bluuebunny/crossref_metadata_2025 huggingface dataset:
Water Sustainability and Climate Change in the EU and Global Context – Policy and Research Responses
Authors: Quevauviller Philippe
Published: September 2010

Climate change impacts on the hydrological cycle (e.g. effects on atmospheric water vapour content, changes of precipitation patterns) have been linked to observed warming over several decades. Higher water temperatures and changes in extremes, including floods and droughts, are projected to affect water quality and exacerbate many forms of water pollution with possible negative impacts on ecosystems and human health, as well as water system reliability and operating costs. In addition, sea-level rise is projected to extend areas of salinisation of groundwater and estuaries, resulting in a decrease of freshwater availability for humans and ecosystems in coastal areas. Besides this, changes in water quantity and quality due to climate change are expected to affect food availability, water access and utilisation, especially in arid and semi-arid areas, as well as the operation of water infrastructure (e.g. hydropower, flood defences, irrigation systems). This chapter discusses how climate change might impact the reliability of current water management systems on the basis of expert reports prepared at global or EU level, namely reports of the Intergovernmental Panel on Climate Change (IPCC) and guidance documents of the Water Framework Directive Common Implementation Strategy. Examples of international research trends are described to illustrate on-going efforts to improve understanding and modelling of climate changes related to the hydrological cycles at scales that are relevant to decision making (possibly linked to policy).
Sobering thoughts at seventy on trivia and serendipity
Authors: Wheatley Denys
Published: September 2010

The Editor‐in‐Chief reflects on a life in biological sciences that has been rewarding through the sheer diversity of interesting phenomenon he has researched, and recalls how holistic thinking had sadly been replaced by rampant reductionism.
Morphology of the sporophyte and gametophyte of the swamp fern, Blechnum serrulatum (Blechnaceae, Pteridophyta)
Authors: Rolleri C. H. , Prada C. , Gabriel y Galán J. M. , Passarelli L. M. , Ciciarelli M. M.
Published: September 2010

In the present paper, we provide a revised, comprehensive description of the sporophyte and gametophyte of the swamp fern, Blechnum serrulatum Rich., from neo- and paleotropical localities. External and internal characters of the sporophyte were analysed, including axes, laminae, pinnae, indusia and spores. Intercellular pectic connections of the parenchyma of the rhizomes are reported for the first time. In stipes, cell walls of the aerenchyma tissue contain filamentous protuberances that are composed primarily of cellulose but contain also fatty substances. The morphology of the gametophyte, from spore germination to gametangia formation, is discussed. The taxonomic significance of the characters is considered, especially in regard to the relationship between B. serrulatum and the closely related B. indicum.
Multiple northern refugia for Asian sacred lotus, an aquatic plant with characteristics of ice-age endurance
Authors: Li Jiao-Kun , Zhou En-Xing , Li Dong-Xu , Huang Shuang-Quan
Published: September 2010

The effect of palaeoclimate on the distribution of aquatic plants is little known, although these plants typically have much broader geographical distributions than their terrestrial counterparts. We investigated the structure of genetic variation of chloroplast DNA in the Asian sacred lotus (Nelumbo nucifera Gaertn (Nelumbonaceae)) in 15 wild populations across China as well as in four populations from India, Japan and Thailand, to infer the refugia of this ancient plant during Quaternary climatic oscillations. We obtained 37 cpDNA haplotypes in 417 individuals from 19 populations. A moderate to high level of chloroplast genetic differentiation (GST = 0.547, NST = 0.691) and significant phylogeographic structure (NST > GST) were observed, suggesting a low level of recurrent seed-mediated gene flow among the populations. The results of AMOVA analysis also showed that more variation was partitioned among (71%) than within populations (29%). The phylogenetic relationships for the recovered haplotypes showed that haplotypes of wild lotus in north-eastern China significantly diverged from those distributed in central and southern regions of China. A high level of haplotype diversity, rather than reduced genetic diversity, in north-eastern China indicated multiple refugia in northern China during the Quaternary glaciations. Lotus plants have the following two characteristics that facilitated survival through Quaternary glaciations: seeds buried in mud remain viable for thousands of years, and self-heating flowers can reproduce in cold temperatures.
Biological indicators of climate change: evidence from long-term flowering records of plants along the Victorian coast, Australia
Authors: Rumpff Libby , Coates Fiona , Morgan John W.
Published: September 2010

