bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental risk and young children’s cognitive and behavioral development
Authors: Pike Alison , Iervolino Alessandra C. , Eley Thalia C. , Price Thomas S. , Plomin Robert
Published: February 2006

Using a longitudinal, large-scale sample of British twins, we addressed the prediction of both cognitive abilities and behavioral adjustment from eight domains of environmental risk: minority status, socio-economic status, maternal medical factors, twin medical factors, maternal depression, chaos within the home environment, and parental feelings towards their children and discipline. Participants included 5765 families with twins (49.1% male) born in 1994 and 1995. Aspects of environmental risk were assessed from birth until the children’s third birthdays; outcome measures were assessed at their fourth birthdays. Overall prediction of outcome (via multiple regression analysis) was moderate (R = .23 -.48). SES and chaos were the strongest predictors for the cognitive outcomes whereas for total behavior problems the more proximal parenting factors were also dominant. Future analyses will investigate these environmental risk indicators in the context of the genetically sensitive twin design.
Self-construal and socio-emotional development among Vietnamese-American adolescents: An examination of different types of self-construal
Authors: Lam Brian Trung
Published: February 2006

This study examined how four different types of self-construal affected perception of socio-emotional adjustment (i.e., anxiety, depression, distress, self-esteem, family cohesion, peer support, pro-substance abuse attitude) and perception of relationship with community (i.e., sense of community, adverse neighborhood) in a sample of 152 Vietnamese-American high-school adolescents. Using cluster analysis, the four-type self-construal model postulated by Kim, Hunter, Miyahara, Horvath, Bresnahan, & Yoon (1996) was replicated in this sample. The bicultural students (i.e., those with strong interdependent and independent self-construal) reported greater perceived adjustment across all measures except anxiety when compared to other groups (marginal, interdependent, and independent) in the study. Implications of the findings are discussed.
The Practice and Politics of Responsive Evaluation
Authors: Abma Tineke A.
Published: February 2006

Responsive evaluation offers a perspective in which evaluation is reframed from the assessment of program interventions on the basis of policy makers' goals to an engagement with and among all stakeholders about the value and meaning of their practice. Responsive evaluators have to be extra sensitive to power relations given the deliberate attempts to acknowledge ambiguity and the plurality of interests and values and to foster genuine dialogue. The author illustrates the practice and politics of responsive evaluation with case examples from two policy fields, arts education and mental health care. In these evaluation studies, process-oriented heuristics have been developed to deal with the unequal social relations and power in responsive evaluation. As such, responsive evaluation offers an interesting example of the politics of evaluation. The emerging heuristics may be helpful to other evaluation approaches.
Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial
Authors: Milligan Donald W. , Wheatley Keith , Littlewood Timothy , Craig Jenny I. O. , Burnett Alan K. ,   for the NCRI Haematological Oncology Clinical Studies Group
Published: February 2006

The optimum chemotherapy schedule for reinduction of patients with high-risk acute myeloid leukemia (relapsed, resistant/refractory, or adverse genetic disease) is uncertain. The MRC AML (Medical Research Council Acute Myeloid Leukemia) Working Group designed a trial comparing fludarabine and high-dose cytosine (FLA) with standard chemotherapy comprising cytosine arabinoside, daunorubicin, and etoposide (ADE). Patients were also randomly assigned to receive filgrastim (G-CSF) from day 0 until neutrophil count was greater than 0.5 × 109/L (or for a maximum of 28 days) and all-trans retinoic acid (ATRA) for 90 days. Between 1998 and 2003, 405 patients were entered: 250 were randomly assigned between FLA and ADE; 356 to G-CSF versus no G-CSF; 362 to ATRA versus no ATRA. The complete remission rate was 61% with 4-year disease-free survival of 29%. There were no significant differences in the CR rate, deaths in CR, relapse rate, or DFS between ADE and FLA, although survival at 4 years was worse with FLA (16% versus 27%, P = .05). Neither the addition of ATRA nor G-CSF demonstrated any differences in the CR rate, relapse rate, DFS, or overall survival between the groups. In conclusion these findings indicate that FLA may be inferior to standard chemotherapy in high-risk AML and that the outcome is not improved with the addition of either G-CSF or ATRA.
Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival
Authors: Starlets Diana , Gore Yael , Binsky Inbal , Haran Michal , Harpaz Nurit , Shvidel Lev , Becker-Herman Shirly , Berrebi Alain , Shachar Idit
Published: February 2006

