bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Molecular Epidemiology of Healthcare-Associated Infections Due to Extended-Spectrumβ-Lactamase (ESBL)–Producing Strains ofEscherichia coliandKlebsiella pneumoniaeThat Harbor Multiple ESBL Genes
Authors: Apisarnthanarak Anucha , Kiratisin Pattarachai , Mundy Linda M.
Published: October 2008

Objectives.

To characterize healthcare-associated infections due to extended-spectrumβ-lactamase (ESBL)-producing strains ofEscherichia coliandKlebsiella pneumoniaethat harbor multiple ESBL genes, as opposed to a single ESBL gene.

Methods.

All patients with a confirmed healthcare-associated infection due to an ESBL-producing strain ofE. coliorK. pneumoniaewere enrolled in the study. Molecular typing of isolates was performed, and the comparative risks and outcomes of patients were analyzed.

Results.

Among 71 patients with healthcare-associated infection due to an ESBL-producing strain ofE. coliorK. pneumoniae, the gene for CTX-M, with or without other ESBL genes, was identified in all 51 (100%) of the patients infected with anE. colistrain and in 18 (90%) of the 20 patients infected with aK. pneumoniaestrain. Of these 71 patients, 17 (24%) met the definition of healthcare-associated infection due to an ESBL-producing strain that harbored multiple genes; in multivariate analysis, previous exposure to 3 or more classes of antibiotics (adjusted odds ratio, 4.5 [95% confidence interval, 1.7-75.2]) was the sole risk factor for healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes. Isolates recovered from patients with healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes were more resistant to various antibiotic classes, and, compared with patients with healthcare-associated infection due to an ESBL-producing strain that harbored a single ESBL gene, they were more likely to have ineffective initial empirical antimicrobial therapy (52% vs 94%; odds ratio, 5.1 [95% confidence interval, 1.04-14.5]).

Conclusions.

CTX-M ESBL is highly prevalent in Thailand. Patients with healthcare-associated infection due to an ESBL-producing strain that harbored multiple ESBL genes were more likely to have had ineffective initial empirical antimicrobial therapy, and, given that antibiotic selection pressure was the only associated risk, we suggest focused antimicrobial stewardship programs to limit the emergence and spread of healthcare-associated infection due to ESBL-producing strains in this middle-income country.
On the lowest two-sided cell in affine Weyl groups
Authors: Guilhot Jérémie
Published: October 2008

Bremke and Xi determined the lowest two-sided cell for affine Weyl groups with unequal parameters and showed that it consists of at most|W0||W_{0}|left cells whereW0W_{0}is the associated finite Weyl group. We prove that this bound is exact. Previously, this was known in the equal parameter case and when the parameters were coming from a graph automorphism. Our argument uniformly works for any choice of parameters.
Admissible 𝑊-graphs
Authors: Stembridge John
Published: October 2008

Given a Coxeter group

W
W

, a

W
W

-graph

Γ
\Gamma

encodes a module

M

Γ

M_{\Gamma }

for the associated Iwahori-Hecke algebra

H

\mathcal {H}

. The strongly connected components of 

Γ
\Gamma

, known as cells, are also

W
W

-graphs, and their modules occur as subquotients in a filtration of

M

Γ

M_{\Gamma }

. Of special interest are the

W
W

-graphs and cells arising from the Kazhdan-Lusztig basis for the regular representation of

H

\mathcal {H}

. We define a

W
W

-graph to be admissible if, like the Kazhdan-Lusztig

W
W

-graphs, it is edge-symmetric, bipartite, and has nonnegative integer edge weights. Empirical evidence suggests that for finite

W
W

, there are only finitely many admissible

W
W

-cells. We provide a combinatorial characterization of admissible

W
W

-graphs, and use it to classify the admissible

W
W

-cells for various finite

W
W

of low rank. In the rank two case, the nontrivial admissible cells turn out to be

A
A

-

D
D

-

E
E

Dynkin diagrams.
Neonatal Fc Receptor Mediates Internalization of Fc in Transfected Human Endothelial Cells
Authors: Goebl Nancy A. , Babbey Clifford M. , Datta-Mannan Amita , Witcher Derrick R. , Wroblewski Victor J. , Dunn Kenneth W.
Published: October 2008

The neonatal Fc receptor, FcRn mediates an endocytic salvage pathway that prevents degradation of IgG, thus contributing to the homeostasis of circulating IgG. Based on the low affinity of IgG for FcRn at neutral pH, internalization of IgG by endothelial cells is generally believed to occur via fluid-phase endocytosis. To investigate the role of FcRn in IgG internalization, we used quantitative confocal microscopy to characterize internalization of fluorescent Fc molecules by HULEC-5A lung microvascular endothelia transfected with GFP fusion proteins of human or mouse FcRn. In these studies, cells transfected with FcRn accumulated significantly more intracellular Fc than untransfected cells. Internalization of FcRn-binding forms of Fc was proportional to FcRn expression level, was enriched relative to dextran internalization in proportion to FcRn expression level, and was blocked by incubation with excess unlabeled Fc. Because we were unable to detect either surface expression of FcRn or surface binding of Fc, these results suggest that FcRn-dependent internalization of Fc may occur through sequestration of Fc by FcRn in early endosomes. These studies indicate that FcRn-dependent internalization of IgG may be important not only in cells taking up IgG from an extracellular acidic space, but also in endothelial cells participating in homeostatic regulation of circulating IgG levels.
Beclin 1 Forms Two Distinct Phosphatidylinositol 3-Kinase Complexes with Mammalian Atg14 and UVRAG
Authors: Itakura Eisuke , Kishi Chieko , Inoue Kinji , Mizushima Noboru
Published: October 2008

