bluuebunny/crossref_metadata_2025 huggingface dataset:
Motor-dependent microtubule disassembly driven by tubulin tyrosination
Authors: Peris Leticia , Wagenbach Michael , Lafanechère Laurence , Brocard Jacques , Moore Ayana T. , Kozielski Frank , Job Didier , Wordeman Linda , Andrieux Annie
Published: June 2009

In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of α-tubulin. The significance of this selective detyrosination of MTs is not understood. In this study, we report that tubulin detyrosination in fibroblasts inhibits MT disassembly. This inhibition is relieved by overexpression of the depolymerizing motor mitotic centromere-associated kinesin (MCAK). Conversely, suppression of MCAK expression prevents disassembly of normal tyrosinated MTs in fibroblasts. Detyrosination of MTs suppresses the activity of MCAK in vitro, apparently as the result of a decreased affinity of the adenosine diphosphate (ADP)–inorganic phosphate- and ADP-bound forms of MCAK for the MT lattice. Detyrosination also impairs MT disassembly in neurons and inhibits the activity of the neuronal depolymerizing motor KIF2A in vitro. These results indicate that MT depolymerizing motors are directly inhibited by the detyrosination of tubulin, resulting in the stabilization of cellular MTs. Detyrosination of transiently stabilized MTs may give rise to persistent subpopulations of disassembly-resistant polymers to sustain subcellular cytoskeletal differentiation.
The thymic medulla: a unique microenvironment for intercellular self-antigen transfer
Authors: Koble Christian , Kyewski Bruno
Published: June 2009

Central tolerance is shaped by the array of self-antigens expressed and presented by various types of thymic antigen-presenting cells (APCs). Depending on the overall signal quality and/or quantity delivered in these interactions, self-reactive thymocytes either apoptose or commit to the T regulatory cell lineage. The cellular and molecular complexity underlying these events has only recently been appreciated. We analyzed the ex vivo presentation of ubiquitous or tissue-restricted self-antigens by medullary thymic epithelial cells (mTECs) and thymic dendritic cells (DCs), the two major APC types present in the medulla. We found that the ubiquitously expressed nuclear neo–self-antigen ovalbumin (OVA) was efficiently presented via major histocompatibility complex class II by mTECs and thymic DCs. However, presentation by DCs was highly dependent on antigen expression by TECs, and hemopoietic cells did not substitute for this antigen source. Accordingly, efficient deletion of OVA-specific T cells correlated with OVA expression by TECs. Notably, OVA was only presented by thymic but not peripheral DCs. We further demonstrate that thymic DCs are constitutively provided in situ with cytosolic as well as membrane-bound mTEC-derived proteins. The subset of DCs displaying transferred proteins was enriched in activated DCs, with these cells being most efficient in presenting TEC-derived antigens. These data provide evidence for a unique, constitutive, and unidirectional transfer of self-antigens within the thymic microenvironment, thus broadening the cellular base for tolerance induction toward promiscuously expressed tissue antigens.
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing
Authors: Pickert Geethanjali , Neufert Clemens , Leppkes Moritz , Zheng Yan , Wittkopf Nadine , Warntjen Moritz , Lehr Hans-Anton , Hirth Sebastian , Weigmann Benno , Wirtz Stefan , Ouyang Wenjun , Neurath Markus F. , Becker Christoph
Published: June 2009

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing.
IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway
Authors: Wang Lin , Yi Tangsheng , Kortylewski Marcin , Pardoll Drew M. , Zeng Defu , Yu Hua
Published: June 2009

Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still unclear. We show that growth of B16 melanoma and MB49 bladder carcinoma is reduced in IL-17−/− mice but drastically accelerated in IFN-γ−/− mice, contributed to by elevated intratumoral IL-17, indicating a role of IL-17 in promoting tumor growth. Adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4+ T cells are the predominant source of IL-17. Enhancement of tumor growth by IL-17 involves direct effects on tumor cells and tumor-associated stromal cells, which bear IL-17 receptors. IL-17 induces IL-6 production, which in turn activates oncogenic signal transducer and activator of transcription (Stat) 3, up-regulating prosurvival and proangiogenic genes. The Th17 response can thus promote tumor growth, in part via an IL-6–Stat3 pathway.
A mutation in Irak2c identifies IRAK-2 as a central component of the TLR regulatory network of wild-derived mice
Authors: Conner James R. , Smirnova Irina I. , Poltorak Alexander
Published: June 2009