CD74 is an integral membrane protein that was thought to function mainly as an MHC class II chaperone. However, CD74 was recently shown to have a role as an accessory-signaling molecule. Our studies demonstrated that CD74 regulates B-cell differentiation by inducing a pathway leading to the activation of transcription mediated by the NF-κB p65/RelA homodimer and its coactivator, TAFII105. Here, we show that CD74 stimulation with anti-CD74 antibody leads to an induction of a signaling cascade resulting in NF-κB activation, entry of the stimulated cells into the S phase, elevation of DNA synthesis, cell division, and augmented expression of BCL-XL. These studies therefore demonstrate that surface CD74 functions as a survival receptor.
A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis
Authors: Nakamura Takanori , Miyakawa Yoshitaka , Miyamura Atsushi , Yamane Akiko , Suzuki Hidenori , Ito Mamoru , Ohnishi Yasuyuki , Ishiwata Norihisa , Ikeda Yasuo , Tsuruzoe Nobutomo
Published: February 2006

NIP-004 is a novel synthetic compound developed to display human thrombopoietin (TPO) receptor (c-Mpl) agonist activity. NIP-004 displays species specificity, stimulating proliferation or differentiation of human c-Mpl–expressing cells such as UT-7/TPO and human CD34+ cells but not murine c-Mpl–expressing cells or cynomolgus monkey cells. To test the mechanism of its action, we constructed mutant forms of c-Mpl; murine c-MplL490H dis-played a response to NIP-004, whereas human c-MplH499L lost this response, indicating that histidine in the transmembrane domain of c-Mpl is essential for its activity. Because histidine is not present in the c-Mpl transmembrane domain of rats, hamsters, rhesus macaques, and cynomolgus monkeys, we examined the in vivo efficacy of NIP-004 using mice that received xenotransplants. In immunodeficient nonobese diabetic (NOD)/Shi-scid, IL-2Rγnull (NOG) mice receiving transplants of umbilical cord blood–derived CD34+ cells, NIP-004 increased human megakaryoblasts, mature megakaryocytes, and circulating human platelets 6-fold, the latter being morphologically and functionally indistinguishable from normal human platelets. These observations indicate that NIP-004 is a novel human c-Mpl activator and induces human thrombopoiesis.
Inefficient cationic lipid-mediated siRNA and antisense oligonucleotide transfer to airway epithelial cells in vivo
Authors: Griesenbach Uta , Kitson Chris , Garcia Escudero Sara , Farley Raymond , Singh Charanjit , Somerton Luci , Painter Hazel , Smith Rbecca L , Gill Deborah R , Hyde Stephen C , Chow Yu-Hua , Hu Jim , Gray Mike , Edbrooke Mark , Ogilvie Varrie , MacGregor Gordon , Scheule Ronald K , Cheng Seng H , Caplen Natasha J , Alton Eric WFW
Published: February 2006

Background

The cationic lipid Genzyme lipid (GL) 67 is the current "gold-standard" for in vivo lung gene transfer. Here, we assessed, if GL67 mediated uptake of siRNAs and asODNs into airway epithelium in vivo.

Methods

Anti-lacZ and ENaC (epithelial sodium channel) siRNA and asODN were complexed to GL67 and administered to the mouse airway epithelium in vivo Transfection efficiency and efficacy were assessed using real-time RT-PCR as well as through protein expression and functional studies. In parallel in vitro experiments were carried out to select the most efficient oligonucleotides.

Results

In vitro, GL67 efficiently complexed asODNs and siRNAs, and both were stable in exhaled breath condensate. Importantly, during in vitro selection of functional siRNA and asODN we noted that asODNs accumulated rapidly in the nuclei of transfected cells, whereas siRNAs remained in the cytoplasm, a pattern consistent with their presumed site of action. Following in vivo lung transfection siRNAs were only visible in alveolar macrophages, whereas asODN also transfected alveolar epithelial cells, but no significant uptake into conducting airway epithelial cells was seen. SiRNAs and asODNs targeted to β-galactosidase reduced βgal mRNA levels in the airway epithelium of K18-lacZ mice by 30% and 60%, respectively. However, this was insufficient to reduce protein expression. In an attempt to increase transfection efficiency of the airway epithelium, we increased contact time of siRNA and asODN using the in vivo mouse nose model. Although highly variable and inefficient, transfection of airway epithelium with asODN, but not siRNA, was now seen. As asODNs more effectively transfected nasal airway epithelial cells, we assessed the effect of asODN against ENaC, a potential therapeutic target in cystic fibrosis; no decrease in ENaC mRNA levels or function was detected.

Conclusion

This study suggests that although siRNAs and asODNs can be developed to inhibit gene expression in culture systems and certain organs in vivo, barriers to nucleic acid transfer in airway epithelial cells seen with large DNA molecules may also affect the efficiency of in vivo uptake of small nucleic acid molecules.
Bronchoscopic assessment of airway retention time of aerosolized xylitol
Authors: Durairaj Lakshmi , Neelakantan Srividya , Launspach Janice , Watt Janet L , Allaman Margaret M , Kearney William R , Veng-Pedersen Peter , Zabner Joseph
Published: February 2006

Background

Human airway surface liquid (ASL) has abundant antimicrobial peptides whose potency increases as the salt concentration decreases. Xylitol is a 5-carbon sugar that has the ability to lower ASL salt concentration, potentially enhancing innate immunity. Xylitol was detected for 8 hours in the ASL after application in airway epithelium in vitro. We tested the airway retention time of aerosolized iso-osmotic xylitol in healthy volunteers.

