bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphoepithelioma‐like carcinoma of the palate: report of a case with a 15‐year follow‐up
Authors: Aydıntuğ Y.S. , Okçu K.M. , Şençimen M. , Altuğ H.A. , Safalı M. , Haznedaroğlu M.
Published: November 2009

Lymphoepithelioma‐like carcinoma (LEC), an undifferentiated carcinoma with pronounced lymphocytic infiltration, is often seen in the nasopharynx as well as in other areas. Intraoral LELC is rare, as reflected by the paucity of cases reported in a major centre, which equates to less than one case per year. The literature search revealed that intraoral LELC has a male predilection [1.5 to 1]. Here we report a case of LELC of the hard palate in a 39‐year‐old woman operated in 1994.
Re‐exposure of impacted maxillary canines: the North Bristol experience
Authors: Fleming C. , Evans M.
Published: November 2009

Aims:  This study aims to find an incidence of surgical re‐exposure of impacted maxillary canines in our unit and to ascertain complications that lead to re‐exposures.

Results:  Two hundred and forty‐nine maxillary canine exposures were carried out on 230 patients in the period 2006–2008. The re‐exposure rate was 2.0% (five out of 249 exposures) and the main complications leading to re‐exposure were debonding of the gold chain in closed exposures, and early loss of periodontal dressing in open exposures.

Conclusion:  Re‐exposures of impacted maxillary canines do occur in our unit but cases are relatively infrequent compared with other studies. Complications occurred with both open and closed exposure techniques; however, there is no evidence to suggest any one particular surgical technique contributes to an increase in the incidence of re‐exposures.
Penetrating orbital trauma
Authors: Portnof J.E. , Liss J. , Cross K.J. , Bouchard N.C. , Spinelli H.M.
Published: November 2009

This case report describes an unusual penetrating orbital trauma, presentation and surgical management.
Bisphosphonates and oral surgery
Authors: Oliver R.
Published: November 2009

Osteonecrosis of the jaws, or the threat of it, because of the use of bisphosphonates, is an increasing problem facing all dentists and oral surgeons. The link is somewhat circumstantial but compelling and there are emerging risk factors that increase a patient's susceptibility to developing osteonecrosis including the use of intravenous bisphosphonates, length of time taking the drug, smoking and possibly a genetic predisposition. There is a lack of randomised trial evidence regarding the best strategies for prevention and treatment of the condition. This article discusses current evidence, largely from observational studies on the development, prevention and management of bisphosphonate‐related osteonecrosis.
On the Modal Content ofA PosterioriNecessities
Authors: TAHKO TUOMAS E.
Published: November 2009

This article challenges the Kripkean interpretation ofa posteriorinecessities. It will be demonstrated, by an analysis of classic examples, that the modal content of supposeda posteriorinecessities is more complicated than the Kripkean line suggests. We will see that further research is needed concerning thea prioriprinciples underlying alla posteriorinecessities. In the course of this analysis it will emerge that the modal content ofa posteriorinecessities can best be described in terms of a Finean conception of modality – by giving essences priority over modality. The upshot of this is that we might be able to establish the necessity of certain supposeda posteriorinecessities bya priorimeans.
TheTractatusTheory of Descriptions
Authors: ROSENKRANTZ MAX
Published: November 2009

In this article I construe Russell's definite description notation as a fragment of an “ideal language”– a language in which, as Russell puts it in the “Logical Atomism” lectures, “the words in a proposition correspond one by one with the components of the corresponding fact.” Russell's notation – containing as it does variables, quantifiers and the identity sign – commits him to an ontology that is lavish indeed. It thus conflicts with the spirit of the theory of descriptions, which is developed in the service of ontological frugality (the elimination of denoting concepts, senses and non‐existent objects). I make use of arguments derived from theTractatusto show that an ideal language need not contain logical signs. I thus defend the spirit of the theory of descriptions while departing from its letter.
Dispositions Unmasked
Authors: HAUSKA JAN
Published: November 2009

The problem of masking is widely regarded as a grave threat to the conditional analysis of dispositions. Unlike the difficulty arising in connection with finkish situations, the problem does not involve the (dis)appearance of a disposition upon the arrival of its activating conditions. Consequently, some promising responses to the finkish cases, in particular David Lewis's reformed analysis, are ill‐equipped to deal with masks. I contend that the difficulty posed by masks can be surmounted by supplementing the counterfactual at the heart of the conditional analysis with a ceteris paribus clause. In spelling out this idea, I first examine the issue of provisos in nomic statements. Then I show how the employment of the ceteris paribus clause escapes the objections that are often raised against it, including the charge that the clause cannot informatively capture all the possible masks of a disposition.
Does the Number of Previous Vaginal Deliveries Affect Overactive Bladder Symptoms and their Response to Treatment?
Authors: WITTE Lambertus P.W. , PESCHERS Ursula , VOGEL Monika , De La ROSETTE Jean J.M.C.H. , MICHEL Martin C.
Published: November 2009

Objectives: To explore associations between the number of vaginal deliveries (primary aim) or gender (secon‐ dary aim) and overactive bladder (OAB) symptoms as well as their response to treatment with a muscarinic antagonist.

Methods: Preplanned secondary analysis of an observational study of solifenacin in OAB patients. Episode frequencies of OAB symptoms, pad use and scores on OAB rating scales were documented in 4450 patients before and after a 12–14 week treatment period with solifenacin 5 or 10 mg.

