bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming status quo bias in the human brain
Authors: Fleming Stephen M. , Thomas Charlotte L. , Dolan Raymond J.
Published: March 2010

Humans often accept the status quo when faced with conflicting choice alternatives. However, it is unknown how neural pathways connecting cognition with action modulate this status quo acceptance. Here we developed a visual detection task in which subjects tended to favor the default when making difficult, but not easy, decisions. This bias was suboptimal in that more errors were made when the default was accepted. A selective increase in subthalamic nucleus (STN) activity was found when the status quo was rejected in the face of heightened decision difficulty. Analysis of effective connectivity showed that inferior frontal cortex, a region more active for difficult decisions, exerted an enhanced modulatory influence on the STN during switches away from the status quo. These data suggest that the neural circuits required to initiate controlled, nondefault actions are similar to those previously shown to mediate outright response suppression. We conclude that specific prefrontal-basal ganglia dynamics are involved in rejecting the default, a mechanism that may be important in a range of difficult choice scenarios.
Principles of conduction and hydrophobic gating in K
+
channels
Authors: Jensen Morten Ø. , Borhani David W. , Lindorff-Larsen Kresten , Maragakis Paul , Jogini Vishwanath , Eastwood Michael P. , Dror Ron O. , Shaw David E.
Published: March 2010

We present the first atomic-resolution observations of permeation and gating in a K
+
channel, based on molecular dynamics simulations of the Kv1.2 pore domain. Analysis of hundreds of simulated permeation events revealed a detailed conduction mechanism, resembling the Hodgkin–Keynes “knock-on” model, in which translocation of two selectivity filter–bound ions is driven by a third ion; formation of this knock-on intermediate is rate determining. In addition, at reverse or zero voltages, we observed pore closure by a novel “hydrophobic gating” mechanism: A dewetting transition of the hydrophobic pore cavity—fastest when K
+
was not bound in selectivity filter sites nearest the cavity—caused the open, conducting pore to collapse into a closed, nonconducting conformation. Such pore closure corroborates the idea that voltage sensors can act to prevent pore collapse into the intrinsically more stable, closed conformation, and it further suggests that molecular-scale dewetting facilitates a specific biological function: K
+
channel gating. Existing experimental data support our hypothesis that hydrophobic gating may be a fundamental principle underlying the gating of voltage-sensitive K
+
channels. We suggest that hydrophobic gating explains, in part, why diverse ion channels conserve hydrophobic pore cavities, and we speculate that modulation of cavity hydration could enable structural determination of both open and closed channels.
Dendritic cells control T cell tonic signaling required for responsiveness to foreign antigen
Authors: Hochweller Kristin , Wabnitz Guido H. , Samstag Yvonne , Suffner Janine , Hämmerling Günter J. , Garbi Natalio
Published: March 2010

Dendritic cells (DCs) are key components of the adaptive immune system contributing to initiation and regulation of T cell responses. T cells continuously scan DCs in lymphoid organs for the presence of foreign antigen. However, little is known about the functional consequences of these frequent T cell–DC interactions without cognate antigen. Here we demonstrate that these contacts in the absence of foreign antigen serve an important function, namely, induction of a basal activation level in T cells required for responsiveness to subsequent encounters with foreign antigens. This basal activation is provided by self-recognition of MHC molecules on DCs. Following DC depletion in mice, T cells became impaired in TCR signaling and immune synapse formation, and consequently were hyporesponsive to antigen. This process was reversible, as T cells quickly recovered when the number of DCs returned to a normal level. The extent of T cell reactivity correlated with the degree of DC depletion in lymphoid organs, suggesting that a full DC compartment guarantees optimal T cell responsiveness. These findings indicate that DCs are specialized cells that not only present foreign antigen, but also promote a “tonic” state in T cells for antigen responsiveness.
Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility
Authors: Hu Yan , Platzer Edward G. , Bellier Audrey , Aroian Raffi V.
Published: March 2010

The soil-transmitted helminths or nematodes (hookworms, whipworms, and Ascaris) are roundworms that infect more than 1 billion of the poorest peoples and are leading causes of morbidity worldwide. Few anthelmintics are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed, and crystal (Cry) proteins made by
Bacillus thuringiensis
are promising new candidates. Combination drug therapies are considered the ideal treatment for infectious diseases. Surprisingly, little work has been done to define the characteristics of anthelmintic combinations. Here, by means of quantitative assays with wild-type and mutants of the roundworm
Caenorhabditis elegans
, we establish a paradigm for studying anthelmintic combinations using Cry proteins and nicotinic acetylcholine receptor (nAChR) agonists, e.g., tribendimidine and levamisole. We find that nAChR agonists and Cry proteins, like Cry5B and Cry21A, mutually display what is known in the HIV field as hypersusceptibility—when the nematodes become resistant to either class, they become hypersensitive to the other class. Furthermore, we find that when Cry5B and nAChR agonists are combined, their activities are strongly synergistic, producing combination index values as good or better than seen with antitumor, anti-HIV, and insecticide combinations. Our study provides a powerful means by which anthelmintic combination therapies can be examined and demonstrate that the combination of nAChR agonists and Cry proteins has excellent properties and is predicted to give improved cure rates while being recalcitrant to the development of parasite resistance.
Brassinosteroids control male fertility by regulating the expression of key genes involved in
Arabidopsis
anther and pollen development
Authors: Ye Qianqian , Zhu Wenjiao , Li Lei , Zhang Shanshan , Yin Yanhai , Ma Hong , Wang Xuelu
Published: March 2010