We investigate the utility of using historical data sources to track changes in flowering time of coastal species in south-eastern Australia in response to recent climate warming. Studies of this nature in the southern hemisphere are rare, mainly because of a paucity of long-term data sources. Despite this, we found there is considerable potential to utilise existing data sourced from herbaria collections and field naturalists’ notes and diaries to identify native plant species suitable as biological indicators of climate change. Of 101 candidate species investigated in the present study, eight were identified as showing a general trend towards earlier flowering over time, indicating a correlation with increasing temperatures. There was some evidence to suggest that species which flower in spring and summer may be more sensitive to changes in temperature. There was a high level of uncertainty regarding the detection of trends, which was a function of the accessibility, abundance and accuracy of the various data sources. However, this uncertainty could be resolved in future studies by combining the datasets from the present study with field monitoring of phenological cycles in climatically different locations. Data held by community groups could be made more accessible if there was a concerted effort to fund collation and digitisation of these records. This might best be achieved by working with community groups, and facilitated through the recent establishment of a community phenological observation database in Australia.
Embryo development of Dyckia pseudococcinea (Pitcairnioideae-Bromeliaceae), an endangered Brazilian species
Authors: Mendes Simone P. , Costa Cecília G. , De Toni Karen L. G.
Published: September 2010

The Brazilian Atlantic Forest is a biodiversity hotspot. Many Bromeliaceae species are important components of this biome, including endemic plants, such as Dyckia pseudococcinea. However, human pressure has resulted in its designation as threatened with extinction. In an attempt to encourage the establishment of subsidised support for in vitro culture protocols that ensure its reproduction, the embryo development of this species was examined by light microscopy. Embryo development initiates with the sporophytic zygote, which undergoes a first cell division that is asymmetrical and transversal. A polarised bicellular proembryo is then formed, with an apical and a basal cell that contribute to the subsequent stages of an Asteraceae-type embryogenesis after successive divisions. Differentiation of the peripheral cells is observed during the post-octant proembryo stage that gives rise to the protoderm. At maturity, the embryo is composed of a cotyledon, shoot and root apical meristems, and a suspensor. The polarisation of the bicellular proembryo and the establishment of the protoderm were identified as the two critical stages in the embryonic development of D. pseudococcinea. Thus, in vitro propagation efforts to produce seedling plants should use proembryos from the tricellular to octant stages in view of their capacity to follow distinct morphogenetic pathways.
Seasonal pollen distribution in the atmosphere of Hobart, Tasmania: preliminary observations and congruence with flowering phenology
Authors: Tng D. Y. P. , Hopf F. , Haberle S. G. , Bowman D. M. J. S.
Published: September 2010

The atmospheric pollen loads of Hobart, Tasmania, Australia, were monitored between September 2007 and July 2009. To examine the match of the airborne pollen composition with the flowering duration of their contributing plants, the phenology of native and non-native plants in various habitats near the pollen-trapping site was undertaken between August 2008 and July 2009. The pollen load was found to have a strong seasonal component associated with the start of spring in September. This is incongruent with the peak flowering season of the total taxa in October. In most taxa, atmospheric pollen signatures appeared before flowering was observed in the field. The presence of most pollen types in the atmosphere also exceeded the observed flowering duration of potential pollen-source taxa. Reasons for this may be related to the sampling effort of phenological monitoring, pollen blown in from earlier flowering populations outside of the sampling area, the ability of pollen to be reworked, and the large pollen production of some wind-pollinated taxa. In 2007–2008, 15 pollen types dominated the atmosphere, accounting for 90% of the airborne pollen load. The top six pollen types belonged to Betula, Cupressaceae, Myrtaceae, Salix, Poaceae and Ulmus. Comparatively, the annual pollen load of Hobart is lower than in most other Australian cities; however, the pollen signal of Betula is inordinately high. Native plants play a minor role as pollen contributors, despite the proximity of native habitats to the pollen-sampling location. The implications of the aerobiological observations are discussed in relation to public health.
Phenology and climate - early Australian botanical records
Authors: Chambers Lynda E. , Keatley Marie R.
Published: September 2010

Historical information from the Hobart Botanical Gardens (1864–1885) was used to identify species and phenological phases that were responsive to climatic variations and have the potential to be used as climate change indicators in southern Australia. Of the 49 species considered, 26 (53%) had at least one phenophase that appeared to be driven by changes in rainfall, minimum temperature, or both. This was particularly true for fruiting species, including currants, pears and plums, and for the phenophases harvest commencement, seed ripening or fall, and fruit ripening.
Langmuir-Blodgett Films of Dinuclear Mercury(II)-Containing Diethynylcarbazole/Polyoxometalate Hybrids: Film Characterization Studies and Potential Optoelectronic Applications
Authors: Liu Li , Chen Ming , Qiao Ling-Xiang , Liu Shi-Zhong , Du Zu-Liang , Wong Wai-Yeung
Published: September 2010

