bluuebunny/crossref_metadata_2025 huggingface dataset:
Reflections on the Christchurch earthquake
Authors: Flanagan P.
Published: October 2011

Background and Objectives  The city of Christchurch in New Zealand suffered a series of major earthquakes during 2010 and 2011. These resulted in significant damage and loss of life. The impact of the earthquakes on New Zealand Blood Service is reviewed in the context of emergency planning and preparedness.

Impact assessment  The requirement for blood and blood components was low and easily met from within existing stocks. The anticipated influx of donors was well managed avoiding unnecessary build‐up of blood components and consequent wastage. The Christchurch Blood Centre was closed for a number of days following each major event. Contingency arrangements for supply to Christchurch and other hospitals in the region were successfully implemented.

Conclusions  Pre‐existing emergency plans are an essential component of emergency preparedness. These must however be flexible to respond to rapidly changing situations. The blood service plan must be integrated into regional and national response plans. Access to timely and accurate information is an important contributor to effective management.
Lecture: Blood Donation Program in the Asia Pacific Region
Authors: Thomas S.
Published: October 2011

As part of the Asia Pacific Blood Network (APBN) comparison of practice program, member countries review blood donor management practices to understand emerging trends in the region, and identify good practice opportunities which may benefit other members.

Our membership includes Australia, Beijing, Hong Kong, Japan, New Zealand, Singapore, South Korea, Taiwan and Thailand. From 2006, we have jointly collected information for a range of donor related measures, including age and sex distribution of donors, criteria for donation, donation volumes and frequencies, transfusion transmitted disease rates, additional donor health screening initiatives and donor deferrals.

Analysis of the donor management information both among member countries, and for individual countries over a period of 4 years, provides a useful window into some of the donor characteristics for our region. Whilst there are significant variations in population size of countries, there are shared trends in donor patterns subsequent to local disasters, reasons for donor deferrals, and the need for continued focus on relevant and effective donor retention and recruitment strategies. We continue to see lower red cell utilisation rates in Asia, in general a younger donor population with higher representation of male donors, and low haemoglobin as the single most common reason for donor deferral for most members.

APBN members are actively pursuing opportunities for shared donor management approaches, and the progress with these strategies in addition to an overview of regional donor measure is provided.
Evidence behind the pathophysiology of TRALI
Authors: Tung J. P. , Minchinton R. M. , Fraser J. F. , Fung Y. L.
Published: October 2011

Transfusion‐related acute lung injury (TRALI) is a serious transfusion complication that may lead to significant morbidity and mortality. This has driven a significant research effort focused on understanding why and how TRALI develops. The ultimate goal must be prevention or at least mitigation of the clinical consequences of TRALI.

The underlying pathophysiology of TRALI is presently best described by two hypotheses which are not mutually exclusive. These are the antibody mediated TRALI mechanism and the two‐event or priming TRALI mechanism. One of the key initial findings in TRALI research was the frequent presence of leucocyte antibodies in associated blood products, providing strong evidence for an antibody driven pathogenesis. In contrast, the two‐event mechanism proposed that these transfused antibodies activated neutrophils that had first been primed by the patient’s clinical condition.

Together, data from haemovigilance programs, clinical reports and experimental findings have led several countries to introduce TRALI risk‐reduction strategies. These include either limiting the transfusion of plasma from female donors or, screening female donors for the presence of leucocyte antibodies. Both approaches are justified by adoption of the immune mechanism as the prime driver of the pathogenesis of TRALI. TRALI incidence has gratifyingly been reduced by these measures. Nevertheless, TRALI cases persist and they remain a major concern because of continuing significant morbidity and mortality.

While the majority of earlier TRALI research has focused on the role of antibodies in TRALI, evidence for the role of non‐antibody factors in TRALI is now growing, based on an increasing number of in vitro, ex vivo and in vivo models. This review aims to present data from such models, which are the foundation for our current understanding of the pathophysiology behind antibody mediated and non‐antibody mediated TRALI.
Developing blood services in the Philippines
Authors: Nalupta C. M. M.
Published: October 2011

The goal of achieving reforms in the Philippine healthcare system has moved our government to push regulations in all key areas. With the objective of ensuring access to safe, quality and affordable blood products, improved facilities and services, the transfusion system in the Philippines is now in focus. Hence, the issuance of several administrative memos to guarantee the achievement of an effective blood service network in the country.
XMRV and blood safety: a case study of science and public pressure
Authors: Dodd R. Y.
Published: October 2011

XMRV is a recently discovered virus, related to mouse endogenous leukemia viruses. It was originally discovered in tissue from human prostate tumours and has been reported to be associated with chronic fatigue syndrome (CFS). Accumulating data suggest that the virus itself is a laboratory artifact and that many, if not all of the reported associations may be due to contamination of samples and or reagents. However, the association of this (and similar) viruses with chronic disease has attracted a great deal of public attention, particularly from CFS patients. Additionally, it was hypothesized that the virus might offer a risk to blood safety, generating additional pressures. Current data and perspectives on the issue will be discussed.
Association between infant formula feeding and dental fluorosis and caries in Australian children
Authors: Do Loc G. , Levy Steven M. , Spencer A. John
Published: October 2011

Objective: The objective of this study was to evaluate associations between patterns of infant formula feeding and dental fluorosis and caries in a representative sample of Australian children.