In a phenotypic screen of the wild-derived mouse strain MOLF/Ei, we describe an earlier and more potent toll-like receptor (TLR)–mediated induction of IL-6 transcription compared with the classical inbred strain C57BL/6J. The phenotype correlated with increased activity of the IκB kinase axis as well as p38, but not extracellular signal-regulated kinase or c-Jun N-terminal kinase, mitogen-activated protein kinase (MAPK) phosphorylation. The trait was mapped to the Why1 locus, which contains Irak2, a gene previously implicated as sustaining the late phase of TLR responses. In the MOLF/Ei TLR signaling network, IRAK-2 promotes early nuclear factor κB (NF-κB) activity and is essential for the activation of p38 MAPK. We identify a deletion in the MOLF/Ei promoter of the inhibitory Irak2c gene, leading to an increased ratio of pro- to antiinflammatory IRAK-2 isoforms. These findings demonstrate that IRAK-2 is an essential component of the early TLR response in MOLF/Ei mice and show a distinct pathway of p38 and NF-κB activation in this model organism. In addition, they demonstrate that studies in evolutionarily divergent model organisms are essential to complete dissection of signal transduction pathways.
Human naive and memory CD4+ T cell repertoires specific for naturally processed antigens analyzed using libraries of amplified T cells
Authors: Geiger Rebekka , Duhen Thomas , Lanzavecchia Antonio , Sallusto Federica
Published: June 2009

The enormous diversity of the naive T cell repertoire is instrumental in generating an immune response to virtually any foreign antigen that can be processed into peptides that bind to MHC molecules. The low frequency of antigen-specific naive T cells, their high activation threshold, and the constrains of antigen-processing and presentation have hampered analysis of naive repertoires to complex protein antigens. In this study, libraries of polyclonally expanded naive T cells were used to determine frequency and antigen dose–response of human naive CD4+ T cells specific for a variety of antigens and to isolate antigen-specific T cell clones. In the naive repertoire, T cells specific for primary antigens, such as KLH and Bacillus anthracis protective antigen, and for recall antigens, such as tetanus toxoid, cytomegalovirus, and Mycobacterium tuberculosis purified protein derivative, were detected at frequencies ranging from 5 to 170 cells per 106 naive T cells. Antigen concentrations required for half-maximal response (EC50) varied over several orders of magnitude for different naive T cells. In contrast, in the memory repertoire, T cells specific for primary antigens were not detected, whereas T cells specific for recall antigens were detected at high frequencies and displayed EC50 values in the low range of antigen concentrations. The method described may find applications for evaluation of vaccine candidates, for testing antigenicity of therapeutic proteins, drugs, and chemicals, and for generation of antigen-specific T cell clones for adoptive cellular immunotherapy.
Inactivation of Animal and Human Prions by Hydrogen Peroxide Gas Plasma Sterilization
Authors: Rogez-Kreuz C. , Yousfi R. , Soufflet C. , Quadrio I. , Yan Z.-X. , Huyot V. , Aubenque C. , Destrez P. , Roth K. , Roberts C. , Favero M. , Clayette P.
Published: June 2009

Prions cause various transmissible spongiform encephalopathies. They are highly resistant to the chemical and physical decontamination and sterilization procedures routinely used in healthcare facilities. The decontamination procedures recommended for the inactivation of prions are often incompatible with the materials used in medical devices. In this study, we evaluated the use of low-temperature hydrogen peroxide gas plasma sterilization systems and other instrument-processing procedures for inactivating human and animal prions. We provide new data concerning the efficacy of hydrogen peroxide against prions from in vitro or in vivo tests, focusing on the following: the efficiency of hydrogen peroxide sterilization and possible interactions with enzymatic or alkaline detergents, differences in the efficiency of this treatment against different prion strains, and the influence of contaminating lipids. We found that gaseous hydrogen peroxide decreased the infectivity of prions and/or the level of the protease-resistant form of the prion protein on different surface materials. However, the efficiency of this treatment depended strongly on the concentration of hydrogen peroxide and the delivery system used in medical devices, because these effects were more pronounced for the new generation of Sterrad technology. The Sterrad NX sterilizer is 100% efficient (0% transmission and no protease-resistant form of the prion protein signal detected on the surface of the material for the mouse-adapted bovine spongiform encephalopathy 6PB1 strain and a variant Creutzfeldt-Jakob disease strain). Thus, gaseous or vaporized hydrogen peroxide efficiently inactivates prions on the surfaces of medical devices.
A new multidimensional continued fraction algorithm
Authors: Tamura Jun-ichi , Yasutomi Shin-ichi
Published: June 2009

It has been believed that the continued fraction expansion of(α,β)(\alpha ,\beta )(1,α,β(1,\alpha ,\betais aQ{\mathbb Q}-basis of a real cubic field))obtained by the modified Jacobi-Perron algorithm is periodic. We conducted a numerical experiment (cf. Table B, Figure 1 and Figure 2) from which we conjecture the non-periodicity of the expansion of(⟨33⟩,⟨93⟩)(\langle \sqrt [3]{3}\rangle , \langle \sqrt [3]{9}\rangle )(⟨x⟩\langle x\rangledenoting the fractional part ofxx). We present a new algorithm which is something like the modified Jacobi-Perron algorithm, and give some experimental results with this new algorithm. From our experiments, we can expect that the expansion of(α,β)(\alpha ,\beta )with our algorithm always becomes periodic for any real cubic field. We also consider real quartic fields.
Fourier expansions and integral representations for the Apostol-Bernoulli and Apostol-Euler polynomials
Authors: Luo Qiu-Ming
Published: June 2009

