bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normalization and binning of historical and multi‐source microsatellite data: overcoming the problems of allele size shift with allelogram
Authors: MORIN PHILLIP A. , MANASTER CARL , MESNICK SARAH L. , HOLLAND ROBERT 
Published: May 2009

AbstractMicrosatellite allele data have long been plagued by size shifts that can at best make it difficult to accurately assign genotypes to allele products, and at worse can cause whole batches of data from different instruments, dates or laboratories to be incorrectly assigned. Although modern genotyping technology (capillary electrophoresis) has overcome many of these problems, concern remains regarding the consistency of scores within a laboratory over time and between laboratories when combining data from multiple sources into a single analysis. There remain a large number of laboratories using older technologies or combining data from multiple sources. In addition, thousands of data sets that could potentially be expanded as samples become available are generally regarded as unusable because of the effort that would be required to validate congruence of genotypes from old and new data sets. We present methods to normalize and bin alleles from multiple data sources using a relatively small set of controls and the freely available program allelogram.
PACT: A Collaborative Team Model for Treating High Conflict Families in Family Court
Authors: Brown Joe H. , Bledsoe Linda , Yankeelov Pamela , Christensen Dana , Rowan Noell L. , Cambron Mary Lou 
Published: May 2009

ABSTRACTThis article describes a court‐community model program for high conflict divorced families that is designed to reduce the level of inter‐parental conflict including: a) child exposure to inter‐parental conflict; and b) the frequency of re‐litigation over residential arrangements and parenting plans. The six‐session (16‐hour) program combines conflict resolution and group/community support. The program provides a “Personal Support Team” and “Personal Plan of Action” to help each parent control emotions and maintain agreement. The results of research conducted to explore the effect of the program on level of triangulation and inter‐parental conflict, as well as the frequency of re‐litigation over parenting plans, residential arrangements, and parenting time are reported.
Families of Origin, Foster Care Experience, and the Transition to Adulthood
Authors: Holland Donna Dea 
Published: May 2009

ABSTRACTThe rising number of young adults transitioning to adulthood from the foster care system has been a focus of prior research. The current study explored foster care youths transitions to adulthood to identify factors that contribute to or inhibit prosocial adult outcomes. Structured data derived from interviews with foster care‐experienced adults and child welfare professionals as well as focus groups with foster care‐experienced adults and foster parents were analyzed using content analysis to examine the transition to adulthood from foster care. Positive or negative life outcomes resulted from two key mechanisms: a) issues related to family of origin (inadequate parenting, abuse); and b) foster care experiences (including a pattern of “drift”). We explore disidentification, a new social psychological concept. Throughout, key players provide policy recommendations for the child welfare system.
Differential LiveMycobacterium tuberculosis-,M. bovisBCG-, Recombinant ESAT6-, and Culture Filtrate Protein 10-Induced Immunity in Tuberculosis
Authors: Hasan Zahra , Jamil Bushra , Ashraf Mussarat , Islam Muniba , Dojki Maqboola , Irfan Muhammad , Hussain Rabia 
Published: May 2009