Results: Women without, and with one, two or more than two vaginal deliveries and men were similar in their baseline characteristics. All groups also exhibited rather similar reductions in symptoms and improvements in rating scales upon treatment.

Conclusion: These data indicate that solifenacin, and perhaps other muscarinic receptor antagonists, are similarly suitable for the treatment of OAB symptoms in both genders, irrespective of previous vaginal deliveries.
Treatment of Obstructive Bladder Dysfunction in Rabbits with Coenzyme Q10 and Alpha Lipoic Acid
Authors: HYDERY Tasmina , SCHULER Catherine , LEGGETT Robert E. , LEVIN Robert M.
Published: November 2009

Objectives: Partial bladder outlet obstruction (PBOO) is one of the major pathological effects of benign prostatic hyperplasia in men. It is well demonstrated that ischemia followed by reperfusion and the resulting generation of free radicals and oxidative damage to proteins occur in our rabbit model of PBOO and are involved in the observed progressive obstructive bladder dysfunction. The aim of the current project was to determine if treatment of obstructed rabbits with alpha lipoic acid and coenzyme Q10 can reverse the urodynamic, biochemical, and physiological responses to PBOO.

Methods: Twenty adult NZW male rabbits were divided into four groups (n = 5 per group): control (sham surgical) animals with no treatment (group 1); control animals treated with coenzyme Q10 + alpha lipoic acid for 3 weeks beginning 4 weeks after surgery (group 2); 7‐week obstructed rabbits (group 3); and 7‐week obstructed rabbits treated for the last 3 weeks with the combination of the two drugs (group 4).

Results: Bladder weight, compliance, volume at micturition and contractile response to all forms of stimulation were reduced following obstruction, but significantly improved after treatment. In addition, the level of reactive oxygen species and reactive nitrogen species damage was significantly reduced by treatment.

Conclusion: Our results provide additional support for the beneficial effects of treatment of PBOO with strong antioxidants.
Measurement of Leak Rate for MEMS Vacuum Packaging
Authors: Gan Zhiyin , Huang Dexiu , Wang Xuefang , Lin Dong , Liu Sheng
Published: November 2009

Many Micro-Electro-Mechanical Systems (MEMS) devices such as accelerators, gyroscopes, uncooled infrared sensors, etc., require vacuum packaging. The vacuum maintaining lifetime directly determines the vacuum packaging reliability. This research presented a quantitative analysis of the relationship between the leak rate and the vacuum maintaining lifetime, and demonstrated that the leak rate measurement plays an important role. This paper also explored the application limitations in vacuum packaging using a helium spectrometer leak tester to measure the leak rate because the measured leak rate was nonlinear with respect to the actual leak size. According to the fact that the damping coefficient changes with the pressure, a tuning fork crystal chip as a pressure sensor was used to monitor the pressure changes in the package cavity. The leak conductance was also calculated from the pressure tracking data to analyze the leak modes; the molecular flow model and gas desorption model were found to fit the measurement results of leak conductance.
The Shear Test as Interface Characterization Tool Applied to the Si-BCB Interface
Authors: Degryse Dominiek , Vandevelde Bart , Beyne Eric , Degrieck Joris
Published: November 2009

Electronic packages are multimaterial structures. Their reliability is a major concern for the electronic industry and therefore widely studied. Apart from the electrical performance, the mechanical stability also needs attention. A dreaded failure cause is delamination. Therefore it is interesting to have a modeling tool, which can provide information on possible delamination risks. In this paper, a short overview of existing appropriate analyzing techniques is presented, focusing on the fracture-mechanics approach. The implementation of the method using energy release rate components is discussed. However, as in all modeling applications, the need for “critical material data” is also at hand. Therefore, the shear test is demonstrated to serve as a characterization tool. The Si-BCB interface is applied as test-case. In order to obtain the critical material data for this interface, a set of experiments is designed and performed. Due to the brittle failure observed in the experiments, only information about the onset of the delamination is obtained, leading to a crack extension locus. By comparing the experimental results and the numerical finite element results, an estimation on this crack extension locus (in the G1-G2 plane) can be made. This information can be used in later calculations on the reliability of components including Si-BCB interfaces.
Fabrication of Miniature CMOS Image Sensor Using Novel Glass Cover Chip Packaging Technique
Authors: Wang Chuen-Ching , Ye Yao-Ting , Lin Jing-Fung
Published: November 2009

This study develops a novel glass cover chip (GCC) technique for the packaging of CMOS image sensors (CIS), in which the glass cover plate is attached directly to the chip using a nonconductive adhesive film. Taking the adhesive force between the glass plate and the chip as a performance indicator, a series of Taguchi trials are performed to establish the optimal GCC processing conditions. The experimental results confirm the feasibility of the proposed packaging technique and indicate a volume reduction of 59.47% compared with the traditional CIS package. Furthermore, the simulation results reveal that the heat dissipation efficiency of the proposed CIS package exceeds that of the traditional package by 245%.
A Novel Ceramic Packaging Technique Using Selective Induction Heating
Authors: Liu Sheng , Liu Wenming , Lin Changyong , Chen Mingxiang
Published: November 2009

A novel ceramic packaging technology by using selective induction heating is presented. Some aspects of this packaging process, including local temperature distribution, hermeticity, tensile strength, and fracture analysis, were tested and evaluated. For high-frequency (f=350 kHz) induction heating, the temperature of cover edges near solder-loop reached up to 320°C in several seconds, hermetic seal of the ceramic package can be promised because of solder reflowing, while the temperature of the ceramic bottom was only about 100°C, so thermal-sensitive devices and integrated circuits inside the ceramic package can be protected from high-temperature damage. Temperature variation and distribution were evaluated by an infrared imager, and it agreed well with simulation results. Finally, tensile strength from 4.0 MPa to 13.0 MPa was achieved and the fracture interfaces were examined and analyzed depending on the induction heating time and packaging pressure.
A Spindle Assembly Checkpoint Protein Functions in Prophase I Arrest and Prometaphase Progression
Authors: Homer Hayden , Gui Liming , Carroll John
Published: November 2009

BubR1 Broadens Its Remit

During mitosis in mammalian somatic cells, BubR1 is indispensable for spindle assembly checkpoint signaling and for establishing contacts between chromosomes and spindle microtubules.