A new family of organometallic/inorganic hybrid Langmuir-Blodgett (LB) films, consisting of organometallic mercury acetylide (OMA) as the π-conjugated organometallic molecule and polyoxometallate (POM, POM = K5BW12O40 or Na5IMo6O24) of the Keggin and Anderson structures as the inorganic composite and docosanoic acid (DA) as the auxiliary film-forming agent, were prepared and well characterized by π–A isotherms, UV-vis absorption and photoluminescence spectra, atomic force microscopy imaging, scanning tunnelling microscopy, and low-angle X-ray diffraction. Our experimental results indicate that stable and well defined monolayer Langmuir and LB films are formed in pure water and POM subphases. There is a quenching effect in the luminescence intensity of the mercury complex when it is made into the LB films due to the enhanced aggregation phenomenon. These alkynylmercury(ii) based LB films exhibit interesting electrical conductivity behaviour, dependent of the characteristics of the POM used. They all reveal decent electrical conductivity, and the tunnelling current can reach ±100 nA when the voltage is set at –5 to +5 V.
NMDA receptors regulate GABA
A
receptor lateral mobility and clustering at inhibitory synapses through serine 327 on the γ2 subunit
Authors: Muir James , Arancibia-Carcamo I. Lorena , MacAskill Andrew F. , Smith Katharine R. , Griffin Lewis D. , Kittler Josef T.
Published: September 2010

Modification of the number of GABA
A
receptors (GABA
A
Rs) clustered at inhibitory synapses can regulate inhibitory synapse strength with important implications for information processing and nervous system plasticity and pathology. Currently, however, the mechanisms that regulate the number of GABA
A
Rs at synapses remain poorly understood. By imaging superecliptic pHluorin tagged GABA
A
R subunits we show that synaptic GABA
A
R clusters are normally stable, but that increased neuronal activity upon glutamate receptor (GluR) activation results in their rapid and reversible dispersal. This dispersal correlates with increases in the mobility of single GABA
A
Rs within the clusters as determined using single-particle tracking of GABA
A
Rs labeled with quantum dots. GluR-dependent dispersal of GABA
A
R clusters requires Ca
2+
influx via NMDA receptors (NMDARs) and activation of the phosphatase calcineurin. Moreover, the dispersal of GABA
A
R clusters and increased mobility of individual GABA
A
Rs are dependent on serine 327 within the intracellular loop of the GABA
A
R γ2 subunit. Thus, NMDAR signaling, via calcineurin and a key GABA
A
R phosphorylation site, controls the stability of synaptic GABA
A
Rs, with important implications for activity-dependent control of synaptic inhibition and neuronal plasticity.
Identification of a gene essential for protoporphyrinogen IX oxidase activity in the cyanobacterium
Synechocystis
sp. PCC6803
Authors: Kato Kazushige , Tanaka Ryouichi , Sano Shinsuke , Tanaka Ayumi , Hosaka Hideo
Published: September 2010

Protoporphyrinogen oxidase (Protox) catalyses the oxidation of protoporphyrinogen IX to protoporphyrin IX during the synthesis of tetrapyrrole molecules. Protox is encoded by the
hemY
gene in eukaryotes and by the
hemG
gene in many γ-proteobacteria, including
Escherichia coli
. It has been suggested that other bacteria possess a yet unidentified type of Protox. To identify a unique bacterial gene encoding Protox, we first introduced the
Arabidopsis hemY
gene into the genome of the cyanobacterium,
Synechocystis
sp. PCC6803. We subsequently mutagenized the cells by transposon tagging and screened the tagged lines for mutants that were sensitive to acifluorfen, which is a specific inhibitor of the
hemY
-type Protox. Several cell lines containing the tagged
slr1790
locus exhibited acifluorfen sensitivity. The
slr1790
gene encodes a putative membrane-spanning protein that is distantly related to the M subunit of NADH dehydrogenase complex I. We attempted to disrupt this gene in the wild-type background of
Synechocystis
, but we were only able to obtain heteroplasmic disruptants. These cells accumulated a substantial amount of protoporphyrin IX, suggesting that the
slr1790
gene is essential for growth and Protox activity of cells. We found that most cyanobacteria and many other bacteria possess
slr1790
homologs. We overexpressed an
slr1790
homolog of
Rhodobacter sphaeroides
in
Escherichia coli
and found that this recombinant protein possesses Protox activity in vitro. These results collectively demonstrate that
slr1790
encodes a unique Protox enzyme and we propose naming the
slr1790
gene “
hemJ.
”
Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in the surface expression of malaria parasite
var
proteins
Authors: Goel Suchi , Valiyaveettil Manojkumar , Achur Rajeshwara N. , Goyal Atul , Mattei Denise , Salanti Ali , Trenholme Katharine R. , Gardiner Donald L. , Gowda D. Channe
Published: September 2010

Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1) family members mediate the adherence of parasite-infected red blood cells (IRBCs) to various host receptors. A previous study has shown that the parasite protein, cytoadherence-linked asexual gene 9 (CLAG9), is also essential for IRBC adherence. However, how CLAG9 influences this process remains unknown. In this study, we show that CLAG9 interacts with VAR2CSA, a PfEMP1 that mediates IRBC adherence to chondroitin 4-sulfate in the placenta. Importantly, our results show that the adherent parasites synthesize CLAG9 at two stages—the early ring and late trophozoite stages. Localization studies revealed that a substantial level of CLAG9 is located mainly at or in close proximity of the IRBC membrane in association with VAR2CSA. Upon treatment of IRBCs with trypsin, a significant amount of CLAG9 (≈150 kDa) was converted into ≈142-kDa polypeptide. Together these data demonstrate that a considerable amount of CLAG9 is embedded in the IRBC membrane such that at least a portion of the polypeptide at either N or C terminus is exposed on the cell surface. In parasites lacking CLAG9, VAR2CSA failed to express on the IRBC surface and was located within the parasite. Based on these findings, we propose that CLAG9 plays a critical role in the trafficking of PfEMP1s onto the IRBC surface. These results have important implications for the development of therapeutics for cerebral, placental, and other cytoadherence-associated malaria illnesses.
Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival
Authors: Hand Timothy W. , Cui Weiguo , Jung Yong Woo , Sefik Esen , Joshi Nikhil S. , Chandele Anmol , Liu Ying , Kaech Susan M.
Published: September 2010

During viral infection, effector CD8 T cells contract to form a population of protective memory cells that is maintained by IL-7 and IL-15. The mechanisms that control effector cell death during infection are poorly understood. We investigated how short- and long-lived antiviral CD8 T cells differentially used the survival and cell growth pathways PI3K/AKT and JAK/STAT5. In response to IL-15, long-lived memory precursor cells activated AKT significantly better than short-lived effector cells. However, constitutive AKT activation did not enhance memory CD8 T-cell survival but rather repressed IL-7 and IL-15 receptor expression, STAT5 phosphorylation, and BCL2 expression. Conversely, constitutive STAT5 activation profoundly enhanced effector and memory CD8 T-cell survival and augmented homeostatic proliferation, AKT activation, and BCL2 expression. Taken together, these data illustrate that effector and memory cell viability depends on properly balanced PI3K/AKT signaling and the maintenance of STAT5 signaling.
Thymopoiesis in mice depends on a
Foxn1
-positive thymic epithelial cell lineage
Authors: Corbeaux Tatiana , Hess Isabell , Swann Jeremy B. , Kanzler Benoît , Haas-Assenbaum Annette , Boehm Thomas
Published: September 2010

The thymus is essential for T-cell development. Here, we focus on the role of the transcription factor Foxn1 in the development and function of thymic epithelial cells (TECs) of the mouse. TECs are of endodermal origin; they initially express
Foxn1
and give rise to orthotopic (thoracic) and additional (cervical) thymi. Using
Foxn1
-directed cytoablation, we show that during embryogenesis, cervical thymi develop a few days after the thoracic lobes, and that bipotent epithelial progenitors of cortical and medullary compartments express
Foxn1
. We also show that following acute selective near-total ablation during embryogenesis, complete regeneration of TECs does not occur, providing an animal model for human thymic aplasia syndromes. Finally, we address the functional role of
Foxn1
-negative TECs that arise postnatally in the mouse. Lineage tracing shows that such
Foxn1
-negative TECs are descendants of
Foxn1
-positive progenitors; furthermore,
Foxn1
-directed subacute intoxication of TECs by polyglutamine-containing EGFP proteins indicates that a presumptive
Foxn1
-independent lineage does not contribute to thymopoietic function of the adult thymus. Our findings therefore support the notion that Foxn1 is the essential transcription factor regulating the differentiation of TECs and that its expression marks the major functional lineage of TECs in embryonic and adult thymic tissue.
Unveiling a phytoplankton hotspot at a narrow boundary between coastal and offshore waters
Authors: Ribalet Francois , Marchetti Adrian , Hubbard Katherine A. , Brown Kristina , Durkin Colleen A. , Morales Rhonda , Robert Marie , Swalwell Jarred E. , Tortell Philippe D. , Armbrust E. Virginia
Published: September 2010

In terrestrial ecosystems, transitional areas between different plant communities (ecotones) are formed by steep environmental gradients and are commonly characterized by high species diversity and primary productivity, which in turn influences the foodweb structure of these regions. Whether comparable zones of elevated diversity and productivity characterize ecotones in the oceans remains poorly understood. Here we describe a previously hidden hotspot of phytoplankton diversity and productivity in a narrow but seasonally persistent transition zone at the intersection of iron-poor, nitrate-rich offshore waters and iron-rich, nitrate-poor coastal waters of the Northeast Pacific Ocean. Novel continuous measurements of phytoplankton cell abundance and composition identified a complex succession of blooms of five distinct size classes of phytoplankton populations within a 100-km–wide transition zone. The blooms appear to be fueled by natural iron enrichment of offshore communities as they are transported toward the coast. The observed succession of phytoplankton populations is likely driven by spatial gradients in iron availability or time since iron enrichment. Regardless of the underlying mechanism, the resulting communities have a strong impact on the regional biogeochemistry as evidenced by the low partial pressure of CO
2
and the nearly complete depletion of nutrients. Enhanced phytoplankton productivity and diversity associated with steep environmental gradients are expected wherever water masses with complementary nutrient compositions mix to create a region more favorable for phytoplankton growth. The ability to detect and track these important but poorly characterized marine ecotones is critical for understanding their impact on productivity and ecosystem structure in the oceans.
Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function
Authors: Ko Han Seok , Lee Yunjong , Shin Joo-Ho , Karuppagounder Senthilkumar S. , Gadad Bharathi Shrikanth , Koleske Anthony J. , Pletnikova Olga , Troncoso Juan C. , Dawson Valina L. , Dawson Ted M.
Published: September 2010

