bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpes Simplex Virus 2 MicroRNA miR-H6 Is a Novel Latency-Associated Transcript-Associated MicroRNA, but Reduction of Its Expression Does Not Influence the Establishment of Viral Latency or the Recurrence Phenotype
Authors: Tang Shuang , Bertke Andrea S. , Patel Amita , Margolis Todd P. , Krause Philip R. 
Published: February 2011

ABSTRACT

The herpes simplex virus 2 (HSV-2) viral microRNA (miRNA) designated miR-H6 is located upstream of the latency-associated transcript (LAT) promoter region on the strand opposite the LAT. Deletion of the LAT promoter and part of LAT exon 1 abolished HSV-2 miR-H6 expression in acutely and latently infected guinea pig dorsal root ganglia (DRG), suggesting that this region is needed both for the expression of LAT-encoded miRNAs and for miR-H6 expression
in vivo
. Relative to cells infected with a viral rescuant, miR-H6 expression was significantly reduced in cells infected with a mutant HSV-2 virus, NotPolyA, with an insertion of a simian virus (SV40) polyadenylation signal sequence between the LAT promoter and miR-H6 sequences. In addition, expression of miR-H6, but not LAT or viral DNA, was significantly reduced in both mouse trigeminal ganglia (TG) and guinea pig DRG latently infected with the NotPolyA mutant. Guinea pigs infected with NotPolyA experienced reduced neurological complications of acute infection relative to those infected with the rescuant, but the recurrence phenotype of the NotPolyA mutant was similar to those of its rescuant and wild-type HSV-2, indicating that reduction of miR-H6 expression is not by itself able to alter the establishment of latency for the wild-type virus or the recurrence phenotype. Furthermore, the mutation in NotPolyA did not affect the propensity of wild-type HSV-2 to establish latency in neurons positive for subtype marker KH10. In contrast to published reports regarding its HSV-1 homolog, HSV-2 miR-H6 did not affect ICP4 expression in transfected or infected cells. We hypothesize that viral miRNAs associated with LAT expression are likely to work collectively, contributing to the phenotype attributed to the LAT.
Regulation of Foamy Virus Protease Activity by Viral RNA: a Novel and Unique Mechanism among Retroviruses
Authors: Hartl Maximilian J. , Bodem Jochen , Jochheim Fabian , Rethwilm Axel , Rösch Paul , Wöhrl Birgitta M. 
Published: February 2011

ABSTRACT

Foamy viruses (FVs) synthesize the Pol precursor protein from a specific transcript. Thus, in contrast to what was found for orthoretroviruses, e.g., human immunodeficiency virus, no Gag-Pol precursor protein is synthesized. Foamy viral Pol consists of a protease (PR) domain, a reverse transcriptase domain, and an integrase domain and is processed into a mature protease-reverse transcriptase (PR-RT) fusion protein and the integrase. Protease activity has to be strictly regulated in order to avoid premature Gag and Pol processing before virus assembly. We have demonstrated recently that FV protease is an inactive monomer with a very weak dimerization tendency and postulated protease activation through dimerization. Here, we identify a specific protease-activating RNA motif (PARM) located in the
pol
region of viral RNA which stimulates PR activity
in vitro
and
in vivo
, revealing a novel and unique mechanism of retroviral protease activation. This mechanism is strikingly different to that of orthoretroviruses, where the protease can be activated even in the absence of viral RNA during the assembly of virus-like particles. Although it has been shown that the integrase domain is important for Pol uptake, activation of the foamy virus protease is integrase independent. We show that at least two foamy virus PR-RT molecules bind to the PARM and only RNAs containing the PARM result in significant activation of the protease. DNA harboring the PARM is not capable of protease activation. Structure determination of the PARM by selective 2′ hydroxyl acylation analyzed by primer extension (SHAPE) revealed a distinct RNA folding, important for protease activation and thus virus maturation.
Recombinant Adenovirus Serotype 26 (Ad26) and Ad35 Vaccine Vectors Bypass Immunity to Ad5 and Protect Nonhuman Primates against Ebolavirus Challenge
Authors: Geisbert Thomas W. , Bailey Michael , Hensley Lisa , Asiedu Clement , Geisbert Joan , Stanley Daphne , Honko Anna , Johnson Joshua , Mulangu Sabue , Pau Maria Grazia , Custers Jerome , Vellinga Jort , Hendriks Jenny , Jahrling Peter , Roederer Mario , Goudsmit Jaap , Koup Richard , Sullivan Nancy J. 
Published: February 2011

