bluuebunny/crossref_metadata_2025 huggingface dataset:
Light, nutrients, and food-chain length constrain planktonic energy transfer efficiency across multiple trophic levels
Authors: Dickman Elizabeth M. , Newell Jennifer M. , González María J. , Vanni Michael J.
Published: November 2008

The efficiency of energy transfer through food chains [food chain efficiency (FCE)] is an important ecosystem function. It has been hypothesized that FCE across multiple trophic levels is constrained by the efficiency at which herbivores use plant energy, which depends on plant nutritional quality. Furthermore, the number of trophic levels may also constrain FCE, because herbivores are less efficient in using plant production when they are constrained by carnivores. These hypotheses have not been tested experimentally in food chains with 3 or more trophic levels. In a field experiment manipulating light, nutrients, and food-chain length, we show that FCE is constrained by algal food quality and food-chain length. FCE across 3 trophic levels (phytoplankton to carnivorous fish) was highest under low light and high nutrients, where algal quality was best as indicated by taxonomic composition and nutrient stoichiometry. In 3-level systems, FCE was constrained by the efficiency at which both herbivores and carnivores converted food into production; a strong nutrient effect on carnivore efficiency suggests a carryover effect of algal quality across 3 trophic levels. Energy transfer efficiency from algae to herbivores was also higher in 2-level systems (without carnivores) than in 3-level systems. Our results support the hypothesis that FCE is strongly constrained by light, nutrients, and food-chain length and suggest that carryover effects across multiple trophic levels are important. Because many environmental perturbations affect light, nutrients, and food-chain length, and many ecological services are mediated by FCE, it will be important to apply these findings to various ecosystem types.
A shared enhancer controls a temporal switch between promoters during
Drosophila
primary sex determination
Authors: González Alejandra N. , Lu Hong , Erickson James W.
Published: November 2008

Sex-lethal
(
Sxl
), the master regulatory gene of
Drosophila
somatic sex determination, is stably maintained in an on or an off state by autoregulatory control of
Sxl
premRNA processing. Establishment of the correct
Sxl
splicing pattern requires the coordinate regulation of two
Sxl
promoters. The first of these promoters,
SxlPe
, responds to the female dose of two X chromosomes to produce a pulse of
Sxl
protein that acts on the premRNA products from the second promoter,
SxlPm
, to establish the splicing loop.
SxlPm
is active in both sexes throughout most of development, but nothing is known about how
SxlPm
is expressed during the transition from X signal assessment to maintenance splicing. We found that
SxlPm
is activated earlier in females than in males in a range of
Drosophila
species, and that its expression overlaps briefly with that of
SxlPe
during the syncytial blastoderm stage. Activation of
SxlPm
depends on the
scute
,
daughterless
, and
runt
transcription factors, which communicate X chromosome dose to
SxlPe
, but is independent of the X signal element
sisA
and the maternal co-repressor
groucho
. We show that DNA sequences regulating the response of
SxlPe
to the X chromosome dose also control the sex-differential response of
SxlPm
. We propose that co-expression of
Sxl
protein and its premRNA substrate facilitates the transition from transcriptional to splicing control, and that delayed activation of
SxlPm
in males buffers against the inappropriate activation of
Sxl
by fluctuations in the strength of the X chromosome signal.
A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization
Authors: Liu Meilian , Zhou Lijun , Xu Aimin , Lam Karen S. L. , Wetzel Michael D. , Xiang Ruihua , Zhang Jingjing , Xin Xiaoban , Dong Lily Q. , Liu Feng
Published: November 2008

Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GST-kappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfide-bond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNFα. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders.
Crystal structure of CD155 and electron microscopic studies of its complexes with polioviruses
Authors: Zhang Ping , Mueller Steffen , Morais Marc C. , Bator Carol M. , Bowman Valorie D. , Hafenstein Susan , Wimmer Eckard , Rossmann Michael G.
Published: November 2008

When poliovirus (PV) recognizes its receptor, CD155, the virus changes from a 160S to a 135S particle before releasing its genome into the cytoplasm. CD155 is a transmembrane protein with 3 Ig-like extracellular domains, D1–D3, where D1 is recognized by the virus. The crystal structure of D1D2 has been determined to 3.5-Å resolution and fitted into ≈8.5-Å resolution cryoelectron microscopy reconstructions of the virus–receptor complexes for the 3 PV serotypes. These structures show that, compared with human rhinoviruses, the virus–receptor interactions for PVs have a greater dependence on hydrophobic interactions, as might be required for a virus that can inhabit environments of different pH. The pocket factor was shown to remain in the virus during the first recognition stage. The present structures, when combined with earlier mutational investigations, show that in the subsequent entry stage the receptor moves further into the canyon when at a physiological temperature, thereby expelling the pocket factor and separating the viral subunits to form 135S particles. These results provide a detailed analysis of how a nonenveloped virus can enter its host cell.
Defined spatial structure stabilizes a synthetic multispecies bacterial community
Authors: Kim Hyun Jung , Boedicker James Q. , Choi Jang Wook , Ismagilov Rustem F.
Published: November 2008

