bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational expression deconvolution in a complex mammalian organ
Authors: Wang Min , Master Stephen R , Chodosh Lewis A 
Published: September 2006

Abstract

Background
Microarray expression profiling has been widely used to identify differentially expressed genes in complex cellular systems. However, while such methods can be used to directly infer intracellular regulation within homogeneous cell populations, interpretation of in vivo gene expression data derived from complex organs composed of multiple cell types is more problematic. Specifically, observed changes in gene expression may be due either to changes in gene regulation within a given cell type or to changes in the relative abundance of expressing cell types. Consequently, bona fide changes in intrinsic gene regulation may be either mimicked or masked by changes in the relative proportion of different cell types. To date, few analytical approaches have addressed this problem.

Results
We have chosen to apply a computational method for deconvoluting gene expression profiles derived from intact tissues by using reference expression data for purified populations of the constituent cell types of the mammary gland. These data were used to estimate changes in the relative proportions of different cell types during murine mammary gland development and Ras-induced mammary tumorigenesis. These computational estimates of changing compartment sizes were then used to enrich lists of differentially expressed genes for transcripts that change as a function of intrinsic intracellular regulation rather than shifts in the relative abundance of expressing cell types. Using this approach, we have demonstrated that adjusting mammary gene expression profiles for changes in three principal compartments – epithelium, white adipose tissue, and brown adipose tissue – is sufficient both to reduce false-positive changes in gene expression due solely to changes in compartment sizes and to reduce false-negative changes by unmasking genuine alterations in gene expression that were otherwise obscured by changes in compartment sizes.

Conclusion
By adjusting gene expression values for changes in the sizes of cell type-specific compartments, this computational deconvolution method has the potential to increase both the sensitivity and specificity of differential gene expression experiments performed on complex tissues. Given the necessity for understanding complex biological processes such as development and carcinogenesis within the context of intact tissues, this approach offers substantial utility and should be broadly applicable to identifying gene expression changes in tissues composed of multiple cell types.
Cancer diagnosis marker extraction for soft tissue sarcomas based on gene expression profiling data by using projective adaptive resonance theory (PART) filtering method
Authors: Takahashi Hiro , Nemoto Takeshi , Yoshida Teruhiko , Honda Hiroyuki , Hasegawa Tadashi 
Published: September 2006

AbstractBackgroundRecent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis and selection of treatment. To accomplish this objective, it is important to establish a sophisticated algorithm that can deal with large quantities of data such as gene expression profiles obtained by DNA microarray analysis.ResultsPreviously, we developed the projective adaptive resonance theory (PART) filtering method as a gene filtering method. This is one of the clustering methods that can select specific genes for each subtype. In this study, we applied the PART filtering method to analyze microarray data that were obtained from soft tissue sarcoma (STS) patients for the extraction of subtype-specific genes. The performance of the filtering method was evaluated by comparison with other widely used methods, such as signal-to-noise, significance analysis of microarrays, and nearest shrunken centroids. In addition, various combinations of filtering and modeling methods were used to extract essential subtype-specific genes. The combination of the PART filtering method and boosting – the PART-BFCS method – showed the highest accuracy. Seven genes among the 15 genes that are frequently selected by this method –MIF,CYFIP2,HSPCB,TIMP3,LDHA,ABR, andRGS3– are known prognostic marker genes for other tumors. These genes are candidate marker genes for the diagnosis of STS. Correlation analysis was performed to extract marker genes that were not selected by PART-BFCS. Sixteen genes among those extracted are also known prognostic marker genes for other tumors, and they could be candidate marker genes for the diagnosis of STS.ConclusionThe procedure that consisted of two steps, such as the PART-BFCS and the correlation analysis, was proposed. The results suggest that novel diagnostic and therapeutic targets for STS can be extracted by a procedure that includes the PART filtering method.
High degree of conservancy among secreted salivary gland proteins from two geographically distant Phlebotomus duboscqi sandflies populations (Mali and Kenya)
Authors: Kato Hirotomo , Anderson Jennifer M , Kamhawi Shaden , Oliveira Fabiano , Lawyer Phillip G , Pham Van My , Sangare Constance Souko , Samake Sibiry , Sissoko Ibrahim , Garfield Mark , Sigutova Lucie , Volf Petr , Doumbia Seydou , Valenzuela Jesus G 
Published: September 2006