ABSTRACTThe high prevalence ofMycobacterium tuberculosismakes it imperative that immune responses to evaluate could be predictive of infection. We investigated liveMycobacterium- and recombinant antigen-induced cytokine and chemokine responses in patients with active tuberculosis (TB) compared with those of healthy controls from an area where TB is endemic (ECs).M. tuberculosis-,M. bovisBCG-, ESAT6-, and culture filtrate protein 10 (CFP10)-induced responses were determined in peripheral blood mononuclear cells from patients with pulmonary TB (n= 38) and ECs (n= 39). The levels of the cytokines gamma interferon (IFN-γ) and interleukin-10 (IL-10) and the chemokines CCL2, CCL3, and CXCL9 were measured. The levels ofM. tuberculosis- and BCG-induced IFN-γ secretion were significantly reduced (P= 0.002 andP< 0.01, respectively), while the amount of IL-10 induced by both virulent (P< 0.01) and avirulent (P= 0.002) mycobacteria was increased in patients with TB. The ESAT6-induced IFN-γ responses were increased in the patients with TB (P= 0.013) compared with those in the EC group. When tuberculin skin test (TST)-negative (TST−; induration, <10 mm) and TST-positive (TST+) donors were studied separately, both TST−and TST+individuals showed increased IFN-γ responses toM. tuberculosiscompared with the responses of the patients with TB (P= 0.037 andP= 0.006, respectively). However, only TST+ECs showed reduced IFN-γ responses to ESAT6 (P= 0.008) compared with the responses of the patients with TB. The levels ofM. tuberculosis-induced CCL2 (P= 0.006) and CXCL9 (P= 0.017) were greater in the patients with TB. The levels of CCL3 secretion in response toMycobacteriumand antigen stimulation were comparable between the two groups. While the levels of ESAT6-induced chemokines did not differ between the patients with TB and the ECs, the levels of CFP10-induced CCL2 (P= 0.01) and CXCL9 (P= 0.001) were increased in the patients. These data indicate differential host IFN-γ, CXCL9, and CCL2 responses to live mycobacteria and mycobacterial antigens and have implications for the identification of potential biomarkers of infection which could be used for the diagnosis of TB.
Comparison of Two Multiple-Locus Variable-Number Tandem-Repeat Analysis Methods for Molecular Strain Typing of Human
Brucella melitensis
Isolates from the Middle East
Authors: Tiller Rebekah V. , De Barun K. , Boshra Marie , Huynh Lynn Y. , Van Ert Matthew N. , Wagner David M. , Klena John , Mohsen T. S. , El-Shafie S. S. , Keim Paul , Hoffmaster Alex R. , Wilkins Patricia P. , Pimentel Guillermo 
Published: May 2009

ABSTRACT

Brucella
species are highly monomorphic, with minimal genetic variation among species, hindering the development of reliable subtyping tools for epidemiologic and phylogenetic analyses. Our objective was to compare two distinct multiple-locus variable-number tandem-repeat analysis (MLVA) subtyping methods on a collection of 101
Brucella melitensis
isolates from sporadic human cases of brucellosis in Egypt (
n
= 83), Qatar (
n
= 17), and Libya (
n
= 1). A gel-based MLVA technique, MLVA-15
IGM
, was compared to an automated capillary electrophoresis-based method, MLVA-15
NAU
, with each MLVA scheme examining a unique set of variable-number tandem repeats. Both the MLVA
IGM
and MLVA
NAU
methods were highly discriminatory, resolving 99 and 101 distinct genotypes, respectively, and were able to largely separate genotypes from Egypt and Qatar. The MLVA-15
NAU
scheme presented higher strain-to-strain diversity in our test population than that observed with the MLVA-15
IGM
assay. Both schemes were able to genetically correlate some strains originating from the same hospital or region within a country. In addition to comparing the genotyping abilities of these two schemes, we also compared the usability, limitations, and advantages of the two MLVA systems and their applications in the epidemiological genotyping of human
B. melitensis
strains.
Genotypic Prediction of Human Immunodeficiency Virus Type 1 CRF02-AG Tropism
Authors: Raymond Stéphanie , Delobel Pierre , Mavigner Maud , Cazabat Michelle , Souyris Corinne , Encinas Stéphanie , Sandres-Sauné Karine , Pasquier Christophe , Marchou Bruno , Massip Patrice , Izopet Jacques 
Published: May 2009

ABSTRACT
We assessed the performance of genotypic algorithms for predicting the tropism of human immunodeficiency virus type 1 coreceptor usage in 52 patients infected with the CRF02-AG subtype. The combined criteria of the 11/25 and net charge rules accurately detected CXCR4-using CRF02-AG viruses, whereas the Geno2pheno tool lacked sensitivity and the position-specific scoring matrix (PSSM) tool WebPSSM lacked specificity.
Characterization of a Highly Conserved Domain within the Severe Acute Respiratory Syndrome Coronavirus Spike Protein S2 Domain with Characteristics of a Viral Fusion Peptide
Authors: Madu Ikenna G. , Roth Shoshannah L. , Belouzard Sandrine , Whittaker Gary R. 
Published: May 2009

