bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting potential change in agricultural sediment inputs to rivers across England and Wales by 2015
Authors: Collins Adrian L. , Anthony Steven G. , Hawley Julia , Turner Tony
Published: July 2009

Recent work has evaluated the gap between current and compliant suspended sediment losses due to farming across England and Wales and the potential for change by 2015. The study adopted the guideline annual average sediment threshold of 25 mg L–1 cited by the European Union Freshwater Fish Directive. Compliance testing required national scale sediment source apportionment to assess the current contributions of diffuse agricultural and urban sector losses, channel bank erosion and point source discharges to the total suspended sediment loads delivered to all rivers. Results suggested that the agricultural sector dominates present day (year 2000) sediment inputs to rivers (1929 kt = 76%) compared with eroding channel banks (394 kt = 15%), diffuse urban sources (147 kt = 6%) and point source discharges (76 kt = 3%). Projected change in farming by 2015, represented by the Business As Usual forecast of structural developments and predicted uptake of sediment mitigation methods, suggested a 9% reduction in sediment losses from the agricultural sector across England and Wales. Further mitigation of diffuse agricultural sediment transfers to watercourses will therefore be necessary to ensure ‘good ecological status’ in some catchments. A similar modelling framework could be applied in other countries.
The distribution and isotopic composition of carbon and nitrogen as indicators of organic-matter fluxes in the Solina Reservoir (south-east Poland)
Authors: Tomaszek Janusz A. , Koszelnik Piotr , Gruca-Rokosz Renata
Published: July 2009

The feasibility of using carbon and nitrogen isotope ratios of sediment organic matter (OM) to elucidate the source and fate of bottom sediment was studied in the Solina Reservoir (south-east Poland). Horizontal and vertical changes in OM, total organic carbon (TOC) and total nitrogen (TN) content, as well as δ15N and δ13C values, in bottom sediments were analysed to establish the extent to which these sediments are terrestrial or internal in origin. Increased proportions of TOC along with slight decreases in TN were noted in the surface layer of shallow water sediment compared with the profundal sites. Upstream shallower C : N and δ15N values amounted to ~15 and ~2‰, respectively, pointing to the allochthonous origin of the OM. In turn, profundal C : N ratios of less than 10 and δ15N values of ~4‰ indicated autochthonous sediment. Values for δ13C did not differ between stations and ranged from –27.39 to –27.66‰. It is therefore suggested that the sediment from the upper shallower stations contains more allochthonous, refractory OM, whereas the profundal stations have planktonic OM enriching the sediment. This combined with the vertical distribution observed for δ15N signalled an intensification of eutrophication over the past few years.
Effect of land use and moisture on phosphorus forms in upland stream beds in South Otago, New Zealand
Authors: McDowell Richard W.
Published: July 2009

Land use can influence stream sediment composition and water quality, whereas moisture status affects sediment phosphorus (P) bioavailability to algae. Declining upland surface-water quality in South Otago, New Zealand, may reflect land-use changes from sheep- to dairy-farming. I sampled sediment (0–20 cm) from streams draining 12 dairy- and 12 sheep-farmed catchments in spring (wet) and autumn (dry). 31P nuclear magnetic resonance (NMR) spectroscopy and the EDTA-fractionation scheme were used to determine different P forms and infer P bioavailability. Significantly more P was present in the sediment of streams draining dairy- than sheep-farmed catchments. Total P did not differ with the moisture regime; however, changes occurred in the following P fractions: acid-soluble organic P, NaOH-P, CaCO3≈P, Fe(OOH)≈P and residual organic P. Extraction for 31P NMR analysis removed 78–85% of sediment total P and isolated five P classes. More bioavailable P such as orthophosphate (23–40% of P extracted) and diesters (2–6% of P extracted) was present in dry than in wet sediments, and in sediments draining dairy streams than in those from sheep-farmed catchments. This indicates substantial reserves of bioavailable P in sediment from these catchments, especially from dairy-farmed catchments, sustaining in-stream P concentrations for many years even without additional P input from land.
Mercury concentration and solid phase speciation changes in the course of early diagenesis in marine coastal sediments (Southern Baltic Sea)
Authors: Beldowski Jacek , Pempkowiak Janusz
Published: July 2009

On reaching the sea, mercury discharged into the environment is deposited on and buried in marine sediments. Diagenetic processes in sediments lead to changes in both mercury concentration and speciation; they may enhance mercury bioavailability and/or lead to mercury remobilisation. Total concentrations and speciation of mercury were measured in dated sediment samples from sites covering a range of different environmental conditions and mercury concentrations. In the course of ~200 year-long diagenetic processes, the dominant changes in mercury speciation have involved diffusion of labile mercury to the overlying water, transformation of organic-bound mercury to HgS under anoxic conditions or to insoluble humin-bound Hg under oxic conditions, and dismutation of HgS into soluble polysulfides under hyperanoxic conditions. Rate constants of labile-to-stable mercury species transformations and the return flux of mercury were calculated on the basis of sediment core geochronology obtained by the 210Pb method. Although the study was performed in a specific area, we believe that the observed processes are valid for other shallow, coastal seas and that the results enable mercury stability in sediments to be assessed in similar areas worldwide.
Short-term variability of intertidal microphytobenthic production using an oxygen microprofiling system
Authors: Denis Lionel , Desreumaux Pierre-Emmanuel
Published: July 2009

