bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue-specific roles of Axin2 in the inhibition and activation of Wnt signaling in the mouse embryo
Authors: Qian Lihui , Mahaffey James P. , Alcorn Heather L. , Anderson Kathryn V.
Published: May 2011

Axin proteins are key negative regulators of the canonical Wnt signal transduction pathway. Although
Axin2
null mice are viable, we identified an unusual ENU-induced recessive allele of
Axin2
,
canp
, that causes midgestation lethality in homozygotes. We show that the

Axin2
canp

mutation is a V26D substitution in an invariant N-terminal sequence motif and that the Axin2
canp
protein is more stable than wild type. As predicted for an increased level of a negative regulator, the

Axin2
canp

mutation leads to decreased Wnt signaling in most tissues, and this can account for most of the morphological phenotypes of

Axin2
canp

mutants. In contrast, there is a paradoxical increase in canonical Wnt activity in the late primitive streak of all

Axin2
canp

mutant embryos that is associated with the formation of an ectopic tail in some mutants. Treatment of wild-type embryos with an inhibitor of Tankyrase that stabilizes Axin proteins also causes inhibition of Wnt signaling in anterior regions of the embryo and a gain of Wnt signaling in the primitive streak. The results indicate that although increased stability of Axin2 leads to a loss of canonical Wnt signaling in most tissues, stabilized Axin2 enhances Wnt pathway activity in a specific progenitor population in the late primitive streak.
Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells
Authors: Itoh Munenari , Kiuru Maija , Cairo Mitchell S. , Christiano Angela M.
Published: May 2011

Embryonic stem cells (ESCs) have an unlimited proliferative capacity and extensive differentiation capability. They are an alternative source for regenerative therapies with a potential role in the treatment of several human diseases. The clinical use of ESCs, however, has significant ethical and biological obstacles related to their derivation from embryos and potential for immunological rejection, respectively. These disadvantages can be circumvented by the alternative use of induced pluripotent stem cells (iPSCs), which are generated from an individual's (autologous) somatic cells by exogenous expression of defined transcription factors and have biological characteristics similar to ESCs. In recent years, patient-specific iPSCs have been generated to study disease mechanisms and develop iPSC-based therapies. The development of iPSC-based therapies for skin diseases requires successful differentiation of iPSCs into cellular components of the skin, including epidermal keratinocytes. Here, we succeeded in generating iPSCs not only from normal human fibroblasts but also from fibroblasts isolated from the skin of two patients with recessive dystrophic epidermolysis bullosa. Moreover, we differentiated both of these iPSCs into keratinocytes with high efficiency, and generated 3D skin equivalents using iPSC-derived keratinocytes, suggesting that they were fully functional. Our studies indicate that autologous iPSCs have the potential to provide a source of cells for regenerative therapies for specific skin diseases.
Methane contamination of drinking water accompanying gas-well drilling and hydraulic fracturing
Authors: Osborn Stephen G. , Vengosh Avner , Warner Nathaniel R. , Jackson Robert B.
Published: May 2011

Directional drilling and hydraulic-fracturing technologies are dramatically increasing natural-gas extraction. In aquifers overlying the Marcellus and Utica shale formations of northeastern Pennsylvania and upstate New York, we document systematic evidence for methane contamination of drinking water associated with shale-gas extraction. In active gas-extraction areas (one or more gas wells within 1 km), average and maximum methane concentrations in drinking-water wells increased with proximity to the nearest gas well and were 19.2 and 64 mg CH
4
 L
-1
(
n
 = 26), a potential explosion hazard; in contrast, dissolved methane samples in neighboring nonextraction sites (no gas wells within 1 km) within similar geologic formations and hydrogeologic regimes averaged only 1.1 mg L
-1
(
P
 < 0.05;
n
 = 34). Average
δ
13
C-CH
4
values of dissolved methane in shallow groundwater were significantly less negative for active than for nonactive sites (-37 ± 7‰ and -54 ± 11‰, respectively;
P
 < 0.0001). These
δ
13
C-CH
4
data, coupled with the ratios of methane-to-higher-chain hydrocarbons, and
δ
2
H-CH
4
values, are consistent with deeper thermogenic methane sources such as the Marcellus and Utica shales at the active sites and matched gas geochemistry from gas wells nearby. In contrast, lower-concentration samples from shallow groundwater at nonactive sites had isotopic signatures reflecting a more biogenic or mixed biogenic/thermogenic methane source. We found no evidence for contamination of drinking-water samples with deep saline brines or fracturing fluids. We conclude that greater stewardship, data, and—possibly—regulation are needed to ensure the sustainable future of shale-gas extraction and to improve public confidence in its use.
Mechanics of surface area regulation in cells examined with confined lipid membranes
Authors: Staykova Margarita , Holmes Douglas P. , Read Clarke , Stone Howard A.
Published: May 2011