We investigate Fourier expansions for the Apostol-Bernoulli and Apostol-Euler polynomials using the Lipschitz summation formula and obtain their integral representations. We give some explicit formulas at rational arguments for these polynomials in terms of the Hurwitz zeta function. We also derive the integral representations for the classical Bernoulli and Euler polynomials and related known results.
Computation of highly ramified coverings
Authors: Vidūnas Raimundas , Kitaev Alexander
Published: June 2009

An almost Belyi covering is an algebraic covering of the projective line, such that all ramified points except one simple ramified point lie above a set of 3 points of the projective line. In general, there are 1-dimensional families of these coverings with a fixed ramification pattern. (That is, Hurwitz spaces for these coverings are curves.) In this paper, three almost Belyi coverings of degrees 11, 12, and 20 are explicitly constructed. We demonstrate how these coverings can be used for computation of several algebraic solutions of the sixth Painlevé equation.
Discontinuous Galerkin method for an evolution equation with a memory term of positive type
Authors: Mustapha Kassem , McLean William
Published: June 2009

We consider an initial value problem for a class of evolution equations incorporating a memory term with a weakly singular kernel bounded by

C
(
t
−
s

)

α
−
1

C(t-s)^{\alpha -1}

, where

0
>
α
>
1

0>\alpha >1

. For the time discretization we apply the discontinuous Galerkin method using piecewise polynomials of degree at most 

q
−
1

q-1

, for

q
=
1

q=1

or 

2
2

. For the space discretization we use continuous piecewise-linear finite elements. The discrete solution satisfies an error bound of order

k
q

+

h
2

ℓ
(
k
)

k^q+h^2\ell (k)

, where

k
k

and

h
h

are the mesh sizes in time and space, respectively, and

ℓ
(
k
)
=
max
(
1
,
log
⁡

k

−
1

)

\ell (k)=\max (1,\log k^{-1})

. In the case 

q
=
2

q=2

, we prove a higher convergence rate of order

k
3

+

h
2

ℓ
(
k
)

k^3+h^2\ell (k)

at the nodes of the time mesh. Typically, the partial derivatives of the exact solution are singular at 

t
=
0

t=0

, necessitating the use of non-uniform time steps. We compare our theoretical error bounds with the results of numerical computations.
An algorithm for finding a nearly minimal balanced set in 𝔽_{𝕡}
Authors: Nedev Zhivko
Published: June 2009

For a prime

p
p

, we call a non-empty subset

S
S

of the group

F

p

\mathbb {F}_p

balanced if every element of

S
S

is the midterm of a three-term arithmetic progression, contained in

S
S

. A result of Browkin, Diviš and Schinzel implies that the size of a balanced subset of

F

p

\mathbb {F}_p

is at least

log

2

⁡
p
+
1

\log _{2} p + 1

. In this paper we present an efficient algorithm which yields a balanced set of size

(
1
+
o
(
1
)
)

log

2

⁡
p

(1 + o(1)) \log _{2} p

as

p
p

grows.
A new algorithm to search for small nonzero |𝑥³-𝑦²| values
Authors: Calvo I. , Herranz J. , Sáez G.
Published: June 2009

In relation to Hall’s conjecture, a new algorithm is presented to search for small nonzero

k
=
|

x
3

−

y
2

|

k=\lvert x^3-y^2\rvert

values. Seventeen new values of

k
>

x

1

/

2

k>x^{1/2}

are reported.
A symmetric error estimate for Galerkin approximations of time-dependent Navier-Stokes equations in two dimensions
Authors: Dupont Todd , Mogultay Itir
Published: June 2009

A symmetric error estimate for Galerkin approximations of solutions of the Navier-Stokes equations in two space dimensions plus time is given. The finite-dimensional function spaces are taken to be divergence-free, and time is left continuous. The estimate is similar to known results for scalar parabolic equations. An application of the result is given for mixed method formulations. A short discussion of examples is included. Finally, there are some remarks about a partial extension to three space dimensions.
On the asymptotics of the trapezoidal rule for the pantograph equation
Authors: Čermák J. , Jánský J.
Published: June 2009

The paper deals with the trapezoidal rule discretization of a class of linear delay differential equations, with a special emphasis on equations with a proportional delay. Our purpose is to analyse the asymptotic properties of the numerical solutions and formulate their upper bounds. We also survey the known results and show that our formulae improve and generalize these results. In particular, we set up conditions under which the numerical solution of the scalar pantograph equation has the same decay rate as the exact solution.
Solving parabolic stochastic partial differential equations via averaging over characteristics
Authors: Milstein G. , Tretyakov M.
Published: June 2009