Mutations in
PARK2/Parkin
, which encodes a ubiquitin E3 ligase, cause autosomal recessive Parkinson disease (PD). Here we show that the nonreceptor tyrosine kinase c-Abl phosphorylates tyrosine 143 of parkin, inhibiting parkin's ubiquitin E3 ligase activity and protective function. c-Abl is activated by dopaminergic stress and by dopaminergic neurotoxins, 1-methyl-4-phenylpyridinium (MPP
+
) in vitro and in vivo by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), leading to parkin inactivation, accumulation of the parkin substrates aminoacyl-tRNA synthetase-interacting multifunctional protein type 2 (AIMP2) (p38/JTV-1) and fuse-binding protein 1 (FBP1), and cell death. STI-571, a c-Abl-family kinase inhibitor, prevents the phosphorylation of parkin, maintaining parkin in a catalytically active and protective state. STI-571’s protective effects require parkin, as shRNA knockdown of parkin prevents STI-571 protection. Conditional knockout of c-Abl in the nervous system also prevents the phosphorylation of parkin, the accumulation of its substrates, and subsequent neurotoxicity in response to MPTP intoxication. In human postmortem PD brain, c-Abl is active, parkin is tyrosine-phosphorylated, and AIMP2 and FBP1 accumulate in the substantia nigra and striatum. Thus, tyrosine phosphorylation of parkin by c-Abl is a major posttranslational modification that inhibits parkin function, possibly contributing to pathogenesis of sporadic PD. Moreover, inhibition of c-Abl may be a neuroprotective approach in the treatment of PD.
Computational model for nanocarrier binding to endothelium validated using in vivo, in vitro, and atomic force microscopy experiments
Authors: Liu Jin , Weller Gregory E. R. , Zern Blaine , Ayyaswamy Portonovo S. , Eckmann David M. , Muzykantov Vladimir R. , Radhakrishnan Ravi
Published: September 2010

A computational methodology based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) has been developed to calculate the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The calculated NC binding free energy landscapes yield binding affinities that agree quantitatively when directly compared against analogous measurements of specific antibody-coated NCs (100 nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in in vitro cell-culture experiments. The effect of antibody surface coverage (
σ

s

) of NC on binding simulations reveals a threshold
σ

s

value below which the NC binding affinities reduce drastically and drop lower than that of single anti-ICAM-1 molecule to ICAM-1. The model suggests that the dominant effect of changing
σ

s

around the threshold is through a change in multivalent interactions; however, the loss in translational and rotational entropies are also important. Consideration of shear flow and glycocalyx does not alter the computed threshold of antibody surface coverage. The computed trend describing the effect of
σ

s

on NC binding agrees remarkably well with experimental results of in vivo targeting of the anti-ICAM-1 coated NCs to pulmonary endothelium in mice. Model results are further validated through close agreement between computed NC rupture-force distribution and measured values in atomic force microscopy (AFM) experiments. The three-way quantitative agreement with AFM, in vitro (cell-culture), and in vivo experiments establishes the mechanical, thermodynamic, and physiological consistency of our model. Hence, our computational protocol represents a quantitative and predictive approach for model-driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.
Deficiency of 5-hydroxyisourate hydrolase causes hepatomegaly and hepatocellular carcinoma in mice
Authors: Stevenson William S. , Hyland Craig D. , Zhang Jian-Guo , Morgan Phillip O. , Willson Tracy A. , Gill Anthony , Hilton Adrienne A. , Viney Elizabeth M. , Bahlo Melanie , Masters Seth L. , Hennebry Sarah , Richardson Samantha J. , Nicola Nicos A. , Metcalf Donald , Hilton Douglas J. , Roberts Andrew W. , Alexander Warren S.
Published: September 2010

With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase in most vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase,Urah, that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutant-encoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lackingUrahsuggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites.
Improvement of φ29 DNA polymerase amplification performance by fusion of DNA binding motifs
Authors: de Vega Miguel , Lázaro José M. , Mencía Mario , Blanco Luis , Salas Margarita
Published: September 2010

