bluuebunny/crossref_metadata_2025 huggingface dataset:
Reverse gate bias-induced degradation of AlGaN/GaN high electron mobility transistors
Authors: Chang Chih-Yang , Anderson Travis , Hite Jennifer , Lu Liu , Lo Chien-Fong , Chu Byung-Hwan , Cheney D. J. , Douglas E. A. , Gila B. P. , Ren F. , Via G. D. , Whiting Patrick , Holzworth R. , Jones K. S. , Jang Soohwan , Pearton S. J.
Published: September 2010

A threshold reverse bias of ∼21 V was observed leading to a sharp increase in the gate current of AlGaN/GaN high electron mobility transistors biased at low source-drain voltage (5 V). The gate current increases by one to two orders of magnitude at this bias, corresponding to an electric field strength around 1.8 MV cm−1. The gate current increased by roughly five orders of magnitude after step-stressing the gate bias from 10 to 42 V in 1 V increments for 1 min at each bias. The drain current was also decreased by ∼20% after this step-stress cycle. The photoluminescence and electroluminescence intensity from the semiconductor is decreased along the periphery of the gate region after stressing and transmission electron microscopy shows a thin native oxide layer under the gate and this disappears as the gate metal reacts with the underlying AlGaN.
Holographic realization of hexagonal two dimensional photonic crystal structures with elliptical geometry
Authors: Hung Yung-Jr , Lee San-Liang , Pan Yen-Ting , Thibeault Brian J. , Coldren Larry A.
Published: September 2010

A complete investigation of holographic photonic crystal structures has been conducted. From both theoretical and experimental results, profiles of resultant patterns under different process conditions can be estimated and controlled. The use of antireflection layers is crucial for realizing submicron photonic crystals with good uniformity over a large area. We successfully realize submicron-scale photonic crystal templates on silicon substrates with an aspect ratio of 2.5 and good quality by a laser holography technique. The samples are highly uniform in an area of >2×2 cm2 and present good reproducibility. A lift-off process is performed to transfer inversed pillar patterns into a chromium hard mask for the following dry etching into silicon substrates. A single-step deep reactive ion etching with controlled mixture of Ar/SF6/C4F8 gases is used to directly transfer pillar patterns into silicon. Transferred patterns with a high aspect ratio and vertical sidewalls (no scalloping) are demonstrated over a large area.
Immunology for Clinicians: A “Trojan Horse” Approach
Authors: Gray Clive M. , Loubser Shayne , Kriel Carina , Mercer Monica , Brookes Heather
Published: September 2010

A South African Web site imparts basic immunology information to clinicians and other health-care workers.
Measurement of Fast Electron Spin Relaxation Times with Atomic Resolution
Authors: Loth Sebastian , Etzkorn Markus , Lutz Christopher P. , Eigler D. M. , Heinrich Andreas J.
Published: September 2010

In a Spin

The relaxation dynamics of electron spins in solid-state systems is of crucial importance for their usage in quantum computation and information storage. The interaction of the spin with its local environment results in lifetimes in the pico- to microsecond range. Thus, high temporal and spatial resolutions are needed to measure the relaxation time with atomic precision.

Loth
et al.

(p.
1628
, see the cover; see the Perspective by

Morgenstern

) used a scanning tunneling microscope with a spin-polarized tip to monitor the electron spin relaxation times of individual atoms adsorbed on a surface. A spin was excited by a pump signal, and its state read out after a variable time delay with a weak probe pulse that produced a spin-sensitive tunneling current. This general technique may be applicable to other systems with fast dynamics.
The Ubiquity of Micrometer-Sized Dust Grains in the Dense Interstellar Medium
Authors: Pagani Laurent , Steinacker Jürgen , Bacmann Aurore , Stutz Amelia , Henning Thomas
Published: September 2010

Dust to Dust

Recently, the so-called coreshine effect was identified in a nearby interstellar cloud. The coreshine effect refers to the scattering of mid-infrared light by micron-sized dust grains in the densest regions of molecular clouds, the places where stars and planets are known to form. Using data from the Spitzer telescope,

Pagani
et al.

(p.
1622
) now show that, rather than being limited to one single molecular cloud, the coreshine effect is common all over our galaxy, but is not universal and could be used to learn about the properties of star-forming cores and the dust therein.
The Rise of Sunflowers
Authors: Stuessy Tod
Published: September 2010

A new fossil suggests the family that includes sunflowers and daisies originated in South America.
Branching Takes Nerve
Authors: Rock Jason R. , Hogan Brigid L. M.
Published: September 2010

Innervation is required to maintain epithelial progenitor cells that support salivary gland growth and development.
Misconduct by Postdocs Leads to Retraction of Papers
Authors: Miller Greg
Published: September 2010

Last week, Mount Sinai School of Medicine said that two postdoctoral fellows working in the lab of noted gene therapy researcher Savio Woo had been fired for research misconduct. In a statement, the school said that Woo had been cleared of any wrongdoing.
A Tricky Balance Between Activists' and Researchers' Rights
Authors: Miller Greg
Published: September 2010

A recent plea bargain by a University of Minnesota sociology graduate student and other cases highlight the difficulty of identifying the small minority of animal-rights activists who break the law and successfully prosecuting those who are charged.
Parlous Times for Seed Banks Spell Trouble for Australian Agriculture
Authors: Finkel Elizabeth
Published: September 2010