The development of anther and pollen is important for male reproduction, and this process is coordinately regulated by many external and internal cues. In this study, we systematically examined the male reproductive phenotypes of a series of brassinosteroid biosynthetic and signaling mutants and found that, besides the expected cell-expansion defects, these mutants also showed reduced pollen number, viability, and release efficiency. These defects were related with abnormal tapetum and microspore development. Using both real-time quantitative RT-PCR and microarray experiments, we found that the expression of many key genes required for anther and pollen development was suppressed in these mutants. ChIP analysis demonstrated that BES1, an important transcription factor for brassinosteroid signaling, could directly bind to the promoter regions of genes encoding transcription factors essential for anther and pollen development,
SPL/NZZ
,
TDF1
,
AMS
,
MS1
, and
MS2
. Taken together, these data lead us to propose that brassinosteroids control male fertility at least in part via directly regulating key genes for anther and pollen development in
Arabidopsis
. Our work provides a unique mechanism to explain how a phytohormone regulates an essential genetic program for plant development.
Plasmodium vivax
clinical malaria is commonly observed in Duffy-negative Malagasy people
Authors: Ménard Didier , Barnadas Céline , Bouchier Christiane , Henry-Halldin Cara , Gray Laurie R. , Ratsimbasoa Arsène , Thonier Vincent , Carod Jean-François , Domarle Olivier , Colin Yves , Bertrand Olivier , Picot Julien , King Christopher L. , Grimberg Brian T. , Mercereau-Puijalon Odile , Zimmerman Peter A.
Published: March 2010

Malaria therapy, experimental, and epidemiological studies have shown that erythrocyte Duffy blood group-negative people, largely of African ancestry, are resistant to erythrocyte
Plasmodium vivax
infection. These findings established a paradigm that the Duffy antigen is required for
P. vivax
erythrocyte invasion.
P. vivax
is endemic in Madagascar, where admixture of Duffy-negative and Duffy-positive populations of diverse ethnic backgrounds has occurred over 2 millennia. There, we investigated susceptibility to
P. vivax
blood-stage infection and disease in association with Duffy blood group polymorphism. Duffy blood group genotyping identified 72% Duffy-negative individuals (

FY*B
ES
/*B
ES

) in community surveys conducted at eight sentinel sites. Flow cytometry and adsorption–elution results confirmed the absence of Duffy antigen expression on Duffy-negative erythrocytes.
P. vivax
PCR positivity was observed in 8.8% (42/476) of asymptomatic Duffy-negative people. Clinical vivax malaria was identified in Duffy-negative subjects with nine
P. vivax
monoinfections and eight mixed
Plasmodium
species infections that included
P. vivax
(4.9 and 4.4% of 183 participants, respectively). Microscopy examination of blood smears confirmed blood-stage development of
P. vivax
, including gametocytes. Genotyping of polymorphic surface and microsatellite markers suggested that multiple
P. vivax
strains were infecting Duffy-negative people. In Madagascar,
P. vivax
has broken through its dependence on the Duffy antigen for establishing human blood-stage infection and disease. Further studies are necessary to identify the parasite and host molecules that enable this Duffy-independent
P. vivax
invasion of human erythrocytes.
AtBAG7
, an
Arabidopsis
Bcl-2–associated athanogene, resides in the endoplasmic reticulum and is involved in the unfolded protein response
Authors: Williams Brett , Kabbage Mehdi , Britt Robert , Dickman Martin B.
Published: March 2010

The Bcl-2–associated athanogene (
BAG
) family is an evolutionarily conserved, multifunctional group of cochaperones that perform diverse cellular functions ranging from proliferation to growth arrest and cell death in yeast, in mammals, and, as recently observed, in plants. The
Arabidopsis
genome contains seven homologs of the
BAG
family, including four with domain organization similar to animal BAGs. In the present study we show that an
Arabidopsis BAG
,
AtBAG7
, is a uniquely localized endoplasmic reticulum (ER)
BAG
that is necessary for the proper maintenance of the unfolded protein response (UPR).
AtBAG7
was shown to interact directly in vivo with the molecular chaperone,
AtBiP2
, by bimolecular fluorescence complementation assays, and the interaction was confirmed by yeast two-hybrid assay. Treatment with an inducer of UPR, tunicamycin, resulted in accelerated cell death of
AtBAG7
-null mutants. Furthermore,
AtBAG7
knockouts were sensitive to known ER stress stimuli, heat and cold. In these knockouts heat sensitivity was reverted successfully to the wild-type phenotype with the addition of the chemical chaperone, tauroursodexycholic acid (TUDCA). Real-time PCR of ER stress proteins indicated that the expression of the heat-shock protein,
AtBiP3
, is selectively up-regulated in
AtBAG7
-null mutants upon heat and cold stress. Our results reveal an unexpected diversity of the plant's
BAG
gene family and suggest that
AtBAG7
is an essential component of the UPR during heat and cold tolerance, thus confirming the cytoprotective role of plant
BAGs
.
Dormancy contributes to the maintenance of microbial diversity
Authors: Jones Stuart E. , Lennon Jay T.
Published: March 2010