Methods: A population‐based study gathered information on fluoride exposure in early childhood. Information on infant formula feeding and fluoridation status was used to group children: three groups in nonfluoridated areas (formula nonuser, user for ≤6 months, and user for 6+ months) and four groups in fluoridated areas (nonuser, user with nonfluoridated water, user with fluoridated water for ≤6 months, and user with fluoridated water for 6+ months). Children aged 8‐13 years were examined for fluorosis using the Thylstrup and Fejerskov (TF) Index. Primary tooth caries experience recorded at age 8‐9 years was extracted from clinical records. Fluorosis cases were defined as having TF 1+ on maxillary incisors. Fluorosis prevalence and primary caries experience were compared across formula user groups in multivariable regression models adjusting for other factors.

Results: Total sample was 588 children. Children in fluoridated areas had higher prevalence of very mild to mild fluorosis, but lower caries experience than those in nonfluoridated areas. Among children in nonfluoridated areas, formula users for 6+ months had significantly higher prevalence of fluorosis compared with nonusers. There was no significant difference in fluorosis prevalence among the formula users in fluoridated areas. Among children in fluoridated areas, formula users with nontap water had higher caries experience.

Conclusion: Infant formula use was associated with higher prevalence of fluorosis in nonfluoridated areas but not in fluoridated areas. Type of water used for reconstituting infant formula in fluoridated areas was associated with caries experience.
Experimental Study of Integrated Multilayer Clamping High Pressure Vessel
Authors: Liang Zhen , Nan Jiang , Sijia Liu
Published: October 2011

The hydrostatic test of integrated multilayer clamping high pressure vessel is performed from 15.7 MPa to 56.52 MPa (1.8 times of the design pressure). The measured stress values have deviation from the Lamè equation (maximum error 34%). The inner wall stress is low while the outer wall stress is high. The layered vessel mechanics model is deduced to analyze the deviation. The inner shell is an external pressure vessel and the outer shell is the internal pressure vessel. The contact of the inner shell and the outer shell generates preload stress. The multilayer structure parameter is a universal nondimensional parameter to calculate the preload stress of layered vessel, and the corrected theory values have smaller error in high pressure (less than 10%). The super hydrostatic test alters the preload stress distribution and the gaps between layers.
On the Stiffness of the Tangent Modulus Tensor in Elastoplasticity
Authors: Nicholson David W. , Silvers Thomas W.
Published: October 2011

In finite element analysis of pressure vessels undergoing elastoplastic deformation, low stiffness of the tangent modulus tensor will engender low stiffness in the tangent stiffness matrix, posing a risk of computational difficulties such as poor convergence. The current investigation presents the explicit tangent modulus tensor in an elastoplastic model based on a Von Mises yield surface with isotropic work hardening, and the associated flow rule. The stiffness of the tangent modulus tensor is assessed by deriving explicit expressions for its minimum eigenvalue using both tensor diagonalization and Rayleigh quotient minimization. The derived expressions are validated computationally. Using the minimum eigenvalue, the stiffness is found to depend on the current path in stress space. The results of the current investigation suggest a way of following a stress path, which bypasses low stiffness, while attaining the prescribed load.
Piezoelectric Wafer Active Sensors for Structural Health Monitoring of Composite Structures Using Tuned Guided Waves
Authors: Giurgiutiu Victor
Published: October 2011

Piezoelectric wafer active sensors (PWAS) are lightweight and inexpensive transducers that enable a large class of structural health monitoring (SHM) applications such as: (a) embedded guided wave ultrasonics, i.e., pitch-catch, pulse-echo, phased arrays; (b) high-frequency modal sensing, i.e., the electro-mechanical (E/M) impedance method; and (c) passive detection (acoustic emission and impact detection). The focus of this paper is on the challenges posed by using PWAS transducers in the composite structures as different from the metallic structures on which this methodology was initially developed. After a brief introduction, the paper reviews the PWAS-based SHM principles. It follows with a discussion of guided wave propagation in composites and PWAS tuning effects. Then, it discusses damage modes in composites. Finally, the paper presents some experimental results with damage detection in composite specimens. Hole damage and impact damage were detected using pitch-catch method with tuned guided waves being sent between a transmitter PWAS and a received PWAS. Root mean square deviation (RMSD) damage index (DI) were shown to correlate well with hole size and impact intensity. The paper ends with summary and conclusion; suggestions for further work are also presented.
Three-Dimensional Numerical Simulation of Random Fiber Composites With High Aspect Ratio and High Volume Fraction
Authors: Jin Bo Cheng , Pelegri Assimina A.
Published: October 2011

Organic and inorganic fiber reinforced composites with various fiber orientation distributions and fiber geometries are abundantly available in several natural and synthetic structures. Inorganic glass fiber composites have been introduced to numerous applications due to their economical fabrication and tailored structural properties. Numerical characterization of such composite materials is necessitated due to their intrinsic statistical nature, since elaborate experiments are prohibitively costly and time consuming. In this work, representative volume elements of unidirectional random filaments and fibers are numerically developed in PYTHON to enhance accuracy and efficiency of complex geometric representations encountered in random fiber networks. A modified random sequential adsorption algorithm is applied to increase the volume fraction of the representative volume elements, and a spatial segment shortest distance algorithm is introduced to construct a 3D random fiber composite with high fiber aspect ratio (100:1) and high volume fraction (31.8%). For the unidirectional fiber networks, volume fractions as high as 70% are achieved when an assortment of circular fiber diameters are used in the representative volume element.
A Mechanics of Materials Model for the Creping Process
Authors: Ramasubramanian Melur K. , Sun Zhaohui , Chen Guang
Published: October 2011

