bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucosal Tissue Tropism and Dissemination of HIV-1 Subtype B Acute Envelope-Expressing Chimeric Virus
Authors: King Deborah F. L. , Siddiqui Asna A. , Buffa Viviana , Fischetti Lucia , Gao Yong , Stieh Daniel , McKay Paul F. , Rogers Paul , Ochsenbauer Christina , Kappes John C. , Arts Eric J. , Shattock Robin J. 
Published: November 2012

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) transmission results from infection with one or a small number of variants from the donor quasispecies. Transmitted/founder (T/F) viruses have recently been identified from acutely infected patients, but the way in which they interact with primary targets of HIV-1 infection is poorly understood. We have conducted a biological characterization of a panel of subtype B T/F acute and chronic envelope (Env)-expressing chimeric virus in primary human target cells and mucosal tissues. Both acute and chronic Envs preferentially replicated in peripheral blood mononuclear cells (PBMC) and a CD4 T-cell line compared to monocyte-derived macrophages, or dendritic cells (DC). In a model of
trans
infection from monocyte-derived dendritic cells to T cells, chimeric virus from acute Envs achieved significantly lower titers compared to chronic Envs. Challenge of primary human mucosal tissues revealed significantly higher levels of replication in chronic Env-expressing virus in rectal tissue compared to cervical and penile tissues and enhanced replication in tonsillar tissue relative to acute Envs. In agreement with data from the DC to T-cell
trans
infection assay, chronic Env-chimeric virus pools were transmitted more efficiently by migratory cells from cervical and penile tissues to CD4
+
T cells than individual acute Env chimeras. These data indicate that virus with HIV-1 Envs of transmitted acute infections preferentially replicate in T cells rather than macrophages or dendritic cells and are less efficiently transmitted from antigen-presenting cells to CD4 T cells than chronic Envs. Such properties together with chemokine (C-C motif) receptor 5 (CCR5) use may confer an advantage for transmission.
Host mTORC1 Signaling Regulates Andes Virus Replication
Authors: McNulty Shannon , Flint Mike , Nichol Stuart T. , Spiropoulou Christina F. 
Published: November 2012

ABSTRACT

Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease characterized by pulmonary edema, with fatality rates of 35 to 45%. Disease occurs following infection with pathogenic New World hantaviruses, such as Andes virus (ANDV), which targets lung microvascular endothelial cells. During replication, the virus scavenges 5′-m
7
G caps from cellular mRNA to ensure efficient translation of viral proteins by the host cell cap-dependent translation machinery. In cells, the mammalian target of rapamycin (mTOR) regulates the activity of host cap-dependent translation by integrating amino acid, energy, and oxygen availability signals. Since there is no approved pharmacological treatment for HPS, we investigated whether inhibitors of the mTOR pathway could reduce hantavirus infection. Here, we demonstrate that treatment with the FDA-approved rapamycin analogue temsirolimus (CCI-779) blocks ANDV protein expression and virion release but not entry into primary human microvascular endothelial cells. This effect was specific to viral proteins, as temsirolimus treatment did not block host protein synthesis. We confirmed that temsirolimus targeted host mTOR complex 1 (mTORC1) and not a viral protein, as knockdown of mTORC1 and mTORC1 activators but not mTOR complex 2 components reduced ANDV replication. Additionally, primary fibroblasts from a patient with tuberous sclerosis exhibited increased mTORC1 activity and increased ANDV protein expression, which were blocked following temsirolimus treatment. Finally, we show that ANDV glycoprotein Gn colocalized with mTOR and lysosomes in infected cells. Together, these data demonstrate that mTORC1 signaling regulates ANDV replication and suggest that the hantavirus Gn protein may modulate mTOR and lysosomal signaling during infection, thus bypassing the cellular regulation of translation.
Biogenesis of the Vaccinia Virus Membrane: Genetic and Ultrastructural Analysis of the Contributions of the A14 and A17 Proteins
Authors: Unger Bethany , Mercer Jason , Boyle Kathleen A. , Traktman Paula 
Published: November 2012