Despite their high productivity and their key role in coastal processes, intertidal areas remain poorly documented because alternating conditions of sediment-water and sediment-air interfaces result in inaccurate temporal estimations of interfacial carbon exchanges. This study describes the short-term variability of microphytobenthic production in an estuarine mudflat (the Canche estuary of the English Channel) by using an autonomous acquisition system for oxygen microprofiles. More than 240 profiles were measured at low and high tide during three deployments performed within a 3-week period (April–May 2007). Additional measurements characterised the surficial sediments (granulometry, porosity, chlorophyll a, temperature, salinity) and incident light. Depth-integrated gross production values were correlated with light intensity and reached up to 146 mg C m–2 h–1, while the turbidity of the overlying water prevented any primary production during immersion. Photosynthesis–irradiance curves were highly variable between field campaigns. Indeed, we have recorded a drastic reduction in microphytobenthic production, which might result from a pulse input of polychaete juveniles (Lanice conchilega). Ephemeral structures, such as invertebrate tubes, are seldom considered as factors that may influence the variability of benthic primary production. Monitoring oxygen microprofiles may be a useful tool for understanding and quantifying the impact of short-term temporal changes on the budgets of microphytobenthic production.
Effects of suspended sediment content on biodegradation of three common endocrine disruptors in river water
Authors: Liu Ying , Sun Weiling , Li Min , Ni Jinren
Published: July 2009

Bisphenol A (BPA), 17β-oestradiol (E2) and 17α-ethynylestradiol (EE2) are common endocrine disruptors (EDs) in river water, and biodegradation is regarded as an important process for their removal from river water. The suspended sediment (SS) content is very high in some rivers, which may affect the biodegradation of these EDs. In this study, the degradation of BPA, E2 and EE2 in river water with different SS contents was investigated using batch experiments. The results show that the biodegradation rates of BPA, E2 and EE2 increase with the SS content in water samples. The half-lives of BPA, E2 and EE2 are 2.44–52.51 days, 0.40–6.38 days and 3.47–25.77 days, respectively, at SS contents ranging from 0 g L–1 to 15 g L–1. Micrographs demonstrate more bacteria in the SS than in the water phase. Higher SS concentrations provide greater surface areas for bacterial attachment and these bacteria apparently accelerate the biodegradation of common EDs.
Control of p53 multimerization by Ubc13 is JNK-regulated
Authors: Topisirovic Ivan , Gutierrez Gustavo J. , Chen Meifan , Appella Ettore , Borden Katherine L. B. , Ronai Ze'ev A.
Published: July 2009

The p53 tumor suppressor protein is a key regulator of cellular proliferation and survival whose function is tightly regulated at the levels of transcription and protein stability. Here, we unveil the fine control of p53 on translationally active polysomes. We have previously reported that Ubc13, an E2 ubiquitin-conjugating enzyme, directly regulates p53 localization and transcriptional activity. We now demonstrate that the association of p53 and Ubc13 on polysomes requires ongoing translation and results in p53 ubiquitination that interferes with its tetramerization. JNK phosphorylation of p53 at Threonine 81 occurring on polysomes is required for the dissociation of Ubc13 from p53, leading to p53 multimerization and transcriptional activation. Inhibition of JNK activity or expression of a nonphosphorylatable mutant of p53 maintains an Ubc13-p53 complex that inhibits p53 multimerization. Our findings reveal a layer in the regulation of p53 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53.
Structural basis for a human glycosylation disorder caused by mutation of the
COG4
gene
Authors: Richardson Brian C. , Smith Richard D. , Ungar Daniel , Nakamura Ayumi , Jeffrey Philip D. , Lupashin Vladimir V. , Hughson Frederick M.
Published: July 2009

The proper glycosylation of proteins trafficking through the Golgi apparatus depends upon the conserved oligomeric Golgi (COG) complex. Defects in COG can cause fatal congenital disorders of glycosylation (CDGs) in humans. The recent discovery of a form of CDG, caused in part by a
COG4
missense mutation changing Arg 729 to Trp, prompted us to determine the 1.9 Å crystal structure of a Cog4 C-terminal fragment. Arg 729 is found to occupy a key position at the center of a salt bridge network, thereby stabilizing Cog4's small C-terminal domain. Studies in HeLa cells reveal that this C-terminal domain, while not needed for the incorporation of Cog4 into COG complexes, is essential for the proper glycosylation of cell surface proteins. We also find that Cog4 bears a strong structural resemblance to exocyst and Dsl1p complex subunits. These complexes and others have been proposed to function by mediating the initial tethering between transport vesicles and their membrane targets; the emerging structural similarities provide strong evidence of a common evolutionary origin and may reflect shared mechanisms of action.
Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in
Apc