Dormancy is a bet-hedging strategy used by a variety of organisms to overcome unfavorable environmental conditions. By entering a reversible state of low metabolic activity, dormant individuals become members of a seed bank, which can determine community dynamics in future generations. Although microbiologists have documented dormancy in both clinical and natural settings, the importance of seed banks for the diversity and functioning of microbial communities remains untested. Here, we develop a theoretical model demonstrating that microbial communities are structured by environmental cues that trigger dormancy. A molecular survey of lake ecosystems revealed that dormancy plays a more important role in shaping bacterial communities than eukaryotic microbial communities. The proportion of dormant bacteria was relatively low in productive ecosystems but accounted for up to 40% of taxon richness in nutrient-poor systems. Our simulations and empirical data suggest that regional environmental cues and dormancy synchronize the composition of active communities across the landscape while decoupling active microbes from the total community at local scales. Furthermore, we observed that rare bacterial taxa were disproportionately active relative to common bacterial taxa, suggesting that microbial rank-abundance curves are more dynamic than previously considered. We propose that repeated transitions to and from the seed bank may help maintain the high levels of microbial biodiversity that are observed in nearly all ecosystems.
The neural code of reward anticipation in human orbitofrontal cortex
Authors: Kahnt Thorsten , Heinzle Jakob , Park Soyoung Q , Haynes John-Dylan
Published: March 2010

An optimal choice among alternative behavioral options requires precise anticipatory representations of their possible outcomes. A fundamental question is how such anticipated outcomes are represented in the brain. Reward coding at the level of single cells in the orbitofrontal cortex (OFC) follows a more heterogeneous coding scheme than suggested by studies using functional MRI (fMRI) in humans. Using a combination of multivariate pattern classification and fMRI we show that the reward value of sensory cues can be decoded from distributed fMRI patterns in the OFC. This distributed representation is compatible with previous reports from animal electrophysiology that show that reward is encoded by different neural populations with opposing coding schemes. Importantly, the fMRI patterns representing specific values during anticipation are similar to those that emerge during the receipt of reward. Furthermore, we show that the degree of this coding similarity is related to subjects’ ability to use value information to guide behavior. These findings narrow the gap between reward coding in humans and animals and corroborate the notion that value representations in OFC are independent of whether reward is anticipated or actually received.
Cell–cell signal-dependent dynamic interactions between HD-GYP and GGDEF domain proteins mediate virulence in
Xanthomonas campestris
Authors: Ryan Robert P. , McCarthy Yvonne , Andrade Maxuel , Farah Chuck S. , Armitage Judith P. , Dow J. Maxwell
Published: March 2010

RpfG is a paradigm for a class of widespread bacterial two-component regulators with a CheY-like receiver domain attached to a histidine-aspartic acid-glycine-tyrosine-proline (HD-GYP) cyclic di-GMP phosphodiesterase domain. In the plant pathogen
Xanthomonas campestris
pv.
campestris
(
Xcc
), a two-component system comprising RpfG and the complex sensor kinase RpfC is implicated in sensing and responding to the diffusible signaling factor (DSF), which is essential for cell–cell signaling. RpfF is involved in synthesizing DSF, and mutations of
rpfF
,
rpfG
, or
rpfC
lead to a coordinate reduction in the synthesis of virulence factors such as extracellular enzymes, biofilm structure, and motility. Using yeast two-hybrid analysis and fluorescence resonance energy transfer experiments in
Xcc
, we show that the physical interaction of RpfG with two proteins with diguanylate cyclase (GGDEF) domains controls a subset of RpfG-regulated virulence functions. RpfG interactions were abolished by alanine substitutions of the three residues of the conserved GYP motif in the HD-GYP domain. Changing the GYP motif or deletion of the two GGDEF-domain proteins reduced
Xcc
motility but not the synthesis of extracellular enzymes or biofilm formation. RpfG–GGDEF interactions are dynamic and depend on DSF signaling, being reduced in the
rpfF
mutant but restored by DSF addition. The results are consistent with a model in which DSF signal transduction controlling motility depends on a highly regulated, dynamic interaction of proteins that influence the localized expression of cyclic di-GMP.
Huwe1 ubiquitin ligase is essential to synchronize neuronal and glial differentiation in the developing cerebellum
Authors: D’Arca Domenico , Zhao Xudong , Xu Wenming , Ramirez-Martinez Nadya C. , Iavarone Antonio , Lasorella Anna
Published: March 2010

We have generated a knockout mouse strain in which the gene coding for the ubiquitin ligase Huwe1 has been inactivated in cerebellar granule neuron precursors (CGNPs) and radial glia. These mice have a high rate of postnatal lethality and profound cerebellar abnormalities. The external granule layer of the cerebellum, which contains CGNPs, is expanded and displays aberrant proliferation and impaired differentiation of the progenitor cell population. The uncontrolled proliferation of the CGNPs is associated with accumulation of the N-Myc oncoprotein, a substrate of Huwe1, and con-sequent activation of the signaling events downstream to N-Myc. Furthermore, loss of Huwe1 in Bergmann glia leads to extensive disorganization of this cell population with layering aberrations, severe granule neuron migration defects, and persistence of ectopic clusters of granule neurons in the external granule layer. Our findings uncover an unexpected role for Huwe1 in regulating Berg-mann glia differentiation and indicate that this ubiquitin ligase orchestrates the programming of the neural progenitors that give rise to neurons and glia in the cerebellum.
Identification of hepatoprotective flavonolignans from silymarin
Authors: Polyak Stephen J. , Morishima Chihiro , Lohmann Volker , Pal Sampa , Lee David Y. W. , Liu Yanze , Graf Tyler N. , Oberlies Nicholas H.
Published: March 2010

Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluated the hepatoprotective actions of the seven major flavonolignans and one flavonoid that comprise silymarin. Activities tested included inhibition of: HCV cell culture infection, NS5B polymerase activity, TNF-α-induced NF-κB transcription, virus-induced oxidative stress, and T-cell proliferation. All compounds were well tolerated by Huh7 human hepatoma cells up to 80 μM, except for isosilybin B, which was toxic to cells above 10 μM. Select compounds had stronger hepatoprotective functions than silymarin in all assays tested except in T cell proliferation. Pure compounds inhibited JFH-1 NS5B polymerase but only at concentrations above 300 μM. Silymarin suppressed TNF-α activation of NF-κB dependent transcription, which involved partial inhibition of IκB and RelA/p65 serine phosphorylation, and p50 and p65 nuclear translocation, without affecting binding of p50 and p65 to DNA. All compounds blocked JFH-1 virus-induced oxidative stress, including compounds that lacked antiviral activity. The most potent compounds across multiple assays were taxifolin, isosilybin A, silybin A, silybin B, and silibinin, a mixture of silybin A and silybin B. The data suggest that silymarin- and silymarin-derived compounds may influence HCV disease course in some patients. Studies where standardized silymarin is dosed to identify specific clinical endpoints are urgently needed.
Post-Paleozoic crinoid radiation in response to benthic predation preceded the Mesozoic marine revolution
Authors: Baumiller Tomasz K. , Salamon Mariusz A. , Gorzelak Przemysław , Mooi Rich , Messing Charles G. , Gahn Forest J.
Published: March 2010

It has been argued that increases in predation over geological time should result in increases in defensive adaptations in prey taxa. Recent in situ and laboratory observations indicate that cidaroid sea urchins feed on live stalked crinoids, leaving distinct bite marks on their skeletal elements. Similar bite marks on fossil crinoids from Poland strongly suggest that these animals have been subject to echinoid predation since the Triassic. Following their near-demise during the end-Permian extinction, crinoids underwent a major evolutionary radiation during the Middle–Late Triassic that produced distinct morphological and behavioral novelties, particularly motile taxa that contrasted strongly with the predominantly sessile Paleozoic crinoid faunas. We suggest that the appearance and subsequent evolutionary success of motile crinoids were related to benthic predation by post-Paleozoic echinoids with their stronger and more active feeding apparatus and that, in the case of crinoids, the predation-driven Mesozoic marine revolution started earlier than in other groups, perhaps soon after the end-Permian extinction.
Global classical solutions of the Boltzmann equation with long-range interactions
Authors: Gressman Philip T. , Strain Robert M.
Published: March 2010

This is a brief announcement of our recent proof of global existence and rapid decay to equilibrium of classical solutions to the Boltzmann equation without any angular cutoff, that is, for long-range interactions. We consider perturbations of the Maxwellian equilibrium states and include the physical cross-sections arising from an inverse-power intermolecular potential
r

-(
p
-1)

with
p
 > 2, and more generally. We present here a mathematical framework for unique global in time solutions for all of these potentials. We consider it remarkable that this equation, derived by Boltzmann (
1
) in 1872 and Maxwell (
2
) in 1867, grants a basic example where a range of geometric fractional derivatives occur in a physical model of the natural world. Our methods provide a new understanding of the effects due to grazing collisions.
Allopregnanolone reverses neurogenic and cognitive deficits in mouse model of Alzheimer's disease
Authors: Wang Jun Ming , Singh Chanpreet , Liu Lifei , Irwin Ronald W. , Chen Shuhua , Chung Eun Ji , Thompson Richard F. , Brinton Roberta Diaz
Published: March 2010

Our previous analyses showed that allopregnanolone (APα) significantly increased proliferation of rodent and human neural progenitor cells in vitro. In this study, we investigated the efficacy of APα to promote neurogenesis in the hippocampal subgranular zone (SGZ), to reverse learning and memory deficits in 3-month-old male triple transgenic mouse model of Alzheimer's (3xTgAD) and the correlation between APα-induced neural progenitor cell survival and memory function in 3xTgAD mice. Neural progenitor cell proliferation was determined by unbiased stereological analysis of BrdU incorporation and survival determined by FACS for BrdU+ cells. Learning and memory function was assessed using the hippocampal-dependent trace eye-blink conditioning paradigm. At 3 months, basal level of BrdU+ cells in the SGZ of 3xTgAD mice was significantly lower relative to non-Tg mice, despite the lack of evident AD pathology. APα significantly increased, in a dose-dependent manner, BrdU+ cells in SGZ in 3xTgAD mice and restored SGZ proliferation to normal magnitude. As with the deficit in proliferation, 3xTgAD mice exhibited deficits in learning and memory. APα reversed the cognitive deficits to restore learning and memory performance to the level of normal non-Tg mice. In 3xTgAD mice, APα-induced survival of neural progenitors was significantly correlated with APα-induced memory performance. These findings suggest that early neurogenic deficits, which were evident before immunodetectable Aβ, may contribute to the cognitive phenotype of AD, and that APα could serve as a regenerative therapeutic to prevent or delay neurogenic and cognitive deficits associated with mild cognitive impairment and Alzheimer's disease.
Plasmacytoid dendritic cells sense hepatitis C virus–infected cells, produce interferon, and inhibit infection
Authors: Takahashi Ken , Asabe Shinichi , Wieland Stefan , Garaigorta Urtzi , Gastaminza Pablo , Isogawa Masanori , Chisari Francis V.
Published: March 2010

