bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Amino-Terminal Domain of Alphavirus Capsid Protein Is Dispensable for Viral Particle Assembly but Regulates RNA Encapsidation through Cooperative Functions of Its Subdomains
Authors: Lulla Valeria , Kim Dal Young , Frolova Elena I. , Frolov Ilya 
Published: September 2013

ABSTRACT
Venezuelan equine encephalitis virus (VEEV) is a pathogenic alphavirus, which circulates in the Central, South, and North Americas, including the United States, and represents a significant public health threat. In recent years, strong progress has been made in understanding the structure of VEEV virions, but the mechanism of their formation has yet to be investigated. In this study, we analyzed the functions of different capsid-specific domains and its amino-terminal subdomains in viral particle formation. Our data demonstrate that VEEV particles can be efficiently formed directly at the plasma membrane without cytoplasmic nucleocapsid preassembly. The entire amino-terminal domain of VEEV capsid protein was found to be dispensable for particle formation. VEEV variants encoding only the capsid's protease domain efficiently produce genome-free VEEV virus-like particles (VLPs), which are very similar in structure to the wild-type virions. The amino-terminal domain of the VEEV capsid protein contains at least four structurally and functionally distinct subdomains, which mediate RNA packaging and the specificity of packaging in particular. The most positively charged subdomain is a negative regulator of the nucleocapsid assembly. The three other subdomains are not required for genome-free VLP formation but are important regulators of RNA packaging. Our data suggest that the positively charged surface of the VEEV capsid-specific protease domain and the very amino-terminal subdomain are also involved in interaction with viral RNA and play important roles in RNA encapsidation. Finally, we show that VEEV variants with mutated capsid acquire compensatory mutations in either capsid or nsP2 genes.
Encapsidation of Host-Derived Factors Correlates with Enhanced Infectivity of Sindbis Virus
Authors: Sokoloski Kevin J. , Snyder Anthony J. , Liu Natalia H. , Hayes Chelsea A. , Mukhopadhyay Suchetana , Hardy Richard W. 
Published: September 2013

ABSTRACT

The genus
Alphavirus
consists of a group of enveloped, single-stranded RNA viruses, many of which are transmitted by arthropods to a wide range of vertebrate host species. Here we report that Sindbis virus (SINV) produced from a representative mammalian cell line consists of at least two unique particle subpopulations, separable on the basis of virion density. In contrast, mosquito-derived SINV consists of a homogeneous population of particles. Our findings indicate that the denser particle subpopulation, SINV
Heavy
, is more infectious on a per-particle basis than SINV
Light
. SINV produced in mosquito cell lines (SINV
C6/36
) exhibited particle-to-PFU ratios similar to those observed for SINV
Heavy
. In mammalian cells, viral RNA was synthesized and accumulated more rapidly following infection with SINV
Heavy
or SINV
C6/36
than following infection with SINV
Light
, due partly to enhanced translation of viral genomic RNA early in infection. Analysis of the individual particle subpopulations indicated that SINV
Heavy
and SINV
C6/36
contain host-derived factors whose presence correlates with the enhanced translation, RNA synthesis, and infectivity observed for these particles.
Chlamydia and gonorrhoea infections and the risk of adverse obstetric outcomes: a retrospective cohort study
Authors: Liu Bette , Roberts Christine L , Clarke Marilyn , Jorm Louisa , Hunt Jennifer , Ward James 
Published: September 2013

