bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of Replication of Porcine Endogenous Retrovirus and Porcine Lymphotropic Herpesvirus Type 1 with Prolonged Pig Cell Microchimerism after Pig-to-Baboon Xenotransplantation
Authors: Issa Nicolas C. , Wilkinson Robert A. , Griesemer Adam , Cooper David K. C. , Yamada Kazuhiko , Sachs David H. , Fishman Jay A. 
Published: October 2008

ABSTRACT

Porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), and porcine lymphotropic herpesvirus (PLHV) are common porcine viruses that may be activated with immunosuppression for xenotransplantation. Studies of viral replication or transmission are possible due to prolonged survival of xenografts in baboon recipients from human decay-accelerating factor transgenic or α-1,3-galactosyltransferase gene knockout miniature swine. Ten baboons underwent xenotransplantation with transgenic pig organs. Graft survival was 32 to 179 days. Recipient serial samples of peripheral blood mononuclear cells (PBMC) and plasma were analyzed for PCMV, PERV, and PLHV-1 nucleic acids and viral replication using quantitative PCR assays. The PBMC contained PERV proviral DNA in 10 animals, PLHV-1 DNA in 6, and PCMV in 2. PERV RNA was not detected in any PBMC or serum samples. Plasma PLHV-1 DNA was detected in one animal. Pig cell microchimerism (pig major histocompatibility complex class I and pig mitochondrial cytochrome
c
oxidase subunit II sequences) was present in all recipients with detectable PERV or PLHV-1 (85.5%). Productive infection of PERV or PLHV-1 could not be demonstrated. The PLHV-1 viral load did not increase in serum over time, despite prolonged graft survival and pig cell microchimerism. There was no association of viral loads with the nature of exogenous immune suppression. In conclusion, PERV provirus and PLHV-1 DNA were detected in baboons following porcine xenotransplantation. Viral detection appeared to be due to persistent pig cell microchimerism. There was no evidence of productive infection in recipient baboons for up to 6 months of xenograft function.
Glycosylation of gp41 of Simian Immunodeficiency Virus Shields Epitopes That Can Be Targets for Neutralizing Antibodies
Authors: Yuste Eloìsa , Bixby Jacqueline , Lifson Jeffrey , Sato Shuji , Johnson Welkin , Desrosiers Ronald 
Published: October 2008

ABSTRACT
Human immunodeficiency virus type 1 and simian immunodeficiency virus possess three closely spaced, highly conserved sites for N-linked carbohydrate attachment in the extracellular domain of the transmembrane protein gp41. We infected rhesus monkeys with a variant of cloned SIVmac239 lacking the second and third sites or with a variant strain lacking all three of SIVmac239's glycosylation sites in gp41. For each mutation, asparagine (N) in the canonical N-X-S/T recognition sequence for carbohydrate attachment was changed to the structurally similar glutamine such that two nucleotide changes would be required for a reversion of the mutated codon. By 16 weeks, experimentally infected monkeys made antibodies that neutralized the mutant viruses to high titers. Such antibodies were not observed in monkeys infected with the parental virus. Thus, new specificities were revealed as a result of the carbohydrate attachment mutations, and antibodies of these specificities had neutralizing activity. Unlike monkeys infected with the parental virus, monkeys infected with the mutant viruses made antibodies that reacted with peptides corresponding to the sequences in this region. Furthermore, there was strong selective pressure for the emergence of variant sequences in this region during the course of infection. By analyzing the neutralization profiles of sequence variants, we were able to define three mutations (Q625R, K631N, and Q634H) in the region of the glycosylation site mutations that conferred resistance to neutralization by plasma from the monkeys infected with mutant virus. Based on the reactivity of antibodies to peptides in this region and the colocalization of neutralization escape mutations, we conclude that N-linked carbohydrates in the ectodomain of the transmembrane protein shield underlying epitopes that would otherwise be the direct targets of neutralizing antibodies.
Epigenetic Silencing of Human Immunodeficiency Virus (HIV) Transcription by Formation of Restrictive Chromatin Structures at the Viral Long Terminal Repeat Drives the Progressive Entry of HIV into Latency
Authors: Pearson Richard , Kim Young Kyeung , Hokello Joseph , Lassen Kara , Friedman Julia , Tyagi Mudit , Karn Jonathan 
Published: October 2008