Homer
et al.

(p.
991
) found that in mouse oocytes during meiosis I, BubR1 was not only required to sustain prophase I arrest but also for promoting the completion of meiosis I. Both effects converge on the Cdh1 coactivator of the multimeric ubiquitin ligase, known as the anaphase-promoting complex, and both functions are required for the production of fertilizable eggs.
A Strain-Driven Morphotropic Phase Boundary in BiFeO
3
Authors: Zeches R. J. , Rossell M. D. , Zhang J. X. , Hatt A. J. , He Q. , Yang C.-H. , Kumar A. , Wang C. H. , Melville A. , Adamo C. , Sheng G. , Chu Y.-H. , Ihlefeld J. F. , Erni R. , Ederer C. , Gopalan V. , Chen L. Q. , Schlom D. G. , Spaldin N. A. , Martin L. W. , Ramesh R.
Published: November 2009

Biffed into Shape

BiFeO
3
is known to have a very large ferroelectric polarization. Although the bulk ground state is rhombohedral (with the electrical polarization along the [111] direction), in thin films and under epitaxial strain, the material can be tetragonally distorted (polarization along [001]).

Zeches
et al.

(p.
977
) show that under compressive strain, these films are monoclinic, a phase that is highly stable because it comprises the same symmetry as the monoclinic phase which has been reported at the so-called morphotropic phase boundaries in technologically important ferroelectrics. This work offers the possibility of obtaining large piezoelectric responses in lead-free systems.
Reflections on Cybersecurity
Authors: Wulf William A. , Jones Anita K.
Published: November 2009

The lack of security in cyberspace may be addressed by learning from the strengths of the Internet.
Newton in Three Dimensions

Let Newton Be!
by Craig Baxter; directed by Patrick Morris

Menagerie Theatre Company, University of Cambridge, UK. October 2009. Commissioned by the Faraday Institute for Science and Religion, Cambridge.
Authors: Stott Rebecca , Morrish Hannah
Published: November 2009

Constructed from Newton's own words, Baxter's play brings to life the complexity and controversy of its subject's character.
U.S. Takes Steps to Use Science To Improve Ties to Muslim World
Authors: Koenig Robert
Published: November 2009

In a surprise announcement, U.S. Secretary of State Hillary Clinton last week named three prominent scientists as special envoys to assess the potential for scientific partnerships with Muslim-majority countries.
Restructuring Physics Labs Brings Delight and Despair
Authors: Allakhverdov Andrey , Pokrovsky Vladimir
Published: November 2009

Four of Russia's most prominent physics labs are to be merged into a new national research center. But a different reform aimed at separating basic and applied research at one of the institutes has researchers up in arms.
Amid Worrisome Signs of Warming, 'Climate Fatigue' Sets In
Authors: Kerr Richard A.
Published: November 2009

As scientists debate whether climate is changing faster than anticipated, some worry that a drumbeat of dire warnings may be helping to erode U.S. public concerns about global warming.
Internal Affairs
Authors: Leslie Mitch
Published: November 2009

Newly discovered cytoplasmic defenses called inflammasomes sound the alarm when pathogens penetrate our cells.
Familial Furunculosis Associated with Community-Acquired Leukocidin-Positive Methicillin-Susceptible
Staphylococcus aureus
ST152
Authors: Pérez-Roth E. , Alcoba-Flórez J. , López-Aguilar C. , Gutiérrez-González I. , Rivero-Pérez B. , Méndez-Álvarez S.
Published: November 2009

Panton-Valentine leukocidin (PVL) is associated with staphylococcal skin and pulmonary infections. Community dissemination of PVL-producing
Staphylococcus aureus
strains constitutes a public health concern. Family transmission and spread of community-acquired leukocidin-positive methicillin-susceptible
S. aureus
ST152 isolates associated with severe clinical symptoms are herein described. Remarkably, ST152 isolates usually are methicillin resistant.
First Report Worldwide of an Infant Botulism Case Due to
Clostridium botulinum
Type E
Authors: Lúquez Carolina , Dykes Janet K. , Yu Patricia A. , Raphael Brian H. , Maslanka Susan E.
Published: November 2009

Clostridium botulinum
type E has been associated with botulism in adults but never in infants. Infant botulism type E cases have been associated with neurotoxigenic strains of
C. butyricum
. We report the first infant botulism case due to
C. botulinum
type E worldwide.
Complete Genome Sequence and Pathogenicity of Two Swine Parainfluenzavirus 3 Isolates from Pigs in the United States
Authors: Qiao Dan , Janke Bruce H. , Elankumaran Subbiah
Published: November 2009