Min
/+

mice with natural ligands
Authors: Kawajiri Kaname , Kobayashi Yasuhito , Ohtake Fumiaki , Ikuta Togo , Matsushima Yoshibumi , Mimura Junsei , Pettersson Sven , Pollenz Richard S. , Sakaki Toshiyuki , Hirokawa Takatsugu , Akiyama Tetsu , Kurosumi Masafumi , Poellinger Lorenz , Kato Shigeaki , Fujii-Kuriyama Yoshiaki
Published: July 2009

Intestinal cancer is one of the most common human cancers. Aberrant activation of the canonical Wnt signaling cascade, for example, caused by adenomatous polyposis coli (APC) gene mutations, leads to increased stabilization and accumulation of β-catenin, resulting in initiation of intestinal carcinogenesis. The aryl hydrocarbon receptor (AhR) has dual roles in regulating intracellular protein levels both as a ligand-activated transcription factor and as a ligand-dependent E3 ubiquitin ligase. Here, we show that the AhR E3 ubiquitin ligase has a role in suppression of intestinal carcinogenesis by a previously undescribed ligand-dependent β-catenin degradation pathway that is independent of and parallel to the APC system. This function of AhR is activated by both xenobiotics and natural AhR ligands, such as indole derivatives that are converted from dietary tryptophan and glucosinolates by intestinal microbes, and suppresses intestinal tumor development in
Apc

Min
/+

mice. These findings suggest that chemoprevention with naturally-occurring and chemically-designed AhR ligands can be used to successfully prevent intestinal cancers.
Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury
Authors: Peng Weiguo , Cotrina Maria L. , Han Xiaoning , Yu Hongmei , Bekar Lane , Blum Livnat , Takano Takahiro , Tian Guo-Feng , Goldman Steven A. , Nedergaard Maiken
Published: July 2009

Traumatic spinal cord injury is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should, in principle, be preventable, no effective treatment options currently exist for patients with acute spinal cord injury (SCI). Excessive release of ATP by the traumatized tissue, followed by activation of high-affinity P2X7 receptors, has previously been implicated in secondary injury, but no clinically relevant strategy by which to antagonize P2X7 receptors has yet, to the best of our knowledge, been reported. Here we have tested the neuroprotective effects of a systemically administered P2X7R antagonist, Brilliant blue G (BBG), in a weight-drop model of thoracic SCI in rats. Administration of BBG 15 min after injury reduced spinal cord anatomic damage and improved motor recovery without evident toxicity. Moreover, BBG treatment directly reduced local activation of astrocytes and microglia, as well as neutrophil infiltration. These observations suggest that BBG not only protected spinal cord neurons from purinergic excitotoxicity, but also reduced local inflammatory responses. Importantly, BBG is a derivative of a commonly used blue food color (FD&C blue No. 1), which crosses the blood–brain barrier. Systemic administration of BBG may thus comprise a readily feasible approach by which to treat traumatic SCI in humans.
Acquired copy number alterations in adult acute myeloid leukemia genomes
Authors: Walter Matthew J. , Payton Jacqueline E. , Ries Rhonda E. , Shannon William D. , Deshmukh Hrishikesh , Zhao Yu , Baty Jack , Heath Sharon , Westervelt Peter , Watson Mark A. , Tomasson Michael H. , Nagarajan Rakesh , O'Gara Brian P. , Bloomfield Clara D. , Mrózek Krzysztof , Selzer Rebecca R. , Richmond Todd A. , Kitzman Jacob , Geoghegan Joel , Eis Peggy S. , Maupin Rachel , Fulton Robert S. , McLellan Michael , Wilson Richard K. , Mardis Elaine R. , Link Daniel C. , Graubert Timothy A. , DiPersio John F. , Ley Timothy J.
Published: July 2009

Cytogenetic analysis of acute myeloid leukemia (AML) cells has accelerated the identification of genes important for AML pathogenesis. To complement cytogenetic studies and to identify genes altered in AML genomes, we performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using 1.85 million feature SNP arrays. Acquired copy number alterations (CNAs) were confirmed using an ultra-dense array comparative genomic hybridization platform. A total of 201 somatic CNAs were found in the 86 AML genomes (mean, 2.34 CNAs per genome), with French-American-British system M6 and M7 genomes containing the most changes (10–29 CNAs per genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, whereas 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several CNA regions were recurrent. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions <5 megabases in size. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes; 6 of 8 UPD calls occurred in samples with a normal karyotype. Collectively, 34 of 86 AML genomes (40%) contained alterations not found with cytogenetics, and 98% of these regions contained genes. Of 86 genomes, 43 (50%) had no CNA or UPD at this level of resolution. In this study of 86 adult AML genomes, the use of an unbiased high-resolution genomic screen identified many genes not previously implicated in AML that may be relevant for pathogenesis, along with many known oncogenes and tumor suppressor genes.
Marijuana craving in the brain
Authors: Filbey Francesca M. , Schacht Joseph P. , Myers Ursula S. , Chavez Robert S. , Hutchison Kent E.
Published: July 2009

