bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful carnivore identification with faecal DNA across a fragmented Amazonian landscape
Authors: MICHALSKI FERNANDA , VALDEZ FERNANDA PEDONE , NORRIS DARREN , ZIEMINSKI CHRIS , KASHIVAKURA CYNTIA KAYO , TRINCA CRISTINE S. , SMITH HEATH B. , VYNNE CARLY , WASSER SAMUEL K. , METZGER JEAN PAUL , EIZIRIK EDUARDO 
Published: June 2011

AbstractThe use of scat surveys to obtain DNA has been well documented in temperate areas, where DNA preservation may be more effective than in tropical forests. Samples obtained in the tropics are often exposed to high humidity, warm temperatures, frequent rain and intense sunlight, all of which can rapidly degrade DNA. Despite these potential problems, we demonstrate successful mtDNA amplification and sequencing for faeces of carnivores collected in tropical conditions and quantify how sample condition and environmental variables influence the success of PCR amplification and species identification. Additionally, the feasibility of genotyping nuclear microsatellites from jaguar (Panthera onca) faeces was investigated. From October 2007 to December 2008, 93 faecal samples were collected in the southern Brazilian Amazon. A total of eight carnivore species was successfully identified from 71% of all samples obtained. Information theoretic analysis revealed that the number of PCR attempts before a successful sequence was an important negative predictor across all three responses (success of species identification, success of species identification from the first sequence and PCR amplification success), whereas the relative importance of the other three predictors (sample condition, season and distance from forest edge) varied between the three responses. Nuclear microsatellite amplification from jaguar faeces had lower success rates (15–44%) compared with those of the mtDNA marker. Our results show that DNA obtained from faecal samples works efficiently for carnivore species identification in the Amazon forest and also shows potential for nuclear DNA analysis, thus providing a valuable tool for genetic, ecological and conservation studies.
Investigating the relationship between justice‐vengeance motivations and punitive sentencing recommendations
Authors: Murray Jennifer , Thomson Mary E. , Cooke David J. , Charles Kathy E. 
Published: June 2011

Purpose. The present research investigated the relationship between underlying justice and vengeance motivations and sentencing recommendations made by expert clinicians, semi‐experts, and lay‐people. It was hypothesized that the semi‐experts would recommend significantly different sentence lengths from those recommended by the expert and lay‐person groups, in line with previous research findings. It was also hypothesized that justice and vengeance motivations would be related to punitive sentencing recommendations, and that these would not be the same across the three levels of expertise.Method. An independent groups design was utilized in the main analysis, with participants belonging to three distinct levels of clinical experience (experts, semi‐experts, and lay‐people). A questionnaire was administered, with participants being measured on levels of justice and vengeance motivations, and asked to recommend appropriate sentence lengths based on nine separate crime‐scenarios. These covariables were correlated and the correlation coefficients were compared across the three levels of expertise.Results. The former hypothesis was not upheld. Findings do, however, support the latter hypothesis, with the key finding indicating that for both justice and vengeance motivations in punitive judgement, it is the lay‐participants who appear distinct from the experts and semi‐experts.Conclusions. The current findings emphasize that while expert and lay‐person judgements may often appear to be the same, different processes and motivations underlying clinical judgements are occurring at the different stages of expertise. With the differences in the relationships between justice and vengeance motivations and judgements found in the current research, it is argued that expert and lay judgements that appear to be the same are, in fact, distinguishable and are related to quite different underlying motivations and decision‐making processes.
Enzyme E2 from Chinese White Shrimp Inhibits Replication of White Spot Syndrome Virus and Ubiquitinates Its RING Domain Proteins
Authors: Chen An-Jing , Wang Shuai , Zhao Xiao-Fan , Yu Xiao-Qiang , Wang Jin-Xing 
Published: June 2011