Two novel paramyxoviruses, 81-19252 (Texas81) and 92-7783 (ISU92), isolated from the brains of pigs in the United States in the 1980s and 1990s, were characterized. The complete genome of Texas81 virus was 15,456 nucleotides (nt) in length, that of ISU92 was 15,480 nt, and both genomes consisted of six nonoverlapping genes, predicted to encode nine proteins, with conserved and complementary 3′ leader and 5′ trailer regions and conserved gene starts, gene stops, and trinucleotide intergenic sequences similar to those in paramyxoviruses. The corresponding genes from these two viruses were similar in length, except for the F genes, of which the ISU92 form had an additional 24-nt U-rich 3′ untranslated region. The P genes of swine viruses were predicted to produce V and D mRNAs by RNA editing (one to four G insertions in Texas81 and one to nine G insertions in ISU92) or C mRNA by alternative translation initiation. Sequence-specific features related to virus replication and host-specific amino acid signatures indicated that these viruses originated from bovine parainfluenzavirus 3 (bPIV3). Phylogenetic analysis of individual genes suggested that these viruses are novel members of the genus
Respirovirus
of the
Paramyxovirinae
subfamily and may be grouped into two subgenotypes of genotype A of bPIV3. Our comprehensive studies revealed that these swine PIV3 are variants of bPIV3 and were possibly transferred from cattle to pigs but failed to establish an active enzootic state. These two viruses were mildly pathogenic to conventionally reared pigs, and results from a limited enzyme-linked immunosorbent assay-based serosurvey of swine farms in Minnesota and Iowa in 2007 and 2008 were negative.
Identification of GBF1 as a Cellular Factor Required for Hepatitis C Virus RNA Replication
Authors: Goueslain Lucie , Alsaleh Khaled , Horellou Pauline , Roingeard Philippe , Descamps Véronique , Duverlie Gilles , Ciczora Yann , Wychowski Czeslaw , Dubuisson Jean , Rouillé Yves
Published: November 2009

In infected cells, hepatitis C virus (HCV) induces the formation of membrane alterations referred to as membranous webs, which are sites of RNA replication. In addition, HCV RNA replication also occurs in smaller membrane structures that are associated with the endoplasmic reticulum. However, cellular mechanisms involved in the formation of HCV replication complexes remain largely unknown. Here, we used brefeldin A (BFA) to investigate cellular mechanisms involved in HCV infection. BFA acts on cell membranes by interfering with the activation of several members of the family of ADP-ribosylation factors (ARF), which can lead to a wide range of inhibitory actions on membrane-associated mechanisms of the secretory and endocytic pathways. Our data show that HCV RNA replication is highly sensitive to BFA. Individual knockdown of the cellular targets of BFA using RNA interference and the use of a specific pharmacological inhibitor identified GBF1, a guanine nucleotide exchange factor for small GTPases of the ARF family, as a host factor critically involved in HCV replication. Furthermore, overexpression of a BFA-resistant GBF1 mutant rescued HCV replication in BFA-treated cells, indicating that GBF1 is the BFA-sensitive factor required for HCV replication. Finally, immunofluorescence and electron microscopy analyses indicated that BFA does not block the formation of membranous web-like structures induced by expression of HCV proteins in a nonreplicative context, suggesting that GBF1 is probably involved not in the formation of HCV replication complexes but, rather, in their activity. Altogether, our results highlight a functional connection between the early secretory pathway and HCV RNA replication.
The Full-Length Isoform of Human Papillomavirus 16 E6 and Its Splice Variant E6* Bind to Different Sites on the Procaspase 8 Death Effector Domain
Authors: Tungteakkhun Sandy S. , Filippova Maria , Fodor Nadja , Duerksen-Hughes Penelope J.
Published: November 2009

Human papillomavirus 16 is a causative agent of most cases of cervical cancer and has also been implicated in the development of some head and neck cancers. The early viral E6 gene codes for two alternatively spliced isoforms, E6
large
and E6*. We have previously demonstrated the differential effects of E6
large
and E6* binding on the expression and stability of procaspase 8, a key mediator of the apoptotic pathway. Additionally, we have reported that E6 binds to the FADD death effector domain (DED) at a novel E6 binding domain. Sequence similarities between the FADD and procaspase 8 DEDs suggested a specific region for E6
large
/procaspase 8 binding, which was subsequently confirmed by mutational analysis as well as by the ability of peptides capable of blocking E6/FADD binding to also block E6
large
/caspase 8 binding. However, the binding of the smaller isoform, E6*, to procaspase 8 occurs at a different region, as deletion and point mutations that disrupt E6
large
/caspase 8 DED binding do not disrupt E6*/caspase 8 DED binding. In addition, peptide inhibitors that can block E6
large
/procaspase 8 binding do not affect the binding of E6* to procaspase 8. These results demonstrate that the residues that mediate E6*/procaspase 8 DED binding localize to a different region on the protein and employ a separate binding motif. This provides a molecular explanation for our initial findings that the two E6 isoforms affect procaspase 8 stability in an opposing manner.
Extrachromosomal Histone H2B Mediates Innate Antiviral Immune Responses Induced by Intracellular Double-Stranded DNA
Authors: Kobiyama Kouji , Takeshita Fumihiko , Jounai Nao , Sakaue-Sawano Asako , Miyawaki Atsushi , Ishii Ken J. , Kawai Taro , Sasaki Shin , Hirano Hisashi , Ishii Norihisa , Okuda Kenji , Suzuki Koichi
Published: November 2009