Australia's seed banks are tumbling like dominoes. This will make it harder for Australia to comply with a genetics resources treaty, which in turn could curtail access to overseas seed collections—a debilitating prospect for a country whose farms rely on imported species.
Mouse Studies Challenge Rare Immune Cell's Powers
Authors: Leslie Mitch
Published: September 2010

The functions of basophils, one of the first immune cells to be identified, continue to confound researchers.
Beating Heart Disease in Diabetes
Authors: Bremer Andrew A.
Published: September 2010

An apoA-I mimetic that prevents fatty lesion formation in diabetic mice may prevent premature heart disease in patients with diabetes.
Antiplatelet Therapy: To Genotype or Not?
Authors: Damani Samir
Published: September 2010

A recent study does not overturn the conclusion that DNA sequence polymorphisms in the hepatic cytochrome 2C19 gene are predictive of future adverse cardiovascular events.
Evaluation of the Safety and Immunogenicity of Two Antigen Concentrations of the Mtb72F/AS02ACandidate Tuberculosis Vaccine in Purified Protein Derivative-Negative Adults
Authors: Leroux-Roels Isabel , Leroux-Roels Geert , Ofori-Anyinam Opokua , Moris Philippe , De Kock Els , Clement Frédéric , Dubois Marie-Claude , Koutsoukos Marguerite , Demoitié Marie-Ange , Cohen Joe , Ballou W. Ripley
Published: September 2010

Tuberculosis (TB) remains a major cause of illness and death worldwide, making a new TB vaccine an urgent public health priority. Purified protein derivative (PPD)-negative adults (n= 50) were equally randomized to receive 3 doses at 1-month intervals (at 0, 1, and 2 months) of one of the following vaccines: Mtb72F/AS02A(10 or 40 μg antigen), Mtb72F/saline (10 or 40 μg antigen), or AS02A. Mtb72F/AS02Arecipients received an additional dose 1 year after the first dose to evaluate if the elicited immune response could be boosted. Mtb72F/AS02Avaccines were locally reactogenic but clinically well tolerated, with transient adverse events (usually lasting between 1 and 4 days) that resolved without sequelae being observed. No vaccine-related serious adverse events were reported. Vaccination with Mtb72F/AS02Ainduced a strong Mtb72F-specific humoral response and a robust Mtb72F-specific CD4+T-cell response, both of which persisted at 9 months after primary immunization and for 1 year after the booster immunization. There was no significant difference between the magnitude of the CD4+T-cell response induced by the 10-μg and 40-μg Mtb72F/AS02Avaccines. The Mtb72F-specific CD4+T cells predominantly expressed CD40L; CD40L and interleukin-2 (IL-2); CD40L and tumor necrosis factor alpha (TNF-α); CD40L, IL-2, and TNF-α; and CD40L, IL-2, TNF-α, and gamma interferon (IFN-γ). Serum IFN-γ, but not TNF-α, was detected 1 day after doses 2 and 3 for the Mtb72F/AS02Avaccine but did not persist. Vaccine-induced CD8+T-cell responses were not detected, and no immune responses were elicited with AS02Aalone. In conclusion, Mtb72F/AS02Ais clinically well tolerated and is highly immunogenic in TB-naïve adults. The 10- and 40-μg Mtb72F/AS02Avaccines show comparable safety and immunogenicity profiles.
Responses to a Conjugate Pneumococcal Vaccine in Preterm Infants Immunized at 2, 3, and 4 Months of Age
Authors: Moss S. J. , Fenton A. C. , Toomey J. A. , Grainger A. J. , Smith J. , Gennery A. R.
Published: September 2010

Preterm infants are at an increased risk of invasive pneumococcal disease infection and, additionally, have a diminished response to
Haemophilus influenzae
type b (Hib) conjugate vaccines. There are little data examining the response of preterm infants to a seven-valent pneumococcal conjugate vaccine (PCV7). We examined the responses of preterm infants immunized at 2, 3, and 4 months of age to PCV7. A total of 133 preterm and 54 term infants were immunized with PCV7 and the
Neisseria meningitidis
group C (MCC), diphtheria, tetanus, pertussis, polio, and Hib vaccines. Pneumococcal serotype-specific IgG was measured by enzyme-linked immunosorbent assay (ELISA) pre- and postimmunization and at 12 months or following a booster of PCV7. Term and preterm responses were compared using linear and logistic regression analyses. Term infants had higher preimmunization geometric mean concentrations (GMCs) for all serotypes. Preterm infants had lower postimmunization GMCs for serotype 23F. Gestational age affected postimmunization GMCs for serotypes 4, 6B, and 23F. Preterm infants were as likely to have levels of ≥0.35 μg/ml as term infants for all serotypes except 23F. The proportions of infants with titers of ≥0.35 μg/ml for all 7 serotypes were comparable between groups. A total of 28 of 29 term infants who received a booster had levels of ≥0.35 μg/ml for all serotypes. One infant had undetectable levels for serotype 6B. Of the 32 preterm infants boosted, 9 had levels of <0.35 μg/ml for 1 serotype, and 1 had levels of <0.35 μg/ml for 2 serotypes. In nonboosted infants, GMCs for all serotypes except 6B had fallen by 12 months of age. These results support the need for a booster dose in the second year of life.
Recombinant PorA, the Major Outer Membrane Protein ofCampylobacter jejuni, Provides Heterologous Protection in an Adult Mouse Intestinal Colonization Model
Authors: Islam Anjum , Raghupathy Raj , Albert M. John
Published: September 2010