Class III phosphatidylinositol 3-kinase (PI3-kinase) regulates multiple membrane trafficking. In yeast, two distinct PI3-kinase complexes are known: complex I (Vps34, Vps15, Vps30/Atg6, and Atg14) is involved in autophagy, and complex II (Vps34, Vps15, Vps30/Atg6, and Vps38) functions in the vacuolar protein sorting pathway. Atg14 and Vps38 are important in inducing both complexes to exert distinct functions. In mammals, the counterparts of Vps34, Vps15, and Vps30/Atg6 have been identified as Vps34, p150, and Beclin 1, respectively. However, orthologues of Atg14 and Vps38 remain unknown. We identified putative mammalian homologues of Atg14 and Vps38. The Vps38 candidate is identical to UV irradiation resistance-associated gene (UVRAG), which has been reported as a Beclin 1-interacting protein. Although both human Atg14 and UVRAG interact with Beclin 1 and Vps34, Atg14, and UVRAG are not present in the same complex. Although Atg14 is present on autophagic isolation membranes, UVRAG primarily associates with Rab9-positive endosomes. Silencing of human Atg14 in HeLa cells suppresses autophagosome formation. The coiled-coil region of Atg14 required for binding with Vps34 and Beclin 1 is essential for autophagy. These results suggest that mammalian cells have at least two distinct class III PI3-kinase complexes, which may function in different membrane trafficking pathways.
Mgr3p and Mgr1p Are Adaptors for the Mitochondrial i-AAA Protease Complex
Authors: Dunn Cory D. , Tamura Yasushi , Sesaki Hiromi , Jensen Robert E.
Published: October 2008

By screening yeast knockouts for their dependence upon the mitochondrial genome, we identified Mgr3p, a protein that associates with the i-AAA protease complex in the mitochondrial inner membrane. Mgr3p and Mgr1p, another i-AAA-interacting protein, form a subcomplex that bind to the i-AAA subunit Yme1p. We find that loss of Mgr3p, like the lack of Mgr1p, reduces proteolysis by Yme1p. Mgr3p and Mgr1p can bind substrate even in the absence of Yme1p, and both proteins are needed for maximal binding of an unfolded substrate by the i-AAA complex. We speculate that Mgr3p and Mgr1p function in an adaptor complex that targets substrates to the i-AAA protease for degradation.
Role of the RAM Network in Cell Polarity and Hyphal Morphogenesis inCandida albicans
Authors: Song Yunkyoung , Cheon Seon Ah , Lee Kyung Eun , Lee So-Yeon , Lee Byung-Kyu , Oh Doo-Byung , Kang Hyun Ah , Kim Jeong-Yoon
Published: October 2008

RAM (regulation of Ace2p transcription factor and polarized morphogenesis) is a conserved signaling network that regulates polarized morphogenesis in yeast, worms, flies, and humans. To investigate the role of the RAM network in cell polarity and hyphal morphogenesis of Candida albicans, each of the C. albicans RAM genes (CaCBK1, CaMOB2, CaKIC1, CaPAG1, CaHYM1, and CaSOG2) was deleted. All C. albicans RAM mutants exhibited hypersensitivity to cell-wall- or membrane-perturbing agents, exhibiting cell-separation defects, a multinucleate phenotype and loss of cell polarity. Yeast two-hybrid and in vivo functional analyses of CaCbk1p and its activator, CaMob2p, the key factors in the RAM network, demonstrated that the direct interaction between the SMA domain of CaCbk1p and the Mob1/phocein domain of CaMob2p was necessary for hyphal growth of C. albicans. Genome-wide transcription profiling of a Camob2 mutant suggested that the RAM network played a role in serum- and antifungal azoles–induced activation of ergosterol biosynthesis genes, especially those involved in the late steps of ergosterol biosynthesis, and might be associated, at least indirectly, with the Tup1p-Nrg1p pathway. Collectively, these results demonstrate that the RAM network is critically required for hyphal growth as well as normal vegetative growth in C. albicans.
Regulation of the Anaphase-promoting Complex–Separase Cascade by Transforming Growth Factor-β Modulates Mitotic Progression in Bone Marrow Stromal Cells
Authors: Fujita Takeo , Epperly Michael W. , Zou Hui , Greenberger Joel S. , Wan Yong
Published: October 2008