ObjectivesTo examine the association between prior chlamydia and gonorrhoea infections and adverse obstetric outcomes.MethodsRecords of women resident in New South Wales, Australia with a singleton first birth during 1999–2008 were linked to chlamydia and gonorrhoea notifications using probabilistic linkage. Obstetric outcomes and potential confounders were ascertained from the birth record. Logistic regression, adjusted for potential confounders was used to estimate the association between a disease notification prior to the birth and adverse birth outcomes: spontaneous preterm birth (SPTB), small for gestational age (SGA) and stillbirth.ResultsAmong 354 217 women, 1.0% (n=3658) had a prior chlamydia notification; 0.06% (n=196) had a prior gonorrhoea notification. The majority of notifications (>80%) occurred before the estimated conception date. 4.1% of women had a SPTB, 12.1% had a SGA baby and 0.6% of women had a stillbirth. Among women with a prior chlamydia notification, the risk of SPTB and stillbirth was increased, aOR 1.17 (95% CI 1.01 to 1.37) and aOR 1.40 (95% CI 1.00 to 1.96) respectively but there was no association with SGA, aOR 0.99 (95% CI 0.89 to 1.09). For women with gonorrhoea the risks for SPTB, stillbirth and SGA were respectively aOR 2.50 (95%CI 1.39 to 4.50), 2.35 (95% CI 0.58 to 9.56) and 0.98 (95% CI 0.58 to 1.68). Among women with a prior chlamydia diagnosis, the risk of SPTB did not differ between women diagnosed >1 year prior to conception, within the year prior to conception or during the pregnancy, (p=0.9).ConclusionsSexually transmissible infections in pregnancy and the preconception period may be important in predicting pregnancy outcomes.
Reaching Economies of Scale to Be a Viable Ongoing Entity
Authors: Long Michael S. , Wijeyaratne Isuru Devaka 
Published: September 2013

This paper empirically considers economies of scale that firms must reach to be considered viable ongoing entities. These are estimated from the selling prices of actual firms in two broad industries — service and manufacturing. For service firms, the minimum size is $10 million in annual revenues and for manufacturing firms, it is smaller at $6 million in sales to reach economies of scale. Traditional economic theory considers firms becoming more efficient with increasing size until they reach an optimal economy of scale. Until they reach that size, we show that they cannot be considered truly ongoing firms and cannot be valued directly as the present value of future earnings. When firms are also independent of their owner/manager, we consider that a viable ongoing entity exists.
Resistance to CDK2 Inhibitors Is Associated with Selection of Polyploid Cells inCCNE1-Amplified Ovarian Cancer
Authors: Etemadmoghadam Dariush , Au-Yeung George , Wall Meaghan , Mitchell Chris , Kansara Maya , Loehrer Elizabeth , Batzios Crisoula , George Joshy , Ftouni Sarah , Weir Barbara A. , Carter Scott , Gresshoff Irma , Mileshkin Linda , Rischin Danny , Hahn William C. , Waring Paul M. , Getz Gad , Cullinane Carleen , Campbell Lynda J. , Bowtell David D. 
Published: September 2013

AbstractPurpose: Amplification of cyclin E1 (CCNE1) is associated with poor outcome in breast, lung, and other solid cancers, and is the most prominent structural variant associated with primary treatment failure in high-grade serous ovarian cancer (HGSC). We have previously shown that CCNE1-amplified tumors show amplicon-dependent sensitivity to CCNE1 suppression. Here, we explore targeting CDK2 as a novel therapeutic strategy in CCNE1-amplified cancers and mechanisms of resistance.Experimental Design: We examined the effect of CDK2 suppression using RNA interference and small-molecule inhibitors in SK-OV-3, OVCAR-4, and OVCAR-3 ovarian cancer cell lines. To identify mechanisms of resistance, we derived multiple, independent resistant sublines of OVCAR-3 to CDK2 inhibitors. Resistant cells were extensively characterized by gene expression and copy number analysis, fluorescence-activated cell sorting profiling and conventional karyotyping. In addition, we explored the relationship between CCNE1 amplification and polyploidy using data from primary tumors.Results: We validate CDK2 as a therapeutic target in CCNE1-amplified cells by showing selective sensitivity to suppression, either by gene knockdown or using small-molecule inhibitors. In addition, we identified two resistance mechanisms, one involving upregulation of CDK2 and another novel mechanism involving selection of polyploid cells from the pretreatment tumor population. Our analysis of genomic data shows that polyploidy is a feature of cancer genomes with CCNE1 amplification.Conclusions: These findings suggest that cyclinE1/CDK2 is an important therapeutic target in HGSC, but that resistance to CDK2 inhibitors may emerge due to upregulation of CDK2 target protein and through preexisting cellular polyploidy. Clin Cancer Res; 19(21); 5960–71. ©2013 AACR.
Coamplification and Cooperation: Toward Identifying Biologically Relevant Oncogenes
Authors: Huang Guochang , Singh Bhuvanesh 
Published: September 2013