Cells are wrapped in inelastic membranes, yet they can sustain large mechanical strains by regulating their area. The area regulation in cells is achieved either by membrane folding or by membrane exo- and endocytosis. These processes involve complex morphological transformations of the cell membrane, i.e., invagination, vesicle fusion, and fission, whose precise mechanisms are still under debate. Here we provide mechanistic insights into the area regulation of cell membranes, based on the previously neglected role of membrane confinement, as well as on the strain-induced membrane tension. Commonly, the membranes of mammalian and plant cells are not isolated, but rather they are adhered to an extracellular matrix, the cytoskeleton, and to other cell membranes. Using a lipid bilayer, coupled to an elastic sheet, we are able to demonstrate that, upon straining, the confined membrane is able to regulate passively its area. In particular, by stretching the elastic support, the bilayer laterally expands without rupture by fusing adhered lipid vesicles; upon compression, lipid tubes grow out of the membrane plane, thus reducing its area. These transformations are reversible, as we show using cycles of expansion and compression, and closely reproduce membrane processes found in cells during area regulation. Moreover, we demonstrate a new mechanism for the formation of lipid tubes in cells, which is driven by the membrane lateral compression and may therefore explain the various membrane tubules observed in shrinking cells.
Functional agonism of insect odorant receptor ion channels
Authors: Jones Patrick L. , Pask Gregory M. , Rinker David C. , Zwiebel Laurence J.
Published: May 2011

In insects, odor cues are discriminated through a divergent family of odorant receptors (ORs). A functional OR complex consists of both a conventional odorant-binding OR and a nonconventional coreceptor (Orco) that is highly conserved across insect taxa. Recent reports have characterized insect ORs as ion channels, but the precise mechanism of signaling remains unclear. We report the identification and characterization of an Orco family agonist, VUAA1, using the
Anopheles gambiae
coreceptor (AgOrco) and other orthologues. These studies reveal that the Orco family can form functional ion channels in the absence of an odor-binding OR, and in addition, demonstrate a first-in-class agonist to further research in insect OR signaling. In light of the extraordinary conservation and widespread expression of the Orco family, VUAA1 represents a powerful new family of compounds that can be used to disrupt the destructive behaviors of nuisance insects, agricultural pests, and disease vectors alike.
Retinoic acid receptor signaling regulates choroid fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme
Authors: Lupo Giuseppe , Gestri Gaia , O'Brien Matthew , Denton Ross M. , Chandraratna Roshantha A. S. , Ley Steven V. , Harris William A. , Wilson Stephen W.
Published: May 2011

Retinoic acid receptor (RAR) signaling is required for morphogenesis of the ventral optic cup and closure of the choroid fissure, but the mechanisms by which this pathway regulates ventral eye development remain controversial and poorly understood. Although previous studies have implicated neural crest–derived periocular mesenchyme (POM) as the critical target of RA action in the eye, we show here that RAR signaling regulates choroid fissure closure in zebrafish by acting on both the ventral optic cup and the POM. We describe RAR-dependent regulation of eight genes in the neuroepithelial cells of the ventral retina and optic stalk and of six genes in the POM and show that these ventral retina/optic stalk and POM genes function independently of each other. Consequently, RAR signaling regulates ventral eye development through two independent, nonredundant mechanisms in different ocular tissues. Furthermore, the identification of two cohorts of genes implicated in ventral eye morphogenesis may help to elucidate the genetic basis of ocular coloboma in humans.
Neuroprotection mediated through estrogen receptor-α in astrocytes
Authors: Spence Rory D. , Hamby Mary E. , Umeda Elizabeth , Itoh Noriko , Du Sienmi , Wisdom Amy J. , Cao Yuan , Bondar Galyna , Lam Jeannie , Ao Yan , Sandoval Francisco , Suriany Silvie , Sofroniew Michael V. , Voskuhl Rhonda R.
Published: May 2011

Estrogen has well-documented neuroprotective effects in a variety of clinical and experimental disorders of the CNS, including autoimmune inflammation, traumatic injury, stroke, and neurodegenerative diseases. The beneficial effects of estrogens in CNS disorders include mitigation of clinical symptoms, as well as attenuation of histopathological signs of neurodegeneration and inflammation. The cellular mechanisms that underlie these CNS effects of estrogens are uncertain, because a number of different cell types express estrogen receptors in the peripheral immune system and the CNS. Here, we investigated the potential roles of two endogenous CNS cell types in estrogen-mediated neuroprotection. We selectively deleted estrogen receptor-α (ERα) from either neurons or astrocytes using well-characterized
Cre-loxP
systems for conditional gene knockout in mice, and studied the effects of these conditional gene deletions on ERα ligand-mediated neuroprotective effects in a well-characterized model of adoptive experimental autoimmune encephalomyelitis (EAE). We found that the pronounced and significant neuroprotective effects of systemic treatment with ERα ligand on clinical function, CNS inflammation, and axonal loss during EAE were completely prevented by conditional deletion of ERα from astrocytes, whereas conditional deletion of ERα from neurons had no significant effect. These findings show that signaling through ERα in astrocytes, but not through ERα in neurons, is essential for the beneficial effects of ERα ligand in EAE. Our findings reveal a unique cellular mechanism for estrogen-mediated CNS neuroprotective effects by signaling through astrocytes, and have implications for understanding the pathophysiology of sex hormone effects in diverse CNS disorders.
Functional relevance of the histone γH2Ax in the response to DNA damaging agents
Authors: Revet Ingrid , Feeney Luzviminda , Bruguera Stephanie , Wilson Wade , Dong Tiffany K. , Oh Dennis H. , Dankort David , Cleaver James E.
Published: May 2011

