bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure similarity measure with penalty for close non-equivalent residues
Authors: Sadreyev Ruslan I. , Shi ShuoYong , Baker David , Grishin Nick V.
Published: March 2009

Motivation:Recent improvement in homology-based structure modeling emphasizes the importance of sensitive evaluation measures that help identify and correct modest distortions in models compared with the target structures. Global Distance Test Total Score (GDT_TS), otherwise a very powerful and effective measure for model evaluation, is still insensitive to and can even reward such distortions, as observed for remote homology modeling in the latest CASP8 (Comparative Assessment of Structure Prediction).

Results:We develop a new measure that balances GDT_TS reward for the closeness of equivalent model and target residues (‘attraction’ term) with the penalty for the closeness of non-equivalent residues (‘repulsion’ term). Compared with GDT_TS, the resulting score, TR (total score with repulsion), is much more sensitive to structure compression both in real remote homologs and in CASP models. TR is correlated yet different from other measures of structure similarity. The largest difference from GDT_TS is observed in models of mid-range quality based on remote homology modeling.

Availability:The script for TR calculation is included in Supplementary Material. TR scores for all server models in CASP8 are available at http://prodata.swmed.edu/CASP8.

Contact:  grishin@chop.swmed.edu

Supplementary information:All scripts and numerical data are available for download at ftp://iole.swmed.edu/pub/tr_score/
In silicoanalysis of promoter regions from cold-induced genes in rice (Oryza sativaL.) andArabidopsis thalianareveals the importance of combinatorial control
Authors: Lindlöf Angelica , Bräutigam Marcus , Chawade Aakash , Olsson Olof , Olsson Björn
Published: March 2009

Motivation:Cold acclimation involves a number of different cellular processes that together increase the freezing tolerance of an organism. The DREB1/CBFs are transcription factors (TFs) that are prominent in the regulation of cold responses in Arabidopsis thaliana, rice and many other crops. We investigated if the expression of DREB1/CBFs and co-expressed genes relies on combinatorial control by several TFs. Our results support this notion and indicate that methods for studying the regulation of complex cellular processes should include identification of combinations of motifs, in addition to searching for individual overrepresented binding sites.

Contact:  angelica.lindlof@his.se

Supplementary information:  Supplementary data are available at Bioinformatics online.
Correction for Wickham
et al.
, Exaggeration and suppression of iridescence: the evolution of two-dimensional butterfly structural colours
Authors: Wickham Shelley , Large Maryanne C. J. , Poladian Leon , Jermiin Lars S.
Published: March 2009

Correction for ‘Exaggeration and suppression of iridescence: the evolution of two-dimensional butterfly structural colours’ by Shelley Wickham, Maryanne C. J. Large, Leon Poladian and Lars S. Jermiin (J. R. Soc. Interface
3
, 99–108.
(doi:
10.1098/rsif.2005.0071
)).

Figure 5 in the print version of this paper is incorrect; the correct figure is as follows.
Partial cation-order and early-stage, phase separation in phase W, Li

x

Co

1−
x

O: 0.075≤
x
≤0.24−0.31
Authors: Wu Y. , Pasero D. , McCabe E.E. , Matsushima Y. , West A.R.
Published: March 2009

We report the characterization using X-ray and neutron powder diffraction, transmission electron microscopy and extended X-ray absorption fine structure of a new, partially ordered rock-salt-like solid solution phase Li

x

Co

1−
x

O: 0.075≤
x
≤0.24−0.31. The cation stacking sequence along [111] consists of alternating planes of Co and Co/Li. Nano-sized domains of this cation-ordered phase appear alongside disordered regions; domain size increases from 2 to 8 nm with increasing Li content. Compositions of ordered and disordered regions are Li- and Co-rich, respectively, and, therefore, the phase exhibits frozen-in, incipient phase separation. This microstructure could be considered as a precursor to precipitation of fully ordered, rhombohedral LiCoO
2
.
A quantum probability explanation for violations of ‘rational’ decision theory
Authors: Pothos Emmanuel M. , Busemeyer Jerome R.
Published: March 2009

Two experimental tasks in psychology, the two-stage gambling game and the Prisoner's Dilemma game, show that people violate the sure thing principle of decision theory. These paradoxical findings have resisted explanation by classical decision theory for over a decade. Aquantumprobability model, based on a Hilbert space representation and Schrödinger's equation, provides a simple and elegant explanation for this behaviour. The quantum model is compared with an equivalent Markov model and it is shown that the latter is unable to account for violations of the sure thing principle. Accordingly, it is argued that quantum probability provides a better framework for modelling human decision-making.
Trill consistency is an age-related assessment signal in banded wrens
Authors: de Kort Selvino R. , Eldermire Erin R.B. , Valderrama Sandra , Botero Carlos A. , Vehrencamp Sandra L.
Published: March 2009

Older males tend to have a competitive advantage over younger males in sexual selection. Therefore, it is expected that signals used in sexual selection change with age. Although song repertoire size in songbirds is often mentioned as an age-related trait, many species, including the banded wren (
Thryothorus pleurostictus
), do not increase their repertoires after the first year. Here, we show that banded wrens reproduce the trill notes in their songs with less variability between them (i.e. more consistently) when they grow older. In a playback experiment, we also show that banded wrens discriminate between younger and older birds based on structural aspects of their song. In a second experiment, banded wrens also respond differentially to natural songs versus songs with artificially enhanced consistency. We argue that consistency in trill note reproduction may be achieved through practice. Sexual selection in the form of male–male competition may therefore operate on a phenotypic trait, the expression of which is enhanced by practice.
STOP1 Regulates Multiple Genes That Protect Arabidopsis from Proton and Aluminum Toxicities
Authors: Sawaki Yoshiharu , Iuchi Satoshi , Kobayashi Yasufumi , Kobayashi Yuriko , Ikka Takashi , Sakurai Nozomu , Fujita Miki , Shinozaki Kazuo , Shibata Daisuke , Kobayashi Masatomo , Koyama Hiroyuki
Published: March 2009

