bluuebunny/crossref_metadata_2025_split huggingface dataset:
The “Bridge” in the Epstein-Barr Virus Alkaline Exonuclease Protein BGLF5 Contributes to Shutoff Activity during Productive Infection
Authors: Horst Daniëlle , Burmeister Wim P. , Boer Ingrid G. J. , van Leeuwen Daphne , Buisson Marlyse , Gorbalenya Alexander E. , Wiertz Emmanuel J. H. J. , Ressing Maaike E. 
Published: June 2012

ABSTRACTReplication of the human herpesvirus Epstein-Barr virus drastically impairs cellular protein synthesis. This shutoff phenotype results from mRNA degradation upon expression of the early lytic-phase protein BGLF5. Interestingly, BGLF5 is the viral DNase, or alkaline exonuclease, homologues of which are present throughout the herpesvirus family. During productive infection, this DNase is essential for processing and packaging of the viral genome. In contrast to this widely conserved DNase activity, shutoff is only mediated by the alkaline exonucleases of the subfamily of gammaherpesviruses. Here, we show that BGLF5 can degrade mRNAs of both cellular and viral origin, irrespective of polyadenylation. Furthermore, shutoff by BGLF5 induces nuclear relocalization of the cytosolic poly(A) binding protein. Guided by the recently resolved BGLF5 structure, mutants were generated and analyzed for functional consequences on DNase and shutoff activities. On the one hand, a point mutation destroying DNase activity also blocks RNase function, implying that both activities share a catalytic site. On the other hand, other mutations are more selective, having a more pronounced effect on either DNA degradation or shutoff. The latter results are indicative of an oligonucleotide-binding site that is partially shared by DNA and RNA. For this, the flexible “bridge” that crosses the active-site canyon of BGLF5 appears to contribute to the interaction with RNA substrates. These findings extend our understanding of the molecular basis for the shutoff function of BGLF5 that is conserved in gammaherpesviruses but not in alpha- and betaherpesviruses.
Genome, Integration, and Transduction of a Novel Temperate Phage of Helicobacter pylori
Authors: Luo Cheng-Hung , Chiou Pei-Yu , Yang Chiou-Ying , Lin Nien-Tsung 
Published: June 2012

ABSTRACTHelicobacter pyloriis a common human pathogen that has been identified to be carcinogenic. This study isolated the temperate bacteriophage 1961P from the lysate of a clinical strain ofH. pyloriisolated in Taiwan. The bacteriophage has an icosahedral head and a short tail, typical of thePodoviridaefamily. Its double-stranded DNA genome is 26,836 bp long and has 33 open reading frames. Only 9 of the predicted proteins have homologs of known functions, while the remaining 24 are only similar to unknown proteins encoded byHelicobacterprophages and remnants. Analysis of sequences proximal to the phage-host junctions suggests that 1961P may integrate into the host chromosome via a mechanism similar to that of bacteriophage lambda. In addition, 1961P is capable of generalized transduction. To the best of our knowledge, this is the first report of the isolation, characterization, genome analysis, integration, and transduction of aHelicobacter pyloriphage.
Human T-Cell Leukemia Virus Type 1 (HTLV-1) bZIP Factor Requires Cellular Transcription Factor JunD To Upregulate HTLV-1 Antisense Transcription from the 3′ Long Terminal Repeat
Authors: Gazon Hélène , Lemasson Isabelle , Polakowski Nicholas , Césaire Raymond , Matsuoka Masao , Barbeau Benoit , Mesnard Jean-Michel , Peloponese Jean-Marie 
Published: June 2012

