bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory T Cells Promote Early Influx of CD8+T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities
Authors: Ruckwardt Tracy J. , Bonaparte Kathryn L. , Nason Martha C. , Graham Barney S. 
Published: January 2009

ABSTRACTIn addition to regulating autoimmunity and antitumor immunity, CD4+CD25+FoxP3+natural regulatory T (Treg) cells are global regulators of adaptive immune responses. Depletion of these cells with the anti-CD25 antibody PC61 prior to primary respiratory syncytial virus (RSV) infection was partial but had several effects on the RSV-specific CD8+response in a hybrid mouse model. Mediastinal lymph node and spleen epitope-specific CD8+T-cell responses were enhanced in Treg-cell-depleted mice at all time points following infection, but responses of Treg-cell-depleted lung show a strikingly different pattern than lymphoid organ responses, with an initial delay in the CD8+T-cell response. The delay in the CD8+T-cell response correlated with a delay both in the early phase of viral clearance and in illness in Treg-cell-depleted mice compared to isotype-treated controls. The lungs of Treg-cell-depleted mice were shown to have increased lung chemokine and cytokine levels 7 days postinfection despite lower CD8+T-cell responses. Following the early delay in the lung response, CD8+T-cell responses at later infection time points were enhanced and increased the severity of illness in depleted mice. Finally, decreasing regulatory T-cell control of the CD8+T-cell response had a greater effect on response of the dominant Kd-restricted M2 epitope consisting of amino acids 82 to 90 (KdM282-90) than on the subdominant DbM187-195epitope response, indicating that regulatory T cells modulate immunodominance disparities in epitope-specific CD8+T-cell responses following primary RSV infection.
Biarsenical Labeling of Vesicular Stomatitis Virus Encoding Tetracysteine-Tagged M Protein Allows Dynamic Imaging of M Protein and Virus Uncoating in Infected Cells
Authors: Das Subash C. , Panda Debasis , Nayak Debasis , Pattnaik Asit K. 
Published: January 2009

ABSTRACT
A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced green fluorescent protein fused in frame with P (PeGFP) in place of P and a fusion matrix protein (monomeric red fluorescent protein fused in frame at the carboxy terminus of M [MmRFP]) at the G-L gene junction, in addition to wild-type (wt) M protein in its normal location, was recovered, but the MmRFP was not incorporated into the virions. Subsequently, we generated recombinant viruses (VSV-PeGFP-ΔM-Mtc and VSV-ΔM-Mtc) encoding M protein with a carboxy-terminal tetracysteine tag (Mtc) in place of the M protein. These recombinant viruses incorporated Mtc at levels similar to M in wt VSV, demonstrating recovery of infectious rhabdoviruses encoding and incorporating a tagged M protein. Virions released from cells infected with VSV-PeGFP-ΔM-Mtc and labeled with the biarsenical red dye (ReAsH) were dually fluorescent, fluorescing green due to incorporation of PeGFP in the nucleocapsids and red due to incorporation of ReAsH-labeled Mtc in the viral envelope. Transport and subsequent association of M protein with the plasma membrane were shown to be independent of microtubules. Sequential labeling of VSV-ΔM-Mtc-infected cells with the biarsenical dyes ReAsH and FlAsH (green) revealed that newly synthesized M protein reaches the plasma membrane in less than 30 min and continues to accumulate there for up to 2 1/2 hours. Using dually fluorescent VSV, we determined that following adsorption at the plasma membrane, the time taken by one-half of the virus particles to enter cells and to uncoat their nucleocapsids in the cytoplasm is approximately 28 min.
Are Human P[14] Rotavirus Strains the Result of Interspecies Transmissions from Sheep or Other Ungulates That Belong to the Mammalian Order
Artiodactyla
?
Authors: Matthijnssens Jelle , Potgieter Christiaan A. , Ciarlet Max , Parreño Viviana , Martella Vito , Bányai Krisztián , Garaicoechea Lorena , Palombo Enzo A. , Novo Luis , Zeller Mark , Arista Serenella , Gerna Giuseppe , Rahman Mustafizur , Van Ranst Marc 
Published: January 2009