The phosphorylation of H2Ax on its S139 site, γH2Ax, is important during DNA double-strand repair and is considered necessary for assembly of repair complexes, but its functional role after other kinds of DNA damage is less clear. We have measured the survival of isogenic mouse cell lines with the H2Ax gene knocked out, and replaced with wild-type or mutant (S139A) H2Ax genes, exposed to a range of agents with varied mechanisms of DNA damage. Knockout and mutant cells were sensitive to γ-rays, etoposide, temozolamide, and endogenously generated reactive oxygen species, each of which can include double-strand breaks among their spectra of DNA lesions. The absence or mutation of H2Ax had no influence on sensitivity to cisplatin or mitomycin C. Although UV light induced the highest levels of γH2Ax, mutation of S139 had no influence on UV sensitivity or the UV DNA damage response. Complete loss of H2Ax reduced the survival of cells exposed to UV light and reduced pChk1 induction, suggesting that sites other than S139 may impact the ATR-pChk1 pathway. The relative intensity of γH2Ax measured in Western blots in wild-type cells did not correlate with the functional importance of γH2Ax. The use of γH2Ax as a general biomarker of DNA damage is therefore potentially misleading because it is not an unambiguous indicator of double-strand breaks, and a significant fraction of DNA repair, especially involving nucleotide excision or crosslink repair, can occur without functional involvement of γH2Ax.
Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway
Authors: Gu Yapeng , Forostyan Tetyana , Sabbadini Roger , Rosenblatt Jody
Published: May 2011

To maintain an intact barrier, epithelia eliminate dying cells by extrusion. During extrusion, a cell destined for apoptosis signals its neighboring cells to form and contract a ring of actin and myosin, which squeezes the dying cell out of the epithelium. Here, we demonstrate that the signal produced by dying cells to initiate this process is sphingosine-1-phosphate (S1P). Decreasing S1P synthesis by inhibiting sphingosine kinase activity or by blocking extracellular S1P access to its receptor prevented apoptotic cell extrusion. Extracellular S1P activates extrusion by binding the S1P2 receptor in the cells neighboring a dying cell, as S1P2 knockdown in these cells or its loss in a zebrafish mutant disrupted cell extrusion. Because live cells can also be extruded, we predict that this S1P pathway may also be important for driving delamination of stem cells during differentiation or invasion of cancer cells.
Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres
Authors: da Silva Lopes Katharina , Pietas Agnieszka , Radke Michael H. , Gotthardt Michael
Published: May 2011

The giant muscle protein titin is an essential structural component of the sarcomere. It forms a continuous periodic backbone along the myofiber that provides resistance to mechanical strain. Thus, the titin filament has been regarded as a blueprint for sarcomere assembly and a prerequisite for stability. Here, a novel titin-eGFP knockin mouse provided evidence that sarcomeric titin is more dynamic than previously suggested. To study the mobility of titin in embryonic and neonatal cardiomyocytes, we used fluorescence recovery after photobleaching and investigated the contribution of protein synthesis, contractility, and calcium load to titin motility. Overall, the kinetics of lateral and longitudinal movement of titin-eGFP were similar. Whereas protein synthesis and developmental stage did not alter titin dynamics, there was a strong, inhibitory effect of calcium on titin mobility. Our results suggest a model in which the largely unrestricted movement of titin within and between sarcomeres primarily depends on calcium, suggesting that fortification of the titin filament system is activity dependent.
Modeling the Spread of Methicillin-Resistant Staphylococcus aureus (MRSA) Outbreaks throughout the Hospitals in Orange County, California
Authors: Lee Bruce Y. , McGlone Sarah M. , Wong Kim F. , Yilmaz S. Levent , Avery Taliser R. , Song Yeohan , Christie Richard , Eubank Stephen , Brown Shawn T. , Epstein Joshua M. , Parker Jon I. , Burke Donald S. , Platt Richard , Huang Susan S.
Published: May 2011

Background.

Since hospitals in a region often share patients, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in one hospital could affect other hospitals.

Methods.

Using extensive data collected from Orange County (OC), California, we developed a detailed agent-based model to represent patient movement among all OC hospitals. Experiments simulated MRSA outbreaks in various wards, institutions, and regions. Sensitivity analysis varied lengths of stay, intraward transmission coefficients (β), MRSA loss rate, probability of patient transfer or readmission, and time to readmission.

Results.

Each simulated outbreak eventually affected all of the hospitals in the network, with effects depending on the outbreak size and location. Increasing MRSA prevalence at a single hospital (from 5% to 15%) resulted in a 2.9% average increase in relative prevalence at all other hospitals (ranging from no effect to 46.4%). Single-hospital intensive care unit outbreaks (modeled increase from 5% to 15%) caused a 1.4% average relative increase in all other OC hospitals (ranging from no effect to 12.7%).

Conclusion.

MRSA outbreaks may rarely be confined to a single hospital but instead may affect all of the hospitals in a region. This suggests that prevention and control strategies and policies should account for the interconnectedness of health care facilities.
Clinical Impact of Blood Cultures Contaminated with Coagulase-Negative Staphylococci at an Academic Medical Center
Authors: van der Heijden Yuri F. , Miller Geraldine , Wright Patty W. , Shepherd Bryan E. , Daniels Titus L. , Talbot Thomas R.
Published: May 2011

Of all blood cultures positive for coagulase-negative staphylococci collected in 1 year at an academic hospital, 100 were selected randomly for review and designated true positives or contaminated. For the 85 patients whose cultures were determined to be contaminated, chart abstractions revealed substantial unnecessary antibiotic administration, additional laboratory tests and procedures, and hospital readmissions.
Investigation of an Outbreak of 2009 Pandemic Influenza A Virus (H1N1) Infections among Healthcare Personnel in a Chicago Hospital
Authors: Magill Shelley S. , Black Stephanie R. , Wise Matthew E. , Kallen Alexander J. , Lee Soo-Jeong , Gardner Tracie , Husain Farah , Srinivasan Arjun , Gerber Susan I. , Jhung Michael
Published: May 2011

