bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Defects of
Cryptococcus neoformans
Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis
Authors: Lee Anthony , Toffaletti Dena L. , Tenor Jennifer , Soderblom Erik J. , Thompson J. Will , Moseley M. Arthur , Price Michael , Perfect John R. 
Published: August 2010

ABSTRACT

Cryptococcus neoformans
is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that
C. neoformans
must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both
Caenorhabditis
elegans
and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (
ena1
Δ), a putative NEDD8 ubiquitin-like protein (
rub1
Δ), and a phosphatidylinositol 4-kinase (
pik1
Δ). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for
C. neoformans
survival in CSF
ex vivo
are necessary for survival and infection in this unique host environment.
Elevated Systemic Levels of Inflammatory Cytokines in Older Women with Persistent Cervical Human Papillomavirus Infection
Authors: Kemp Troy J. , Hildesheim Allan , García-Piñeres Alfonso , Williams Marcus C. , Shearer Gene M. , Rodriguez Ana Cecilia , Schiffman Mark , Burk Robert , Freer Enrique , Bonilla Jose , Herrero Rolando , Pinto Ligia A. 
Published: August 2010

Abstract
Background: Defects in lymphoproliferative responses to mitogens/antigens in women &gt;45 years old with a persistent type-specific human papillomavirus (HPV) infection have been reported.
Methods: To determine whether these defects were associated with altered cytokine profiles, plasma and peripheral blood mononuclear cell (PBMC) culture supernatants from 50 cases (oversampled for their reduced lymphoproliferative ability) and 50 uninfected controls (oversampled for their robust lymphoproliferative ability) were examined for 24 cytokines using multiplexed bead–based immunoassays and ELISA.
Results: The following plasma cytokines were significantly increased in cases relative to controls (cases versus controls; median pg/mL): interleukin (IL)-6, 393.1 versus 14.5; IL-8, 1,128.5 versus 43.9; tumor necrosis factor-α (TNF-α), 164.1 versus 9.2; macrophage inflammatory protein-1α (MIP-1α), 1,368.9 versus 25.5; granulocyte macrophage colony-stimulating factor (GM-CSF), 13.8 versus 7.3; IL-1β, 8.3 versus 1.6 (all P &lt; 0.0001); and IL-1α, 218.2 versus 169.5 (P = 0.02). We focused our analysis on the cytokines IL-6, IL-8, TNF-α, and MIP-1α due to their high fold change (&gt;10) and highly statistically significant difference between cases and controls. Length of persistence or type of infection (high risk and low risk) did not affect these differences. IL-6, TNF-α, and MIP-1α levels were also increased in unstimulated PBMC culture supernatants from cases compared with controls (P &lt; 0.05), however, the cytokine levels from phytohemagglutinin-stimulated PBMC culture supernatants were significantly lower in the cases (P &lt; 0.0001).
Conclusions: Persistent HPV infection in older women with evidence of immune deficit is associated with an increase in systemic inflammatory cytokines.
Impact: Future studies are needed to determine whether the inflammatory profile is age dependent and to examine the role that inflammatory cytokines play in HPV-induced progression from infection to cervical cancer. Cancer Epidemiol Biomarkers Prev; 19(8); 1954–9. ©2010 AACR.
The Response of Performance Metrics for Binary Forecasts to Hedging that Approaches Random Change
Authors: Brill Keith F. , Pyle Matthew 
Published: August 2010

Abstract
Critical performance ratio (CPR) expressions for the eight conditional probabilities associated with the 2 × 2 contingency table of outcomes for binary (dichotomous “yes” or “no”) forecasts are derived. Two are shown to be useful in evaluating the effects of hedging as it approaches random change. The CPR quantifies how the probability of detection (POD) must change as frequency bias changes, so that a performance measure (or conditional probability) indicates an improved forecast for a given value of frequency bias. If yes forecasts were to be increased randomly, the probability of additional correct forecasts (hits) is given by the detection failure ratio (DFR). If the DFR for a performance measure is greater than the CPR, the forecast is likely to be improved by the random increase in yes forecasts. Thus, the DFR provides a benchmark for the CPR in the case of frequency bias inflation. If yes forecasts are decreased randomly, the probability of removing a hit is given by the frequency of hits (FOH). If the FOH for a performance measure is less than the CPR, the forecast is likely to be improved by the random decrease in yes forecasts. Therefore, the FOH serves as a benchmark for the CPR if the frequency bias is decreased. The closer the FOH (DFR) is to being less (greater) than or equal to the CPR, the more likely it may be to enhance the performance measure by decreasing (increasing) the frequency bias. It is shown that randomly increasing yes forecasts for a forecast that is itself better than a randomly generated forecast can improve the threat score but is not likely to improve the equitable threat score. The equitable threat score is recommended instead of the threat score whenever possible.
Increasing physical activity in patients with arthritis: a tailored health promotion program
Authors: Ehrlich-Jones Linda , Mallinson Trudy , Fischer Heidi , Bateman Jillian , Semanik Pamela A. , Spring Bonnie , Ruderman Eric , Chang Rowland W. 
Published: August 2010