This paper shows that for microbial communities, “fences make good neighbors.” Communities of soil microorganisms perform critical functions: controlling climate, enhancing crop production, and remediation of environmental contamination. Microbial communities in the oral cavity and the gut are of high biomedical interest. Understanding and harnessing the function of these communities is difficult: artificial microbial communities in the laboratory become unstable because of “winner-takes-all” competition among species. We constructed a community of three different species of wild-type soil bacteria with syntrophic interactions using a microfluidic device to control spatial structure and chemical communication. We found that defined microscale spatial structure is both necessary and sufficient for the stable coexistence of interacting bacterial species in the synthetic community. A mathematical model describes how spatial structure can balance the competition and positive interactions within the community, even when the rates of production and consumption of nutrients by species are mismatched, by exploiting nonlinearities of these processes. These findings provide experimental and modeling evidence for a class of communities that require microscale spatial structure for stability, and these results predict that controlling spatial structure may enable harnessing the function of natural and synthetic multispecies communities in the laboratory.
Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contraction and results in postnatal death in mice
Authors: Chi Mei , Zhou Yingbi , Vedamoorthyrao Srikanth , Babu Gopal J. , Periasamy Muthu
Published: November 2008

The physiological relevance of smooth muscle myosin isoforms SM1 and SM2 has not been understood. In this study we generated a mouse model specifically deficient in SM2 myosin isoform but expressing SM1, using an exon-specific gene targeting strategy. The SM2 homozygous knockout (SM2
−/−
) mice died within 30 days after birth, showing pathologies including segmental distention of alimentary tract, retention of urine in renal pelvis, distension of bladder, and the development of end-stage hydronephrosis. In contrast, the heterozygous (SM2
+/−
) mice appeared normal and reproduced well. In SM2
−/−
bladder smooth muscle the loss of SM2 myosin was accompanied by a concomitant down-regulation of SM1 and a reduced number of thick filaments. However, muscle strips from SM2
−/−
bladder showed increased contraction to K
+
depolarization or in response to M3 receptor agonist Carbachol. An increase of contraction was also observed in SM2
−/−
aorta. However, the SM2
−/−
bladder was associated with unaltered regulatory myosin light chain (MLC20) phosphorylation. Moreover, other contractile proteins, such as α-actin and tropomyosin, were not altered in SM2
−/−
bladder. Therefore, the loss of SM2 myosin alone could have induced hypercontractility in smooth muscle, suggesting that distinctly from SM1, SM2 may negatively modulate force development during smooth muscle contraction. Also, because SM2
−/−
mice develop lethal multiorgan dysfunctions, we propose this regulatory property of SM2 is essential for normal contractile activity in postnatal smooth muscle physiology.
Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea
Authors: Dabdoub Alain , Puligilla Chandrakala , Jones Jennifer M. , Fritzsch Bernd , Cheah Kathryn S. E. , Pevny Larysa H. , Kelley Matthew W.
Published: November 2008

Sox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in
SOX2
cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain- and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea.
T cell apoptosis at the maternal–fetal interface in early human pregnancy, involvement of galectin-1
Authors: Kopcow Hernan D. , Rosetti Florencia , Leung Yiuka , Allan David S. J. , Kutok Jeffrey L. , Strominger Jack L.
Published: November 2008

The human fetus is not rejected by the maternal immune system despite expressing paternal antigens. Natural killer cells, the major lymphocyte population of the human decidua (dNKs), express genes with immunomodulatory potential. These include galectin-1 (gal1), a lectin with apoptotic activity on activated CD8
+
T cells, Th1 and Th17 CD4
+
cells. Although many cell types at the maternal–fetal interface also produce gal1, its production by dNKs has been used here to study its function in pregnancy. Media conditioned by dNKs containing gal1 induced apoptosis of activated T cells. This effect was blocked by anti-gal1 antibodies. Decidual T (dT) cells but not peripheral T (pT) cells bound gal1 and presented a distinct glycophenotype compatible with sensitivity to gal1. Annexin V staining, TUNEL, and hypodiploidy showed a substantial proportion of apoptotic dT cells. Immunohistochemistry revealed widespread expression of gal1 as well as periglandular apoptotic dT foci that colocalized with dNKs. Thus, secretion of gal1 by dNKs and other decidual cells contributes to the generation of an immune-privileged environment at the maternal–fetal interface.
Quantitative single-molecule imaging by confocal laser scanning microscopy
Authors: Vukojević Vladana , Heidkamp Marcus , Ming Yu , Johansson Björn , Terenius Lars , Rigler Rudolf
Published: November 2008