In May 2009, we investigated a hospital outbreak of pandemic H1N1 (pH1N1) infection among healthcare personnel (HCP). Thirteen (65%) of 20 HCP with pH1N1 infection had healthcare-associated cases, which were primarily attributed to transmission among HCP. Eleven (55%) of HCP with pH1N1 infection worked for 1 day or more after the onset of illness. Personnel working with mild illness may have contributed to transmission among HCP.
Hospital-Wide Reduction in Central Line–Associated Bloodstream Infections: A Tale of Two Small Community Hospitals
Authors: Gozu Aysegul , Clay Colleen , Younus Faheem
Published: May 2011

Despite increasing awareness of central line-associated bloodstream infections (CLABSIs) in general wards, published strategies come from intensive care units (ICUs) of large tertiary care centers. After implementing a central line insertion checklist, two community hospitals experienced an 86% reduction in CLABSI rates in ICUs and a 57% reduction in non-ICU settings over 36 months.
Peripheral Venous Catheter-Related Staphylococcus aureus Bacteremia
Authors: Trinh T. Tony , Chan Philip A. , Edwards Omega , Hollenbeck Brian , Huang Brian , Burdick Nancy , Jefferson Julie A. , Mermel Leonard A.
Published: May 2011

Objective.

Better understand the incidence, risk factors, and outcomes of peripheral venous catheter (PVC)-related Staphylococcus aureus bacteremia.

Design.

Retrospective study of PVC-related S. aureus bacteremias in adult patients from July 2005 through March 2008. A point-prevalence survey was performed January 9, 2008, on adult inpatients to determine PVC utilization; patients with a PVC served as a cohort to assess risk factors for PVC-related S. aureus bacteremia.

Setting.

Tertiary care teaching hospital.

Results.

Twenty-four (18 definite and 6 probable) PVC-related S. aureus bacteremias were identified (estimated incidence density, 0.07 per 1,000 catheter-days), with a median duration of catheterization of 3 days (interquartile range, 2-6). Patients with PVC-related S. aureus bacteremia were significantly more likely to have a PVC in the antecubital fossa (odds ratio [OR], 6.5), a PVC placed in the emergency department (OR, 6.0), or a PVC placed at an outside hospital (P = .005), with a longer duration of catheterization (P < .001). These PVCs were significantly less likely to have been inserted in the hand (OR, 0.23) or placed on an inpatient medical unit (OR, 0.17). Mean duration of antibiotic treatment was 19 days (95% confidence interval, 15-23 days); 42% (10/24) of cases encountered complications. We estimate that there may be as many as 10,028 PVC-related S. aureus bacteremias yearly in US adult hospitalized inpatients.

Conclusion.

PVC-related S. aureus bacteremia is an underrecognized complication. PVCs inserted in the emergency department or at outside institutions, PVCs placed in the antecubital fossa, and those with prolonged dwell times are associated with such infections.
Hand Hygiene, and Not Ertapenem Use, Contributed to Reduction of Carbapenem-Resistant Pseudomonas aeruginosa Rates
Authors: Santos Rodrigo Pires dos , Jacoby Thalita , Machado Denise Pires , Lisboa Thiago , Gastal Sandra Ludwig , Nagel Fabiano Márcio , Kuplich Nádia Mora , Konkewicz Loriane , Lovatto Carem Gorniak , Pires Márcia Rosane , Goldani Luciano Zubaran
Published: May 2011

Objective.

To evaluate the impact of ertapenem use in Pseudomonas aeruginosa carbapenem resistance, taking into account the volume of antimicrobial consumption, the consumption by the entire hospital of alcohol-based antiseptic hand rub, and the density rate of invasive practices.

Design.

Before-and-after trial.

Setting.

A tertiary care university hospital in southern Brazil.

Methods.

Ertapenem was first added to the hospital formulary in June 2006, and it was excluded in February 2009. We evaluated Pseudomonas aeruginosa resistance rates through 3 study periods: period 1, before ertapenem use (17 months); period 2, during ertapenem use (33 months); and period 3, after exclusion of ertapenem (15 months).

Results.

After introduction of ertapenem, there was a significant decrease in median consumption of imipenem or meropenem, from 2.6 to 2.2 defined daily doses (DDDs) per 100 patient-days (level change from 0.04 to -1.08; P < .01), and an increase in the use of these medications after ertapenem exclusion, from 2.2 to 3.3 DDDs per 100 patient-days (level change from -0.14 to 0.91; P < .01), by segmented regression analysis. There was no difference in the incidence density of carbapenem-resistant P. aeruginosa infection related to ertapenem use throughout the study periods. However, by multiple regression analysis, the reduction in the rate of carbapenem-resistant P. aeruginosa infection correlated significantly with the increase in the volume of alcohol used as hand sanitizer, which was from 660.7 mL per 100 patient-days in period 1 to 2,955.1 mL per 100 patient-days in period 3 (P = .04). Ertapenem use did not impact the rate of carbapenem-resistant P. aeruginosa infection.

Conclusions.