Hepatitis C virus (HCV), a member of the
Flaviviridae
family, is a single-stranded positive-sense RNA virus that infects >170 million people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Despite its ability to block the innate host response in infected hepatocyte cell lines in vitro, HCV induces a strong type 1 interferon (IFN) response in the infected liver. The source of IFN in vivo and how it is induced are currently undefined. Here we report that HCV-infected cells trigger a robust IFN response in plasmacytoid dendritic cells (pDCs) by a mechanism that requires active viral replication, direct cell-cell contact, and Toll-like receptor 7 signaling, and we show that the activated pDC supernatant inhibits HCV infection in an IFN receptor-dependent manner. Importantly, the same events are triggered by HCV subgenomic replicon cells but not by free virus particles, suggesting the existence of a novel cell-cell RNA transfer process whereby HCV-infected cells can activate pDCs to produce IFN without infecting them. These results may explain how HCV induces IFN production in the liver, and they reveal a heretofore unsuspected aspect of the innate host response to viruses that can subvert the classical sensing machinery in the cells they infect, and do not infect or directly activate pDCs.
Actin oligomers hit the assembly line
Authors: Short Ben
Published: March 2010

Study identifies a new way for actin filaments to polymerize in vivo.
Focal adhesions are sites of integrin extension
Authors: Askari Janet A. , Tynan Christopher J. , Webb Stephen E.D. , Martin-Fernandez Marisa L. , Ballestrem Christoph , Humphries Martin J.
Published: March 2010

Integrins undergo global conformational changes that specify their activation state. Current models portray the inactive receptor in a bent conformation that upon activation converts to a fully extended form in which the integrin subunit leg regions are separated to enable ligand binding and subsequent signaling. To test the applicability of this model in adherent cells, we used a fluorescent resonance energy transfer (FRET)–based approach, in combination with engineered integrin mutants and monoclonal antibody reporters, to image integrin α5β1 conformation. We find that restricting leg separation causes the integrin to adopt a bent conformation that is unable to respond to agonists and mediate cell spreading. By measuring FRET between labeled α5β1 and the cell membrane, we find extended receptors are enriched in focal adhesions compared with adjacent regions of the plasma membrane. These results demonstrate definitely that major quaternary rearrangements of β1-integrin subunits occur in adherent cells and that conversion from a bent to extended form takes place at focal adhesions.
Factors Associated with Increased Healthcare Worker Influenza Vaccination
Rates: Results from a National Survey of University Hospitals and Medical
Centers
Authors: Talbot Thomas R. , Dellit Timothy H. , Hebden Joan , Sama Danny , Cuny Joanne
Published: March 2010

Objective.

To ascertain which components of healthcare worker (HCW) influenza
vaccination programs are associated with higher vaccination rates.

Design.

Survey.

Setting.

University-affiliated hospitals.

Methods.

Participating hospitals were surveyed with regard to their institutional
HCW influenza vaccination program for the 2007-2008 influenza season. Topics
assessed included vaccination adherence and availability, use of declination
statements, education methods, accountability, and data reporting. Factors
associated with higher vaccination rates were ascertained.

Results.

Fifty hospitals representing 368,696 HCWs participated in the project. The
median vaccination rate was 55.0% (range, 25.6%-80.6%); however, the types of
HCWs targeted by vaccination programs varied. Programs with the following
components had significantly higher vaccination rates: weekend provision of
vaccine (58.8% in those with this feature vs 43.9% in those without;
P = .01), train-the-trainer programs (59.5% vs
46.5%; P = .005), report of vaccination rates to
administrators (57.2% vs 48.1%; P = .04) or to the
board of trustees (63.9% vs 53.4%; P = .01), a
letter sent to employees emphasizing the importance of vaccination (59.3% vs
47%; P = .01), and any form of visible leadership
support (57.9% vs 36.9%; P = .01). Vaccination rates
were not significantly different between facilities that did and those that did
not require a signed declination form for HCWs who refused vaccination (56.9%
vs 55.1%; P = .68), although the precise content of
such statements varied.

Conclusions.

Vaccination programs that emphasized accountability to the highest levels
of the organization, provided weekend access to vaccination, and used
train-the-trainer programs had higher vaccination coverage. Of concern, the
types of HCWs targeted by vaccination programs differed, and uniform
definitions will be essential in the event of public reporting of vaccination
rates.
Composition bias and the origin of ORFan genes
Authors: Yomtovian Inbal , Teerakulkittipong Nuttinee , Lee Byungkook , Moult John , Unger Ron
Published: March 2010

Motivation: Intriguingly, sequence analysis of genomes reveals that a large number of genes are unique to each organism. The origin of these genes, termed ORFans, is not known. Here, we explore the origin of ORFan genes by defining a simple measure called ‘composition bias’, based on the deviation of the amino acid composition of a given sequence from the average composition of all proteins of a given genome.

Results: For a set of 47 prokaryotic genomes, we show that the amino acid composition bias of real proteins, random ‘proteins’ (created by using the nucleotide frequencies of each genome) and ‘proteins’ translated from intergenic regions are distinct. For ORFans, we observed a correlation between their composition bias and their relative evolutionary age. Recent ORFan proteins have compositions more similar to those of random ‘proteins’, while the compositions of more ancient ORFan proteins are more similar to those of the set of all proteins of the organism. This observation is consistent with an evolutionary scenario wherein ORFan genes emerged and underwent a large number of random mutations and selection, eventually adapting to the composition preference of their organism over time.