Immunity againstCampylobacter jejuni, a major food-borne pathogen causing diarrhea, is largely serotype specific. The major outer membrane protein (MOMP) ofC. jejuni, PorA, is a common antigen with the potential to provide broad protection. Adult BALB/c mice were orally immunized with a recombinant glutathioneS-transferase (GST) fused to PorA prepared fromCampylobacter jejuniC31 (O:6,7) (GST-PorA) combined with a modified heat-labile enterotoxin ofEscherichia colias an adjuvant and later orally challenged with C31 strain or three heterologous strains: 48 (O:19), 75 (O:3), and 111 (O:1,44). Protection from colonization with the challenge organism was studied by fecal screening daily for 9 days. Serum and intestinal lavage fluid antibodies against the vaccine and Sarkosyl-purified MOMP from C31 were measured by using an enzyme-linked immunosorbent assay. The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48,P< 0.001), 29% (for strain 75,P< 0.005), and 42% (for strain 111,P< 0.001) for the 9-day period compared to control mice given phosphate-buffered saline. Thus, PorA provided appreciable protection against colonization with heterologous serotypes.
PsrP, a Protective Pneumococcal Antigen, Is Highly Prevalent in Children with Pneumonia and Is Strongly Associated with Clonal Type
Authors: Muñoz-Almagro Carmen , Selva Laura , Sanchez Carlos J. , Esteva Cristina , de Sevilla Mariona F. , Pallares Roman , Orihuela Carlos J.
Published: September 2010

Invasive pneumococcal disease (IPD) is a major health problem worldwide. Due to ongoing serotype replacement, current efforts are focused in an attempt to identify the pneumococcal antigens that could be used in a next-generation multivalent protein vaccine. The objective of our study was to use real-time PCR to determine the distribution and clonal type variability of PsrP, a protective pneumococcal antigen, among pneumococcal isolates from children with IPD or healthy nasopharyngeal carriers.
psrP
was detected in 52.4% of the 441 strains tested. While no differences were determined when the prevalence of
psrP
in colonizing strains (
n
= 89) versus that in all invasive strains (
n
= 352) was compared, a strong trend was observed when the prevalence of
psrP
in all pneumonia isolates (
n
= 209) and colonizing isolates (
P
= 0.067) was compared, and a significant difference was observed when the prevalence in all pneumonia isolates and those causing bacteremia (
n
= 76) was compared (
P
= 0.001). An age-dependent distribution of
psrP
was also observed, with the incidence of
psrP
being the greatest in strains isolated from children >2 years of age (
P
= 0.02). Strikingly, the presence of
psrP
within a serotype was highly dependent on the clonotype, with all isolates of invasive clones such as clonal complex 306 carrying
psrP
(
n
= 88), whereas for sequence type 304, only 1 of 19 isolates carried
psrP
; moreover, this was inversely correlated with antibiotic susceptibility. This finding suggests that inclusion of
psrP
in a vaccine formulation would not target resistant strains. We conclude that
psrP
is highly prevalent in strains that cause IPD but is most prevalent in strains isolated from older children with pneumonia. These data support the potential use of PsrP as one component in a multivalent protein-based vaccine.
Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification ofNocardiaSpecies
Authors: Verroken A. , Janssens M. , Berhin C. , Bogaerts P. , Huang T.-D. , Wauters G. , Glupczynski Y.
Published: September 2010

The identification ofNocardiaspecies, usually based on biochemical tests together with phenotypicin vitrosusceptibility and resistance patterns, is a difficult and lengthy process owing to the slow growth and limited reactivity of these bacteria. In this study, a panel of 153 clinical and reference strains ofNocardiaspp., altogether representing 19 different species, were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). As reference methods for species identification, full-length 16S rRNA gene sequencing and phenotypical biochemical and enzymatic tests were used. In a first step, a complementary homemade reference database was established by the analysis of 110Nocardiaisolates (pretreated with 30 min of boiling and extraction) in the MALDI BioTyper software according to the manufacturer's recommendations for microflex measurement (Bruker Daltonik GmbH, Leipzig, Germany), generating a dendrogram with species-specific cluster patterns. In a second step, the MALDI BioTyper database and the generated database were challenged with 43 blind-coded clinical isolates ofNocardiaspp. Following addition of the homemade database in the BioTyper software, MALDI-TOF MS provided reliable identification to the species level for five species of which more than a single isolate was analyzed. Correct identification was achieved for 38 of the 43 isolates (88%), including 34 strains identified to the species level and 4 strains identified to the genus level according to the manufacturer's log score specifications. These data suggest that MALDI-TOF MS has potential for use as a rapid (<1 h) and reliable method for the identification ofNocardiaspecies without any substantial costs for consumables.
Initial Identification and Characterization of an Emerging Zoonotic Influenza Virus Prior to Pandemic Spread
Authors: Metzgar David , Baynes Darcie , Myers Christopher A. , Kammerer Peter , Unabia Michelle , Faix Dennis J. , Blair Patrick J.
Published: September 2010