ABSTRACT

Vaccinia virus membrane biogenesis requires the A14 and A17 proteins. We show here that both proteins can associate with membranes co- but not posttranslationally, and we perform a structure function analysis of A14 and A17 using inducible recombinants. In the absence of A14, electron-dense virosomes and distinct clusters of small vesicles accumulate; in the absence of A17, small vesicles form a corona around the virosomes. When the proteins are induced at 12 h postinfection (hpi), crescents appear at the periphery of the electron-dense virosomes, with the accumulated vesicles likely contributing to their formation. A variety of mutant alleles of A14 and A17 were tested for their ability to support virion assembly. For A14, biologically important motifs within the N-terminal or central loop region affected crescent maturation and the immature virion (IV)→mature virion (MV) transition. For A17, truncation or mutation of the N terminus of A17 engendered a phenotype consistent with the N terminus of A17 recruiting the D13 scaffold protein to nascent membranes. When N-terminal processing was abrogated, virions attempted to undergo the IV-to-MV transition without removing the D13 scaffold and were therefore noninfectious and structurally aberrant. Finally, we show that A17 is phosphorylated exclusively within the C-terminal tail and that this region is a direct substrate of the viral F10 kinase.
In vivo
, the biological competency of A17 was reduced by mutations that prevented its serine-threonine phosphorylation and restored by phosphomimetic substitutions. Precleavage of the C terminus or abrogation of its phosphorylation diminished the IV→MV maturation; a block to cleavage spared virion maturation but compromised the yield of infectious virus.
Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study)
Authors: Mullol Joaquim , Alobid Isam , Mariño-Sánchez Franklin , Quintó Llorenç , de Haro Josep , Bernal-Sprekelsen Manuel , Valero Antonio , Picado Cèsar , Marin Concepció 
Published: November 2012

ObjectivesTo investigate olfaction in general population, prevalence of olfactory dysfunction and related risk factors.DesignCross-sectional population-based survey, distributing four microencapsulated odorants (rose, banana, musk and gas) and two self-administered questionnaires (odour description; epidemiology/health status).SettingThe survey was distributed to general population through a bilingual (Catalan, Spanish) newspaper in Catalonia (Spain), on December 2003.ParticipantsNewspaper readers of all ages and gender; 9348 surveys were analysed from the 10 783 returned.Main outcome measuresCharacteristics of surveyed population, olfaction by age and gender, smell self-perception and smell impairment risk factors. Terms normosmia, hyposmia and anosmia were used when participants detected, recognised or identified all four, one to three or none of the odours, respectively.ResultsSurvey profile was a 43-year-old woman with medium–high educational level, living in a city. Olfaction was considered normal in 80.6% (detection), 56% (recognition/memory) and 50.7% (identification). Prevalence of smell dysfunction was 19.4% for detection (0.3% anosmia, 19.1% hyposmia), 43.5% for recognition (0.2% anosmia, 43.3% hyposmia) and 48.8% for identification (0.8% anosmia, 48% hyposmia). Olfaction was worse (p<0.0001) in men than in women through all ages. There was a significant age-related smell detection decline however smell recognition and identification increased up to fourth decade and declined after the sixth decade of life. Risk factors for anosmia were: male gender, loss of smell history and poor olfactory self-perception for detection; low educational level, poor self-perception and pregnancy for recognition; and older age, poor self-perception and history of head trauma and loss of smell for identification. Smoking and exposure to noxious substances were mild protective factors for smell recognition.ConclusionsSense of smell in women is better than in men suggesting a learning process during life with deterioration in older ages. Poor self-perception, history of smell loss, head trauma and pregnancy are potential risk factors for olfactory disorders.
Time trend in hospitalised chronic lower respiratory diseases among Danish building and construction workers, 1981–2009: a cohort study
Authors: Tüchsen Finn , Hannerz Harald , Mølgaard Ellen Fisher , Brauer Charlotte , Kirkeskov Lilli 
Published: November 2012

