bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Era for Career Development and HRD
Authors: Hite Linda M. , McDonald Kimberly S.
Published: January 2008

The problem and the solution. Career development (CD), long considered a primary function of HRD, has been eclipsed in recent years by changing employer—employee loyalties, increasing interest in portable careers, and the growing importance of subjective career goals. Instead of abandoning CD in the wake of such significant changes, HRD needs to review the evolving career landscape and respond to the diverse needs of individuals and systems. It is a new era for CD and HRD.
Creating Career-Conducive Organizations: A Primary Intervention Approach
Authors: Gilbreath Brad
Published: January 2008

The problem and the solution. This article introduces the concept of career-conducive organizations and suggests ways human resource development (HRD) professionals can help to create them. A healthy psychosocial environment is proposed to be the foundation of career conduciveness. A case is made for making healthy psychosocial environments one of an organizations' primary goals and for HRD playing a significant role in achieving this goal. Methods for improving the workplace psychosocial environment are discussed, including stress audits, work environment monitoring, person— environment matching, and participatory action research. It is argued that creating career-conducive organizations is not only an important strategic HRD contribution but also an important quality-of-life contribution and an ethical duty.
The Baby Boom Generation and Career Management: A Call to Action
Authors: Callanan Gerard A. , Greenhaus Jeffrey H.
Published: January 2008

The problem and the solution. The aging and ultimate retirement of the baby boom generation represents a major demographic and sociological phenomenon that has far reaching implications for organizations, the government, and society as a whole. For organizations, the baby boom workforce is a paradox, simultaneously representing both a critical success factor and potential drag on corporate performance and financial resources. Given this paradox, this article first provides a description of the significant issues and challenges that the baby boom generation presents to organizations currently and in the future. It then discusses contemporary organizational attitudes toward the baby boom workforce as well as the related career management programs aimed at this cohort. In a “call to action” for organizations, we conclude by recommending a number of career management and human resource development actions that should, collectively, allow organizations to proactively respond to the challenges posed by the aging of baby boom generation.
Tutorial Action as a Resource to Improve Higher Education
Authors: Ricoy Lorenzo Carmen , Pino Juste Margarita
Published: January 2008

This article describes a qualitative study, and it focuses on the analysis of the dynamics surrounding tutorial action in higher education. The authors have tried to determine the specific needs of the students by identifying and examining the functions associated with tutorial action. Several action guidelines aimed at improving tutorial function are proposed.
Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome
Authors: Robinson Blaine W. , Cheung Nai-Kong V. , Kolaris Christos P. , Jhanwar Suresh C. , Choi John K. , Osheroff Neil , Felix Carolyn A.
Published: January 2008

We prospectively observed a child exposed to intensive multimodality therapy for metastatic neuroblastoma from emergence of a MLL translocation to disease diagnosis. The t(4;11)(p12;q23) was detected in the marrow 17 months after starting treatment following topoisomerase II poisons, alkylating agents, local radiation, hematopoietic stem cell transplantation, anti-GD2 monoclonal antibody with granulocyte macrophage–colony-stimulating factor, and a high cumulative dose of oral etoposide. Reciprocal genomic breakpoint junctions and fusion transcripts joined MLL with FRYL, the Drosophila melanogaster protein homologue of which regulates cell fate. Etoposide metabolites induced topoisomerase II cleavage complexes that could form both breakpoint junctions. Cells harboring the translocation replaced the marrow without clinical evidence of leukemia and differentiation appeared unaffected for 37 months. Subsequent bilineage dysplasia and increased blasts in addition to the translocation fulfilled criteria for MDS. The MEIS1 target gene of typical MLL fusion oncoproteins was underexpressed before and at MDS diagnosis. These results are consistent with repair of topoisomerase II cleavage from etoposide metabolites as the translocation mechanism, whereas other agents in the regimen may have contributed to progression of the clone with the translocation to MDS. MLL-FRYL did not increase MEIS1 expression, conferred a proliferative advantage without altering differentiation, and had protracted latency to disease.
Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations
Authors: Li Sai , Kralovics Robert , De Libero Gennaro , Theocharides Alexandre , Gisslinger Heinz , Skoda Radek C.
Published: January 2008

We studied the lineage distribution of JAK2 mutations in peripheral blood of 8 polycythemia vera (PV) patients with exon 12 mutations and in 21 PV patients with JAK2-V617F. Using a quantitative allele discrimination assay, we detected exon 12 mutations in purified granulocytes, monocytes, and platelets of 8 patients studied, but lymphoid cells showed variable involvement and the mutation was absent in T cells. Endogenous erythroid colonies grew in all patients analyzed. One patient displayed erythroid colonies homozygous for the exon 12 mutation with evidence for mitotic recombination on chromosome 9p. In some patients with exon 12 mutations or JAK2-V617F, a proportion of endogenous erythroid colonies were negative for both JAK2 mutations. One patient carried 2 independent clones: one with an exon 12 mutation and a second with JAK2-V617F. The finding of clonal heterogeneity is compatible with the hypothesis that additional clonal events are involved in the pathogenesis of PV.
Increased numbers of circulating hematopoietic stem/progenitor cells are chronically maintained in patients treated with the CD49d blocking antibody natalizumab
Authors: Bonig Halvard , Wundes Annette , Chang Kai-Hsin , Lucas Sylvia , Papayannopoulou Thalia
Published: January 2008