ABSTRACT

Infection with the human T-cell leukemia virus type 1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia (ATL), a fatal malignancy characterized by the uncontrolled proliferation of virally infected CD4
+
T cells. The HTLV-1 basic leucine zipper factor (HBZ) is believed to contribute to development and maintenance of ATL. Unlike the other HTLV-1 genes, the
hbz
gene is encoded on the complementary strand of the provirus and therefore is not under direct control of the promoter within the 5′ long terminal repeat (LTR) of the provirus. This promoter can undergo inactivating genetic or epigenetic changes during the course of ATL that eliminates expression of all viral genes except that of
hbz
. In contrast, repressive modifications are not known to occur on the
hbz
promoter located in the 3′ LTR, and
hbz
expression has been consistently detected in all ATL patient samples. Although Sp1 regulates basal transcription from the HBZ promoter, other factors that activate transcription remain undefined. In this study, we used a proviral reporter construct deleted of the 5′ LTR to show that HBZ upregulates its own expression through cooperation with JunD. Activation of antisense transcription was apparent in serum-deprived cells in which the level of JunD was elevated, and elimination of JunD expression by gene knockout or shRNA-mediated knockdown abrogated this effect. Activation through HBZ and JunD additionally required Sp1 binding at the
hbz
promoter. These data favor a model in which JunD is recruited to the promoter through Sp1, where it heterodimerizes with HBZ thereby enhancing its activity. Separately,
hbz
gene expression led to an increase in JunD abundance, and this effect correlated with emergence of features of transformed cells in immortalized fibroblasts. Overall, our results suggest that JunD represents a novel therapeutic target for the treatment of ATL.
Selected Drugs with Reported Secondary Cell-Differentiating Capacity Prime Latent HIV-1 Infection for Reactivation
Authors: Shishido Takao , Wolschendorf Frank , Duverger Alexandra , Wagner Frederic , Kappes John , Jones Jennifer , Kutsch Olaf 
Published: June 2012

ABSTRACT

Reactivation of latent HIV-1 infection is considered our best therapeutic means to eliminate the latent HIV-1 reservoir. Past therapeutic attempts to systemically trigger HIV-1 reactivation using single drugs were unsuccessful. We thus sought to identify drug combinations consisting of one component that would lower the HIV-1 reactivation threshold and a synergistic activator. With aclacinomycin and dactinomycin, we initially identified two FDA-approved drugs that primed latent HIV-1 infection in T cell lines and in primary T cells for reactivation and facilitated complete reactivation at the population level. This effect was correlated not with the reported primary drug effects but with the cell-differentiating capacity of the drugs. We thus tested other cell-differentiating drugs/compounds such as cytarabine and aphidicolin and found that they also primed latent HIV-1 infection for reactivation. This finding extends the therapeutic promise of
N
′-
N
′-hexamethylene-bisacetamide (HMBA), another cell-differentiating agent that has been reported to trigger HIV-1 reactivation, into the group of FDA-approved drugs. To this end, it is also noteworthy that suberoylanilide hydroxamic acid (SAHA), a polar compound that was initially developed as a second-generation cell-differentiating agent using HMBA as a structural template and which is now marketed as the histone deacetylase (HDAC) inhibitor vorinostat, also has been reported to trigger HIV-1 reactivation. Our findings suggest that drugs with primary or secondary cell-differentiating capacity should be revisited as HIV-1-reactivating agents as some could potentially be repositioned as candidate drugs to be included in an induction therapy to trigger HIV-1 reactivation.
Paramecium bursaria Chlorella Virus 1 Proteome Reveals Novel Architectural and Regulatory Features of a Giant Virus
Authors: Dunigan David D. , Cerny Ronald L. , Bauman Andrew T. , Roach Jared C. , Lane Leslie C. , Agarkova Irina V. , Wulser Kurt , Yanai-Balser Giane M. , Gurnon James R. , Vitek Jason C. , Kronschnabel Bernard J. , Jeanniard Adrien , Blanc Guillaume , Upton Chris , Duncan Garry A. , McClung O. William , Ma Fangrui , Van Etten James L. 
Published: June 2012