ABSTRACT

Many viral fusion proteins are primed by proteolytic cleavage near their fusion peptides. While the coronavirus (CoV) spike (S) protein is known to be cleaved at the S1/S2 boundary, this cleavage site is not closely linked to a fusion peptide. However, a second cleavage site has been identified in the severe acute respiratory syndrome CoV (SARS-CoV) S2 domain (R797). Here, we investigated whether this internal cleavage of S2 exposes a viral fusion peptide. We show that the residues immediately C-terminal to the SARS-CoV S2 cleavage site SFIEDLLFNKVTLADAGF are very highly conserved across all CoVs. Mutagenesis studies of these residues in SARS-CoV S, followed by cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for residues L803, L804, and F805 in membrane fusion. Mutation of the most N-terminal residue (S798) had little or no effect on membrane fusion. Biochemical analyses of synthetic peptides corresponding to the proposed S2 fusion peptide also showed an important role for this region in membrane fusion and indicated the presence of α-helical structure. We propose that proteolytic cleavage within S2 exposes a novel internal fusion peptide for SARS-CoV S, which may be conserved across the
Coronaviridae
.
Features Distinguishing Epstein-Barr Virus Infections of Epithelial Cells and B Cells: Viral Genome Expression, Genome Maintenance, and Genome Amplification
Authors: Shannon-Lowe Claire , Adland Emily , Bell Andrew I. , Delecluse Henri-Jacques , Rickinson Alan B. , Rowe Martin 
Published: May 2009

ABSTRACT

Epstein-Barr virus (EBV) is associated with malignant diseases of lymphoid and epithelial cell origin. The tropism of EBV is due to B-cell-restricted expression of CD21, the major receptor molecule for the virus. However, efficient infection of CD21
−
epithelial cells can be achieved via transfer from EBV-coated B cells. We compare and contrast here the early events following in vitro infection of primary B cells and epithelial cells. Using sensitive, quantitative reverse transcription-PCR assays for several latent and lytic transcripts and two-color immunofluorescence staining to analyze expression at the single cell level, we confirmed and extended previous reports indicating that the two cell types support different patterns of transcription. Furthermore, whereas infection of B cells with one or two copies of EBV resulted in rapid amplification of the viral genome to >20 copies per cell, such amplification was not normally observed after infection of primary epithelial cells or undifferentiated epithelial lines. In epithelial cells, EBNA1 expression was detected in only ca. 40% of EBER
+
cells, and the EBV genome was subsequently lost during prolonged culture. One exception was that infection of AGS, a gastric carcinoma line, resulted in maintenance of EBNA1 expression and amplification of the EBV episome. In contrast to B cells, where amplification of the EBV episome occurred even with a replication-defective BZLF1-knockout virus, amplification in AGS cells was dependent upon early lytic cycle gene expression. These data highlight the influence of the host cell on the outcome of EBV infection with regard to genome expression, amplification, and maintenance.
Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques
Authors: Sexton Amy , De Rose Robert , Reece Jeanette C. , Alcantara Sheilajen , Loh Liyen , Moffat Jessica M. , Laurie Karen , Hurt Aeron , Doherty Peter C. , Turner Stephen J. , Kent Stephen J. , Stambas John 
Published: May 2009

ABSTRACTThere is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker β7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.
Dissecting the Unique Nucleotide Specificity of Mimivirus Nucleoside Diphosphate Kinase
Authors: Jeudy Sandra , Lartigue Audrey , Claverie Jean-Michel , Abergel Chantal 
Published: May 2009