Craving is one of the primary behavioral components of drug addiction, and cue-elicited craving is an especially powerful form of this construct. While cue-elicited craving and its underlying neurobiological mechanisms have been extensively studied with respect to alcohol and other drugs of abuse, the same cannot be said for marijuana. Cue-elicited craving for other drugs of abuse is associated with increased activity in a number of brain areas, particularly the reward pathway. This study used functional magnetic resonance imaging (fMRI) to examine cue-elicited craving for marijuana. Thirty-eight regular marijuana users abstained from use for 72 h and were presented with tactile marijuana-related and neutral cues while undergoing a fMRI scan. Several structures in the reward pathway, including the ventral tegmental area, thalamus, anterior cingulate, insula, and amygdala, demonstrated greater blood oxygen level dependent (BOLD) activation in response to the marijuana cue as compared with the neutral cue. These regions underlie motivated behavior and the attribution of incentive salience. Activation of the orbitofrontal cortex and nucleus accumbens was also positively correlated with problems related to marijuana use, such that greater BOLD activation was associated with greater number of items on a marijuana problem scale. Thus, cue-elicited craving for marijuana activates the reward neurocircuitry associated with the neuropathology of addiction, and the magnitude of activation of these structures is associated with severity of cannabis-related problems. These findings may inform the development of treatment strategies for cannabis dependence.
Extraordinary synergy in the mechanical properties of polymer matrix composites reinforced with 2 nanocarbons
Authors: Prasad K. Eswar , Das Barun , Maitra Urmimala , Ramamurty Upadrasta , Rao C. N. R.
Published: July 2009

One of the applications of nanomaterials is as reinforcements in composites, wherein small additions of nanomaterials lead to large enhancements in mechanical properties. There have been extensive studies in the literature on composites where a polymer matrix is reinforced by a single nanomaterial such as carbon nanotubes. In this article, we examine the significant synergistic effects observed when 2 different types of nanocarbons are incorporated in a polymer matrix. Thus, binary combinations of nanodiamond, few-layer graphene, and single-walled nanotubes have been used to reinforce polyvinyl alcohol. The mechanical properties of the resulting composites, evaluated by the nanoindentation technique, show extraordinary synergy, improving the stiffness and hardness by as much as 400% compared to those obtained with single nanocarbon reinforcements. These results suggest a way of designing advanced materials with extraordinary mechanical properties by incorporating small amounts of 2 nanomaterials such as graphene plus nanodiamond or nanodiamond plus carbon nanotube.
Potent neutralization of anthrax edema toxin by a humanized monoclonal antibody that competes with calmodulin for edema factor binding
Authors: Chen Zhaochun , Moayeri Mahtab , Zhao Huaying , Crown Devorah , Leppla Stephen H. , Purcell Robert H.
Published: July 2009

This study describes the isolation and characterization of a neutralizing monoclonal antibody (mAb) against anthrax edema factor, EF13D. EF13D neutralized edema toxin (ET)-mediated cyclic AMP (cAMP) responses in cells and protected mice from both ET-induced footpad edema and systemic ET-mediated lethality. The antibody epitope was mapped to domain IV of EF. The mAb was able to compete with calmodulin (CaM) for EF binding and displaced CaM from EF-CaM complexes. EF-mAb binding affinity (0.05–0.12 nM) was 50- to 130-fold higher than that reported for EF-CaM. This anti-EF neutralizing mAb could potentially be used alone or with an anti-PA mAb in the emergency prophylaxis and treatment of anthrax infection.
Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein
Authors: Ferreon Josephine C. , Martinez-Yamout Maria A. , Dyson H. Jane , Wright Peter E.
Published: July 2009

The adenovirus early region 1A (E1A) oncoprotein mediates cell transformation by deregulating host cellular processes and activating viral gene expression by recruitment of cellular proteins that include cyclic-AMP response element binding (CREB) binding protein (CBP)/p300 and the retinoblastoma protein (pRb). While E1A is capable of independent interaction with CBP/p300 or pRb, simultaneous binding of both proteins is required for maximal biological activity. To obtain insights into the mechanism by which E1A hijacks the cellular transcription machinery by competing with essential transcription factors for binding to CBP/p300, we have determined the structure of the complex between the transcriptional adaptor zinc finger-2 (TAZ2) domain of CBP and the conserved region-1 (CR1) domain of E1A. The E1A CR1 domain is unstructured in the free state and upon binding folds into a local helical structure mediated by an extensive network of intermolecular hydrophobic contacts. By NMR titrations, we show that E1A efficiently competes with the N-terminal transactivation domain of p53 for binding to TAZ2 and that pRb interacts with E1A at 2 independent sites located in CR1 and CR2. We show that pRb and the CBP TAZ2 domain can bind simultaneously to the CR1 site of E1A to form a ternary complex and propose a structural model for the pRb:E1A:CBP complex on the basis of published x-ray data for homologous binary complexes. These observations reveal the molecular basis by which E1A inhibits p53-mediated transcriptional activation and provide a rationale for the efficiency of cellular transformation by the adenoviral E1A oncoprotein.
CT-X antigen expression in human breast cancer
Authors: Grigoriadis Anita , Caballero Otavia L. , Hoek Keith S. , da Silva Leonard , Chen Yao-Tseng , Shin Sandra J. , Jungbluth Achim A. , Miller Lance D. , Clouston David , Cebon Jonathan , Old Lloyd J. , Lakhani Sunil R. , Simpson Andrew J. G. , Neville A. Munro
Published: July 2009