Abstract
Identification of biologically relevant genes from genomic assays is limited by the complexity of changes present in most solid tumors. Assessing for coactivation of functionally related genes resulted in the identification of SENP2, DCUN1D1, and DVL3—consensus candidates that drive selection for 3q amplification in lung squamous cell carcinomas. Clin Cancer Res; 19(20); 5549–51. ©2013 AACR.
Better Performance of CARs Deprived of the PD-1 Brake
Authors: Morales-Kastresana Aizea , Labiano Sara , Quetglas José I. , Melero Ignacio 
Published: September 2013

Abstract
Immunotherapies often permit combinations to increase efficacy. Two approaches are currently leading our field: adoptive therapy with T cells transfected with chimeric antigen receptors and monoclonal antibodies blocking the PD-1/PD-L1 (B7-H1) axis. In this issue of Clinical Cancer Research, preclinical evidence for a synergistic combination of such approaches is reported. Clin Cancer Res; 19(20); 5546–8. ©2013 AACR.
A brief review of genus Catopta Staudinger, 1899 (Lepidoptera: Cossidae) with description of a new species from China
Authors: YAKOVLEV ROMAN V. , SALDAITIS AIDAS , KONS HUGO JR. , BORTH ROBERT 
Published: September 2013

A checklist of the genus Catopta Staudinger, 1889 is presented. A new species, С. dusii sp. nov., from the Xiling Xue Shan Mountains of in the Noth West China’s Sichuan Province is described.
A new species of Anchylorhynchus Schoenherr (Coleoptera: Curculionidae) from the Amazon, with a record of a new host palm for the genus
Authors: VALENTE ROBERTA DE MELO , DE MEDEIROS BRUNO AUGUSTO SOUZA 
Published: September 2013

Anchylorhynchus vanini sp. nov. from the Amazon is described, including the mouthparts and male genitalia. The new species is compared with similar species within the genus and the key to the species of Anchylorhynchus provided by Vaurie (1954) is modified to include the new species. Adult specimens were collected in flowers of the palm Syagrus vermicularis Noblick and additional collections in other palms species suggest that this association is specific. This is the first record of the palm Syagrus vermicularis as host for a species of Anchylorhynchus.
Preventive coping among people with severe mental illness in daily life: Strategies used and associations with mood
Authors: Yanos Philip T , Rosario Arlety 
Published: September 2013

Background: Preventive coping refers to efforts that are taken to reduce the likelihood of experiencing, or lessen the impact of, stress in the future. Aims: The present investigation explored the use of preventive strategies in daily life among people with severe mental illness, and examined the association between types of preventive strategies used and end-of-day mood. Methods: Participants included 27 adults diagnosed with severe mental illness who completed up to 20 daily interviews each (375 interviews were completed in total), which assessed preventive coping and end-of-day mood. Results: The most commonly (across participants) and frequently (within participant days) endorsed preventive strategies were accessing social support and engaging in activities/hobbies. Participants tended to have less positive mood at end-of-day on days in which either no, or more passive, strategies were used. Conclusions: Findings supported that preventive strategies are frequently used by members of this population, and that accessing social support and engaging in activities/hobbies are the most frequently used preventive strategies. Findings also suggest that the use of no or more passive preventive strategies was associated with less positive mood at end of day.
Telephone Versus Face-to-Face Interviews
Authors: Vogl Susanne 
Published: September 2013

Usually, semistructured interviews are conducted face-to-face, and because of the importance of personal contact in qualitative interviews, telephone interviews are often discounted. Missing visual communication can make a telephone conversation appear less personal and more anonymous but can also help prevent some distortions and place the power imbalance between adult interviewer and (child) respondent into perspective. In this article telephone and face-to-face interviews are compared in order to analyse the general applicability of telephone interviews and their peculiarities when researching children. The data consists of 112 semistructured interviews with 56 children aged 5, 7, 9 and 11, conducted in Germany. Each child was interviewed twice; once on the telephone and once face-to-face. By triangulating qualitative and quantitative analytical steps, both interview modes are compared from a number of perspectives. The results showed very little difference between the two modes of interview and therefore challenge the reluctance to conduct semistructured telephone interviews, both in qualitative research and with children. Dependent on the research question, relevant distinctions could be the lower interviewer involvement, the lower number of opinions and suggestions stated by respondents and fewer signs of tension and tension release in telephone interviews.
Topical Levobupivacaine Efficacy in Pain Control after Functional Endoscopic Sinus Surgery
Authors: Yılmaz Süleyman , Yıldızbaş Şahnur , Güçlü Ender , Yaman Hüseyin , Yalçın Sezen Gülbin 
Published: September 2013