ABSTRACT

A limited number of human G6P[14] rotavirus strains that cause gastroenteritis in humans have been isolated in Europe and Australia. The complete genome sequences were determined for five of these human strains—B10925-97 (isolated in Belgium in 1997), 111/05-27 (Italy, 2005), PA169 (Italy, 1987), MG6 (Australia, 1993), and Hun5 (Hungary, 1997)—and their genetic relatedness to animal rotavirus strains was evaluated by sequencing the complete genome of the sheep rotavirus OVR762 (G8P[14]; Spain, 2002), the guanaco (
Lama guanicoe
) rotavirus strains Arg/Chubut/99 and Arg/Río Negro/98 (G8P[14] and G8P[1], respectively; Argentina, 1999 and 1998), the sable antelope strain RC-18/08 (G6P[14]; South Africa, 2008), and the bovine rotavirus strain Arg/B383/98 (G15P[11]; Argentina, 1998). These analyses revealed an overall consensus genomic constellation (G6/G8)-P[14]-I2-(R2/R5)-C2-M2-(A3/A11)-N2-T6-(E2/E12)-H3, together with a few gene reassortments, and the phylogenetic analyses confirmed that the P[14] human strains evaluated in this study were closely related to rotavirus strains isolated from sheep, cattle, goats, guanacos, and antelopes and to rabbits (albeit to a lesser extent), suggesting that one (or more) of these animal species might be the source of the human G6P[14] strains. The main feature of the genotype and phylogenetic analyses was the close overall genomic relatedness between the five human G6P[14] rotavirus strains and the ovine and antelope rotavirus strains. Taken together, these data strongly suggest a common origin for the human P[14] strains and those of the even-toed ungulates belonging to the mammalian order
Artiodactyla
, with sheep probably playing a key role in the interspecies transmission responsible for the introduction of P[14] rotavirus strains into the human population.
The Major Portal of Entry of Koi Herpesvirus in
Cyprinus carpio
Is the Skin
Authors: Costes B. , Raj V. Stalin , Michel B. , Fournier G. , Thirion M. , Gillet L. , Mast J. , Lieffrig F. , Bremont M. , Vanderplasschen A. 
Published: January 2009

ABSTRACT

Koi herpesvirus (KHV), recently designated
Cyprinid herpesvirus 3
, is the causative agent of a lethal disease in koi and common carp. In the present study, we investigated the portal of entry of KHV in carp by using bioluminescence imaging. Taking advantage of the recent cloning of the KHV genome as a bacterial artificial chromosome (BAC), we produced a recombinant plasmid encoding a firefly luciferase (LUC) expression cassette inserted in the intergenic region between open reading frame (ORF) 136 and ORF 137. Two viral strains were then reconstituted from the modified plasmid, the FL BAC 136 LUC excised strain and the FL BAC 136 LUC TK revertant strain, including a disrupted and a wild-type thymidine kinase (TK) locus, respectively. In vitro, the two recombinant strains replicated comparably to the parental FL strain. The FL BAC 136 LUC TK revertant strain was shown in vitro to induce a bioluminescent signal allowing the detection of single positive cells as early as 24 h postinfection, while in vivo, it induced KHV infection in carp that was indistinguishable from that induced by the parental FL strain. To identify the KHV portal of entry, carp were analyzed by bioluminescence imaging at different times postinfection with the FL BAC 136 LUC TK revertant strain. These analyses demonstrated that the skin of the fish covering the fins and also the body is the major portal of entry for KHV in carp. Finally, to further demonstrate the role of the skin as the KHV portal of entry, we constructed an original system, nicknamed “U-tube,” to perform percutaneous infection restricted to the posterior part of the fish. All the data obtained in the present study demonstrate that the skin, and not the gills, is the major portal of entry for KHV in carp.
A Key Role for Heat Shock Protein 70 in the Localization and Insertion of Tombusvirus Replication Proteins to Intracellular Membranes
Authors: Wang Robert Yung-Liang , Stork Jozsef , Nagy Peter D. 
Published: January 2009