ABSTRACT

The molecular mechanisms utilized by human immunodeficiency virus (HIV) to enter latency are poorly understood. Following the infection of Jurkat T cells with lentiviral vectors that express Tat in
cis
, gene expression is progressively silenced. Silencing is greatly enhanced when the lentiviral vectors carry an attenuated Tat gene with the H13L mutation. Individual clones of lentivirus-infected cells showed a wide range of shutdown rates, with the majority showing a 50% silencing frequency between 30 to 80 days. The silenced clones characteristically contained a small fraction (0 to 15%) of activated cells that continued to express d2EGFP. When d2EGFP
+
and d2EGFP
−
cell populations were isolated from the shutdown clones, they quickly reverted to the original distribution of inactive and active cells, suggesting that the d2EGFP
+
cells arise from stochastic fluctuations in gene expression. The detailed analysis of transcription initiation and elongation using chromatin immunoprecipitation (ChIP) assays confirms that Tat levels are restricted in the latently infected cells but gradually rise during proviral reactivation. ChIP assays using clones of latently infected cells demonstrate that the latent proviruses carry high levels of deacetylated histones and trimethylated histones. In contrast, the cellular genes IκBα and GAPDH had high levels of acetylated histones and no trimethylated histones. The levels of trimethylated histone H3 and HP1-α associated with HIV proviruses fell rapidly after tumor necrosis factor alpha activation. The progressive shutdown of HIV transcription following infection suggests that epigenetic mechanisms targeting chromatin structures selectively restrict HIV transcription initiation. This decreases Tat production below the levels that are required to sustain HIV gene expression.
Experimental Evolution of Human Influenza Virus H3 Hemagglutinin in the Mouse Lung Identifies Adaptive Regions in HA1 and HA2
Authors: Keleta Liya , Ibricevic Aida , Bovin Nicolai V. , Brody Steven L. , Brown Earl G. 
Published: October 2008

ABSTRACT
The genetic basis for virulence and host switching in influenza A viruses (FLUAV) is largely unknown. Because the hemagglutinin (HA) protein is a determinant of these properties, HA evolution was mapped in an experimental model of mouse lung adaptation. Variants of prototype A/Hong Kong/1/68 (H3N2) (wild-type [wt] HK) human virus were selected in both longitudinal and parallel studies of lung adaptation. Mapping of HA mutations found in 11 independently derived mouse-adapted populations of wt HK identified 27 mutations that clustered within two distinct regions in or near the globular frameworks of the HA1 and HA2 subunits. The adaptive mutations demonstrated multiple instances of convergent evolution involving four amino acid positions (162, 210, and 218 in HA1 and 154 in HA2). By use of reverse genetics, convergent HA mutations were shown to affect cell tropism by enhancing infection and replication in primary mouse tracheal epithelial cells in vitro and mouse lung tissue in vivo. Adaptive HA mutations were multifunctional, affecting both median pH of fusion and receptor specificity. Specific mutations within both adaptive regions were shown to increase virulence in a mouse lung model. The occurrence of mutations in the HA1 and HA2 adaptive regions of natural FLUAV host range and virulent variants of avian and mammalian viruses is discussed. This study has identified adaptive sites and regions within the HA1 and HA2 subunits that may guide future studies of viral adaptation and evolution in nature.
Role of Ebola Virus VP30 in Transcription Reinitiation
Authors: Martínez Miguel J. , Biedenkopf Nadine , Volchkova Valentina , Hartlieb Bettina , Alazard-Dany Nathalie , Reynard Olivier , Becker Stephan , Volchkov Viktor 
Published: October 2008

ABSTRACT
VP30 is a phosphoprotein essential for the initiation of Ebola virus transcription. In this work, we have studied the effect of mutations in VP30 phosphorylation sites on the ebolavirus replication cycle by using a reverse genetics system. We demonstrate that VP30 is involved in reinitiation of gene transcription and that this activity is affected by mutations at the phosphorylation sites.
Overexpression of Thiol/Disulfide Isomerases Enhances Membrane Fusion Directed by the Newcastle Disease Virus Fusion Protein
Authors: Jain Surbhi , McGinnes Lori W. , Morrison Trudy G. 
Published: October 2008