Methods

After a screening spirometry, volunteers received 10 ml of nebulized 5% xylitol. Bronchoscopy was done at 20 minutes (n = 6), 90 minutes (n = 6), and 3 hours (n = 5) after nebulization and ASL was collected using microsampling probes, followed by bronchoalveolar lavage (BAL). Xylitol concentration was measured by nuclear magnetic resonance spectroscopy and corrected for dilution using urea concentration.

Results

All subjects tolerated nebulization and bronchoscopy well. Mean ASL volume recovered from the probes was 49 ± 23 μl. The mean ASL xylitol concentration at 20, 90, and 180 minutes was 1.6 ± 1.9 μg/μl, 0.6 ± 0.6 μg/μl, and 0.1 ± 0.1 μg/μl, respectively. Corresponding BAL concentration corrected for dilution was consistently lower at all time points. The terminal half-life of aerosolized xylitol obtained by the probes was 45 minutes with a mean residence time of 65 minutes in ASL. Corresponding BAL values were 36 and 50 minutes, respectively.

Conclusion

After a single dose nebulization, xylitol was detected in ASL for 3 hours, which was shorter than our in vitro measurement. The microsampling probe performed superior to BAL when sampling bronchial ASL.
RibAlign: a software tool and database for eubacterial phylogeny based on concatenated ribosomal protein subunits
Authors: Teeling Hanno , Gloeckner Frank Oliver
Published: February 2006

Background

Until today, analysis of 16S ribosomal RNA (rRNA) sequences has been the de-facto gold standard for the assessment of phylogenetic relationships among prokaryotes. However, the branching order of the individual phlya is not well-resolved in 16S rRNA-based trees. In search of an improvement, new phylogenetic methods have been developed alongside with the growing availability of complete genome sequences. Unfortunately, only a few genes in prokaryotic genomes qualify as universal phylogenetic markers and almost all of them have a lower information content than the 16S rRNA gene. Therefore, emphasis has been placed on methods that are based on multiple genes or even entire genomes. The concatenation of ribosomal protein sequences is one method which has been ascribed an improved resolution. Since there is neither a comprehensive database for ribosomal protein sequences nor a tool that assists in sequence retrieval and generation of respective input files for phylogenetic reconstruction programs, RibAlign has been developed to fill this gap.

Results

RibAlign serves two purposes: First, it provides a fast and scalable database that has been specifically adapted to eubacterial ribosomal protein sequences and second, it provides sophisticated import and export capabilities. This includes semi-automatic extraction of ribosomal protein sequences from whole-genome GenBank and FASTA files as well as exporting aligned, concatenated and filtered sequence files that can directly be used in conjunction with the PHYLIP and MrBayes phylogenetic reconstruction programs.

Conclusion

Up to now, phylogeny based on concatenated ribosomal protein sequences is hampered by the limited set of sequenced genomes and high computational requirements. However, hundreds of full and draft genome sequencing projects are on the way, and advances in cluster-computing and algorithms make phylogenetic reconstructions feasible even with large alignments of concatenated marker genes. RibAlign is a first step in this direction and may be particularly interesting to scientists involved in whole genome sequencing of representatives of new or sparsely studied eubacterial phyla. RibAlign is available athttp://www.megx.net/ribalign
Prediction of protein continuum secondary structure with probabilistic models based on NMR solved structures
Authors: Bodén Mikael , Yuan Zheng , Bailey Timothy L
Published: February 2006

Background

The structure of proteins may change as a result of the inherent flexibility of some protein regions. We develop and explore probabilistic machine learning methods for predicting a continuum secondary structure, i.e. assigning probabilities to the conformational states of a residue. We train our methods using data derived from high-quality NMR models.

Results

Several probabilistic models not only successfully estimate the continuum secondary structure, but also provide a categorical output on par with models directly trained on categorical data. Importantly, models trained on the continuum secondary structure are also better than their categorical counterparts at identifying the conformational state for structurally ambivalent residues.

Conclusion

Cascaded probabilistic neural networks trained on the continuum secondary structure exhibit better accuracy in structurally ambivalent regions of proteins, while sustaining an overall classification accuracy on par with standard, categorical prediction methods.
In search of functional association from time-series microarray data based on the change trend and level of gene expression
Authors: He Feng , Zeng An-Ping
Published: February 2006

Background

The increasing availability of time-series expression data opens up new possibilities to study functional linkages of genes. Present methods used to infer functional linkages between genes from expression data are mainly based on a point-to-point comparison. Change trends between consecutive time points in time-series data have been so far not well explored.