ABSTRACT

Recent studies have shown that the ubiquitin (Ub) proteasome pathway (UPP) is closely related to immune defense. We have identified a ubiquitin-conjugating enzyme, E2, from the Chinese white shrimp,
Fenneropenaeus chinensis
(FcUbc). Injection of recombinant FcUbc protein (rFcUbc) reduced the mortality of shrimp infected with white spot syndrome virus (WSSV) and inhibited replication of WSSV. rFcUbc, but not a mutant FcUbc (mFcUbc), bound to WSSV RING domains (WRDs) from four potential E3 ligase proteins of WSSV
in vitro
. Importantly, rFcUbc could ubiquitinate the RING domains (named WRD2 and WRD3) of WSSV277 and WSSV304 proteins
in vitro
and the two proteins in WSSV-infected
Drosophila melanogaster
Schneider 2 (S2) cells. Furthermore, overexpression of FcUbc increased ubiquitination of WSSV277 and WSSV304 during WSSV infection. In summary, our study demonstrates that FcUbc from Chinese white shrimp inhibited WSSV replication and could ubiquitinate WSSV RING domain-containing proteins. This is the first report about antiviral function of Ubc E2 in shrimp.
Analysis of Rab GTPase-Activating Proteins Indicates that Rab1a/b and Rab43 Are Important for Herpes Simplex Virus 1 Secondary Envelopment
Authors: Zenner Helen L. , Yoshimura Shin-ichiro , Barr Francis A. , Crump Colin M. 
Published: June 2011

ABSTRACT

Assembly of herpes simplex virus 1 (HSV-1) occurs in the cytoplasm, where the capsid and tegument bud into host cell membranes. It is at this point that the viral glycoproteins are incorporated into the virion, as they are located at the assembly site. We investigated the role of the Rab GTPases in coordinating the assembly process by overexpressing 37 human Rab GTPase-activating proteins (GAPs) and assessing infectious titers. Rab GTPases are key cellular regulators of membrane trafficking events that, by their membrane association and binding of effector proteins, ensure the appropriate fusion of membranes. We identified that TBC1D20 and RN-tre and their partner Rabs, Rab1a/b and Rab43, respectively, are important for virion assembly. In the absence of Rab1a/b, the viral glycoproteins are unable to traffic from the endoplasmic reticulum to the assembly compartment, and thus unenveloped particles build up in the cytoplasm. The defect resulting from Rab43 depletion is somewhat more complex, but it appears that the fragmentation and dispersal of the
trans
-Golgi network and associated membranes render these compartments unable to support secondary envelopment.
Identification of a Phosphorylation Site within the P Protein Important for mRNA Transcription and Growth of Parainfluenza Virus 5
Authors: Sun Dengyun , Luthra Priya , Xu Pei , Yoon Haeyoung , He Biao 
Published: June 2011

ABSTRACT
The viral RNA-dependent RNA polymerase (vRdRp) of paramyxovirus consists of the large (L) protein and the phosphoprotein (P). P is heavily phosphorylated, and it is thought that the phosphorylation of P plays a role in regulating viral RNA synthesis. However, no phosphorylation site within the P protein in paramyxovirus has been identified as playing a positive role in viral RNA synthesis in virus infection. Using mass spectrometry analysis, the threonine residue at position 286 of P of parainfluenza virus 5 (PIV5) was found phosphorylated. Mutation of T286 to alanine (T286A), aspartic acid (T286D), or glutamic acid (T286E) reduced minigenome activity. Recombinant virus containing a mutation at the T286 position (rPIV5-P-T286A) grew slower than wild-type virus; viral mRNA synthesis and protein expression of rPIV5-P-T286A were delayed. Biochemical studies showed that the binding of NP or L protein with the P mutants or tetramer formation by the mutant P proteins was unaltered from that for wild-type P. While we failed to rescue rPIV5-P-T286E virus, several revertant viruses were obtained. All non-wild-type revertants had mutations at T286 and showed defects in both minigenome activity and viral growth. This is the first time that a phosphorylation site within the P protein in paramyxovirus has been found to play a positive role in viral mRNA synthesis and virus growth.
Conservation of a Packaging Signal and the Viral Genome RNA Packaging Mechanism in Alphavirus Evolution
Authors: Kim Dal Young , Firth Andrew E. , Atasheva Svetlana , Frolova Elena I. , Frolov Ilya 
Published: June 2011

