bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced expression of a vesicle trafficking-related ATPase SKD1 decreases salt tolerance in Arabidopsis
Authors: Ho Li-Wei , Yang Ting-Ting , Shieh Shyan-Shu , Edwards Gerald E. , Yen Hungchen E.
Published: September 2010

In this study we present the functional characterisation of SKD1 (suppressor of K+ transport growth defect) in salt tolerance of higher plants. SKD1 participates in endosome-mediated protein sorting and expression of SKD1 is salt-induced in Na+ storage cells of halophyte ice plant. Transgenic Arabidopsis with reduced SKD1 expression were generated by expressing AtSKD1 in antisense orientation. Relative root growth rate of antisense seedlings was slower than that of wild-type seedlings under salt treatment. The Na+/K+ ratio doubled in the antisense seedlings compared with the wild-type seedlings indicating a loss in Na+/K+ homeostasis. The PSII activity dropped following one week of salt-stress in antisense plants whereas wild-type plants maintained normal activity. Upon germination, transgenic seedlings developed multiple roots where each root had lower density of lateral roots. Application of 1-naphthaleneacetic acid restored the ability of transgenic seedlings to form lateral roots. Expression profiling analyses revealed that expressions of one stress-related kinase, several salt-induced transcription factors and one auxin efflux transporter were altered in antisense seedlings. With decreased expression of SKD1, plants experience a reduced salinity response and altered root development indicating the importance of intracellular vesicular trafficking in both auxin-mediated plant growth and in maintaining ion homeostasis under salt stress.
The role of oomycete effectors in plant - pathogen interactions
Authors: Hardham Adrienne R. , Cahill David M.
Published: September 2010

Plants constantly come into contact with a diverse range of microorganisms that are potential pathogens, and they have evolved multi-faceted physical and chemical strategies to inhibit pathogen ingress and establishment of disease. Microbes, however, have developed their own strategies to counteract plant defence responses. Recent research on plant–microbe interactions has revealed that an important part of the infection strategies of a diverse range of plant pathogens, including bacteria, fungi and oomycetes, is the production of effector proteins that are secreted by the pathogen and that promote successful infection by manipulating plant structure and metabolism, including interference in plant defence mechanisms. Pathogen effector proteins may function either in the extracellular spaces within plant tissues or within the plant cell cytoplasm. Extracellular effectors include cell wall degrading enzymes and inhibitors of plant enzymes that attack invading pathogens. Intracellular effectors move into the plant cell cytoplasm by as yet unknown mechanisms where, in incompatible interactions, they may be recognised by plant resistance proteins but where, in compatible interactions, they may suppress the plant’s immune response. This article presents a brief overview of our current understanding of the nature and function of effectors produced by oomycete plant pathogens.
Phylogenetics and revised taxonomy of the Australian freshwater cod genus, Maccullochella (Percichthyidae)
Authors: Nock Catherine J. , Elphinstone Martin S. , Rowland Stuart J. , Baverstock Peter R.
Published: September 2010

Determining the phylogenetic and taxonomic relationships among allopatric populations can be difficult, especially when divergence is recent and morphology is conserved. We used mitochondrial sequence data from the control region and three protein-coding genes (1253 bp in total) and genotypes determined at 13 microsatellite loci to examine the evolutionary relationships among Australia’s largest freshwater fish, the Murray cod, Maccullochella peelii peelii, from the inland Murray–Darling Basin, and its allopatric sister taxa from coastal drainages, the eastern freshwater cod, M. ikei, and Mary River cod, M. peelii mariensis. Phylogenetic analyses provided strong support for taxon-specific clades, with a clade containing both of the eastern taxa reciprocally monophyletic to M. peelii peelii, suggesting a more recent common ancestry between M. ikei and M. peelii mariensis than between the M. peelii subspecies. This finding conflicts with the existing taxonomy and suggests that ancestral Maccullochella crossed the Great Dividing Range in the Pleistocene and subsequently diverged in eastern coastal drainages. Evidence from the present study, in combination with previous morphological and allozymatic data, demonstrates that all extant taxa are genetically and morphologically distinct. The taxonomy of Maccullochella is revised, with Mary River cod now recognised as a species, Maccullochella mariensis, a sister species to eastern freshwater cod, M. ikei. As a result of the taxonomic revision, Murray cod is M. peelii.
Collaborative photo-identification and monitoring of grey nurse sharks (Carcharias taurus) at key aggregation sites along the eastern coast of Australia
Authors: Barker Sean M. , Williamson Jane E.
Published: September 2010

Before the worldwide decline of the ‘globally vulnerable’ Carcharias taurus may be addressed, an understanding of its migratory patterns and locations, and/or times when sharks may be vulnerable, is required to identify habitats that are critical to its survival. A collaborative framework for photo-identification and monitoring of C. taurus may greatly assist with conservation management initiatives. Images of C. taurus were sourced from public submissions to the www.spotashark.com (verified 12 February 2009) website and during targeted surveys. A computer-assisted program (I3S) was used to match the images of sharks photographically from the database. Research revealed patterns of movement, site utilisation and population structure similar to those in previous tagging studies. With the use of an underwater camera and two laser-scaling devices, 408 individual sharks were identified. Average occupancy times at two locations in New South Wales (NSW), Australia, were 308 days (Fish Rock) and 363 days (Magic Point). Seventeen individuals undertook northward or southward movements, averaging 350 km. The present study showed that a broad-based technique for data acquisition, coupled with rigorous evaluation of photographic identifications can provide support for local research and management programs and may aid with the conservation of the C. taurus species worldwide.
Consequences of realistic patterns of biodiversity loss: an experimental test from the intertidal zone
Authors: Walker Meaghan K. , Thompson Ross M.
Published: September 2010