The manufacture of low density paper such as tissue and towel utilizes the creping process that consists of adhesively bonding the paper in wet state onto the surface of a smooth drying cylinder and scraping it off with a blade once dried. In this paper, a mechanics of materials description of the creping process is presented. Based upon previous experimental observations, the mechanism of this creping process is proposed as a periodic debonding with a strength-of-materials failure criterion applied and buckling sequence of an elastic thin film. Numerical calculations show results consistent with experimental data and known industrial observations. Crepe wavelength versus creping angle data from experiments can be satisfactorily reproduced by a reasonable set of values for input parameters to the model. Parametric study shows the adhesive shear strength and the sheet stiffness most significantly affect the crepe wavelength and the creping force. The model provides guidance in understanding and optimizing the creping process to produce high quality products.
Globalization, Land Use, and the Invasion of West Nile Virus
Authors: Kilpatrick A. Marm
Published: October 2011

Many invasive species that have been spread through the globalization of trade and travel are pathogens. A paradigmatic case is the introduction of West Nile virus (WNV) into North America in 1999. A decade of research on the ecology and evolution of WNV includes three findings that provide insight into the outcome of future pathogen introductions. First, WNV transmission in North America is highest in urbanized and agricultural habitats, in part because the hosts and vectors of WNV are abundant in human-modified areas. Second, after its introduction, the virus quickly adapted to infect local mosquito vectors more efficiently than the originally introduced strain. Third, highly focused feeding patterns of the mosquito vectors of WNV result in unexpected host species being important for transmission. This research provides a framework for predicting and preventing the emergence of foreign vector-borne pathogens.
Cerebellum Shapes Hippocampal Spatial Code
Authors: Rochefort Christelle , Arabo Arnaud , André Marion , Poucet Bruno , Save Etienne , Rondi-Reig Laure
Published: October 2011

Cerebellar protein kinase C–dependent mechanisms process self-motion information needed for spatial representation and accurate navigation.
Dynamics of the Reaction of Methane with Chlorine Atom on an Accurate Potential Energy Surface
Authors: Czakó Gábor , Bowman Joel M.
Published: October 2011

Theory helps explain the counterintuitive impacts of vibrational excitation in a widely studied reaction.
Eddies Masquerade as Planetary Waves
Authors: McGillicuddy Dennis J.
Published: October 2011

Variabilities in sea-level and upper-ocean chlorophyll reveal the systematic influence of nonlinear eddies.
Rethink Summer Student Research
Authors: Carrero-Martínez Franklin A.
Published: October 2011

Research and training at institutions serving minority students may suffer as top students leave for other schools each summer.
Mass Spectrometry of Intact V-Type ATPases Reveals Bound Lipids and the Effects of Nucleotide Binding
Authors: Zhou Min , Morgner Nina , Barrera Nelson P. , Politis Argyris , Isaacson Shoshanna C , Matak-Vinković Dijana , Murata Takeshi , Bernal Ricardo A. , Stock Daniela , Robinson Carol V.
Published: October 2011

The effect of lipids and nucleotides on the soluble head domain and membrane base domain is examined in an intact adenosine triphosphatase.
The Strength of Electrical Synapses
Authors: Hestrin Shaul
Published: October 2011

The strength of electrical synapses in the mammalian brain can be modulated by neuronal activity.
Up Close with Membrane Lipid-Protein Complexes
Authors: Whitelegge Julian
Published: October 2011

State-of-the-art mass spectrometry reveals how many specific lipids are bound to membrane proteins.
Mice Orally Immunized with a Transgenic Plant Expressing the Glycoprotein of Crimean-Congo Hemorrhagic Fever Virus
Authors: Ghiasi S. M. , Salmanian A. H. , Chinikar S. , Zakeri S.
Published: October 2011

While Crimean-Congo hemorrhagic fever (CCHF) has a high mortality rate in humans, the associated virus (CCHFV) does not induce clinical symptoms in animals, but animals play an important role in disease transmission to humans. Our aim in this study was to examine the immunogenicity of the CCHFV glycoprotein when expressed in the root and leaf of transgenic plants via hairy roots and stable transformation of tobacco plants, respectively. After confirmatory analyses of transgenic plant lines and quantification of the expressed glycoprotein, mice were either fed with the transgenic leaves or roots, fed the transgenic plant material and injected subcutaneously with the plant-made CCHFV glycoprotein (fed/boosted), vaccinated with an attenuated CCHF vaccine (positive control), or received no treatment (negative control). All immunized groups had a consistent rise in anti-glycoprotein IgG and IgA antibodies in their serum and feces, respectively. The mice in the fed/boosted group showed a significant rise in specific IgG antibodies after a single boost. Our results imply that oral immunization of animals with edible materials from transgenic plants is feasible, and further assessments are under way. In addition, while the study of CCHF is challenging, our protocol should be further used to study CCHFV infection in the knockout mouse model and virus neutralization assays in biosafety level 4 laboratories.
Comparative Effectiveness of Dried-Plasma Hepatitis B Virus Viral Load (VL) Testing in Three Different VL Commercial Platforms Using ViveST for Sample Collection
Authors: Zanoni Michelle , Giron Leila B. , Vilhena Cintia , Sucupira Maria Cecilia , Lloyd Robert M. , Diaz Ricardo Sobhie
Published: October 2011