Cancer/testis (CT) genes are predominantly expressed in human germ line cells, but not somatic tissues, and frequently become activated in different cancer types. Several CT antigens have already proved to be useful biomarkers and are promising targets for therapeutic cancer vaccines. The aim of the present study was to investigate the expression of CT antigens in breast cancer. Using previously generated massively parallel signature sequencing (MPSS) data, together with 9 publicly available gene expression datasets, the expression pattern of CT antigens located on the X chromosome (CT-X) was interrogated. Whereas a minority of unselected breast cancers was found to contain CT-X transcripts, a significantly higher expression frequency was detected in estrogen and progesterone receptor (ER) negative breast cancer cell lines and primary breast carcinomas. A coordinated pattern of CT-X antigen expression was observed, with MAGEA and NY-ESO-1/CTAG1B being the most prevalent antigens. Immunohistochemical staining confirmed the correlation of CT-X antigen expression and ER negativity in breast tumors and demonstrated a trend for their coexpression with basal cell markers. Because of the limited therapeutic options for ER-negative breast cancers, vaccines based on CT-X antigens might prove to be useful.
Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses
Authors: Everts Bart , Perona-Wright Georgia , Smits Hermelijn H. , Hokke Cornelis H. , van der Ham Alwin J. , Fitzsimmons Colin M. , Doenhoff Michael J. , van der Bosch Jürgen , Mohrs Katja , Haas Helmut , Mohrs Markus , Yazdanbakhsh Maria , Schramm Gabriele
Published: July 2009

Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1–depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1–mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.
The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1)
Authors: Steinfelder Svenja , Andersen John F. , Cannons Jennifer L. , Feng Carl G. , Joshi Manju , Dwyer Dennis , Caspar Pat , Schwartzberg Pamela L. , Sher Alan , Jankovic Dragana
Published: July 2009

Schistosoma mansoni eggs contain factors that trigger potent Th2 responses in vivo and condition mouse dendritic cells (DCs) to promote Th2 lymphocyte differentiation. Using an in vitro bystander polarization assay as the readout, we purified and identified the major Th2-inducing component from soluble egg extract (SEA) as the secreted T2 ribonuclease, omega-1. The Th2-promoting activity of omega-1 was found to be sensitive to ribonuclease inhibition and did not require MyD88/TRIF signaling in DCs. In common with unfractioned SEA, the purified native protein suppresses lipopolysaccharide-induced DC activation, but unlike SEA, it fails to trigger interleukin 4 production from basophils. Importantly, omega-1–exposed DCs displayed pronounced cytoskeletal changes and exhibited decreased antigen-dependent conjugate formation with CD4+ T cells. Based on this evidence, we hypothesize that S. mansoni omega-1 acts by limiting the interaction of DCs with CD4+ T lymphocytes, thereby lowering the strength of the activation signal delivered.
Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23–Th17 pathway
Authors: Espinosa Alexander , Dardalhon Valerie , Brauner Susanna , Ambrosi Aurelie , Higgs Rowan , Quintana Fransisco J. , Sjöstrand Maria , Eloranta Maija-Leena , Ní Gabhann Joan , Winqvist Ola , Sundelin Birgitta , Jefferies Caroline A. , Rozell Björn , Kuchroo Vijay K. , Wahren-Herlenius Marie
Published: July 2009

Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren's syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 may promote development of systemic autoimmune diseases has not been explored. To address this issue, we generated Ro52-null mice (Ro52−/−), which appear phenotypically normal if left unmanipulated. However, Ro52−/− mice develop severe dermatitis extending from the site of tissue injury induced by ear tags. The affected mice further develop several signs of systemic lupus with hypergammaglobulinemia, autoantibodies to DNA, proteinuria, and kidney pathology. Ro52, which was recently identified as an E3 ligase, mediates ubiquitination of several members of the interferon regulatory factor (IRF) family, and the Ro52-deficient mice have an enhanced production of proinflammatory cytokines that are regulated by the IRF transcription factors, including cytokines involved in the Th17 pathway (interleukin [IL] 6, IL-12/IL-23p40, and IL-17). Loss of IL-23/IL-17 by genetic deletion of IL-23/p19 in the Ro52−/− mice conferred protection from skin disease and systemic autoimmunity. These data reveal that the lupus-associated Ro52 protein is an important negative regulator of proinflammatory cytokine production, and they provide a mechanism by which a defective Ro52 function can lead to tissue inflammation and systemic autoimmunity through the IL-23–Th17 pathway.
Myocyte necrosis underlies progressive myocardial dystrophy in mouse dsg2-related arrhythmogenic right ventricular cardiomyopathy
Authors: Pilichou Kalliopi , Remme Carol Ann , Basso Cristina , Campian Maria E. , Rizzo Stefania , Barnett Phil , Scicluna Brendon P. , Bauce Barbara , van den Hoff Maurice J.B. , de Bakker Jacques M.T. , Tan Hanno L. , Valente Marialuisa , Nava Andrea , Wilde Arthur A.M. , Moorman Antoon F.M. , Thiene Gaetano , Bezzina Connie R.
Published: July 2009