The method of characteristics (the averaging over the characteristic formula) and the weak-sense numerical integration of ordinary stochastic differential equations together with the Monte Carlo technique are used to propose numerical methods for linear stochastic partial differential equations (SPDEs). Their orders of convergence in the mean-square sense and in the sense of almost sure convergence are obtained. A variance reduction technique for the Monte Carlo procedures is considered. Layer methods for linear and semilinear SPDEs are constructed and the corresponding convergence theorems are proved. The approach developed is supported by numerical experiments.
Computational verification of the Birch and Swinnerton-Dyer conjecture for individual elliptic curves
Authors: Grigorov Grigor , Jorza Andrei , Patrikis Stefan , Stein William , Tarniţǎ Corina
Published: June 2009

We describe theorems and computational methods for verifying the Birch and Swinnerton-Dyer conjectural formula for specific elliptic curves over 

Q

\mathbb {Q}

of analytic ranks

0
0

and

1
1

. We apply our techniques to show that if

E
E

is a non-CM elliptic curve over 

Q

\mathbb {Q}

of conductor

≤
1000

\leq 1000

and rank

0
0

or

1
1

, then the Birch and Swinnerton-Dyer conjectural formula for the leading coefficient of the

L
L

-series is true for 

E
E

, up to odd primes that divide either Tamagawa numbers of 

E
E

or the degree of some rational cyclic isogeny with domain 

E
E

. Since the rank part of the Birch and Swinnerton-Dyer conjecture is a theorem for curves of analytic rank

0
0

or

1
1

, this completely verifies the full conjecture for these curves up to the primes excluded above.
Harish-Chandra bimodules for quantized Slodowy slices
Authors: Ginzburg Victor
Published: June 2009

The Slodowy slice is an especially nice slice to a given nilpotent conjugacy class in a semisimple Lie algebra. Premet introduced noncommutative quantizations of the Poisson algebra of polynomial functions on the Slodowy slice.

In this paper, we define and study Harish-Chandra bimodules over Premet’s algebras. We apply the technique of Harish-Chandra bimodules to prove a conjecture of Premet concerning primitive ideals, to define projective functors, and to construct “noncommutative resolutions” of Slodowy slices via translation functors.
Inference of the impact of insertion sequence (IS) elements on bacterial genome diversification through analysis of small-size structural polymorphisms in Escherichia coli O157 genomes
Authors: Ooka Tadasuke , Ogura Yoshitoshi , Asadulghani Md , Ohnishi Makoto , Nakayama Keisuke , Terajima Jun , Watanabe Haruo , Hayashi Tetsuya
Published: June 2009

Mobile genetic elements play important roles in the evolution and diversification of bacterial genomes. In enterohemorrhagic Escherichia coli O157, a major factor that affects genomic diversity is prophages, which generate most of the large-size structural polymorphisms (LSSPs) observed in O157 genomes. Here, we describe the results of a systematic analysis of numerous small-size structural polymorphisms (SSSPs) that were detected by comparing the genomes of eight clinical isolates with a sequenced strain, O157 Sakai. Most of the SSSPs were generated by genetic events associated with only two insertion sequence (IS) elements, IS629 and ISEc8, and a number of genes that were inactivated or deleted by these events were identified. Simple excisions of IS629 and small deletions (footprints) formed by the excision of IS629, both of which are rarely described in bacteria, were also detected. In addition, the distribution of IS elements was highly biased toward prophages, prophage-like integrative elements, and plasmids. Based on these and our previous results, we conclude that, in addition to prophages, these two IS elements are major contributors to the genomic diversification of O157 strains and that LSSPs have been generated mainly by bacteriophages and SSSPs by IS elements. We also suggest that IS elements possibly play a role in the inactivation and immobilization of incoming phages and plasmids. Taken together, our results reveal the true impact of IS elements on the diversification of bacterial genomes and highlight their novel role in genome evolution.
mGene: Accurate SVM-based gene finding with an application to nematode genomes
Authors: Schweikert Gabriele , Zien Alexander , Zeller Georg , Behr Jonas , Dieterich Christoph , Ong Cheng Soon , Philips Petra , De Bona Fabio , Hartmann Lisa , Bohlen Anja , Krüger Nina , Sonnenburg Sören , Rätsch Gunnar
Published: June 2009

We present a highly accurate gene-prediction system for eukaryotic genomes, called mGene. It combines in an unprecedented manner the flexibility of generalized hidden Markov models (gHMMs) with the predictive power of modern machine learning methods, such as Support Vector Machines (SVMs). Its excellent performance was proved in an objective competition based on the genome of the nematodeCaenorhabditis elegans. Considering the average of sensitivity and specificity, the developmental version of mGene exhibited the best prediction performance on nucleotide, exon, and transcript level for ab initio and multiple-genome gene-prediction tasks. The fully developed version shows superior performance in 10 out of 12 evaluation criteria compared with the other participating gene finders, including Fgenesh++ and Augustus. An in-depth analysis of mGene's genome-wide predictions revealed that ≈2200 predicted genes were not contained in the current genome annotation. Testing a subset of 57 of these genes by RT-PCR and sequencing, we confirmed expression for 24 (42%) of them. mGene missed 300 annotated genes, out of which 205 were unconfirmed. RT-PCR testing of 24 of these genes resulted in a success rate of merely 8%. These findings suggest that even the gene catalog of a well-studied organism such asC. eleganscan be substantially improved by mGene's predictions. We also provide gene predictions for the four nematodesC. briggsae,C. brenneri,C. japonica, andC. remanei. Comparing the resulting proteomes among these organisms and to the known protein universe, we identified many species-specific gene inventions. In a quality assessment of several available annotations for these genomes, we find that mGene's predictions are most accurate.
New software for the singular value decomposition of time-resolved crystallographic data
Authors: Zhao Yi , Schmidt Marius
Published: June 2009