Results

In this work we present a new method based on extracting main features of the change trend and level of gene expression between consecutive time points. The method, termed as trend correlation (TC), includes two major steps: 1, calculating a maximal local alignment of change trend score by dynamic programming and a change trend correlation coefficient between the maximal matched change levels of each gene pair; 2, inferring relationships of gene pairs based on two statistical extraction procedures. The new method considers time shifts and inverted relationships in a similar way as the local clustering (LC) method but the latter is merely based on a point-to-point comparison. The TC method is demonstrated with data from yeast cell cycle and compared with the LC method and the widely used Pearson correlation coefficient (PCC) based clustering method. The biological significance of the gene pairs is examined with several large-scale yeast databases. Although the TC method predicts an overall lower number of gene pairs than the other two methods at a same p-value threshold, the additional number of gene pairs inferred by the TC method is considerable: e.g. 20.5% compared with the LC method and 49.6% with the PCC method for a p-value threshold of 2.7E-3. Moreover, the percentage of the inferred gene pairs consistent with databases by our method is generally higher than the LC method and similar to the PCC method. A significant number of the gene pairs only inferred by the TC method are process-identity or function-similarity pairs or have well-documented biological interactions, including 443 known protein interactions and some known cell cycle related regulatory interactions. It should be emphasized that the overlapping of gene pairs detected by the three methods is normally not very high, indicating a necessity of combining the different methods in search of functional association of genes from time-series data. For a p-value threshold of 1E-5 the percentage of process-identity and function-similarity gene pairs among the shared part of the three methods reaches 60.2% and 55.6% respectively, building a good basis for further experimental and functional study. Furthermore, the combined use of methods is important to infer more complete regulatory circuits and network as exemplified in this study.

Conclusion

The TC method can significantly augment the current major methods to infer functional linkages and biological network and is well suitable for exploring temporal relationships of gene expression in time-series data.
Hubs of knowledge: using the functional link structure in Biozon to mine for biologically significant entities
Authors: Shafer Paul , Isganitis Timothy , Yona Golan
Published: February 2006

Background

Existing biological databases support a variety of queries such as keyword or definition search. However, they do not provide any measure of relevance for the instances reported, and result sets are usually sorted arbitrarily.

Results

We describe a system that builds upon the complex infrastructure of the Biozon database and applies methods similar to those of Google to rank documents that match queries. We explore different prominence models and study the spectral properties of the corresponding data graphs. We evaluate the information content of principal and non-principal eigenspaces, and test various scoring functions which combine contributions from multiple eigenspaces. We also test the effect of similarity data and other variations which are unique to the biological knowledge domain on the quality of the results. Query result sets are assessed using a probabilistic approach that measures the significance of coherence between directly connected nodes in the data graph. This model allows us, for the first time, to compare different prominence models quantitatively and effectively and to observe unique trends.

Conclusion

Our tests show that the ranked query results outperform unsorted results with respect to our significance measure and the top ranked entities are typically linked to many other biological entities. Our study resulted in a working ranking system of biological entities that was integrated into Biozon at http://biozon.org.
Genetic relationship and diversity in a sesame (Sesamum indicum L.) germplasm collection using amplified fragment length polymorphism (AFLP)
Authors: Laurentin Hernán E , Karlovsky Petr
Published: February 2006

Background

Sesame is an important oil crop in tropical and subtropical areas. Despite its nutritional value and historic and cultural importance, the research on sesame has been scarce, particularly as far as its genetic diversity is concerned. The aims of the present study were to clarify genetic relationships among 32 sesame accessions from the Venezuelan Germplasm Collection, which represents genotypes from five diversity centres (India, Africa, China-Korea-Japan, Central Asia and Western Asia), and to determine the association between geographical origin and genetic diversity using amplified fragment length polymorphism (AFLP).

Results

Large genetic variability was found within the germplasm collection. A total of 457 AFLP markers were recorded, 93 % of them being polymorphic. The Jaccard similarity coefficient ranged from 0.38 to 0.85 between pairs of accessions. The UPGMA dendrogram grouped 25 of 32 accessions in two robust clusters, but it has not revealed any association between genotype and geographical origin. Indian, African and Chinese-Korean-Japanese accessions were distributed throughout the dendrogram. A similar pattern was obtained using principal coordinates analysis. Genetic diversity studies considering five groups of accessions according to the geographic origin detected that only 20 % of the total diversity was due to diversity among groups using Nei's coefficient of population differentiation. Similarly, only 5% of the total diversity was attributed to differences among groups by the analysis of molecular variance (AMOVA). This small but significant difference was explained by the fact that the Central Asia group had a lower genetic variation than the other diversity centres studied.

