results suggest that the immunoproteasome is a novel drug target in treatment of Hashimoto's thyroiditis in particular and cell-mediated autoimmune diseases in general.
Which cropland greenhouse gas mitigation options give the greatest benefits in different world regions? Climate and soil‐specific predictions from integrated empirical models
Authors: Hillier Jonathan , Brentrup Frank , Wattenbach Martin , Walter Christof , Garcia‐Suarez Tirma , Mila‐i‐Canals Llorenç , Smith Pete
Published: February 2012

Major sources of greenhouse gas (GHG) emissions from agricultural crop production are nitrous oxide (N2O) emissions resulting from the application of mineral and organic fertilizer, and carbon dioxide (CO2) emissions from soil carbon losses. Consequently, choice of fertilizer type, optimizing fertilizer application rates and timing, reducing microbial denitrification and improving soil carbon management are focus areas for mitigation. We have integrated separate models derived from global data on fertilizer‐induced soil N2O emissions, soil nitrification inhibitors, and the effects of tillage and soil inputs of soil C stocks into a single model to determine optimal mitigation options as a function of soil type, climate, and fertilization rates. After Monte Carlo sampling of input variables, we aggregated the outputs according to climate, soil and fertilizer factors to consider the benefits of several possible emissions mitigation strategies, and identified the most beneficial option for each factor class on a per‐hectare basis. The optimal mitigation for each soil‐climate‐region was then mapped to propose geographically specific optimal GHG mitigation strategies for crops with varying N requirements. The use of empirical models reduces the requirements for validation (as they are calibrated on globally or continentally observed phenomena). However, as they are relatively simple in structure, they may not be applicable for accurate site‐specific prediction of GHG emissions. The value of this modelling approach is for initial screening and ranking of potential agricultural mitigation options and to explore the potential impact of regional agricultural GHG abatement policies. Given the clear association between management practice and crop productivity, it is essential to incorporate characterization of the yield effect on a given crop before recommending any mitigation practice.
Rapid loss of glacial ice reveals stream community assembly processes
Authors: Brown Lee E. , Milner Alexander M.
Published: February 2012

Glacial retreat creates new habitat which is colonized and developed by plants and animals during the process of primary succession. While there has been much debate about the relative role of deterministic and stochastic processes during terrestrial succession, evidence from freshwater ecosystems remains minimal and a general consensus is lacking. Using a unique 27 years record of community assembly following glacial recession in southeast Alaska, we demonstrate significant change in the trait composition of stream invertebrate communities as catchment glacial cover decreased from ∼70% to zero. Functional diversity increased significantly as glacier cover decreased and taxonomic richness increased. Null modelling approaches led to a key finding that niche filtering processes were dominant when glacial cover was extensive, reflecting water temperature and dispersal constraints. Thereafter the community shifted towards co‐occurrence of stochastic and deterministic assembly processes. A further novel discovery was that intrinsic functional redundancy developed throughout the study, particularly because new colonizers possessed similar traits to taxa already present. Rapid glacial retreat is occurring in Arctic and alpine environments worldwide and the assembly processes observed in this study provide new fundamental insights into how glacially influenced stream ecosystems will respond. The findings support tolerance as a key primary successional mechanism in this system, and have broader value for developing our understanding of how biological communities in river ecosystems assemble or restructure in response to environmental change.
Characterizing the binding motifs of 11 common human HLA‐DP and HLA‐DQ molecules using NNAlign
Authors: Andreatta Massimo , Nielsen Morten
Published: February 2012

Compared with HLA‐DR molecules, the specificities of HLA‐DP and HLA‐DQ molecules have only been studied to a limited extent. The description of the binding motifs has been mostly anecdotal and does not provide a quantitative measure of the importance of each position in the binding core and the relative weight of different amino acids at a given position. The recent publication of larger data sets of peptide‐binding to DP and DQ molecules opens the possibility of using data‐driven bioinformatics methods to accurately define the binding motifs of these molecules. Using the neural network‐based method NNAlign, we characterized the binding specificities of five HLA‐DP and six HLA‐DQ among the most frequent in the human population. The identified binding motifs showed an overall concurrence with earlier studies but revealed subtle differences. The DP molecules revealed a large overlap in the pattern of amino acid preferences at core positions, with conserved hydrophobic/aromatic anchors at P1 and P6, and an additional hydrophobic anchor at P9 in some variants. These results confirm the existence of a previously hypothesized supertype encompassing the most common DP alleles. Conversely, the binding motifs for DQ molecules appear more divergent, displaying unconventional anchor positions and in some cases rather unspecific amino acid preferences.