Use of alcohol-based hand gel, rather than ertapenem, was associated with a reduction in the rates of carbapenem-resistant P. aeruginosa infection. Measures to reduce resistance must include factors other than just antimicrobial stewardship programs alone.
Improving Influenza Vaccination of Healthcare Workers by Means of Quality Improvement Tools
Authors: Cadena Jose , Prigmore Teresa , Bowling Jason , Ayala Beth Ann , Kirkman Leni , Parekh Amruta , Scepanski Theresa , Patterson Jan E.
Published: May 2011

For a healthcare worker seasonal influenza vaccination quality improvement project, interventions included support of leadership, distribution of vaccine kits, grand rounds, an influenza website, a Screensaver, e-mails, phone messages, and audit feedback. Vaccination rates increased from 58.8% to 76.6% (P < .01). Quality improvement increased the voluntary vaccination rate but did not achieve a rate more than 80%.
Demagnetizing effects in stacked rectangular prisms
Authors: Christensen D V , Nielsen K K , Bahl C R H , Smith A
Published: May 2011

A numerical, magnetostatic model of the internal magnetic field of a rectangular prism is extended to the case of a stack of rectangular prisms. The model enables the calculation of the spatially resolved, three-dimensional internal field in such a stack given any magnetic state function, stack configuration, temperature distribution and applied magnetic field. In this paper the model is applied to the case of a stack of parallel, ferromagnetic rectangular prisms and the resulting internal field is found as a function of the orientation of the applied field, the number of prisms in the stack, the spacing between the prisms and the packing density of the stack. The results show that the resulting internal field is far from being equal to the applied field and that the various stack configurations investigated affect the resulting internal field significantly and non-linearly. The results have a direct impact on the design of, e.g., active magnetic regenerators made of stacked rectangular prisms in terms of optimizing the internal field.
Modelling of plasma bullet propagation along a helium jet in ambient air
Authors: Naidis G V
Published: May 2011

The results of simulation of positive streamer propagation along a helium jet in ambient air are presented. A two-dimensional axially symmetric streamer model, accounting for variation of helium–air mixture composition in the jet, is used. The obtained distributions of plasma parameters have a ring-shaped structure, typical for plasma bullets. The calculated radial profiles of emitting nitrogen molecules agree with experimental data.
Photodissociation of HOD via the C̃1B1 State: OD/OH Branching Ratio and OD Bond Dissociation Energy
Authors: Cheng Li-na , Cheng Yuan , Yuan Kai-jun , Guo Qing , Wang Tao , Dai Dong-xu , Yang Xue-ming
Published: May 2011

Photodissociation of jet-cooled HOD via the C̃ state around 124 nm has been studied using the H(D)-atom Rydberg tagging time-of-flight technique. Rotational state resolved action spectrum and the product translational energy distribution spectra have been recorded for both D+OH and H+OD dissociation channels. Product channel OH/OD branching ratios for the individual C̃-X̃ rotational transition have been determined. A comparison is also given with the B̃-X̃ and Ã-X̃ transitions. In addition, the dissociation energy of the OD bond in HOD has been determined accurately to be 41751.3±5 cm−1.
Asymmetry in the Strong-field Photodetachment of H− by Linearly Polarized Few-cycle Pulses
Authors: Bai Li-hua , Liu Yu-heng , Cui Ting-ting , Wang Yan , Zhang Hui-fang
Published: May 2011

Photodetachment of H− irradiated by linearly polarized few-cycle laser field is investigated by time-dependent Schrödinger equation numerically. The photo-electron left-right asymmetry parameter as a function of carrier-envelop (CE) phase of few-cycle pulses is attained. We confirm the asymmetry of photoelectron distribution in H− photodetachment and find that the maximal asymmetry parameter of H− is equal to that of H atom under the same conditions but the corresponding CE phases are quite different. Thus a CE phase shift appears. Compared to that of H atom and field free electron, the zero asymmetry CE phase shift is sensitively affected by Coulomb field. The Coulomb effect on the asymmetry of H− photodetachment mainly behaves in the CE phase shift of H− instead of the amplitude of asymmetry parameter curve.
First Principles Study of Half-metallic Properties at MnSb/GaSb(001) Interface
Authors: Sartipi Elmira , Hojabri Alireza , Bouchani Arash , Homayion Shakib Mohammad
Published: May 2011

Density functional theory calculations are performed to study the structural, electronic and magnetic properties of hexagonal NiAs type and cubic zinc blende type MnSb structure and interface of zinc blende MnSb with GaSb(001). We used generalized gradiant approximation to calculate the exchange-correlation term in bulk and interface determination. The zinc blende structure of MnSb is found to be ferromagnetic half-metal with a total moment of 4 μB per formula unit. Results show that the half-metallicity character is preserved at MnSb/GaSb(001) interface. The magnetic moment of Mn atom in interface is reduced and the magnetic moment of the interface Sb atom is equal to the average of the corresponding bulk values in two sides of the interface. The band alignment properties are also computed and a rather large minority valance band offset of about 1.25 eV is obtained in this heterojunction.
DFT Study on Molecular Structures and ROS Scavenging Mechanisms of Novel Antioxidants fromLespedeza Virgata
Authors: Li Min-jie , Zhang Liang-miao , Liu Wei-xia , Lu Wen-cong
Published: May 2011