ObjectiveThe aim of this study was to find out the efficacy of a polyvinyl alcohol (PVA) sponge (Merocel Kennedy; Medtronic Xomed, Jacksonville, Florida) sinus pack soaked with levobupivacaine hydrochloride to control postoperative pain and analgesic need following functional endoscopic sinus surgery (FESS).Study DesignThe study was designed as a prospective, double‐blind, randomized, controlled study. Forty‐one patients who underwent FESS were included in the analysis.SettingA tertiary referral hospital in Turkey.Materials and MethodsPatients who underwent FESS were divided into 2 groups. The PVA sponge sinus packs were soaked with 5 mL of levobupivacaine hydrochloride (chirocaine 25 mg/10 mL; Abbott, Nycomed Pharma AS, Elverum, Norway) in group I and with 5 mL of saline in group II.Main Outcome MeasuresPostoperative pain levels were recorded using a visual analog scale (VAS score, 0‐100) at 30 minutes and 1, 2, 8, 12, and 24 hours.ResultsThere were no statistically significant differences between groups regarding age, sex, and American Society of Anesthesiologists status. Postoperative VAS values at 30 minutes and 1, 2, 8, 12, and 24 hours were significantly lower in group I than in group II (P <. 05). Supplemental analgesia amount was significantly lower in group I than in group II (P =. 003).ConclusionUsing levobupivacaine‐soaked PVA sponge sinus packs after FESS is an effective, easy, and quick method to control postoperative pain, and it improves patient comfort and tolerability.
PRDM1/BLIMP1 is commonly inactivated in anaplastic large T-cell lymphoma
Authors: Boi Michela , Rinaldi Andrea , Kwee Ivo , Bonetti Paola , Todaro Maria , Tabbò Fabrizio , Piva Roberto , Rancoita Paola M. V. , Matolcsy András , Timar Botond , Tousseyn Thomas , Rodríguez-Pinilla Socorro Maria , Piris Miguel A. , Beà Sílvia , Campo Elias , Bhagat Govind , Swerdlow Steven H. , Rosenwald Andreas , Ponzoni Maurilio , Young Ken H. , Piccaluga Pier Paolo , Dummer Reinhard , Pileri Stefano , Zucca Emanuele , Inghirami Giorgio , Bertoni Francesco 
Published: September 2013

Key Points
The commonest lesions in anaplastic large cell lymphomas are losses at 17p13 and at 6q21, concomitant in up to one-quarter of the cases. PRDM1 (BLIMP1) gene (6q21) is inactivated by multiple mechanisms and acts as a tumor suppressor gene in anaplastic large B-cell lymphoma.
Profiling circulating microRNA expression in a mouse model of nerve allotransplantation
Authors: Rau Cheng-Shyuan , Yang Johnson Chia-Shen , Wu Shao-Chun , Chen Yi-Chun , Lu Tsu-Hsiang , Lin Ming-Wei , Wu Yi-Chan , Tzeng Siou-Ling , Wu Chia-Jung , Hsieh Ching-Hua 
Published: September 2013

Abstract

Background
The lack of noninvasive biomarkers of rejection remains a challenge in the accurate monitoring of deeply buried nerve allografts and precludes optimization of therapeutic intervention. This study aimed to establish the expression profile of circulating microRNAs (miRNAs) during nerve allotransplantation with or without immunosuppression.

Results
Balb/c mice were randomized into 3 experimental groups, that is, (1) untreated isograft (Balb/c → Balb/c), (2) untreated allograft (C57BL/6 → Balb/c), and (3) allograft (C57BL/6 → Balb/c) with FK506 immunosuppression. A 1-cm Balb/c or C57BL/6 donor sciatic nerve graft was transplanted into sciatic nerve gaps created in recipient mice. At 1, 3, 7, 10, and 14 d after nerve transplantation, nerve grafts, whole blood, and sera were obtained for miRNA expression analysis with an miRNA array and subsequent validation with quantitative real-time PCR (qRT-PCR). Three circulating miRNAs (miR-320, miR-762, and miR-423-5p) were identified in the whole blood and serum of the mice receiving an allograft with FK506 immunosuppression, within 2 weeks after nerve allotransplantation. However, these 3 circulating miRNAs were not expressed in the nerve grafts. The expression of all these 3 upregulated circulating miRNAs significantly decreased at 2, 4, and 6 d after discontinuation of FK506 immunosuppression. In the nerve graft, miR-125-3b and miR-672 were significantly upregulated in the mice that received an allograft with FK506 only at 7 d after nerve allotransplantation.