ABSTRACT

The analysis of the
Acanthamoeba polyphaga
mimivirus genome revealed the first virus-encoded nucleoside diphosphate kinase (NDK), an enzyme that is central to the synthesis of RNA and DNA, ubiquitous in cellular organisms, and well conserved among the three domains of life. In contrast with the broad specificity of cellular NDKs for all types of ribo- and deoxyribonucleotides, the mimivirus enzyme exhibits a strongly preferential affinity for deoxypyrimidines. In order to elucidate the molecular basis of this unique substrate specificity, we determined the three-dimensional (3D) structure of the
Acanthamoeba polyphaga
mimivirus NDK alone and in complex with various nucleotides. As predicted from a sequence comparison with cellular NDKs, the 3D structure of the mimivirus enzyme exhibits a shorter Kpn loop, previously recognized as a main feature of the NDK active site. The structure of the viral enzyme in complex with various nucleotides also pinpointed two residue changes, both located near the active site and specific to the viral NDK, which could explain its stronger affinity for deoxynucleotides and pyrimidine nucleotides. The role of these residues was explored by building a set of viral NDK variants, assaying their enzymatic activities, and determining their 3D structures in complex with various nucleotides. A total of 26 crystallographic structures were determined at resolutions ranging from 2.8 Å to 1.5 Å. Our results suggest that the mimivirus enzyme progressively evolved from an ancestral NDK under the constraints of optimizing its efficiency for the replication of an AT-rich (73%) viral genome in a thymidine-limited host environment.
The Trifunctional Antibody Ertumaxomab Destroys Tumor Cells That Express Low Levels of Human Epidermal Growth Factor Receptor 2
Authors: Jäger Michael , Schoberth Alexandra , Ruf Peter , Hess Jürgen , Lindhofer Horst 
Published: May 2009

AbstractHuman epidermal growth factor receptor 2 (HER2/neu) is an important target for the treatment of the breast cancers in which it is overexpressed. However, no approved anti-HER2/neu therapy is available for the majority of breast cancer patients, who express HER2/neu at low levels (with scores of 1+ or 2+/fluorescence in situ hybridization–negative). The trifunctional antibody ertumaxomab targets HER2/neu, CD3, and activating Fcγ receptors. In presence of ertumaxomab, tri-cell complexes consisting of tumor cells, T cells, and accessory cells form to cause tumor cell lysis. In a phase I trial with metastatic breast cancer patients, ertumaxomab could be applied safely and resulted in radiographically confirmed clinical responses. In this study, we compare ertumaxomab- and trastuzumab-mediated killing of cancer cell lines that express HER2/neu at low and high levels. Under optimal conditions for trastuzumab-mediated destruction of HER2/neu-overexpressing cells, only ertumaxomab was able to mediate the elimination of tumor cell lines that express HER2/neu at low levels (1+). Ertumaxomab-mediated activity was accompanied by a Th1-based cytokine release, a unique mode of action of trifunctional antibodies. Competitive binding studies with trastuzumab and 520C9 mapped the binding site of ertumaxomab to the extracellular regions II and III of the HER2/neu ectodomain. This site is distinct from the binding site of trastuzumab, so that HER2/neu-expressing tumor cells can be eliminated by ertumaxomab in the presence of high amounts of trastuzumab. The ability of ertumaxomab to induce cytotoxicity against various tumor cell lines, including those with low HER2/neu antigen density, may provide a novel therapeutic option for breast cancer patients who are not eligible for trastuzumab treatment. [Cancer Res 2009;69(10):4270–6]
Host Genetic Variants in the Interleukin-6 Promoter Predict Poor Outcome in Patients with Estrogen Receptor-Positive, Node-Positive Breast Cancer
Authors: DeMichele Angela , Gray Robert , Horn Michelle , Chen Jinbo , Aplenc Richard , Vaughan William P. , Tallman Martin S. 
Published: May 2009