Studies of the effects of biodiversity on ecosystem function (BDEF) have largely found positive, saturating relationships. However, these studies have been criticised for generating species loss randomly when real extinctions are strongly biased toward rare species. We investigated BDEF relationships in the mollusc fauna of an intertidal rock platform at Griffiths Point, San Remo, south-east Victoria, Australia. Field surveys found that areas with the lowest function (mollusc biomass) were associated with lowest diversity. Excluding individual species from experimental enclosures affected function differentially depending on species’ initial abundance. Rectangular enclosures were attached to the rock platform enabling molluscs to be enclosed while allowing sea water to flow through. Removal of the most abundant species had a positive effect on mollusc biomass, suggesting an inhibition of the other species in the community. In the absence of the most common species, the less abundant species were more productive in combination than when present singly. Taken collectively, these results provide evidence for a relationship between biodiversity and ecosystem function which is a product of both diversity per se and species identity.
Perspectives on empirical approaches for ocean color remote sensing of chlorophyll in a changing climate
Authors: Dierssen Heidi M.
Published: September 2010

Phytoplankton biomass and productivity have been continuously monitored from ocean color satellites for over a decade. Yet, the most widely used empirical approach for estimating chlorophyll
a
(Chl) from satellites can be in error by a factor of 5 or more. Such variability is due to differences in absorption and backscattering properties of phytoplankton and related concentrations of colored-dissolved organic matter (CDOM) and minerals. The empirical algorithms have built-in assumptions that follow the basic precept of biological oceanography—namely, oligotrophic regions with low phytoplankton biomass are populated with small phytoplankton, whereas more productive regions contain larger bloom-forming phytoplankton. With a changing world ocean, phytoplankton composition may shift in response to altered environmental forcing, and CDOM and mineral concentrations may become uncoupled from phytoplankton stocks, creating further uncertainty and error in the empirical approaches. Hence, caution is warranted when using empirically derived Chl to infer climate-related changes in ocean biology. The Southern Ocean is already experiencing climatic shifts and shows substantial errors in satellite-derived Chl for different phytoplankton assemblages. Accurate global assessments of phytoplankton will require improved technology and modeling, enhanced field observations, and ongoing validation of our “eyes in space.”
Cells navigate with a local-excitation, global-inhibition-biased excitable network
Authors: Xiong Yuan , Huang Chuan-Hsiang , Iglesias Pablo A. , Devreotes Peter N.
Published: September 2010

Cells have an internal compass that enables them to move along shallow chemical gradients. As amoeboid cells migrate, signaling events such as Ras and PI3K activation occur spontaneously on pseudopodia. Uniform stimuli trigger a symmetric response, whereupon cells stop and round up; then localized patches of activity appear as cells spread. Finally cells adapt and resume random migration. In contrast, chemotactic gradients continuously direct signaling events to the front of the cell. Local-excitation, global-inhibition (LEGI) and reaction–diffusion models have captured some of these features of chemotaxing cells, but no system has explained the complex response kinetics, sensitivity to shallow gradients, or the role of recently observed propagating waves within the actin cytoskeleton. We report here that Ras and PI3K activation move in phase with the cytoskeleton events and, drawing on all of these observations, propose the LEGI-biased excitable network hypothesis. We formulate a model that simulates most of the behaviors of chemotactic cells: In the absence of stimulation, there are spontaneous spots of activity. Stimulus increments trigger an initial burst of patches followed by localized secondary events. After a few minutes, the system adapts, again displaying random activity. In gradients, the activity patches are directed continuously and selectively toward the chemoattractant, providing an extraordinary degree of amplification. Importantly, by perturbing model parameters, we generate distinct behaviors consistent with known classes of mutants. Our study brings together heretofore diverse observations on spontaneous cytoskeletal activity, signaling responses to temporal stimuli, and spatial gradient sensing into a unified scheme.
Galectin-9 trafficking regulates apical-basal polarity in Madin–Darby canine kidney epithelial cells
Authors: Mishra Rashmi , Grzybek Michal , Niki Toshiro , Hirashima Mitsuomi , Simons Kai
Published: September 2010

Galectins are unconventionally secreted lectins that participate in the formation of glycoprotein lattices that perform a variety of cell surface functions. Galectins also bind glycosphingolipid headgroups with as yet unclear implications for cellular physiology. We report a specific interaction between galectin-9 and the Forssman glycosphingolipid (FGL) that is important for polarizing Madin–Darby canine kidney epithelial cells. Galectin-9 knockdown leads to a severe loss of epithelial polarity that can be rescued by addition of the recombinant protein. The FGL glycan is identified as the surface receptor that cycles galectin-9 to the Golgi apparatus from which the protein is recycled back to the apical surface. Together our results suggest a model wherein such glycosphingolipid–galectin couples form a circuit between the Golgi apparatus and the cell surface that in an epithelial context facilitates the apical sorting of proteins and lipids.
Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome
Authors: Pan Feng , Aldridge Georgina M. , Greenough William T. , Gan Wen-Biao
Published: September 2010