ABSTRACT
Alphaviruses are a group of small, enveloped viruses which are widely distributed on all continents. In infected cells, alphaviruses display remarkable specificity in RNA packaging by encapsidating only their genomic RNA while avoiding packaging of the more abundant viral subgenomic (SG), cellular messenger and transfer RNAs into released virions. In this work, we demonstrate that in spite of evolution in geographically isolated areas and accumulation of considerable diversity in the nonstructural and structural genes, many alphaviruses belonging to different serocomplexes harbor RNA packaging signals (PSs) which contain the same structural and functional elements. Their characteristic features are as follows. (i) Sindbis, eastern, western, and Venezuelan equine encephalitis and most likely many other alphaviruses, except those belonging to the Semliki Forest virus (SFV) clade, have PSs which can be recognized by the capsid proteins of heterologous alphaviruses. (ii) The PS consists of 4 to 6 stem-loop RNA structures bearing conserved GGG sequences located at the base of the loop. These short motifs are integral elements of the PS and can function even in the artificially designed PS. (iii) Mutagenesis of the entire PS or simply the GGG sequences has strong negative effects on viral genome packaging and leads to release of viral particles containing mostly SG RNAs. (iv) Packaging of RNA appears to be determined to some extent by the number of GGG-containing stem-loops, and more than one stem-loop is required for efficient RNA encapsidation. (v) Viruses of the SFV clade are the exception to the general rule. They contain PSs in the nsP2 gene, but their capsid protein retains the ability to use the nsP1-specific PS of other alphaviruses. These new discoveries regarding alphavirus PS structure and function provide an opportunity for the development of virus variants, which are irreversibly attenuated in terms of production of infectious virus but release high levels of genome-free virions.
Lack of Correlation of Central Nervous System Inflammation and Neuropathology with the Development of Seizures following Acute Virus Infection
Authors: Libbey Jane E. , Kennett Nikki J. , Wilcox Karen S. , White H. Steve , Fujinami Robert S. 
Published: June 2011

ABSTRACTInfection of C57BL/6 mice by the intracerebral route with the Daniels (DA) strain of Theiler's murine encephalomyelitis virus (TMEV) resulted in acute behavioral seizures in approximately 50% of the mice. By titration, the viral dose correlated with the percentage of mice developing seizures; however, neuropathological changes were similar over the dose range, and viral clearance from the brains occurred uniformly by day 14 postinfection (p.i.). Other TMEV strains and mutants (GDVII, WW, BeAn 8386 [BeAn], DApBL2M, H101) induced seizures in C57BL/6 mice to various degrees. The BeAn strain and DApBL2M mutant were similar to the DA strain in the percentages of mice developing seizures and neuropathological changes and in the extent of infected cells. The GDVII and WW strains caused 100% mortality by days 5 and 6 p.i., respectively, at which time neuropathological changes and neuronal infection were extensive. The H101 mutant induced seizures and caused 100% mortality by day 7 p.i.; however, only minor neuropathological changes and few infected cells were observed. Thus, in H101 mutant infections, it appears that elevated levels of cytokines, rather than neuronal cell death, play the dominant role in seizure induction.
A Recombinant Vesicular Stomatitis Virus Bearing a Lethal Mutation in the Glycoprotein Gene Uncovers a Second Site Suppressor That Restores Fusion
Authors: Stanifer Megan L. , Cureton David K. , Whelan Sean P. J. 
Published: June 2011

ABSTRACT

Vesicular stomatitis virus
(VSV), a prototype of the
Rhabdoviridae
family, contains a single surface glycoprotein (G) that is responsible for attachment to cells and mediates membrane fusion. Working with the Indiana serotype of VSV, we employed a reverse genetic approach to produce fully authentic recombinant viral particles bearing lethal mutations in the G gene. By altering the hydrophobicity of the two fusion loops within G, we produced a panel of mutants, W72A, Y73A, Y116A, and A117F, that were nonfusogenic. Propagation of viruses bearing those lethal mutations in G completely depended on complementation by expression of the glycoprotein from the heterologous New Jersey serotype of VSV. The nonfusogenic G proteins oligomerize and are transported normally to the cell surface but fail to mediate acid pH-triggered membrane fusion. The nonfusogenic G proteins also interfered with the ability of wild-type G to mediate fusion, either by formation of mixed trimers or by inhibition of trimer function during fusion. Passage of one recombinant virus, A117F, identified a second site suppressor of the fusion block, E76K. When analyzed in the absence of the A117F substitution, E76K rendered G more sensitive to acid pH-triggered fusion, suggesting that this compensatory mutation is destabilizing. Our work provides a set of authentic recombinant VSV particles bearing lethal mutations in G, confirms that the hydrophobic fusion loops of VSV G protein are critical for membrane fusion, and underscores the importance of the sequence elements surrounding the hydrophobic tips of the fusion loops in driving fusion. This study has implications for understanding dominant targets for inhibition of G-mediated fusion. Moreover, the recombinant viral particles generated here will likely be useful in dissecting the mechanism of G-catalyzed fusion as well as study steps of viral assembly.
Multiple CCR5 Conformations on the Cell Surface Are Used Differentially by Human Immunodeficiency Viruses Resistant or Sensitive to CCR5 Inhibitors
Authors: Berro Reem , Klasse Per Johan , Lascano Danny , Flegler Ayanna , Nagashima Kirsten A. , Sanders Rogier W. , Sakmar Thomas P. , Hope Thomas J. , Moore John P. 
Published: June 2011