Blockade of CD49d-mediated lymphocyte trafficking has been used therapeutically for certain autoimmune diseases, such as multiple sclerosis (MS). In addition to negative effects on the trafficking of mature lymphocytes to sites of inflammation, CD49d blockade in mice and monkeys rapidly mobilizes hematopoietic stem/progenitor cells (HSPCs) capable of short- and long-term engraftment. Here we aimed to ascertain the effects of treatment with antifunctional anti-CD49d antibody in humans (MS patients receiving infusions of the CD49d-blocking antibody natalizumab) on levels of circulating HSPCs after a single dose of antibody or after long-term treatment. On average, 6-fold elevated levels of circulating CD34+ cells and colony-forming unit-culture (CFU-C) were achieved within 1 day of the first dose of natalizumab, and similar levels were continuously maintained under monthly natalizumab infusions. The blood of natalizumab-treated subjects also contained SCID-repopulating cells. The fate of these circulating HSPCs and their clinical relevance for MS patients remains to be determined.
Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells
Authors: Gotoh Kazuhito , Tanaka Yoshihiko , Nishikimi Akihiko , Inayoshi Ayumi , Enjoji Munechika , Takayanagi Ryoichi , Sasazuki Takehiko , Fukui Yoshinori
Published: January 2008

The migratory properties of dendritic cells (DCs) are important for their functions. Although several chemokines and their receptors have been implicated in DC migration, the downstream signaling molecules are largely unknown. Here we show that DOCK2, a hematopoietic cell-specific CDM family protein, is indispensable for migration of plasmacytoid DCs (pDCs), but not myeloid DCs (mDCs). Although DOCK2-deficiency did not affect development of pDCs, DOCK2-deficient (DOCK2−/−) mice exhibited a severe reduction of pDCs in the spleen and lymph nodes. Adoptive transfer experiments revealed that DOCK2−/− pDCs failed to migrate into the periarteriolar lymphoid sheaths of the spleen. In DOCK2−/− pDCs, chemokine-induced Rac activation was severely impaired, resulting in the reduction of motility and the loss of polarity during chemotaxis. In contrast, DOCK2−/− mDCs did not show any defects in Rac activation and migration. These results indicate that pDCs and mDCs use distinct molecules to activate Rac during chemotaxis.
Immunologic ignorance of vascular endothelial cells expressing minor histocompatibility antigen
Authors: Bolinger Beatrice , Krebs Philippe , Tian Yinghua , Engeler Daniel , Scandella Elke , Miller Simone , Palmer Douglas C. , Restifo Nicholas P. , Clavien Pierre-Alain , Ludewig Burkhard
Published: January 2008

Endothelial cells (ECs) presenting minor histocompatibility antigen (mhAg) are major target cells for alloreactive effector CD8+ T cells during chronic transplant rejection and graft-versus-host disease (GVHD). The contribution of ECs to T-cell activation, however, is still a controversial issue. In this study, we have assessed the antigen-presenting capacity of ECs in vivo using a transgenic mouse model with beta-galactosidase (β-gal) expression confined to the vascular endothelium (Tie2-LacZ mice). In a GVHD-like setting with adoptive transfer of β-gal–specific T-cell receptor–transgenic T cells, β-gal expression by ECs was not sufficient to either activate or tolerize CD8+ T cells. Likewise, transplantation of fully vascularized heart or liver grafts from Tie2-LacZ mice into nontransgenic recipients did not suffice to activate β-gal–specific CD8+ T cells, indicating that CD8+ T-cell responses against mhAg cannot be initiated by ECs. Moreover, we could show that spontaneous activation of β-gal–specific CD8+ T cells in Tie2-LacZ mice was exclusively dependent on CD11c+ dendritic cells (DCs), demonstrating that mhAgs presented by ECs remain immunologically ignored unless presentation by DCs is granted.
LeARN: a platform for detecting, clustering and annotating non-coding RNAs
Authors: Noirot Céline , Gaspin Christine , Schiex Thomas , Gouzy Jérôme
Published: January 2008

Background

In the last decade, sequencing projects have led to the development of a number of annotation systems dedicated to the structural and functional annotation of protein-coding genes. These annotation systems manage the annotation of the non-protein coding genes (ncRNAs) in a very crude way, allowing neither the edition of the secondary structures nor the clustering of ncRNA genes into families which are crucial for appropriate annotation of these molecules.

Results

LeARN is a flexible software package which handles the complete process of ncRNA annotation by integrating the layers of automatic detection and human curation.