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is caused by transcriptional inactivation of the X-linked
fragile X mental retardation 1
(
FMR1
) gene. FXS is associated with increased density and abnormal morphology of dendritic spines, the postsynaptic sites of the majority of excitatory synapses. To better understand how lack of the
FMR1
gene function affects spine development and plasticity, we examined spine formation and elimination of layer 5 pyramidal neurons in the whisker barrel cortex of
Fmr1
KO mice with a transcranial two-photon imaging technique. We found that the rates of spine formation and elimination over days to weeks were significantly higher in both young and adult KO mice compared with littermate controls. The heightened spine turnover in KO mice was due to the existence of a larger pool of “short-lived” new spines in KO mice than in controls. Furthermore, we found that the formation of new spines and the elimination of existing ones were less sensitive to modulation by sensory experience in KO mice. These results indicate that the loss of
Fmr1
gene function leads to ongoing overproduction of transient spines in the primary somatosensory cortex. The insensitivity of spine formation and elimination to sensory alterations in
Fmr1
KO mice suggest that the developing synaptic circuits may not be properly tuned by sensory stimuli in FXS.
Antagonistic Functions of Two Stardust Isoforms inDrosophilaPhotoreceptor Cells
Authors: Bulgakova Natalia A. , Rentsch Michaela , Knust Elisabeth
Published: September 2010

Membrane-associated guanylate kinases (MAGUKs) are scaffolding proteins that organize supramolecular protein complexes, thereby partitioning the plasma membrane into spatially and functionally distinct subdomains. Their modular organization is ideally suited to organize protein complexes with cell type- or stage-specific composition, or both. Often more than one MAGUK isoform is expressed by one gene in the same cell, yet very little is known about their individual in vivo functions. Here, we show that two isoforms of Drosophila stardust, Sdt-H (formerly called Sdt-B2) and Sdt-D, which differ in their N terminus, are expressed in adult photoreceptors. Both isoforms associate with Crumbs and PATJ, constituents of the conserved Crumbs–Stardust complex. However, they form distinct complexes, localized at the stalk, a restricted region of the apical plasma membrane. Strikingly, Sdt-H and Sdt-D have antagonistic functions. While Sdt-H overexpression increases stalk membrane length and prevents light-dependent retinal degeneration, Sdt-D overexpression reduces stalk length and enhances light-dependent retinal degeneration. These results suggest that a fine-tuned balance of different Crumbs complexes regulates photoreceptor homeostasis.
A Centrosome-autonomous Signal That Involves Centriole Disengagement Permits Centrosome Duplication in G2 Phase after DNA Damage
Authors: Inanç Burcu , Dodson Helen , Morrison Ciaran G.
Published: September 2010

DNA damage can induce centrosome overduplication in a manner that requires G2-to-M checkpoint function, suggesting that genotoxic stress can decouple the centrosome and chromosome cycles. How this happens is unclear. Using live-cell imaging of cells that express fluorescently tagged NEDD1/GCP-WD and proliferating cell nuclear antigen, we found that ionizing radiation (IR)-induced centrosome amplification can occur outside S phase. Analysis of synchronized populations showed that significantly more centrosome amplification occurred after irradiation of G2-enriched populations compared with G1-enriched or asynchronous cells, consistent with G2 phase centrosome amplification. Irradiated and control populations of G2 cells were then fused to test whether centrosome overduplication is allowed through a diffusible stimulatory signal, or the loss of a duplication-inhibiting signal. Irradiated G2/irradiated G2 cell fusions showed significantly higher centrosome amplification levels than irradiated G2/unirradiated G2 fusions. Chicken–human cell fusions demonstrated that centrosome amplification was limited to the irradiated partner. Our finding that only the irradiated centrosome can duplicate supports a model where a centrosome-autonomous inhibitory signal is lost upon irradiation of G2 cells. We observed centriole disengagement after irradiation. Although overexpression of dominant-negative securin did not affect IR-induced centrosome amplification, Plk1 inhibition reduced radiation-induced amplification. Together, our data support centriole disengagement as a licensing signal for DNA damage-induced centrosome amplification.
Ligand Targeting of EphA2 Enhances Keratinocyte Adhesion and Differentiation via Desmoglein 1
Authors: Lin Samantha , Gordon Kristin , Kaplan Nihal , Getsios Spiro
Published: September 2010