Objective: Despite recent studies showing the benefit of physical activity for people with arthritis, the vast majority of persons with arthritis are not sufficiently physically active. The purpose of this report is to describe a tailored health promotion intervention aimed at increasing physical activity among persons with arthritis. The intervention is designed to be useful for health systems and insurers interested in a chronic disease management program that could be disseminated to large populations of arthritis patients. Methods: The intervention is carried out by a clinician who is designated as the client’s physical activity advocate. The approach emphasizes motivational interviewing, individualized goal setting, tailored strategies for increasing physical activity and for monitoring progress, and a plan of 2 years of follow-up. The intervention includes a standardized assessment of barriers to and strengths supporting increased lifestyle physical activity. A randomized, controlled trial is underway to evaluate the efficacy and cost-effectiveness of this intervention. Conclusion: This intervention is unique in that it implements a program tailored to the individual that focuses on lifestyle physical activity and long-term monitoring. The approach recognizes that persons with arthritis present with varying levels of motivation for change in physical activity and that behavior change can take a long time to become habitual.
CCR7 impairs hematopoiesis after hematopoietic stem cell transplantation increasing susceptibility to invasive aspergillosis
Authors: Hartigan Adam J. , Kallal Lara E. , Hogaboam Cory M. 
Published: August 2010

AbstractHematopoietic stem cell transplantation (HSCT) is limited by patient susceptibility to opportunistic infections. One of the most devastating infections after HSCT is invasive aspergillosis (IA), a life-threatening disease caused by Aspergillus fumigatus. Transplantation of hematopoietic stem cells (HSCs) and myeloid progenitor cells (MPCs) has been shown to mediate protection against IA, but little is known about the factors that regulate HSC and MPC cell expansion after transplantation. Herein, we investigated the role of CCR7 in a murine model of IA after combined HSC and MPC transplantation into lethally irradiated wild-type (WT) mice. Nonirradiated CCR7−/− mice had expanded populations of HSCs in the bone marrow and spleen, compared with WT mice. Irradiated WT mice reconstituted with CCR7−/− HSCs and MPCs had increased survival, decreased fungal burden, and enhanced myeloid leukocyte numbers during IA, compared with WT controls. In addition, WT mice reconstituted with WT HSCs and MPCs and treated with anti-CCR7 exhibited accelerated myeloid cell expansion similar to that observed in CCR7−/−→WT chimeras. Thus, removal of the inhibitory effects of CCR7 through genetic alteration or ligand immunoneutralization enhanced myeloid reconstitution, thereby accelerating fungal clearance in a murine model of IA.
Identification of testis-relevant genes using in silico analysis from testis ESTs and cDNA microarray in the black tiger shrimp (Penaeus monodon)
Authors: Wongsurawat Thidathip , Leelatanawit Rungnapa , Thamniemdee Natechanok , Uawisetwathana Umaporn , Karoonuthaisiri Nitsara , Menasveta Piamsak , Klinbunga Sirawut 
Published: August 2010

Abstract

Background
Poor reproductive maturation of the black tiger shrimp (Penaeus monodon) in captivity is one of the serious threats to sustainability of the shrimp farming industry. Understanding molecular mechanisms governing reproductive maturation processes requires the fundamental knowledge of integrated expression profiles in gonads of this economically important species. In P. monodon, a non-model species for which the genome sequence is not available, expressed sequence tag (EST) and cDNA microarray analyses can help reveal important transcripts relevant to reproduction and facilitate functional characterization of transcripts with important roles in male reproductive development and maturation.