Conclusion

This software provides the infrastructure to deal properly with ncRNAs in the framework of any annotation project. It fills the gap between existing prediction software, that detect independent ncRNA occurrences, and public ncRNA repositories, that do not offer the flexibility and interactivity required for annotation projects. The software is freely available from the download section of the website http://bioinfo.genopole-toulouse.prd.fr/LeARN
MeInfoText: associated gene methylation and cancer information from text mining
Authors: Fang Yu-Ching , Huang Hsuan-Cheng , Juan Hsueh-Fen
Published: January 2008

Background

DNA methylation is an important epigenetic modification of the genome. Abnormal DNA methylation may result in silencing of tumor suppressor genes and is common in a variety of human cancer cells. As more epigenetics research is published electronically, it is desirable to extract relevant information from biological literature. To facilitate epigenetics research, we have developed a database called MeInfoText to provide gene methylation information from text mining.

Description

MeInfoText presents comprehensive association information about gene methylation and cancer, the profile of gene methylation among human cancer types and the gene methylation profile of a specific cancer type, based on association mining from large amounts of literature. In addition, MeInfoText offers integrated protein-protein interaction and biological pathway information collected from the Internet. MeInfoText also provides pathway cluster information regarding to a set of genes which may contribute the development of cancer due to aberrant methylation. The extracted evidence with highlighted keywords and the gene names identified from each methylation-related abstract is also retrieved. The database is now available at http://mit.lifescience.ntu.edu.tw/.

Conclusion

MeInfoText is a unique database that provides comprehensive gene methylation and cancer association information. It will complement existing DNA methylation information and will be useful in epigenetics research and the prevention of cancer.
The midgut transcriptome of Lutzomyia longipalpis: comparative analysis of cDNA libraries from sugar-fed, blood-fed, post-digested and Leishmania infantum chagasi-infected sand flies
Authors: Jochim Ryan C , Teixeira Clarissa R , Laughinghouse Andre , Mu Jianbing , Oliveira Fabiano , Gomes Regis B , Elnaiem Dia-Eldin , Valenzuela Jesus G
Published: January 2008

Background

In the life cycle of Leishmania within the alimentary canal of sand flies the parasites have to survive the hostile environment of blood meal digestion, escape the blood bolus and attach to the midgut epithelium before differentiating into the infective metacyclic stages. The molecular interactions between the Leishmania parasites and the gut of the sand fly are poorly understood. In the present work we sequenced five cDNA libraries constructed from midgut tissue from the sand fly Lutzomyia longipalpis and analyzed the transcripts present following sugar feeding, blood feeding and after the blood meal has been processed and excreted, both in the presence and absence of Leishmania infantum chagasi.

Results

Comparative analysis of the transcripts from sugar-fed and blood-fed cDNA libraries resulted in the identification of transcripts differentially expressed during blood feeding. This included upregulated transcripts such as four distinct microvillar-like proteins (LuloMVP1, 2, 4 and 5), two peritrophin like proteins, a trypsin like protein (Lltryp1), two chymotrypsin like proteins (LuloChym1A and 2) and an unknown protein. Downregulated transcripts by blood feeding were a microvillar-like protein (LuloMVP3), a trypsin like protein (Lltryp2) and an astacin-like metalloprotease (LuloAstacin). Furthermore, a comparative analysis between blood-fed and Leishmania infected midgut cDNA libraries resulted in the identification of the transcripts that were differentially expressed due to the presence of Leishmania in the gut of the sand fly. This included down regulated transcripts such as four microvillar-like proteins (LuloMVP1,2, 4 and 5), a Chymotrypsin (LuloChym1A) and a carboxypeptidase (LuloCpepA1), among others. Upregulated midgut transcripts in the presence of Leishmania were a peritrophin like protein (LuloPer1), a trypsin-like protein (Lltryp2) and an unknown protein.

Conclusion

This transcriptome analysis represents the largest set of sequence data reported from a specific sand fly tissue and provides further information of the transcripts present in the sand fly Lutzomyia longipalpis. This analysis provides the detailed information of molecules present in the midgut of this sand fly and the transcripts potentially modulated by blood feeding and by the presence of the Leishmania parasite. More importantly, this analysis suggests that Leishmania infantum chagasi alters the expression profile of certain midgut transcripts in the sand fly during blood meal digestion and that this modulation may be relevant for the survival and establishment of the parasite in the gut of the fly. Moreover, this analysis suggests that these changes may be occurring during the digestion of the blood meal and not afterwards.
Sub-grouping and sub-functionalization of the RIFIN multi-copy protein family
Authors: Joannin Nicolas , Abhiman Saraswathi , Sonnhammer Erik L , Wahlgren Mats
Published: January 2008

Background

Parasitic protozoans possess many multicopy gene families which have central roles in parasite survival and virulence. The number and variability of members of these gene families often make it difficult to predict possible functions of the encoded proteins. The families of extra-cellular proteins that are exposed to a host immune response have been driven via immune selection to become antigenically variant, and thereby avoid immune recognition while maintaining protein function to establish a chronic infection.