EphA2 is a receptor tyrosine kinase that is engaged and activated by membrane-linked ephrin-A ligands residing on adjacent cell surfaces. Ligand targeting of EphA2 has been implicated in epithelial growth regulation by inhibiting the extracellular signal-regulated kinase 1/2 (Erk1/2)-mitogen activated protein kinase (MAPK) pathway. Although contact-dependent EphA2 activation was required for dampening Erk1/2-MAPK signaling after a calcium switch in primary human epidermal keratinocytes, the loss of this receptor did not prevent exit from the cell cycle. Incubating keratinocytes with a soluble ephrin-A1-Fc peptide mimetic to target EphA2 further increased receptor activation leading to its down-regulation. Moreover, soluble ligand targeting of EphA2 restricted the lateral expansion of epidermal cell colonies without limiting proliferation in these primary cultures. Rather, ephrin-A1-Fc peptide treatment promoted epidermal cell colony compaction and stratification in a manner that was associated with increased keratinocyte differentiation. The ligand-dependent increase in keratinocyte adhesion and differentiation relied largely upon the up-regulation of desmoglein 1, a desmosomal cadherin that maintains the integrity and differentiated state of suprabasal keratinocytes in the epidermis. These data suggest that keratinocytes expressing EphA2 in the basal layer may respond to ephrin-A1–based cues from their neighbors to facilitate entry into a terminal differentiation pathway.
Heparan Sulfate Acts as a Bone Morphogenetic Protein Coreceptor by Facilitating Ligand-induced Receptor Hetero-oligomerization
Authors: Kuo Wan-Jong , Digman Michelle A. , Lander Arthur D.
Published: September 2010

Cell surface heparan sulfate (HS) not only binds several major classes of growth factors but also sometimes potentiates their activities—an effect usually termed “coreception.” A view that coreception is due to the stabilization of growth factor–receptor interactions has emerged primarily from studies of the fibroblast growth factors (FGFs). Recent in vivo studies have strongly suggested that HS also plays an important role in regulating signaling by the bone morphogenetic proteins (BMPs). Here, we provide evidence that the mechanism of coreception for BMPs is markedly different from that established for FGFs. First, we demonstrate a direct, stimulatory role for cell surface HS in the immediate signaling activities of BMP2 and BMP4, and we provide evidence that HS–BMP interactions are required for this effect. Next, using several independent assays of ligand binding and receptor assembly, including coimmunoprecipitation, cross-linking, and fluorescence fluctuation microscopy, we show that HS does not affect BMP binding to type I receptor subunits but instead enhances the subsequent recruitment of type II receptor subunits to BMP-type I receptor complexes. This suggests a view of HS as a catalyst of the formation of signaling complexes, rather than as a stabilizer of growth factor binding.
Membrane Delivery to the Yeast Autophagosome from the Golgi–Endosomal System
Authors: Ohashi Yohei , Munro Sean
Published: September 2010

While many of the proteins required for autophagy have been identified, the source of the membrane of the autophagosome is still unresolved with the endoplasmic reticulum (ER), endosomes, and mitochondria all having been evoked. The integral membrane protein Atg9 is delivered to the autophagosome during starvation and in the related cytoplasm-to-vacuole (Cvt) pathway that occurs constitutively in yeast. We have examined the requirements for delivery of Atg9-containing membrane to the yeast autophagosome. Atg9 does not appear to originate from mitochondria, and Atg9 cannot reach the forming autophagosome directly from the ER or early Golgi. Components of traffic between Golgi and endosomes are known to be required for the Cvt pathway but do not appear required for autophagy in starved cells. However, we find that pairwise combinations of mutations in Golgi-endosomal traffic components apparently only required for the Cvt pathway can cause profound defects in Atg9 delivery and autophagy in starved cells. Thus it appears that membrane that contains Atg9 is delivered to the autophagosome from the Golgi-endosomal system rather than from the ER or mitochondria. This is underestimated by examination of single mutants, providing a possible explanation for discrepancies between yeast and mammalian studies on Atg9 localization and autophagosome formation.
Paradoxical Instability–Activity Relationship Defines a Novel Regulatory Pathway for Retinoblastoma Proteins
Authors: Acharya Pankaj , Raj Nitin , Buckley Martin S. , Zhang Liang , Duperon Stephanie , Williams Geoffrey , Henry R. William , Arnosti David N.
Published: September 2010

The Retinoblastoma (RB) transcriptional corepressor and related family of pocket proteins play central roles in cell cycle control and development, and the regulatory networks governed by these factors are frequently inactivated during tumorigenesis. During normal growth, these proteins are subject to tight control through at least two mechanisms. First, during cell cycle progression, repressor potential is down-regulated by Cdk-dependent phosphorylation, resulting in repressor dissociation from E2F family transcription factors. Second, RB proteins are subject to proteasome-mediated destruction during development. To better understand the mechanism for RB family protein instability, we characterized Rbf1 turnover in Drosophila and the protein motifs required for its destabilization. We show that specific point mutations in a conserved C-terminal instability element strongly stabilize Rbf1, but strikingly, these mutations also cripple repression activity. Rbf1 is destabilized specifically in actively proliferating tissues of the larva, indicating that controlled degradation of Rbf1 is linked to developmental signals. The positive linkage between Rbf1 activity and its destruction indicates that repressor function is governed in a manner similar to that described by the degron theory of transcriptional activation. Analogous mutations in the mammalian RB family member p107 similarly induce abnormal accumulation, indicating substantial conservation of this regulatory pathway.
SeqEM: an adaptive genotype-calling approach for next-generation sequencing studies
Authors: Martin E. R. , Kinnamon D. D. , Schmidt M. A. , Powell E. H. , Zuchner S. , Morris R. W.
Published: September 2010

Motivation: Next-generation sequencing presents several statistical challenges, with one of the most fundamental being determining an individual's genotype from multiple aligned short read sequences at a position. Some simple approaches for genotype calling apply fixed filters, such as calling a heterozygote if more than a specified percentage of the reads have variant nucleotide calls. Other genotype-calling methods, such as MAQ and SOAPsnp, are implementations of Bayes classifiers in that they classify genotypes using posterior genotype probabilities.