ABSTRACT

Resistance to small-molecule CCR5 inhibitors arises when HIV-1 variants acquire the ability to use inhibitor-bound CCR5 while still recognizing free CCR5. Two isolates, CC101.19 and D1/85.16, became resistant via four substitutions in the gp120 V3 region and three in the gp41 fusion peptide (FP), respectively. The binding characteristics of a panel of monoclonal antibodies (MAbs) imply that several antigenic forms of CCR5 are expressed at different levels on the surfaces of U87-CD4-CCR5 cells and primary CD4
+
T cells, in a cell-type-dependent manner. CCR5 binding and HIV-1 infection inhibition experiments suggest that the two CCR5 inhibitor-resistant viruses altered their interactions with CCR5 in different ways. As a result, both mutants became generally more sensitive to inhibition by CCR5 MAbs, and the FP mutant is specifically sensitive to a MAb that stains discrete cell surface clusters of CCR5 that may correspond to lipid rafts. We conclude that some MAbs detect different antigenic forms of CCR5 and that inhibitor-sensitive and -resistant viruses can use these CCR5 forms differently for entry in the presence or absence of CCR5 inhibitors.
Parvovirus B19 Infection of Human Primary Erythroid Progenitor Cells Triggers ATR-Chk1 Signaling, Which Promotes B19 Virus Replication
Authors: Luo Yong , Lou Sai , Deng Xuefeng , Liu Zhengwen , Li Yi , Kleiboeker Steve , Qiu Jianming 
Published: June 2011

ABSTRACT

Human parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells of the human bone marrow. Although the mechanism by which the B19V genome replicates in these cells has not been studied in great detail, accumulating evidence has implicated involvement of the cellular DNA damage machinery in this process. Here, we report that, in
ex vivo
-expanded human erythroid progenitor cells, B19V infection induces a broad range of DNA damage responses by triggering phosphorylation of all the upstream kinases of each of three repair pathways: ATM (ataxia-telangiectasi mutated), ATR (ATM and Rad3 related), and DNA-PKcs (DNA-dependent protein kinase catalytic subunit). We found that phosphorylated ATM, ATR, and DNA-PKcs, and also their downstream substrates and components (Chk2, Chk1, and Ku70/Ku80 complex, respectively), localized within the B19V replication center. Notably, inhibition of kinase phosphorylation (through treatment with either kinase-specific inhibitors or kinase-specific shRNAs) revealed requirements for signaling of ATR and DNA-PKcs, but not ATM, in virus replication. Inhibition of the ATR substrate Chk1 led to similar levels of decreased virus replication, indicating that signaling via the ATR-Chk1 pathway is critical to B19V replication. Notably, the cell cycle arrest characteristic of B19V infection was not rescued by interference with the activity of any of the three repair pathway kinases.
Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype
Authors: Ricardo Sara , Vieira André Filipe , Gerhard Renê , Leitão Dina , Pinto Regina , Cameselle-Teijeiro Jorge F , Milanezi Fernanda , Schmitt Fernando , Paredes Joana 
Published: June 2011

Background and AimThe study of CD44/CD24 and ALDH1 expression is the most accurate method to identify cancer stem cells (CSC) from breast cancer populations. However, the overlap between CD44+CD24−/lowand ALDH1highCSC phenotypes in breast cancer seems to be very small, as well as their distribution among intrinsic breast cancer subtypes. Due to this discrepancy, it is imperative to improve the understanding of breast CSC marker distribution.Methods466 invasive breast carcinomas and eight breast cancer cell lines were analysed for the expression of CD44, CD24 and ALDH1, to evaluate their distribution among the distinct molecular subtypes.ResultsBasal-like tumours (76.5%) contained the higher percentage of cells with the CSC phenotype CD44+CD24−/low(p<0.0001). From ALDH1-positive cases, 39.4% were also basal-like tumours (p<0.0001). The analysis of breast cancer cell lines indicated that luminal cell lines are mainly enriched in a CD44−/lowCD24+cell population, basal/mesenchymal breast cancer cell lines are enriched in the CD44+CD24−/lowphenotype, whereas the remaining basal/epithelial cell lines are mainly positive for both markers. ALDH1 activity was mainly found in HER-OE and basal/epithelial breast cancer cell.ConclusionsCD44+CD24−/lowand ALDH1+phenotypes seem to identify CSC with distinct levels of differentiation. It seems that the paramount method and biomarkers that identify breast CSC within the distinct molecular subtypes need to be better explored, because it is pivotal to translate the CSC concept to clinical practice. In the future, the recognition of reliable markers to distinguish the CSC pool in each molecular subtype will be decisive for the development of specific target therapies.
COMPLEX ACTION SUPPORT FROM COINCIDENCES OF COUPLINGS
Authors: NIELSEN H. B. 
Published: June 2011