ABSTRACT

The 331-kbp chlorovirus
Paramecium bursaria
chlorella virus 1 (PBCV-1) genome was resequenced and annotated to correct errors in the original 15-year-old sequence; 40 codons was considered the minimum protein size of an open reading frame. PBCV-1 has 416 predicted protein-encoding sequences and 11 tRNAs. A proteome analysis was also conducted on highly purified PBCV-1 virions using two mass spectrometry-based protocols. The mass spectrometry-derived data were compared to PBCV-1 and its host
Chlorella variabilis
NC64A predicted proteomes. Combined, these analyses revealed 148 unique virus-encoded proteins associated with the virion (about 35% of the coding capacity of the virus) and 1 host protein. Some of these proteins appear to be structural/architectural, whereas others have enzymatic, chromatin modification, and signal transduction functions. Most (106) of the proteins have no known function or homologs in the existing gene databases except as orthologs with proteins of other chloroviruses, phycodnaviruses, and nuclear-cytoplasmic large DNA viruses. The genes encoding these proteins are dispersed throughout the virus genome, and most are transcribed late or early-late in the infection cycle, which is consistent with virion morphogenesis.
Antiretroviral Agents Effectively Block HIV Replication after Cell-to-Cell Transfer
Authors: Permanyer Marc , Ballana Ester , Ruiz Alba , Badia Roger , Riveira-Munoz Eva , Gonzalo Encarna , Clotet Bonaventura , Esté José A. 
Published: June 2012

ABSTRACT

Cell-to-cell transmission of HIV has been proposed as a mechanism contributing to virus escape to the action of antiretrovirals and a mode of HIV persistence during antiretroviral therapy. Here, cocultures of infected HIV-1 cells with primary CD4
+
T cells or lymphoid cells were used to evaluate virus transmission and the effect of known antiretrovirals. Transfer of HIV antigen from infected to uninfected cells was resistant to the reverse transcriptase inhibitors (RTIs) zidovudine (AZT) and tenofovir, but was blocked by the attachment inhibitor IgGb12. However, quantitative measurement of viral DNA production demonstrated that all anti-HIV agents blocked virus replication with similar potency to cell-free virus infections. Cell-free and cell-associated infections were equally sensitive to inhibition of viral replication when HIV-1 long terminal repeat (LTR)-driven green fluorescent protein (GFP) expression in target cells was measured. However, detection of GFP by flow cytometry may incorrectly estimate the efficacy of antiretrovirals in cell-associated virus transmission, due to replication-independent Tat-mediated LTR transactivation as a consequence of cell-to-cell events that did not occur in short-term (48-h) cell-free virus infections. In conclusion, common markers of virus replication may not accurately correlate and measure infectivity or drug efficacy in cell-to-cell virus transmission. When accurately quantified, active drugs blocked proviral DNA and virus replication in cell-to-cell transmission, recapitulating the efficacy of antiretrovirals in cell-free virus infections and
in vivo
.
Lineage-Specific Differences between Human and Simian Immunodeficiency Virus Regulation of gp120 Trimer Association and CD4 Binding
Authors: Finzi Andrés , Pacheco Beatriz , Xiang Shi-Hua , Pancera Marie , Herschhorn Alon , Wang Liping , Zeng Xing , Desormeaux Anik , Kwong Peter D. , Sodroski Joseph 
Published: June 2012

ABSTRACT
Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both viruses, the gp120 N/C termini and the inner domain β-sandwich and layer 2 support the noncovalent association of gp120 with the envelope glycoprotein trimer. Layer 1 of the SIVmac gp120 inner domain contributes more to trimer association than the corresponding region of HIV-1 gp120. On the other hand, layer 1 plays an important role in stabilizing the CD4-bound conformation of HIV-1 but not SIVmac gp120 and thus contributes to HIV-1 binding to CD4. In SIVmac, CD4 binding is instead enhanced by tryptophan 375, which fills the Phe 43 cavity of gp120. Activation of SIVmac by soluble CD4 is dependent on tryptophan 375 and on layer 1 residues that determine a tight association of gp120 with the trimer. Distinct biological requirements for CD4 usage have resulted in lineage-specific differences in the HIV-1 and SIV gp120 structures that modulate trimer association and CD4 binding.
Trend Reversal in Lake Michigan Contribution to Snowfall
Authors: Bard Luke , Kristovich David A. R. 
Published: June 2012