Alteration of the tumor microenvironment by aberrant stromal cells influences many aspects of cell biology, including differentiation of stem cells and tumor metastasis. The role of transforming growth factor (TGF)-β signaling in stromal cells of the tissue microenvironment is critical to both pathways. We examined murine marrow stromal cells with deletion of Smad3 and found that they have an altered cell cycle profile, with a higher fraction of cells in G2/M phase. Deletion of Smad3 significantly abrogates TGF-β signaling and suppresses phosphorylation of CDC27–anaphase-promoting complex (APC) during mitosis, thereby resulting in elevated cyclin-dependent kinase (CDK)1 activity via increased levels of cyclin B. Enhanced CDK1 activity due to deregulation of APC leads in turn to hyperphosphorylation of separase, impeding chromatid separation. A residue Ser1126Ala mutation in separase specifically abolished separase hyperphosphorylation in Smad3-deficient cells. The present results unveil a new function for the TGF-β pathway in the regulation of APC to mediate chromatid separation during mitosis.
Role of LPA4/p2y9/GPR23 in Negative Regulation of Cell Motility
Authors: Lee Zendra , Cheng Ching-Ting , Zhang Helen , Subler Mark A. , Wu Jinhua , Mukherjee Abir , Windle Jolene J. , Chen Ching-Kang , Fang Xianjun
Published: October 2008

Lysophosphatidic acid (LPA) is a ligand of multiple G protein–coupled receptors. The LPA1–3receptors are members of the endothelial cell differentiation gene (Edg) family. LPA4/p2y9/GPR23, a member of the purinergic receptor family, and recently identified LPA5/GPR92 and p2y5 are structurally distant from the canonical Edg LPA receptors. Here we report targeted disruption of lpa4in mice. Although LPA4-deficient mice displayed no apparent abnormalities, LPA4-deficient mouse embryonic fibroblasts (MEFs) were hypersensitive to LPA-induced cell migration. Consistent with negative modulation of the phosphatidylinositol 3 kinase pathway by LPA4, LPA4deficiency potentiated Akt and Rac but decreased Rho activation induced by LPA. Reconstitution of LPA4converted LPA4-negative cells into a less motile phenotype. In support of the biological relevance of these observations, ectopic expression of LPA4strongly inhibited migration and invasion of human cancer cells. When coexpressed with LPA1in B103 neuroblastoma cells devoid of endogenous LPA receptors, LPA4attenuated LPA1-driven migration and invasion, indicating functional antagonism between the two subtypes of LPA receptors. These results provide genetic and biochemical evidence that LPA4is a suppressor of LPA-dependent cell migration and invasion in contrast to the motility-stimulating Edg LPA receptors.
CCAAT/Enhancer-binding Protein β Promotes Osteoblast Differentiation by Enhancing Runx2 Activity with ATF4
Authors: Tominaga Hiroyuki , Maeda Shingo , Hayashi Makoto , Takeda Shu , Akira Shizuo , Komiya Setsuro , Nakamura Takashi , Akiyama Haruhiko , Imamura Takeshi
Published: October 2008

Although CCAAT/enhancer-binding protein β (C/EBPβ) is involved in osteocalcin gene expression in osteoblast in vitro, the physiological importance of and molecular mechanisms governing C/EBPβ in bone formation remain to be elucidated. In particular, it remains unclear whether C/EBPβ acts as a homodimer or a heterodimer with other proteins during osteoblast differentiation. Here, deletion of the C/EBPβ gene from mice resulted in delayed bone formation with concurrent suppression of chondrocyte maturation and osteoblast differentiation. The expression of type X collagen as well as chondrocyte hypertrophy were suppressed in mutant bone, providing new insight into the possible roles of C/EBPβ in chondrocyte maturation. In osteoblasts, luciferase reporter, gel shift, DNAP, and ChIP assays demonstrated that C/EBPβ heterodimerized with activating transcription factor 4 (ATF4), another basic leucine zipper transcription factor crucial for osteoblast maturation. This complex interacted and transactivated osteocalcin-specific element 1 (OSE1) of the osteocalcin promoter. C/EBPβ also enhanced the synergistic effect of ATF4 and Runx2 on osteocalcin promoter transactivation by enhancing their interaction. Thus, our results provide evidence that C/EBPβ is a crucial cofactor in the promotion of osteoblast maturation by Runx2 and ATF4.
Distinct Isoforms of the RFX Transcription Factor DAF-19 Regulate Ciliogenesis and Maintenance of Synaptic Activity
Authors: Senti Gabriele , Swoboda Peter
Published: October 2008

Neurons form elaborate subcellular structures such as dendrites, axons, cilia, and synapses to receive signals from their environment and to transmit them to the respective target cells. In the worm Caenorhabditis elegans, lack of the RFX transcription factor DAF-19 leads to the absence of cilia normally found on 60 sensory neurons. We now describe and functionally characterize three different isoforms of DAF-19. The short isoform DAF-19C is specifically expressed in ciliated sensory neurons and sufficient to rescue all cilia-related phenotypes of daf-19 mutants. In contrast, the long isoforms DAF-19A/B function in basically all nonciliated neurons. We discovered behavioral and cellular phenotypes in daf-19 mutants that depend on the isoforms daf-19a/b. These novel synaptic maintenance phenotypes are reminiscent of synaptic decline seen in many human neurodegenerative disorders. The C. elegans daf-19 mutant worms can thus serve as a molecular model for the mechanisms of functional neuronal decline.
The Yeast LATS/Ndr Kinase Cbk1 Regulates Growth via Golgi-dependent Glycosylation and Secretion
Authors: Kurischko Cornelia , Kuravi Venkata K. , Wannissorn Nattha , Nazarov Pavel A. , Husain Michelle , Zhang Chao , Shokat Kevan M. , McCaffery J. Michael , Luca Francis C.
Published: October 2008