Conclusions
We identified the circulating miR-320, miR-762, and miR-423-5p as potential biomarkers for monitoring the immunosuppression status of the nerve allograft. However, further research is required to investigate the mechanism behind the dysregulation of these markers and to evaluate their prognostic value in nerve allotransplantation.
Study of the in vivo role of Mce2R, the transcriptional regulator of mce2 operon in Mycobacterium tuberculosis
Authors: Forrellad Marina Andrea , Bianco María Verónica , Blanco Federico Carlos , Nuñez Javier , Klepp Laura Inés , Vazquez Cristina Lourdes , Santangelo María de la Paz , Rocha Rosana Valeria , Soria Marcelo , Golby Paul , Gutierrez Maximiliano Gabriel , Bigi Fabiana 
Published: September 2013

Abstract

Background
Tuberculosis is one of the leading causes of mortality throughout the world. Mycobacterium tuberculosis, the agent of human tuberculosis, has developed strategies involving proteins and other compounds called virulence factors to subvert human host defences and damage and invade the human host. Among these virulence-related proteins are the Mce proteins, which are encoded in the mce1, mce2, mce3 and mce4 operons of M. tuberculosis. The expression of the mce2 operon is negatively regulated by the Mce2R transcriptional repressor. Here we evaluated the role of Mce2R during the infection of M. tuberculosis in mice and macrophages and defined the genes whose expression is in vitro regulated by this transcriptional repressor.

Results
We used a specialized transduction method for generating a mce2R mutant of M. tuberculosis H37Rv. Although we found equivalent replication of the MtΔmce2R mutant and the wild type strains in mouse lungs, overexpression of Mce2R in the complemented strain (MtΔmce2RComp) significantly impaired its replication. During in vitro infection of macrophages, we observed a significantly increased association of the late endosomal marker LAMP-2 to MtΔmce2RComp-containing phagosomes as compared to MtΔmce2R and the wild type strains. Whole transcriptional analysis showed that Mce2R regulates mainly the expression of the mce2 operon, in the in vitro conditions studied.

Conclusions
The findings of the current study indicate that Mce2R weakly represses the in vivo expression of the mce2 operon in the studied conditions and argue for a role of the proteins encoded in Mce2R regulon in the arrest of phagosome maturation induced by M. tuberculosis.
Investigation of CCL18 and A1AT as potential urinary biomarkers for bladder cancer detection
Authors: Miyake Makito , Ross Shanti , Lawton Adrienne , Chang Myron , Dai Yunfeng , Mengual Lourdes , Alcaraz Antonio , Giacoia Evan Gomes , Goodison Steve , Rosser Charles J 
Published: September 2013

Abstract

Background
In this study, we further investigated the association of two biomarkers, CCL18 and A1AT, with bladder cancer (BCa) and evaluated the influence of potentially confounding factors in an experimental model.

Methods
In a cohort of 308 subjects (102 with BCa), urinary concentrations of CCL18 and A1AT were assessed by enzyme-linked immunosorbent assay (ELISA). In an experimental model, benign or cancerous cells, in addition to blood, were added to urines from healthy controls and analyzed by ELISA. Lastly, immunohistochemical staining for CCL18 and A1AT in human bladder tumors was performed.

Results
Median urinary protein concentrations of CCL18 (52.84 pg/ml vs. 11.13 pg/ml, p < 0.0001) and A1AT (606.4 ng/ml vs. 120.0 ng/ml, p < 0.0001) were significantly elevated in BCa subjects compared to controls. Furthermore, the addition of whole blood to pooled normal urine resulted in a significant increase in both CCL18 and A1AT. IHC staining of bladder tumors revealed CCL18 immunoreactivity in inflammatory cells only, and there was no significant increase in these immunoreactive cells within benign and cancerous tissue and no association with BCa grade nor stage was noted. A1AT immunoreactivity was observed in the cytoplasm of epithelia cells and intensity of immunostaining increased with tumor grade, but not tumor stage.

Conclusions
Further development of A1AT as a diagnostic biomarker for BCa is warranted.