A new approach to quantitative single-molecule imaging by confocal laser scanning microscopy (CLSM) is presented. It relies on fluorescence intensity distribution to analyze the molecular occurrence statistics captured by digital imaging and enables direct determination of the number of fluorescent molecules and their diffusion rates without resorting to temporal or spatial autocorrelation analyses. Digital images of fluorescent molecules were recorded by using fast scanning and avalanche photodiode detectors. In this way the signal-to-background ratio was significantly improved, enabling direct quantitative imaging by CLSM. The potential of the proposed approach is demonstrated by using standard solutions of fluorescent dyes, fluorescently labeled DNA molecules, quantum dots, and the Enhanced Green Fluorescent Protein in solution and in live cells. The method was verified by using fluorescence correlation spectroscopy. The relevance for biological applications, in particular, for live cell imaging, is discussed.
Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association
Authors: Watkins Janis L. , Lewandowski Katherine T. , Meek Sarah E. M. , Storz Peter , Toker Alex , Piwnica-Worms Helen
Published: November 2008

The Par-1 protein kinases are conserved from yeast to humans, where they function as key polarity determinants. The mammalian Par-1 family is comprised of 4 members (Par-1a, -b, -c, and -d). Previously, we demonstrated that atypical protein kinase C (aPKC) phosphorylates the Par-1 kinases on a conserved threonine residue (T595) to regulate localization and kinase activity. Here, we demonstrate that Par-1b is also regulated by another arm of the PKC pathway, one that involves novel PKCs (nPKC) and protein kinase D. Treatment of cells with the PKC activator phorbol-12-myristate-13-acetate (PMA) potently stimulated phosphorylation of Par-1b on serine 400 (S400), a residue that is conserved in all 4 mammalian Par-1 kinases as well as the fly ortholog. We demonstrate that PMA stimulates nPKC to activate PKD, which in turn directly phosphorylates Par-1b on S400 to positively regulate 14-3-3 binding and to negatively regulate membrane association. Thus, 2 arms of the PKC pathway regulate interactions between Par-1b and 14-3-3 proteins: one involving aPKC and the other nPKC/PKD.
A chimeric Cre recombinase with regulated directionality
Authors: Warren David , Laxmikanthan Gurunathan , Landy Arthur
Published: November 2008

From bacterial viruses to humans, site-specific recombination and transposition are the major pathways for rearranging genomes on both long- and short-time scales. The site-specific pathways can be divided into 2 groups based on whether they are stochastic or regulated. Recombinases Cre and λ Int are well-studied examples of each group, respectively. Both have been widely exploited as powerful and flexible tools for genetic engineering: Cre primarily in vivo and λ Int primarily in vitro. Although Cre and Int use the same mechanism of DNA strand exchange, their respective reaction pathways are very different. Cre-mediated recombination is bidirectional, unregulated, does not require accessory proteins, and has a minimal symmetric DNA target. We show that when Cre is fused to the small N-terminal domain of Int, the resulting chimeric Cre recombines complex higher-order DNA targets comprising >200 bp encoding 16 protein-binding sites. This recombination requires the IHF protein, is unidirectional, and is regulated by the relative levels of the 3 accessory proteins, IHF, Xis, and Fis. In one direction, recombination depends on the Xis protein, and in the other direction it is inhibited by Xis. It is striking that regulated directionality and complexity can be conferred in a simple chimeric construction. We suggest that the relative ease of constructing a chimeric Cre with these properties may simulate the evolutionary interconversions responsible for the large variety of site-specific recombinases observed in Archaea, Eubacteria, and Eukarya.
Counselling in primary care: a systematic review of the evidence
Authors: Brettle Alison , Hill Andy , Jenkins Peter
Published: November 2008

Primary objective: To undertake a systematic review which aimed to locate, appraise and synthesise evidence to obtain a reliable overview of the clinical effectiveness, cost‐effectiveness and user perspectives regarding counselling in primary care.

Main results: Evidence from 26 studies was presented as a narrative synthesis and demonstrated that counselling is effective in the short term, is as effective as CBT with typical heterogeneous primary care populations and more effective than routine primary care for the treatment of non‐specific generic psychological problems, anxiety and depression. Counselling may reduce levels of referrals to psychiatric services, but does not appear to reduce medication, the number of GP consultations or overall costs. Patients are highly satisfied with the counselling they have received in primary care and prefer counselling to medication for depression. Conclusions and implications for future research: This review demonstrates the value of counselling as a valid choice for primary care patients and as a broadly effective therapeutic intervention for a wide range of generic psychological conditions presenting in the primary care setting. More rigorous clinical and cost‐effectiveness trials are needed together with surveys of more typical users of primary care services.
RhoA–ROCK and p38MAPK-MSK1 mediate vitamin D effects on gene expression, phenotype, and Wnt pathway in colon cancer cells
Authors: Ordóñez-Morán Paloma , Larriba María Jesús , Pálmer Héctor G. , Valero Ruth A. , Barbáchano Antonio , Duñach Mireia , de Herreros Antonio García , Villalobos Carlos , Berciano María Teresa , Lafarga Miguel , Muñoz Alberto
Published: November 2008