Saccharomyces cerevisiae Cbk1 is a LATS/Ndr protein kinase and a downstream component of the regulation of Ace2 and morphogenesis (RAM) signaling network. Cbk1 and the RAM network are required for cellular morphogenesis, cell separation, and maintenance of cell integrity. Here, we examine the phenotypes of conditional cbk1 mutants to determine the essential function of Cbk1. Cbk1 inhibition severely disrupts growth and protein secretion, and triggers the Swe1-dependent morphogenesis checkpoint. Cbk1 inhibition also delays the polarity establishment of the exocytosis regulators Rab-GTPase Sec4 and its exchange factor Sec2, but it does not interfere with actin polarity establishment. Cbk1 binds to and phosphorylates Sec2, suggesting that it regulates Sec4-dependent exocytosis. Intriguingly, Cbk1 inhibition causes a >30% decrease in post-Golgi vesicle accumulation in late secretion mutants, indicating that Cbk1 also functions upstream of Sec2-Sec4, perhaps at the level of the Golgi. In agreement, conditional cbk1 mutants mislocalize the cis-Golgi mannosyltransferase Och1, are hypersensitive to the aminoglycoside hygromycin B, and exhibit diminished invertase and Sim1 glycosylation. Significantly, the conditional lethality and hygromycin B sensitivity of cbk1 mutants are suppressed by moderate overexpression of several Golgi mannosyltransferases. These data suggest that an important function for Cbk1 and the RAM signaling network is to regulate growth and secretion via Golgi and Sec2/Sec4-dependent processes.
SNARE Function Is Not Involved in Early Endosome Docking
Authors: Geumann Ulf , Barysch Sina Victoria , Hoopmann Peer , Jahn Reinhard , Rizzoli Silvio O.
Published: October 2008

Docking and fusion of transport vesicles constitute elementary steps in intracellular membrane traffic. While docking is thought to be initiated by Rab-effector complexes, fusion is mediated by SNARE (N-ethylmaleimide-sensitive factor [NSF] attachment receptor) proteins. However, it has been recently debated whether SNAREs also play a role in the establishment or maintenance of a stably docked state. To address this question, we have investigated the SNARE dependence of docking and fusion of early endosomes, one of the central sorting compartments in the endocytic pathway. A new, fluorescence-based in vitro assay was developed, which allowed us to investigate fusion and docking in parallel. Similar to homotypic fusion, docking of early endosomes is dependent on the presence of ATP and requires physiological temperatures. Unlike fusion, docking is insensitive to the perturbation of SNARE function by means of soluble SNARE motifs, SNARE-specific Fabfragments, or by a block of NSF activity. In contrast, as expected, docking is strongly reduced by interfering with the synthesis of phosphatidyl inositol (PI)-3 phosphate, with the function of Rab-GTPases, as well as with early endosomal autoantigen 1 (EEA1), an essential tethering factor. We conclude that docking of early endosomes is independent of SNARE function.
The C-Terminal Tail Region of Nonmuscle Myosin II Directs Isoform-specific Distribution in Migrating Cells
Authors: Sandquist Joshua C. , Means Anthony R.
Published: October 2008

Nonmuscle myosin II isoforms A and B (hereafter, IIA and IIB) perform unique roles in cell migration, even though both isoforms share the same basic molecular functions. That IIA and IIB assume distinct subcellular distribution in migrating cells suggests that discrete spatiotemporal regulation of each isoform's activity may provide a basis for its unique migratory functions. Here, we make the surprising finding that swapping a small C-terminal portion of the tail between IIA and IIB inverts the distinct distribution of these isoforms in migrating cells. Moreover, swapping this region between isoforms also inverts their specific turnover properties, as assessed by fluorescence recovery after photobleaching and Triton solubility. These data, acquired through the use of chimeras of IIA and IIB, suggest that the C-terminal region of the myosin heavy chain supersedes the distinct motor properties of the two isoforms as the predominant factor directing isoform-specific distribution. Furthermore, our results reveal a correlation between isoform solubility and distribution, leading to the proposal that the C-terminal region regulates isoform distribution by tightly controlling the amount of each isoform that is soluble and therefore available for redistribution into new protrusions.
The AP-2 Adaptor β2 Appendage Scaffolds Alternate Cargo Endocytosis
Authors: Keyel Peter A. , Thieman James R. , Roth Robyn , Erkan Elif , Everett Eric T. , Watkins Simon C. , Heuser John E. , Traub Linton M.
Published: October 2008