Mutations in the cardiac desmosomal protein desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We studied the explanted heart of a proband carrying the DSG2-N266S mutation as well as transgenic mice (Tg-NS) with cardiac overexpression of the mouse equivalent of this mutation, N271S-dsg2, with the aim of investigating the pathophysiological mechanisms involved. Transgenic mice recapitulated the clinical features of ARVC, including sudden death at young age, spontaneous ventricular arrhythmias, cardiac dysfunction, and biventricular dilatation and aneurysms. Investigation of transgenic lines with different levels of transgene expression attested to a dose-dependent dominant-negative effect of the mutation. We demonstrate for the first time that myocyte necrosis is the key initiator of myocardial injury, triggering progressive myocardial damage, including an inflammatory response and massive calcification within the myocardium, followed by injury repair with fibrous tissue replacement, and myocardial atrophy. These observations were supported by findings in the explanted heart from the patient. Insight into mechanisms initiating myocardial damage in ARVC is a prerequisite to the future development of new therapies aimed at delaying onset or progression of the disease.
Use of a T Cell Interferon-γ Release Assay to Evaluate Tuberculosis Risk in Newly Qualified Physicians in Singapore Healthcare Institutions
Authors: Chee C. B. E. , Lim L. K. Y. , Barkham T. M. , Koh D. R. , Lam S. O. , Shen L. , Wang Y. T.
Published: July 2009

Background.

Surveillance for latent tuberculosis in high-risk groups such as healthcare workers is limited by the nonspecificity of the tuberculin skin test (TST) in BCG-vaccinated individuals. The Mycobacterium tuberculosis antigen-specific interferon-γ release assays (IGRAs) show promise for more accurate latent tuberculosis detection in such groups.

Objective.

To compare the utility of an IGRA, the T-SPOT.TB assay, with that of the TST in healthcare workers with a high rate of BCG vaccination.

Methods.

Two hundred seven medical students from 2 consecutive cohorts underwent the T-SPOT.TB test and the TST in their final year of study. Subjects with negative baseline test results underwent repeat testing after working for 1 year as junior physicians in Singapore's public hospitals.

Results.

The baseline TST result was an induration 10 mm or greater in diameter in 177 of the 205 students who returned to have their TST results evaluated (86.3%), while the baseline T-SPOT.TB assay result was positive in 9 (4.3%) of the students. Repeat T-SPOT.TB testing in 182 baseline-negative subjects showed conversion in 9 (4.9%). A repeat TST in 18 subjects with baseline-negative TST results did not reveal any TST result conversion.

Conclusions.

The high rate of positive baseline TST results in our BCG-vaccinated healthcare workers renders the TST unsuitable as a surveillance tool in this tuberculosis risk group. Use of an IGRA has enabled the detection and treatment of latent tuberculosis in this group. Our T-SPOT.TB conversion rate highlights the need for greater tuberculosis awareness and improved infection control practices in our healthcare institutions.
Competition Between Two Excitation-dissociation Channels for Molecular Ions
Authors: Lai Li-kun , Zhang Li-min , Yang Mao-ping , Zhou Dan-na
Published: July 2009

When the molecular ions XYZ+ (XY2+) are excited simultaneously from an electronic state E0 into two higher electronic states E and E with supervened dissociation or predissociation, competition between the and excitation-dissociation channels occurs. A theoretical model is provided to deal with the competition of the two excitation-dissociation channels with more than two kinds of ionic products for XYZ+ (XY2+). Supposing that the photo-excitation rates of two states E and E are much less than their dissociation or pre-dissociation rates, a theoretical equation can be deduced to fit the measured data, which reflects the dependence of the product branching ratios on the intensity ratios of two excitation lasers. From the fitted parameters the excitation cross section ratios are obtained. In experiment, we studied the competition between two excitation-dissociation channels of CO2+. By measuring the dependence of the product branching ratio on the intensity ratio of two dissociation lasers and fitting the experiment data with the theoretical equation, excitation cross section ratios were deduced.
Analytical Dielectric Spectrum Formula Based on Representative Frequencies
Authors: Kong Bo , Fu Ke-xiang , Shan Min-hua , Li Xiang-yuan
Published: July 2009