AbstractOne of the most notable ways the Laurentian Great Lakes impact the region’s climate is by augmenting snowfall in downwind locations during autumn and winter months. Among many negative consequences, this surplus of snow can cause substantial property damage to homes and can escalate the number of traffic accident–related injuries and fatalities. The consensus among several previous studies is that lake-effect snowfall increased during the twentieth century in various locations in the Great Lakes region. The goal of this study is to better understand variability and long-term trends in Lake Michigan’s lake-contribution snowfall (LCS). LCS accounts for both lake-effect and lake-enhanced events. In addition, this study updates findings from previous investigations using snowfall observations found by a recent study to be appropriate for climate studies. It is demonstrated that considerable variability exists in 5-yr periods of LCS east and south of Lake Michigan from 1920 to 2005. A general increase in LCS from the early 1920s to the 1950–80 period at locations typically downwind of the lake was found. Thereafter, LCS decreased through the early 2000s, indicating a distinct trend reversal that is not reported by earlier studies. The reasons for this reversal are unclear. The reversal is consistent with observed increasing minimum temperatures during winter months after the 1970s, however.
Improved Reconstruction of Global Precipitation since 1900
Authors: Smith Thomas M. , Arkin Phillip A. , Ren Li , Shen Samuel S. P. 
Published: June 2012

Abstract
An improved land–ocean global monthly precipitation anomaly reconstruction is developed for the period beginning in 1900. Reconstructions use the available historical data and statistics developed from the modern satellite-sampled period to analyze variations over the historical presatellite period. This paper documents the latest in a series of precipitation reconstructions developed by the authors. Although the reconstruction principle is still the minimization of mean-squared error, this latest reconstruction includes the following three major improvements over previous reconstructions: (i) an improved method that first produces an annual first guess, which is then adjusted using a monthly increment analysis; (ii) improved use of oceanic observations in the annual first guess using a canonical correlation analysis; and (iii) reinjection of gauge data where those data are available. These improvements allow more confident analyses and evaluations of global precipitation variations over the reconstruction period. Quantitative error estimates for the reconstruction are being developed and will be documented in a later paper.
Impact of Salinity Constraints on the Simulated Mean State and Variability in a Coupled Seasonal Forecast Model
Authors: Zhao Mei , Hendon Harry H. , Alves Oscar , Yin Yonghong , Anderson David 
Published: June 2012

Abstract
The authors assess the sensitivity of the simulated mean state and coupled variability to systematic initial state salinity errors in seasonal forecasts using the Australian Bureau of Meteorology Predictive Ocean Atmosphere Model for Australia (POAMA) coupled model. This analysis is based on two sets of hindcasts that were initialized from old and new ocean initial conditions, respectively. The new ocean initial conditions are provided by an ensemble multivariate analysis system that assimilates subsurface temperatures and salinity and is a clear improvement over the previous system, which was based on univariate optimal interpolation, using static error covariances and assimilating only temperature without updating salinity.
Large systematic errors in the salinity field around the thermocline region of the tropical western and central Pacific produced by the old assimilation scheme are shown to have strong impacts on the predicted mean state and variability in the tropical Pacific for the entire 9 months of the forecast. Forecasts initialized from the old scheme undergo a rapid and systematic adjustment of density that causes large persistent changes in temperature both locally in the western and central Pacific thermocline, but also remotely in the eastern Pacific via excitation of equatorial waves. The initial subsurface salinity errors in the western and central Pacific ultimately result in an altered surface climate because of induced temperature changes in the thermocline that trigger a coupled feedback in the eastern Pacific. These results highlight the importance of accurately representing salinity in initial conditions for climate prediction on seasonal and potentially multiyear time scales.
People living with psychotic illness in 2010: The second Australian national survey of psychosis
Authors: Morgan Vera A , Waterreus Anna , Jablensky Assen , Mackinnon Andrew , McGrath John J , Carr Vaughan , Bush Robert , Castle David , Cohen Martin , Harvey Carol , Galletly Cherrie , Stain Helen J , Neil Amanda L , McGorry Patrick , Hocking Barbara , Shah Sonal , Saw Suzy 
Published: June 2012