The independently folded appendages of the large α and β2 subunits of the endocytic adaptor protein (AP)-2 complex coordinate proper assembly and operation of endocytic components during clathrin-mediated endocytosis. The β2 subunit appendage contains a common binding site for β-arrestin or the autosomal recessive hypercholesterolemia (ARH) protein. To determine the importance of this interaction surface in living cells, we used small interfering RNA-based gene silencing. The effect of extinguishing β2 subunit expression on the internalization of transferrin is considerably weaker than an AP-2 α subunit knockdown. We show the mild sorting defect is due to fortuitous substitution of the β2 chain with the closely related endogenous β1 subunit of the AP-1 adaptor complex. Simultaneous silencing of both β1 and β2 subunit transcripts recapitulates the strong α subunit RNA interference (RNAi) phenotype and results in loss of ARH from endocytic clathrin coats. An RNAi-insensitive β2-yellow fluorescent protein (YFP) expressed in the β1 + β2-silenced background restores cellular AP-2 levels, robust transferrin internalization, and ARH colocalization with cell surface clathrin. The importance of the β appendage platform subdomain over clathrin for precise deposition of ARH at clathrin assembly zones is revealed by a β2-YFP with a disrupted ARH binding interface, which does not restore ARH colocalization with clathrin. We also show a β-arrestin 1 mutant, which engages coated structures in the absence of any G protein-coupled receptor stimulation, colocalizes with β2-YFP and clathrin even in the absence of an operational clathrin binding sequence. These findings argue against ARH and β-arrestin binding to a site upon the β2 appendage platform that is later obstructed by polymerized clathrin. We conclude that ARH and β-arrestin depend on a privileged β2 appendage site for proper cargo recruitment to clathrin bud sites.
IPEP: an in silico tool to examine proteolytic peptides for mass spectrometry
Authors: Lu Dihui , Liu Richard Z. , Izumi Victoria , Fenstermacher David , Haura Eric B. , Koomen John , Eschrich Steven A.
Published: October 2008

Peptide-based proteomics supports identification and quantification as well as localization of post-translational modifications (PTMs) within proteins extracted from biological samples. The ‘bottom-up’ approach involves the digestion of proteins into peptide fragments that can be detected and sequenced with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A web-based application, iPEP, was developed to compare the effectiveness of different proteolytic digests in detecting specific sequences. Furthermore, peptide populations can be examined to help optimize detection of certain groups of proteins relative to the proteome and the digested peptidome. The application reports proteolytic peptide sequences, theoretical molecular weights and functional annotations using Gene Ontology (GO) terms. The iPEP tool can assist with experimental design by maximizing the detection of proteins, consensus sites and modified residues of interest for individual proteins or as part of large-scale proteomic assays.

Availability:  http://ipep.moffitt.org

Contact:  steven.eschrich@moffitt.org; john.koomen@moffitt.org
Inferring population history withDIY ABC: a user-friendly approach to approximate Bayesian computation
Authors: Cornuet Jean-Marie , Santos Filipe , Beaumont Mark A. , Robert Christian P. , Marin Jean-Michel , Balding David J. , Guillemaud Thomas , Estoup Arnaud
Published: October 2008

Summary: Genetic data obtained on population samples convey information about their evolutionary history. Inference methods can extract part of this information but they require sophisticated statistical techniques that have been made available to the biologist community (through computer programs) only for simple and standard situations typically involving a small number of samples. We propose here a computer program (DIY ABC) for inference based on approximate Bayesian computation (ABC), in which scenarios can be customized by the user to fit many complex situations involving any number of populations and samples. Such scenarios involve any combination of population divergences, admixtures and population size changes. DIY ABC can be used to compare competing scenarios, estimate parameters for one or more scenarios and compute bias and precision measures for a given scenario and known values of parameters (the current version applies to unlinked microsatellite data). This article describes key methods used in the program and provides its main features. The analysis of one simulated and one real dataset, both with complex evolutionary scenarios, illustrates the main possibilities of DIY ABC.

Availability: The software DIY ABC is freely available at http://www.montpellier.inra.fr/CBGP/diyabc.

Contact:  j.cornuet@imperial.ac.uk

Supplementary information: Supplementary data are also available at http://www.montpellier.inra.fr/CBGP/diyabc
GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus
Authors: Zhu Yuelin , Davis Sean , Stephens Robert , Meltzer Paul S. , Chen Yidong
Published: October 2008

The NCBI Gene Expression Omnibus (GEO) represents the largest public repository of microarray data. However, finding data in GEO can be challenging. We have developed GEOmetadb in an attempt to make querying the GEO metadata both easier and more powerful. All GEO metadata records as well as the relationships between them are parsed and stored in a local MySQL database. A powerful, flexible web search interface with several convenient utilities provides query capabilities not available via NCBI tools. In addition, a Bioconductor package, GEOmetadb that utilizes a SQLite export of the entire GEOmetadb database is also available, rendering the entire GEO database accessible with full power of SQL-based queries from within R.

Availability: The web interface and SQLite databases available at http://gbnci.abcc.ncifcrf.gov/geo/. The Bioconductor package is available via the Bioconductor project. The corresponding MATLAB implementation is also available at the same website.

Contact:  yidong@mail.nih.gov
A flexible forward simulator for populations subject to selection and demography
Authors: Hernandez Ryan D.
Published: October 2008

Summary: This article introduces a new forward population genetic simulation program that can efficiently generate samples from populations with complex demographic histories under various models of natural selection. The program (SFS_CODE) is highly flexible, allowing the user to simulate realistic genomic regions with several loci evolving according to a variety of mutation models (from simple to context-dependent), and allows for insertions and deletions. Each locus can be annotated as either coding or non-coding, sex-linked or autosomal, selected or neutral, and have an arbitrary linkage structure (from completely linked to independent).

Availability: The source code (written in the C programming language) is available at http://sfscode.sourceforge.net, and a web server (http://cbsuapps.tc.cornell.edu/sfscode.aspx) allows the user to perform simulations using the high-performance computing cluster hosted by the Cornell University Computational Biology Service Unit.