ABSTRACT
Newcastle disease virus (NDV) fusion (F) protein directs membrane fusion, which is required for virus entry and cell-cell fusion. We have previously shown that free thiols are present in cell surface-expressed NDV F protein and that blocking the production of free thiols by thiol-disulfide exchange inhibitors inhibited the membrane fusion mediated by F protein (J Virol. 81:2328-2339, 2007). Extending these observations, we evaluated the role of the overexpression of two disulfide bond isomerases, protein disulfide isomerase (PDI) and ERdj5, in cell-cell fusion mediated by NDV glycoproteins. The overexpression of these isomerases resulted in significantly increased membrane fusion, as measured by syncytium formation and content mixing. The overexpression of these isomerases enhanced the production of free thiols in F protein when expressed without hemagglutination-neuraminidase (HN) protein but decreased free thiols in F protein expressed with HN protein. By evaluating the binding of conformation-sensitive antibodies, we found that the overexpression of these isomerases favored a postfusion conformation of surface-expressed F protein in the presence of HN protein. These results suggest that isomerases belonging to the PDI family catalyze the production of free thiols in F protein, and free thiols in F protein facilitate membrane fusion mediated by F protein.
Heparan Sulfate-Independent Cell Binding and Infection with Furin-Precleaved Papillomavirus Capsids
Authors: Day Patricia M. , Lowy Douglas R. , Schiller John T. 
Published: October 2008

ABSTRACT
Papillomavirus infection normally involves virion binding to cell surface heparan sulfate proteoglycans (HSPGs). However, we found that human papillomavirus type 16 pseudovirions efficiently bound and infected cells lacking HSPGs if their L2 capsid protein was precleaved by furin, a cellular protease required for infection. The inability of pseudovirions to efficiently bind and infect cultured primary keratinocytes was also overcome by furin precleavage, suggesting that the defect involves altered HSPG modification. We conclude that the primary function of HSPG binding is to enable cell surface furin cleavage of L2 and that binding to a distinct cell surface receptor(s) is a subsequent step of papillomavirus infection.
Simian Immunodeficiency Virus (SIV)-Specific CD8+T-Cell Responses in Vervet African Green Monkeys Chronically Infected with SIVagm
Authors: Zahn Roland C. , Rett Melisa D. , Korioth-Schmitz Birgit , Sun Yue , Buzby Adam P. , Goldstein Simoy , Brown Charles R. , Byrum Russell A. , Freeman Gordon J. , Letvin Norman L. , Hirsch Vanessa M. , Schmitz Jörn E. 
Published: October 2008

ABSTRACTAfrican green monkeys (AGM) do not develop overt signs of disease following simian immunodeficiency virus (SIV) infection. While it is still unknown how natural hosts like AGM can cope with this lentivirus infection, a large number of investigations have shown that CD8+T-cell responses are critical for the containment of AIDS viruses in humans and Asian nonhuman primates. Here we have compared the phenotypes of T-cell subsets and magnitudes of SIV-specific CD8+T-cell responses in vervet AGM chronically infected with SIVagm and rhesus monkeys (RM) infected with SIVmac. In comparison to RM, vervet AGM exhibited weaker signs of immune activation and associated proliferation of CD8+T cells as detected by granzyme B, Ki-67, and programmed death 1 staining. By gamma interferon enzyme-linked immunospot assay and intracellular cytokine staining, SIV Gag- and Env-specific immune responses were detectable at variable but lower levels in vervet AGM than in RM. These observations demonstrate that natural hosts like SIV-infected vervet AGM develop SIV-specific T-cell responses, but the disease-free course of infection does not depend on the generation of robust CD8+T-cell responses.
Application of Calcined Layered Double Hydroxides as Catalysts for Abatement of N2O Emissions
Authors: Obalová Lucie , Kovanda František , Jirátová Květuše , Pacultová Kateřina , Lacný Zdenek 
Published: October 2008

The results of catalytic decomposition of N2O over mixed oxide catalysts obtained by calcination of layered double hydroxides (LDHs) are summarized. Mixed oxides were prepared by thermal treatment (500 °C) of coprecipitated LDH precursors with general chemical composition of MII1-xMIIIx(OH)2(CO3)x/2·yH2O, where MII was Ni, Co, Cu and/or Mg, MIII was Mn, Fe and/or Al, and the MII/MIII molar ratio was adjusted to 2. The influence of chemical composition of the MII-MIII mixed oxide catalysts on their activity and stability in N2O decomposition was examined. The highest N2O conversion was reached over Ni-Al (4:2) and Co-Mn-Al (4:1:1) catalysts. Their suitability for practical application was proved in simulated process stream in the presence of O2, NO, NO2 and H2O. It was found that N2O conversion decreased with increasing amount of oxygen in the feed. The presence of NO in the feed caused a slight decrease in N2O conversion. A strong decrease in the reaction rate was observed over the Ni-Al catalyst in the presence of NO2 while no N2O conversion decrease was observed over the Co-Mn-Al catalyst. Water vapor inhibited the N2O decomposition over all tested catalysts. The obtained kinetic data for N2O decomposition in a simulated process stream over the Co-Mn-Al catalyst were used for a preliminary reactor design. The packed bed volume necessary for N2O emission abatement in a HNO3 production plant was calculated as 35 m3 for waste gas flow rate of 30 000 m3 h-1.
Aromatic Transformation in Fluidized Bed Reactors
Authors: Rabiu Sule , Al-Khattaf Sulaiman 
Published: October 2008