The Arabidopsis (Arabidopsis thaliana) mutant stop1 (for sensitive to proton rhizotoxicity1) carries a missense mutation at an essential domain of the histidine-2-cysteine-2 zinc finger protein STOP1. Transcriptome analyses revealed that various genes were down-regulated in the mutant, indicating that STOP1 is involved in signal transduction pathways regulating aluminum (Al)- and H+-responsive gene expression. The Al hypersensitivity of the mutant could be caused by down-regulation of AtALMT1 (for Arabidopsis ALUMINUM-ACTIVATED MALATE TRANSPORTER1) and ALS3 (ALUMINUM-SENSITIVE3). This hypothesis was supported by comparison of Al tolerance among T-DNA insertion lines and a transgenic stop mutant carrying cauliflower mosaic virus 35S∷AtALMT1. All T-DNA insertion lines of STOP1, AtALMT1, and ALS3 were sensitive to Al, but introduction of cauliflower mosaic virus 35S∷AtALMT1 did not completely restore the Al tolerance of the stop1 mutant. Down-regulation of various genes involved in ion homeostasis and pH-regulating metabolism in the mutant was also identified by microarray analyses. CBL-INTERACTING PROTEIN KINASE23, regulating a major K+ transporter, and a sulfate transporter, SULT3;5, were down-regulated in the mutant. In addition, integral profiling of the metabolites and transcripts revealed that pH-regulating metabolic pathways, such as the γ-aminobutyric acid shunt and biochemical pH stat pathways, are down-regulated in the mutant. These changes could explain the H+ hypersensitivity of the mutant and would make the mutant more susceptible in acid soil stress than other Al-hypersensitive T-DNA insertion lines. Finally, we showed that STOP1 is localized to the nucleus, suggesting that the protein regulates the expression of multiple genes that protect Arabidopsis from Al and H+ toxicities, possibly as a transcription factor.
Two Chlamydomonas CTR Copper Transporters with a Novel Cys-Met Motif Are Localized to the Plasma Membrane and Function in Copper Assimilation
Authors: Page M. Dudley , Kropat Janette , Hamel Patrice P. , Merchant Sabeeha S.
Published: March 2009

Inducible high-affinity copper uptake is key to copper homeostasis in Chlamydomonas  reinhardtii. We generated cDNAs and updated gene models for four genes, CTR1, CTR2, CTR3, and COPT1, encoding CTR-type copper transporters in Chlamydomonas. The expression of CTR1, CTR2, and CTR3 increases in copper deficient cells and in response to hypoxia or Ni2+ supplementation; this response depends on the transcriptional activator CRR1. A copper response element was identified by mutational analysis of the 5′ upstream region of CTR1. Functional analyses identify CTR1 and CTR2 as the assimilatory transporters of Chlamydomonas based on localization to the plasma membrane and ability to rescue a Saccharomyces cerevisiae mutant defective in high-affinity copper transport. The Chlamydomonas CTRs contain a novel Cys-Met motif (CxxMxxMxxC-x5/6-C), which occurs also in homologous proteins in other green algae, amoebae, and pathogenic fungi. CTR3 appears to have arisen by duplication of CTR2, but CTR3 lacks the characteristic transmembrane domains found in the transporters, suggesting that it may be a soluble protein. Thus, Chlamydomonas CTR genes encode a distinct subset of the classical CTR family of Cu(I) transporters and represent new targets of CRR1-dependent signaling.
The functioning antigens: beyond just as the immunological targets
Authors: Hirohashi Yoshihiko , Torigoe Toshihiko , Inoda Satoko , Kobayasi Jun–ichi , Nakatsugawa Munehide , Mori Takashi , Hara Isao , Sato Noriyuki
Published: March 2009

Antigenic peptides derived from tumor‐associated antigens (TAAs) facilitate peptide cancer vaccine therapies. With the recent progress in cancer immunity research, huge amounts of antigenic peptides have already been reported. Clinical trials using such peptides are underway now all over the world. Some reports have shown the efficacy of peptide vaccine therapies. However, others ended with unfavorable results, suggesting fundamental underlying problems. One major mechanism that negates the peptide vaccine therapy is tumor escape from immunological systems caused by loss of antigens. TAAs that are used in cancer vaccine therapies may be divided into two major groups: functioning antigens and non‐functioning antigens. A ‘functioning antigen’ could be defined as a TAA that is essential for tumor growth, is expressed in several kinds of malignancies and shows homogenous expression in cancerous tissues. It is not difficult to imagine that antigen loss will occur easily with non‐functioning antigens as a target of cancer vaccine therapy. Thus, it is essential to use functioning antigens for successful cancer vaccine therapy. In this review, we discuss the functioning antigens and their categorization in detail. (Cancer Sci 2009; 100: 798–806)
Phase I/II and pharmacokinetic study of cladribine with 2‐h infusion in Japanese patients with relapsed indolent B‐cell lymphoma mostly pretreated with rituximab
Authors: Tobinai Kensei , Watanabe Takashi , Tanimoto Kazuki , Maruyama Dai , Nakata Masanobu , Itoh Kuniaki , Morishima Yasuo , Ogura Michinori , Usui Noriko , Kasai Masaharu , Terauchi Takashi , Nawano Shigeru , Matsusako Masaki , Matsuno Yoshihiro , Nakamura Shigeo , Mori Shigeo , Ohashi Yasuo
Published: March 2009