Contact:  rhernandez@uchicago.edu

Supplementary information: An extensive user's manual, perfor-mance statistics, and comparisons of patterns of genetic variation generated by SFS_CODE to theoretical expectations under various non-stationary demographic histories and models of natural selection are available on the project website: http://sfscode.sourceforge.net.
Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats
Authors: Hwang Hye Suk , Kim Yoo Sung , Ryu Yeon Hee , Lee Ji Eun , Lee Young Seop , Yang Eun Jin , Choi Sun-Mi , Lee Myeong Soo
Published: October 2008

Using spontaneously hypertensive rats (SHR), this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining nitric oxide (NO) levels in plasma and nitric oxide synthase (NOS) levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20) or to a non‐acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail‐cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS) and neuronal NOS (nNOS) protein expression in the mesenteric artery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than EA at non‐acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.
Learning decreases heterospecific courtship and mating in fruit flies
Authors: Dukas Reuven
Published: October 2008

Recent theory and data suggest that adaptive use of learning in the context of sexual behaviour could contribute to assortative mating. Experiments examining this issue indicated that male
Drosophila persimilis
that experienced courtship and rejection by heterospecific females exhibited significantly lower levels of heterospecific courtship and mating compared with those of inexperienced males. These results indicate that experience in the context of sexual behaviour in fruit flies could reduce gene flow between diverging populations, which may contribute to incipient speciation.
Telencephalon enlargement by the convergent evolution of expanded subventricular zones
Authors: Striedter Georg F , Charvet Christine J
Published: October 2008

Some mammals and birds independently evolved an enlarged telencephalon. They appear to have done so, at least in part, by developing a thick telencephalic subventricular zone (SVZ). We suggest that this correlation between telencephalic enlargement and SVZ expansion is due to a mechanical constraint acting on the proliferative ventricular zone (VZ). Essentially, we argue that rapid proliferation in the VZ after post-mitotic cells in the overlying mantle zone have begun to form limits the VZ's tangential expandability and forces some proliferating cells to emigrate from the VZ and expand the pool of proliferating cells that comprise the SVZ.
The recruitment of different compartments within a muscle depends on the mechanics of the movement
Authors: Wakeling James M
Published: October 2008

Muscles are commonly assumed to have uniform activations across their bellies. Yet animal studies have shown that different regions across a muscle can vary in their architecture, fibre type, levels of activation and the transfer of forces to the bones and tendons. The purpose of this study was to test whether regional variations in activity occurred across the soleus, medial gastrocnemius and lateral gastrocnemius in man, and whether these regional variations changed with altered mechanical demands on the limb. Arrays of surface electrodes were placed over these muscles and the electromyograms (EMG) measured for a range of cycling tasks where the resistance and pedal velocity was independently altered. Significant variations in the magnitude and timing of the EMG occurred across these muscles, which were most pronounced in the gastrocnemii and occurred in both the proximodistal and mediolateral directions. The patterns of variation across the muscles changed in response to the altered mechanical demands during the cycling. It is likely that the muscle fascicles in the gastrocnemii contribute varied mechanical functions to the contractions that depend on both their location within the muscle belly and on the mechanical requirements of the movement.
The optical sensitivity of compound eyes: theory and experiment compared
Authors: Frederiksen Rikard , Warrant Eric J
Published: October 2008

The Land sensitivity equation is a well-known tool for comparing optical performance between eyes. Despite this, the equation has never been experimentally tested. Here, we present, to our knowledge, the first experimental validation of the equation. We have investigated different insect species active at different intensities, and possessing different types of compound eyes, to compare ratios of calculated sensitivities to ratios determined experimentally. Experimental optical sensitivities were measured by adjusting the intensity of an external light source until photoreceptors in the different eyes produced roughly equal numbers of photon responses (‘bumps’) per second. The sensitivity ratios obtained in this manner agree well with those obtained using the equation. We conclude that the Land equation remains an excellent tool for comparing sensitivities between different eyes.
Why are there so few smart mammals (but so many smart birds)?
Authors: Isler Karin , Van Schaik Carel P
Published: October 2008

The expensive brain hypothesis predicts an interspecific link between relative brain size and life-history pace. Indeed, animals with relatively large brains have reduced rates of growth and reproduction. However, they also have increased total lifespan. Here we show that the reduction in production with increasing brain size is not fully compensated by the increase in lifespan. Consequently, the maximum rate of population increase (rmax) is negatively correlated with brain mass. This result is not due to a confounding effect of body size, indicating that the well-known correlation betweenrmaxand body size is driven by brain size, at least among homeothermic vertebrates. Thus, each lineage faces a ‘grey ceiling’, i.e. a maximum viable brain size, beyond whichrmaxis so low that the risk of local or species extinction is very high. We found that the steep decline inrmaxwith brain size is absent in taxa with allomaternal offspring provisioning, such as cooperatively breeding mammals and most altricial birds. These taxa thus do not face a lineage-specific grey ceiling, which explains the far greater number of independent origins of large brain size in birds than mammals. We also predict that (absolute and relative) brain size is an important predictor of macroevolutionary extinction patterns.
Metabolic ageing in individual zebra finches
Authors: Moe Børge , Rønning Bernt , Verhulst Simon , Bech Claus
Published: October 2008