Results: Here, we propose a novel genotype-calling algorithm that, in contrast to the other methods, estimates parameters underlying the posterior probabilities in an adaptive way rather than arbitrarily specifying them a priori. The algorithm, which we call SeqEM, applies the well-known Expectation-Maximization algorithm to an appropriate likelihood for a sample of unrelated individuals with next-generation sequence data, leveraging information from the sample to estimate genotype probabilities and the nucleotide-read error rate. We demonstrate using analytic calculations and simulations that SeqEM results in genotype-call error rates as small as or smaller than filtering approaches and MAQ. We also apply SeqEM to exome sequence data in eight related individuals and compare the results to genotypes from an Illumina SNP array, showing that SeqEM behaves well in real data that deviates from idealized assumptions.

Conclusion: SeqEM offers an improved, robust and flexible genotype-calling approach that can be widely applied in the next-generation sequencing studies.

Availability and implementation: Software for SeqEM is freely available from our website: www.hihg.org under Software Download.

Contact:  emartin1@med.miami.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
SpotXplore: a Cytoscape plugin for visual exploration of hotspot expression in gene regulatory networks
Authors: Westenberg Michel A. , Roerdink Jos B.T.M. , Kuipers Oscar P. , van Hijum Sacha A.F.T.
Published: September 2010

Summary: SpotXplore is a plugin for Cytoscape for extraction and visualization of differentially expressed subnetworks (hotspots) from gene networks. The hotspot-based visualization approach enables interactive exploration of regulatory interactions in differentially expressed gene sets, and it allows a researcher to explore gene expression in direct relation to the affected cellular gene network. The hotspots provide a view beyond the commonly used metabolic pathways and gene ontologies.

Availability:  http://www.win.tue.nl/∼mwestenb/spotxplore/

Contact:  m.a.westenberg@tue.nl

Supplementary information: Example data and user manual are available at SpotXplore's web site.
MOBI: a web server to define and visualize structural mobility in NMR protein ensembles
Authors: Martin Alberto J. M. , Walsh Ian , Tosatto Silvio C. E.
Published: September 2010

Motivation: MOBI is a web server for the identification of structurally mobile regions in NMR protein ensembles. It provides a binary mobility definition that is analogous to the commonly used definition of intrinsic disorder in X-ray crystallographic structures. At least three different use cases can be envisaged: (i) visualization of NMR mobility for structural analysis; (ii) definition of regions for reliable comparative modelling in protein structure prediction and (iii) definition of mobility in analogy to intrinsic disorder. MOBI uses structural superposition and local conformational differences to derive a robust binary mobility definition that is in excellent agreement with the manually curated definition used in the CASP8 experiment for intrinsic disorder in NMR structure. The output includes mobility-coloured PDB files, mobility plots and a FASTA formatted sequence file summarizing the mobility results.

Availability: The MOBI server and supplementary methods are available for non-commercial use at URL: http://protein.bio.unipd.it/mobi/

Contact:  silvio.tosatto@unipd.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
DisGeNET: a Cytoscape plugin to visualize, integrate, search and analyze gene–disease networks
Authors: Bauer-Mehren Anna , Rautschka Michael , Sanz Ferran , Furlong Laura I.
Published: September 2010

Summary: DisGeNET is a plugin for Cytoscape to query and analyze human gene–disease networks. DisGeNET allows user-friendly access to a new gene–disease database that we have developed by integrating data from several public sources. DisGeNET permits queries restricted to (i) the original data source, (ii) the association type, (iii) the disease class or (iv) specific gene(s)/disease(s). It represents gene–disease associations in terms of bipartite graphs and provides gene centric and disease centric views of the data. It assists the user in the interpretation and exploration of the genetic basis of human diseases by a variety of built-in functions. Moreover, DisGeNET permits multicolouring of nodes (genes/diseases) according to standard disease classification for expedient visualization.

Availability: DisGeNET is compatible with Cytoscape 2.6.3 and 2.7.0, please visit http://ibi.imim.es/DisGeNET/DisGeNETweb.html for installation guide, user tutorial and download

Contact:  lfurlong@imim.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease
Authors: Kwon Beom‐June , Kim Dong‐Bin , Jang Sung‐Won , Yoo Ki‐Dong , Moon Keun‐Woong , Shim Byung Ju , Ahn Seo‐Hee , Cho Eun‐Ju , Rho Tae‐Ho , Kim Jae‐Hyung
Published: September 2010

Aims

The long‐term prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFPEF) and coexistent chronic obstructive pulmonary disease (COPD) has not been previously investigated. The primary aim of this study was to determine whether the long‐term prognosis of HFPEF patients with COPD differs from that of heart failure patients with reduced left ventricular ejection fraction (HFREF) and COPD. The secondary aim was to identify independent predictors of event‐free survival in patients with HF and COPD.