AbstractBackgroundSalivary proteins from sandflies are potential targets for exploitation as vaccines to controlLeishmaniainfection; in this work we tested the hypothesis that salivary proteins from geographically distantPhlebotomus duboscqisandfly populations are highly divergent due to the pressure exerted by the host immune response. Salivary gland cDNA libraries were prepared from wild-caughtP. duboscqifrom Mali and recently colonised flies of the same species from Kenya.ResultsTranscriptome and proteome analysis resulted in the identification of the most abundant salivary gland-secreted proteins. Orthologues of these salivary proteins were identified by phylogenetic tree analysis. Moreover, comparative analysis between the orthologues of these two different populations resulted in a high level of protein identity, including the predicted MHC class II T-cell epitopes from all these salivary proteins.ConclusionThese data refute the hypothesis that salivary proteins from geographically distinct populations of the same Phlebotomus sandfly species are highly divergent. They also suggest the potential for using the same species-specific components in a potential vector saliva-based vaccine.
Functional assessment of older patients in the emergency department: comparison between standard instruments, medical records and physicians' perceptions
Authors: Rodríguez-Molinero Alejandro , López-Diéguez María , Tabuenca Ana I , de la Cruz Juan J , Banegas José R 
Published: September 2006

Abstract

Background
We evaluated the accuracy of physician recognition of functional status impairment in older emergency departments (ED) patients. In particular, we evaluated the accuracy of medical records (a comparison of the information in the medical record with the functional status based on proxy interviews), and the accuracy of physician knowledge (a comparison of the information obtained from the responsible physician with the functional status based on proxy interviews).

Methods
Cross-sectional study on 101 frail older patients selected at random from among those attending ED, their ED physicians, and respondents. The study was conducted at ED in four general university teaching hospitals in a city, from July through November 2003. Functional data shown on patients' medical records were compared against functional data obtained from respondents (family members), using Kendall's Tau-b statistic. In addition patients' Katz Indices (which assesses six basic activities of daily living – basic ADL) based on interviews with ED physicians were compared against those obtained from respondents, using the coefficient of concordance weighted kappa (κ). Each patient and his respondent were paired with a single physician.

Results
The correlation between information on dependence for basic ADL obtained from medical records and that furnished by respondents, was 0.41 (95% CI 0.27–0.55). Concordance between the respective Katz Indices obtained from physicians and respondents was 0.47 (95% CI 0.38–0.57).

Conclusion
Older subjects' functional status is not properly assessed by emergency department physicians.
β3-adrenergic receptor gene, body mass index, bone mineral density and fracture risk in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES)
Authors: Wang Claire Y , Nguyen Nguyen D , Morrison Nigel A , Eisman John A , Center Jacqueline R , Nguyen Tuan V 
Published: September 2006

Abstract

Background
Recent studies have suggested that the Arg allele of β3-adrenergic receptor (ADRB3) gene is associated with body mass index (BMI), which is an important predictor of bone mineral density (BMD) and fracture risk. However, whether the ADRB3 gene polymorphism is associated with fracture risk has not been investigated. The aim of study was to examine the inter-relationships between ADRB3 gene polymorphisms, BMI, BMD and fracture risk in elderly Caucasians.

Methods
Genotypes of the ADRB3 gene were determined in 265 men and 446 women aged 60+ in 1989 at entry into the study, whose BMD were measured by DXA (GE Lunar, WI USA) at baseline. During the follow-up period (between 1989 and 2004), fractures were ascertained by reviewing radiography reports and personal interviews.