Ninety-six samples from hepatitis B virus (HBV)-infected individuals were used to compare ViveST samples to frozen samples in COBAS TaqMan, RealArt, and VERSANT. Correlation (
r
) between ViveST samples and frozen samples was 0.99 in all three platforms. Correlations among tests using frozen samples were 0.96 for COBAS and RealArt, 0.94 for COBAS and VERSANT, and 0.97 for VERSANT and RealArt. The results indicate that ViveST may be useful in clinical practice. Different HBV-VL platforms correlated well with one another.
Significant Finding of Bordetella holmesii DNA in Nasopharyngeal Samples from French Patients with Suspected Pertussis
Authors: Njamkepo Elisabeth , Bonacorsi Stéphane , Debruyne Monique , Gibaud Sophie Anne , Guillot Sophie , Guiso Nicole
Published: October 2011

Pertussis is routinely diagnosed with real-time PCR based on insertion sequence IS
481
, which is not specific for
Bordetella pertussis
. We conducted a retrospective study using real-time PCRs specific for
Bordetella pertussis
and for
Bordetella holmesii
on 177 samples positive for IS
481
PCR.
Bordetella holmesii
DNA was detected in 20.3% samples collected from adolescents and adults.
Diagnosis of Invasive Aspergillosis by a Commercial Real-Time PCR Assay for Aspergillus DNA in Bronchoalveolar Lavage Fluid Samples from High-Risk Patients Compared to a Galactomannan Enzyme Immunoassay
Authors: Torelli Riccardo , Sanguinetti Maurizio , Moody Adrian , Pagano Livio , Caira Morena , De Carolis Elena , Fuso Leonello , De Pascale Gennaro , Bello Giuseppe , Antonelli Massimo , Fadda Giovanni , Posteraro Brunella
Published: October 2011

Culture-independent molecular techniques such as real-time PCRs offer the potential for early diagnosis of invasive aspergillosis (IA), thereby reducing the disease-associated mortality rate. PCR-based testing is presently excluded from disease-defining consensus criteria due to lack of standardization and clinical validation. A single-center prospective study was conducted to investigate the performance of the commercially available MycAssayAspergillustest for detectingAspergillusDNA in patients with suspicion of IA. To this end, a total of 158 bronchoalveolar lavage (BAL) fluid specimens that were consecutively collected from hematology (n= 68) and intensive care unit (n= 90) patients were examined. Sixteen of 17 (94.1%) specimens from patients with proven/probable IA were MycAssay positive, and 15 of these 16 patients were also positive by an “in-house” PCR assay. A total of 139 of 141 (98.6%) specimens from patients without proven/probable IA were MycAssay negative. Fifteen of 16 (94.1%) MycAssay-positive patients were also positive for BAL fluid galactomannan (GM) at an index cutoff of ≥1.0 (index range, 1.1 to 8.3), as were 3 patients without IA but with pulmonary fusariosis. Interestingly, in seven of the PCR-positive BAL specimens that tested culture positive forAspergillusspecies, cycle threshold values were earlier than those of specimens with a culture-negative result. In conclusion, the MycAssayAspergillusPCR appears to be a sensitive and specific molecular test for the diagnosis of IA, and its performance is comparable to that of the GM assay. However, more large studies are necessary to firmly establish its clinical utility in high-risk settings.
Sensitive and Specific Modified Hodge Test for KPC and Metallo-Beta- Lactamase Detection in Pseudomonas aeruginosa by Use of a Novel Indicator Strain, Klebsiella pneumoniae ATCC 700603
Authors: Pasteran Fernando , Veliz Omar , Rapoport Melina , Guerriero Leonor , Corso Alejandra
Published: October 2011

We evaluated the ability of the modified Hodge test to discriminate between KPC- and metallo-beta-lactamase (MBL)-producing
Pseudomonas aeruginosa
isolates and carbapenemase nonproducers. With
Escherichia coli
ATCC 25922 as the indicator strain, the MHT resulted in low sensitivity, specificity, and repeatability. Replacing the indicator strain with
Klebsiella pneumoniae
ATCC 700603 led to an improved performance (100%, 97%, 0%, and 100% sensitivity, specificity, indeterminate results and repeatability, respectively).
Case of Diffuse Lepromatous Leprosy Associated with “Mycobacterium lepromatosis”
Authors: Vera-Cabrera Lucio , Escalante-Fuentes Wendy G. , Gomez-Flores Minerva , Ocampo-Candiani Jorge , Busso Philippe , Singh Pushpendra , Cole Stewart T.
Published: October 2011

An 86-year-old female patient from northeast Mexico presented with diffuse lepromatous leprosy (DLL). Sequence analysis of four genes (
rrs
,
rpoB
,
sigA
, and
hsp65
) from the skin biopsy specimen identified “
Mycobacterium lepromatosis
.” This is the first independent confirmation of a case of DLL due to
M. lepromatosis
.
True Microbiota Involved in Chronic Lung Infection of Cystic Fibrosis Patients Found by Culturing and 16S rRNA Gene Analysis
Authors: Rudkjøbing Vibeke B. , Thomsen Trine R. , Alhede Morten , Kragh Kasper N. , Nielsen Per H. , Johansen Ulla R. , Givskov Michael , Høiby Niels , Bjarnsholt Thomas
Published: October 2011