Oxidative stress is suggested as a contributor to the ageing process. Knowledge of the relationship between age and energy expenditure may contribute to our understanding of ageing patterns, due to the link between oxygen consumption and free radical production. However, studies on basal metabolic rate (BMR) and age have generally been cross-sectional, which may confound estimates of the age effect due to disproportionate mortality (also known as ‘selective disappearance’). We therefore performed a longitudinal study of BMR using captive zebra finches (Taeniopygia guttata) up to 5 years of age. BMR declined with age in individuals of both sexes when body mass was controlled for. Males gained mass with age while females did not. There was no evidence for disproportionate mortality with respect to BMR in either sex. To our knowledge, this is the first longitudinal study of avian BMR over such a long proportion of the lifespan of the study species.
Testing Thayer's hypothesis: can camouflage work by distraction?
Authors: Stevens Martin , Graham Julia , Winney Isabel S , Cantor Abi
Published: October 2008

One of the oldest theories of animal camouflage predicts that apparently conspicuous markings enhance concealment. Such ‘distraction’ marks are hypothesized to work by drawing the viewer's attention away from salient features, such as the body outline, that would otherwise reveal the animal. If distraction marks enhance concealment, then they offer a route for animals to combine camouflage markings with conspicuous signalling strategies, such as warning signals. However, the theory has never been tested and remains controversial. By using camouflaged artificial prey presented to wild avian predators, we test whether distractive markings enhance concealment. In contrast to predictions, we find that markings, both circular and irregular shapes, increase predation compared with unmarked targets. Markings became increasingly costly as their contrast against the prey increased. Our experiments failed to find any empirical support for the hypothesis that distraction markings are an important aspect of camouflage in animals.
Conservation and conflict between endangered desert fishes
Authors: Gumm Jennifer M , Snekser Jennifer L , Itzkowitz Murray
Published: October 2008

Conservation of naturally sympatric endangered species requires unique considerations. While impacts of invasive species garner much attention, interactions between endangered species must also be managed. The endangered Leon Springs pupfish,
Cyprinodon bovinus
, has suffered a population decline due to decreasing natural habitat. As breeding habitat is lost,
C. bovinus
is also adversely affected by the sympatric, endangered Pecos gambusia,
Gambusia nobilis
. Here, we document interactions between these species, finding significantly more
G. nobilis
accumulated at pupfish spawning events than randomly distributed on breeding grounds in the absence of spawning. As a known egg predator, our results suggest that
G. nobilis
presence at spawnings may further decrease pupfish numbers while also altering the evolutionary dynamics of
C. bovinus
breeding tactics. Habitat restoration may decrease
Gambusia
concentrations or influence
C. bovinus
breeding behaviour and increase the number of territorial males resulting in viable population sizes for both critically endangered fishes.
Optimal movement in the prey strikes of weakly electric fish: a case study of the interplay of body plan and movement capability
Authors: Postlethwaite Claire M , Psemeneki Tiffany M , Selimkhanov Jangir , Silber Mary , MacIver Malcolm A
Published: October 2008

Animal behaviour arises through a complex mixture of biomechanical, neuronal, sensory and control constraints. By focusing on a simple, stereotyped movement, the prey capture strike of a weakly electric fish, we show that the trajectory of a strike is one which minimizes effort. Specifically, we model the fish as a rigid ellipsoid moving through a fluid with no viscosity, governed by Kirchhoff's equations. This formulation allows us to exploit methods of discrete mechanics and optimal control to compute idealized fish trajectories that minimize a cost function. We compare these with the measured prey capture strikes of weakly electric fish from a previous study. The fish has certain movement limitations that are not incorporated in the mathematical model, such as not being able to move sideways. Nonetheless, we show quantitatively that the computed least-cost trajectories are remarkably similar to the measured trajectories. Since, in this simplified model, the basic geometry of the idealized fish determines the favourable modes of movement, this suggests a high degree of influence between body shape and movement capability. Simplified minimal models and optimization methods can give significant insight into how body morphology and movement capability are closely attuned in fish locomotion.
Drag force acting on a neuromast in the fish lateral line trunk canal. II. Analytical modelling of parameter dependencies
Authors: Humphrey Joseph A.C.
Published: October 2008

In Part I of this two-part study, the coupled flows external and internal to the fish lateral line trunk canal were consecutively calculated by solving the Navier–Stokes (N–S) equations numerically in each domain. With the external flow known, the solution for the internal flow was obtained using a parallelepiped to simulate the neuromast cupula present between a pair of consecutive pores, allowing the calculation of the drag force acting on the neuromast cupula. While physically rigorous and accurate, the numerical approach is tedious and inefficient since it does not readily reveal the parameter dependencies of the drag force. In Part II of this work we present an analytically based physical–mathematical model for rapidly calculating the drag force acting on a neuromast cupula. The cupula is well approximated as an immobile sphere located inside a tube-shaped canal segment of circular cross section containing a constant property fluid in a steady-periodic oscillating state of motion. The analytical expression derived for the dimensionless drag force is of the form

, where |
F
N
| is the amplitude of the drag force; |
P
L
−
P
R
| is the amplitude of the pressure difference driving the flow in the interpore tube segment;
d
/
D
is the ratio of sphere diameter to tube diameter;
L
t
/
D
is the ratio of interpore tube segment length to tube diameter; and

is the oscillating flow kinetic Reynolds number (a dimensionless frequency). Present results show that the dimensionless drag force amplitude increases with decreasing
L
t
/
D
and maximizes in the range 0.65≤
d
/
D
≤0.85, depending on the values of
L
t
/
D
and