Results
In this study, a conventional testis EST library was exploited to reveal novel transcripts. A total of 4,803 ESTs were unidirectionally sequenced and analyzed in silico using a customizable data analysis package, ESTplus. After sequence assembly, 2,702 unique sequences comprised of 424 contigs and 2,278 singletons were identified; of these, 1,133 sequences are homologous to genes with known functions. The sequences were further characterized according to gene ontology categories (41% biological process, 24% molecular function, 35% cellular component). Through comparison with EST libraries of other tissues of P. monodon, 1,579 transcripts found only in the testis cDNA library were identified. A total of 621 ESTs have not been identified in penaeid shrimp. Furthermore, cDNA microarray analysis revealed several ESTs homologous to testis-relevant genes were more preferentially expressed in testis than in ovary. Representatives of these transcripts, homologs of saposin (PmSap) and Dmc1 (PmDmc1), were further characterized by RACE-PCR. The more abundant expression levels in testis than ovary of PmSap and PmDmc1 were verified by quantitative real-time PCR in juveniles and wild broodstock of P. monodon.

Conclusions
Without a genome sequence, a combination of EST analysis and high-throughput cDNA microarray technology can be a useful integrated tool as an initial step towards the identification of transcripts with important biological functions. Identification and expression analysis of saposin and Dmc1 homologs demonstrate the power of these methods for characterizing functionally important genes in P. monodon.
Mutations in the WTX- gene are found in some high-grade microsatellite instable (MSI-H) colorectal cancers
Authors: Scheel Silvio K , Porzner Marc , Pfeiffer Sabine , Ormanns Steffen , Kirchner Thomas , Jung Andreas 
Published: August 2010

AbstractBackgroundGenetically, colorectal cancers (CRCs) can be subdivided into tumors with chromosomal instability (CIN) or microsatellite instability (MSI). In both types of CRCs genes that are involved in the degradation of β-CATENIN are frequently mutated. Whereas in CIN CRCsAPC(Adenomatous Polyposis Coli) is affected in most cases, high grade MSI (MSI-H) CRCs frequently display mutations in various genes, like theAPC-,AXIN2- orCTNNBI(β-CATENIN) gene itself. Recently in Wilms tumors,WTX(Wilms tumor gene on the X-chromosome) was discovered as another gene involved in the destruction of β-CATENIN. As theWTX-gene harbors a short T6-microsatellite in its N-terminal coding region, we hypothesized that frameshift-mutations might occur in MSI-H CRCs in theWTXgene, thus additionally contributing to the stabilization of β-CATENIN in human CRCs.MethodsDNA was extracted from 632 formalin-fixed, paraffin-embedded metastatic CRCs (UICCIV) and analyzed for MSI-H by investigating the stability of the highly sensitive microsatellite markers BAT25 and BAT26 applying fluorescence capillary electrophoresis (FCE). Then, in the MSI-H cases, well described mutational hot spot regions from theAPC-,AXIN2- andCTNNBIgenes were analyzed for genomic alterations by didesoxy-sequencing while theWTXT6-microsatellite was analyzed by fragment analysis. Additionally, the PCR products of T5-repeats were subcloned and mutations were validated using didesoxy-sequencing. Furthermore, theKRASand theBRAFproto-oncogenes were analyzed for the most common activating mutations applying pyro-sequencing. mRNA expression ofWTXfrom MSI-H and MSS cases and a panel of colorectal cancer cell lines was investigated using reverse transcription (RT-) PCR and FCE.ResultsIn our cohort of 632 metastatic CRCs (UICCIV) we identified 41 MSI-H cases (6.5%). Two of the 41 MSI-H cases (4.8%) displayed a frameshift mutation in the T6-repeat resulting in a T5sequence. Only one case, a male patient, expressed the mutatedWTXgene while being wild type for all other investigated genes.ConclusionMutations in theWTX-gene might compromise the function of the β-CATENIN destruction complex in only a small fraction of MSI-H CRCs thus contributing to the process of carcinogenesis.
Association between weight perception and socioeconomic status among adults in the Seychelles
Authors: Alwan Heba , Viswanathan Bharathi , Williams Julita , Paccaud Fred , Bovet Pascal 
Published: August 2010

Abstract

Background
Few studies have examined the association between weight perception and socioeconomic status (SES) in sub-Saharan Africa, and none made this association based on education, occupation and income simultaneously.

Methods
Based on a population-based survey (n = 1255) in the Seychelles, weight and height were measured and self-perception of one's own body weight, education, occupation, and income were assessed by a questionnaire. Individuals were considered to have appropriate weight perception when their self-perceived weight matched their actual body weight.

Results
The prevalence of overweight and obesity was 35% and 28%, respectively. Multivariate analysis among overweight/obese persons showed that appropriate weight perception was directly associated with actual weight, education, occupation and income, and that it was more frequent among women than among men. In a model using all three SES indicators together, only education (OR = 2.5; 95% CI: 1.3-4.8) and occupation (OR = 2.3; 95% CI: 1.2-4.5) were independently associated with appropriate perception of being overweight. The OR reached 6.9 [95% CI: 3.4-14.1] when comparing the highest vs. lowest categories of SES based on a score including all SES indicators and 6.1 [95% CI: 3.0-12.1] for a score based on education and occupation.