Two cases of febrile respiratory illness associated with untypeable influenza A virus were identified in Southern California in March 2009. One was initially detected as influenza virus using an experimental diagnostic device in a clinical trial, while the other was detected at a local reference lab using a diagnostic PCR assay. In both cases, analyses yielded negative results for strain-specific tests targeting circulating strains of influenza A virus (seasonal H1 and H3). These two samples became the first reported cases of the pandemic 2009/H1N1 influenza virus. The first reportable characterization was made from the second collected specimen on 15 April 2009 at the Centers for Disease Control and Prevention central lab using traditional culture and sequencing methods. The novel nature of the strain and its apparent zoonotic origins were initially characterized using the first collected specimen at the Naval Health Research Center in San Diego, CA, on 13 April using an experimental molecular analysis tool, PCR electro-spray ionization-mass spectrometry (PCR/ESI-MS), designed to amplify PCR products from any strain of influenza virus and to generate informative (phylogenetic) strain identifications through mass spectrometry of PCR amplicons. The ability of this high-throughput tool to correctly identify both well-characterized and novel influenza strains offers the possibility to integrate surveillance for emerging strains with on-site rapid diagnosis used for patient management, shortening the times between the emergence of new strains, their detection and identification, and appropriate public health response activities. Here we describe the initial characterization of the pandemic 2009/H1N1 influenza strain and discuss the possible roles of diagnostic tools with discovery potential.
Evaluation of
Escherichia coli
Cell Response to Antibiotic Treatment by Use of Raman Spectroscopy with Laser Tweezers
Authors: Moritz Tobias J. , Polage Christopher R. , Taylor Douglas S. , Krol Denise M. , Lane Stephen M. , Chan James W.
Published: September 2010

Laser tweezers Raman spectroscopy was used to detect the cellular response of
Escherichia coli
cells to penicillin G-streptomycin and cefazolin. Time-dependent intensity changes of several Raman peaks at 729, 1,245, and 1,660 cm
−1
enabled untreated cells and cells treated with the different antibiotic drugs to be distinguished.
Thogoto Virus Infection Induces Sustained Type I Interferon Responses That Depend on RIG-I-Like Helicase Signaling of Conventional Dendritic Cells
Authors: Kochs Georg , Bauer Stefanie , Vogt Carola , Frenz Theresa , Tschopp Jürg , Kalinke Ulrich , Waibler Zoe
Published: September 2010

Type I interferon (IFN-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. Many viral infections lead to an acute, transient IFN expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. Robust IFN expression often is conferred by specialized plasmacytoid dendritic cells (pDC) and may depend on positive-feedback amplification via the type I IFN receptor (IFNAR). Here, we show that mice infected with Thogoto virus (THOV), which is an influenza virus-like orthomyxovirus transmitted by ticks, mounted sustained IFN responses that persisted up to 72 h after infection. For this purpose, we used a variant of THOV lacking its IFN-antagonistic protein ML, an elongated version of the matrix (M) protein [THOV(ΔML)]. Of note, large amounts of type I IFN were also found in the serum of mice lacking the IFNAR. Early IFN-α expression seemed to depend on Toll-like receptor (TLR) signaling, whereas prolonged IFN-α responses strictly depended on RIG-I-like helicase (RLH) signaling. Unexpectedly, THOV(ΔML)-infected bone marrow-derived pDC (BM-pDC) produced only moderate IFN levels, whereas myeloid DC (BM-mDC) showed massive IFN induction that was IPS-1-dependent, suggesting that BM-mDC are involved in the massive, sustained IFN production in THOV(ΔML)-infected animals. Thus, our data are compatible with the model that THOV(ΔML) infection is sensed in the acute phase via TLR and RLH systems, whereas at later time points only RLH signaling is responsible for the induction of sustained IFN responses.
Calcium Flux between the Endoplasmic Reticulum and Mitochondrion Contributes to Poliovirus-Induced Apoptosis
Authors: Brisac Cynthia , Téoulé François , Autret Arnaud , Pelletier Isabelle , Colbère-Garapin Florence , Brenner Catherine , Lemaire Christophe , Blondel Bruno
Published: September 2010

We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca
2+
) concentration in neuroblastoma IMR5 cells, at least partly through Ca
2+
release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP
3
R) and ryanodine receptor (RyR) channels. This leads to Ca
2+
accumulation in mitochondria through the mitochondrial Ca
2+
uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca
2+
concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis.
Proteasome InhibitionIn VivoPromotes Survival in a Lethal Murine Model of Severe Acute Respiratory Syndrome
Authors: Ma Xue-Zhong , Bartczak Agata , Zhang Jianhua , Khattar Ramzi , Chen Limin , Liu Ming Feng , Edwards Aled , Levy Gary , McGilvray Ian D.
Published: September 2010

Ubiquitination is a critical regulator of the host immune response to viral infection, and many viruses, including coronaviruses, encode proteins that target the ubiquitination system. To explore the link between coronavirus infection and the ubiquitin system, we asked whether protein degradation by the 26S proteasome plays a role in severe coronavirus infections using a murine model of SARS-like pneumonitis induced by murine hepatitis virus strain 1 (MHV-1).In vitro, the pretreatment of peritoneal macrophages with inhibitors of the proteasome (pyrrolidine dithiocarbamate [PDTC], MG132, and PS-341) markedly inhibited MHV-1 replication at an early step in its replication cycle, as evidenced by inhibition of viral RNA production. Proteasome inhibition also blocked viral cytotoxicity in macrophages, as well as the induction of inflammatory mediators such as IP-10, gamma interferon (IFN-γ), and monocyte chemoattractant protein 1 (MCP-1).In vivo, intranasal inoculation of MHV-1 results in a lethal pneumonitis in A/J mice. Treatment of A/J mice with the proteasome inhibitor PDTC, MG132, or PS-341 led to 40% survival (P< 0.01), with a concomitant improvement of lung histology, reduced pulmonary viral replication, decreased pulmonary STAT phosphorylation, and reduced pulmonary inflammatory cytokine expression. These data demonstrate that inhibition of the cellular proteasome attenuates pneumonitis and cytokine gene expressionin vivoby reducing MHV-1 replication and the resulting inflammatory response. The results further suggest that targeting the proteasome may be an effective new treatment for severe coronavirus infections.
Role of Erythropoietin Receptor Signaling in Parvovirus B19 Replication in Human Erythroid Progenitor Cells
Authors: Chen Aaron Yun , Guan Wuxiang , Lou Sai , Liu Zhengwen , Kleiboeker Steve , Qiu Jianming
Published: September 2010