The molecular structure and radical scavenging activity of three novel antioxidants from Lespedeza Virgata, lespedezavirgatol, lespedezavirgatal, and lespedezacoumestan, have been studied using density functional theory with the B3LYP and BhandHLYP methods. The optimized geometries of neutral, radical cation, radical and anion forms were obtained at the B3LYP/6–31G(d) level, in which it was found that all the most stable conformations contain intramolecular hydrogen bonds. The same results were obtained from the MP2 method. The homolytic O—H bond dissociation enthalpy and the adiabatic ionization potential of neutral and anion forms for the three new antioxidants and adiabatic electron affinity and H-atom affinity for hydroxyl radical, superoxide anion radical, and hydrogen peroxide radical were determined both in gas phase and in aqueous solution using IEF-PCM and CPCM model with UAHF or Bondi cavity. The antioxidant activities and reactive oxygen species scavenging mechanisms were then discussed, and the results obtained from different methods are consistent. Furthermore, the antioxidant activities are consistent with the experimental findings of the compounds under investigation.
Plane continua and totally disconnected sets of buried points
Authors: van Mill Jan , Tuncali Murat
Published: May 2011

It is shown that there is a continuum in the plane whose set of buried points is totally disconnected and weakly 1-dimensional, but not zero-dimensional. This answers a problem of Curry, Mayer and Tymchatyn.
Transcriptional activation of histone H4 by C/EBPβ during the mitotic clonal expansion of 3T3-L1 adipocyte differentiation
Authors: Zhang You-You , Li Xi , Qian Shu-Wen , Guo Liang , Huang Hai-Yan , He Qun , Liu Yuan , Ma Chun-Gu , Tang Qi-Qun
Published: May 2011

CCAAT enhancer binding protein β (C/EBPβ) is required for both mitotic clonal expansion (MCE) and terminal differentiation during the 3T3-L1 adipocyte differentiation program. Whereas the mechanism of C/EBPβ during terminal differentiation is well understood, the mechanism of C/EBPβ in MCE is not. We provide evidence that histone H4, the most conserved cell cycle–related histone, the change of which is strictly correlated with DNA content change during the cell cycle, is transcriptionally activated by C/EBPβ during MCE. Expression of histone H4 is increased at 16 h after induction when 3T3-L1 preadipocytes synchronously reenter S phase, which is correlated with the sequential phosphorylation and activation of C/EBPβ, and expression was partially suppressed when A-C/EBP (dominant negative for C/EBP protein) was overexpressed. One C/EBP-binding site was identified in one of the histone H4 gene promoters (hist4h4), confirmed by both electrophoretic mobility shift assay and chromatin immunoprecipitation assay. C/EBP-binding sites were also found in 9 of 11 other histone H4 promoters, which can also be transactivated by C/EBPβ. Knockdown of C/EBPβ by stealth small interfering RNA partially decreased H4 gene expression and arrested cells in G1 phase as indicated by bromodeoxyuridine incorporation and fluorescence-activated cell sorting analysis of DNA content. This study provides new insights into why C/EBPβ is required for MCE during 3T3-L1 adipocyte differentiation and why C/EBPβ plays important roles in the proliferation of other cell types.
Genome annotation test with validation on transcription start site and ChIP-Seq for Pol-II binding data
Authors: Bedo Justin , Kowalczyk Adam
Published: May 2011

Motivation: Many ChIP-Seq experiments are aimed at developing gold standards for determining the locations of various genomic features such as transcription start or transcription factor binding sites on the whole genome. Many such pioneering experiments lack rigorous testing methods and adequate ‘gold standard’ annotations to compare against as they themselves are the most reliable source of empirical data available. To overcome this problem, we propose a self-consistency test whereby a dataset is tested against itself. It relies on a supervised machine learning style protocol for in silico annotation of a genome and accuracy estimation to guarantee, at least, self-consistency.

Results: The main results use a novel performance metric (a calibrated precision) in order to assess and compare the robustness of the proposed supervised learning method across different test sets. As a proof of principle, we applied the whole protocol to two recent ChIP-Seq ENCODE datasets of STAT1 and Pol-II binding sites. STAT1 is benchmarked against in silico detection of binding sites using available position weight matrices. Pol-II, the main focus of this paper, is benchmarked against 17 algorithms for the closely related and well-studied problem of in silico transcription start site (TSS) prediction. Our results also demonstrate the feasibility of in silico genome annotation extension with encouraging results from a small portion of annotated genome to the remainder.

Availability: Available from http://www.genomics.csse.unimelb.edu.au/gat.

Contact:  justin.bedo@nicta.com.au; adam.kowalczyk@nicta.com.au

Supplementary Information:  Supplementary data are available at Bioinformatics online.
On the Fixed-Effects Vector Decomposition
Authors: Breusch Trevor , Ward Michael B. , Nguyen Hoa Thi Minh , Kompas Tom
Published: May 2011

This paper analyzes the properties of the fixed-effects vector decomposition estimator, an emerging and popular technique for estimating time-invariant variables in panel data models with group effects. This estimator was initially motivated on heuristic grounds, and advocated on the strength of favorable Monte Carlo results, but with no formal analysis. We show that the three-stage procedure of this decomposition is equivalent to a standard instrumental variables approach, for a specific set of instruments. The instrumental variables representation facilitates the present formal analysis that finds: (1) The estimator reproduces exactly classical fixed-effects estimates for time-varying variables. (2) The standard errors recommended for this estimator are too small for both time-varying and time-invariant variables. (3) The estimator is inconsistent when the time-invariant variables are endogenous. (4) The reported sampling properties in the original Monte Carlo evidence do not account for presence of a group effect. (5) The decomposition estimator has higher risk than existing shrinkage approaches, unless the endogeneity problem is known to be small or no relevant instruments exist.
Resistant Starch and Starch Thermal Characteristics in Exotic Corn Lines Grown in Temperate and Tropical Environments
Authors: Pollak Linda M. , Scott M. Paul , Duvick Susan A.
Published: May 2011