Fragments of double-stranded DNA (dsDNA) forming a right-handed helical structure (B-DNA) stimulate cells to produce type I interferons (IFNs). While an adaptor molecule, IFN-β promoter stimulator 1 (IPS-1), mediates dsDNA-induced cellular signaling in human cells, the underlying molecular mechanism is not fully understood. Here, we demonstrate that the extrachromosomal histone H2B mediates innate antiviral immune responses in human cells. H2B physically interacts with IPS-1 through the association with a newly identified adaptor, CIAO (
C
OOH-terminal
i
mportin 9-related
a
daptor
o
rganizing histone H2B and IPS-1), to transmit the cellular signaling for dsDNA but not immunostimulatory RNA. Extrachromosomal histone H2B was biologically crucial for cell-autonomous responses to protect against multiplication of DNA viruses but not an RNA virus. Thus, the present findings provide evidence indicating that the extrachromosomal histone H2B is engaged in the signaling pathway initiated by dsDNA to trigger antiviral innate immune responses.
Herpes Simplex Virus Type 1 (HSV-1)-Induced Apoptosis in Human Dendritic Cells as a Result of Downregulation of Cellular FLICE-Inhibitory Protein and Reduced Expression of HSV-1 Antiapoptotic Latency-Associated Transcript Sequences
Authors: Kather Angela , Raftery Martin J. , Devi-Rao Gayathri , Lippmann Juliane , Giese Thomas , Sandri-Goldin Rozanne M. , Schönrich Günther
Published: November 2009

Herpes simplex virus type 1 (HSV-1) is one of the most frequent and successful human pathogens. It targets immature dendritic cells (iDCs) to interfere with the antiviral immune response. The mechanisms underlying apoptosis of HSV-1-infected iDCs are not fully understood. Previously, we have shown that HSV-1-induced apoptosis of iDCs is associated with downregulation of the cellular FLICE-inhibitory protein (c-FLIP), a potent inhibitor of caspase-8-mediated apoptosis. In this study, we prove that HSV-1 induces degradation of c-FLIP in a proteasome-independent manner. In addition, by using c-FLIP-specific small interfering RNA (siRNA) we show for the first time that downregulation of c-FLIP expression is sufficient to drive uninfected iDCs into apoptosis, underlining the importance of this molecule for iDC survival. Surprisingly, we also observed virus-induced c-FLIP downregulation in epithelial cells and many other cell types that do not undergo apoptosis after HSV-1 infection. Microarray analyses revealed that HSV-1-encoded latency-associated transcript (LAT) sequences, which can substitute for c-FLIP as an inhibitor of caspase-8-mediated apoptosis, are much less abundant in iDCs as compared to epithelial cells. Finally, iDCs infected with an HSV-1 LAT knockout mutant showed increased apoptosis when compared to iDCs infected with the corresponding wild-type HSV-1. Taken together, our results demonstrate that apoptosis of HSV-1-infected iDCs requires both c-FLIP downregulation and diminished expression of viral LAT.
Hepatitis C Virus (HCV) Sequence Variation Induces an HCV-Specific T-Cell Phenotype Analogous to Spontaneous Resolution
Authors: Kasprowicz Victoria , Kang Yu-Hoi , Lucas Michaela , Schulze zur Wiesch Julian , Kuntzen Thomas , Fleming Vicki , Nolan Brian E. , Longworth Steven , Berical Andrew , Bengsch Bertram , Thimme Robert , Lewis-Ximenez Lia , Allen Todd M. , Kim Arthur Y. , Klenerman Paul , Lauer Georg M.
Published: November 2009

Hepatitis C virus (HCV)-specific CD8
+
T cells in persistent HCV infection are low in frequency and paradoxically show a phenotype associated with controlled infections, expressing the memory marker CD127. We addressed to what extent this phenotype is dependent on the presence of cognate antigen. We analyzed virus-specific responses in acute and chronic HCV infections and sequenced autologous virus. We show that CD127 expression is associated with decreased antigenic stimulation after either viral clearance or viral variation. Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127
+
T cells is driven by viral variation.
Identification of the Cellular Prohibitin 1/Prohibitin 2 Heterodimer as an Interaction Partner of the C-Terminal Cytoplasmic Domain of the HIV-1 Glycoprotein
Authors: Emerson Vanessa , Holtkotte Denise , Pfeiffer Tanya , Wang I-Hsuan , Schnölzer Martina , Kempf Tore , Bosch Valerie
Published: November 2009

Our studies aim to elucidate the functions carried out by the very long, and in its length highly conserved, C-terminal cytoplasmic domain (Env-CT) of the HIV-1 glycoprotein. Mass spectrometric analysis of cellular proteins bound to a tagged version of the HIV Env-CT led to the identification of the prohibitin 1 and 2 proteins (Phb1 and Phb2). These ubiquitously expressed proteins, which exist as stable heterodimers, have been shown to have multiple functions within cells and to localize to multiple cellular and extracellular compartments. The specificity of binding of the Phb1/Phb2 complex to the Env-CT was confirmed in various manners, including coimmunoprecipitation with authentic provirally encoded, full-length Env. Strong binding was dependent on Env residues 790 to 800 and could be severely inhibited by the double mutation L799R/L800Q but not by mutation of these amino acids individually. Analysis of the respective mutant virions revealed that their different abilities to bind Phb1/Phb2 correlated with their replicative properties. Thus, mutated virions with single mutations [HIV-Env-(L799R) and HIV-Env-(L800Q)] replicated similarly to wild-type HIV, but HIV-Env-(L799R/L800Q) virions, which cannot bind Phb1/Phb2, exhibited a cell-dependent replicative phenotype similar to that of HIV-Env-Tr712, lacking the entire Env-CT domain. Thus, replicative spread was achieved, although somewhat delayed, in “permissive” MT-4 cells but failed to occur in “nonpermissive” H9 T cells. These results point to binding of the Phb1/Phb2 complex to the Env-CT as being of importance for replicative spread in nonpermissive cells, possibly by modulating critical Phb-dependent cellular process(es).
Envelope Vaccination Shapes Viral Envelope Evolution following Simian Immunodeficiency Virus Infection in Rhesus Monkeys
Authors: Basavapathruni Aravind , Yeh Wendy W. , Coffey Rory T. , Whitney James B. , Hraber Peter T. , Giri Ayush , Korber Bette T. , Rao Srinivas S. , Nabel Gary J. , Mascola John R. , Seaman Michael S. , Letvin Norman L.
Published: November 2009