ABSTRACT

Plus-stranded RNA viruses coopt host proteins to promote their robust replication in infected hosts.
Tomato bushy stunt tombusvirus
(TBSV) is a model virus that can replicate a small replicon RNA in
Saccharomyces cerevisiae
and in plants. The tombusvirus replicase complex contains heat shock protein 70 (Hsp70), an abundant cytosolic chaperone, which is required for TBSV replication. To dissect the function of Hsp70 in TBSV replication, in this paper we use an Hsp70 mutant (
ssa1 ssa2
) yeast strain that supports a low level of TBSV replication. Using confocal laser microscopy and cellular fractionation experiments, we find that the localization of the viral replication proteins changes to the cytosol in the mutant cells from the peroxisomal membranes in wild-type cells. An in vitro membrane insertion assay shows that Hsp70 promotes the integration of the viral replication proteins into subcellular membranes. This step seems to be critical for the assembly of the viral replicase complex. Using a gene-silencing approach and quercetin as a chemical inhibitor to downregulate Hsp70 levels, we also confirm the significance of cytosolic Hsp70 in the replication of TBSV and other plant viruses in a plant host. Taken together, our results suggest that cytosolic Hsp70 plays multiple roles in TBSV replication, such as affecting the subcellular localization and membrane insertion of the viral replication proteins as well as the assembly of the viral replicase.
Induction of APOBEC3 In Vivo Causes Increased Restriction of Retrovirus Infection
Authors: Okeoma Chioma M. , Low Audrey , Bailis Will , Fan Hung Y. , Peterlin B. Matija , Ross Susan R. 
Published: January 2009

ABSTRACTAPOBEC3 proteins are important cellular factors that restrict infection by a number of viruses, including human immunodeficiency virus type 1 (HIV-1). Previously, we found that the mouse APOBEC3 (mA3) restricts infection by mouse mammary tumor virus (MMTV) in its natural host. Dendritic cells (DCs) are the first in vivo targets of MMTV infection. In this study, we demonstrate that mA3 expressed in target cells restricts MMTV infection in DCs ex vivo and in vivo. By comparing infection of DCs from mA3+/+and mA3−/−mice with one-hit viruses, we show that mA3 expression in target cells blocked MMTV infection at a postentry step and acted together with virion-packaged mA3 to inhibit infection. Similar results were obtained upon infection of mouse DCs with HIV-1 cores pseudotyped with vesicular stomatitis virus G protein. In addition, treatment of cells or mice with lipopolysaccharide (LPS) caused increased levels of mA3 expression and rendered them resistant to MMTV infection. Alpha interferon treatment had a similar effect. This LPS-induced resistance to infection was seen only in mA3+/+mice and not in mA3−/−mice, arguing that mA3 is the major anti-MMTV restriction factor that is induced upon DC maturation. Thus, increasing the levels of this intrinsic antiretroviral factor in vivo can lead to increased levels of restriction because of higher levels of both cell-intrinsic as well as virion-packaged APOBEC3.
HLA-Associated Viral Mutations Are Common in Human Immunodeficiency Virus Type 1 Elite Controllers
Authors: Miura Toshiyuki , Brumme Chanson J. , Brockman Mark A. , Brumme Zabrina L. , Pereyra Florencia , Block Brian L. , Trocha Alicja , John Mina , Mallal Simon , Harrigan P. Richard , Walker Bruce D. 
Published: January 2009

ABSTRACT

Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8
+
T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma
gag
,
pol
, and
nef
sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC, compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HIV-1 infection.
Expression of Murine APOBEC3 Alleles in Different Mouse Strains and Their Effect on Mouse Mammary Tumor Virus Infection
Authors: Okeoma Chioma M. , Petersen Josiah , Ross Susan R. 
Published: January 2009

ABSTRACT

Recent work has shown that mouse APOBEC3 restricts infection by mouse mammary tumor virus (MMTV) and murine leukemia virus (MLV) and that there are polymorphic APOBEC3 alleles found in different inbred mouse strains. For example, C57BL/6 mice, which are resistant to Friend MLV (F-MLV), encode a APOBEC3 gene different from that encoded by F-MLV-susceptible BALB/c mice; the predominant RNA produced in C57BL/6 mice lacks exon 5 (mA3
−5
) and encodes a protein with 15 polymorphic amino acids. It has also been reported that BALB/c mice produce only a variant RNA that lacks exon 2 (mA3
−2
). In this study, we examined the effect of these polymorphic APOBEC3 proteins on MMTV infection. We found that the major RNA made in C57BL/6 and B10.BR mice lacks exon 5 but that BALB/c and C3H/HeN mice predominantly express an RNA that contains all nine exons. In addition to producing the splice variant, C57BL/6 and B10.BR cells and tissues had levels of mA3 RNA fivefold higher than those from BALB/c and C3H/HeN mice. A cloned C57BL/6-derived mA3 protein lacking exon 5 inhibited MMTV infection better than a cloned full-length protein derived from 129/Ola RNA when packaged into MMTV virions. We also tested dendritic cells derived from different inbred mouse strains for their abilities to be infected by MMTV and showed that susceptibility to infection correlated with the presence of the exon 5-encoding allele. In vivo susceptibility to infection cosegregated with the inherited mA3 allele in a C57BL/6 × BALB/c backcross analysis. Moreover, virus produced in vivo in the mammary tissue of mA3 knockout and BALB/c mice was more infectious than that produced in the tissue of C57BL/6 mice. These data indicate that mA3 plays a role in the genetics of susceptibility and resistance to MMTV infection.
A case-control study on occupational risk factors for sino-nasal cancer
Authors: d’Errico A , Pasian S , Baratti A , Zanelli R , Alfonzo S , Gilardi L , Beatrice F , Bena A , Costa G 
Published: January 2009