Conclusion

We found that our sesame collection was genetically very variable and did not show an association between geographical origin and AFLP patterns. This result suggests that there was considerable gene flow among diversity centres. Future germplasm collection strategies should focus on sampling a large number of plants. Covering many diversity centres is less important because each centre represents a major part of the total diversity in sesame, Central Asia centre being the only exception. The same recommendation holds for the choice of parents for segregant populations used in breeding projects. The traditional assumption that selecting genotypes of different geographical origin will maximize the diversity available to a breeding project does not hold in sesame.
Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism
Authors: Buyske Steven , Williams Tanishia A , Mars Audrey E , Stenroos Edward S , Ming Sue X , Wang Rong , Sreenath Madhura , Factura Marivic F , Reddy Chitra , Lambert George H , Johnson William G
Published: February 2006

Background

Certain loci on the human genome, such as glutathione S-transferase M1 (GSTM1), do not permit heterozygotes to be reliably determined by commonly used methods. Association of such a locus with a disease is therefore generally tested with a case-control design. When subjects have already been ascertained in a case-parent design however, the question arises as to whether the data can still be used to test disease association at such a locus.

Results

A likelihood ratio test was constructed that can be used with a case-parents design but has somewhat less power than a Pearson's chi-squared test that uses a case-control design. The test is illustrated on a novel dataset showing a genotype relative risk near 2 for the homozygous GSTM1 deletion genotype and autism.

Conclusion

Although the case-control design will remain the mainstay for a locus with a deletion, the likelihood ratio test will be useful for such a locus analyzed as part of a larger case-parent study design. The likelihood ratio test has the advantage that it can incorporate complete and incomplete case-parent trios as well as independent cases and controls. Both analyses support (p= 0.046 for the proposed test,p= 0.028 for the case-control analysis) an association of the homozygous GSTM1 deletion genotype with autism.
Horizontal gene transfer from Bacteria to rumen Ciliates indicates adaptation to their anaerobic, carbohydrates-rich environment
Authors: Ricard Guénola , McEwan Neil R , Dutilh Bas E , Jouany Jean-Pierre , Macheboeuf Didier , Mitsumori Makoto , McIntosh Freda M , Michalowski Tadeusz , Nagamine Takafumi , Nelson Nancy , Newbold Charles J , Nsabimana Eli , Takenaka Akio , Thomas Nadine A , Ushida Kazunari , Hackstein Johannes HP , Huynen Martijn A
Published: February 2006

Background

The horizontal transfer of expressed genes from Bacteria into Ciliates which live in close contact with each other in the rumen (the foregut of ruminants) was studied using ciliate Expressed Sequence Tags (ESTs). More than 4000 ESTs were sequenced from representatives of the two major groups of rumen Cilates: the order Entodiniomorphida (Entodinium simplex, Entodinium caudatum, Eudiplodinium maggii, Metadinium medium, Diploplastron affine, Polyplastron multivesiculatum and Epidinium ecaudatum) and the order Vestibuliferida, previously called Holotricha (Isotricha prostoma, Isotricha intestinalis and Dasytricha ruminantium).

Results

A comparison of the sequences with the completely sequenced genomes of Eukaryotes and Prokaryotes, followed by large-scale construction and analysis of phylogenies, identified 148 ciliate genes that specifically cluster with genes from the Bacteria and Archaea. The phylogenetic clustering with bacterial genes, coupled with the absence of close relatives of these genes in the Ciliate Tetrahymena thermophila, indicates that they have been acquired via Horizontal Gene Transfer (HGT) after the colonization of the gut by the rumen Ciliates.

Conclusion

Among the HGT candidates, we found an over-representation (>75%) of genes involved in metabolism, specifically in the catabolism of complex carbohydrates, a rich food source in the rumen. We propose that the acquisition of these genes has greatly facilitated the Ciliates' colonization of the rumen providing evidence for the role of HGT in the adaptation to new niches.
Transcriptome analysis of a cnidarian – dinoflagellate mutualism reveals complex modulation of host gene expression
Authors: Rodriguez-Lanetty Mauricio , Phillips Wendy S , Weis Virginia M
Published: February 2006

Background

Cnidarian – dinoflagellate intracellular symbioses are one of the most important mutualisms in the marine environment. They form the trophic and structural foundation of coral reef ecosystems, and have played a key role in the evolutionary radiation and biodiversity of cnidarian species. Despite the prevalence of these symbioses, we still know very little about the molecular modulators that initiate, regulate, and maintain the interaction between these two different biological entities. In this study, we conducted a comparative host anemone transcriptome analysis using a cDNA microarray platform to identify genes involved in cnidarian – algal symbiosis.

Results

We detected statistically significant differences in host gene expression profiles between sea anemones (Anthopleura elegantissima) in a symbiotic and non-symbiotic state. The group of genes, whose expression is altered, is diverse, suggesting that the molecular regulation of the symbiosis is governed by changes in multiple cellular processes. In the context of cnidarian – dinoflagellate symbioses, we discuss pivotal host gene expression changes involved in lipid metabolism, cell adhesion, cell proliferation, apoptosis, and oxidative stress.