Parvovirus B19 (B19V) infection is highly restricted to human erythroid progenitor cells. Although previous studies have led to the theory that the basis of this tropism is receptor expression, this has been questioned by more recent observation. In the study reported here, we have investigated the basis of this tropism, and a potential role of erythropoietin (Epo) signaling, in erythroid progenitor cells (EPCs) expanded
ex vivo
from CD34
+
hematopoietic cells in the absence of Epo (CD36
+
/Epo
−
EPCs). We show, first, that CD36
+
/Epo
−
EPCs do not support B19V replication, in spite of B19V entry, but Epo exposure either prior to infection or after virus entry enabled active B19V replication. Second, when Janus kinase 2 (Jak2) phosphorylation was inhibited using the inhibitor AG490, phosphorylation of the Epo receptor (EpoR) was also inhibited, and B19V replication in
ex vivo
-expanded erythroid progenitor cells exposed to Epo (CD36
+
/Epo
+
EPCs) was abolished. Third, expression of constitutively active EpoR in CD36
+
/Epo
−
EPCs led to efficient B19V replication. Finally, B19V replication in CD36
+
/Epo
+
EPCs required Epo, and the replication response was dose dependent. Our findings demonstrate that EpoR signaling is absolutely required for B19V replication in
ex vivo
-expanded erythroid progenitor cells after initial virus entry and at least partly accounts for the remarkable tropism of B19V infection for human erythroid progenitors.
Crystal Structure of a Virus-Encoded Putative Glycosyltransferase
Authors: Xiang Ye , Baxa Ulrich , Zhang Ying , Steven Alasdair C. , Lewis Gentry L. , Van Etten James L. , Rossmann Michael G.
Published: September 2010

The chloroviruses (family
Phycodnaviridae
), unlike most viruses, encode some, if not most, of the enzymes involved in the glycosylation of their structural proteins. Annotation of the gene product B736L from chlorovirus NY-2A suggests that it is a glycosyltransferase. The structure of the recombinantly expressed B736L protein was determined by X-ray crystallography to 2.3-Å resolution, and the protein was shown to have two nucleotide-binding folds like other glycosyltransferase type B enzymes. This is the second structure of a chlorovirus-encoded glycosyltransferase and the first structure of a chlorovirus type B enzyme to be determined. B736L is a retaining enzyme and belongs to glycosyltransferase family 4. The donor substrate was identified as GDP-mannose by isothermal titration calorimetry and was shown to bind into the cleft between the two domains in the protein. The active form of the enzyme is probably a dimer in which the active centers are separated by about 40 Å.
Vaccinia Virus D4 Mutants Defective in Processive DNA Synthesis Retain Binding to A20 and DNA
Authors: Druck Shudofsky Abigail M. , Silverman Janice Elaine Y. , Chattopadhyay Debasish , Ricciardi Robert P.
Published: September 2010

Genome replication is inefficient without processivity factors, which tether DNA polymerases to their templates. The vaccinia virus DNA polymerase E9 requires two viral proteins, A20 and D4, for processive DNA synthesis, yet the mechanism of how this tricomplex functions is unknown. This study confirms that these three proteins are necessary and sufficient for processivity, and it focuses on the role of D4, which also functions as a uracil DNA glycosylase (UDG) repair enzyme. A series of D4 mutants was generated to discover which sites are important for processivity. Three point mutants (K126V, K160V, and R187V) which did not function in processive DNA synthesis, though they retained UDG catalytic activity, were identified. The mutants were able to compete with wild-type D4 in processivity assays and retained binding to both A20 and DNA. The crystal structure of R187V was resolved and revealed that the local charge distribution around the substituted residue is altered. However, the mutant protein was shown to have no major structural distortions. This suggests that the positive charges of residues 126, 160, and 187 are required for D4 to function in processive DNA synthesis. Consistent with this is the ability of the conserved mutant K126R to function in processivity. These mutants may help unlock the mechanism by which D4 contributes to processive DNA synthesis.
Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4/K10) Is a Novel Interaction Partner of CSL/CBF1, the Major Downstream Effector of Notch Signaling
Authors: Heinzelmann Katharina , Scholz Barbara A. , Nowak Agnes , Fossum Even , Kremmer Elisabeth , Haas Juergen , Frank Ronald , Kempkes Bettina
Published: September 2010

In cells infected with the Kaposi's sarcoma-associated herpesvirus (KSHV), CSL/CBF1 signaling is essential for viral replication and promotes the survival of KSHV-infected cells. CSL/CBF1 is a DNA adaptor molecule which recruits coactivator and corepressor complexes to regulate viral and cellular gene transcription and which is a major downstream effector molecule of activated Notch. The interaction of KSHV RTA and LANA with CSL/CBF1 has been shown to balance the lytic and latent viral life cycle. Here we report that a third KSHV protein, viral interferon regulatory factor 4 (vIRF4/K10), but none of the three other KSHV-encoded vIRFs, interacts with CSL/CBF1. Two regions of vIRF4 with dissimilar affinities contribute to CSL/CBF1 binding. Similar to Notch, vIRF4 targets the hydrophobic pocket in the beta trefoil domain of CSL/CBF1 through a short peptide motif which closely resembles a motif found in Notch but does not strictly follow the ΦWΦP consensus conserved in human and mouse Notch proteins. Our results suggest that vIRF4 might compete with Notch for CSL/CBF1 binding and signaling.
Autographa californica
Multiple Nucleopolyhedrovirus Ac92 (ORF92, P33) Is Required for Budded Virus Production and Multiply Enveloped Occlusion-Derived Virus Formation
Authors: Wu Wenbi , Passarelli A. Lorena
Published: September 2010