ABSTRACT

The use of adenoviruses (Ad) as vaccine vectors against a variety of pathogens has demonstrated their capacity to elicit strong antibody and cell-mediated immune responses. Adenovirus serotype C vectors, such as Ad serotype 5 (Ad5), expressing Ebolavirus (EBOV) glycoprotein (GP), protect completely after a single inoculation at a dose of 10
10
viral particles. However, the clinical application of a vaccine based on Ad5 vectors may be hampered, since impairment of Ad5 vaccine efficacy has been demonstrated for humans and nonhuman primates with high levels of preexisting immunity to the vector. Ad26 and Ad35 segregate genetically from Ad5 and exhibit lower seroprevalence in humans, making them attractive vaccine vector alternatives. In the series of studies presented, we show that Ad26 and Ad35 vectors generate robust antigen-specific cell-mediated and humoral immune responses against EBOV GP and that Ad5 immune status does not affect the generation of GP-specific immune responses by these vaccines. We demonstrate partial protection against EBOV by a single-shot Ad26 vaccine and complete protection when this vaccine is boosted by Ad35 1 month later. Increases in efficacy are paralleled by substantial increases in T- and B-cell responses to EBOV GP. These results suggest that Ad26 and Ad35 vectors warrant further development as candidate vaccines for EBOV.
Marburg Virus VP40 Antagonizes Interferon Signaling in a Species-Specific Manner
Authors: Valmas Charalampos , Basler Christopher F. 
Published: February 2011

ABSTRACT

Marburgviruses are zoonotic pathogens that cause lethal hemorrhagic fever in humans and nonhuman primates. However, they do not cause lethal disease in immunocompetent mice unless they are adapted to this species. The adaptation process can therefore provide insight into the specific virus-host interactions that determine virulence. In primate cells, the
Lake Victoria marburgvirus
Musoke strain (MARV) VP40 matrix protein antagonizes alpha/beta interferon (IFN-α/β) and IFN-γ signaling by inhibiting the activation of the cellular tyrosine kinase Jak1. Here, VP40 from the Ravn strain (RAVV VP40)—from a distinct Marburg virus clade—is demonstrated to also inhibit IFN signaling in human cells. However, neither MARV nor RAVV VP40 effectively inhibited IFN-signaling in mouse cells, as assessed by assays of the antiviral effects of IFN-α/β and the IFN-α/β-induced phosphorylation of Jak1, STAT1, and STAT2. In contrast, the VP40 from a mouse-adapted RAVV (maRAVV) did inhibit IFN signaling. Effective Jak1 inhibition correlated with the species from which the cells were derived and did not depend upon whether Jak1 was of human or mouse origin. Of the seven amino acid changes that accumulated in VP40 during mouse adaptation, two (V57A and T165A) are sufficient to allow efficient IFN signaling antagonism by RAVV VP40 in mouse cells. The same two changes also confer efficient IFN antagonist function upon MARV VP40 in mouse cells. The mouse-adaptive changes did not affect the budding of RAVV VP40 in mouse cells, suggesting that this second major function of VP40 did not undergo adaptation. These data identify an apparent determinant of RAVV host range and virulence and define specific genetic determinants of this function.
Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies
Authors: Wu Xueling , Changela Anita , O'Dell Sijy , Schmidt Stephen D. , Pancera Marie , Yang Yongping , Zhang Baoshan , Gorny Miroslaw K. , Phogat Sanjay , Robinson James E. , Stamatatos Leonidas , Zolla-Pazner Susan , Kwong Peter D. , Mascola John R. 
Published: February 2011

ABSTRACT
HIV-1 is neutralized by a class of antibodies that preferentially recognize a site formed on the assembled viral spike. Such quaternary structure-specific antibodies have diverse neutralization breadths, with antibodies PG16 and PG9 able to neutralize 70 to 80% of circulating HIV-1 isolates while antibody 2909 is specific for strain SF162. We show that alteration between a rare lysine and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. Quaternary structure-specific antibodies appear to target antigenic variants of the same epitope, with neutralization breadth determined by the prevalence of recognized variants among circulating isolates.
The Progression from MGUS to Smoldering Myeloma and Eventually to Multiple Myeloma Involves a Clonal Expansion of Genetically Abnormal Plasma Cells
Authors: López-Corral Lucía , Gutiérrez Norma C. , Vidriales Maria Belén , Mateos Maria Victoria , Rasillo Ana , García-Sanz Ramón , Paiva Bruno , San Miguel Jesús F. 
Published: February 2011