According to experimental data available for the complex refractive index of particular dielectrics, a dielectric spectrum formula is proposed by the least square fitting technique combined with selected natural frequencies. From the dielectric spectrum formula, the spectra of optical and dielectric constants can be obtained in the whole frequency region. Three dielectrics, water, ethanol, and toluene, are taken as examples. In the region where the experimental data are available, the spectra of the optical constants calculated by the formula are in good agreement with the real refractive spectrum obtained by KramersKronig (KK) transform and the experimental imaginary refractive spectrum. In the region where no experimental data are available, the extrapolation of our formula can make predictions. The merits of the present treatment are that we are able to get the uniform spectrum formula, without splitting into different frequency sections, and the analytical form of the dielectric spectra will be useful in the theoretical description of solvation dynamics.
X-ray and DFT Study of Glaucocalyxin A Compound with Cytotoxic Activity
Authors: Wang Fu-dong , Wang Tao , Wu An-an , Ding Lan , Wang Han-qing
Published: July 2009

The title compound glaucocalyxin A (1) (7, 14-dihydroxy-ent-kaur-16-en-3,15-dione) isolated from the leaves of isodon excisoides was characterized by IR, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC, and EIMS, and its crystal structure was determined by single-crystal X-ray diffraction. The X-ray crystal structure revealed that the molecular backbone of the chosen crystal is a tetracyclic system, including three six-membered rings and a five-membered ring, and the three six-membered rings are in a chair-like conformation. The five-membered ring adopts a twisted envelope-like conformation, and its geometrical parameters were compared with theoretical calculations at the B3LYP and HF level of theory. The molecules form extensive networks through the intra- and intermolecular hydrogen bonds. The experimental NMR data were interpreted with the aid of magnetic shielding constant calculations, by means of the GIAO (gauge-lncluding atomic orbitals) method. Calculated and experimental results were compared with a satisfactory level of agreement. Molecular electrostatic potential map was used in an attempt to identify key features of the diterpenoid glaucocalyxin A that is necessary for its activity. Calculations of molecular electrostatic potential and stabilization energies suggest that the protonation of glaucocalyxin A will be able to occur on carbonyl oxygen atoms.
Superacid Catalyst SO42/ZrO2-La2O3 Prepared by Ultrasonic Co-precipitation and Low Temperature Aging
Authors: Chen Tong-yun , Chu Xiang-feng , Hu Ke-liang
Published: July 2009

Sulfated zirconia-lanthana (SO42/ZrO2-La2O3) precursors were prepared by ultrasonic coprecipitation method and followed by aging at different temperature. The precursors were treated by 0.5 mol/L H2SO4. Samples of SO42/ZrO2-La2O3 nano-crystalline catalysts were obtained by baking the treated precursors at different temperatures. The acidic properties of SO42/ZrO2-La2O3 were tested by the Hammett indicator method. The phase composition, specific area, particle structure, and surface state were characterized by X-ray diffraction, BET, transmission electron microscopy, infrared spectrum, and X-ray photoelectron spectroscopy. The catalytic activities were estimated by esterification of acetic acid with glycerin. It was shown that the catalyst prepared by ultrasonic stirring and low temperature (15C) exhibited highly active sites and high catalytic property.
Preparation of Manganese Oxide Hollow Spheres Using pH-responsive Microgels as Templates
Authors: Zhang Wei , Zhang Zhi-cheng
Published: July 2009

Manganese oxide hollow spheres were prepared by a novel and facile approach using pH-responsive microgels as templates. The final products were thoroughly characterized with X-ray powder diffraction, thermogravimetric analysis, scanning electron microscopy, Fourier transform infrared, and transmission electron microscopy. The results reveal that the shell thickness of manganese oxide hollow spheres increased with the dosage of KMnO4, which implies that a controllable and feasible strategy for manganese oxide hollow spheres preparation has been established. Further studies on the microgels template showed some of them had an irreversible swelling/deswelling transition due to the uneven cross-link extent. Based on the results, a probable formation mechanism for the hollow spheres was proposed.
Profiling the repertoire of phenotypes influenced by environmental cues that occur during asexual reproduction
Authors: Dombrovsky Aviv , Arthaud Laury , Ledger Terence N. , Tares Sophie , Robichon Alain
Published: July 2009

The aphid Acyrthosiphon pisum population is composed of different morphs, such as winged and wingless parthenogens, males, and sexual females. The combined effect of reduced photoperiodicity and cold in fall triggers the apparition of sexual morphs. In contrast they reproduce asexually in spring and summer. In our current study, we provide evidence that clonal individuals display phenotypic variability within asexual morph categories. We describe that clones sharing the same morphological features, which arose from the same founder mother, constitute a repertoire of variants with distinct behavioral and physiological traits. Our results suggest that the prevailing environmental conditions influence the recruitment of adaptive phenotypes from a cohort of clonal individuals exhibiting considerable molecular diversity. However, we observed that the variability might be reduced or enhanced by external factors, but is never abolished in accordance with a model of stochastically produced phenotypes. This overall mechanism allows the renewal of colonies from a few adapted individuals that survive drastic episodic changes in a fluctuating environment.
Exon-trapping mediated by the human retrotransposon SVA
Authors: Hancks Dustin C. , Ewing Adam D. , Chen Jesse E. , Tokunaga Katsushi , Kazazian Haig H.
Published: July 2009