The
Autographa californica
multiple nucleopolyhedrovirus
orf92
(
p33
),
ac92
, is one of 31 genes carried in all sequenced baculovirus genomes, thus suggesting an essential function. Ac92 has homology to the family of flavin adenine dinucleotide-linked sulfhydryl oxidases and is related to the ERV/ALR family of sulfhydryl oxidases. The role of
ac92
during virus replication is unknown. Ac92 was associated with the envelope of both budded and occlusion-derived virus (ODV). To investigate the role of Ac92 during virus replication, an
ac92
-knockout bacmid was generated through homologous recombination in
Escherichia coli
. Titration and plaque assays showed no virus spread in
ac92
-knockout bacmid DNA-transfected insect cells. Deletion of
ac92
did not affect viral DNA replication. However,
ac92
-knockout bacmid DNA-transfected cells lacked multiply enveloped occlusion-derived nucleocapsids; instead, singly enveloped nucleocapsids were detected. To gain insight into the requirement for sulfhydryl oxidation during virus replication, a virus was constructed in which the Ac92 C
155
XXC
158
amino acids, important for sulfhydryl oxidase activity, were mutated to A
155
XXA
158
. The mutant virus exhibited a phenotype similar to that of the knockout virus, suggesting that the C-X-X-C motif was essential for sulfhydryl oxidase activity and responsible for the altered ODV phenotype.
Immunization with Different Viral Antigens Alters the Pattern of T Cell Exhaustion and Latency in Herpes Simplex Virus Type 1-Infected Mice
Authors: Allen Sariah J. , Mott Kevin R. , Zandian Mandana , Ghiasi Homayon
Published: September 2010

We have shown previously that immunization with herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) exacerbated corneal scarring (CS) in ocularly infected mice. In this study, we investigated whether higher levels of CS were correlated with higher levels of latency and T cell exhaustion in gK-immunized mice. BALB/c mice were vaccinated with baculovirus-expressed gK or gD or mock immunized. Twenty-one days after the third immunization, mice were ocularly infected with 2 × 10
4
PFU/eye of virulent HSV-1 strain McKrae. On day 5 postinfection, virus replication in the eye was measured, and on day 30 postinfection, infiltration of the trigeminal ganglia (TG) by CD4, CD8, programmed death 1 (PD-1), and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was monitored by immunohistochemistry and quantitative real-time PCR (qRT-PCR). This study demonstrated that higher levels of CS were correlated with higher levels of latency, and this was associated with the presence of significantly higher numbers of CD4
+
PD-1
+
and CD8
+
PD-1
+
cells in the TG of the gK-immunized group than in both the gD- and mock-immunized groups. Levels of exhaustion associated with Tim-3 were the same among gK- and mock-vaccinated groups but higher than levels in the gD-vaccinated group. In this study, we have shown for the first time that both PD-1 and Tim-3 contribute to T cell exhaustion and an increase of latency in the TG of latently infected mice.
High Natural Permissivity of Primary Rabbit Cells for HIV-1, with a Virion Infectivity Defect in Macrophages as the Final Replication Barrier
Authors: Tervo Hanna-Mari , Keppler Oliver T.
Published: September 2010

An immunocompetent, permissive, small-animal model would be valuable for the study of human immunodeficiency virus type 1 (HIV-1) pathogenesis and for the testing of drug and vaccine candidates. However, the development of such a model has been hampered by the inability of primary rodent cells to efficiently support several steps of the HIV-1 replication cycle. Although transgenesis of the HIV receptor complex and human cyclin T1 have been beneficial, additional late-phase blocks prevent robust replication of HIV-1 in rodents and limit the range of
in vivo
applications. In this study, we explored the HIV-1 susceptibility of rabbit primary T cells and macrophages. Envelope-specific and coreceptor-dependent entry of HIV-1 was achieved by expressing human CD4 and CCR5. A block of HIV-1 DNA synthesis, likely mediated by TRIM5, was overcome by limited changes to the HIV-1
gag
gene. Unlike with mice and rats, primary cells from rabbits supported the functions of the regulatory viral proteins Tat and Rev, Gag processing, and the release of HIV-1 particles at levels comparable to those in human cells. While HIV-1 produced by rabbit T cells was highly infectious, a macrophage-specific infectivity defect became manifest by a complex pattern of mutations in the viral genome, only part of which were deamination dependent. These results demonstrate a considerable natural HIV-1 permissivity of the rabbit species and suggest that receptor complex transgenesis combined with modifications in
gag
and possibly
vif
of HIV-1 to evade species-specific restriction factors might render lagomorphs fully permissive to infection by this pathogenic human lentivirus.
Sequences from Ancestral Single-Stranded DNA Viruses in Vertebrate Genomes: the
Parvoviridae
and
Circoviridae
Are More than 40 to 50 Million Years Old
Authors: Belyi Vladimir A. , Levine Arnold J. , Skalka Anna Marie
Published: September 2010