The active vitamin D metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proliferation and promotes differentiation of colon cancer cells through the activation of vitamin D receptor (VDR), a transcription factor of the nuclear receptor superfamily. Additionally, 1,25(OH)2D3 has several nongenomic effects of uncertain relevance. We show that 1,25(OH)2D3 induces a transcription-independent Ca2+ influx and activation of RhoA–Rho-associated coiled kinase (ROCK). This requires VDR and is followed by activation of the p38 mitogen-activated protein kinase (p38MAPK) and mitogen- and stress-activated kinase 1 (MSK1). As shown by the use of chemical inhibitors, dominant-negative mutants and small interfering RNA, RhoA–ROCK, and p38MAPK-MSK1 activation is necessary for the induction of CDH1/E-cadherin, CYP24, and other genes and of an adhesive phenotype by 1,25(OH)2D3. RhoA–ROCK and MSK1 are also required for the inhibition of Wnt–β-catenin pathway and cell proliferation. Thus, the action of 1,25(OH)2D3 on colon carcinoma cells depends on the dual action of VDR as a transcription factor and a nongenomic activator of RhoA–ROCK and p38MAPK-MSK1.
Cardiolipin provides an essential activating platform for caspase-8 on mitochondria
Authors: Gonzalvez Francois , Schug Zachary T. , Houtkooper Riekelt H. , MacKenzie Elaine D. , Brooks David G. , Wanders Ronald J.A. , Petit Patrice X. , Vaz Frédéric M. , Gottlieb Eyal
Published: November 2008

Cardiolipin is a mitochondria-specific phospholipid known to be intimately involved with apoptosis. However, the lack of appropriate cellular models to date restricted analysis of its role in cell death. The maturation of cardiolipin requires the transacylase tafazzin, which is mutated in the human disorder Barth syndrome. Using Barth syndrome patient-derived cells and HeLa cells in which tafazzin was knocked down, we show that cardiolipin is required for apoptosis in the type II mitochondria-dependent response to Fas stimulation. Cardiolipin provides an anchor and activating platform for caspase-8 translocation to, and embedding in, the mitochondrial membrane, where it oligomerizes and is further activated, steps that are necessary for an efficient type II apoptotic response.
A kinesin-13 mutant catalytically depolymerizes microtubules in ADP
Authors: Wagenbach Michael , Domnitz Sarah , Wordeman Linda , Cooper Jeremy
Published: November 2008

The kinesin-13 motor protein family members drive the removal of tubulin from microtubules (MTs) to promote MT turnover. A point mutation of the kinesin-13 family member mitotic centromere-associated kinesin/Kif2C (E491A) isolates the tubulin-removal conformation of the motor, and appears distinct from all previously described kinesin-13 conformations derived from nucleotide analogues. The E491A mutant removes tubulin dimers from stabilized MTs stoichiometrically in adenosine triphosphate (ATP) but is unable to efficiently release from detached tubulin dimers to recycle catalytically. Only in adenosine diphosphate (ADP) can the mutant catalytically remove tubulin dimers from stabilized MTs because the affinity of the mutant for detached tubulin dimers in ADP is low relative to lattice-bound tubulin. Thus, the motor can regenerate for further cycles of disassembly. Using the mutant, we show that release of tubulin by kinesin-13 motors occurs at the transition state for ATP hydrolysis, which illustrates a significant divergence in their coupling to ATP turnover relative to motile kinesins.
Histone H3 lysine 56 acetylation by Rtt109 is crucial for chromosome positioning
Authors: Hiraga Shin-ichiro , Botsios Sotirios , Donaldson Anne D.
Published: November 2008

Correct intranuclear organization of chromosomes is crucial for many genome functions, but the mechanisms that position chromatin are not well understood. We used a layered screen to identify Saccharomyces cerevisiae mutants defective in telomere localization to the nuclear periphery. We find that events in S phase are crucial for correct telomere localization. In particular, the histone chaperone Asf1 functions in telomere peripheral positioning. Asf1 stimulates acetylation of histone H3 lysine 56 (H3K56) by the histone acetyltransferase Rtt109. Analysis of rtt109Δ and H3K56 mutants suggests that the acetylation/deacetylation cycle of the H3K56 residue is required for proper telomere localization. The function of H3K56 acetylation in localizing chromosome domains is not confined to telomeres because deletion of RTT109 also prevents the correct peripheral localization of a newly identified S. cerevisiae “chromosome-organizing clamp” locus. Because chromosome positioning is subject to epigenetic inheritance, H3K56 acetylation may mediate correct chromosome localization by facilitating accurate transmission of chromatin status during DNA replication.
Cytoplasmic diffusion: molecular motors mix it up
Authors: Brangwynne Clifford P. , Koenderink Gijsje H. , MacKintosh Frederick C. , Weitz David A.
Published: November 2008

Random motion within the cytoplasm gives rise to molecular diffusion; this motion is essential to many biological processes. However, in addition to thermal Brownian motion, the cytoplasm also undergoes constant agitation caused by the activity of molecular motors and other nonequilibrium cellular processes. Here, we discuss recent work that suggests this activity can give rise to cytoplasmic motion that has the appearance of diffusion but is significantly enhanced in its magnitude and which can play an important biological role, particularly in cytoskeletal assembly.
Cdc42 controls spindle orientation to position the apical surface during epithelial morphogenesis
Authors: Jaffe Aron B. , Kaji Noriko , Durgan Joanne , Hall Alan
Published: November 2008