Contact:  ron@biocoml.ls.biu.ac.il

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fire Blight of Apples and Pears: Epidemiological Concepts Comprising the Maryblyt Forecasting Program
Authors: Biggs Alan R. , Turechek W. W.
Published: March 2010

This article describes the fire blight prediction model Maryblyt, developed by Steiner and Lightner, and its recent release in the first Windows-compatible version. A brief discussion of the biological basis for the model is provided, including its integrated use of multiple cumulative heat unit “clocks.” Furthermore, we describe the recent release of Maryblyt v. 7 for Windows, which is available for free.

Accepted for publication 1 December 2009. Published 15 March 2010.
First Report of Sugar Beet Seedling Rust Caused by Puccinia subnitens in Nebraska
Authors: Harveson Robert M.
Published: March 2010

This is the first report of seedling rust on sugar beets and common lambsquarters in Nebraska. It is also the first report of the pycnial stage of P. subnitens from natural infections and documentation of multiple infections of sugar beet leaves beyond the seedling stage. The unusually cool and wet weather during May and June 2009 likely contributed to the high incidence of fields with rust.

Accepted for publication 17 December 2009. Published 15 March 2010.
Predicted crystal structures of tetramethylsilane and tetramethylgermane and an experimental low-temperature structure of tetramethylsilane
Authors: Wolf Alexandra K. , Glinnemann Jürgen , Fink Lothar , Alig Edith , Bolte Michael , Schmidt Martin U.
Published: March 2010

No crystal structure at ambient pressure is known for tetramethylsilane, Si(CH3)4, which is used as a standard in NMR spectroscopy. Possible crystal structures were predicted by global lattice-energy minimizations using force-field methods. The lowest-energy structure corresponds to the high-pressure room-temperature phase (Pa\overline{3},Z= 8). Low-temperature crystallization at 100 K resulted in a single crystal, and its crystal structure has been determined. The structure corresponds to the predicted structure with the second lowest energy rank. In X-ray powder analyses this is the only observed phase between 80 and 159 K. For tetramethylgermane, Ge(CH_3)_4, no experimental crystal structure is known. Global lattice-energy minimizations resulted in 47 possible crystal structures within an energy range of 5 kJ mol−1. The lowest-energy structure was found in Pa\overline{3},Z= 8.
Change in electronic structure in a six-coordinate copper(II) complex accompanied by an anion order/disorder transition
Authors: Kilner Colin A. , Halcrow Malcolm A.
Published: March 2010

A variable-temperature crystallographic study of [Cu(LOH)2][ClO4]2·2(CH3)2CO [LOH= 2,6-bis(hydroxyiminomethyl)pyridine] between 30 and 300 K is presented. The complex exhibits an unusual electronic structure at room temperature with a {d_{z^2}}1ground state, corresponding to an axially compressed ligand coordination geometry about the copper ion. This reflects a suppression of the pseudo-Jahn–Teller distortion that is normally shown by copper(II) compounds with this ligand geometry [Halcrowet al.(2004).New J. Chem.28, 228–233]. On cooling the compound undergoes an abrupt structural change at 157 ± 3 K, that does not involve a change in the space group (P\bar 1), but causes significant changes tocand the unit-cell angles. This reflects a conformational rearrangement of the complex dication, towards a more typical pseudo-Jahn–Teller elongated coordination geometry. This occurs concurrently with a crystallographic ordering of one of the two perchlorate anions, and a significant displacement of the two lattice acetone molecules. The transformation involves displacements of up to 0.5 Å in the non-H atoms of the structure at 30 K, compared with their positions at 300 K. The change in coordination geometry of the complex around 157 K is reflected in a small reduction in its magnetic moment near that temperature.
The diet of Clinitrachus argentatus (Blennioidei: Clinidae) in the northern Aegean and Marmara Seas
Authors: Ozen O. , Altin A. , Ayyildiz H.
Published: March 2010

Differences in the diet composition of small (28–42 mm total length, LT) and large (43–75 mm LT) individuals of the cline Clinitrachus argentatus (Clinidae) were evident. Smaller individuals preyed mainly on copepods, whereas larger individuals ate mainly amphipods, isopods, brachyurans and polychaetes.
Monazite Coatings on Fibers: II, Coating without Strength Degradation
Authors: Boakye Emmanuel E. , Hay Randall S. , Mogilevsky Pavel , Douglas L. M.
Published: March 2010

Washed and unwashed rhabdophane (LaPO4·xH2O) sols were used to apply monazite coatings to 3M Nextel 720 and 610 fibers. This precursor was designed to minimize stress corrosion from gaseous decomposition products at high temperature. The coatings were heat‐treated in‐line at 900°–1300°C, in air, using a continuous vertical coater with immiscible liquid displacement. Coatings were characterized by optical microscopy, scanning electron microscopy, and transmission electron microscopy. The sol was characterized with light‐scattering and zeta‐potential measurements. Precursor phase evolution was studied with differential thermal analysis/thermogravimetric analysis and X‐ray diffractometry. The washed sol had a higher pH and lower weight loss than the unwashed sol. The as‐coated fibers were tensile tested, along with coated fibers heat‐treated in air at 1200°C for 100 h. The precursor was slightly phosphate‐rich, and this excess phosphate reacted with alumina in the fiber to occasionally make very small (<10 nm) pockets of AlPO4 at the coating–fiber interface after 100 h at 1200°C. Both washed and unwashed sols made coated fibers with higher tensile strengths than those of coated fibers made from other precursors, and the washed sol may actually have slightly increased fiber strength when in‐line heat treatments at <1200°C were used. A small amount of AlPO4 may also have helped seal preexisting flaws. Degradation mechanisms during fiber coating are discussed in this paper.
Synthesis of Lead Nickel Niobate–Lead Zirconate Titanate Solid Solutions by a B‐site Precursor Method
Authors: Robert Gilles , Maeder Marlyse Demartin , Damjanovic Dragan , Setter Nava
Published: March 2010