Results
The allelic frequencies of the Trp and the Arg alleles were 0.925 and 0.075 respectively, and the relative frequencies of genotypes Trp/Trp, Trp/Arg and Arg/Arg 0.857, 0.138 and 0.006 respectively. There was no significant association between BMI and ADRB3 genotypes (p = 0.10 in women and p = 0.68 in men). There was also no significant association between ADRB3 genotypes and lumbar spine or femoral neck BMD in either men and women. Furthermore, there were no significant association between ADRB3 genotypes and fracture risk in both women and men, either before or after adjusting for and, BMD and BMI.

Conclusion
The present data suggested that in Caucasian population the contribution of ADRB3 genotypes to the prediction of BMI, BMD and fracture risk is limited.
Inter-annual growth of Arctic charr (Salvelinus alpinus, L.) in relation to climate variation
Authors: Kristensen David M , Jørgensen Thomas R , Larsen Rasmus K , Forchhammer Mads C , Christoffersen Kirsten S 
Published: September 2006

Abstract

Background
Major changes in climate have been observed in the Arctic and climate models predict further amplification of the enhanced greenhouse effect at high-latitudes leading to increased warming. We propose that warming in the Arctic may affect the annual growth conditions of the cold adapted Arctic charr and that such effects can already be detected retrospectrally using otolith data.

Results
Inter-annual growth of the circumpolar Arctic charr (Salvelinus alpinus, L.) was analysed in relation to climatic changes observed in the Arctic during the last two decades. Arctic charr were sampled from six locations at Qeqertarsuaq in West Greenland, where climate data have been recorded since 1990. Two fish populations met the criteria of homogeny and, consequently, only these were used in further analyses. The results demonstrate a complex coupling between annual growth rates and fluctuations in annual mean temperatures and precipitation. Significant changes in temporal patterns of growth were observed between cohorts of 1990 and 2004.

Conclusion
Differences in pattern of growth appear to be a consequence of climatic changes over the last two decades and we thereby conclude that climatic affects short term and inter-annual growth as well as influencing long term shifts in age-specific growth patterns in population of Arctic charr.
Comparison of chromosomal and array-based comparative genomic hybridization for the detection of genomic imbalances in primary prostate carcinomas
Authors: Ribeiro Franclim R , Henrique Rui , Hektoen Merete , Berg Marianne , Jerónimo Carmen , Teixeira Manuel R , Lothe Ragnhild A 
Published: September 2006

Abstract

Background
In order to gain new insights into the molecular mechanisms involved in prostate cancer, we performed array-based comparative genomic hybridization (aCGH) on a series of 46 primary prostate carcinomas using a 1 Mbp whole-genome coverage platform. As chromosomal comparative genomic hybridization (cCGH) data was available for these samples, we compared the sensitivity and overall concordance of the two methodologies, and used the combined information to infer the best of three different aCGH scoring approaches.

Results
Our data demonstrate that the reliability of aCGH in the analysis of primary prostate carcinomas depends to some extent on the scoring approach used, with the breakpoint estimation method being the most sensitive and reliable. The pattern of copy number changes detected by aCGH was concordant with that of cCGH, but the higher resolution technique detected 2.7 times more aberrations and 15.2% more carcinomas with genomic imbalances. We additionally show that several aberrations were consistently overlooked using cCGH, such as small deletions at 5q, 6q, 12p, and 17p. The latter were validated by fluorescence in situ hybridization targeting TP53, although only one carcinoma harbored a point mutation in this gene. Strikingly, homozygous deletions at 10q23.31, encompassing the PTEN locus, were seen in 58% of the cases with 10q loss.

Conclusion
We conclude that aCGH can significantly improve the detection of genomic aberrations in cancer cells as compared to previously established whole-genome methodologies, although contamination with normal cells may influence the sensitivity and specificity of some scoring approaches. Our work delineated recurrent copy number changes and revealed novel amplified loci and frequent homozygous deletions in primary prostate carcinomas, which may guide future work aimed at identifying the relevant target genes. In particular, biallelic loss seems to be a frequent mechanism of inactivation of the PTEN gene in prostate carcinogenesis.
The virion-associated incoming HIV-1 RNA genome is not targeted by RNA interference
Authors: Westerhout Ellen M , ter Brake Olivier , Berkhout Ben 
Published: September 2006

Abstract

Background
RNA interference (RNAi) has proven to be a powerful tool to suppress gene expression and can be used as a therapeutic strategy against human pathogenic viruses such as human immunodeficiency virus type 1 (HIV-1). Theoretically, RNAi-mediated inhibition can occur at two points in the replication cycle, upon viral entry before reverse transcription of the RNA genome, and on the newly transcribed viral RNA transcripts. There have been conflicting results on whether RNAi can target the RNA genome of infecting HIV-1 particles. We have addressed this issue with HIV-1-based lentiviral vectors.