Singular value decomposition (SVD) has been successfully used in the analysis of time-resolved crystallographic data. A new software package for Linux-based operating systems, calledSVD4TX, has been developed. In contrast to an earlier version of the SVD program, written in Fortran, the new program provides a GTK+-based graphical user interface for easy user guidance through the entire SVD process. New features, such as an improved, more stable routine to determine a compatible kinetic mechanism, are implemented in theSVD4TXprogram package so that it provides almost all the necessary tools for a semi-automatic and effective SVD-based analysis of time-resolved crystallographic data in one program package.
Evaluation of particle statistics in powder diffractometry by a spinner-scan method
Authors: Ida T. , Goto T. , Hibino H.
Published: June 2009

The uncertainty in measured diffraction intensities caused by particle statistics, which originates from the limited number of crystallites satisfying the diffraction condition, has been evaluated by a step-scan measurement about the rotation angle of a specimen-spinning attachment of a laboratory powder X-ray diffractometer. The residual statistical variance of the spinner-scan intensity data, after subtraction of periodic drift and variance caused by counting statistics, was assigned to the variance caused by particle statistics. Particle statistics for a standard Si powder (NIST SRM640c) and three size fractions (nominally 3–7, 8–12 and 18–22 µm in Stokes diameter) of quartz powder separated by a sedimentation method have been analysed by scanning electron microscopy (SEM) and the spinner-scan method using a powder X-ray diffractometer. It has been confirmed that the observed ratio of the squared diffraction-peak intensity to the variance caused by particle statistics is proportional to the multiplicity of reflections predicted by the crystal structure. The spinner-scan intensity data for the standard Si powder (NIST SRM640c), the effective particle diameter of which was estimated at 5.6 µm by SEM image analysis, was used as the standard for crystallite-size evaluation of quartz powder based on analysis of spinner-scan data. The effective crystallite diameters of the three quartz powder samples have been estimated at 6.5 (2), 11.7 (2) and 22.8 (2) µm by the analysis of the spinner-scan data, while the effective particle diameters evaluated by SEM image analysis are 7.1, 12 and 25 µm, respectively. Other possible applications of the analysis of particle statistics based on the spinner-scan method are also discussed.
High-throughput powder diffraction V: the use of Raman spectroscopy with and without X-ray powder diffraction data
Authors: Barr Gordon , Cunningham Gordon , Dong Wei , Gilmore Christopher J. , Kojima Takashi
Published: June 2009

In high-throughput crystallography it is possible to accumulate large numbers of powder diffraction patterns on a series of related compounds, often polymorphs, salts or co-crystals. In previous papers [Gilmore, Barr & Paisley (2004).J. Appl. Cryst.37, 231–242; Barr, Dong & Gilmore (2004).J. Appl. Cryst.37, 243–252] it has been shown how such data can be analysed by generating an (n×n) correlation matrix,ρ, by correlatingnfull powder diffraction patterns, point by point. Theρmatrix is used as a source of dendrograms and metric multidimensional plots in three or more dimensions which classify the patterns into sets related by similarity. In this paper, it is shown how Raman spectroscopy data can be used by themselves or as an adjunct to powder diffraction data by combining the two techniques using the individual differences scaling method (INDSCAL) of Carroll & Chang [Psychometria, (1970),35, 283–319]. The method is very robust, and can be extended to other forms of spectroscopy. It is available as an option in the commercialPolySNAP3computer program.
Differential response of Vibrio cholerae planktonic and biofilm cells to autoinducer 2 deficiency
Authors: Ali Syed A. , Benitez Jorge A.
Published: June 2009

The formation of biofilm communities enhances the persistence of Vibrio cholerae in aquatic environments. Biofilm production is repressed by the quorum‐sensing regulator HapR in response to the accumulation of CAI‐1 and AI‐2. CAI‐1 is the strongest input signal activating HapR, whereas the role of AI‐2 remains ill‐defined. In the present study, we show that a V. cholerae luxS (AI‐2‐defective) mutant made increased biofilm. Interestingly, cells in the biofilm were more responsive to AI‐2 deficiency than cells from the planktonic population.
Transcription activator‐like type III effector AvrXa27 depends on OsTFIIAγ5 for the activation of Xa27 transcription in rice that triggers disease resistance to Xanthomonas oryzae pv. oryzae
Authors: GU KEYU , TIAN DONGSHENG , QIU CHENGXIANG , YIN ZHONGCHAO
Published: June 2009