A modified processing method for lead nickel niobate–lead zirconate titanate (Pb(Ni1/3Nb2/3)O3–Pb(Zr,Ti)O3, PNN–PZT) solid solutions is presented. This method is based on the high‐temperature synthesis of a precursor that contains all the B‐site cations (Ti, Zr, Ni, and Nb). This synthesis yields a diphasic mixture that contains a ZrTiO4‐like phase and a rutile‐like phase. Both phases exhibit a cationic valence of 4; thus, it is concluded that the mixing of Ni and Nb cations is adequate for the preparation of PNN–PZT solid solutions. Indeed, a pure perovskite phase has been obtained after calcination with lead oxide for compositions that contain 40 and 50 mol% PNN. Moreover, their electromechanical properties have been shown to be superior to values reported for standard columbite routes. This conclusion has been interpreted in terms of enhanced chemical homogeneity.
Low‐Temperature Sintering, Densification, and Properties of Z‐type Hexaferrite with Bi2O3 Additives
Authors: Zhang Hongguo , Li Longtu , Zhou Ji , Yue Zhenxing , Gui Zhilun
Published: March 2010

The effect of the addition of Bi2O3 on the densification, low‐temperature sintering, and electromagnetic properties of Z‐type planar hexaferrite was investigated. The results show that Bi2O3 additives can improve the densification and promote low‐temperature sintering of Z‐type hexaferrite prepared by a solid‐state reaction method. The presence of Bi2O3 in the grain boundaries and the generation of Fe2+ degrade the initial permeability of the samples but make the quality factor and cut‐off frequency increase. Various possible mechanisms involved in generating these effects were also discussed.
Thermal Decomposition of Zircon Refractories
Authors: Pavlik Robert S. , Holland Hans J. , Payzant E. Andrew
Published: March 2010

Zircon can be used to make refractory brick for the glass industry. At elevated temperatures it is known to dissociate into silica and zirconia. This study was undertaken because one of the factors that can adversely affect the quality of the glass melted in zircon‐lined tanks is the degree of dissociation. The thermal dissociation of purified and unpurified zircon refractory was studied by ambient‐ and high‐temperature X‐ray diffraction (HTXRD) to understand the high‐temperature performance of brick made from this material. Most of the data were collected on powders at or below 1650°C; however, data were collected between 1400° and 2000°C. In addition, small pieces of the refractory were heated to 1650°C, cooled to room temperature, and then examined under ambient conditions. The degree of dissociation was shown to be dependent on purity, particle size, peak temperature, and time at temperature. The HTXRD dissociation was monitored using the intensity of the tetragonal zirconia peaks. The monoclinic polymorph was measured in the ambient runs. High‐temperature mass spectrometry (HTMS) showed that the silica is vaporized at elevated temperatures.
Analyses of Multiple Film Cracking in Film/Substrate Systems
Authors: Hsueh Chun‐Hway
Published: March 2010

Multiple film cracking in a film/substrate system is analyzed in the present study. The system is subjected to residual stresses before loading. A constant displacement rate is applied unidirectionally to stretch the system. An analytical model is developed to derive the stress distribution in the system, and the film‐cracking problem is analyzed using both the strength and the energy criteria. The predicted crack spacing as a function of the applied strain is compared with experimental measurements of multiple cracking of SiOx films with various thicknesses on poly(ethylene terephthalate) substrates. Comparison is also made between the present and other predictions.
Strain Hardening in Superplastic Codoped Yttria‐Stabilized Tetragonal‐Zirconia Polycrystals
Authors: Sasaki Kazutaka , Nakano Manabu , Mimurada Junpei , Ikuhara Yiichi , Sakuma Taketo
Published: March 2010

The superplastic characteristics of 3‐mol%‐yttria‐stabilized tetragonal‐zirconia polycrystals (3Y‐TZP) were drastically improved by the combined addition of germanium oxide and other oxides (titanium, magnesium, and calcium), resulting in up to 1000% elongation under optimum conditions. Extensive work hardening of the codoped compositions for temperatures >1400°C was observed. Dynamic grain growth was not a sufficient mechanism to explain this anomalous high strain hardening. The appearance of a cubic phase that caused abnormal grain growth during testing may have resulted in increased flow stress, which resulted in exaggerated work hardening.
Phase Relationship between 3C‐ and 6H‐Silicon Carbide at High Pressure and High Temperature
Authors: Sugiyama Shin , Togaya Motohiro
Published: March 2010