Patients suffering from cystic fibrosis (CF) develop chronic lung infection. In this study, we investigated the microorganisms present in transplanted CF lungs (
n
= 5) by standard culturing and 16S rRNA gene analysis. A correspondence between culturing and the molecular methods was observed. In conclusion, standard culturing seems reliable for the identification of the dominating pathogens.
Mutations of Gln64 in the HIV-1 gp41 N-Terminal Heptad Repeat Render Viruses Resistant to Peptide HIV Fusion Inhibitors Targeting the gp41 Pocket
Authors: Yu Xiaowen , Lu Lu , Cai Lifeng , Tong Pei , Tan Suiyi , Zou Peng , Meng Fanxia , Chen Ying-hua , Jiang Shibo
Published: October 2011

To prove that the peptidic HIV-1 fusion inhibitors containing the pocket-binding domain (PBD) mainly target the hydrophobic pocket in the gp41 N-terminal heptad repeat (NHR), we constructed pseudoviruses by replacement of Q64 in the gp41 pocket region with Ala (Q64A) or Leu (Q64L). These viruses were highly resistant to C34 and CP32M containing the PBD, while they were susceptible to T20 (enfuvirtide) lacking the PBD but containing the GIV-motif-binding domain (GBD) and lipid-binding domain (LBD). They were also sensitive to C52L, which contains the PBD, GBD, and LBD. Those mutations may disrupt the hydrophilic interaction between Q64 in the NHR and N113 in the peptides containing the PBD. This report provides insights into the mechanisms of drug resistance, with implications for the design of novel HIV fusion and entry inhibitors.
A Novel Self-Replicating Chimeric Lentivirus-Like Particle
Authors: Jurgens Christy K. , Young Kelly R. , Madden Victoria J. , Johnson Philip R. , Johnston Robert E.
Published: October 2011

Successful live attenuated vaccines mimic natural exposure to pathogens without causing disease and have been successful against several viruses. However, safety concerns prevent the development of attenuated human immunodeficiency virus (HIV) as a vaccine candidate. If a safe, replicating virus vaccine could be developed, it might have the potential to offer significant protection against HIV infection and disease. Described here is the development of a novel self-replicating chimeric virus vaccine candidate that is designed to provide natural exposure to a lentivirus-like particle and to incorporate the properties of a live attenuated virus vaccine without the inherent safety issues associated with attenuated lentiviruses. The genome from the alphavirus Venezuelan equine encephalitis virus (VEE) was modified to express SHIV89.6P genes encoding the structural proteins Gag and Env. Expression of Gag and Env from VEE RNA in primate cells led to the assembly of particles that morphologically and functionally resembled lentivirus virions and that incorporated alphavirus RNA. Infection of CD4
+
cells with chimeric lentivirus-like particles was specific and productive, resulting in RNA replication, expression of Gag and Env, and generation of progeny chimeric particles. Further genome modifications designed to enhance encapsidation of the chimeric virus genome and to express an attenuated simian immunodeficiency virus (SIV) protease for particle maturation improved the ability of chimeric lentivirus-like particles to propagate in cell culture. This study provides proof of concept for the feasibility of creating chimeric virus genomes that express lentivirus structural proteins and assemble into infectious particles for presentation of lentivirus immunogens in their native and functional conformation.
Small but Sufficient: the Rhodococcus Phage RRH1 Has the Smallest Known Siphoviridae Genome at 14.2 Kilobases
Authors: Petrovski Steve , Dyson Zoe A. , Seviour Robert J. , Tillett Daniel
Published: October 2011

Bacteriophages are considered to be the most abundant biological entities on the planet. The
Siphoviridae
are the most commonly encountered tailed phages and contain double-stranded DNA with an average genome size of ∼50 kb. This paper describes the isolation from four different activated sludge plants of the phage RRH1, which is polyvalent, lysing five
Rhodococcus
species. It has a capsid diameter of only ∼43 nm. Whole-genome sequencing of RRH1 revealed a novel circularly permuted DNA sequence (14,270 bp) carrying 20 putative open reading frames. The genome has a modular arrangement, as reported for those of most
Siphoviridae
phages, but appears to encode only structural proteins and carry a single lysis gene. All genes are transcribed in the same direction. RRH1 has the smallest genome yet of any described functional
Siphoviridae
phage. We demonstrate that lytic phage can be recovered from transforming naked DNA into its host bacterium, thus making it a potentially useful model for studying gene function in phages.
Length Variations in the NA Stalk of an H7N1 Influenza Virus Have Opposite Effects on Viral Excretion in Chickens and Ducks
Authors: Hoffmann T. W. , Munier S. , Larcher T. , Soubieux D. , Ledevin M. , Esnault E. , Tourdes A. , Croville G. , Guérin J.-L. , Quéré P. , Volmer R. , Naffakh N. , Marc D.
Published: October 2011

A deletion of ∼20 amino acids in the stalk of neuraminidase is frequently observed upon transmission of influenza A viruses from waterfowl to domestic poultry. A pair of recombinant H7N1 viruses bearing either a short- or long-stalk neuraminidase was genetically engineered. Inoculation of the long-stalk-neuraminidase virus resulted in a higher cloacal excretion in ducks and led conversely to lower-level oropharyngeal excretion in chickens, associated with a higher-level local immune response and better survival. Therefore, a short-stalk neuraminidase is a determinant of viral adaptation and virulence in chickens but is detrimental to virus replication and shedding in ducks.
Contributions of the Epstein-Barr Virus EBNA1 Protein to Gastric Carcinoma
Authors: Sivachandran Nirojini , Dawson Christopher W. , Young Lawrence S. , Liu Fei-Fei , Middeldorp Jaap , Frappier Lori
Published: October 2011