The transcription activator‐like (TAL) type III effector AvrXa27 from Xanthomonas oryzae pv. oryzae (Xoo) strain PXO99A activates the transcription of the host resistance gene Xa27, which results in disease resistance to bacterial blight (BB) in rice. In this study, we show that AvrXa27‐activated Xa27 transcription requires host general transcription factor OsTFIIAγ5. The V39E substitution in OsTFIIAγ5, encoded by the recessive resistance gene xa5 in rice, greatly attenuates this activation in xa5 and Xa27 double homozygotes on inoculation with Xa27‐incompatible strains. The xa5 gene also causes attenuation in the induction of Xa27 by AvrXa27 expressed in rice. The xa5‐mediated attenuation of Xa27‐mediated resistance to PXO99A is recessive. Intriguingly, xa5‐mediated resistance to xa5‐incompatible strains is also down‐regulated in the xa5 and Xa27 double homozygotes. In addition, AvrXa27 expressed in planta shows weak virulence activity in the xa5 genetic background and causes enhanced susceptibility of the plants to BB inoculation. The results suggest that TAL effectors target host general transcription factors to directly manipulate the host transcriptional machinery for virulence and/or avirulence. The identification of xa5‐mediated attenuation of Xa27‐mediated resistance to Xoo provides a guideline for breeding resistance to BB when pyramiding xa5 with other resistance genes.
Bet‐hedging and the orientation of juvenile passerines in fall migration
Authors: Reilly James R. , Reilly Robert J.
Published: June 2009

1. Bet‐hedging of innate migratory orientation of juvenile passerines may be a fitness‐enhancing strategy for fall migration. Experimental studies support the view that juvenile passerines on their first migration to unknown winter grounds orient on a predetermined vector programme and make little or no adjustment for wind displacement. This trait, coupled with the unpredictable profile of wind speed and direction that the juvenile will encounter during migration, suggests that the fitness of a parent’s juvenile offspring will be highly variable from year to year. Under these circumstances, within‐clutch phenotypic variation in migratory orientation may be evolutionarily favoured.

2. To explore this hypothesis, a migration model is developed for a small passerine with breeding grounds in New England and winter grounds in the Caribbean. Parameterization is based on life history data of the neotropical migrantDendroica caerulescens, the black‐throated blue warbler. The model is simulated for the offspring of 20 000 adult females under each of a wide range of potential orientation programmes, incorporating stochastic wind profiles along potential migratory routes, based on 7 years of wind data for eastern North America.

3. Under these simulations, bet‐hedging in the form of within‐clutch variation of migratory orientation strongly dominates within‐clutch homogeneity, yielding higher geometric mean fitness in all vector programmes considered.

4. The simulation results provide a potential explanation for the variation observed in the tracks of juvenile passerines. Bet‐hedging also explains the extensively‐documented ‘coastal effect’ in which fall banding stations along the Atlantic coast of the United States consistently capture a much higher percentage of juvenile birds than do more inland stations.

5. Bet‐hedging is consistent with the published finding that slower flying birds exhibit greater variation in their migratory orientation than faster flying birds.

6. The bet‐hedging model of migratory orientation presented in this paper provides a theoretical structure capable of organizing a diverse collection of field and laboratory observations as predictable consequences of an evolutionarily favoured strategy. This theory may constitute a major advance in our understanding of bird migration and thus justifies the design and execution of new laboratory and field experiments to assess its power and predictive reach.
Effects of temperature on disease progression and swimming stamina in Ichthyophonus‐infected rainbow trout, Oncorhynchus mykiss (Walbaum)
Authors: Kocan R , Hershberger P , Sanders G , Winton J
Published: June 2009

Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 °C, 15 °C and 20 °C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced mean‐day‐to‐death at higher temperature. In a second experiment, Ichthyophonus‐infected fish were reared at 15 °C for 16 weeks then subjected to forced swimming at 10 °C, 15 °C and 20 °C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 °C (P = 0.02) and highly significant at 20 °C (P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas.
An audit of the use of breakaway techniques in a large psychiatric hospital: a replication study
Authors: DICKENS G. , ROGERS G. , ROONEY C. , Mc GUINNESS A. , DOYLE D.
Published: June 2009

Accessible summary

Breakaway techniques are a set of physical skills which are intended to help someone ‘break away’ from an aggressor. They are taught to most people who work in mental health services in the UK because assault against staff is quite common. Considerable time and money is spent teaching breakaway techniques, and it is important people should be able to remember the skills. However, breakaway training can be quite complex and we do not know whether people are able to recall the techniques if they get assaulted.

We asked people who work in a large psychiatric hospital who had received breakaway training to take part in this study and 147 people agreed to do so. One of us simulated an assault on each participant and asked them to use the techniques that they had been taught to break away from the assault. Two breakaway experts watched the simulation and judged whether the participant used the correct techniques to separate from the aggressor.