. It is also found that in the biologically relevant range of dimensionless frequencies 1≤

≤20 and segment lengths 4≤
L
t
/
D
≤16, the sphere tube (neuromast–canal) system acts as a low-pass filter for values
d
/
D
≤0.75, approximately. For larger values of
d
/
D
the system is equally sensitive to all frequencies, but the drag force is significantly decreased. Comparisons with N–S calculations of the drag force show good agreement with the analytical model results. By revealing the parameter dependencies of the drag force, the model serves to guide biological understanding and the optimized design of corresponding bioinspired artificial sensors.
Introduction. Ecological immunology
Authors: Schulenburg Hinrich , Kurtz Joachim , Moret Yannick , Siva-Jothy Michael T
Published: October 2008

An organism's fitness is critically reliant on its immune system to provide protection against parasites and pathogens. The structure of even simple immune systems is surprisingly complex and clearly will have been moulded by the organism's ecology. The aim of this review and the theme issue is to examine the role of different ecological factors on the evolution of immunity. Here, we will provide a general framework of the field by contextualizing the main ecological factors, including interactions with parasites, other types of biotic as well as abiotic interactions, intraspecific selective constraints (life-history trade-offs, sexual selection) and population genetic processes. We then elaborate the resulting immunological consequences such as the diversity of defence mechanisms (e.g. avoidance behaviour, resistance, tolerance), redundancy and protection against immunopathology, life-history integration of the immune response and shared immunity within a community (e.g. social immunity and microbiota-mediated protection). Our review summarizes the concepts of current importance and directs the reader to promising future research avenues that will deepen our understanding of the defence against parasites and pathogens.
Presence of free haptoglobin alpha 1S-subunit in acute porcine reproductive and respiratory syndrome virus infection
Authors: Gnanandarajah Josephine S. , Dvorak Cheryl M. T. , Johnson Craig R. , Murtaugh Michael P.
Published: October 2008

The biochemical events triggered by viral infection are critical to the outcome of a host immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) causes the most significant disease of swine worldwide. Onset of infection is insidious and subclinical. Clinical signs may not appear for days and antibodies cannot be detected for a week or more. To understand better the early pathophysiological response of swine to PRRSV infection and its inapparent onset, we examined serum samples in the first days of infection for evidence of early biochemical changes. Sera from pigs infected with various isolates of PRRSV were extracted to remove high molecular mass proteins, desalted and analysed by matrix assisted laser desorption/ionization–time of flight mass spectrometry (MS). Comparative analysis of low molecular mass serum protein profiles revealed that one protein, with anm/zvalue of 9244±2, appeared within 1 day of infection. The 9244±2 peak was identified as the alpha 1S (α1S)-subunit of porcine haptoglobin (Hp) by tandem MS sequencing and confirmed by immunoblotting with anti-porcine Hp antibody. Hp is an acute phase haem-binding protein consisting ofα–βheterodimers that is secreted from the liver in response to stresses, including infection. However, the presence of freeα1S-subunit in response to infection is novel and may provide new insights into biochemical processing of Hp and its role in disease pathogenesis, including PRRS.
Inhibition of 2-Oxoglutarate Dehydrogenase in Potato Tuber Suggests the Enzyme Is Limiting for Respiration and Confirms Its Importance in Nitrogen Assimilation
Authors: Araújo Wagner L. , Nunes-Nesi Adriano , Trenkamp Sandra , Bunik Victoria I. , Fernie Alisdair R.
Published: October 2008

The 2-oxoglutarate dehydrogenase complex constitutes a mitochondrially localized tricarboxylic acid cycle multienzyme system responsible for the conversion of 2-oxoglutarate to succinyl-coenzyme A concomitant with NAD+ reduction. Although regulatory mechanisms of plant enzyme complexes have been characterized in vitro, little is known concerning their role in plant metabolism in situ. This issue has recently been addressed at the cellular level in nonplant systems via the use of specific phosphonate inhibitors of the enzyme. Here, we describe the application of these inhibitors for the functional analysis of the potato (Solanum tuberosum) tuber 2-oxoglutarate dehydrogenase complex. In vitro experiments revealed that succinyl phosphonate (SP) and a carboxy ethyl ester of SP are slow-binding inhibitors of the 2-oxoglutarate dehydrogenase complex, displaying greater inhibitory effects than a diethyl ester of SP, a phosphono ethyl ester of SP, or a triethyl ester of SP. Incubation of potato tuber slices with the inhibitors revealed that they were adequately taken up by the tissue and produced the anticipated effects on the in situ enzyme activity. In order to assess the metabolic consequences of the 2-oxoglutarate dehydrogenase complex inhibition, we evaluated the levels of a broad range of primary metabolites using an established gas chromatography-mass spectrometry method. We additionally analyzed the rate of respiration in both tuber discs and isolated mitochondria. Finally, we evaluated the metabolic fate of radiolabeled acetate, 2-oxoglutarate or glucose, and 13C-labeled pyruvate and glutamate following incubation of tuber discs in the presence or absence of either SP or the carboxy ethyl ester of SP. The data obtained are discussed in the context of the roles of the 2-oxoglutarate dehydrogenase complex in respiration and carbon-nitrogen interactions.