Vertebrate genomic assemblies were analyzed for endogenous sequences related to any known viruses with single-stranded DNA genomes. Numerous high-confidence examples related to the
Circoviridae
and two genera in the family
Parvoviridae
, the parvoviruses and dependoviruses, were found and were broadly distributed among 31 of the 49 vertebrate species tested. Our analyses indicate that the ages of both virus families may exceed 40 to 50 million years. Shared features of the replication strategies of these viruses may explain the high incidence of the integrations.
Synthesis, characterization, and thermal properties of benzylammonium pentaborate [C6H5CH2NH3][B5O6(OH)4]
Authors: Beckett Michael A. , Horton Peter N. , Hursthouse Michael B. , Timmis James L. , Varma K. Sukumar
Published: September 2010

[C6H5CH2NH3][B5O6(OH)4] was obtained as colourless crystals in high yield from a MeOH/ H2O (1:1) solution of benzylamine and boric acid (1:5). A single-crystal X-ray study confirmed that the solid-state structure was comprised of a supramolecular H-bonded pentaborate anion lattice, templated by the benzylammonium cations which occupy positions within the lattice cavities. Each pentaborate anion formed 4 H-bonds to 4 neighbouring pentaborate anions at α,α,α,β acceptor sites. Additionally, each cation H-bonds to 3 pentaborate anions. Crystals were monoclinic, P21/c, with a = 9.3511(2) Å, b = 14.5157(4) Å, c = 10.4670(2) Å, β = 90.778(2)°, T = 120 K, V = 1420.64(6) Å3, and Z = 4. TGA/DSC analysis showed that [C6H5CH2NH3][B5O6(OH)4] thermally decomposed in air at 800 °C to 2.5B2O3, via a low-temperature (200–250 °C) dehydration step to a condensed pentaborate.
The value of multidisciplinary nutritional gastroenterology clinics for intestinal failure and other gastrointestinal patients
Authors: Muddu Ajay Kiran , Stroud Michael A
Published: September 2010

An increasing number of patients have chronic intestinal failure (IF) or other problems needing nutritional support. These patients need regular input from gastroenterologists, nutrition nurse specialists and dietitians, but traditionally these healthcare professionals see them separately. Here the authors describe their experience of a combined regional nutritional gastroenterology clinic and outline strategies that can avoid the need for home parenteral nutrition (HPN) or intravenous fluids in most cases. Over a 1-year period, 73 patients attended their clinic, with the majority (74%) coming from their own catchment area of 500 000. Of the 63 patients with IF, 49 had short bowel syndrome. 38 of the patients with IF (60%) could be managed with dietary and pharmacological modifications alone, while eight (13%) needed enteral tube feeding and 17 (27%) HPN or intravenous fluids. However, only nine (53%) of the 17 patients referred from other centres specifically for HPN instigation actually needed HPN or intravenous fluids. Patient satisfaction with the combined multidisciplinary clinic was high, with 85% of patients preferring to be seen within this model of outpatient care, although questionnaire response rates were low. The authors have therefore shown that a multidisciplinary nutritional gastroenterology clinic can provide effective patient-centred care and can minimise the need for invasive and costly intravenous nutritional support. Clinics of this type should be an integral part of the current plans to implement regional IF services.
Assessment of tobacco control advocacy behavioural capacity among students at schools of public health in China
Authors: Yang Tingzhong , Abdullah Abu S , Rockett Ian R H , Li Mu , Zhou Yuhua , Ma Jun , Ji Huaping , Zheng Jianzhong , Zhang Yuhong , Wang Liming
Published: September 2010

Objectives

To evaluate student tobacco control advocacy behavioural capacity using longitudinal trace data.

Methods

A tobacco control advocacy curriculum was developed and implemented at schools of public health (SPH) or departments of public health in seven universities in China. Participants comprised undergraduate students studying the public health curriculum in these 13 Universities. A standardised assessment tool was used to evaluate their tobacco control advocacy behavioural capacity. Repeated measures analysis of variance, paired t tests and paired χ2tests were used to determine differences between dependent variables across time. Multivariate analysis of variance (MANOVA) and multivariate logistic regression were used to assess treatment effects between intervention and control sites.

Results

Respective totals of 426 students in the intervention group and 338 in the control group were available for the evaluation. Approximately 90% of respondents were aged 21 years or older and 56% were women. Findings show that the capacity building program significantly improved public health student advocacy behavioural capacity, including advocacy attitude, interest, motivation and anti-secondhand smoke behaviours. The curriculum did not impact student smoking behaviour.

Conclusions

This study provides sufficient evidence to support the implementation of tobacco control advocacy training at Chinese schools of public health.
Temperature and photoperiodic control of flower initiation in a New Guinea Impatiens hybrid
Authors: Simmonds John
Published: September 2010

The effects of photoperiod and temperature on flower initiation and the rate of node production in a New Guinea hybrid Impatiens cv. Starburst were investigated. The node of first flower initiation was not a reliable estimate of the time of flower initiation unless treatment influences on the rate of node production were also considered. Plants maintained at 25 °C responded as quantitative short-day plants; the time of flower initiation was earlier, and the degree of flowering was greater, in 8- and 14-h photoperiods than in 18-h photoperiods. In short (12-h) photoperiods flowering was modulated by temperature. The time of flower initiation was reduced from 27 days at 25 °C to 13 days at 20 °C and to 10 days at 15 °C. Night-break experiments indicated that flowering at 25 °C was subject to photoperiodic control but at 15 °C the plants were "day-neutral."
The effect of temperature on the content of the medullary depsidone salazinic acid in Ramalina siliquosa (lichens)
Authors: Hamada N.
Published: September 2010