The establishment of apical–basal polarity within a single cell and throughout a growing tissue is a key feature of epithelial morphogenesis. To examine the underlying mechanisms, the human intestinal epithelial cell line Caco-2 was grown in a three-dimensional matrix to generate a cystlike structure, where the apical surface of each epithelial cell faces a fluid-filled central lumen. A discrete apical domain is established as early as the first cell division and between the two daughter cells. During subsequent cell divisions, the apical domain of each daughter cell is maintained at the center of the growing structure through a combination of mitotic spindle orientation and asymmetric abscission. Depletion of Cdc42 does not prevent the establishment of apical–basal polarity in individual cells but rather disrupts spindle orientation, leading to inappropriate positioning of apical surfaces within the cyst. We conclude that Cdc42 regulates epithelial tissue morphogenesis by controlling spindle orientation during cell division.
Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases
Authors: Yun Chawon , Wang Yonggang , Mukhopadhyay Debaditya , Backlund Peter , Kolli Nagamalleswari , Yergey Alfred , Wilkinson Keith D. , Dasso Mary
Published: November 2008

Ubiquitin-like protein/sentrin-specific proteases (Ulp/SENPs) mediate both processing and deconjugation of small ubiquitin-like modifier proteins (SUMOs). Here, we show that Ulp/SENP family members SENP3 and SENP5 localize within the granular component of the nucleolus, a subnucleolar compartment that contains B23/nucleophosmin. B23/nucleophosmin is an abundant shuttling phosphoprotein, which plays important roles in ribosome biogenesis and which has been strongly implicated in hematopoietic malignancies. Moreover, we found that B23/nucleophosmin binds SENP3 and SENP5 in Xenopus laevis egg extracts and that it is essential for stable accumulation of SENP3 and SENP5 in mammalian tissue culture cells. After either codepletion of SENP3 and SENP5 or depletion of B23/nucleophosmin, we observed accumulation of SUMO proteins within nucleoli. Finally, depletion of these Ulp/SENPs causes defects in ribosome biogenesis reminiscent of phenotypes observed in the absence of B23/nucleophosmin. Together, these results suggest that regulation of SUMO deconjugation may be a major facet of B23/nucleophosmin function in vivo.
Genetic algorithms for simultaneous variable and sample selection in metabonomics
Authors: Cavill Rachel , Keun Hector C. , Holmes Elaine , Lindon John C. , Nicholson Jeremy K. , Ebbels Timothy M. D.
Published: November 2008

Motivation: Metabolic profiles derived from high resolution 1H-NMR data are complex, therefore statistical and machine learning approaches are vital for extracting useful information and biological insights. Focused modelling on targeted subsets of metabolites and samples can improve the predictive ability of models, and techniques such as genetic algorithms (GAs) have a proven utility in feature selection problems. The Consortium for Metabonomic Toxicology (COMET) obtained temporal NMR spectra of urine from rats treated with model toxins and stressors. Here, we develop a GA approach which simultaneously selects sets of samples and spectral regions from the COMET database to build robust, predictive classifiers of liver and kidney toxicity.

Results: The results indicate that using simultaneous sample and variable selection improved performance by over 9% compared with either method alone. Simultaneous selection also halved computation time. Successful classifiers repeatedly selected particular variables indicating that this approach can aid defining biomarkers of toxicity. Novel visualizations of the results from multiple computations were developed to aid the interpretability of which samples and variables were frequently selected. This method provides an efficient way to determine the most discriminatory variables and samples for any post-genomic dataset.

Availability: GA code available from http://www1.imperial.ac.uk/medicine/people/r.cavill/

Contact:  r.cavill@imperial.ac.uk; t.ebbels@imperial.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Selecting MPAs to conserve groundfish biodiversity: the consequences of failing to account for catchability in survey trawls
Authors: Fraser Helen M. , Greenstreet S. P. R. , Piet Gerjan J.
Published: November 2008

Fraser, H. M., Greenstreet, S. P. R., and Piet, G. J. 2009. Selecting MPAs to conserve groundfish biodiversity: the consequences of failing to account for catchability in survey trawls. – ICES Journal of Marine Science, 66: 82–89. Fishing has affected North Sea groundfish species diversity. Defining Marine Protected Areas (MPAs) to address this will rely on groundfish surveys. Species-specific catch efficiencies vary between trawl gears, and apparent species diversity distributions are influenced by the type of gear used in each survey. It may be that no single survey depicts actual diversity distributions. Two MPA scenarios designed to protect groundfish species diversity are described, the first based on unadjusted International Bottom Trawl Survey data and the second based on the same data adjusted to take account of catchability. Spatial overlap between these scenarios is low. Assuming that the adjusted data best describe the actual species diversity distribution, the level of diversity safeguarded by MPAs, based on unadjusted data, is determined. A fishing effort redistribution model is used to estimate the increase in fishing activity that is likely to occur in MPAs that take catchability into account, if closed areas based solely on the unadjusted groundfish data were implemented. Our results highlight the need to take survey-gear catchability into account when designating MPAs to address fish-species diversity issues.
Application of Fourier transform infrared spectroscopic imaging to the study of effects of age and dietary
l
-arginine on aortic lesion composition in cholesterol-fed rabbits
Authors: Palombo Francesca , Cremers Stephanie G. , Weinberg Peter D. , Kazarian Sergei G.
Published: November 2008