In this work three important aromatic transformations, namely: toluene disproportionation, toluene methylation and m-xylene isomerization, were investigated in a riser simulator which closely mimics the operation of commercial fluidized bed reactors. The transformations were studied over a ZSM-5 based catalyst with medium acidity of 0.23 mmol/g and a series of Y zeolites of acidities between 0.55 and 0.03 mmol/g. For pure toluene feed, it was observed that conversion over the ZSM-5 based catalyst and the weakly acidic Y zeolite (USY-1) was very low. However, with the highly acidic Y zeolite (H-Y), significant toluene conversion was observed with paring reaction more prominent than disproportionation. On the other hand, when toluene was alkylated with methanol, higher toluene conversions were achieved over both the ZSM-5 based and the weakly acidic USY-1 catalysts as compared to when pure toluene feed was used. In addition, p-xylene/o-xylene (P/O) ratios higher than the equilibrium values were obtained in the reaction product over both catalysts. Finally, for m-xylene isomerization it was found that m-xylene conversion increased initially as the acidity of the catalyst increased up to 0.1 mmol/g beyond which any further increase in acidity resulted in a slight decrease in the m-xylene conversion.
Synthesis and Structure of Permethylcyclopentadienyltitanium Diisopropoxide Zwitterionic Complex
Authors: Varga Vojtech , Pinkas Jiří , Císařová Ivana , Gyepes Róbert , Mach Karel , Kubišta Jiří , Horáček Michal 
Published: October 2008

Half-sandwich pentamethylcyclopentadienyltitanium chloroisopropoxides [Ti(η5-C5Me5)-Ti(Oi-Pr)nCl3-n] (n = 1 (1) or 2 (2)) and methylisopropoxides [Ti(η5-C5Me5)Ti(Oi-Pr)nMe3-n] (n = 1 (3) or 2 (4)) were prepared and characterized by spectroscopic methods, and compound 1 by single crystal X-ray diffraction analysis. Compounds 3 and 4 were reacted with an equimolar quantity of B(C6F5)3, however, only compound 4 afforded a crystalline product of limited stability at ambient temperature. Its single crystal X-ray diffraction analysis revealed that it is the zwitterionic complex [(η5-C5Me5)Ti(Oi-Pr)2]+[(μ-Me)B(C6F5)3]- (5) and its crystal structure is very similar to the recently reported tert-butoxy complex [(η5-C5Me5)-Ti(Ot-Bu)2]+[(μ-Me)B(C6F5)3]- (6). The 1H, 13C, and 19F NMR spectra in C6D6 solution also showed the features analogous to those of 6. 1D NOESY experiments proved a close through space interaction of irradiated C5Me5 or OCHMe2 protons with the bridging Ti···Me-B group. The NMR data indicate the inner sphere ion pair structure of 5 in C6D6, like for 6. The crystal structure geometry of the C-H bonds of the Ti···Me-B group fulfils conditions for their agostic interaction with the titanium centre. Although structurally similar to 6, compound 5 is less thermally stable apparently due to a lower bulkiness of Oi-Pr group compared to that of Ot-Bu group.
Common acute oncological emergencies: diagnosis, investigation and management
Authors: Walji N , Chan A K , Peake D R 
Published: October 2008

Abstract
In the UK an aging population is resulting in more people being diagnosed with cancer, and an increasing number of treatment options means that many patients live significantly longer with their disease. It is anticipated therefore that an increasing number of patients will present to primary and secondary care with acute complications of cancer, or the treatment thereof. Many doctors have limited experience in managing patients with cancer and acute oncological emergencies. This article reviews the diagnosis and management of four common oncological emergencies: febrile neutropenia, metastatic spinal cord compression, superior vena cava obstruction, and malignancy associated hypercalcaemia. It is vital to recognise these conditions, as failure to implement immediate and appropriate treatment may result in significant morbidity or death.
Cross-sectional survey of disturbed behaviour in patients in general hospitals in Leeds
Authors: Kannabiran M , Deshpande S , Walling A , Alagarsamy J , Protheroe D , Trigwell P 
Published: October 2008

Abstract

Aim
To describe the prevalence and nature of disturbed behaviour, in the general hospital setting.