ObjectivesTo show trends in age-standardised hospital admission ratios (SHR) for chronic lower respiratory diseases, estimated for Danish construction workers over three time periods (1981–1990, 1991–2000, 2001–2009).DesignWithin consecutive cohorts of all male building and construction workers in Denmark, selected occupations: bricklayers, carpenters, electricians, painters, plumbers and ‘other construction workers’ were followed up for hospitalisation due to chronic lower respiratory diseases. SHR was calculated for each occupation and time period. Time trend was calculated for construction workers at large using Poisson regression.SettingDenmark.ParticipantsAll gainfully employed male building and construction workers aged 20 or more.Primary and secondary outcome measuresAge-standardised and gender-standardised hospitalisation ratios (SHR).ResultsThe number of hospitalised construction workers at large was reduced from 1134 in the first 10-year period to 699 in the last 9-year period. Among all Danish males, it was, however, even more reduced as reflected in the expected number that was down from 1172 to 617. Hence, SHR increased from 97 during 1981–1990, 100 during 1991–2000 to 113 during 2001–2009. It means that SHR increased with an average rate of 0.76% per year (95% CI 0.28 to 1.24) during the study period. A low SHR=72 (95% CI 60 to 87) was found among carpenters in 1981–1990. From 2001 to 2009, high SHRs were found among painters (SHR=147; 95% CI 111 to 192) and plumbers (SHR=132; 95% CI 101 to 171). In general, the selected groups of construction workers had, however, a low or average SHR due to chronic lower respiratory diseases.ConclusionsThe number of hospitalised workers, suffering from chronic lower respiratory diseases, was reduced over time for construction workers, but for all economically active men, it was reduced even more. Therefore, SHR due to chronic lower respiratory diseases increased over time in the construction industry at large.
Weekend admissions as an independent predictor of mortality: an analysis of Scottish hospital admissions
Authors: Handel Adam E , Patel Sunil V , Skingsley Andrew , Bramley Katrina , Sobieski Roma , Ramagopalan Sreeram V 
Published: November 2012

ObjectivesWeekend admissions have been shown to be associated with an increased risk of mortality compared with weekday admissions for many diagnoses. We analysed emergency department admissions within the Scottish National Health Service to investigate whether mortality is increased in case of weekend emergency department admissions.DesignA cohort study.SettingScotland National Health Service (NHS) emergency departments.Participants5 271 327 emergency department admissions between 1999 and 2009. We included all patients admitted via emergency departments recorded in the Scottish Morbidity Records (SMR01) in NHS, Scotland for whom complete demographic data were available.Primary outcome measuresDeath as recorded by the General Register Office (GRO).ResultsThere was a significantly increased probability of death associated with a weekend emergency admission compared with admission on a weekday (unadjusted OR 1.27, 95% CI 1.26 to 1.28, p<0.0001; adjusted for year of admission, gender, age, deprivation quintile and number of comorbidities OR 1.42, 95% CI 1.40 to 1.43, p<0.0001).ConclusionsDespite a general reduction in mortality over the last 11 years, there is still a significant excess mortality associated with weekend emergency admissions. Further research should be undertaken to identify the precise mechanisms underlying this effect so that measures can be put in place to reduce patient mortality.
Genetic and epigenetic markers in the evaluation of pancreatic masses
Authors: Ginestà Mireia M , Mora Josefina , Mayor Regina , Farré Antoni , Peinado Miquel Angel , Busquets Juli , Serrano Teresa , Capellá Gabriel , Fabregat Joan 
Published: November 2012