Conclusion

Our data do not support the existence of symbiosis-specific genes involved in controlling and regulating the symbiosis. Instead, it appears that the symbiosis is maintained by altering expression of existing genes involved in vital cellular processes. Specifically, the finding of key genes involved in cell cycle progression and apoptosis have led us to hypothesize that a suppression of apoptosis, together with a deregulation of the host cell cycle, create a platform that might be necessary for symbiont and/or symbiont-containing host cell survival. This first comprehensive molecular examination of the cnidarian – dinoflagellate associations provides critical insights into the maintenance and regulation of the symbiosis.
The expansion of the metazoan microRNA repertoire
Authors: Hertel Jana , Lindemeyer Manuela , Missal Kristin , Fried Claudia , Tanzer Andrea , Flamm Christoph , Hofacker Ivo L , Stadler Peter F ,   The Students of Bioinformatics Computer Labs 2004 and 2005
Published: February 2006

Background

MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript.

Results

We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozen ancient microRNA clusters.

Conclusion

Our results suggest that microRNA innovation is an ongoing process. Major expansions of the metazoan miRNA repertoire coincide with the advent of bilaterians, vertebrates, and (placental) mammals.
Pooled DNA genotyping on Affymetrix SNP genotyping arrays
Authors: Kirov George , Nikolov Ivan , Georgieva Lyudmila , Moskvina Valentina , Owen Michael J , O'Donovan Michael C
Published: February 2006

Background

Genotyping technology has advanced such that genome-wide association studies of complex diseases based upon dense marker maps are now technically feasible. However, the cost of such projects remains high. Pooled DNA genotyping offers the possibility of applying the same technologies at a fraction of the cost, and there is some evidence that certain ultra-high throughput platforms also perform with an acceptable accuracy. However, thus far, this conclusion is based upon published data concerning only a small number of SNPs.

Results

In the current study we prepared DNA pools from the parents and from the offspring of 30 parent-child trios that have been extensively genotyped by the HapMap project. We analysed the two pools with Affymetrix 10 K Xba 142 2.0 Arrays. The availability of the HapMap data allowed us to validate the performance of 6843 SNPs for which we had both complete individual and pooled genotyping data. Pooled analyses averaged over 5–6 microarrays resulted in highly reproducible results. Moreover, the accuracy of estimating differences in allele frequency between pools using this ultra-high throughput system was comparable with previous reports of pooling based upon lower throughput platforms, with an average error for the predicted allelic frequencies differences between the two pools of 1.37% and with 95% of SNPs showing an error of < 3.2%.

Conclusion

Genotyping thousands of SNPs with DNA pooling using Affymetrix microarrays produces highly accurate results and can be used for genome-wide association studies.
Sex-dependent gene expression in early brain development of chicken embryos
Authors: Scholz Birger , Kultima Kim , Mattsson Anna , Axelsson Jeanette , Brunström Björn , Halldin Krister , Stigson Michael , Dencker Lennart
Published: February 2006

Background

Differentiation of the brain during development leads to sexually dimorphic adult reproductive behavior and other neural sex dimorphisms. Genetic mechanisms independent of steroid hormones produced by the gonads have recently been suggested to partly explain these dimorphisms.

Results

Using cDNA microarrays and real-time PCR we found gene expression differences between the male and female embryonic brain (or whole head) that may be independent of morphological differentiation of the gonads. Genes located on the sex chromosomes (ZZ in males and ZW in females) were common among the differentially expressed genes, several of which (WPKCI-8,HINT,MHM non-coding RNA) have previously been implicated in avian sex determination. A majority of the identified genes were more highly expressed in males. Three of these genes (CDK7,CCNHandBTF2-P44) encode subunits of the transcription factor IIH complex, indicating a role for this complex in neuronal differentiation.

Conclusion

In conclusion, this study provides novel insights into sexually dimorphic gene expression in the embryonic chicken brain and its possible involvement in sex differentiation of the nervous system in birds.
Older adults' beliefs about physician-estimated life expectancy: a cross-sectional survey
Authors: Kistler Christine E , Lewis Carmen L , Amick Halle R , Bynum Debra L , Walter Louise C , Watson Lea C
Published: February 2006

Background

Estimates of life expectancy assist physicians and patients in medical decision-making. The time-delayed benefits for many medical treatments make an older adult's life expectancy estimate particularly important for physicians. The purpose of this study is to assess older adults' beliefs about physician-estimated life expectancy.