Bacteriophage φ29 DNA polymerase is a unique enzyme endowed with two distinctive properties, high processivity and faithful polymerization coupled to strand displacement, that have led to the development of protocols to achieve isothermal amplification of limiting amounts of both circular plasmids and genomic DNA. To enhance the amplification efficiency of φ29 DNA polymerase, we have constructed chimerical DNA polymerases by fusing DNA binding domains to the C terminus of the polymerase. The results show that the addition of Helix-hairpin-Helix [(HhH)
2
] domains increases DNA binding of the hybrid polymerases without hindering their replication rate. In addition, the chimerical DNA polymerases display an improved and faithful multiply primed DNA amplification proficiency on both circular plasmids and genomic DNA and are unique φ29 DNA polymerase variants with enhanced amplification performance. The reported chimerical DNA polymerases will contribute to make φ29 DNA polymerase-based amplification technologies one of the most powerful tools for genomics.
Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task
Authors: Goldstein Rita Z. , Woicik Patricia A. , Maloney Thomas , Tomasi Dardo , Alia-Klein Nelly , Shan Juntian , Honorio Jean , Samaras Dimitris , Wang Ruiliang , Telang Frank , Wang Gene-Jack , Volkow Nora D.
Published: September 2010

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.
Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor
Authors: Watson Philip A. , Chen Yinan F. , Balbas Minna D. , Wongvipat John , Socci Nicholas D. , Viale Agnes , Kim Kwanghee , Sawyers Charles L.
Published: September 2010

Androgen receptor (AR) splice variants lacking the ligand binding domain (ARVs), originally isolated from prostate cancer cell lines derived from a single patient, are detected in normal and malignant human prostate tissue, with the highest levels observed in late stage, castration-resistant prostate cancer. The most studied variant (called AR-V7 or AR3) activates AR reporter genes in the absence of ligand and therefore, could play a role in castration resistance. To explore the range of potential ARVs, we screened additional human and murine prostate cancer models using conventional and next generation sequencing technologies and detected several structurally diverse AR isoforms. Some, like AR-V7/AR3, display gain of function, whereas others have dominant interfering activity. We also find that ARV expression increases acutely in response to androgen withdrawal, is suppressed by testosterone, and in some models, is coupled to full-length AR (AR-FL) mRNA production. As expected, constitutively active, ligand-independent ARVs such as AR-V7/AR3 are sufficient to confer anchorage-independent (in vitro) and castration-resistant (in vivo) growth. Surprisingly, this growth is blocked by ligand binding domain-targeted antiandrogens, such as MDV3100, or by selective siRNA silencing of AR-FL, indicating that the growth-promoting effects of ARVs are mediated through AR-FL. These data indicate that the increase in ARV expression in castrate-resistant prostate cancer is an acute response to castration rather than clonal expansion of castration or antiandrogen-resistant cells expressing gain of function ARVs, and furthermore, they provide a strategy to overcome ARV function in the clinic.
A review of factors limiting recovery of Pacific herring stocks in Canada
Authors: Schweigert Jacob F. , Boldt Jennifer L. , Flostrand Linnea , Cleary Jaclyn S.
Published: September 2010

Schweigert, J. F., Boldt, J. L., Flostrand, L., and Cleary, J. S. 2010. A review of factors limiting recovery of Pacific herring stocks in Canada. – ICES Journal of Marine Science, 67: 1903–1913. On the west coast of Canada, Pacific herring (Clupea pallasi) supported an intensive reduction fishery from the early 1930s until the collapse of all five major stocks in the late 1960s, which then recovered rapidly following a fishery closure. Despite conservative harvests, abundance has declined again recently, with little evidence of recovery. We investigated the effect of bottom-up forcing by zooplankton abundance, top-down forcing by fish and mammal predators, and the effects of sardine abundance as potential competitors on the natural mortality of the herring stock on the west coast of Vancouver Island. Herring mortality was positively related to Thysanoessa spinifera and southern chaetognaths and negatively to pteropod abundance. Estimated predation on herring decreased significantly during the years 1973–2008, with the main consumers changing from fish to mammals. However, the correlation with herring mortality was negative, whereas there was a significant positive relationship with sardine abundance. Population recovery is expected to be facilitated by a combination of factors, including adequate food supply, limited or reduced predation (including fishing), and limited competition particularly for wasp–waist systems, where different forage species may occupy similar niches.
Dyspepsia and heartburn: a clinical challenge
Authors: TALLEY N. J.
Published: September 2010