Only a small minority (14%) of people used the correct procedures taught to them in order to break away from an assault. However, most people (80%) did manage to break away from the assault even if they did not use the techniques taught to them.

This study provides further evidence that breakaway training may be too complex for people to recall in real‐life situations. More research is needed to find out what types of training are best recalled. Techniques that most closely resemble instinctual responses may be better remembered.

This paper describes an audit study of the effectiveness of breakaway training conducted in a specialist inpatient mental health hospital. Breakaway techniques comprise a set of physical skills to help separate or break away from an aggressor in a safe manner, but do not involve the use of restraint. Staff (n= 147) were assessed on their ability to break away from simulations of potentially life‐threatening scenarios in a timely manner, and using the techniques taught in annual breakaway or refresher training. We found that only 14% (21/147) of participants correctly used the taught techniques to break away within 10 s. However, 80% of people were able to break away from the scenarios within 10 s but did not use the techniques taught to them. This audit reinforces questions about breakaway training raised in a previous study. It further demonstrates the need for a national curriculum for physical intervention training and development of the evidence base for the content of such training as a priority.
Preventive child‐focused family work: development of instrument in adult psychiatry
Authors: KORHONEN T. , VEHVILÄINEN‐JULKUNEN K. , PIETILÄ A.‐M. , KATTAINEN E.
Published: June 2009

Accessible summary

This paper provides a tool to measure support for parenting, children and family relationships for families affected by parental mental disorder in adult psychiatric clinical practice.

This study describes the elements of child‐focused family work in order to promote development and mental health of clients' children in adult psychiatric care.

It is well‐known that a parent's mental disorder has a significant psychosocial influence on the development of her or his children. This study reports the development process and psychometric testing of the preventive child‐focused family work (PCF‐FW) questionnaire in adult psychiatric settings. The PCF‐FW instrument was developed to measure support for parenting, dependent children and family relationships in order to promote child development and mental health in adult psychiatry. A 133‐item PCF‐FW questionnaire was developed; the content validity, construct validity and reliability of the instrument were ensured by expert review, pilot test and internal consistency. The final instrument was distributed to all nurses (n= 608), including registered nurses (n= 373) and practical mental health nurses (n= 235), working in 45 adult psychiatric units in five university hospitals in Finland. Some 51% of all nurses responded. Correlation variables in each subscale varied between 0.1 and 0.8. Cronbach's alpha coefficients were 0.55–0.95 in each subscale, demonstrating the moderate to excellent internal consistency of the instrument. The Cronbach's alpha coefficient for the entire instrument was 0.94. In spite of some caveats, such as possible response biases, the present study suggests that the PCF‐FW instrument is a valid and reliable tool for studying preventive child‐focused family working in adult psychiatry.
Observation intervention: time for an overview
Authors: KETTLES A. M. , ADDO M. A.
Published: June 2009

Accessible summary

There is still a lack of research evidence about observation intervention practice and the evidence that does exist is low‐quality.

This article explores the observation literature but not in the traditional literature review sense; rather, it takes the approach of clinical and local practice and the application of the literature to practice.

The time has come to take the evidence base for observation intervention to the level of evaluation research.

Much material on the subject of observation is not published and few people at local level have an overview of how the intervention has changed over time or how the policies have been implemented.

This paper aims to illustrate the nature and extent of research and development work related to observation practice over the last 28 years. It aims to show both local Scottish work and the National picture, how there is still a lack of research evidence despite all the work that has taken place and what needs to be performed to explore observation practice for the future. It is not intended to be a literature review in the traditional sense. Observation has not been studied enough to know the continuing ever‐changing picture of what goes on in the reality of practice. There are now studies examining observation but none of these are ‘gold standard’ randomized controlled trials; some are quantitative and some are qualitative audit or guidelines all based at a lower level in research evidence terms. The time has come to take the evidence base to the next level through evaluative research.
Ongoing ecological divergence in an emerging genomic model
Authors: ARNEGARD MATTHEW E.
Published: June 2009

Much of Earth’s biodiversity has arisen through adaptive radiation. Important avenues of phenotypic divergence during this process include the evolution of body size and life history (Schluter 2000). Extensive adaptive radiations of cichlid fishes have occurred in the Great Lakes of Africa, giving rise to behaviours that are remarkably sophisticated and diverse across species. In Tanganyikan shell‐brooding cichlids of the tribe Lamprologini, tremendous intraspecific variation in body size accompanies complex breeding systems and use of empty snail shells to hide from predators and rear offspring. A study byTakahashiet al.(2009)in this issue ofMolecular Ecologyreveals the first case of genetic divergence between dwarf and normal‐sized morphs of the same nominal lamprologine species,Telmatochromis temporalis. Patterns of population structure suggest that the dwarf, shell‐dwelling morph ofT. temporalismight have arisen from the normal, rock‐dwelling morph independently in more than one region of the lake, and that pairs of morphs at different sites may represent different stages early in the process of ecological speciation. The findings of Takahashiet al.are important first steps towards understanding the evolution of these intriguing morphs, yet many questions remain unanswered about the mating system, gene flow, plasticity and selection. Despite these limitations, descriptive work like theirs takes on much significance in African cichlids due to forthcoming resources for comparative genomics.
The essential histone‐like protein HU plays a major role in Deinococcus radiodurans nucleoid compaction
Authors: Nguyen Hong Ha , De La Tour Claire Bouthier , Toueille Magali , Vannier Françoise , Sommer Suzanne , Servant Pascale
Published: June 2009