Methods and results

We investigated 184 patients with coexistent HF and COPD. Heart failure with preserved left ventricular ejection fraction was present in 98 cases (53%) and HFREF in the remaining 86 cases (47%). Mean follow‐up time was 731 ± 369 days. Cardiovascular/pulmonary hospitalization or mortality occurred in 71 patients (39%). No significant difference was observed between the two study groups in terms of event‐free survival (P = 0.457), but event‐free survival was found to be independently associated with New York Heart Association (NYHA) class [III vs. I, hazard ratio (HR) 2.92, 95% confidence interval (CI) 1.09–7.82], Global initiative for chronic Obstructive Lung Disease (GOLD) stage (III vs. I, HR 3.20, 95% CI 1.33–7.68), systemic hypertension (SHT; HR 2.99, 95% CI 1.41–6.33), and pulmonary hypertension (PH; HR 4.35, 95% CI 1.95–9.68).

Conclusion

In HF patients with coexisting COPD, cardiovascular and pulmonary event‐free survival of HFPEF was found to be similar to that of HFREF over 3 years follow‐up. Furthermore, severe NYHA class, severe GOLD stage, SHT, and PH were found to be independent predictors of event‐free survival.
Heart failure severity, as determined by loop diuretic dosages, predicts the risk of developing diabetes after myocardial infarction: a nationwide cohort study
Authors: Andersson Charlotte , Norgaard Mette L. , Hansen Peter R. , Fosbøl Emil L. , Schmiegelow Michelle , Weeke Peter , Olesen Jonas B. , Raunsø Jakob , Jørgensen Casper H. , Vaag Allan , Køber Lars , Torp‐Pedersen Christian , Gislason Gunnar H.
Published: September 2010

Aims

Heart failure (HF) is associated with increased insulin resistance, but the consequences of HF for development of diabetes are not well studied. The aim of the present study was to investigate the relationship between HF severity and risk of developing diabetes in a nationwide cohort of patients with myocardial infarction (MI).

Methods and results

Patients discharged from first‐time MI during 1997–2006 and not previously treated with glucose‐lowering medications (GLM) or loop diuretics were identified from Danish nationwide registers. Heart failure severity was determined by loop diuretic dosage after discharge. Patients were followed until first claimed prescription of GLM, death, or until the end of 2006. The cohort comprised 50 874 patients. A total of 3006 (6%) had mild (loop‐diuretic dosage ≤40 mg/day), 5383 (11%) moderate (>40–120 mg/day), and 1127 (2%) severe (>120 mg/day) HF. During follow‐up, 2531 (5%) patients developed diabetes. Increasing HF severity was associated with increased risk of diabetes, but the use of renin–angiotensin system inhibitors (RASi) attenuated the risk (P‐value for interaction between the HF group and RASi <0.05). Compared with no HF, the adjusted hazard ratios (95% confidence interval) for the development of diabetes were 1.34 (1.11–1.63), 1.63 (1.40–1.90), and 1.68 (1.25–2.25) for mild, moderate, and severe HF with RASi treatment; and 1.45 (1.13–1.88), 1.90 (1.56–2.33), and 3.02 (2.01–4.54) for mild, moderate, and severe HF without RASi treatment.

Conclusion

Heart failure predicts the development of diabetes in a severity‐dependent manner among patients with MI. Focus on increased predisposition to diabetes is warranted and needs further investigations.
Generic and disease‐specific quality of life as a predictor of long‐term mortality in heart failure
Authors: Zuluaga Maria Clemencia , Guallar‐Castillón Pilar , López‐García Esther , Banegas José R. , Conde‐Herrera Manuel , Olcoz‐Chiva Maite , Rodríguez‐Pascual Carlos , Rodriguez‐Artalejo Fernando
Published: September 2010

Aims

Although the vital prognosis of heart failure (HF) is generally poor, it varies substantially between patients. This study examined whether health‐related quality of life (HRQoL) predicts long‐term mortality in HF. It also evaluated the role of generic and disease‐specific HRQoL questionnaires.

Methods and results

We studied 416 patients admitted for HF‐related emergencies to four hospitals in Spain in 2000–2001. Health‐related quality of life was measured at study baseline with a generic questionnaire, the SF‐36, and with a disease‐specific one, the Minnesota Living with Heart Failure (MLWHF) questionnaire. Patients were followed prospectively to 2007 to ascertain all‐cause mortality. During follow‐up, 290 (69.7%) patients died. After adjustment for biomedical, healthcare, and social variables, a poor mental component summary (MCS) score on the SF‐36 was associated with higher mortality [hazard ratio (HR) 1.38; 95% confidence interval (CI) 1.06–1.76]. For MLWHF, a poor physical component summary (PCS) score predicted higher mortality (HR 1.31; 95% CI 1.01–1.70). In a stepwise Cox model that included the PCS scores of both the SF‐36 and the MLWHF, only the PCS of the MLWHF was retained with P < 0.05. However, when both MCS scores were included, only the MCS of the SF‐36 was retained with P < 0.05.