Diet-induced atherosclerotic lesions in the descending thoracic segment of rabbit aorta were analysed
ex vivo
by micro-attenuated total reflection (ATR)–Fourier transform infrared (FTIR) spectroscopic imaging. The distribution and chemical character of lipid deposits within the arterial wall near intercostal branch ostia were assessed in histological sections from immature and mature rabbits fed cholesterol with or without
l
-arginine supplements. Previous studies have shown that both these properties change with age in cholesterol-fed rabbits, putatively owing to changes in the synthesis of nitric oxide (NO) from
l
-arginine. Immature animals developed lesions at the downstream margin of the branch ostium, whereas lipid deposition was observed at the lateral margins in mature animals. Dietary
l
-arginine supplements had beneficial effects in mature rabbit aorta, with overall disappearance of the plaques; on the other hand, they caused only a slight decrease of the lipid load in lesions at the downstream margin of the ostium in immature rabbits. ATR–FTIR imaging enabled differences in the lipid to protein density ratio of atherosclerotic lesions caused by age and diet to be visualized. Lipid deposits in immature rabbits showed higher relative absorbance values of their characteristic spectral bands compared with those in immature
l
-arginine-fed rabbits and mature rabbits. The multivariate methods of principal component analysis (PCA) and factor analysis (FA) were employed, and relevant chemical and structural information were obtained. Two distinct protein constituents of the intima–media layer at different locations of the wall were identified using the method of FA. This approach provides a valuable means of investigating the structure and chemistry of complex heterogeneous systems. It has potential for
in vivo
diagnosis of pathology.
Epileptogenesis due to glia-mediated synaptic scaling
Authors: Savin Cristina , Triesch Jochen , Meyer-Hermann Michael
Published: November 2008

Homeostatic regulation of neuronal activity is fundamental for the stable functioning of the cerebral cortex. One form of homeostatic synaptic scaling has been recently shown to be mediated by glial cells that interact with neurons through the diffusible messenger tumour necrosis factor-α (TNF-α). Interestingly, TNF-α is also used by the immune system as a pro-inflammatory messenger, suggesting potential interactions between immune system signalling and the homeostatic regulation of neuronal activity. We present the first computational model of neuron–glia interaction in TNF-α-mediated synaptic scaling. The model shows how under normal conditions the homeostatic mechanism is effective in balancing network activity. After chronic immune activation or TNF-α overexpression by glia, however, the network develops seizure-like activity patterns. This may explain why under certain conditions brain inflammation increases the risk of seizures. Additionally, the model shows that TNF-α diffusion may be responsible for epileptogenesis after localized brain lesions.
A metapopulation modelling framework for gonorrhoea and other sexually transmitted infections in heterosexual populations
Authors: Chen Mark I. , Ghani Azra C. , Edmunds W. John
Published: November 2008

Gonorrhoea continues to be a public health problem in the UK, and is the second most common bacterial sexually transmitted infection (STI) after chlamydia. In the UK, gonorrhoea is disproportionately concentrated in epidemiologically distinct subpopulations, with much higher incidence rates in young people, some ethnic minorities and inner city subpopulations. The original model of STI transmission proposed by Hethcote and Yorke explained some of these features through the concept of the ‘core group’. Since then, several authors have modified the original model approach to include multiple sexual activity classes, but found this modelling approach to be inadequate when applied to low-prevalence settings such as the UK. We present a metapopulation framework for modelling gonorrhoea and other STIs. The model proposes that the epidemiology of gonorrhoea is largely driven by subpopulations with higher than average concentrations of individuals with high sexual risk activity. We show how this conceptualization of gonococcal epidemiology overcomes key limitations associated with some of the prior efforts to model gonorrhoea. We also use the model to explain several epidemiological features of gonorrhoea, such as its asymmetric distribution across subpopulations, and the contextual risk experienced by members of at-risk subpopulations. Finally, we extend the model to explain the distribution of other STIs, using chlamydia as an example of a more ubiquitous bacterial STI.
Nanoscale adhesion, friction and wear studies of biomolecules on silane polymer-coated silica and alumina-based surfaces
Authors: Bhushan Bharat , Kwak Kwang Joo , Gupta Samit , Lee Stephen C
Published: November 2008