The correlation between the content of the medullary depsidone salazinic acid in Ramalina siliquosa and some environmental factors (precipitation, sunshine, temperature) was examined. The salazinic acid content of the plants is higher where the annual mean temperature is higher, and the content of the plants growing on the dark-colored rock or on the southern face of the rock is higher than that of the plants growing on the light-colored rock or on the northern face of the rock, probably because the temperature on or near the surface of the former is higher than that of the latter. No significant correlation is observed between the salazinic acid content and the amount of precipitation or sunshine at the habitat. Temperature may be an important factor affecting the content of salazinic acid.
Transport of fluorescein in trichomes of Lycopersicon esculentum
Authors: Barclay Gregor F. , Peterson Carol A. , Tyree Melvin T.
Published: September 2010

Translocation of the dye disodium fluorescein (uranin) in trichomes of Lycopersicon esculentum (tomato) was nonpolar and proportional to the square root of time. Inhibition of cytoplasmic streaming by cytochalasin B had no effect on the rate of dye movement. On the other hand, disruption of plasmodesmatal connections between adjacent cells by plasmolysis strongly diminished the rate of fluorescein translocation. Subsequent deplasmolysis of the cells did not remove the inhibiting effect of plasmolysis. The data are consistent with the interpretation that dye movement proceeds by diffusion, the rate-limiting step being transport through plasmodesmatal connections.
Vegetation–environment relations in a brackish marsh, Lulu Island, Richmond, B.C.
Authors: Hutchinson Ian
Published: September 2010

A study of plant–environment relations was conducted on the foreshore marshes of Lulu Island in the Fraser River delta. Analysis of tidal records indicated that the marsh platform could be subdivided into three elevational zones: a low marsh dominated by Scirpus americanus and S. maritimus; a middle marsh dominated by Carex lyngbyei, Triglochin maritimum, and S. maritimus; and a high marsh community of Agrostis exarata, Potentilla pacifica, Distichlis spicata, and Typha latifolia. This is interpreted as a successional sequence. The low marsh experiences a maximum continuous submergence of 21–16 h, the middle marsh a maximum of 8 h, and the high marsh a maximum continuous exposure of > 200 h. ANOVA results demonstrate the overwhelming importance of elevation (Typha, Potentilla, Distichlis) and elevation–salinity interactions (Scirpus spp., Carex, Agrostis) as controls on plant distribution. In addition substrate texture and moisture content are significantly associated with variations in species abundance. The Lulu Island marshes are floristically and ecologically similar to estuarine and deltaic marshes of Washington and Oregon. Variations in vegetation and successional pattern within this group are likely a function of fluvial regimes, which influence salinity and sediment characteristics.
Phytohormone changes in Bouteloua gracilis infected by vesicular–arbuscular mycorrhizae. II. Altered levels of gibberellin-like substances and abscisic acid in the host plant
Authors: Allen Michael F. , Moore Jr. Thomas S. , Christensen Martha
Published: September 2010

Bouteloua gracilis (H.B.K.) Lag ex Steud (blue grama) was grown in a defined medium with and without the vesicular–arbuscular mycorrhizal fungus Glomus fasciculatus for 50 days. Levels of gibberellin-like substances (GA) and a substance like abscisic acid (ABA) of mycorrhizal and nonmycorrhizal plants were measured using the barley half-seed bioassay and UV detection of peaks from a μ-Bondapak–NH2 anion exchange high-performance liquid chromatograph column, respectively. Infection by mycorrhizal fungi resulted in significantly increased GA activity in the leaves and a tendency for decreased activity in the roots. ABA concentration decreased in leaves of infected plants but remained unchanged in roots. Increased levels of GA with reduced ABA in the leaves may alter substantially the physiology of B. gracilis.
Pathogenicity of Trichoderma spp. on the sclerotia of Sclerotinia sclerotiorum
Authors: Santos A. F. Dos , Dhingra O. D.
Published: September 2010

One isolate of Trichoderma viride, 12 of T. koningii, 5 of T. harzianum, 11 of T. pseudokoningii, and 9 Trichoderma spp. obtained from 15 soils by baiting with the sclerotia of Sclerotinia sclerotiorum were tested for pathogenicity and aggressiveness in vitro and in field soil against the latter. Five isolates of T. koningii, two of T. harzianum, three of T. pseudokoningii, and one of an unidentified species killed 62–100% of the sclerotia within 25 days when tested in vitro. Two isolates of T. koningii killed 100% of the sclerotia within 7 days. One isolate of T. koningii killed 100% of the sclerotia within 60 days under field conditions, when soil was infested with 104, 106, or 108conidia/g. The rate of decline was more rapid at inoculum level of 106 and 108conidia/g of soil than at 104.
Hydraulic piping—theoretical and experimental findings
Authors: Kälin M.
Published: September 2010

The safety factor for piping by heave was conceived as a minimum criterion (probably in 1929 by Baumgart and Davidenkoff, certainly in 1943 by Terzaghi). The minimum condition of the criterion is frequently omitted. This paper gives the relation of the criterion to first principles and indicates solutions for the piece-wise homogeneous and linear inhomogeneous soil. Theoretical and experimental evidence shows that the omission of the minimum condition yields upper bound estimates for the safety factor and is equivalent to assuming homogeneity. It is concluded that in general the assumption of homogeneity is significantly on the unsafe side.