We conducted a phase I/II study to investigate the toxicity, pharmacokinetics, and efficacy profiles of cladribine with 2‐h intravenous infusion for five consecutive days every four weeks in Japanese patients with relapsed indolent B‐cell lymphoma. This was a dose‐escalation study to confirm the safety of the doses which have been recommended for Caucasian patients (phase I), and to further evaluate the efficacy and safety (phase II). In the phase I portion for nine patients, no dose‐limiting toxicities were observed at levels 1 (0.09 mg/kg/day, n = 3) and 2 (0.12 mg/kg/day, n = 6). No appreciable accumulation of plasma cladribine concentration was suggested. We enrolled a total of 20 patients, and an additional 14 patients in the phase II portion at level 2 (0.12 mg/kg/day). Eighteen patients, including 13 with follicular lymphoma, were eligible for efficacy evaluation, and 15 (83%) were pretreated with rituximab. The overall response rate was 50% (9/18; 80% confidence interval, 35–65%), with 11% (2/18) complete response. With a median follow‐up of 296 days, the estimated median time to progression for 18 eligible patients was 382 days. The most frequent adverse events were hematologic toxicities, including grade 4 neutropenia. Non‐hematologic toxicities were mild. In conclusion, cladribine with 2‐h intravenous infusion for five consecutive days every four weeks is effective with acceptable toxicities for Japanese patients with relapsed indolent B‐cell lymphoma, including those pretreated with rituximab. (Cancer Sci 2009; 100: 1344–1350)
Review article: the diagnosis and management of alcoholic hepatitis
Authors: COHEN S. M. , AHN J.
Published: March 2009

Background  Alcoholic hepatitis is a severe, cholestatic liver disease occurring in patients with alcohol abuse. Mortality is substantial; however, therapies may improve clinical outcomes.

Aim  To provide an updated review of the epidemiology, diagnosis, staging and treatment of alcoholic hepatitis.

Methods  A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed.

Results  Severe alcoholic hepatitis occurs in a small fraction of patients who abuse alcohol. The 28‐day mortality ranges from 30% to 50% in most series. Diagnosis is generally based on clinical features, with a limited role for liver biopsy. Beneficial treatment options include alcohol abstinence and nutritional therapy. Despite variable results in clinical trials, corticosteroids and pentoxifylline appear to provide moderate survival benefit. Anti‐tumour necrosis factor agents and antioxidants have not proven beneficial, and should be limited to clinical trials. Liver transplant is not a frequent option given the active or recent alcohol use.

Conclusions  Severe alcoholic hepatitis is a clinically‐diagnosed condition associated with significant mortality. Alcohol abstinence and nutritional therapy have been associated with improved clinical parameters and should be considered in all patients. Corticosteroid therapy and pentoxifylline therapy appear to show moderate survival benefit and should be considered as first‐line therapeutic agents.
Review article: adherence to medication for chronic hepatitis C – building on the model of human immunodeficiency virus antiretroviral adherence research
Authors: WEISS J. J. , BRÄU N. , STIVALA A. , SWAN T. , FISHBEIN D.
Published: March 2009

Background Treatment of hepatitis C virus (HCV) infection with pegylated interferon/ribavirin achieves sustained virological response in up to 56% of HCV mono‐infected patients and 40% of HCV/human immunodeficiency virus (HIV)‐co‐infected patients. The relationship of patient adherence to outcome warrants study.

Aim To review comprehensively research on patient‐missed doses to HCV treatment and discuss applicable research from adherence to HIV antiretroviral therapy.

Methods Publications were identified by PubMed searches using the keywords: adherence, compliance, hepatitis C virus, interferon and ribavirin.

Results The term ‘non‐adherence’ differs in how it is used in the HCV from the HIV literature. In HCV, ‘non‐adherence’ refers primarily to dose reductions by the clinician and early treatment discontinuation. In contrast, in HIV, ‘non‐adherence’ refers primarily to patient‐missed doses. Few data have been published on the rates of missed dose adherence to pegylated interferon/ribavirin and its relationship to virological response.

Conclusions As HCV treatment becomes more complex with new classes of agents, adherence will be increasingly important to treatment success as resistance mutations may develop with suboptimal dosing of HCV enzyme inhibitors. HIV adherence research can be applied to that on HCV to establish accurate methods to assess adherence, investigate determinants of non‐adherence and develop strategies to optimize adherence.
Influence of the mechanical behaviour of brittle–ductile fold–thrust belts on the development of foreland basins
Authors: Simpson Guy D. H.
Published: March 2009