Methods

We performed a mixed qualitative-quantitative cross-sectional study in which 116 healthy adults aged 70+ were recruited from two local retirement communities. We interviewed them regarding their beliefs about physician-estimated life expectancy in the context of a larger study on cancer screening beliefs. Semi-structured interviews of 80 minutes average duration were performed in private locations convenient to participants. Demographic characteristics as well as cancer screening beliefs and beliefs about life expectancy were measured. Two independent researchers reviewed the open-ended responses and recorded the most common themes. The research team resolved disagreements by consensus.

Results

This article reports the life-expectancy results portion of the larger study. The study group (n = 116) was comprised of healthy, well-educated older adults, with almost a third over 85 years old, and none meeting criteria for dementia. Sixty-four percent (n = 73) felt that their physicians could not correctly estimate their life expectancy. Sixty-six percent (n = 75) wanted their physicians to talk with them about their life expectancy. The themes that emerged from our study indicate that discussions of life expectancy could help older adults plan for the future, maintain open communication with their physicians, and provide them knowledge about their medical conditions.

Conclusion

The majority of the healthy older adults in this study were open to discussions about life expectancy in the context of discussing cancer screening tests, despite awareness that their physicians' estimates could be inaccurate. Since about a third of participants perceived these discussions as not useful or even harmful, physicians should first ascertain patients' preferences before discussing their life expectancies.
Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease
Authors: Ratziu Vlad , Massard Julien , Charlotte Frederic , Messous Djamila , Imbert-Bismut Françoise , Bonyhay Luninita , Tahiri Mohamed , Munteanu Mona , Thabut Dominique , Cadranel Jean François , Le Bail Brigitte , de Ledinghen Victor , Poynard Thierry ,   for the LIDO Study Group and the CYTOL study group
Published: February 2006

Background

Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions. The aim of this study was to determine the diagnostic utility of non-invasive markers of fibrosis, validated in chronic viral hepatitis and alcoholic liver disease (FibroTest, FT), in patients with NAFLD.

Methods

170 patients with suspected NAFLD were prospectively included in a reference center (Group 1), 97 in a multicenter study (Group 2) and 954 blood donors as controls. Fibrosis was assessed on a 5 stage histological scale validated by Kleiner et al from F0 = none, F1 = perisinusoidal or periportal, F2 = perisinusoidal and portal/periportal, F3 = bridging and F4 = cirrhosis. Histology and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) were assessed.

Results

In both groups FT has elevated and not different AUROCs for the diagnosis of advanced fibrosis (F2F3F4): 0.86 (95%CI 0.77–0.91) versus 0.75 (95%CI 0.61–0.83; P = 0.10), and for F3F4: 0.92 (95%CI 0.83–0.96) versus 0.81 (95%CI 0.64–0.91; P = 0.12) in Group1 and Group 2 respectively. When the 2 groups were pooled together a FT cutoff of 0.30 had a 90% NPV for advanced fibrosis (Se 77%); a FT cutoff of 0.70 had a 73% PPV for advanced fibrosis (Sp 98%).

Conclusion

In patients with NAFLD, FibroTest, a simple and non-invasive quantitative estimate of liver fibrosis reliably predicts advanced fibrosis.
Epidemiological trends in nosocomial candidemia in intensive care
Authors: Bassetti Matteo , Righi Elda , Costa Alessandro , Fasce Roberta , Molinari Maria Pia , Rosso Raffaella , Pallavicini Franco Bobbio , Viscoli Claudio
Published: February 2006

Background

Infection represents a frequent complication among patients in Intensive Care Units (ICUs) and mortality is high. In particular, the incidence of fungal infections, especially due to Candida spp., has been increasing during the last years.

Methods

In a retrospective study we studied the etiology of candidemia in critically ill patients over a five-year period (1999–2003) in the ICU of the San Martino University Hospital in Genoa, Italy.

Results

In total, 182 episodes of candidaemia were identified, with an average incidence of 2.22 episodes/10 000 patient-days/year (range 1.25–3.06 episodes). Incidence of candidemia increased during the study period from 1.25 in 1999 to 3.06/10 000 patient-days/year in 2003. Overall, 40% of the fungemia episodes (74/182) were due to C.albicans, followed by C. parapsilosis(23%), C.glabrata (15%), C.tropicalis (9%) and other species (13%). Candidemia due to non-albicans species increased and this was apparently correlated with an increasing use of azoles for prophylaxis or empirical treatment.

Conclusion

The study demonstrates a shift in the species of Candida causing fungemia in a medical and surgical ICU population during a 5 year period. The knowledge of the local epidemiological trends in Candida species isolated in blood cultures is important to guide therapeutic choices.
Patterns of sexually transmitted infections in adolescents and youth in Dar es Salaam, Tanzania
Authors: Chalamilla Guerino , Mbwana Judica , Mhalu Fred , Mmari Eunice , Majigo Mtebe , Swai Andrew , Urassa Willy , Sandstrom Eric
Published: February 2006

Background

Syndromic management of STIs has been advocated as simplified and cheap approach. Youth have been reported to be at increased risk of acquiring STIs which can facilitate HIV transmission. We have investigated the relationship between the syndromic management and specific aetiology diagnosis and its relationship with HIV infection and health seeking behaviour among youth attending a reproductive health clinic in Dar es Salaam, Tanzania.