Conclusion

The SF‐36 MCS and the MLWHF PCS predict long‐term mortality in patients with HF. Future research should identify the determinants of HRQoL and refine interventions to improve it.
Intestinal Mucosal Permeability of Severely Underweight and Nonmalnourished Bangladeshi Children and Effects of Nutritional Rehabilitation
Authors: Hossain Md Iqbal , Nahar Baitun , Hamadani Jena D , Ahmed Tahmeed , Roy Anjan Kumar , Brown Kenneth H
Published: September 2010

Objective:

Lactulose/mannitol (L/M) intestinal permeability tests were completed to compare the intestinal function of severely underweight children recovering from diarrhea and other illnesses and of nonmalnourished children from the same communities, and to evaluate the effects of food supplementation, with or without psychosocial stimulation, on the changes in intestinal function among the underweight children.

Patients and Methods:

Seventy‐seven malnourished children completed intestinal permeability studies at baseline and 3 months after receiving 1 of the following randomly assigned treatment regimens: group‐C—fortnightly follow‐up at community‐based follow‐up units, including growth monitoring and promotion, health education, and micronutrient supplementation, n = 17; group‐SF—same as group‐C plus supplementary food (SF) to provide 150 to 300 kcal/day, n = 23; group‐PS—same as group‐C plus psychosocial stimulation (PS), n = 17; or group‐SF + PS—same as group‐C plus SF and PS, n = 20. Seventeen nonmalnourished children were included as comparison subjects.

Results:

The malnourished children's mean ± SD initial age was 13.1 ± 4.0 months, their mean weight‐for‐age z score was −3.82 ± 0.61, and their median (interquartile range) urinary L/M recovery ratio was 0.16 (0.10–0.28). Eighty‐four percent of the children had L/M ≥0.07, suggestive of impaired intestinal function. The median L/M of the malnourished children was significantly greater than that of 17 relatively well‐nourished children (median 0.09; interquartile range 0.05–0.12; P = 0.001). There were no significant differences in baseline characteristics of the severely malnourished children by treatment group. Following treatment, the L/M ratio improved in all of the groups (P < 0.001), but there were no significant differences in these changes by treatment group. There was a significant positive association between weight gain and the magnitude of improvement in L/M ratio (r = 0.30, P = 0.012).

Conclusions:

Intestinal mucosal function, as measured by sugar permeability, is impaired among severely underweight children. Intestinal permeability improves in relation to weight gain, but intestinal mucosal recovery is not specifically related to the types or amount of food supplementation or PS provided in this trial.
Examining the Relative Validity of an Adult Food Frequency Questionnaire in Children and Adolescents
Authors: Shatenstein Bryna , Amre Devendra , Jabbour Mira , Feguery Houda
Published: September 2010

Background and Objective:

Dietary factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). The aim of the study was to assess the accuracy of a food frequency questionnaire (FFQ) developed in French and English for adults 18 years and older, among subjects ages 7 to 18 years participating in a prospective cohort study.

Patients and Methods:

Healthy children and adolescents ages 7 to 18 years were recruited from outpatient orthopedic clinics in a Montréal pediatric hospital. Of the 131 recruits, 65 (86% Francophone) provided a complete 78‐item semiquantitative FFQ and 3‐day nonconsecutive food records (3D‐FR). Parents of young children completed both instruments, whereas older children and adolescents completed them on their own. The FFQ were analyzed using Microsoft Access software for customized data entry and the 3D‐FR were analyzed using CANDAT software, both based on the 2007b Canadian Nutrient File.

Results:

The FFQ overestimated intakes relative to the 3D‐FR by around 15%. Spearman rank correlation coefficients between test and reference methods were positive, largely ranged from 0.22 (vitamin C) to 0.57 (saturated fat), and were generally statistically significant (0.05< P < 0.0001). Stronger associations between test and reference methods were found for adolescents (13–18 years) and for girls. Some 77% of participants were jointly classified into the same half of the distribution, with 39% exact agreement and only 6% frank misclassification.

Conclusions:

The FFQ can be confidently used to rank young subjects on a range of nutrient intakes with the potential to provide useful information on dietary risk factors in the etiology of inflammatory bowel disease. Accuracy could be enhanced by improving completion quality of FFQs, notably by young adolescent boys.
Uneven distribution of cryptic diversity among higher taxa of parasitic worms
Authors: Poulin Robert
Published: September 2010

Cryptic species cause problems for estimates of biodiversity. In the case of parasites, cryptic species also plague efforts to detect potential zoonotic diseases or invasive pathogens. It is crucial to determine whether the likelihood of finding cryptic species differs among higher parasite taxa, to better calibrate estimates of diversity and monitor diseases. Using published reports of cryptic species of helminth parasites identified using molecular tools, I show that the number of species found is strongly related to the number of parasite individuals sequenced, weakly influenced by the number of host species from which parasites were obtained, and unaffected by the genetic markers used. After correction for these factors, more cryptic species of trematodes are found than in other helminth taxa. Although several features distinguish trematodes from other helminths, it is probable that our inability to discriminate among sibling species of trematodes results from their lack of structures serving as species-specific morphological markers. The available data suggest that current estimates of helminth diversity may need to be doubled (tripled for trematodes) to better reflect extant diversity.
Extreme male leg polymorphic asymmetry in a new empidine dance fly (Diptera: Empididae)
Authors: Daugeron Christophe , Plant Adrian , Winkler Isaac , Stark Andreas , Baylac Michel
Published: September 2010