Objectives:Sino-nasal cancer has been consistently associated with exposure to wood dust, leather dust, nickel and chromium compounds; for other occupational hazards, the findings are somewhat mixed. The aim of this study was to investigate the risk of sino-nasal epithelial cancer (SNEC) by histological type with prior exposure to suspected occupational risk factors and, in particular, those in metalworking.Methods:Between 1996 and 2000, incident cases were collected on a monthly basis from hospitals throughout the Piedmont region of Italy by the regional Sino-nasal Cancer Registry. A questionnaire on occupational history, completed by 113 cases and 336 hospital controls, was used to assign exposure to occupational hazards. The relationship between SNEC and cumulative exposure to these hazards was explored using unconditional logistic regression to statistically adjust for age, sex, smoking and co-exposures, allowing for a 10-year latency period.Results:The risk of adenocarcinoma was significantly increased with ever-exposure to wood dust (odds ratio; OR = 58.6), and to leather dust (OR = 32.8) and organic solvents (OR = 4.3) after controlling for wood dust, whereas ever-exposure to welding fumes (OR = 3.7) and arsenic (OR = 4.4) significantly increased the risk for squamous cell carcinoma. For each of these hazards, a significant increasing trend in risk across ordered cumulative exposure categories was found and, except for arsenic, a significantly increased risk with ever-exposure at low intensity. Treating cumulative exposure on a continuous scale, a significant effect of textile dusts was also observed for adenocarcinoma. For a mixed group of other histological types, a significant association was found with wood dust and organic solvents.Conclusions:Some occupational risk factors for SNEC were confirmed, and dose–response relationships were observed for other hazards that merit further investigation. The high risk for adenocarcinoma with low-intensity exposure to wood dust lends support for a reduction in the occupational threshold value.
Issues with network address translation for SCTP
Authors: Hayes David A. , But Jason , Armitage Grenville 
Published: January 2009

A Stream Control Transmission Protocol (SCTP) capable Network Address Translation (NAT) device is necessary to support the wider deployment of the SCTP protocol. The key issues for an SCTP NAT are SCTP's control chunk multiplexing and multi-homing features. Control chunk multiplexing can expose an SCTP NAT to possible Denial of Service attacks. These can be mitigated through the use of chunk and parameter processing limits.
Multiple and changing IP addresses during an SCTP association, mean that SCTP NATs cannot operate in the way conventional UDP/TCP NATs operate. Tracking these multiple global IP addresses can help in avoiding lookup table conflicts, however, it can also result in circumstances that can lead to NAT state inconsistencies. Our analysis shows that tracking global IP addresses is not necessary in most expected practical installations.
We use our FreeBSD SCTP NAT implementation, alias_sctp to examine the performance implications of tracking global IP addresses. We find that typical memory usage doubles and that the processing requirements are significant for installations that experience high association arrival rates.
In conclusion we provide practical recommendations for a secure stable SCTP NAT installation.
Clemency as Cruelty: Forgiveness and Force in the Dying Prayers of Jesus and Stephen
Authors: Matthews Shelly 
Published: January 2009