Objective: The 2010 Survey of High Impact Psychosis (SHIP) is Australia’s second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data. Methods: The survey covered 1.5 million people aged 18–64 years, approximately 10% of Australians in this age group. A two-phase design was used. In phase 1, screening for psychosis took place in public mental health services and non-government organizations supporting people with mental illness. In phase 2, 1825 of those screen-positive for psychosis were randomly selected and interviewed. Data collected included symptomatology, substance use, functioning, service utilization, medication use, education, employment, housing, and physical health including fasting blood samples. Results: The estimated 1-month treated prevalence of psychotic disorders in public treatment services was 3.1 people per 1000 population; the 12-month treated prevalence was 4.5 people per 1000. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia/schizoaffective disorder. One-half (49.5%) reported attempting suicide in their lifetime and two-thirds (63.2%) were rated as impaired in their ability to socialize. Over half (54.8%) had metabolic syndrome. The proportion currently smoking was 66.1%. Educational achievement was low. Only 21.5% were currently employed. Key changes in the 12 years since the first survey included: a marked drop in psychiatric inpatient admissions; a large increase in the proportion attending community mental health clinics; increased use of rehabilitation services and non-government organizations supporting people with mental illness; a major shift from typical to atypical antipsychotics; and large increases in the proportions with lifetime alcohol or drug abuse/dependence. Conclusion: People with psychotic illness face multiple challenges. An integrated approach to service provision is needed to ensure that their living requirements and needs for social participation are met, in addition to their very considerable mental and physical health needs.
Treatment for severe and enduring anorexia nervosa: A review
Authors: Hay Phillipa J , Touyz Stephen , Sud Rishi 
Published: June 2012

Objective: Many patients with anorexia nervosa develop an intractable and debilitating illness course. Our aims were to (i) conduct a systematic review of randomised controlled trials (RCTs) of treatment for chronic anorexia nervosa participants, and (ii) identify research informing novel therapeutic approaches for this group. Methods: Systematic search (SCOPUS plus previous reviews date 2011) of literature for (i) RCTs of treatment that included anorexia nervosa participants with a mean duration of illness of at least 3 years, (ii) studies reporting new treatments addressing factors associated with chronicity. Results: Evidence of efficacy for treatment approaches in severe and enduring anorexia nervosa is limited. Only one unpublished RCT designed to test a specific psychological approach for these patients was identified. There is a probable advantage for specialist psychotherapy over treatment as usual, and a promising study of relapse prevention with cognitive behaviour therapy (CBT) for anorexia nervosa (CBT-AN). Open trials have, however, reported developments in psychological therapies that warrant further specific evaluation. These include forms of CBT modified for anorexia nervosa, cognitive remediation therapy with emotion skills training, the Maudsley Model for Treatment of Adults with Anorexia Nervosa, the Community Outreach Partnership Program, Specialist Supportive Clinical Management and the approach of Strober with its emphasis on therapeutic alliance and flexible goals. Conclusions: Treatment trials need to move beyond targeting core eating disorder pathology (primarily weight restoration) and examine efficacy and effectiveness in minimising harm and reducing personal and social costs of chronic illness. There is also a need to develop better definitions of chronicity, with or without treatment ‘resistance’ specifiers.
Parental views of food-safety education in a Japanese primary school
Authors: Horikawa Haruka , Akamatsu Rie , Horiguchi Itsuko , Marui Eiji 
Published: June 2012

Objective: This study examined Japanese mothers’ satisfaction with food-safety education in primary schools, compared the characteristics of mothers who were not satisfied, and identified topics that should be included in food-safety education, according to mothers. Design: An online survey was conducted in March 2011 in Japan. The questionnaire included topics related to food-safety education and satisfaction regarding food-safety education. Setting: Japanese mothers with children attending primary school were asked to complete an online questionnaire. Method: A total of 1,300 mothers completed questionnaires. The sample was divided into two groups according to median scores for satisfaction with food-safety education, and chi-square tests were used to compare data related to other questions. The numbers of mothers who selected each topic for inclusion in food-safety education were calculated. Results: Participants were divided into two groups; high satisfaction ( n = 796, 61.2%) and low satisfaction ( n = 504, 38.8%). The low-satisfaction group consisted of mothers who described government action related to the food-safety problem as ‘inadequate’ ( n = 305, 60.5%) and who disagreed with the notion that food items can be 100% safe ( n = 146, 29.0%). More than half of the mothers endorsed ‘judging freshness’, ‘reading food labels’, and ‘food additives’ as important topics to include in food-safety education. Conclusion: Japanese mothers who were not satisfied with food-safety education were more likely to consider government actions inadequate and to disagree with the notion that food items can be 100% safe. Mothers wanted schools to teach not only the prevention of food-borne illnesses but also other topics related to food safety.