Results

We have combined phylogenetic and function shift analyses to study the evolution of the RIFIN proteins, which are antigenically variant and are encoded by the largest multicopy gene family in Plasmodium falciparum. We show that this family can be subdivided into two major groups that we named A- and B-RIFIN proteins. This suggested sub-grouping is supported by a recently published study that showed that, despite the presence of the Plasmodium export (PEXEL) motif in all RIFIN variants, proteins from each group have different cellular localizations during the intraerythrocytic life cycle of the parasite. In the present study we show that function shift analysis, a novel technique to predict functional divergence between sub-groups of a protein family, indicates that RIFINs have undergone neo- or sub-functionalization.

Conclusion

These results question the general trend of clustering large antigenically variant protein groups into homogenous families. Assigning functions to protein families requires their subdivision into meaningful groups such as we have shown for the RIFIN protein family. Using phylogenetic and function shift analysis methods, we identify new directions for the investigation of this broad and complex group of proteins.
Combined effect of CCND1 and COMT polymorphisms and increased breast cancer risk
Authors: Onay Ummiye V , Aaltonen Kirsimari , Briollais Laurent , Knight Julia A , Pabalan Noel , Kilpivaara Outi , Andrulis Irene L , Blomqvist Carl , Nevanlinna Heli , Ozcelik Hilmi
Published: January 2008

Background

Estrogens are crucial tumorigenic hormones, which impact the cell growth and proliferation during breast cancer development. Estrogens are metabolized by a series of enzymes including COMT, which converts catechol estrogens into biologically non-hazardous methoxyestrogens. Several studies have also shown the relationship between estrogen and cell cycle progression through activation of CCND1 transcription.

Methods

In this study, we have investigated the independent and the combined effects of commonly occurring CCND1 (Pro241Pro, A870G) and COMT (Met108/158Val) polymorphisms to breast cancer risk in two independent Caucasian populations from Ontario (1228 breast cancer cases and 719 population controls) and Finland (728 breast cancer cases and 687 population controls). Both COMT and CCND1 polymorphisms have been previously shown to impact on the enzymatic activity of the coded proteins.

Results

Here, we have shown that the high enzymatic activity genotype of CCND1High (AA) was associated with increased breast cancer risk in both the Ontario [OR: 1.3, 95%CI (1.0–1.69)] and the Finland sample [OR: 1.4, 95%CI (1.01–1.84)]. The heterozygous COMTMedium (MetVal) and the high enzymatic activity of COMTHigh (ValVal) genotype was also associated with breast cancer risk in Ontario cases, [OR: 1.3, 95%CI (1.07–1.68)] and [OR: 1.4, 95%CI (1.07–1.81)], respectively. However, there was neither a statistically significant association nor increased trend of breast cancer risk with COMTHigh (ValVal) genotypes in the Finland cases [OR: 1.0, 95%CI (0.73–1.39)]. In the combined analysis, the higher activity alleles of the COMT and CCND1 is associated with increased breast cancer risk in both Ontario [OR: 2.22, 95%CI (1.49–3.28)] and Finland [OR: 1.73, 95%CI (1.08–2.78)] populations studied. The trend test was statistically significant in both the Ontario and Finland populations across the genotypes associated with increasing enzymatic activity.

Conclusion

Using two independent Caucasian populations, we have shown a stronger combined effect of the two commonly occurring CCND1 and COMT genotypes in the context of breast cancer predisposition.
Risk adjustment performance of Charlson and Elixhauser comorbidities in ICD-9 and ICD-10 administrative databases
Authors: Li Bing , Evans Dewey , Faris Peter , Dean Stafford , Quan Hude
Published: January 2008

Background

The performance of the Charlson and Elixhauser comorbidity measures in predicting patient outcomes have been well validated with ICD-9 data but not with ICD-10 data, especially in disease specific patient cohorts. The objective of this study was to assess the performance of these two comorbidity measures in the prediction of in-hospital and 1 year mortality among patients with congestive heart failure (CHF), diabetes, chronic renal failure (CRF), stroke and patients undergoing coronary artery bypass grafting (CABG).

Methods

A Canadian provincial hospital discharge administrative database was used to define 17 Charlson comorbidities and 30 Elixhauser comorbidities. C-statistic values were calculated to evaluate the performance of two measures. One year mortality information was obtained from the provincial Vital Statistics Department.

Results

The absolute difference between ICD-9 and ICD-10 data in C-statistics ranged from 0 to 0.04 across five cohorts for the Charlson and Elixhauser comorbidity measures predicting in-hospital or 1 year mortality. In the models predicting in-hospital mortality using ICD-10 data, the C-statistics ranged from 0.62 (for stroke) – 0.82 (for diabetes) for Charlson measure and 0.62 (for stroke) to 0.83 (for CABG) for Elixhauser measure.

Conclusion

The change in coding algorithms did not influence the performance of either the Charlson or Elixhauser comorbidity measures in the prediction of outcome. Both comorbidity measures were still valid prognostic indicators in the ICD-10 data and had a similar performance in predicting short and long term mortality in the ICD-9 and ICD-10 data.
Correlates of current cigarette smoking among school-going adolescents in Punjab, India: results from the Global Youth Tobacco Survey 2003
Authors: Siziya Seter , Muula Adamson S , Rudatsikira Emmanuel
Published: January 2008

Background

Smoking is a leading cause of morbidity and mortality globally. There is therefore need to identify relevant factors associated with smoking among adolescents in order to better tailor public health interventions aimed at preventing smoking.