BackgroundMethylation markers have shown promise in the early diagnosis of pancreatic carcinoma. The aim of this study was to assess the diagnostic utility of hypermethylation status of candidate genes in combination withKRASmutation detection in the evaluation of pancreatic masses.Experimental designSixty-one fine needle aspirates of pancreatic masses (43 pancreatic adenocarcinomas and 18 chronic pancreatitis) were studied. Methylation status ofHRH2,EN1,SPARC,CDH13andAPCwere analysed using melting curve analysis after DNA bisulfite treatment.KRASmutations were also analysed.ResultsThe methylation panel had a sensitivity of 73% (27 of 37, CI 95% 56 to 86%) and a specificity of 100% whenever two or more promoters were found hypermethylated.KRASmutations showed a sensitivity of 77% (33 of 43, CI 95% 62 to 88%) and a specificity of 100%. Both molecular analyses added useful information to cytology by increasing the number of informative cases. When genetic and epigenetic analyses were combined sensitivity was 84% (36 of 43 CI 95% 69 to 93%) maintaining a 100% specificity.ConclusionsAnalysis of hypermethylation status of a panel of genes andKRASmutation detection offer a similar diagnostic yield in the evaluation of pancreatic masses. The combined molecular analysis increases the number of informative cases without diminishing specificity.
Balloon remodeling for aneurysm coil embolization with the coaxial lumen Scepter C balloon catheter: initial experience at a high volume center
Authors: Spiotta Alejandro M , Miranpuri Amrendra , Hawk Harris , Chaudry M Imran , Turk Aquilla S , Turner Raymond D 
Published: November 2012

IntroductionThe use of balloon remodeling allows for the treatment of aneurysms that were previously considered to be poor candidates for coil embolization. The Scepter C (Microvention, Tustin, California, USA) is a novel temporary occlusion balloon system with a dual coaxial lumen catheter. The design accommodates a more steerable 0.014 inch guidewire with improved control for delivery to the target lesion. We describe our initial experience with the use of this device for balloon remodeling to assist during aneurysm coil embolization.MethodsAll aneurysms that were treated with balloon remodeling employing the Scepter C balloon at a single institution (Medical University of South Carolina) from the time it was available in October 2011 to July 2012 were evaluated. Patient demographics, aneurysm characteristics, procedural success, and adverse events were assessed.Results52 aneurysms were treated in 48 patients (45 women, three men) with a mean age of 59.3±11 years (mean±SD). Mean aneurysm height was 5.9±3 mm, width 4.4±2 mm with a 3.1±2 mm broad neck. A variety of aneurysms were treated. The most commonly utilized size was the 4 mm×10 mm (n=33) balloon. A Raymond 1 (complete occlusion) was achieved in the majority (n=44; 84.6%) of aneurysms, Raymond 2 (residual neck) in five, and Raymond 3 (residual aneurysm) in five. There was one complication (1.9%) attributed directly to balloon use.ConclusionsOur initial experience with the dual coaxial lumen Scepter C occlusion balloon catheter demonstrates its feasibility for use in balloon remodeling for aneurysm coil embolization. A variety of aneurysms at different locations were treated with satisfactory initial angiographic results and adverse event rates.
Efficacy of in‐feed medication with chlortetracycline in a farrow‐to‐finish herd against a clinical outbreak of respiratory disease in fattening pigs
Authors: Del Pozo Sacristán R. , Rodríguez A. L. , Sierens A. , Vranckx K. , Boyen F. , Dereu A. , Haesebrouck F. , Maes D. G. D. 
Published: November 2012

The efficacy of chlortetracycline (CTC) in‐feed medication to treat pigs with clinical respiratory disease was investigated in a farrow‐to‐finish pig herd infected with Mycoplasma hyopneumoniae, and with clinical respiratory disease in growing pigs. In total, 533 pigs were included. The animals were vaccinated against M hyopneumoniae and porcine circovirus type 2 at weaning. At onset of clinical respiratory disease, they were randomly allocated to one of the following treatment groups: chlortetracycline 1 (CTC1) (two consecutive weeks, 500 ppm), chlortetracycline 2 (CTC2) (two non‐consecutive weeks, with a non‐medicated week interval in between, 500 ppm) or tylosin (T) (three consecutive weeks, 100 ppm). Performance (daily weight gain, feed conversion ratio), pneumonia lesions at slaughter and clinical parameters (respiratory disease score) were assessed. Only numeric differences in favour of the CTC2 group were obtained for the performance and the clinical parameters. The prevalence of pneumonia lesions was 20.5, 13.1 and 23.0 per cent (P<0.05) for the CTC1, CTC2 and T groups, respectively. The study demonstrated that CTC, when administered at onset of clinical respiratory disease via the feed at a dose of 500 ppm during two alternative weeks, was able to decrease the prevalence of pneumonia lesions, and numerically reduce performance losses and clinical signs.
Steroid diffusion into the navicular bursa occurs in horses affected by palmar foot pain
Authors: Manfredi J. M. , Boyce M. , Malone E. D. , Anderson C. , Anderson L. B. , Trumble T. N. 
Published: November 2012