The phase relationship between 3C‐ and 6H‐SiC is investigated in the pressure range 2.5–6.5 GPa and the temperature range 400°–2500°C, by analyzing recovered samples, using X‐ray diffractometry and Raman‐scattering techniques. The phase transition from 3C‐ to 6H‐SiC occurs at 2200°C and 2.5 GPa. In the pressure range >4.5 GPa, 6H‐SiC transforms to 3C‐SiC at 2500°C, via an intermediate state, as indicated by broadening peaks in the X‐ray diffraction profile. Thermodynamically, 3C‐SiC appears to be the low‐temperature stable form, and the temperature of transition to 6H‐SiC, which is stable at high temperature, appears to increase with pressure.
Advances in understanding the pathogenesis of chronic thromboembolic pulmonary hypertension
Authors: Lang Irene
Published: March 2010

Chronic thromboembolic pulmonary hypertension (CTEPH) comprises organizing thrombotic obstructions in the pulmonary arteries. While roughly 40% of CTEPH cases are not preceded by a venous thromboembolic event, 0·1–5·1% of acute pulmonary thromboemboli evolve into organized obstructions of the pulmonary artery. In patients with predominantly proximal disease, surgical pulmonary endarterectomy provides a potential cure of the disease. For years, the scientific debate of CTEPH was mainly focused around its thromboembolic nature because of striking dissimilarities to classical venous thromboembolism, for example, the lack of risk factors for venous thrombosis, the lack of clinically apparent pulmonary embolism in many patients, the difficulty to reproduce the disease in animal models of thrombosis, and the nature of the pulmonary vascular obstructions that are dissociated from the degree of hemodynamic compromise. Recent studies have confirmed an association between venous thromboembolism and the evolution of CTEPH, and have shed light on disease‐modifying conditions.
Anti‐thymocyte globulin plus etanercept as therapy for myelodysplastic syndromes (MDS): a phase II study
Authors: Scott Bart L. , Ramakrishnan Aravind , Fosdal Mark , Storer Barry , Becker Pamela , Petersdorf Steve , Deeg H.Joachim
Published: March 2010

Immunosuppressive therapies have proven valuable in treating patients with myelodysplastic syndromes (MDS). We evaluated the combination of equine anti‐thymocyte globulin (ATGAM®) and the soluble tumour necrosis factor receptor, etanercept (Enbrel®), in a phase II trial. Twenty‐five patients with MDS [4‐refractory anaemia (RA), 2‐RA with ring sideroblasts, 15‐refractory cytopenia with multilineage dysplasia (RCMD), 3‐RCMD and ring sideroblasts, 1‐RA with excess blasts type 1] in International Prognostic Staging System risk groups low (n = 11) or intermediate‐1 (n = 14) were enrolled. All patients were platelet or red cell transfusion‐dependent. Nineteen patients completed therapy with ATG at 40 mg/kg per day for four consecutive days, followed by etanercept, 25 mg subcutaneous twice a week for 2 weeks, every month for 4 months. Thirteen patients had haematological improvement (HI)‐erythroid, 2 HI‐neutrophil, and 6 HI‐platelet. One patient with a co‐existing diagnosis of multiple sclerosis and rheumatoid arthritis had a complete remission. The overall response by intent to treat analysis among the 25 patients was 56% (95% confidence interval 35–56%). Four patients did not complete their first course of therapy and one patient did not survive to the 8‐week post‐treatment assessment. Among patients who completed treatment and survived to the 8‐week assessment, 70% had at least haematological responses lasting for at least 5 to more than 36 months. Thus, combination therapy with ATG and etanercept was active and safe in patients with MDS.
Correlation of transient elastography with APRI and FIB‐4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection
Authors: VIDOVIC N. , LOCHOWSKY R. S. , GOLDMANN G. , ROCKSTROH J. , WASMUTH J. C. , SPENGLER U. , SAUERBRUCH T. , LAMMERT F. , OLDENBURG J. , GRÜNHAGE F.
Published: March 2010

Summary.  Patients with inherited bleeding disorders frequently suffer from chronic hepatitis C virus (HCV) mono‐ or human immunodeficiency virus (HIV)/HCV coinfection. Non‐invasive markers for liver fibrosis are warranted for these patients. We tested a large cohort of haemophilic patients with HCV mono‐ or HIV/HCV coinfection for correlation of transient elastography (TE) with two simple surrogate markers of liver fibrosis and for differences in fibrosis stages according to these markers. We prospectively enrolled HCV‐positive patients with congenital bleeding disorders with or without HIV coinfection. Liver function tests and platelet counts were determined and TE was performed. Aspartate aminotransferase‐to‐platelet ratio index (APRI) and a simple index called FIB‐4 were calculated and results were correlated with TE. A total number of 174 patients were included (23% HCV, 36% HIV/HCV coinfected, 33% with cleared HCV and 8% with ongoing HIV but cleared HCV). TE correlated significantly with APRI and FIB‐4 (r = 0.60; P < 0.001 and r = 0.54; P < 0.001 respectively). This correlation was pronounced in patients with ongoing HCV infection (r = 0.67; P < 0.001 and r = 0.60; P < 0.001). Prediction of advanced fibrosis resulted in concordance rates >80% with combinations of TE plus APRI and APRI plus FIB‐4. HIV/HCV coinfected patients did not present with advanced fibrosis stages when compared with HCV‐monoinfected patients. Combinations of two non‐invasive markers may significantly reduce the number of liver biopsies in patients with bleeding disorders and advanced liver fibrosis. Furthermore, our data support previous studies that observed a favourable outcome in patients with HIV/HCV and a preserved immune function in times of highly active antiretroviral therapy.