The evolution of envelope mutations by replicating primate immunodeficiency viruses allows these viruses to escape from the immune pressure mediated by neutralizing antibodies. Vaccine-induced anti-envelope antibody responses may accelerate and/or alter the specificity of the antibodies, thus shaping the evolution of envelope mutations in the replicating virus. To explore this possibility, we studied the neutralizing antibody response and the envelope sequences in rhesus monkeys vaccinated with either
gag
-
pol
-
nef
immunogens or
gag
-
pol
-
nef
immunogens in combination with
env
and then infected with simian immunodeficiency virus (SIV). Using a pseudovirion neutralization assay, we demonstrate that envelope vaccination primed for an accelerated neutralizing antibody response following virus challenge. To monitor viral envelope evolution in these two cohorts of monkeys, full-length envelopes from plasma virus isolated at weeks 37 and 62 postchallenge were sequenced by single genome amplification to identify sites of envelope mutations. We show that
env
vaccination was associated with a change in the pattern of envelope mutations. Prevalent mutations in sequences from
gag
-
pol
-
nef
vaccinees included deletions in both variable regions 1 and 4 (V1 and V4), whereas deletions in the
env
vaccinees occurred only in V1. These data show that
env
vaccination altered the focus of the antibody-mediated selection pressure on the evolution of envelope following SIV challenge.
Attenuation of Vesicular Stomatitis Virus Encephalitis through MicroRNA Targeting
Authors: Kelly Elizabeth J. , Nace Rebecca , Barber Glen N. , Russell Stephen J.
Published: November 2009

Vesicular stomatitis virus (VSV) has long been regarded as a promising recombinant vaccine platform and oncolytic agent but has not yet been tested in humans because it causes encephalomyelitis in rodents and primates. Recent studies have shown that specific tropisms of several viruses could be eliminated by engineering microRNA target sequences into their genomes, thereby inhibiting spread in tissues expressing cognate microRNAs. We therefore sought to determine whether microRNA targets could be engineered into VSV to ameliorate its neuropathogenicity. Using a panel of recombinant VSVs incorporating microRNA target sequences corresponding to neuron-specific or control microRNAs (in forward and reverse orientations), we tested viral replication kinetics in cell lines treated with microRNA mimics, neurotoxicity after direct intracerebral inoculation in mice, and antitumor efficacy. Compared to picornaviruses and adenoviruses, the engineered VSVs were relatively resistant to microRNA-mediated inhibition, but neurotoxicity could nevertheless be ameliorated significantly using this approach, without compromise to antitumor efficacy. Neurotoxicity was most profoundly reduced in a virus carrying four tandem copies of a neuronal mir125 target sequence inserted in the 3′-untranslated region of the viral polymerase (L) gene.
Sequential Recruitment of the Endoplasmic Reticulum and Chloroplasts for Plant Potyvirus Replication
Authors: Wei Taiyun , Huang Tyng-Shyan , McNeil Jamie , Laliberté Jean-François , Hong Jian , Nelson Richard S. , Wang Aiming
Published: November 2009

The replication of positive-strand RNA viruses occurs in cytoplasmic membrane-bound virus replication complexes (VRCs). Depending on the virus, distinct cellular organelles such as the endoplasmic reticulum (ER), chloroplast, mitochondrion, endosome, and peroxisome are recruited for the formation of VRC-associated membranous structures. Previously, the 6,000-molecular-weight protein (6K) of plant potyviruses was shown to be an integral membrane protein that induces the formation of 6K-containing membranous vesicles at endoplasmic reticulum (ER) exit sites for potyvirus genome replication. Here, we present evidence that the 6K-induced vesicles predominantly target chloroplasts, where they amalgamate and induce chloroplast membrane invaginations. The vesicular transport pathway and actomyosin motility system are involved in the trafficking of the 6K vesicles from the ER to chloroplasts. Viral RNA, double-stranded RNA, and viral replicase components are concentrated at the 6K vesicles that associate with chloroplasts in infected cells, suggesting that these chloroplast-bound 6K vesicles are the site for potyvirus replication. Taken together, these results suggest that plant potyviruses sequentially recruit the ER and chloroplasts for their genome replication.
Residues in the Heptad Repeat A Region of the Fusion Protein Modulate the Virulence of Sendai Virus in Mice
Authors: Luque Laura E. , Bridges Olga A. , Mason John N. , Boyd Kelli L. , Portner Allen , Russell Charles J.
Published: November 2009