Proteins on biomicroelectromechanical systems (BioMEMS) confer specific molecular functionalities. In planar FET sensors (field-effect transistors, a class of devices whose protein-sensing capabilities we demonstrated in physiological buffers), interfacial proteins are analyte receptors, determining sensor molecular recognition specificity. Receptors are bound to the FET through a polymeric interface, and gross disruption of interfaces that removes a large percentage of receptors or inactivates large fractions of them diminishes sensor sensitivity. Sensitivity is also determined by the distance between the bound analyte and the semiconductor. Consequently, differential properties of surface polymers are design parameters for FET sensors. We compare thickness, surface roughness, adhesion, friction and wear properties of silane polymer layers bound to oxides (SiO
2
and Al
2
O
3
, as on AlGaN HFETs). We compare those properties of the film–substrate pairs after an additional deposition of biotin and streptavidin. Adhesion between protein and device and interfacial friction properties affect FET reliability because these parameters affect wear resistance of interfaces to abrasive insult
in vivo
. Adhesion/friction determines the extent of stickage between the interface and tissue and interfacial resistance to mechanical damage. We document systematic, consistent differences in thickness and wear resistance of silane films that can be correlated with film chemistry and deposition procedures, providing guidance for rational interfacial design for planar AlGaN HFET sensors.
Nonlinear dynamic and pattern bifurcations in a model for spatial patterns in young mussel beds
Authors: Wang Rong-Hua , Liu Quan-Xing , Sun Gui-Quan , Jin Zhen , van de Koppel Johan
Published: November 2008

Young mussel beds on soft sediments can display large-scale regular spatial patterns. This phenomenon can be explained relatively simply by a reaction–diffusion–advection (RDA) model of the interaction between algae and mussel, which includes the diffusive spread of mussel and the advection of algae. We present a detailed analysis of pattern formation in this RDA model. We derived the conditions for differential-flow instability that cause the formation of spatial patterns, and then systematically investigated how these patterns depend on model parameters. We also present a detailed study of the patterned solutions in the full nonlinear model, using numerical bifurcation analysis of the ordinary differential equations, which were obtained from the RDA model. We show that spatial patterns occur for a wide range of algal concentrations, even when algal concentration is much lower than the prediction by linear analysis in the RDA model. That is to say, spatial patterns result from the interaction of nonlinear terms. Moreover, patterns with different wavelength, amplitude and movement speed may coexist. The results obtained are consistent with the previous observation that self-organization allows mussels to persist with algal concentrations that would not permit survival of mussels in a homogeneous bed.
Post-translational regulation of activation-induced cytidine deaminase
Authors: Basu Uttiya , Franklin Andrew , Alt Frederick W
Published: November 2008

The assembled
immunoglobulin
genes in the B cells of mice and humans are altered by distinct processes known as class switch recombination (CSR) and somatic hypermutation, leading to diversification of the antibody repertoire. These two DNA modification processes are initiated by the B cell-specific protein factor activation-induced cytidine deaminase (AID). AID is post-translationally modified by phosphorylation at multiple sites, although functional significance during CSR has been implicated only for phosphorylation at serine-38 (S38). Although multiple laboratories have demonstrated that AID function is regulated via phosphorylation at S38, the precise biological role of S38 phosphorylation has been a topic of debate. Here, we discuss our interpretation of the significance of AID regulation via phosphorylation and also discuss how this form of AID regulation may have evolved in higher organisms.
Hydraulic Failure Defines the Recovery and Point of Death in Water-Stressed Conifers
Authors: Brodribb Tim J. , Cochard Hervé
Published: November 2008

This study combines existing hydraulic principles with recently developed methods for probing leaf hydraulic function to determine whether xylem physiology can explain the dynamic response of gas exchange both during drought and in the recovery phase after rewatering. Four conifer species from wet and dry forests were exposed to a range of water stresses by withholding water and then rewatering to observe the recovery process. During both phases midday transpiration and leaf water potential (Ψleaf) were monitored. Stomatal responses to Ψleaf were established for each species and these relationships used to evaluate whether the recovery of gas exchange after drought was limited by postembolism hydraulic repair in leaves. Furthermore, the timing of gas-exchange recovery was used to determine the maximum survivable water stress for each species and this index compared with data for both leaf and stem vulnerability to water-stress-induced dysfunction measured for each species. Recovery of gas exchange after water stress took between 1 and >100 d and during this period all species showed strong 1:1 conformity to a combined hydraulic-stomatal limitation model (r  2 = 0.70 across all plants). Gas-exchange recovery time showed two distinct phases, a rapid overnight recovery in plants stressed to <50% loss of leaf hydraulic conductance (K  leaf) and a highly Ψleaf-dependent phase in plants stressed to >50% loss of K  leaf. Maximum recoverable water stress (Ψmin) corresponded to a 95% loss of K  leaf. Thus, we conclude that xylem hydraulics represents a direct limit to the drought tolerance of these conifer species.
Circadian Clock Proteins LHY and CCA1 Regulate SVP Protein Accumulation to Control Flowering in Arabidopsis
Authors: Fujiwara Sumire , Oda Atsushi , Yoshida Riichiro , Niinuma Kanae , Miyata Kana , Tomozoe Yusuke , Tajima Takeomi , Nakagawa Mayu , Hayashi Kounosuke , Coupland George , Mizoguchi Tsuyoshi
Published: November 2008