Abstract
Purpose: Genetic aberrations detected in multiple myeloma (MM) have also been reported in the premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Our aim was to investigate in depth the level of clonal heterogeneity of recurrent genetic abnormalities in these conditions.
Experimental Design: Immunoglobulin heavy chain (IGH) translocations, 13q14 and 17p13 deletions, and 1q21 gains using FISH were evaluated in 90 MGUS, 102 high-risk SMM, and 373 MM. To this end, we not only purified plasma cells (PC) for the FISH analysis (purity &gt; 90%), but subsequently, we examined the correlation between the proportion of PC with cytogenetic changes and the number of clonal PC present in the same sample, as measured by multiparametric flow cytometry.
Results: We observed a significant difference between the proportion of clonal PC with specific genetic abnormalities in MGUS compared with SMM and in SMM compared with MM. Thus, the median proportion of PC with IGH translocations globally considered, t(11;14) and 13q deletions was significantly lower in MGUS than in SMM, and in SMM than in MM [IGH translocations: 34% vs. 57% vs. 76%; t(11;14): 38% vs. 61% vs. 81%; and 13q deletion: 37% vs. 61% vs. 74% in MGUS, SMM, and MM, respectively]. For t(4;14), the difference was significant in the comparison between MGUS/SMM and MM and for 1q between MGUS and SMM/MM.
Conclusions: This study demonstrates that the progression from MGUS to SMM, and eventually to MM, involves a clonal expansion of genetically abnormal PC. Clin Cancer Res; 17(7); 1692–700. ©2011 AACR.
Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis
Authors: Sumegi Janos , Barnes Michael G. , Nestheide Shawnagay V. , Molleran-Lee Susan , Villanueva Joyce , Zhang Kejian , Risma Kimberly A. , Grom Alexei A. , Filipovich Alexandra H. 
Published: February 2011

Abstract
Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically heterogeneous autosomal recessive immune disorder that results when the critical regulatory pathways that mediate immune defense mechanisms and the natural termination of immune/inflammatory responses are disrupted or overwhelmed. To advance the understanding of FHL, we performed gene expression profiling of peripheral blood mononuclear cells from 11 children with untreated FHL. Total RNA was isolated and gene expression levels were determined using microarray analysis. Comparisons between patients with FHL and normal pediatric controls (n = 30) identified 915 down-regulated and 550 up-regulated genes with more than or equal to 2.5-fold difference in expression (P ≤ .05). The expression of genes associated with natural killer cell functions, innate and adaptive immune responses, proapoptotic proteins, and B- and T-cell differentiation were down-regulated in patients with FHL. Genes associated with the canonical pathways of interleukin-6 (IL-6), IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling and genes encoding of antiapoptotic proteins were overexpressed in patients with FHL. This first study of genome-wide expression profiling in children with FHL demonstrates the complexity of gene expression patterns, which underlie the immunobiology of FHL.
Myosin-cross-reactive antigen (MCRA) protein from Bifidobacterium breve is a FAD-dependent fatty acid hydratase which has a function in stress protection
Authors: Rosberg-Cody Eva , Liavonchanka Alena , Göbel Cornelia , Ross R Paul , O'Sullivan Orla , Fitzgerald Gerald F , Feussner Ivo , Stanton Catherine 
Published: February 2011

Abstract

Background
The aim of this study was to determine the catalytic activity and physiological role of myosin-cross-reactive antigen (MCRA) from Bifidobacterium breve NCIMB 702258. MCRA from B. breve NCIMB 702258 was cloned, sequenced and expressed in heterologous hosts (Lactococcus and Corynebacterium) and the recombinant proteins assessed for enzymatic activity against fatty acid substrates.

Results
MCRA catalysed the conversion of palmitoleic, oleic and linoleic acids to the corresponding 10-hydroxy fatty acids, but shorter chain fatty acids were not used as substrates, while the presence of trans-double bonds and double bonds beyond the position C12 abolished hydratase activity. The hydroxy fatty acids produced were not metabolised further. We also found that heterologous Lactococcus and Corynebacterium expressing MCRA accumulated increasing amounts of 10-HOA and 10-HOE in the culture medium. Furthermore, the heterologous cultures exhibited less sensitivity to heat and solvent stresses compared to corresponding controls.