Results
We determined the transduction efficiency of a lentiviral vector, as measured by GFP expressing cells, which reflects the number of successful integration events in a cell line stably expressing shNef. We did not observe a difference in the transduction efficiency comparing lentiviral vectors with or without the Nef target sequence in their genome. The results were similar with particles pseudotyped with either the VSV-G or HIV-1 envelope. Additionally, no reduced transduction efficiencies were observed with multiple other shRNAs targeting the vector genome or with synthetic siNef when transiently transfected prior to transduction.

Conclusion
Our findings indicate that the incoming HIV-1 RNA genome is not targeted by RNAi, probably due to inaccessibility to the RNAi machinery. Thus, therapeutic RNAi strategies aimed at preventing proviral integration should be targeting cellular receptors or co-factors involved in pre-integration events.
Genetic analysis of Thailand hantavirus in Bandicota indica trapped in Thailand
Authors: Hugot Jean-Pierre , Plyusnina Angelina , Herbreteau Vincent , Nemirov Kirill , Laakkonen Juha , Lundkvist Åke , Supputamongkol Yupin , Henttonen Heikki , Plyusnin Alexander 
Published: September 2006

Abstract
Sixty one tissue samples from several rodent species trapped in five provinces of Thailand were examined for the presence of hantaviral markers by enzyme-immunoassay and immunoblotting. Four samples, all from the great bandicoot rat Bandicota indica, were confirmed positive for the hantaviral N-antigen. Two of them were trapped in Nakhon Pathom province, the other two in Nakhon Ratchasima province, approximately 250 km from the other trapping site. When analysed by RT-nested PCR, all four rodents were found positive for the hantaviral S- and M-segment nucleotide sequences. Genetic analysis revealed that the four newly described wild-type strains belong to Thailand hantavirus. On the phylogenetic trees they formed a well-supported cluster within the group of Murinae-associated hantaviruses and shared a recent common ancestor with Seoul virus.
A rapid ethnographic study of breastfeeding in the North and South of Italy
Authors: Quintero Romero Sofia , Bernal Rosa , Barbiero Chiara , Passamonte Raquel , Cattaneo Adriano 
Published: September 2006

Abstract

Background
The past ten years have witnessed a rising trend in the prevalence and duration of breastfeeding in Italy, but breastfeeding rates increase in an unequal way; they are higher in the North of Italy than in the South. The purpose of this study was to describe the experiences, expectations and beliefs of a sample of mothers, and to identify differences, if any, between the North and the South of Italy.

Methods
The study was conducted in two regions of Italy, Friuli Venezia Giulia in the Northeast and Basilicata in the South. Two hundred and seventy-nine mothers of infants and children 6 to 23 months of age were interviewed using an 85-item questionnaire including closed and open questions on infant feeding experiences and beliefs, sources of information and support, reasons for intended and actual choices and practices, and some demographic and social variables. Face-to-face interviews were conducted between May 2001 and September 2002. Quantitative and qualitative methods were used for data analysis.

Results
The distribution of the mothers by age, education, employment and parity did not differ from that of the general population of the two regions. The reported rates of initiation and duration of breastfeeding were also similar: 95% started breastfeeding, exclusive breastfeeding was 32% at three and 9% at six months, with 64% and 35% of any breastfeeding, respectively. Some differences were reported in the rates of full breastfeeding, reflecting different ages of introduction of non-nutritive fluids. These, as well as nutritive fluids – including infant formula – and complementary foods, were introduced far too early. Advice on infant feeding was generally provided by health professionals and often was not based on up-to-date recommendations. Mothers were generally aware of the advantages of breastfeeding, but at the same time reported problems that they were not able to solve alone or through social and health system support. Most mothers would welcome the support of a peer counsellor. More mothers in Basilicata than in Friuli Venezia Giulia reported difficulties with breastfeeding related to returning to work and were not familiar with their rights on breastfeeding and maternity leave.