Corn as a food that is heated and cooled to allow starch retrogradation has higher levels of resistant starch (RS). Increasing the amount of RS can make corn an even healthier food and may be accomplished by breeding and selection, especially by using exotic germplasm. Sixty breeding lines of introgressed exotic germplasm backgrounds, selected for high yield, were grown in three tropical and temperate locations and analyzed for starch thermal characteristics and RS levels. Although actual values for all starch characteristics were within normal levels, most characteristics had significant genotypic effects, and all had significant location effects. Thermal properties of retrograded starch were more influenced by the environment than the thermal properties of raw starch, making retrograded starch traits more heritable than raw starch traits. This suggests that a breeding strategy based on retrograded starch traits will have a better chance of success than a breeding strategy based on raw starch traits. A significant genotype effect for RS levels indicates that genotypic selection to raise the level of RS and increase the healthful aspects of corn food should be successful. Significant location effects indicate that breeders using winter nurseries to accelerate their breeding progress need to be careful when making selections using RS data collected on seed grown in the tropics. A small but highly significant correlation between RS and some thermal characteristics, especially percentage of retrogradation, indicates that we may be able to select promising genotypes for RS selection based on our extensive database of thermal characteristics collected on a wide number of diverse corn lines.
Fusarium graminearum Species Complex Associated with Maize Crowns and Roots in the KwaZulu-Natal Province of South Africa
Authors: Lamprecht S. C. , Tewoldemedhin Y. T. , Botha W. J. , Calitz F. J.
Published: May 2011

Thirty-three isolates of the Fusarium graminearum species complex obtained from diseased maize (Zea mays) crowns and roots in the Winterton district, KwaZulu-Natal province of South Africa were identified to species level. Their pathogenicity and virulence to maize ‘PHI 32D96B’ seedlings were determined under glasshouse conditions, with seedling survival and growth and crown and root rot as criteria. Phylogenetic analyses using the 3-O-acetyltransferase (Tri101) gene region sequences revealed the presence of F. boothii (2 isolates), F. graminearum sensu stricto (26 isolates), and F. meridionale (5 isolates) in the F. graminearum species complex associated with diseased maize crowns and roots. Pathogenicity results showed that F. boothii was the most and F. meridionale the least virulent of the three species. F. boothii and F. graminearum sensu stricto significantly reduced survival of seedlings and all three species caused significant reduction in growth and significantly more crown and root rot than the control (uninoculated). This is the first report of F. boothii, F. graminearum sensu stricto, and F. meridionale associated with diseased maize crowns and roots and their pathogenicity and virulence as soilborne pathogens on maize seedlings in South Africa.
Association of a Novel DNA Virus with the Grapevine Vein-Clearing and Vine Decline Syndrome
Authors: Zhang Yu , Singh Kashmir , Kaur Ravneet , Qiu Wenping
Published: May 2011

A severe vein-clearing and vine decline syndrome has emerged on grapevines (Vitis vinifera) and hybrid grape cultivars in the Midwest region of the United States. The typical symptoms are translucent vein-clearing on young leaves, short internodes and decline of vine vigor. Known viral pathogens of grapevines were not closely associated with the syndrome. To obtain a comprehensive profile of viruses in a diseased grapevine, small RNAs were enriched and two cDNA libraries were constructed from a symptomatic grapevine and a symptomless grapevine, respectively. Deep sequencing of the two cDNA libraries showed that the most abundant viral small RNAs align with the genomes of viruses in the genus Badnavirus, the family Caulimoviridae. Amplification of the viral DNA by polymerase chain reaction allowed the assembly of the whole genome sequence of a grapevine DNA virus, which shared the highest homology with the Badnavirus sequences. This is the first report of a DNA virus in grapevines. The new DNA virus is closely associated with the vein-clearing symptom, and thus has been given a provisional name Grapevine vein clearing virus (GVCV). GVCV was detected in six grapevine cultivars showing vein-clearing and vine decline syndrome in Missouri, Illinois, and Indiana, suggesting its wide distribution in the Midwest region of the United States. Discovery of DNA viruses in grapevines merits further studies on their epidemics and economic impact on grape production worldwide.
Meta-Analysis of Yield Response of Hybrid Field Corn to Foliar Fungicides in the U.S. Corn Belt
Authors: Paul P. A. , Madden L. V. , Bradley C. A. , Robertson A. E. , Munkvold G. P. , Shaner G. , Wise K. A. , Malvick D. K. , Allen T. W. , Grybauskas A. , Vincelli P. , Esker P.
Published: May 2011