Method
A cross-sectional survey was conducted, from July to October 2006, in all adult inpatient wards within the six general hospitals in Leeds of patients presenting with disturbed behaviour in the preceding 7 days. Disturbed behaviour was defined as behaviour interfering with care of the patient or with that of other patients, or behaviour that placed the patient, the staff or others at risk. Anonymised data were collected using a semi-structured questionnaire.

Results
All of the 87 hospital wards were studied, containing a total of 1773 beds. 42 male and 26 female patients (n = 68) were identified by nursing staff as patients with disturbed behaviour in the time period covered, with 33 patients being ⩽65 years of age and 35 being elderly (&gt;65 years of age). An almost equal proportion of the younger and older patient groups placed themselves or others at risk. In the majority of cases, aggressive behaviour by patients was directed towards staff rather than other patients. 60 patients required additional staff time due to the disturbed behaviour, 34 required additional medication, and 22 patients were referred to liaison psychiatry.

Conclusions
Disturbed behaviour presents in the general hospital in less than 4% of patients, both above and below the age of 65 years, but consumes a disproportionate amount of resources. Responses required to manage this include additional medication, additional staff time or other interventions. The quantity and nature of disturbed behaviour in the general hospital have implications for effective service provision and development.
Changing education to improve patient care
Authors: Leach D C 
Published: October 2008

Abstract
Health professionals need competencies in improvement skills if they are to contribute usefully to improving patient care. Medical education programmes in the USA have not systematically taught improvement skills to residents (registrars in the UK). The Accreditation Council for Graduate Medical Education (ACGME) has recently developed and begun to deploy a competency based model for accreditation that may encourage the development of improvement skills by the 100 000 residents in accredited programmes. Six competencies have been identified for all physicians, independent of specialty, and measurement tools for these competencies have been described. This model may be applicable to other healthcare professions. This paper explores patterns that inhibit efforts to change practice and proposes an educational model to provide changes in management skills based on trainees' analysis of their own work.
Precipitation Characteristics of Trade Wind Clouds during RICO Derived from Radar, Satellite, and Aircraft Measurements
Authors: Snodgrass Eric R. , Di Girolamo Larry , Rauber Robert M. 
Published: October 2008

Abstract
Precipitation characteristics of trade wind clouds over the Atlantic Ocean near Barbuda are derived from radar and aircraft data and are compared with satellite-observed cloud fields collected during the Rain in Cumulus over the Ocean (RICO) field campaign. S-band reflectivity measurements Z were converted to rainfall rates R using a Z–R relationship derived from aircraft measurements. Daily rainfall rates varied from 0 to 22 mm day−1. The area-averaged rainfall rate for the 62-day period was 2.37 mm day−1. If corrected for evaporation below cloud base, this value is reduced to 2.23 mm day−1, which translates to a latent heat flux to the atmosphere of 63 W m−2. When compared with the wintertime ocean-surface latent heat flux from this region, the average return of water to the ocean through precipitation processes within the trade wind layer during RICO was 31%–39%. A weak diurnal cycle was observed in the area-averaged rainfall rate. The magnitude of the rainfall and the frequency of its occurrence had a maximum in the predawn hours and a minimum in the midmorning to early afternoon on 64% of the days. Radar data were collocated with data from the Multiangle Imaging Spectroradiometer (MISR) to develop relationships between cloud-top height, cloud fraction, 866-nm bidirectional reflectance factor (BRF), and radar-derived precipitation. The collocation took place at the overpass time of ∼1045 local time. These relationships revealed that between 5.5% and 10.5% of the cloudy area had rainfall rates that were &gt; 0.1 mm h−1, and between 1.5% and 3.5% of the cloudy area had rainfall rates that were &gt;1 mm h−1. Cloud-top heights between ∼3 and 4 km and BRFs between 0.4 and 1.0 contributed ∼50% of the total rainfall. For cloudy pixels having detectable rain, average rainfall rates increased from ∼1 to 4 mm h−1 as cloud-top heights increased from ∼1 to 4 km. Rainfall rates were closely tied to the type of mesoscale organization, with much of the rainfall originating from shallow (&lt;5 km) cumulus clusters shaped as arcs associated with cold-pool outflows.