A two‐dimensional mathematical model considering coupling between a deforming elasto‐visco‐plastic fold–thrust belt, flexural subsidence and diffusional surface processes is solved using the Finite Element Method to investigate how the mechanical behaviour of brittle–ductile wedges influences the development of foreland basins. Results show that, depending mainly on the strength of the basal décollement, two end‐member types of foreland basin are possible. When the basal detachment is relatively strong, the foreland basin system is characterised by: (1) Highly asymmetrical orogen formed by thrusts concentrated in the incoming pro‐wedge. (2) Sedimentation on retro‐side takes place in one major foredeep basin which grows throughout orogen evolution. (3) Deposition on the pro‐side occurs initially in the foredeep, and continues in the wedge‐top before isolated basins are advected towards the orogen core where they become uplifted and exhumed. (4) Most pro‐wedge basins show an upward progression from low altitude, foredeep deposits at the base to high altitude, wedge‐top deposits near the surface. In contrast, when the basal detachment behaves weakly due to the presence of low viscosity material such as salt, the foreland basin system is characterised by (1) Broad, low relief orogen showing little preferential vergence and predominance of folding relative to faulting. (2) Deposition mainly in wedge‐top basins showing growth strata. (3) Many basins are initiated contemporaneously but form discontinuously due to the locus of active deformation jumping back and forth between different structures. Model results successfully reproduce first order observations of deforming brittle–ductile wedges and foreland basins. Moreover, the results support and provide a framework for understanding the existence of two main end‐member foreland basin types, simple and complex, associated with fold–thrust belts whose detachments are relatively strong and weak, respectively.
Replicative potential of human natural killer cells
Authors: Fujisaki Hiroyuki , Kakuda Harumi , Imai Chihaya , Mullighan Charles G. , Campana Dario
Published: March 2009

The replicative potential of human CD56+ CD3− natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukaemic cell line K562 genetically modified to express 4‐1BB ligand and interleukin 15 (K562‐mb15‐41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged from 1·6 × 105 to 1·2 × 1011% (median, 5·9 × 106%; n = 7) of those originally seeded. However, NK cells eventually became unresponsive to stimulation and died. Their demise could be suppressed by enforcing the expression of the human telomerase reverse transcriptase gene (TERT). TERT‐overexpressing NK cells continued to proliferate in response to K562‐mb15‐41BBL stimulation for more than 1 year of culture, while maintaining a normal karyotype and genotype. Long‐lived NK cells had high cytotoxicity against myeloid and T‐lineage leukaemic cells. They remained susceptible to genetic manipulation, becoming highly cytotoxic to B‐lineage leukaemic cells after expression of anti‐CD19 signaling receptors. Thus, human NK cells have a replicative potential similar to that of T lymphocytes and their lifespan can be significantly prolonged by an increase in TERT activity. We suggest that the methods described here should have many applications in studies of NK cell biology and NK cell‐based therapies.
Ex vivo expanded telomerase-specific T cells are effective in an orthotopic mouse model for pancreatic adenocarcinoma
Authors: Hassanin H , Serba S , Schmidt J , Märten A
Published: March 2009

Telomerase activity is over-expressed in nearly all pancreatic carcinomas, but not in chronic pancreatitis. Here, we investigated various protocols for expansion of telomerase-specific T cells for adoptive cell transfer and their use in a syngeneic pancreatic carcinoma mouse model. Telomerase-specific T cells were generated by stimulation of splenocytes from peptide-immunized donor mice with either interleukin (IL)-2, IL-15, artificial antigen-presenting cells, anti-signalling lymphocyte activation molecule (SLAM) microbeads or allogeneic dendritic cells in combination with a limited dilution assay. T cells were tested for antigen specificity in vitro and for anti-tumour activity in syngeneic mice with orthotopically implanted tumours pretreated with cyclophosphamide. The immune cells from recipients were immunophenotyped. During a period of 2 weeks, the expansion approach using IL-2 was very successful in generating a high number of telomerase-specific CD8+ T cells without losing their function after adoptive cell transfer. Significantly slower tumour growth rate and less metastasis were observed after adoptively transferring telomerase specific CD8+ T cells, expanded using IL-2. Further investigations showed that anti-tumour efficacy was associated with a significant shift from naive CD8+ T cells to CD8+ central memory T cells, as well as recruitment of a high number of dendritic cells. Remarkable amounts of telomerase-specific T cells were detectable in the tumour. Generation of telomerase-specific T cells is feasible, whereat IL-2-based protocols seemed to be most effective and efficient. Antigen-specific T cells showed significant cytotoxic activity in a syngeneic, orthotopic mouse model, whereas central memory T cells but not effector memory T cells appear to be of high importance.
Changes in topsoil carbon stock in the Tibetan grasslands between the 1980s and 2004
Authors: YANG YUANHE , FANG JINGYUN , SMITH PETE , TANG YANHONG , CHEN ANPING , JI CHENGJUN , HU HUIFENG , RAO SHENG , TAN KUN , HE JIN‐SHENG
Published: March 2009

Climate warming is likely inducing carbon loss from soils of northern ecosystems, but little evidence comes from large‐scale observations. Here we used data from a repeated soil survey and remote sensing vegetation index to explore changes in soil organic carbon (SOC) stock on the Tibetan Plateau during the past two decades. Our results showed that SOC stock in the top 30 cm depth in alpine grasslands on the plateau amounted to 4.4 Pg C (1 Pg=1015 g), with an overall average of 3.9 kg C m−2. SOC changes during 1980s–2004 were estimated at −0.6 g C m−2 yr−1, ranging from −36.5 to 35.8 g C m−2 yr−1 at 95% confidence, indicating that SOC stock in the Tibetan alpine grasslands remained relatively stable over the sampling periods. Our findings are nonconsistent with previous reports of loss of soil C in grassland ecosystems due to the accelerated decomposition with warming. In the case of the alpine grasslands on the Tibetan Plateau studied here, we speculate that increased rates of decomposition as soils warmed during the last two decades may have been compensated by increased soil C inputs due to increased grass productivity. These results suggest that soil C stock in terrestrial ecosystems may respond differently to climate change depending on ecosystem type, regional climate pattern, and intensity of human disturbance.
Endogenous CD100 promotes glomerular injury and macrophage recruitment in experimental crescentic glomerulonephritis
Authors: Li Ming , O’Sullivan Kim M. , Jones Lynelle K. , Lo Cecilia , Semple Timothy , Kumanogoh Atsushi , Kikutani Hitoshi , Holdsworth Stephen R. , Kitching Richard
Published: March 2009