While the molecular basis of fusion (F) protein refolding during membrane fusion has been studied extensively in vitro, little is known about the biological significance of membrane fusion activity in parainfluenza virus replication and pathogenesis in vivo. Two recombinant Sendai viruses, F-L179V and F-K180Q, were generated that contain F protein mutations in the heptad repeat A region of the ectodomain, a region of the protein known to regulate F protein activation. In vitro, the F-L179V virus caused increased syncytium formation (cell-cell membrane fusion) yet had a rate of replication and levels of F protein expression and cleavage similar to wild-type virus. The F-K180Q virus had a reduced replication rate along with reduced levels of F protein expression, cleavage, and fusogenicity. In DBA/2 mice, the hyperfusogenic F-L179V virus induced greater morbidity and mortality than wild-type virus, while the attenuated F-K180Q virus was much less pathogenic. During the first week of infection, virus replication and inflammation in the lungs were similar for wild-type and F-L179V viruses. After approximately 1 week of infection, the clearance of F-L179V virus was delayed, and more extensive interstitial inflammation and necrosis were observed in the lungs, affecting entire lobes of the lungs and having significantly greater numbers of syncytial cell masses in alveolar spaces on day 10. On the other hand, the slower-growing F-K180Q virus caused much less extensive inflammation than wild-type virus, presumably due to its reduced replication rate, and did not cause observable syncytium formation in the lungs. Overall, the results show that residues in the heptad repeat A region of the F protein modulate the virulence of Sendai virus in mice by influencing both the spread and clearance of the virus and the extent and severity of inflammation. An understanding of how the F protein contributes to infection and inflammation in vivo may assist in the development of antiviral therapies against respiratory paramyxoviruses.
Mixed-Species Yield-per-Recruitment Analyses Accounting for Technological Interactions
Authors: Murawski S. A.
Published: November 2009

Multipecies fishery assessment models may be divided into two general categories: those involving analyses of the trophic interdependence of species (biological interactions) and those addressing the question of co-occurrence in fishing gear (technological interactions). Certainly, both categories of interactions may occur simultaneously. Nevertheless, the latter class of models is probably adequate if major species of interest exhibit a high degree of mutually exclusive food resource partitioning, and interspecific competition for food is low. In this study, multispecies analogs of the Thompson–Bell yield-per-recruit model are developed for alternative situations in which species groups (assemblages) are exploited solely by one fishery, and when several fisheries (defined by gear type, seasonal changes in species mix, etc), exploit the same species concurrently and/or sequentially. Species included in the analyses are assumed to have negligible trophic dependence. Equilibrium fishery yields (in aggregate and for individual species) are computed as functions of standardized effort levels and retention characteristics of gear (e.g. mesh size). The multiple fishery model allows for variable harvest strategies with respect to gear selectivity and effort levels among component fisheries. Simultation output includes total and individual equilibrium species yields, exploitation rates, and mean fish weights in the catch for all fisheries combined, and each separately. Applications of the models are illustrated for mixed-species otter trawl fisheries exploiting primarily Atlantic cod, Gadus morhua, haddock, Melanogrammus aeglefinus, yellowtail flounder, Limanda ferruginea, and winter flounder, Pseudopleuronectes americanus, in the Georges Bank region off the northeastern United States. Results emphasize the potential for growth underfishing or overfishing of individual species/stocks when total system yield is the optimization criterion.
Interaction entre le débit et les populations de tacons (Salmo salar) de la rivière Matamec, Québec
Authors: Frenette M. , Caron M. , Julien P. , Gibson R. J.
Published: November 2009

Given the hypothesis that in a river, the population of young salmon (Salmo salar), called parr after the first year, is directly related to the discharge-variable physical characteristics of the habitats, a multiple linear regression analysis was carried out between the parr population estimates in the Matamec River (north shore of the Gulf of St. Lawrence) and the minimum, average, and maximum discharges for monthly and seasonal periods. The most significative variables were obtained for the minimum discharge before flooding (around April), the average August discharge of the year before last (2 yr before), and the average July discharge of the previous year. These discharges corresponded to critical biological periods for the young salmon present in the river and were used to develop a prediction model that was loaded with data covering the period 1971–77. The predictions obtained were 95% significant when the three independant parameters were used jointly and reached more than 66% when only one parameter was taken into account. Overall, it is shown that the discharge is an important limiting factor directly influencing salmon survival in streams.
Use of Erythrocyte Measurements to Identify Triploid Salmonids
Authors: Benfey T. J. , Sutterlin A. M. , Thompson R. J.
Published: November 2009

Triploid landlocked Atlantic salmon (Salmo salar) were identified using microspectrophotometry to measure the DNA content of Feulgen-stained erythrocytes. Blood cell sizing by means of a Coulter Counter Channelyzer was a highly effective alternative for screening triploids, comparable with flow cytometry in speed and accuracy. The statistical analysis of various erythrocyte dimensions measured from blood smears was also a valid method for identifying triploids. No mosaic polyploids were found, and the existence of such fish is questioned.
Predation Risk and Foraging in Juvenile Pink (Oncorhynchus gorbuscha) and Chum Salmon (O. keta)
Authors: Magnhagen Carin
Published: November 2009