In recent years it has been widely accepted that the symptom patterns of dyspepsia should be distinguished from heartburn. Dyspepsia is now defined as pain or discomfort centred in the upper abdomen while heartburn is a burning retrosternal pain or discomfort. Both of these symptoms can, of course, be present in a single patient. In the general population, the annual prevalences of recurrent dyspepsia and heartburn (more than once a month) are approximately 25% and 15%, respectively, in Western nations. When these standard definitions are applied the prevalences of these symptoms differ only modestly from country to country. Gastro‐oesophageal reflux disease probably accounts for approximately 25% of patients with dyspepsia, based on endoscopy and 24‐hour pH monitoring results. The prevalence of dyspepsia and heartburn in the population remains stable from year to year. Symptoms disappear in approximately 30% of patients each year but this is balanced by the onset of symptoms in others. It has not proved clinically useful to subdivide dyspepsia into symptom subgroups based on expert opinion. Medical advice is sought by only a minority of patients with dyspepsia or heartburn and, while psychological factors and to a lesser extent symptom severity are important, there is little information on the reasons why advice is sought. The economic impact of dyspepsia and heartburn is substantial because of the high prevalence of these symptoms. Despite the importance of dyspepsia and heartburn in the population, their long‐term natural history remains inadequately described.
Evaluation and significance of reflux from the duodenum and stomach
Authors: SMOUT A. J. P. M.
Published: September 2010

Duodeno‐gastric and gastro‐oesophageal reflux are of potential significance in the pathogenesis of dyspepsia and heartburn. However, convincing evidence that duodeno‐gastric reflux, in itself, causes symptoms is not yet available, and none of the techniques designed to measure duodeno‐gastric reflux has gained broad clinical acceptance. Monitoring of oesophageal pH has become the gold standard, however, for demonstrating gastro‐oesophageal reflux disease, and the technique has become fairly standardized. The importance of measuring gastro‐oesophageal reflux is not so much to differentiate normal (physiological) reflux from abnormal (pathological) reflux, but rather to assess the effect of treatment and to quantify the relationship between gastro‐oesophageal reflux and symptoms. To achieve the latter, a number of indices have been described and tested, with which the temporal association between reflux and symptoms can be expressed quantitatively. It has become clear that troublesome symptoms may be induced by reflux in the absence of oesophagitis and even pathological oesophageal acid exposure. Primary indications for oesophageal pH monitoring are: reflux symptoms in the absence of oesophagitis, atypical symptoms (with or without oesophagitis), non‐cardiac chest pain, and an unsatisfactory response to the treatment of gastro‐oesophageal reflux disease.
Review article: Homing of mucosal immune cells—a possible connection between intestinal and articular inflammation
Authors: BRANDTZAEG Per.
Published: September 2010

An adaptive immune system has developed to protect mucosa, mainly by performing immune exclusion with secretory antibodies (SIgA and SIgM) but also by down‐regulating pro‐inflammatory antibody responses and delayed type hypersensitivity against harmless soluble proteins and the indigenous bacterial flora. In general, mucosal immunopathology appears to represent abrogation of such mucosal tolerance mechanisms. An important consequence is disturbance of the ‘gatekeeper’ function normally performed by the microvasculature through complementary sets of tightly regulated adhesion molecules on mucosal endothelium and circulating leukocytes. The B cells responsible for local polymeric immunoglobulin (Ig) production (mainly dimeric IgA) are stimulated initially in organized lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to secretory tissues all over the body. Mucous membranes are thus furnished with primed B cells in an integrated way, ensuring a variety of secretory antibody specificities at every exocrine site. There is currently great interest in exploiting this integrated or ‘common’ mucosal immune system for topical vaccination against pathogenic infectious agents and also to induce therapeutic peripheral tolerance to ameliorate T‐cell‐mediated autoimmune diseases. Moreover, homing of immune cells from the gut to the inflamed synovium may represent a modifiable link between intestinal immunity and chronic arthropathies.
Review article: How relevant to human inflammatory bowel disease are current animal models of intestinal inflammation?
Authors: SARTOR R. B.
Published: September 2010

New rodent models of chronic intestinal inflammation are mediated by a TH1‐cell and macrophage dominated immune response to luminal bacterial constituents. The pathology of these spontaneous and induced models differ widely and caution is needed when assessing the comparative aspects of such animal models and human inflammatory bowel diseases (IBD). Considerable immunological and therapeutic evidence suggests that chronic and immune‐mediated models are relevant in human IBD and that pathogenic principles are similar. However, animal models have not been able to duplicate exactly the pathological characteristics of ulcerative colitis or Crohn's disease, indicating a need for caution in extrapolating data from experimental models to human IBD.
Recognition of neglect and early response: overview of a systematic review of the literature
Authors: Daniel Brigid , Taylor Julie , Scott Jane
Published: September 2010

This paper summarizes the key findings from a systematic literature review that sought to identify existing evidence about the ways in which the needs of neglected children and their parents are signalled and the response to those needs. Using systematic review guidelines, 14 databases were searched for primary research studies published in English from 1995 to 2005. An initial 20 480 items were systematically filtered down to 63 papers for inclusion. The evidence suggests that, while there is little evidence about how needs for help are directly signalled, there is considerable evidence about how needs are indirectly signalled. There is evidence that professionals can identify signs of neglect, but are not always clear about the best response. There remain gaps in evidence about how best to respond to neglected needs, especially within schools.
Long‐term periodic anthelmintic treatments are associated with increased allergen skin reactivity
Authors: Endara P. , Vaca M. , Chico M. E. , Erazo S. , Oviedo G. , Quinzo I. , Rodriguez A. , Lovato R. , Moncayo A.‐L. , Barreto M. L. , Rodrigues L. C. , Cooper P. J.
Published: September 2010

Background
The low prevalence of allergic disease in the rural tropics has been attributed to the protective effects of chronic helminth infections. There is concern that treatment‐based control programmes for these parasites may lead to an increase in the prevalence of allergic diseases.