A new dance fly (Empididae: Empidinae) with hugely modified male fore tarsus, either on the right, left, both or neither sides, is described from Japan. Such massive polymorphic asymmetry occurring with so high an incidence in a population is previously unreported. In view of the courtship behaviour of other Empidinae, we hypothesize that the oversized tarsus is a secondary sexual character employed by males for attracting females. Alternative hypotheses are also discussed. We suggest that this extraordinary new species is a potential model for the study of mating biology in Empidinae and the evolution of mating systems in general.
Engineering extracellular matrix through nanotechnology
Authors: Kelleher Cassandra M. , Vacanti Joseph P.
Published: September 2010

The goal of tissue engineering is the creation of a living device that can restore, maintain or improve tissue function. Behind this goal is a new idea that has emerged from twentieth century medicine, science and engineering. It is preceded by centuries of human repair and replacement with non-living materials adapted to restore function and cosmetic appearance to patients whose tissues have been destroyed by disease, trauma or congenital abnormality. The nineteenth century advanced replacement and repair strategies based on moving living structures from a site of normal tissue into a site of defects created by the same processes. Donor skin into burn wounds, tendon transfers, intestinal replacements into the urinary tract, toes to replace fingers are all examples. The most radical application is that of vital organ transplantation in which a vital part such as heart, lung or liver is removed from one donor, preserved for transfer and implanted into a patient dying of end-stage organ failure. Tissue engineering and regenerative medicine have advanced a general strategy combining the cellular elements of living tissue with sophisticated biomaterials to produce living structures of sufficient size and function to improve patients' lives. Multiple strategies have evolved and the application of nanotechnology can only improve the field. In our era, by necessity, any medical advance must be successfully commercialized to allow widespread application to help the greatest number of patients. It follows that business models and regulatory agencies must adapt and change to enable these new technologies to emerge. This brief review will discuss the science of nanotechnology and how it has been applied to this evolving field. We will then briefly summarize the history of commercialization of tissue engineering and suggest that nanotechnology may be of use in breeching the barriers to commercialization although its primary mission is to improve the technology by solving some remaining and vexing problems in its science and engineering aspects.
The nosocomial transmission rate of animal-associated ST398 meticillin-resistantStaphylococcus aureus
Authors: Bootsma Martin C. J. , Wassenberg Marjan W. M. , Trapman Pieter , Bonten Marc J. M.
Published: September 2010

The global epidemiology of meticillin-resistantStaphylococcus aureus(MRSA) is characterized by different clonal lineages with different epidemiological behaviour. There are pandemic hospital clones (hospital-associated (HA-)MRSA), clones mainly causing community-acquired infections (community-associated (CA-)MRSA, mainly USA300) and an animal-associated clone (ST398) emerging in European and American livestock with subsequent spread to humans. Nosocomial transmission capacities (RA) of these different MRSA types have never been quantified. Using two large datasets from MRSA outbreaks in Dutch hospitals (dataset 1, the UMC Utrecht for 144 months; dataset 2, 51 hospitals for six months) and a recently developed mathematical model, we determined the genotype-specificRAfor ST398 and non-ST398 isolates (categorized as HA-MRSA), using observational data, the detection rate of MRSA carriage and the discharge rate from hospital as the input. After detection of 42 MRSA index cases in dataset 1 (all non-ST398 MRSA) 5076 people were screened, yielding 30 secondary cases. In dataset 2, 75 index cases (51 non-ST398 MRSA and 24 ST398) resulted in 7892 screened individuals and 56 and three secondary cases for non-ST398 MRSA and ST398, respectively. The ratio between discharge and the detection rate was 2.7.RAvalues (95% confidence interval (CI)) were 0.68 (0.47–0.95) for non-ST398 MRSA in dataset 1, 0.93 (0.71–1.21) for non-ST398 MRSA in dataset 2 and 0.16 (0.04–0.40) for ST398. TheRAratio between non-ST398 MRSA and ST398 was 5.90 (95% CI 2.24–23.81). ST398 is 5.9 times less transmissible than non-ST398 MRSA in Dutch hospitals, which may allow less stringent transmission-control measures for ST398 MRSA.
Julian Huxley, general biology and the London Zoo, 1935–42
Authors: Cain Joe
Published: September 2010

While Secretary of the Zoological Society of London (1935–42), Julian Huxley used that institution to undertake several types of reform related to his promotion of ‘general biology’. Huxley's goal was to place synthetic, analytical and explanatory work at the centre of the life sciences. Here, zoological specifics served only as instances of generic processes. Huxley's campaigning fitted both into his own lifelong obsession with synoptic views and into much larger transformations in the epistemic culture of the life sciences during the interwar years. However, such campaigns also had their detractors, and the Zoological Society of London provides a superb example of the backlash provoked against these reforms. In 1942 that backlash led directly to Huxley's dismissal as Secretary of that society. This episode serves as a reminder to understand the plurality of views in play during any historical period. In this case, general biology was resisted in a factional dispute over what should be the priority of the life sciences: objects versus processes, induction versus explanation, and particulars versus generics.