Methods

We used data from the Global Youth Tobacco Survey (GYTS) conducted in 2003 in Punjab, India, on 2014 adolescents of whom 58.9% were males. We conducted a weighted logistic regression analysis, adjusting for age and sex, to determine associations between predictor variables and current tobacco smoking status.

Results

A total of 2014 adolescents participated in the survey in 2003, and of these 58.9% were males. Male respondents tended to be older than females (21.2% of males, and 13.1% of females were of age 16 years or above). The percent of males and females in the other age groups were: 23.0% and 28.6% for <14 years, 27.3% and 31.0% for 14 years, and 28.4% and 27.0% for 15 years, respectively. The following factors were positively associated with smoking: adolescents who received pocket money; adolescents who had parents who smoked, chewed or applied tobacco; adolescents who said that boys or girls who smoke or chew tobacco have more friends; adolescents who said that smoking or chewing tobacco makes boys look less attractive; adolescents who said that there is no difference in weight between smokers and non-smokers; adolescents who said that smoking makes one gain weight; and adolescents who had most or all of their closest friends who smoked. The factors that were negatively associated with smoking were: adolescents who said that boys or girls who smoke or chew tobacco have less number of friends; adolescents who said that girls who smoke or chew tobacco are less attractive; and adolescents who had some of their closest friends who smoked.

Conclusion

The observed associations between current smoking on one hand and peer smoking, and perception that boys who smoke are less attractive on the other, deserve further studies. The factors reported in the current study should be considered in the design of public health interventions aimed to reduce adolescent cigarette smoking.
Var transcription profiling of Plasmodium falciparum 3D7: assignment of cytoadherent phenotypes to dominant transcripts
Authors: Gölnitz Uta , Albrecht Letusa , Wunderlich Gerhard
Published: January 2008

Background

Cytoadherence ofPlasmodium falciparum-infected red blood cells is mediated byvargene-encodedP. falciparumerythrocyte membrane protein-1 and host receptor preference depends in most cases on which of the 50–60vargenes per genome is expressed. Enrichment of phenotypically homogenous parasites by panning on receptor expressing cells is fundamental for the identification of the correspondingvartranscript.

Methods

P. falciparum3D7 parasites were panned on several transfected CHO-cell lines and theirvartranscripts analysed by i) reverse transcription/PCR/cloning/sequencing using a universal DBLα specific oligonucleotide pair and ii) by reverse transcription followed by quantitative PCR using 57 different oligonucleotide pairs.

Results

Each cytoadherence selected parasite line also adhered to untransfected CHO-745 cells and upregulation of thevargene PFD995/PFD1000c was consistently associated with cytoadherence to all but one CHO cell line. In addition, parasites panned on different CHO cell lines revealed candidatevargenes which reproducibly associated to the respective cytoadherent phenotype. The transcription profile obtained by RT-PCR/cloning/sequencing differed significantly from that of RT-quantitative PCR.

Conclusion

Transfected CHO cell lines are of limited use for the creation of monophenotypic cytoadherent parasite lines. Nevertheless, 3D7 parasites can be reproducibly selected for the transcription of different determinedvargenes without genetic manipulation. Most importantly,vartranscription analysis by RT-PCR/cloning/sequencing may lead to erroneous interpretation ofvartranscription profiles.
Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile
Authors: Cifola Ingrid , Spinelli Roberta , Beltrame Luca , Peano Clelia , Fasoli Ester , Ferrero Stefano , Bosari Silvano , Signorini Stefano , Rocco Francesco , Perego Roberto , Proserpio Vanessa , Raimondo Francesca , Mocarelli Paolo , Battaglia Cristina
Published: January 2008

Background

Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.

Results

We performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.

Conclusion

By combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.
Low-volume muscular endurance and strength training during 3-week forearm immobilization was effective in preventing functional deterioration
Authors: Matsumura Mika , Ueda Chihoko , Shiroishi Kiyoshi , Esaki Kazuki , Ohmori Fumiko , Yamaguchi Kuniko , Ichimura Shiro , Kurosawa Yuko , Kime Ryotaro , Osada Takuya , Murase Norio , Katsumura Toshihito , Hoshika Akinori , Hamaoka Takafumi
Published: January 2008

Purpose

The purpose of this study was to determine whether endurance and strength hand grip exercises during 3-week upper limb immobilization preserve muscle oxidative capacity, endurance performance and strength.