The use of foliar fungicides on field corn has increased greatly over the past 5 years in the United States in an attempt to increase yields, despite limited evidence that use of the fungicides is consistently profitable. To assess the value of using fungicides in grain corn production, random-effects meta-analyses were performed on results from foliar fungicide experiments conducted during 2002 to 2009 in 14 states across the United States to determine the mean yield response to the fungicides azoxystrobin, pyraclostrobin, propiconazole + trifloxystrobin, and propiconazole + azoxystrobin. For all fungicides, the yield difference between treated and nontreated plots was highly variable among studies. All four fungicides resulted in a significant mean yield increase relative to the nontreated plots (P < 0.05). Mean yield difference was highest for propiconazole + trifloxystrobin (390 kg/ha), followed by propiconazole + azoxystrobin (331 kg/ha) and pyraclostrobin (256 kg/ha), and lowest for azoxystrobin (230 kg/ha). Baseline yield (mean yield in the nontreated plots) had a significant effect on yield for propiconazole + azoxystrobin (P < 0.05), whereas baseline foliar disease severity (mean severity in the nontreated plots) significantly affected the yield response to pyraclostrobin, propiconazole + trifloxystrobin, and propiconazole + azoxystrobin but not to azoxystrobin. Mean yield difference was generally higher in the lowest yield and higher disease severity categories than in the highest yield and lower disease categories. The probability of failing to recover the fungicide application cost (ploss) also was estimated for a range of grain corn prices and application costs. At the 10-year average corn grain price of $0.12/kg ($2.97/bushel) and application costs of $40 to 95/ha, ploss for disease severity <5% was 0.55 to 0.98 for pyraclostrobin, 0.62 to 0.93 for propiconazole + trifloxystrobin, 0.58 to 0.89 for propiconazole + azoxystrobin, and 0.91 to 0.99 for azoxystrobin. When disease severity was >5%, the corresponding probabilities were 0.36 to 95, 0.25 to 0.69, 0.25 to 0.64, and 0.37 to 0.98 for the four fungicides. In conclusion, the high ploss values found in most scenarios suggest that the use of these foliar fungicides is unlikely to be profitable when foliar disease severity is low and yield expectation is high.
Genetic Structure of Xiphinema pachtaicum and X. index Populations Based on Mitochondrial DNA Variation
Authors: Gutiérrez-Gutiérrez Carlos , Castillo Pablo , Cantalapiedra-Navarrete Carolina , Landa Blanca B. , Derycke Sofie , Palomares-Rius Juan E.
Published: May 2011

The dagger nematodes Xiphinema pachtaicum and X. index are two of the most widespread and frequently occurring Xiphinema spp. co-infesting vineyards and other crops and natural habitats worldwide. Sexual reproduction is rare in these species. The primary objective of this study was to determine the genetic structure of X. pachtaicum and X. index populations using eight and seven populations, respectively, from different “wine of denomination of origin (D.O.) zones” in Spain and Sardinia (Italy), by studying mitochondrial (cytochrome oxidase c subunit 1 or COI) and nuclear (D2-D3 expansion segments of 28S rDNA) markers. Both Xiphinema spp. showed low intraspecific divergence among COI sequences, ranging from 0.2% (1 base substitution) to 2.3% (10 substitutions) in X. pachtaicum and from 0.2% (1 base substitution) to 0.4% (2 substitutions) in X. index. Population genetic structure was strong for both species. Nevertheless, molecular differences among grapevine-growing areas were not significant, and intrapopulation diversity was very low. It is hypothesized that this genetic homogeneity in the nematode populations reflects their predominant parthenogenetic reproduction mode and low dispersal abilities. Our results also show that X. pachtaicum populations in Spain have possibly been established from two different populations of origin. Results also demonstrated that the two DNA regions studied are suitable diagnostic markers for X. index and X. pachtaicum.
Combined Use of Biocontrol Agents to Manage Plant Diseases in Theory and Practice
Authors: Xu X.-M. , Jeffries P. , Pautasso M. , Jeger M. J.
Published: May 2011

Effective use of biological control agents (BCAs) is a potentially important component of sustainable agriculture. Recently, there has been an increasing interest among researchers in using combinations of BCAs to exploit potential synergistic effects among them. The methodology for investigating such synergistic effects was reviewed first and published results were then assessed for available evidence for synergy. Correct formulation of hypotheses based on the theoretical definition of independence (Bliss independence or Loewe additivity) and the subsequent and statistical testing for the independence–synergistic–antagonistic interactions have rarely been carried out thus far in studies on biocontrol of plant diseases. Thus, caution must be taken when interpreting reported “synergistic” effects without assessing the original publications. Recent theoretical modeling work suggested that disease suppression from combined use of two BCAs was, in general, very similar to that achieved by the more efficacious one, indicating no synergistic but more likely antagonistic interactions. Only in 2% of the total 465 published treatments was there evidence for synergistic effects among BCAs. In the majority of the cases, antagonistic interactions among BCAs were indicated. Thus, both theoretical and experimental studies suggest that, in combined use of BCAs, antagonistic interactions among BCAs are more likely to occur than synergistic interactions. Several research strategies, including formulation of synergy hypotheses in relation to biocontrol mechanisms, are outlined to exploit microbial mixtures for uses in biocontrol of plant diseases.
Three-dimensional reconstruction of Heterocapsa circularisquama RNA virus by electron cryo-microscopy
Authors: Miller Jennifer L. , Woodward Jeremy , Chen Shaoxia , Jaffer Mohammed , Weber Brandon , Nagasaki Keizo , Tomaru Yuji , Wepf Roger , Roseman Alan , Varsani Arvind , Sewell Trevor
Published: May 2011

Heterocapsa circularisquama RNA virus is a non-enveloped icosahedral ssRNA virus infectious to the harmful bloom-forming dinoflagellate, H. circularisquama, and which is assumed to be the major natural agent controlling the host population. The viral capsid is constructed from a single gene product. Electron cryo-microscopy revealed that the virus has a diameter of 34 nm and T = 3 symmetry. The 180 quasi-equivalent monomers have an unusual arrangement in that each monomer contributes to a ‘bump’ on the surface of the protein. Though the capsid protein probably has the classic ‘jelly roll’ β-sandwich fold, this is a new packing arrangement and is distantly related to the other positive-sense ssRNA virus capsid proteins. The handedness of the structure has been determined by a novel method involving high resolution scanning electron microscopy of the negatively stained viruses and secondary electron detection.