Conclusions
MCRA protein in B. breve can be classified as a FAD-containing double bond hydratase, within the carbon-oxygen lyase family, which may be catalysing the first step in conjugated linoleic acid (CLA) production, and this protein has an additional function in bacterial stress protection.
The Complete Mitochondrial Genome of an 11,450-year-old Aurochsen (Bos primigenius) from Central Italy
Authors: Lari Martina , Rizzi Ermanno , Mona Stefano , Corti Giorgio , Catalano Giulio , Chen Kefei , Vernesi Cristiano , Larson Greger , Boscato Paolo , De Bellis Gianluca , Cooper Alan , Caramelli David , Bertorelle Giorgio 
Published: February 2011

Abstract

Background

Bos primigenius, the aurochs, is the wild ancestor of modern cattle breeds and was formerly widespread across Eurasia and northern Africa. After a progressive decline, the species became extinct in 1627. The origin of modern taurine breeds in Europe is debated. Archaeological and early genetic evidence point to a single Near Eastern origin and a subsequent spread during the diffusion of herding and farming. More recent genetic data are instead compatible with local domestication events or at least some level of local introgression from the aurochs. Here we present the analysis of the complete mitochondrial genome of a pre-Neolithic Italian aurochs.

Results
In this study, we applied a combined strategy employing both multiplex PCR amplifications and 454 pyrosequencing technology to sequence the complete mitochondrial genome of an 11,450-year-old aurochs specimen from Central Italy. Phylogenetic analysis of the aurochs mtDNA genome supports the conclusions from previous studies of short mtDNA fragments - namely that Italian aurochsen were genetically very similar to modern cattle breeds, but highly divergent from the North-Central European aurochsen.

Conclusions
Complete mitochondrial genome sequences are now available for several modern cattle and two pre-Neolithic mtDNA genomes from very different geographic areas. These data suggest that previously identified sub-groups within the widespread modern cattle mitochondrial T clade are polyphyletic, and they support the hypothesis that modern European breeds have multiple geographic origins.
The living microarray: a high-throughput platform for measuring transcription dynamics in single cells
Authors: Rajan Saravanan , Djambazian Haig , Dang Huan Chu Pham , Sladek Rob , Hudson Thomas J 
Published: February 2011

Abstract

Background
Current methods of measuring transcription in high-throughput have led to significant improvements in our knowledge of transcriptional regulation and Systems Biology. However, endpoint measurements obtained from methods that pool populations of cells are not amenable to studying time-dependent processes that show cell heterogeneity.

Results
Here we describe a high-throughput platform for measuring transcriptional changes in real time in single mammalian cells. By using reverse transfection microarrays we are able to transfect fluorescent reporter plasmids into 600 independent clusters of cells plated on a single microscope slide and image these clusters every 20 minutes. We use a fast-maturing, destabilized and nuclear-localized reporter that is suitable for automated segmentation to accurately measure promoter activity in single cells. We tested this platform with synthetic drug-inducible promoters that showed robust induction over 24 hours. Automated segmentation and tracking of over 11 million cell images during this period revealed that cells display substantial heterogeneity in their responses to the applied treatment, including a large proportion of transfected cells that do not respond at all.

Conclusions
The results from our single-cell analysis suggest that methods that measure average cellular responses, such as DNA microarrays, RT-PCR and chromatin immunoprecipitation, characterize a response skewed by a subset of cells in the population. Our method is scalable and readily adaptable to studying complex systems, including cell proliferation, differentiation and apoptosis.
The maternal and early embryonic transcriptome of the milkweed bug Oncopeltus fasciatus
Authors: Ewen-Campen Ben , Shaner Nathan , Panfilio Kristen A , Suzuki Yuichiro , Roth Siegfried , Extavour Cassandra G 
Published: February 2011

Abstract

Background
Most evolutionary developmental biology ("evo-devo") studies of emerging model organisms focus on small numbers of candidate genes cloned individually using degenerate PCR. However, newly available sequencing technologies such as 454 pyrosequencing have recently begun to allow for massive gene discovery in animals without sequenced genomes. Within insects, although large volumes of sequence data are available for holometabolous insects, developmental studies of basally branching hemimetabolous insects typically suffer from low rates of gene discovery.