CD100 participates in adaptive immune responses and is important in neural cell migration. To determine the role of endogenous CD100 in severe glomerular inflammation, we induced experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of sensitized normal and CD100‐deficient (CD100−/−) mice. Fewer CD100−/− glomeruli exhibited crescent formation or severe histological changes. Antigen‐specific immune responses were reduced in CD100−/− mice. There was less interferon (IFN)‐γ and interleukin (IL)‐4 production by splenocytes and fewer activated T and B cells were present in lymph nodes of immunized CD100−/− mice. Serum antigen‐specific immunoglobulin (IgG) levels were also decreased. Glomerular macrophage and CD4+ cell infiltration, and IgG and C3 deposition were attenuated. Normal kidneys expressed mRNA for CD100 and plexin‐B1 (the tissue receptor of CD100). Direct immunofluorescence showed that renal‐CD100 protein was predominantly in tubules, while plexin‐B1 was present in both glomeruli and tubules. To determine whether glomerular plexin‐B1 mediates leucocyte recruitment via leucocyte CD100, recruitment was studied after passive transfer of heterologous antibody (attracting neutrophils) or isologous antibody (attracting macrophages). Glomerular macrophages were reduced in CD100−/− mice, but neutrophil recruitment was equivalent, consistent with CD100 expression on macrophages, but not neutrophils. CD100 promotes severe nephritogenic immune responses and leucocyte CD100–glomerular plexin‐B1 interactions enhance macrophage recruitment to glomeruli.
Correlation between recombinase activating gene 1 ubiquitin ligase activity and V(D)J recombination
Authors: Simkus Carrie , Bhattacharyya Anamika , Zhou Ming , Veenstra Timothy D. , Jones Jessica M.
Published: March 2009

The really interesting new gene (RING) finger ubiquitin ligase domain of the recombinase activating gene 1 (RAG1) V(D)J recombinase protein adopts a standard cross‐brace architecture but co‐ordinates three zinc ions as opposed to the canonical two. We demonstrated previously that disruption of the conserved zinc co‐ordination sites resulted in loss of structural integrity and ubiquitin ligase (E3) activity and interfered with the ability of full‐length RAG1 to support recombination. Here we present evidence that amino acids surrounding the third, non‐canonical site also contribute to functional interaction with the ubiquitin conjugating (E2) enzyme CDC34, while certain residues on the RING domain’s surface important for interaction between other E2–E3 pairs are less critical to the functional RAG1–CDC34 interaction in this assay. Partial reduction of ubiquitin ligase activity was significantly correlated with reduction in the ability of RAG1 to support recombination of extra‐chromosomal substrates (r = 0·805, P = 0·009). While poly‐ubiquitin chains could be generated, RAG1 did not promote rapid chain extension following mono‐ubiquitylation of substrate, regardless of the E2 enzyme used. No single ubiquitin lysine mutant disrupted the ability of CDC34 to form ubiquitin chains on RAG1, and mass spectrometric analysis of the poly‐ubiquitylated products indicated ubiquitin chain linkages through lysines 48 and 11. These data suggest that RAG1 promotes a mono‐ubiquitylation reaction that is required for optimal levels of V(D)J recombination.
Ganglioside GT1b protects human spermatozoa from hydrogen peroxide‐induced DNA and membrane damage
Authors: Gavella Mirjana , Garaj‐Vrhovac Verica , Lipovac Vaskresenija , Antica Mariastefania , Gajski Goran , Car Nikica
Published: March 2009

We have reported previously that various gangliosides, the sialic acid containing glycosphingolipids, provide protection against sperm injury caused by reactive oxygen species (ROS). In this study, we investigated the effect of treatment of human spermatozoa with ganglioside GT1b on hydrogen peroxide (H2O2)‐induced DNA fragmentation and plasma membrane damage. Single‐cell gel electrophoresis (Comet assay) used in the assessment of sperm DNA integrity showed thatin vitrosupplemented GT1b (100 μm) significantly reduced DNA damage induced by H2O2(200 μm) (p < 0.05). Measurements of Annexin V binding in combination with the propidium iodide vital dye labelling demonstrated that the spermatozoa pre‐treated with GT1b exhibited a significant increase (p < 0.05) in the percentage of live cells with intact membrane and decreased phosphatidylserine translocation after exposure to H2O2. Flow cytometry using the intracellular ROS‐sensitive fluorescence dichlorodihydrofluorescein diacetate dye employed to investigate the transport of the extracellularly supplied H2O2into the cell interior revealed that ganglioside GT1b completely inhibited the passage of H2O2through the sperm membrane. These results suggest that ganglioside GT1b may protect human spermatozoa from H2O2‐induced damage by rendering sperm membrane more hydrophobic, thus inhibiting the diffusion of H2O2across the membrane.
Positive effects of soil nitrogen pulses on individuals can have negative consequences for population growth during drought in a herbaceous desert perennial
Authors: Peek Michael S. , Forseth Irwin N.
Published: March 2009

Resource pulses generally result in a burst of biological activity at multiple scales. For plants, the increased activity is generally considered positive due to an overall up‐regulation of physiological activity during the pulse. Longer‐term effects remain an understudied aspect of resource pulses.