Approximately 10% of gastric carcinomas (GC) are comprised of cells latently infected with Epstein-Barr virus (EBV); however, the mechanism by which EBV contributes to the development of this malignancy is unclear. We have investigated the cellular effects of the only EBV nuclear protein expressed in GC, EBNA1, focusing on promyelocytic leukemia (PML) nuclear bodies (NBs), which play important roles in apoptosis, p53 activation, and tumor suppression. AGS GC cells infected with EBV were found to contain fewer PML NBs and less PML protein than the parental EBV-negative AGS cells, and these levels were restored by silencing EBNA1. Conversely, EBNA1 expression was sufficient to induce the loss of PML NBs and proteins in AGS cells. Consistent with PML functions, EBNA1 expression decreased p53 activation and apoptosis in response to DNA damage and resulted in increased cell survival. In addition, EBNA1 mutants unable to bind CK2 kinase or ubiquitin-specific protease 7 had decreased ability to induce PML loss and to interfere with p53 activation. PML levels in EBV-positive and EBV-negative GC biopsy specimens were then compared by immunohistochemistry. Consistent with the results in the AGS cells, EBV-positive tumors had significantly lower PML levels than EBV-negative tumors. The results indicate that EBV infection of GC cells leads to loss of PML NBs through the action of EBNA1, resulting in impaired responses to DNA damage and promotion of cell survival. Therefore, PML disruption by EBNA1 is one mechanism by which EBV may contribute to the development of gastric cancer.
Changes in the Nasopharyngeal Carcinoma Nuclear Proteome Induced by the EBNA1 Protein of Epstein-Barr Virus Reveal Potential Roles for EBNA1 in Metastasis and Oxidative Stress Responses
Authors: Cao Jennifer Yinuo , Mansouri Sheila , Frappier Lori
Published: October 2011

Epstein-Barr virus (EBV) infection is causatively associated with a variety of human cancers, including nasopharyngeal carcinoma (NPC). The only viral nuclear protein expressed in NPC is EBNA1, which can alter cellular properties in ways that may promote oncogenesis. Here, we used
2-d
imensional
di
fference
g
el
e
lectrophoresis (2-D DiGE) to profile changes in the nuclear proteome that occur after stable expression of EBNA1 in the EBV-negative NPC cell line CNE2. We found that EBNA1 consistently altered the levels of a small percentage of the nuclear proteins. The identification of 19 of these proteins by mass spectrometry revealed that EBNA1 upregulated three proteins affecting metastatic potential (stathmin 1, maspin, and Nm23-H1) and several proteins in the oxidative stress response pathway, including the antioxidants superoxide dismutase 1 (SOD1) and peroxiredoxin 1 (Prx1). Western blot analysis verified that EBNA1 expression upregulated and EBNA1 silencing downregulated these proteins. In addition, transcripts for stathmin 1 were induced by EBNA1, whereas EBNA1 only affected Prx1 and SOD1 at the protein level. Further investigation of the EBNA1 effects on the redox pathway showed that long-term EBNA1 expression in NPC resulted in increased reactive oxygen species (ROS) and increased levels of the NADPH oxidases NOX1 and NOX2, known to generate ROS. In addition, EBNA1 depletion in EBV-positive cells decreased NOX2 and ROS. The results show multiple roles for EBNA1 in the oxidative stress response pathway and suggest mechanisms by which EBNA1 may promote NPC metastases.
The Vaccinia Virus-Encoded Bcl-2 Homologues Do Not Act as Direct Bax Inhibitors
Authors: Postigo Antonio , Way Michael
Published: October 2011

Many viruses, including members of several poxvirus genera, encode inhibitors that block apoptosis by simultaneously binding the proapoptotic Bcl-2 proteins Bak and Bax. The
Orthopoxvirus
vaccinia virus encodes the Bcl-2-like F1 protein, which sequesters Bak but not Bax. However, N1, a potent virulence factor, is reported to be antiapoptotic and to interact with Bax. Here we investigated whether vaccinia virus inhibits Bak/Bax-dependent apoptosis via the cooperative action of F1 and N1. We found that Western Reserve (WR) and ΔN1L viruses inhibited drug- and infection-induced apoptosis equally. Meanwhile, infections with ΔF1L or ΔN1L/F1L virus resulted in similar levels of Bax activation and apoptosis. Outside the context of infection, N1 did not block drug- or Bax-induced cell death or interact with Bax. In addition to F1 and N1, vaccinia virus encodes further structural homologs of Bcl-2 proteins that are conserved in orthopoxviruses, including A46, A52, B14, C1, C6, C16/B22, K7, and N2. However, we found that these do not associate with Bax or inhibit drug-induced cell death. Based on our findings that N1 is not an antiapoptotic protein, we propose that the F1 orthologs represent the only orthopoxvirus Bcl-2 homolog to directly inhibit the Bak/Bax checkpoint.
High-Resolution Profiling and Analysis of Viral and Host Small RNAs during Human Cytomegalovirus Infection
Authors: Stark Thomas J. , Arnold Justin D. , Spector Deborah H. , Yeo Gene W.
Published: October 2011