Our model (Refs. 1–7) with a complex action in a functional integral formulation with path integrals extending over all times, both past and future, is reviewed. Several numerical relations between coupling constants are presented as supporting evidence. The new evidence is that several more hitherto unexplained coincidences are explained by our model:(1) The "scale problem" is solved because the Higgs field expectation value is predicted to be very small compared to say some fundamental scale, that might be the Planck scale.(2) The Higgs VEV need not be just zero, but rather is predicted to be so that the running top-quark Yukawa coupling just is about to be unity at this scale; in this way the (weak) scale easily becomes "exponentially small." Instead of the top-Yukawa we should rather say the highest flavor Yukawa coupling here.These predictions are only achieved by allowing the principle of minimization of the imaginary part of the action SI(history) to a certain extent adjust some coupling constants in addition to the initial conditions.If supersymmetric partners are not found at LHC it would strengthen the need for a "solution" to the hierarchy problem in our direction of an explanation via a fine-tuning scheme inside the Standard Model, from say minimizing "the imaginary part of the action" in our complex action model.
Myeloid-Derived Suppressor Cell Inhibition of the IFN Response in Tumor-Bearing Mice
Authors: Mundy-Bosse Bethany L. , Lesinski Gregory B. , Jaime-Ramirez Alena C. , Benninger Kristen , Khan Mahmood , Kuppusamy Periannan , Guenterberg Kristan , Kondadasula Sri Vidya , Chaudhury Abhik Ray , La Perle Krista M. , Kreiner Melanie , Young Gregory , Guttridge Denis C. , Carson William E. 
Published: June 2011

AbstractOur group and others have determined that immune effector cells from patients with advanced cancers exhibit reduced activation of IFN signaling pathways. We hypothesized that increases in immune regulatory cells termed myeloid-derived suppressor cells (MDSC) could interfere with the host immune response to tumors by inhibiting immune cell responsiveness to IFNs. The C26 murine adenocarcinoma model was employed to study immune function in advanced malignancy. C26-bearing mice had significantly elevated levels of GR1+CD11b+ MDSC as compared with control mice, and splenocytes from tumor-bearing mice exhibited reduced phosphorylation of STAT1 (P-STAT1) on Tyr701 in response to IFN-α or IFN-γ. This inhibition was seen in splenic CD4+ and CD8+ T cells as well as natural killer cells. In vitro coculture experiments revealed that MDSC inhibited the IFN responsiveness of splenocytes from normal mice. Treatment of C26-bearing mice with gemcitabine or an anti-GR1 antibody led to depletion of MDSC and restored splenocyte IFN responsiveness. Spleens from C26-bearing animals displayed elevated levels of iNOS protein and nitric oxide. In vitro treatment of splenocytes with a nitric oxide donor led to a decreased STAT1 IFN response. The elevation in nitric oxide in C26-bearing mice was associated with increased levels of nitration on STAT1. Finally, splenocytes from iNOS knockout mice bearing C26 tumors exhibited a significantly elevated IFN response as compared with control C26 tumor-bearing mice. These data suggest that nitric oxide produced by MDSC can lead to reduced IFN responsiveness in immune cells. Cancer Res; 71(15); 5101–10. ©2011 AACR.
Overcoming Chemotherapy Resistance in Prostate Cancer
Authors: Madan Ravi A. , Pal Sumanta Kumar , Sartor Oliver , Dahut William L. 
Published: June 2011

Abstract
Although treatment for prostate cancer has improved over the past several years, taxanes remain the only form of chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In addition to the promising therapeutic cancer vaccines and newly developed agents targeting androgen receptor signaling, chemotherapy-based treatments will likely continue to play a significant role in patients with mCRPC. Recently published data that showed that a second taxane (cabazitaxel) extends survival after progression on docetaxel was a significant step forward, but also highlighted the need to overcome taxane resistance in prostate cancer. Preliminary evidence suggests that several treatment strategies may improve the activity of taxanes in prostate cancer and perhaps enhance clinical outcomes. Clin Cancer Res; 17(12); 3892–902. ©2011 AACR.