Habitat choice and foraging activities of juvenile pink (Oncorhynchus gorbuscha) and chum salmon (O. keta) from the Fraser River estuary were studied to determine whether their behaviour changed in response to predation risk and hunger level. In aquaria with and without predators, the fish were given a choice of two habitats open water with a high prey density and vegetation with a low prey density; these habitats have advantages of high energy intake and protection from predators, respectively. Pink salmon were found more frequently in the vegetation when predators were present than otherwise. When hungry, however, pink salmon occupied the open area to a greater extent than when satiated. Chum salmon did not show as much difference in habitat choice as pink. In the presence of predators, satiated pink salmon ate less than hungry ones and also less than the fish without predators. Chum salmon did not show any differences in food intake in the different treatments. Thus, pink salmon responded to predation risk to a greater extent than did chum, in terms of habitat choice and food intake, and demonstrated a trade-off between predator avoidance and foraging.
Acute Toxicity of Binary Mixtures of Five Cations (Cu2+, Cd2+, Zn2+, Mg2+, and K+) to the Freshwater Amphipod Gammarus lacustris (Sars): Alternative Descriptive Models
Authors: March B. G. E. de
Published: November 2009

The combined results of 10 acute toxicity experiments, each testing the joint toxicity of two of the ions Cu2+, Cd2+, Zn2+, Mg2+, and K+, were examined in terms of different response surface models which could be used to make decisions about limiting toxic components in mixtures. The classical probit model for simple similar action described experimental results satisfactorily with a model R2 of 0.282; equations in which probit(p) was described directly by a linear combination of toxicant concentrations fit data significantly better, with an R2 of 0.527. Equations with more complex linear terms and appropriate weighting factors applied to the residual sums of squares yielded R2 values up to 0.931. Predicted LC50 values were midrange compared with published values. Based on the linear description of the probit response, K or Mg in combination with either of Cu, Cd, or Zn had additive effects, the combinations Cu and Cd, Cu and Zn, and Cd and Zn had more-than-additive effects, and Mg and K had less-than-additive effects. The relationships between the response surfaces, other described modes of joint action, the toxic units model, and mixture toxicity indices are discussed.
Effect of pH on Speciation and Toxicity of Aluminum to Rainbow Trout (Salmo gairdneri)
Authors: Ramamoorthy S.
Published: November 2009

Alum (aluminum sulphate) is used in many water treatment plants as a flocculant. The resultant settled floe (called alum sludge) may be discharged into receiving waters. This study reports the effect of pH on the speciation of released aluminum (Al) from fresh sludge and Al uptake and toxicity to fish in river water in the presence of abiotic substrates enclosed in dialysis sacs. This study shows that freshly precipitated alum sludge holds Al effectively within a wide range of pH (4.50–10.0) and that abiotic substrates compete with the biota as represented by fish for Al. Fish mortalities observed could be due to colloidal particles and acid- and Al-induced stress at pH 4.50, to colloidal particles at pH 6.00, and to high alkalinity at pH 10.0. At pH 7–9, Al in water, present essentially as filterable nonexchangeable Al (FNEX-Al), was not lethal to fish.
Mitochondrial DNA Variation in Great Lakes Walleye (Stizostedion vitreum) Populations
Authors: Billington Neil , Hebert Paul D. N.
Published: November 2009

Mitochondrial DNA variation was examined in 141 walleye (Stizostedion vitreum) from 10 populations in the Great Lakes basin. Twenty-two hexanucleotide sequence recognition endonucleases were used, of which six (Ava I, Bst EII, Cla I, Dra I, Nco I, and Sca I) revealed polymorphisms between fish. Nine mitochondrial clones were resolved which fell into two major groups that differed in their Nco I and Sca I fragment patterns. The "A" group predominates in the eastern Great Lakes, while the "B" group predominates in the west. The geographical distribution of these two groups suggests that Great Lakes walleye persisted in at least two refugia during the last glaciation. The study revealed several rare mitochondrial genotypes which may prove useful in creating genetically marked brood stocks. Since mtDNA is maternally inherited, such markers would provide information on both the survival and long-term reproductive success of stocked fish.
Focal Scale Damage Among Chum Salmon (Oncorhynchus keta) of Hokkaido, Japan
Authors: Bigler Brian
Published: November 2009

Fifty percent of chum salmon (Oncorhynchus keta) sampled from seven hatcheries in Hokkaido, Japan, were found to have either damage to the osseous scale layer where a hole resulted or intrusion of the osseous layer into the underlying fibrillary plate. Damage resulting in a hole is not related to age, body size, sex, or hatchery stock size. Intrusion of the osseous layer is similarly not related to body size, sex, or stock size; however, this phenomenon may be related to age. All damage was confined to the first, and rarely extended into the second, annual growth zone, suggesting occurrence during that period and retention of the mark throughout the life cycle. No evidence was found to support the hypothesis that either type of focal scale damage is a result of reduced diet. Examination of historical records from one hatchery revealed that the phenomenon of a hole has occurred for at least the past 10 yr at that location. It is not presently possible to identify hatchery of origin using these traits; however, such permanent, uniformly occurring traits may be of use in the identification of chum salmon originating from Hokkaido.
Sustained Exercise Increases Plasma Growth Hormone Concentrations in Two Anadromous Salmonids
Authors: Barrett Bruce A. , McKeown Brian A.
Published: November 2009

Sustained exercise for 24 h at 1.5 body lengths per second (bl/s) resulted in a severalfold increase in the plasma growth hormone (GH) concentration of steelhead trout (Salmo gairdneri) and coho salmon (Oncorhynchus kisutch). Peak levels occurred 10 min postexercise and returned to basal levels within 4 h of exercise termination. GH levels exhibited a steady increase after the fourth hour of exercise and peaked at 24 h. Individuals exercised for 48 h did not exceed plasma GH levels of the 24-h peak.