Human cytomegalovirus (HCMV) contributes its own set of microRNAs (miRNAs) during lytic infection of cells, likely fine-tuning conditions important for viral replication. To enhance our understanding of this component of the HCMV-host transcriptome, we have conducted deep-sequencing analysis of small RNAs (smRNA-seq) from infected human fibroblast cells. We found that HCMV-encoded miRNAs accumulate to ∼20% of the total smRNA population at late stages of infection, and our analysis led to improvements in viral miRNA annotations and identification of two novel HCMV miRNAs, miR-US22 and miR-US33as. Both of these miRNAs were capable of functionally repressing synthetic targets in transient transfection experiments. Additionally, through cross-linking and immunoprecipitation (CLIP) of Argonaute (Ago)-bound RNAs from infected cells, followed by high-throughput sequencing, we have obtained direct evidence for incorporation of all HCMV miRNAs into the endogenous host silencing machinery. Surprisingly, three HCMV miRNA precursors exhibited differential incorporation of their mature miRNA arms between Ago2 and Ago1 complexes. Host miRNA abundances were also affected by HCMV infection, with significant upregulation observed for an miRNA cluster containing miR-96, miR-182, and miR-183. In addition to miRNAs, we also identified novel forms of virus-derived smRNAs, revealing greater complexity within the smRNA population during HCMV infection.
Complete Genome Sequence of a Coxsackievirus A22 Strain in Hong Kong Reveals a Natural Intratypic Recombination Event
Authors: Yip Cyril C. Y. , Lau Susanna K. P. , Woo Patrick C. Y. , Chan Kwok-Hung , Yuen Kwok-Yung
Published: October 2011

Coxsackievirus A22 (CVA22) belongs to the species human enterovirus C in the
Picornaviridae
family. We report the first complete genome sequence of CVA22 with natural intratypic recombination between CVA22 prototype strain Chulman and CVA22 strain ban99-10427, identified in the stool of a patient in Hong Kong.
Analysis of the Interaction between the Essential Herpes Simplex Virus 1 Tegument Proteins VP16 and VP1/2
Authors: Svobodova Stanislava , Bell Susanne , Crump Colin M.
Published: October 2011

The incorporation of tegument proteins into the herpes simplex virus 1 (HSV-1) virion during virion assembly is thought to be a complex, multistage process occurring via numerous interactions between the tegument and the capsid, within the tegument, and between the tegument and the envelope. Here, we set out to examine if the direct interaction between two essential tegument proteins VP1/2 and VP16 is required for connecting the inner tegument with the outer tegument. By using glutathione
S
-transferase (GST) pulldowns, we identified an essential role of lysine 343 in VP16, mutation of which to a neutral amino acid abrogated the interaction between VP1/2 and VP16. When the K343A substitution was inserted into the gene encoding VP16 (UL48) of the viral genome, HSV-1 replicated successfully although its growth was delayed, and final titers were reduced compared to titers of wild-type virus. Surprisingly, the mutated VP16 was incorporated into virions at levels similar to those of wild-type VP16. However, the analysis of VP16 on cytoplasmic capsids by fluorescence microscopy showed that VP16 associated with cytoplasmic capsids less efficiently when the VP16-VP1/2 interaction was inhibited. This implies that the direct interaction between VP1/2 and VP16 is important for the efficiency/timing of viral assembly but is not essential for HSV-1 replication in cell culture. These data also support the notion that the incorporation of tegument proteins into the herpesviruses is a very complex process with significant redundancy.
The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H
Authors: Binka Mawuena , Ooms Marcel , Steward Myeika , Simon Viviana
Published: October 2011

The APOBEC3 family comprises seven cytidine deaminases (APOBEC3A [A3A] to A3H), which are expressed to various degrees in HIV-1 susceptible cells. The HIV-1 Vif protein counteracts APOBEC3 restriction by mediating its degradation by the proteasome. We hypothesized that Vif proteins from various HIV-1 subtypes differ in their abilities to counteract different APOBEC3 proteins. Seventeen Vif alleles from seven HIV-1 subtypes were tested for their abilities to degrade and counteract A3G, A3F, and A3H haplotype II (hapII). We show that most Vif alleles neutralize A3G and A3F efficiently but display differences with respect to the inhibition of A3H hapII. The majority of non-subtype B Vif alleles tested presented some activity against A3H hapII, with two subtype F Vif variants being highly effective in counteracting A3H hapII. The residues required for activity were mapped to two residues in the amino-terminal region of Vif (positions 39F and 48H). Coimmunoprecipitations showed that these two amino acids were necessary for association of Vif with A3H hapII. These findings suggest that the A3H hapII binding site in Vif is distinct from the regions important for A3G and A3F recognition and that it requires specific amino acids at positions 39 and 48. The differential Vif activity spectra, especially against A3H hapII, suggest adaptation to APOBEC3 repertoires representative of different human ancestries. Phenotypic assessment of anti-APOBEC3 activity of Vif variants against several cytidine deaminases will help reveal the requirement for successful replication
in vivo
and ultimately point to interventions targeting the Vif-APOBEC3 interface.
Amino Acid Changes in Hemagglutinin Contribute to the Replication of Oseltamivir-Resistant H1N1 Influenza Viruses
Authors: Ginting Teridah Ernala , Shinya Kyoko , Kyan Yukihiro , Makino Akiko , Matsumoto Naomi , Kaneda Satoko , Kawaoka Yoshihiro
Published: October 2011