Results
We used 454 pyrosequencing to sequence over 500 million bases of cDNA from the ovaries and embryos of the milkweed bug Oncopeltus fasciatus, which lacks a sequenced genome. This indirectly developing insect occupies an important phylogenetic position, branching basal to Diptera (including fruit flies) and Hymenoptera (including honeybees), and is an experimentally tractable model for short-germ development. 2,087,410 reads from both normalized and non-normalized cDNA assembled into 21,097 sequences (isotigs) and 112,531 singletons. The assembled sequences fell into 16,617 unique gene models, and included predictions of splicing isoforms, which we examined experimentally. Discovery of new genes plateaued after assembly of ~1.5 million reads, suggesting that we have sequenced nearly all transcripts present in the cDNA sampled. Many transcripts have been assembled at close to full length, and there is a net gain of sequence data for over half of the pre-existing O. fasciatus accessions for developmental genes in GenBank. We identified 10,775 unique genes, including members of all major conserved metazoan signaling pathways and genes involved in several major categories of early developmental processes. We also specifically address the effects of cDNA normalization on gene discovery in de novo transcriptome analyses.

Conclusions
Our sequencing, assembly and annotation framework provide a simple and effective way to achieve high-throughput gene discovery for organisms lacking a sequenced genome. These data will have applications to the study of the evolution of arthropod genes and genetic pathways, and to the wider evolution, development and genomics communities working with emerging model organisms.
[The sequence data from this study have been submitted to GenBank under study accession number SRP002610 (http://www.ncbi.nlm.nih.gov/sra?term=SRP002610). Custom scripts generated are available at http://www.extavourlab.com/protocols/index.html. Seven Additional files are available.]
Studies on Escherichia coliHflKC suggest the presence of an unidentified λ factor that influences the lysis-lysogeny switch
Authors: Bandyopadhyay Kaustav , Parua Pabitra K , Datta Ajit B , Parrack Pradeep 
Published: February 2011

Abstract

Background
The lysis-lysogeny decision in the temperate coliphage λ is influenced by a number of phage proteins (CII and CIII) as well as host factors, viz. Escherichia coli HflB, HflKC and HflD. Prominent among these are the transcription factor CII and HflB, an ATP-dependent protease that degrades CII. Stabilization of CII promotes lysogeny, while its destabilization induces the lytic mode of development. All other factors that influence the lytic/lysogenic decision are known to act by their effects on the stability of CII. Deletion of hflKC has no effect on the stability of CII. However, when λ infects ΔhflKC cells, turbid plaques are produced, indicating stabilization of CII under these conditions.

Results
We find that CII is stabilized in ΔhflKC cells even without infection by λ, if CIII is present. Nevertheless, we also obtained turbid plaques when a ΔhflKC host was infected by a cIII-defective phage (λcIII

67
). This observation raises a fundamental question: does lysogeny necessarily correlate with the stabilization of CII? Our experiments indicate that CII is indeed stabilized under these conditions, implying that stabilization of CII is possible in ΔhflKC cells even in the absence of CIII, leading to lysogeny.

Conclusion
We propose that a yet unidentified CII-stabilizing factor in λ may influence the lysis-lysogeny decision in ΔhflKC cells.
Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers
Authors: Domínguez-Sánchez María S , Sáez Carmen , Japón Miguel A , Aguilera Andrés , Luna Rosa 
Published: February 2011

Abstract

Background
One key step in gene expression is the biogenesis of mRNA ribonucleoparticle complexes (mRNPs). Formation of the mRNP requires the participation of a number of conserved factors such as the THO complex. THO interacts physically and functionally with the Sub2/UAP56 RNA-dependent ATPase, and the Yra1/REF1/ALY RNA-binding protein linking transcription, mRNA export and genome integrity. Given the link between genome instability and cancer, we have performed a comparative analysis of the expression patterns of THOC1, a THO complex subunit, and ALY in tumor samples.

Methods
The mRNA levels were measured by quantitative real-time PCR and hybridization of a tumor tissue cDNA array; and the protein levels and distribution by immunostaining of a custom tissue array containing a set of paraffin-embedded samples of different tumor and normal tissues followed by statistical analysis.

Results
We show that the expression of two mRNP factors, THOC1 and ALY are altered in several tumor tissues. THOC1 mRNA and protein levels are up-regulated in ovarian and lung tumors and down-regulated in those of testis and skin, whereas ALY is altered in a wide variety of tumors. In contrast to THOC1, ALY protein is highly detected in normal proliferative cells, but poorly in high-grade cancers.

Conclusions
These results suggest a differential connection between tumorogenesis and the expression levels of human THO and ALY. This study opens the possibility of defining mRNP biogenesis factors as putative players in cell proliferation that could contribute to tumor development.