Objective
We measured the impact of 15–17 years of anthelmintic treatment with ivermectin on the prevalence of allergen skin test reactivity and allergic symptoms in school‐age children.

Methods
The prevalence of allergen skin test reactivity, exercise‐induced bronchospasm and allergic symptoms was compared between school‐age children living in communities that had received community‐based treatments with ivermectin (for onchocerciasis control) for a period of 15–17 years with those living in geographically adjacent communities that had received no ivermectin.

Results
The prevalence of allergen skin test reactivity was double in children living in treated communities compared with those in untreated communities (16.7% vs. 8.7%, adjusted OR 2.10, 95% CI 1.50–2.94, P<0.0001), and the effect was mediated partly by a reduced prevalence of Trichuris trichiura among treated children. Ivermectin treatments were associated with an increased prevalence of recent eczema symptoms (adjusted OR 2.24, 95% CI 1.05–4.78, P=0.04) but not symptoms of asthma or rhino‐conjunctivitis. The effect on eczema symptoms was not associated with reductions in geohelminth infections.

Conclusion
Long‐term periodic treatments with ivermectin were associated with an increased prevalence of allergen skin test reactivity. There was some evidence that treatment was associated with an increased prevalence of recent eczema symptoms but not those of asthma or rhino‐conjunctivitis.

Cite this as: P. Endara, M. Vaca, M. E. Chico, S. Erazo, G. Oviedo, I. Quinzo, A. Rodriguez R. Lovato, A.‐L. Moncayo, M. L. Barreto, L. C. Rodrigues and P. J. Cooper, Clinical & Experimental Allergy, 2010 (40) 1669–1677.
Near‐infrared spectroscopy for within‐field soil characterization: small local calibrations compared with national libraries spiked with local samples
Authors: Wetterlind J. , Stenberg B.
Published: September 2010

The advantage of using near‐infrared spectroscopy to increase sample point density in soil mapping on farms relies on the number of conventional laboratory analyses for the calibrations being kept to a minimum. This study compared the performance of small farm‐scale calibrations (25 samples) with a larger national soil library (396 samples) and tested whether a site‐specific sample set selected from the national library, consisting of the 50 samples that were spectrally most similar to those of the local sites, could increase performance. In addition, the national library and selected subsets were augmented (‘spiked’) with up to 25 local calibration samples to test whether that had any additional effect on prediction errors and bias. Calibrations were made for predicting within‐field variation in clay, silt, sand, soil organic carbon (SOC), pH and phosphorus. Selecting a subset of samples from the national library did not improve the results compared with using the entire national library. However, spiking both libraries with local samples reduced the root mean squared error of prediction (RMSEP) considerably, mainly through a decrease in bias, and often resulted in comparable results to the local calibrations. There was a tendency for better clay and SOC predictions from spiking a reduced national library compared with spiking the entire national library, sometimes even resulting in better predictions than using the local calibrations. However, using local calibrations seems to be the best alternative for predicting soil properties at the farm or field scale, even with as few as 25 samples.
Human Tribbles homolog 1 functions as a negative regulator of retinoic acid receptor
Authors: Imajo Masamichi , Nishida Eisuke
Published: September 2010

Tribbles encode an evolutionarily conserved protein family that regulates cell proliferation, motility, metabolism and oncogenic transformation. Emerging evidence suggests that Tribbles function as adaptor or scaffold proteins to facilitate the degradation of their target proteins and to control the activation of various key signaling pathways. In this study, we uncover a novel function of human Tribbles homolog 1 (Trib1) as a regulator of retinoic acid receptor (RAR) signaling. We show that shRNA‐mediated knockdown of Trib1 promotes transcriptional activity of RARs, leading to enhanced expression of endogenous RAR‐target genes. Moreover, our results show that Trib1 directly interacts with RARα and retinoid X receptor‐α (RXRα) through its kinase‐like domain. Consistently, Trib1 colocalizes with RARα and RXRα in the nucleus. Biochemical analyses show that the ligand‐binding domain (LBD) of RARα mediates the interaction with Trib1. Ligand treatment, however, does not affect the binding of Trib1 to RARα/RXRα. Furthermore, a putative LXXLL motif, which is a potential LBD‐binding site and locates in the kinase‐like domain of Trib1, is not required for the binding. These results suggest a unique feature of the binding. Taken together, these results suggest that Trib1 functions as a negative regulator of RARs and shed new light on the molecular mechanisms for nuclear receptor‐mediated transcriptional repression.