Conclusions
Appropriately perceiving one's weight as too high was associated with different SES indicators, female sex and being actually overweight. These findings suggest means and targets for clinical and population-based interventions for weight control. Further studies should examine whether these differences in weight perception underlie differences in cognitive skills, healthy weight norms, or body size ideals.
Comparing interfacial dynamics in protein-protein complexes: an elastic network approach
Authors: Zen Andrea , Micheletti Cristian , Keskin Ozlem , Nussinov Ruth 
Published: August 2010

Abstract

Background
The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces.

Results
The interface dynamics was characterized by means of an elastic network model for 22 representative dimers covering three main interface types. The three groups gather dimers sharing the same interface but with good (type I) or poor (type II) similarity of the overall fold, or dimers sharing only one of the semi-interfaces (type III). The set comprises obligate dimers, which are complexes for which no structural representative of the free form(s) is available. Considerations were accordingly limited to bound and unbound forms of the monomeric subunits of the dimers. We proceeded by first computing the mobility of amino acids at the interface of the bound forms and compare it with the mobility of (i) other surface amino acids (ii) interface amino acids in the unbound forms. In both cases different dynamic patterns were observed across interface types and depending on whether the interface belongs to an obligate or non-obligate complex.

Conclusions
The comparative investigation indicated that the mobility of amino acids at the dimeric interface is generally lower than for other amino acids at the protein surface. The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex. In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones. The results suggest that these structurally- and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.
Artemisone effective against murine cerebral malaria
Authors: Waknine-Grinberg Judith H , Hunt Nicholas , Bentura-Marciano Annael , McQuillan James A , Chan Ho-Wai , Chan Wing-Chi , Barenholz Yechezkel , Haynes Richard K , Golenser Jacob 
Published: August 2010

AbstractBackgroundArtemisinins are the newest class of drug approved for malaria treatment. Due to their unique mechanism of action, rapid effect on Plasmodium, and high efficacy in vivo, artemisinins have become essential components of malaria treatment. Administration of artemisinin derivatives in combination with other anti-plasmodials has become the first-line treatment for uncomplicated falciparum malaria. However, their efficiency in cases of cerebral malaria (CM) remains to be determined.MethodsThe efficacy of several artemisinin derivatives for treatment of experimental CM was evaluated in ICR or C57BL/6 mice infected byPlasmodium bergheiANKA. Both mouse strains serve as murine models for CM.ResultsArtemisone was the most efficient drug tested, and could prevent death even when administered at relatively late stages of cerebral pathogenesis. No parasite resistance to artemisone was detected in recrudescence. Co-administration of artemisone together with chloroquine was more effective than monotherapy with either drug, and led to complete cure. Artemiside was even more effective than artemisone, but this substance has yet to be submitted to preclinical toxicological evaluation.ConclusionsAltogether, the results support the use of artemisone for combined therapy of CM.
IDOMAL: an ontology for malaria
Authors: Topalis Pantelis , Mitraka Elvira , Bujila Ioana , Deligianni Elena , Dialynas Emmanuel , Siden-Kiamos Inga , Troye-Blomberg Marita , Louis Christos 
Published: August 2010

Abstract

Background
Ontologies are rapidly becoming a necessity for the design of efficient information technology tools, especially databases, because they permit the organization of stored data using logical rules and defined terms that are understood by both humans and machines. This has as consequence both an enhanced usage and interoperability of databases and related resources. It is hoped that IDOMAL, the ontology of malaria will prove a valuable instrument when implemented in both malaria research and control measures.

Methods
The OBOEdit2 software was used for the construction of the ontology. IDOMAL is based on the Basic Formal Ontology (BFO) and follows the rules set by the OBO Foundry consortium.

Results
The first version of the malaria ontology covers both clinical and epidemiological aspects of the disease, as well as disease and vector biology. IDOMAL is meant to later become the nucleation site for a much larger ontology of vector borne diseases, which will itself be an extension of a large ontology of infectious diseases (IDO). The latter is currently being developed in the frame of a large international collaborative effort.

Conclusions
IDOMAL, already freely available in its first version, will form part of a suite of ontologies that will be used to drive IT tools and databases specifically constructed to help control malaria and, later, other vector-borne diseases. This suite already consists of the ontology described here as well as the one on insecticide resistance that has been available for some time. Additional components are being developed and introduced into IDOMAL.