Methods

Ten healthy adult men underwent non-dominant forearm immobilization by plaster cast for 21 days. Five healthy adult subjects were designated as the immobilization (IMM) group and five were designated as the immobilization + training (IMM+TRN) group. Grip strength, forearm circumference, dynamic handgrip endurance and muscle oxygenation response were measured before and after the 21 day immobilization period. Using near-infrared spectroscopy (NIRS), muscle oxygen consumption recovery (VO2mus) was recorded after a submaximal exercise and the recovery time constant (TcVO2mus) was calculated. Reactive hyperemic oxygenation recovery was evaluated after 5 minutes ischemia. Two training programs were performed by the IMM+TRN group twice a week. One exercise involved a handgrip exercise at 30% maximum voluntary contraction (MVC) at a rate of 1 repetition per 1 second until exhaustion (about 60 seconds). The other involved a handgrip exercise at 70% MVC for 2 seconds with a 2 second rest interval, repeated 10 times (40 seconds).

Results

There was a significant group-by-time interaction between the IMM and IMM+TRN groups in the TcVO2mus (p = 0.032, F = 6.711). A significant group-by-time interaction was observed between the IMM and IMM+TRN groups in the MVC (p = 0.001, F = 30.415) and in grip endurance (p = 0.014, F = 9.791). No significant group-by-time interaction was seen in forearm circumference and reactive hyperemic oxygenation response either in IMM or IMM+TRN group.

Conclusion

The training programs during immobilization period used in this experiment were effective in preventing a decline in muscle oxidative function, endurance and strength.
Cross-cultural adaptation of the Child Perceptions Questionnaire 11–14 (CPQ11–14) for the Brazilian Portuguese language
Authors: Goursand Daniela , Paiva Saul M , Zarzar Patrícia M , Ramos-Jorge Maria L , Cornacchia Gianfilippo M , Pordeus Isabela A , Allison Paul J
Published: January 2008

Background

Oral-Health-Related Quality of Life (OHRQoL) instruments are being used with increasing frequency in oral health surveys. However, these instruments are not available in all countries or all languages. The availability of cross-culturally valid, multi-lingual versions of instruments is important for epidemiological research. The Child Perceptions Questionnaire 11–14 (CPQ11–14) is an OHRQoL instrument that assesses the impact of oral conditions on the quality of life of children and adolescents. The objective of the current study was to carry out the cross-cultural adaptation of CPQ11–14for the Brazilian Portuguese language.

Methods

After translation and cross-cultural adaptation, the CPQ11–14was tested on 160 11-to-14-year-old children who were clinically and radiographically examined for the presence or absence of dental caries. The children were receiving dental care at the Pediatric Dental and Orthodontic clinics of the Federal University of Minas Gerais, Brazil. To test the quality of the translation, 17 children answered the questionnaire. The internal consistency of the instrument was assessed by Cronbach's Alpha Coefficient and the test-retest reliability by Intraclass Correlation Coefficient (ICC).

Results

The mean CPQ11–14score were 24.5 [standard deviation (SD) 18.27] in the group with caries and 12.89 [SD 10.95] in the group without caries. Median scores were 20 and 10 in the groups with and without caries, respectively (p< 0.001). Significant associations were identified between caries status and all CPQ domains (p< 0.05). Internal reliability was confirmed by a Cronbach's alpha coefficient of 0.86. Test-retest reliability revealed satisfactory reproducibility (ICC = 0.85). The questionnaire proved to be a valid instrument. Construct validity was satisfactory, demonstrating highly significant correlations with global indicators for the total scale and subscales. The CPQ11–14score was able to discriminate between different oral conditions (groups without and with untreated caries).

Conclusion

The present study demonstrated that the CPQ11–14is applicable to children in Brazil. It has satisfactory psychometric properties, but further research is required to evaluate these properties in a population study.
Small cell carcinoma of the appendix
Authors: O'Kane Anna M , O'Donnell Mark E , Shah Rajeev , Carey Declan P , Lee Jack
Published: January 2008

Background

An extrapulmonary small cell carcinoma is a rare condition. It has similar histological features to pulmonary small cell carcinoma and is equally aggressive.

Case presentation

We present the case of a 60-year-old woman who presented with right upper quadrant pain. Computerised tomography revealed an appendiceal lesion and multiple liver metastases. Exploratory laparotomy and right hemicolectomy was performed with histopathological analysis confirming a primary small cell carcinoma of her appendix.

Conclusion

This is the first reported case of a pure extrapulmonary carcinoma arising from the appendix.
The complete genome sequence of a Crimean-Congo Hemorrhagic Fever virus isolated from an endemic region in Kosovo
Authors: Duh Darja , Nichol Stuart T , Khristova Marina L , Saksida Ana , Hafner-Bratkovič Iva , Petrovec Miroslav , Dedushaj Iusuf , Ahmeti Salih , Avšič-Županc Tatjana
Published: January 2008