The nucleoid of radioresistant bacteria, including D. radiodurans, adopts a highly condensed structure that remains unaltered after exposure to high doses of irradiation. This structure may contribute to radioresistance by preventing the dispersion of DNA fragments generated by irradiation. In this report, we focused our study on the role of HU protein, a nucleoid‐associated protein referred to as a histone‐like protein, in the nucleoid compaction of D. radiodurans. We demonstrate, using a new system allowing conditional gene expression, that HU is essential for viability in D. radiodurans. Using a tagged HU protein and immunofluorescence microscopy, we show that HU protein localizes all over the nucleoid and that when HU is expressed from a thermosensitive plasmid, its progressive depletion at the non‐permissive temperature generates decondensation of DNA before fractionation of the nucleoid into several entities and subsequent cell lysis. We also tested the effect of the absence of Dps, a protein also involved in nucleoid structure. In contrast to the drastic effect of HU depletion, no change in nucleoid morphology and cell viability was observed in dps mutants compared with the wild‐type, reinforcing the major role of HU in nucleoid organization and DNA compaction in D. radiodurans.
Hfq affects the expression of the LEE pathogenicity island in enterohaemorrhagic Escherichia coli
Authors: Hansen Anne‐Marie , Kaper James B.
Published: June 2009

Colonization of the intestinal epithelium by enterohaemorrhagic Escherichia coli (EHEC) is characterized by an attaching and effacing (A/E) histopathology. The locus of enterocyte effacement (LEE) pathogenicity island encodes many genes required for the A/E phenotype including the global regulator of EHEC virulence gene expression, Ler. The LEE is subject to a complex regulatory network primarily targeting ler transcription. The RNA chaperone Hfq, implicated in post‐transcriptional regulation, is an important virulence factor in many bacterial pathogens. Although post‐transcriptional regulation of EHEC virulence genes is known to occur, a regulatory role of Hfq in EHEC virulence gene expression has yet to be defined. Here, we show that an hfq mutant expresses increased levels of LEE‐encoded proteins prematurely, leading to earlier A/E lesion formation relative to wild type. Hfq indirectly affects LEE expression in exponential phase independent of Ler by negatively controlling levels of the regulators GrlA and GrlR through post‐transcriptional regulation of the grlRA messenger. Moreover, Hfq negatively affects LEE expression in stationary phase independent of GrlA and GrlR. Altogether, Hfq plays an important role in co‐ordinating the temporal expression of the LEE by controlling grlRA expression at the post‐transcriptional level.
Biofeedback therapy in fecal incontinence and constipation
Authors: Enck P. , Van Der Voort I. R. , Klosterhalfen S.
Published: June 2009

Abstract  We examine the collected evidence for efficacy of biofeedback therapy (BFT) in incontinence and constipation by means of meta‐analysis of randomized controlled trials. PubMed search was performed to identify treatment trials that match quality criteria (adequate control groups, randomization). They were entered into meta‐analyses using fixed effect models and computing odds ratio (OR) and 95% confidence interval (CI) of treatment effects. For constipation, eight BFT trials were identified. In four trials, electromyographic (EMG) BFT was compared to non‐BFT treatments (laxatives, placebo, sham training and botox injection), while in the remaining four studies EMG BFT was compared to other BFT (balloon pressure, verbal feedback) modes. Meta‐analyses revealed superiority of BFT to non‐BFT (OR: 3.657; 95% CI: 2.127–6.290, P < 0.001) but equal efficacy of EMG BFT to other BF applications (OR: 1.436; CI: 0.692–3.089; P = 0.319). For fecal incontinence, a total of 11 trials were identified, of which six compared BFT to other treatment options (sensory training, pelvic floor exercise and electrical stimulation) and five compared one BFT option to other modalities of BFT. BFT was equal effective than non‐BFT therapy (OR: 1.189, CI: 0.689–2.051, P = 0.535). No difference was found when various modes BFT were compared (OR: 1.278, CI: 0.736–2.220, P = 0.384). Included trials showed a substantial lack of quality and harmonization, e.g. variable endpoints and missing psychological assessment across studies. BFT for pelvic floor dyssynergia shows substantial specific therapeutic effect while BFT for incontinence is still lacking evidence for efficacy. However, in both conditions the mode of BFT seems to play a minor role.