We monitored the short‐ and long‐term effects of nitrogen (N) pulse to the long‐lived desert perennial, Cryptantha flava. One group of plants were treated with a one‐time application of N in the spring of 1999, a second group received two N pulses (one in the spring of 1999 and one in the spring of 2000), and a third group received ambient N (controls).

In the short‐term, N‐pulse treated plants rapidly increased leaf N concentrations, which in turn increased physiological activity and growth. But these responses were mediated by the availability of precipitation.

In a year with above‐average precipitation, all plants increased in size, but N‐treated plants grew more and had higher reproductive outputs than control plants. However, when the N pulse was followed by below‐average precipitation in the next year, plants with the highest growth rates due to N pulses experienced greater reduction in size and reproduction coupled with increased mortality rates relative to controls.

At the population level a matrix model showed higher population growth rates in wetter years for N‐treated plants compared to controls, but in drier years, N‐treated plants showed lower growth rates. Size hierarchies were restructured as a result of the combination of variability in precipitation and N pulses creating more even size distributions.

Synthesis. The high degree of spatial heterogeneity of N pulses offers opportunities for enhanced growth and reproduction to individuals of C. flava within the larger population. Small plants with access to high soil N were able to maintain high survival, growth rates and reproduction as long as precipitation was adequate. However, increased N inputs probably resulted in a trade‐off between reproduction and survival in small plants when precipitation was limiting. The high degree of unpredictability of resources in time and space ultimately contributes to the size hierarchies in this population and the variability in population growth rates.
Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program
Authors: Janszky I. , Mukamal K. J. , Ljung R. , Ahnve S. , Ahlbom A. , Hallqvist J.
Published: March 2009

Objectives.  To assess the long‐term effects of chocolate consumption amongst patients with established coronary heart disease.

Design.  In a population‐based inception cohort study, we followed 1169 non‐diabetic patients hospitalized with a confirmed first acute myocardial infarction (AMI) between 1992 and 1994 in Stockholm County, Sweden, as part of the Stockholm Heart Epidemiology Program. Participants self‐reported usual chocolate consumption over the preceding 12 months with a standardized questionnaire distributed during hospitalization and underwent a health examination 3 months after discharge. Participants were followed for hospitalizations and mortality with national registries for 8 years.

Results.  Chocolate consumption had a strong inverse association with cardiac mortality. When compared with those never eating chocolate, the multivariable‐adjusted hazard ratios were 0.73 (95% confidence interval, 0.41–1.31), 0.56 (0.32–0.99) and 0.34 (0.17–0.70) for those consuming chocolate less than once per month, up to once per week and twice or more per week respectively. Chocolate consumption generally had an inverse but weak association with total mortality and nonfatal outcomes. In contrast, intake of other sweets was not associated with cardiac or total mortality.

Conclusions.  Chocolate consumption was associated with lower cardiac mortality in a dose dependent manner in patients free of diabetes surviving their first AMI. Although our findings support increasing evidence that chocolate is a rich source of beneficial bioactive compounds, confirmation of this strong inverse relationship from other observational studies or large‐scale, long‐term, controlled randomized trials is needed.
Major cysteine peptidases of Entamoeba histolytica are required for aggregation and digestion of erythrocytes but are dispensable for phagocytosis and cytopathogenicity
Authors: Irmer Henriette , Tillack Manuela , Biller Laura , Handal Ghassan , Leippe Matthias , Roeder Thomas , Tannich Egbert , Bruchhaus Iris
Published: March 2009

Cysteine peptidases of Entamoeba histolytica (EhCPs) are considered to be important pathogenicity factors. It has been described that under standard axenic culture conditions, only three (ehcp‐a1, ehcp‐a2 and ehcp‐a5) out of approximately 50 cysteine peptidase genes present in the E. histolytica genome are substantially expressed, thus representing the set of major EhCPs. In this study, transcriptional silencing of the major peptidase genes was used to characterize their physiological role in more detail. Analysing the transfectants a fourth major cysteine peptidase activity belonging to EhCP‐A7 could be characterized. Neither cytopathic activity nor phagocytosis of erythrocytes was altered in CP‐inactivated amoebae. However, a significant difference in haemolytic activity was observed. EhCP‐A1 and EhCP‐A7 apparently had no influence on haemolytic activity, whereas transfectants silenced for ehcp‐a5 as well as those silenced for all major peptidases showed a significant reduction in their haemolytic activity. Furthermore, cells silenced for ehcp‐a1 and ehcp‐a7 and more effectively cells silenced in all major ehcps were impaired in digesting of phagocytosed erythrocytes. Moreover, amoebae silenced for all major peptidase genes lost the ability to form aggregates of erythrocytes prior to phagocytosis.
Expression of immune modulator cytokines in human fulminant amoebic colitis
Authors: SIERRA‐PUENTE R. E. , CAMPOS‐RODRÍGUEZ R. , JARILLO‐LUNA R. A. , MUÑOZ‐FERNÁNDEZ L. , RODRÍGUEZ M. G. , MUÑOZ‐ORTEGA M. H. , VENTURA‐JUÁREZ J.
Published: March 2009