Although most human retrotransposons are inactive, both inactive and active retrotransposons drive genome evolution and may influence transcription through various mechanisms. In humans, three retrotransposon families are still active, but one of these, SVA, remains mysterious. Here we report the identification of a new subfamily of SVA, which apparently formed after an alternative splicing event where the first exon of the MAST2 gene spliced into an intronic SVA and subsequently retrotransposed. Additional examples of SVA retrotransposing upstream exons due to splicing into SVA were also identified in other primate genomes. After molecular and computational experiments, we found a number of functional 3′ splice sites within many different transcribed SVAs across the human and chimpanzee genomes. Using a minigene splicing construct containing an SVA, we observed splicing in cell culture, along with SVA exonization events that introduced premature termination codons (PTCs). These data imply that an SVA residing within an intron in the same orientation as the gene may alter normal gene transcription either by gene-trapping or by introducing PTCs through exonization, possibly creating differences within and across species.
GenGIS: A geospatial information system for genomic data
Authors: Parks Donovan H. , Porter Michael , Churcher Sylvia , Wang Suwen , Blouin Christian , Whalley Jacqueline , Brooks Stephen , Beiko Robert G.
Published: July 2009

The increasing availability of genetic sequence data associated with explicit geographic and ecological information is offering new opportunities to study the processes that shape biodiversity. The generation and testing of hypotheses using these data sets requires effective tools for mathematical and visual analysis that can integrate digital maps, ecological data, and large genetic, genomic, or metagenomic data sets. GenGIS is a free and open-source software package that supports the integration of digital map data with genetic sequences and environmental information from multiple sample sites. Essential bioinformatic and statistical tools are integrated into the software, allowing the user a wide range of analysis options for their sequence data. Data visualizations are combined with the cartographic display to yield a clear view of the relationship between geography and genomic diversity, with a particular focus on the hierarchical clustering of sites based on their similarity or phylogenetic proximity. Here we outline the features of GenGIS and demonstrate its application to georeferenced microbial metagenomic, HIV-1, and human mitochondrial DNA data sets.
Relationship of vitamin D and parathyroid hormone with obesity and body composition in African Americans
Authors: Valiña‐Tóth Anna Liza B. , Lai Zongshan , Yoo Wonsuk , Abou‐Samra Abdul , Gadegbeku Crystal A. , Flack John M.
Published: July 2009

Background  Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25‐hydroxyvitamin D (25‐OH D) and elevated parathyroid hormone (PTH). The relationship of 25‐OH D and PTH with body composition and size in AA is not well known.

Objective  To determine the relationship of 25‐OH D and PTH levels with body composition and anthropometric measures.

Design  A cross‐sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS‐sponsored weight loss/salt‐sensitivity trial.

Measurements  Multivariable linear regression analyses were used to explore the relationship of 25‐OH D and PTH with body composition, determined by dual‐energy X‐ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: (i) normal (25‐OH D >50 nmol/l, PTH ≤65 pg/ml), (ii) low 25‐OH D and normal PTH and (iii) low 25‐OH D and high PTH.

Results  Age, gender and season‐adjusted regression analyses showed that PTH was directly correlated with total (P = 0·02), truncal (P = 0·03) and extremity (P = 0·03) fat mass, while 25‐OH D was inversely related to truncal fat mass (P = 0·02). Total fat mass in groups 1–3, respectively, was 30·0, 34·0 and 37·4 kg (P = 0·008); truncal fat mass was 13·4, 15·9 and 17·6 kg (P = 0·006) and extremity fat mass was 15·8, 16·9 and 19·7 kg (P = 0·02). Lean mass did not differ across the three groups.

Conclusions  Our findings show that lower 25‐OH D and raised PTH are both correlated, though in opposite directions, with fat mass, fat distribution and anthropometric measures in adult AA.
Seagrass patch size affects fish responses to edges
Authors: Smith Timothy M. , Hindell Jeremy S. , Jenkins Greg P. , Connolly Rod M.
Published: July 2009

1. Patch area and proximity of patch edge can influence ecological processes across patchy landscapes and may interact with each other. Different patch sizes have different amounts of core habitat, potentially affecting animal abundances at the edge and middle of patches. In this study, we tested if edge effects varied with patch size.

2. Fish were sampled in 10 various‐sized seagrass patches (114–5934 m2) using a small (0·5 m2) push net in three positions within each patch: the seagrass edge, 2 m into a patch and in the middle of a patch.

3. The two most common species showed an interaction between patch size and the edge–interior difference in abundance. In the smallest patches, pipefish (Stigmatopora nigra) were at similar densities at the edge and interior, but with increasing patch size, the density at the edge habitat increased. For gobies (Nesogobius maccullochi), the pattern was exactly the opposite.

4. This is the first example from a marine system of how patch size can influence the magnitude and pattern of edge effects.

5. Both patch area and edge effects need to be considered in the development of conservation and management strategies for seagrass habitats.