The Balkan region and Kosovo in particular, is a well-known Crimean-Congo hemorrhagic fever (CCHF) endemic region, with frequent epidemic outbreaks and sporadic cases occurring with a hospitalized case fatality of approximately 30%. Recent analysis of complete genome sequences of diverse CCHF virus strains showed that the genome plasticity of the virus is surprisingly high for an arthropod-borne virus. High levels of nucleotide and amino acid differences, frequent RNA segment reassortment and even RNA recombination have been recently described. This diversity illustrates the need to determine the complete genome sequence of CCHF virus representatives of all geographically distinct endemic areas, particularly in light of the high pathogenicity of the virus and its listing as a potential bioterrorism threat. Here we describe the first complete CCHF virus genome sequence of a virus (strain Kosova Hoti) isolated from a hemorrhagic fever case in the Balkans. This virus strain was isolated from a fatal CCHF case, and passaged only twice on Vero E6 cells prior to sequence analysis. The virus total genome was found to be 19.2 kb in length, consisting of a 1672 nucleotide (nt) S segment, a 5364 nt M segment and a 12150 nt L segment. Phylogenetic analysis of CCHF virus complete genomes placed the Kosova Hoti strain in the Europe/Turkey group, with highest similarity seen with Russian isolates. The virus M segments are the most diverse with up to 31 and 27% differences seen at the nt and amino acid levels, and even 1.9% amino acid difference found between the Kosova Hoti and another strain from Kosovo (9553-01). This suggests that distinct virus strains can coexist in highly endemic areas.
Sargassum fusiformefraction is a potent and specific inhibitor of HIV-1 fusion and reverse transcriptase
Authors: Paskaleva Elena E , Lin Xudong , Duus Karen , McSharry James J , Veille Jean-Claude L , Thornber Carol , Liu Yanze , Lee David Yu-Wei , Canki Mario
Published: January 2008

Sargassum fusiforme (Harvey) Setchell has been shown to be a highly effective inhibitor of HIV-1 infection. To identify its mechanism of action, we performed bioactivity-guided fractionation on Sargassum fusiforme mixture. Here, we report isolation of a bioactive fraction SP4-2 (S. fusiforme), which at 8 μg/ml inhibited HIV-1 infection by 86.9%, with IC50 value of 3.7 μg. That represents 230-fold enhancement of antiretroviral potency as compared to the whole extract. Inhibition was mediated against both CXCR4 (X4) and CCR5 (R5) tropic HIV-1. Specifically, 10 μg/ml SP4-2 blocked HIV-1 fusion and entry by 53%. This effect was reversed by interaction of SP4-2 with sCD4, suggesting that S. fusiforme inhibits HIV-1 infection by blocking CD4 receptor, which also explained observed inhibition of both X4 and R5-tropic HIV-1. SP4-2 also inhibited HIV-1 replication after virus entry, by directly inhibiting HIV-1 reverse transcriptase (RT) in a dose dependent manner by up to 79%. We conclude that the SP4-2 fraction contains at least two distinct and biologically active molecules, one that inhibits HIV-1 fusion by interacting with CD4 receptor, and another that directly inhibits HIV-1 RT. We propose that S. fusiforme is a lead candidate for anti-HIV-1 drug development.
Human 14-3-3 gamma protein results in abnormal cell proliferation in the developing eye of Drosophila melanogaster
Authors: Hong Sophia W , Qi Wenqing , Brabant Marc , Bosco Giovanni , Martinez Jesse D
Published: January 2008

Background

14-3-3 proteins are a family of adaptor proteins that participate in a wide variety of cellular processes. Recent evidence indicates that the expression levels of these proteins are elevated in some human tumors providing circumstantial evidence for their involvement in human cancers. However, the mechanism through which these proteins act in tumorigenesis is uncertain.

Results

To determine whether elevated levels of 14-3-3 proteins may perturb cell growth we overexpressed human 14-3-3 gamma (h14-3-3 gamma) in Drosophila larvae using the heat shock promoter or theGMR-Gal4driver and then examined the effect that this had on cell proliferation in the eye imaginal discs of third instar larvae. We found that induction of h14-3-3 gamma resulted in the abnormal appearance of replicating cells in the differentiating proneural photoreceptor cells of eye imaginal discs where h14-3-3 gamma was driven by the heat shock promoter. Similarly, we found that driving h14-3-3 gamma expression specifically in developing eye discs with theGMR-Gal4driver resulted in increased numbers of replicative cells following the morphogenetic furrow. Interestingly, we found that the effects of overexpressing h1433 gamma on eye development were increased in a genetic background whereString(cdc25) function was compromised.

Conclusion

Taken together our results indicate that h14-3-3 gamma can promote abnormal cell proliferation and may act through Cdc25. This has important implications for 14-3-3 gamma as an oncogene as it suggests that elevated levels of 14-3-3 may confer a growth advantage to cells that overexpress it.
Is it more dangerous to perform inadequate packing?
Authors: Aydin Unal , Yazici Pinar , Zeytunlu Murat , Coker Ahmet
Published: January 2008