Human fulminant amoebic colitis (FAC) is characterized by ulceration and inflammation of the colon. The specific mixture of pro‐inflammatory and anti‐inflammatory cytokines may participate in either the host defense or in the pathogenesis of amoebic colitis. Therefore, we studied the expression of IL‐8, IL‐10, IL‐4, TGF‐β and IFN‐γ in human FAC patients and controls through immunohistochemistry analysis. The number of cells expressing IL‐8, IL‐4 and IL‐10 was significantly enhanced in all FAC samples compared to the control samples. However, the expression of TGF‐ β in patients was low in the colonic mucosa and high in the lamina propria compared with the control. No expression of IFN‐γ was found in the controls or FAC samples. The production of IL‐8 by intestinal epithelial cells may play a role in the pathogenesis of amoebic infection, because this cytokine attracts neutrophils, which lead to an inflammatory reaction that results in tissue damage. The predominant expression of the macrophage down‐regulating cytokines, IL‐4, IL‐10 and TGF‐β, or the Th2‐type immune response could inhibit a cell‐mediated immune response, which in turn would facilitate parasite invasion in these tissues.
Abiotic versus biotic controls on the development of the Fairmont Hot Springs carbonate deposit, British Columbia, Canada
Authors: RAINEY DUSTIN K. , JONES BRIAN
Published: March 2009

The relict Fairmont Hot Springs deposit, formed largely of carbonates, covers an area of 0·5 km2, and is up to 16 m thick. The triangle‐shaped discharge apron, which broadens down‐valley, is divided into a proximal part with beds dipping at <10° and a distal part with beds dipping at 10° to 15°. The deposit is formed of the: (1) Basal Macrophyte; (2) Lower Carbonate; (3) Middle Clastic; (4) Upper Carbonate; and (5) Upper Clastic Sequences. Two charcoal samples embedded in the Lower Carbonate Sequence yielded dates of 8690 ± 90 and 8270 ± 70 cal yr bp, indicating that much of the deposit formed post‐glacially during the Early to Mid‐Holocene. Deposit aggradation ceased in the Mid to Late Holocene when the Fairmont Creek valley was incised. The Lower and Upper Carbonate Sequences, which are the thickest sequences, are composed of nearly equal parts of travertine (abiotic) and tufa (biotic), with feather dendrite travertine, radiating dendrite travertine and stromatolite tufa dominating. Competition between calcite precipitation rates and biotic growth rates controlled the distribution of tufa and travertine across the discharge apron. Calcite and biotic growth rates were controlled largely by flow velocity across the apron which, in turn, was controlled by topography and regular fluctuations in spring water discharge volume. During times of high spring discharge, slow sheet flow over the proximal part of the apron promoted stromatolite growth, whereas fast, turbulent flow on the distal part of the apron induced rapid feather dendrite formation. During times of low spring discharge, quiescent, shallow evaporative pools, conducive to radiating dendrite formation, formed on the proximal part of the apron, whereas slow flow on the distal part promoted stromatolite growth. Facies with high calcite supersaturation experienced rapid abiotic dendrite growth that precluded most biotic growth.
Killer immunoglobulin‐like receptors (KIR2DL2 and/or KIR2DS2) in presence of their ligand (HLA‐C1 group) protect against chronic myeloid leukaemia
Authors: Middleton D. , Diler A. S. , Meenagh A. , Sleator C. , Gourraud P. A.
Published: March 2009

We have analysed the frequency of killer immunoglobulin‐like receptors (KIR) in cohorts of patients from Turkey with acute lymphocyte leukaemia (n = 52), acute myeloid leukaemia (n = 54) and chronic myeloid leukaemia (CML) (n = 52) and compared the results with 154 controls. We also examined the frequencies of human leucocyte antigen (HLA)‐C groups, ‐Bw4, ‐Bw6 and where appropriate the combination of the KIR gene and its ligand. We found several statistically significant results between the patients and the controls. We proposed a model in CML of protection via KIR2DL2 and/or KIR2DS2 with the presence of the ligand HLA‐C1 group and susceptibility via HLA‐Bw4 homozygosity (i.e. absence of HLA‐Bw6).
Mycobacterium gordonae urinary infection in a renal transplant recipient
Authors: Pinho L. , Santos J. , Oliveira G. , Pestana M.
Published: March 2009

Abstract: The authors present a case of urinary infection by a non‐tuberculous mycobacteria (NTM) species, Mycobacterium gordonae, in a renal transplant recipient. A 29‐year‐old female patient had persistent sterile pyuria after her second kidney transplant. An NTM, M. gordonae, was isolated, and the patient was started on antituberculous treatment, with resolution of leukocyturia. Ureteral stenosis with hydronephrosis and deterioration of allograft function was diagnosed later on and, despite the introduction of intraureteral catheter and resolution of hydronephrosis, there was no recovery of baseline renal function. She ultimately resumed dialysis after a severe pyelonephritis. The authors discuss the problems of establishing diagnosis of infection (versus colonization) by NTM and highlight the difficulty of treating these infections, especially because of the possible interaction with immunosuppressant agents, facilitating anti‐allograft immune response.
Workers compensation and occupational health and safety in the Australian agricultural industry
Authors: Guthrie Robert , Westaway Jennifer , Goldacre Lisa
Published: March 2009

Objectives:  The objective of this paper is to review the available workers compensation and occupational health and safety data and the legal framework in relation to the agricultural industry to explore whether any factors highlight the need to pay special attention to the particular circumstances of those engaged in the industry.

Design:  This paper explores some of the special features of the agricultural industry, looking first at agricultural worker fatalities and injuries as a matter of ongoing concern for all participants in this industry, government, as well as occupational health and workers compensation authorities. The paper analyses how occupational health and workers compensation laws may have special application to this industry. Finally, the paper considers some workers compensation provisions that have particular application to the agricultural industry.