Conclusion
Programmes for the protection, promotion and support of breastfeeding in these and similar regions of Italy should concentrate on better training of health professionals with regards to lactation management, communication, and counselling skills. The addition of trained peer counsellors could reinforce the work done by the health system and, through community involvement, could help change social prejudice in the mid- and long-term. The differences between regions should be taken into account in formulating these programmes to avoid increasing, and possibly to decrease, the current gaps.
Metabolic labeling of plant cell cultures with K15NO3 as a tool for quantitative analysis of proteins and metabolites
Authors: Engelsberger Wolfgang R , Erban Alexander , Kopka Joachim , Schulze Waltraud X 
Published: September 2006

Abstract
Strategies for robust quantitative comparison between different biological samples are of high importance in experiments that address biological questions beyond the establishment of protein lists. Here, we propose the use of 15N-KNO3 as the only nitrogen source in Arabidopsis cell cultures in order to achieve a metabolically fully labeled cell population. Proteins from such metabolically labeled culture are distinguishable from unlabeled protein populations by a characteristic mass shift that depends on the amino acid composition of the tryptic peptide analyzed. In addition, the metabolically labeled cell extracts are also suitable for comparative quantitative analysis of nitrogen-containing cellular metabolic complement. Protein extracts from unlabeled and from standardized 15N-labeled cells were combined into one sample for joined analytical processing. This has the advantage of (i) reduced experimental variability and (ii) immediate relative quantitation at the level of single extracted peptide and metabolite spectra. Together ease and accuracy of relative quantitation for profiling experiments is substantially improved. The metabolic labeling strategy has been validated by mixtures of protein extracts and metabolite extracts from the same cell cultures in known ratios of labeled to unlabeled extracts (1:1, 1:4, and 4:1). We conclude that saturating metabolic 15N-labeling provides a robust and affordable integrative strategy to answer questions in quantitative proteomics and nitrogen focused metabolomics.
Cri du Chat syndrome
Authors: Cerruti Mainardi Paola 
Published: September 2006

AbstractThe Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-). The incidence ranges from 1:15,000 to 1:50,000 live-born infants. The main clinical features are a high-pitched monochromatic cry, microcephaly, broad nasal bridge, epicanthal folds, micrognathia, abnormal dermatoglyphics, and severe psychomotor and mental retardation. Malformations, although not very frequent, may be present: cardiac, neurological and renal abnormalities, preauricular tags, syndactyly, hypospadias, and cryptorchidism. Molecular cytogenetic analysis has allowed a cytogenetic and phenotypic map of 5p to be defined, even if results from the studies reported up to now are not completely in agreement. Genotype-phenotype correlation studies showed a clinical and cytogenetic variability. The identification of phenotypic subsets associated with a specific size and type of deletion is of diagnostic and prognostic relevance. Specific growth and psychomotor development charts have been established. Two genes, Semaphorin F (SEMAF) andδ-catenin (CTNND2), which have been mapped to the "critical regions", are potentially involved in cerebral development and their deletion may be associated with mental retardation in CdCS patients. Deletion of the telomerase reverse transcriptase (hTERT) gene, localised to 5p15.33, could contribute to the phenotypic changes in CdCS. The critical regions were recently refined by using array comparative genomic hybridisation. The cat-like cry critical region was further narrowed using quantitative polymerase chain reaction (PCR) and three candidate genes were characterised in this region. The diagnosis is based on typical clinical manifestations. Karyotype analysis and, in doubtful cases, FISH analysis will confirm the diagnosis. There is no specific therapy for CdCS but early rehabilitative and educational interventions improve the prognosis and considerable progress has been made in the social adjustment of CdCS patients.