Palmar foot pain is frequently treated by steroid injections into the distal interphalangeal joint (DIPJ) in the anticipation that the steroid will diffuse to the navicular bursa and palmar foot structures. The object of this study was to determine if triamcinolone acetonide (TA) would in fact be able to locally diffuse from the DIPJ into the navicular bursa in horses affected by palmar foot pain. Both forelimb DIPJs (nine horses) were injected with 10 mg of TA. Navicular bursa fluid samples, both forelimb and one hind limb (systemic control), were analysed for TA with high‐performance liquid chromatography/tandem mass spectrometry (HPLC‐MS/MS) six hours later. Foot radiographs were graded (0–4) on severity of changes. Forelimb navicular bursa TA concentrations (mean±sd log10, 3.20±0.56) were significantly higher than systemic control concentrations (mean±sd log10, 1.89±0.3) (P<0.0001). Horses with a radiographic grade of >2 were four times as likely to have TA log10 concentrations less than 3.2 (158.49 ng/ml). TA locally diffused from the DIPJ into the navicular bursa in horses affected by palmar foot pain; TA concentrations decreased as radiographic severity increased.
Metallogeny of the Marco zone, Corvet Est, disseminated gold deposit, James Bay, Quebec, Canada
Authors: Aucoin Martin , Beaudoin Georges , Creaser Robert A. , Archer Paul 
Published: November 2012

The Corvet Est gold deposit is hosted by Archean rocks of the Superior Province in the James Bay region, northern Quebec, Canada. The Marco zone is hosted by amphibolite-grade, strongly foliated volcanic rocks and consists of disseminated gold, with an apparent thickness ranging from 1.8 to 39.5 m and gold grades up to 23 g·t–1 over 1 m, that is continuous along strike for ∼1.3 km. The lithotectonic sequence comprises footwall basaltic andesite amphibolite overlain by a lenticular unit of metadacite and then by hanging-wall basaltic andesite amphibolite, all intruded by quartz–feldspar porphyry dikes. Dacite, basaltic andesite amphibolite, and quartz–feldspar porphyry show a calc-alkaline to transitional affinity and plot in the plate margin arc basalt field, with typical volcanic arc trace element patterns. Mineralization consists of pyrite, arsenopyrite, pyrrhotite, chalcopyrite, and gold, disseminated in deformed dacite, in andesite amphibolite, and in quartz–feldspar porphyry dikes. Dacite and andesite display weak alteration characterized by silicification. Native gold forms inclusions in metamorphic quartz, garnet, feldspar, arsenopyrite, and pyrite or free grains interstitial to quartz, feldspar, pyrite, chalcopyrite, and arsenopyrite. Free gold in late quartz veins cut the sericitized metamorphic fabric. Inclusion and interstitial native gold within minerals annealed during metamorphism shows that gold mineralization is pre- to syn-metamorphic, with some gold remobilized in later veins. Rhenium–osmium dating of arsenopyrite yields an isochron age of 2663 ± 13 Ma for mineralization and a weighted average model age of 2632 ± 7 Ma for arsenopyrite formed during peak metamorphism. The ∼2663 Ma arsenopyrite has a low initial 187Os/188Os of 0.19 ± 0.10, suggesting a juvenile crust or a mantle Os source. The sulfur isotope composition of Marco zone pyrite and arsenopyrite shows that sulfur could have been leached from its volcanic host rocks or from reduction of Archean seawater. The Corvet Est deposit is interpreted to be an orogenic gold deposit (2663 Ma) deformed and recrystallized during amphibolite-grade metamorphism (2632 Ma).