Oseltamivir-resistant H1N1 influenza viruses emerged in 2007 to 2008 and have subsequently circulated widely. However, prior to 2007 to 2008, viruses possessing the neuraminidase (NA) H274Y mutation, which confers oseltamivir resistance, generally had low growth capability. NA mutations that compensate for the deleterious effect of the NA H274Y mutation have since been identified. Given the importance of the functional balance between hemagglutinin (HA) and NA, we focused on amino acid changes in HA. Reverse genetic analysis showed that a mutation at residue 82, 141, or 189 of the HA protein promotes virus replication in the presence of the NA H274Y mutation. Our findings thus identify HA mutations that contributed to the replacement of the oseltamivir-sensitive viruses of 2007 to 2008.
Mutations at the Base of the Icosahedral Five-Fold Cylinders of Minute Virus of Mice Induce 3′-to-5′ Genome Uncoating and Critically Impair Entry Functions
Authors: Cotmore Susan F. , Tattersall Peter
Published: October 2011

The linear single-stranded DNA genome of minute virus of mice can be ejected, in a 3′-to-5′ direction, via a cation-linked uncoating reaction that leaves the 5′ end of the DNA firmly complexed with its otherwise intact protein capsid. Here we compare the phenotypes of four mutants, L172T, V40A, N149A, and N170A, which perturb the base of cylinders surrounding the icosahedral 5-fold axes of the virus, and show that these structures are strongly implicated in 3′-to-5′ release. Although noninfectious at 37°C, all mutants were viable at 32°C, showed a temperature-sensitive cell entry defect, and, after proteolysis of externalized VP2 N termini, were unable to protect the VP1 domain, which is essential for bilayer penetration. Mutant virus yields from multiple-round infections were low and were characterized by the accumulation of virions containing subgenomic DNAs of specific sizes. In V40A, these derived exclusively from the 5′ end of the genome, indicative of 3′-to-5′ uncoating, while L172T, the most impaired mutant, had long subgenomic DNAs originating from both termini, suggesting additional packaging portal defects. Compared to the wild type, genome release
in vitro
following cation depletion was enhanced for all mutants, while only L172T released DNA, in both directions, without cation depletion following proteolysis at 37°C. Analysis of progeny from single-round infections showed that uncoating did not occur during virion assembly, release, or extraction. However, unlike the wild type, the V40A mutant extensively uncoated during cell entry, indicating that the V40-L172 interaction restrains an uncoating trigger mechanism within the endosomal compartment.
Generation of HIV Latency in Humanized BLT Mice
Authors: Denton Paul W. , Olesen Rikke , Choudhary Shailesh K. , Archin Nancy M. , Wahl Angela , Swanson Michael D. , Chateau Morgan , Nochi Tomonori , Krisko John F. , Spagnuolo Rae Ann , Margolis David M. , Garcia J. Victor
Published: October 2011

Here we demonstrate that a combination of tenofovir, emtricitabine, and raltegravir effectively suppresses peripheral and systemic HIV replication in humanized BLT mice. We also demonstrate that antiretroviral therapy (ART)-treated humanized BLT mice harbor latently infected resting human CD4
+
T cells that can be induced
ex vivo
to produce HIV. We observed that the levels of infected resting human CD4
+
T cells present in BLT mice are within the range of those observed circulating in patients undergoing suppressive ART. These results demonstrate the potential of humanized BLT mice as an attractive model for testing the
in vivo
efficacy of novel HIV eradication strategies.
Do nurse and patient injuries share common antecedents? An analysis of associations with safety climate and working conditions
Authors: Taylor Jennifer A , Dominici Francesca , Agnew Jacqueline , Gerwin Daniel , Morlock Laura , Miller Marlene R
Published: October 2011

Background

Safety climate and nurses' working conditions may have an impact on both patient outcomes and nurse occupational health, but these outcomes have rarely been examined concurrently.

Objective

To examine the association of unit-level safety climate and specific nurse working conditions with injury outcomes for both nurses and patients in a single hospital.

Research design

A cross-sectional study was conducted using nursing-unit level and individual-level data at an urban, level-one trauma centre in the USA. Multilevel logistic regressions were used to examine associations among injury outcomes, safety climate and working conditions on 29 nursing units, including a total of 723 nurses and 28 876 discharges.

Measures

Safety climate was measured in 2004 using the Safety Attitudes Questionnaire (SAQ). Working conditions included registered nursing hours per patient day (RNHPPD) and unit turnover. Patient injuries included 290 falls, 167 pulmonary embolism/deep vein thrombosis (PE/DVT), and 105 decubitus ulcers. Nurse injury was defined as a reported needle-stick, splash, slip, trip, or fall (n=78). Working conditions and outcomes were measured in 2005.

Results

The study found a negative association between two SAQ domains, Safety and Teamwork, with the odds of both decubitus ulcers and nurse injury. RNHPPD showed a negative association with patient falls and decubitus ulcers. Unit turnover was positively associated with nurse injury and PE/DVT, but negatively associated with falls and decubitus ulcers.

Conclusions

Safety climate was associated with both patient and nurse injuries, suggesting that patient and nurse safety may actually be linked outcomes. The findings also indicate that increased unit turnover should be considered a risk factor for nurse and patient injuries.