Peri-hepatic packing procedure, which is the basic damage control technique for the treatment of hepatic hemorrhage, is one of the cornerstones of the surgical strategy for abdominal trauma. The purpose of this study was to evaluate the efficacy of the perihepatic packing procedure by comparing the outcomes of appropriately and inappropriately performed interventions. Trauma patients with liver injury were retrospectively evaluated. The patients who had undergone adequate packing were classified as Group A, and the patients who had undergone inappropriate packing, as Group B. Over a five-year period, nineteen patients underwent perihepatic packing. Thirteen of these patients were referred by other hospitals. Of 13 patients, 9 with inappropriate packing procedure due to insertion of intraabdominal drainage catheter (n=4) and underpacking (n=5) were evaluated in Group B, and the others (n=10) with adequate packing were assessed in Group A. Mean 3 units of blood were transfused in Group A and unpacking procedure was performed in the 24th hour. Only 3 (30%) patients required segment resection with homeostasis, and the mortality rate was 20% (2/10 patients). In Group B, 4 patients required repacking in the first 6 hrs. Mean 8 units of blood were transfused until unpacking procedure. The mortality rate was 44% (4/9 patients). The length of intensive care unit stay and requirement of blood transfusion were statistically significantly lower in Group A (p < 0.05). The mortality rate of this group was also lower. However, the difference between the groups for mortality rates was not statistically significant. This study emphasizes that efficacy of the procedure is one of the determinants that affects the results, and inadequate or inappropriate packing may easily result in poor outcome.
Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction
Authors: Franke Raimo , Müller Melanie , Wundrack Nicole , Gilles Ernst-Dieter , Klamt Steffen , Kähne Thilo , Naumann Michael
Published: January 2008

Background

The hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of tissues, including epithelial cells, on binding to the receptor tyrosine kinase c-Met. Abnormal c-Met signalling contributes to tumour genesis, in particular to the development of invasive and metastatic phenotypes. The human microbial pathogen Helicobacter pylori can induce chronic gastritis, peptic ulceration and more rarely, gastric adenocarcinoma. The H. pylori effector protein cytotoxin associated gene A (CagA), which is translocated via a type IV secretion system (T4SS) into epithelial cells, intracellularly modulates the c-Met receptor and promotes cellular processes leading to cell scattering, which could contribute to the invasiveness of tumour cells. Using a logical modelling framework, the presented work aims at analysing the c-Met signal transduction network and how it is interfered by H. pylori infection, which might be of importance for tumour development.

Results

A logical model of HGF and H. pylori induced c-Met signal transduction is presented in this work. The formalism of logical interaction hypergraphs (LIH) was used to construct the network model. The molecular interactions included in the model were all assembled manually based on a careful meta-analysis of published experimental results. Our model reveals the differences and commonalities of the response of the network upon HGF and H. pylori induced c-Met signalling. As another important result, using the formalism of minimal intervention sets, phospholipase Cγ1 (PLCγ1) was identified as knockout target for repressing the activation of the extracellular signal regulated kinase 1/2 (ERK1/2), a signalling molecule directly linked to cell scattering in H. pylori infected cells. The model predicted only an effect on ERK1/2 for the H. pylori stimulus, but not for HGF treatment. This result could be confirmed experimentally in MDCK cells using a specific pharmacological inhibitor against PLCγ1. The in silico predictions for the knockout of two other network components were also verified experimentally.

Conclusion

This work represents one of the first approaches in the direction of host-pathogen systems biology aiming at deciphering signalling changes brought about by pathogenic bacteria. The suitability of our network model is demonstrated by an in silico prediction of a relevant target against pathogen infection.
Can clinically relevant prognostic subsets of breast cancer patients with four or more involved axillary lymph nodes be identified through immunohistochemical biomarkers? A tissue microarray feasibility study
Authors: Crabb Simon J , Bajdik Chris D , Leung Samuel , Speers Caroline H , Kennecke Hagen , Huntsman David G , Gelmon Karen A
Published: January 2008

Introduction

Primary breast cancer involving four or more axillary lymph nodes carries a poor prognosis. We hypothesized that use of an immunohistochemical biomarker scoring system could allow for identification of variable risk subgroups.

Methods

Patients with four or more positive axillary nodes were identified from a clinically annotated tissue microarray of formalin-fixed paraffin-embedded primary breast cancers and randomized into a 'test set' and a 'validation set'. A prospectively defined prognostic scoring model was developed in the test set and was further assessed in the validation set combining expression for eight biomarkers by immunohistochemistry, including estrogen receptor, human epidermal growth factor receptors 1 and 2, carbonic anhydrase IX, cytokeratin 5/6, progesterone receptor, p53 and Ki-67. Survival outcomes were analyzed by the Kaplan–Meier method, log rank tests and Cox proportional-hazards models.

Results

A total of 313 eligible patients were identified in the test set for whom 10-year relapse-free survival was 38.3% (SEM 2.9%), with complete immunohistochemical data available for 227. Tumor size, percentage of positive axillary nodes and expression status for the progesterone receptor, Ki-67 and carbonic anhydrase IX demonstrated independent prognostic significance with respect to relapse-free survival. Our combined biomarker scoring system defined three subgroups in the test set with mean 10-year relapse-free survivals of 75.4% (SEM 7.0%), 35.3% (SEM 4.1%) and 19.3% (SEM 7.0%). In the validation set, differences in relapse-free survival for these subgroups remained statistically significant but less marked.

Conclusion

Biomarkers assessed here carry independent prognostic value for breast cancer with four or more positive axillary nodes and identified clinically relevant prognostic subgroups. This approach requires refinement and validation of methodology.