Abstract
Interleukin-6 modulates immune response, estrogen production, and growth pathways in breast cancer. We evaluated the effect of several common, functional interleukin-6 promoter variants in node-positive breast cancer patients enrolled on a multicenter, cooperative group, adjuvant chemotherapy trial to determine whether these variants were associated with clinical outcome overall and by estrogen receptor tumor phenotype. Genomic DNA and clinical data were collected from a clinical trial of adjuvant anthracycline-based chemotherapy followed by randomization to high-dose cyclophosphamide/thiotepa or observation (Intergroup Trial 0121). Genotyping for -174G&gt;C (rs1800795), -597G&gt;A (rs1800797), and -572G&gt;C (rs1800796) was done by site-specific PCR and PyroSequencing, whereas the -373AnTn repeat was directly sequenced. Log-rank tests and Cox modeling were used to compare outcomes by genotype/haplotype and other factors. Three hundred forty-six patients (64% of trial) had corresponding genotype/clinical data available and did not differ from overall trial participants. After adjustment, patients with estrogen receptor-positive tumors and genotypes 597 GG or 174 GG had significantly worse disease-free survival [hazard ratio (HR), 1.6; P = 0.02 and HR, 1.71; P = 0.007, respectively], whereas the 373 8A12T repeat appeared to be protective (HR, 0.62; P = 0.02). The presence of at least one copy of the haplotype ([-597G, -572G, -373[10A/11T], -174G]) was associated with worse disease-free survival (HR, 1.46; P = 0.04). Kaplan-Meier plots show that all patients in this group relapsed by 24 months from diagnosis. This poor-risk haplotype was quite common overall (estimated frequency, 0.20) and twice as frequent among Blacks (estimated frequency, 0.41). [Cancer Res 2009;69(10):4184–91]
Intracellular Bacterial Vectors That Induce CD8+ T Cells with Similar Cytolytic Abilities but Disparate Memory Phenotypes Provide Contrasting Tumor Protection
Authors: Stark Felicity C. , Sad Subash , Krishnan Lakshmi 
Published: May 2009

Abstract
Induction of a functional CD8+ T-cell response is the important criterion for cancer vaccines, and it is unclear whether acute or chronic live vectors are better suited for cancer antigen delivery. We have evaluated the tumor protective ability of two recombinant vectors, Listeria monocytogenes (LM) and Salmonella typhimurium (ST), both expressing ovalbumin (OVA). Although both vectors induced a similar OVA-specific CD8+ T-cell response in the long term, LM-OVA induced mainly central-phenotype (TCM, CD44highCD62Lhigh), whereas ST-OVA induced mainly effector-phenotype (TEM, CD44highCD62Llow) cells. Both vectors induced functional OVA-specific CD8+ T cells that expressed IFN-γ and killed targets specifically in vivo. However, only LM-OVA–vaccinated mice were protected against B16-OVA tumors. This correlated to the ability of CD8+ T cells generated against LM-OVA, but not against ST-OVA, to produce interleukin 2 and exhibit profound homeostatic and antigen-induced proliferation in vivo. Furthermore, adoptive transfer of memory CD8+ T cells generated against LM-OVA (but not against ST-OVA) into recipient mice resulted in their trafficking to tumor-draining lymph nodes conferring protection. Although cytotoxicity and IFN-γ production are considered to be the principal functions of memory CD8+ T cells, the vaccine delivery strategy may also influence memory CD8+ T-cell quality, and ability to proliferate and traffic to tumors. Thus, for efficacy, cancer vaccines should be selected for their ability to induce self-renewing memory CD8+ T cells (CD44highIL-7RαhighCD62Lhigh) besides their effector functions. [Cancer Res 2009;69(10):4327–34]
Activation of Src by Protein Tyrosine Phosphatase 1B Is Required for ErbB2 Transformation of Human Breast Epithelial Cells
Authors: Arias-Romero Luis E. , Saha Sayanti , Villamar-Cruz Olga , Yip Shu-Chin , Ethier Stephen P. , Zhang Zhong-Yin , Chernoff Jonathan 
Published: May 2009

Abstract
Protein tyrosine phosphatase (PTP) 1B plays a major role in inhibiting signaling from the insulin and leptin receptors. Recently, PTP1B was found to have an unexpected positive role in ErbB2 signaling in a mouse model of breast cancer, but the mechanism underlying this effect has been unclear. Using human breast epithelial cells grown in a three-dimensional matrix, we found that PTP1B, but not the closely related enzyme T-cell PTP, is required for ErbB2 transformation in vitro. Activation of ErbB2, but not ErbB1, increases PTP1B expression, and increased expression of PTP1B activates Src and induces a Src-dependent transformed phenotype. These findings identify a molecular mechanism by which PTP1B links an important oncogenic receptor tyrosine kinase to signaling pathways that promote aberrant cell division and survival in human breast epithelial cells. [Cancer Res 2009;69(11):4582–8]