Conclusions:  Our survey of the available data and literature leads to the conclusion that the dangerous nature of agricultural work and the special legal and economic framework in which that work is undertaken identify the agricultural industry as presenting Australian Governments and specialist authorities with particular challenges in relation to improving workplace safety and reducing workplace injury.
Health behaviours of young, rural residents: A case study
Authors: Bourke Lisa , Humphreys John , Lukaitis Fiona
Published: March 2009

Objective:  To analyse self‐reported health behaviours of young people from a rural community and the factors influencing their behaviours.

Methods:  Interviews were conducted with 19 young people, 11 parents and 10 key informants from a small rural Victorian community, asking about teenage health behaviours and the factors influencing these behaviours.

Results:  Young people ate both healthy and unhealthy foods, most participated in physical activity, few smoked and most drank alcohol. The study found that community level factors, including community norms, peers, access issues and geographic isolation, were particularly powerful in shaping health behaviours, especially alcohol consumption. Smoking was influenced by social participation in the community and national media health campaigns. Diet and exercise behaviour were influenced by access and availability, convenience, family, peers and local and non‐local cultural influences.

Conclusion and implications:  The rural context, including less access to and choice of facilities and services, lower incomes, lack of transport and local social patterns (including community norms and acceptance), impact significantly on young people's health behaviours. Although national health promotion campaigns are useful aspects of behaviour modification, much greater focus on the role and importance of the local contexts in shaping health decisions of young rural people is required.
Generational attitudes of rural mental health nurses
Authors: Crowther Andrew , Kemp Michael
Published: March 2009

Objective:  To determine how attitudes of rural mental health nurses differ across generations.

Design:  Survey.

Setting:  Mental health services in rural New South Wales.

Participants:  Practising mental health nurses.

Main outcome measures:  Survey responses.

Results:  Survey response rate 44%. A total of 89 mental health nurses, clustered in inpatient units and community health centres, responded. Of these nurses, 4 were veterans, 52 baby boomers, 17 Generation X and 5 Generation Y.

Conclusions:  There are significant differences in how mental health nurses from different generations view their work, and in what is expected from managers. Managers need to modify traditional working styles, allowing greater flexibility of employment. They must also accept lower staff retention rates, and facilitate the development of younger staff.
The DriveABLE Competence Screen as a predictor of on‐road driving in a clinical sample
Authors: Korner‐Bitensky Nicol , Sofer Susan
Published: March 2009

Background/aim:  There is growing concern regarding the need for screening of older drivers. The objective of this study was to determine whether the DriveABLE Competence Screen, a computerised test, predicts on‐road driving outcome in clients referred for a driving assessment.

Methods:  This retrospective study evaluated the predictive validity of pre‐road testing using the DriveABLE Screen. Fifty‐two clients with varying health conditions were consecutively referred to a private practice that conducts comprehensive driving evaluations. Screen results are classified as recommend cessation of driving, indeterminate (requires on‐road evaluation), or no evidence of reduced competence. The DriveABLE Road Test classifies subjects as pass, borderline pass, or fail.

Results:  Sensitivity, specificity, positive and negative predictive values were generated using the Road Test as the criterion outcome. The positive predictive validity of the Screen in identifying those who would fail the Road Test was 97% (n= 32 of 33). The negative predictive validity was 47%. The sensitivity was 76% with a corresponding specificity of 90%.

Conclusion:  The DriveABLE Screen, when used as a case finding tool, is highly predictive of clients who will fail an on‐road driving evaluation.
Decreased CD3+CD16+ natural killer‐like T‐cell percentage and zeta‐chain expression accompany chronic inflammation in haemodialysis patients
Authors: ELEFTHERIADIS THEODOROS , KARTSIOS CHARALAMBOS , YIANNAKI EFI , ANTONIADI GEORGIA , KAZILA POLIZO , PLIAKOS KONSTANTINOS , LIAKOPOULOS VASSILIOS , MARKALA DIMITRA
Published: March 2009

Aim:  Clinical and experimental data indicate a deficient immune response in haemodialysis (HD) patients. Natural killer‐like (NKL) T cells express on their surface both the T‐cell antigen receptor (TCR) and a diverse set of NK‐cell receptors (NKR) and share properties of both T cells and NK cells. ζ‐Chain phosphorylation is an early event that follows TCR activation or some NKR activation. The ζ‐chain of both T cell and NK cells is downregulated in many chronic inflammatory states, HD included. In the present study, NKL T‐cell percentage and ζ‐chain expression in HD patients were evaluated.

Methods:  Thirty‐three stable HD patients and 30 healthy volunteers were enrolled into the study. NKL T‐cell percentage and NKL T‐cell ζ‐chain mean fluorescence intensity (MFI) were evaluated with flow cytometry. The inflammatory markers C‐reactive protein, interleukin‐6 and tumour necrosis factor‐α were measured in the serum by means of enzyme‐linked immunosorbent assay.

Results:  All the evaluated markers of inflammation were increased in HD patients. In these patients, NKL T‐cell percentage (1.71 ± 1.69% vs 3.94 ± 3.86%) and ζ‐chain MFI (3.66 ± 2.79 vs 7.03 ± 7.91) were decreased.

Conclusions:  NKL T‐cell percentage and ζ‐chain expression is decreased in HD patients. Taking into consideration the continuously increasing age of the HD patients and that normally NKL T‐cell numbers increase with age counteracting the impaired T‐cell and NK‐cell function accompanying advancing age, the above NKL T‐cell disturbances could contribute to the impaired immune response in this population. Measures towards alleviating chronic inflammation could partially restore NKL T‐cell impairment.