AbstractThis article clarifies the significance of the dying forgiveness prayers of Jesus and Stephen by placing them aside related bodies of literature including biblical and extra-biblical narratives of persecuted prophets and the suffering righteous, the literature of the Maccabean martyrs, the ethical exhortations to enemy love and non-retaliation in the Sermon on the Mount/Plain, and Roman discourse on clemency. Against a recent cluster of scholarship attempting to situate the prayers fully within Jewish scriptural traditions in order to argue that Luke-Acts is not anti-Jewish, it argues that the prayers function to construct a break between the Ioudaioi and the Christianoi. The dying forgiveness prayers are for Luke a Christian proprium. They are potentially more radical than Jesus' ethical teaching on enemy love and non-retaliation, since the former constitute a challenge to the framework of talionic justice which the latter need not. The threat of the forgiveness prayers to the talionic framework of cosmic justice prompted the modification, and even the suppression, of the prayers in some quarters. Those who embraced and celebrated the prayers without modification, like Luke himself, seemed to have understood them intransitively as idealizing the hero who so prays but as having no effect on the prayer's objects. The article concludes with consideration of the Roman discourse on clemency, which functions similarly. Awareness of the cruelty implicit in Roman clemency serves to illuminate the potentially violent effects of certain iterations of the forgiveness prayers, including those preserved in Luke-Acts.
Reconsidering the Book and the Sword: A Rhetoric of Passivity in Rabbinic Hermeneutics
Authors: Berkowitz Beth 
Published: January 2009

AbstractThe motif of the "book and the sword" as it appears in a Babylonian Talmud martyrdom narrative suggests that Torah and violence are mutually exclusive. This essay will explore in what ways the book and the sword have a more complicated relationship within the Babylonian Talmud and its sources than this narrative suggests. The essay will focus attention on a posture of interpretive passivity that rabbinic legislators adopt in a variety of legal contexts in which their audience's physical and social welfare is at stake, including criminal execution and women's claims upon their husbands. The essay will contrast the representation of the rabbi who laments, "What can I do? For behold the Torah said …" to the creative hermeneutics he in fact exercises. The essay will argue that this idiom, as it appears in several tannaitic texts and then is expanded in Babylonian talmudic texts, is unusual within Antiquity in giving explicit expression to embarrassment about scriptural canon. The essay proposes that the stereotyping of early rabbis as hermeneutically passive by Babylonian talmudic editors allows them to highlight their own exegetical and judicial activism as they transform inherited sources. The essay considers what the representation of hermeneutically passive rabbinic judges can reveal about the complex relationship between legal exegesis, judicial authority, and violence within rabbinic literature, from early to late, from Palestine to Babylonia.
Israelite Exiles in Media: A New Look at ND 2443+
Authors: Galil Gershon 
Published: January 2009

AbstractThis paper reexamines ND 2443+, a Neo-Assyrian administrative record excavated at Calah in 1952, and first published by Barbara Parker in 1961 (Iraq 23, pp. 27-28). A new translation of this important text is presented, followed by a few notes and a discussion on the relation between the Israelite exile Hilqī-Iāu, and the city Sagbat/Bīt-Sagbat in Media. The text should be dated to the last years of Tiglath-pileser III since it mentions Bēl-Harrān-bēlu-usur, the nāgir ekalli, first appointed ca. 775 B.C., and the Israelites Hilqī-Iāu and Gir-Iāu, probably exiled from Israel after the 733-732 B.C. campaign. In light of the new interpretation of ND 2443+ the issue of “the cities of Media” (1 Kgs 17:6; 18:14) is reconsidered, and it is suggested that ND 2443+ indicates the deportation of Israelites to Media in the last years of Tiglath-pileser III.
The existential impact of starting corticosteroid treatment as symptom control in advanced metastatic cancer
Authors: Lundström S , Fürst CJ , Friedrichsen M , Strang P 
Published: January 2009

Treatment with corticosteroids often results in increased appetite, reduced nausea and improved well-being in patients with advanced metastatic cancer. Therefore, we have studied the existential impact of starting corticosteroid treatment as symptom control in this patient group using qualitative content analysis with both a descriptive and an interpretative focus. Ten patients were interviewed before and after 1 week of treatment with 4 mg betamethasone. Prior to treatment, patients reported distressing symptoms, deterioration and diminished autonomy, symbolising threat and death. Corticosteroid treatment produced symptom relief in the majority of the patients. They reported enhanced physical abilities and experienced feelings of a more normalized life and strengthened autonomy, symbolising health and hope. This transfer from threat to hope has important existential consequences in end-of-life care and should be addressed when communicating goals of treatment and care with the patient and family.