The floral regulators GIGANTEA (GI), CONSTANS (CO), and FLOWERING LOCUS T (FT) play key roles in the photoperiodic flowering responses of the long-day plant Arabidopsis thaliana. The GI-CO-FT pathway is highly conserved in plants. Here, we demonstrate that the circadian clock proteins LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK–ASSOCIATED1 (CCA1) not only repressed the floral transition under short-day and long-day conditions but also accelerated flowering when the plants were grown under continuous light (LL). LHY and CCA1 accelerated flowering in LL by promoting FT expression through a genetic pathway that appears to be independent of the canonical photoperiodic pathway involving GI and CO proteins. A genetic screen revealed that the late-flowering phenotype of the lhy;cca1 double mutant under LL was suppressed through mutations in SHORT VEGETATIVE PHASE (SVP), a MADS box transcription factor. Yeast two-hybrid analysis demonstrated an interaction between SVP and FLOWERING LOCUS C, and genetic analysis indicated that these two proteins act as partially redundant repressors of flowering time. SVP protein accumulated in lhy;cca1 plants under LL. We propose a model in which LHY and CCA1 accelerate flowering in part by reducing the abundance of SVP and thereby antagonizing its capacity to repress FT expression under LL.
Cinnamoylmalononitriles as corrosion inhibitors for mild steel in hydrochloric acid solution
Authors: Fouda A.S. , El‐Ewady Y.A. , Abo‐El‐Enien O.M. , Agizah F.A.
Published: November 2008

Purpose

The purpose of this paper is to show the effect of cinnamoylmalononitrile (CMN) compounds on the corrosion inhibition of carbon steel in HCl and the effect of some substituent groups on the corrosion inhibition.

Design/methodology/approach

Several papers have been published (1900‐1999), which aimed to investigate and explain the effect of organic compounds on the corrosion inhibition process. Two methods were used to determine the corrosion rate, weight loss and galvanostatic polarization. Additionally, the effects of temperature and concentration of the inhibitors were studied. The thermodynamic parameters for the process were computed and discussed.

Findings

The paper finds that surface analytical techniques such as X‐ray photoelectron spectroscopy and Auger spectroscopy can shed more light, on the mechanism of corrosion inhibition.

Research limitations/implications

The use of donating and withdrawing groups will improve understanding of the mechanisms of corrosion and inhibition. However, the paper does not use the technique of impedance measurement for comparison purposes.

Practical implications

Other steel alloys and compounds with large or small molecular weights can be used for comparison.

Originality/value

The use of CMN compounds as corrosion inhibitors for carbon steel in HCl provides more information on carbon steel corrosion for academic and starting researchers.
Galvanizing pre‐treatment with hydrogen
Authors: Hussey Timothy S. , Stratton Paul F.
Published: November 2008

Purpose

Before being galvanized, long products like tube, wire and strip need to be cleaned to remove oils and oxides that would inhibit the galvanizing process. Ideally, this process would be instantaneous so that production rates were not compromised and would require no energy. The purpose of this paper is to describe an investigation where rapid induction heating was combined with counter current flow of a hydrogen‐rich atmosphere to reduce and evacuate surface oxides and residual drawing compounds before continuous galvanizing.

Design/methodology/approach

Experiments were carried out to simulate the continuous hot‐dip galvanizing of steel wire.

Findings

The results suggested that, under the experimental conditions, lightly oxidized layers could be reduced in less than 2 s and give galvanized layers with good adhesion. High efficiency induction heating minimized the energy input required.

Originality/value

The use of this technology can maximize galvanizing line speeds while maintaining quality with the minimum environmental impact.
Modified zinc oxide‐phosphate core‐shell pigments in solvent‐based paints
Authors: Ahmed Nivin M.
Published: November 2008

Purpose

The purpose of this paper is to present a new trend of anticorrosive pigments based on bulk (core) of zinc oxide covered with a surface layer of phosphates.

Design/methodology/approach

A new batch of pigments based on core‐shell theory containing a core (bulk) of cheap oxides covered by a layer of phosphates were prepared. These new pigments combined the properties of both components besides being more economically feasible. Simple chemical techniques were used to prepare these pigments. Characterization of these pigments using X‐ray diffraction and scanning electron microscopy was carried out. Evaluation of these pigments using international standard testing methods was estimated. These pigments were incorporated in solvent‐based paint formulations based on medium oil alkyd resin. The physico‐mechanical properties of dry films and their corrosion properties using an accelerated laboratory test in 3.5 percent NaCl for 28 days were tested.

Findings

It was found that those pigments based essentially on zinc oxide covered with a surface layer of phosphates were easily prepared, are economically feasible and can successfully replace original phosphates with similar efficiency in their corrosion protection behaviour.

Practical implications

These pigments can be applied in other polymer composites, e.g. rubber and plastics, as a reinforcing agent.

Originality/value

The prepared pigments are environmentally friendly and can replace other hazardous pigments (e.g. chromates) with almost the same quality in their performance; also they can be used in industries other than paints, e.g. paper, rubber and plastics composites.