Methods

Between September 1998 and February 1999 among 1895 adolescents and youth below 25 years seen in the clinic 199 (10.5%) were randomly selected and consented to participate in the study. A standard questionnaire was administered. Blood and vaginal or urethral specimens were taken and investigated for STI causative agents.

Results

Among a total of 199 studied adolescents and youth 22.6 % were teenagers, with fewer females 17.8% than males; 27.5% (p < 0.018). 20.8% of the females compared to 11.5% in males were HIV infected. Genital discharge was the most common complaint which was reported in 54.1% of male and 63.4 % of female patients. All males with gonorrhoea and four out of five with Chlamydia were given appropriate treatment with syndromic management, while 28% women with gonorrhoea or Chlamydia received appropriate treatment by syndromic management. All patients found with active syphilis by serology had not complained of genital ulcers and would not have been assigned to syndromic treatment for syphilis at the initial visit.

Conclusion

The burden of STIs in this youth population is large indicating that youth are at increased risk of STIs and will certainly require youth friendly clinics. There is a need to refine the current syndromic management guidelines.
Diagnostic accuracy of the neurological upper limb examination I: Inter-rater reproducibility of selected findings and patterns
Authors: Jepsen Jorgen R , Laursen Lise H , Hagert Carl-Goran , Kreiner Svend , Larsen Anders I
Published: February 2006

Background

We have previously assessed the reproducibility of manual testing of the strength in 14 individual upper limb muscles in patients with or without upper limb complaints. This investigation aimed at additionally studying sensory disturbances, the mechanosensitivity of nerve trunks, and the occurrence of physical findings in patterns which may potentially reflect a peripheral neuropathy. The reproducibility of this part of the neurological examination has never been reported.

Methods

Two blinded examiners performed a semi-quantitative assessment of 82 upper limbs (strength in 14 individual muscles, sensibility in 7 homonymous territories, and mechanosensitivity of nerves at 10 locations). Based on the topography of nerves and their muscular and cutaneous innervation we defined 10 neurological patterns each suggesting a focal neuropathy. The individual findings and patterns identified by the two examiners were compared.

Results

Strength, sensibility to touch, pain and vibration, and mechanosensitivity were predominantly assessed with moderate to very good reproducibility (median κ-values 0.54, 0.69, 0.48, 0.58, and 0.53, respectively). The reproducibility of the defined patterns was fair to excellent (median correlation coefficient = 0.75) and the overall identification of limbs with/without pattern(s) was good (κ = 0.75).

Conclusion

This first part of a study on diagnostic accuracy of a selective neurological examination has demonstrated a promising inter-rater reproducibility of individual neurological items and patterns. Generalization and clinical feasibility require further documentation: 1) Reproducibility in cohorts of other composition, 2) validity with comparison to currently applied standards, and 3) potential benefits that can be attained by the examination.
How much attention is needed towards men who sell sex to men for HIV prevention in India?
Authors: Dandona Lalit , Dandona Rakhi , Kumar G Anil , Gutierrez Juan Pablo , McPherson Sam , Bertozzi Stefano M ,   the ASCI FPP Study Team
Published: February 2006

Background

HIV prevention in India has mostly focussed on heterosexual transmission. Data on homosexual transmission are not readily available from India. We therefore assessed the probability of acquiring and transmitting HIV for men who sell sex to men and compared this with women who sell sex in India.

Methods

Sexual behaviour characteristics of 6661 men who have sex with men and 6648 women who sell sex were obtained in the Indian state of Andhra Pradesh through confidential interviews. These, along with estimates of HIV rates among them and risk of HIV transmission per unprotected sex act from other sources, were used to calculate their annual probability of acquiring and transmitting HIV.

Results

Of 6661 men who have sex with men in this sample, 1776 (26.7%) had sold sex to men. For every 1000 men who sell sex to men, annually 146 (95% confidence interval [CI] 116–179) would acquire HIV and HIV would be transmitted to 55 (95% CI 42–71) men who do not sell sex or women. These estimates were higher by 6.7 (95% CI 4.9–9.2) times for acquiring HIV and 2.5 (95% CI 2.0–3.2) times for transmitting HIV to sex partners outside their group, as compared with similar estimates for women who sell sex. In this sample, the average annual probability of acquiring HIV was higher among men who have sex with men but do not sell sex as compared with women who sell sex.

Conclusion

These data indicate that men who sell sex to men are at much higher risk of acquiring and transmitting HIV than women who sell sex. Therefore, men who sell sex to men and their clients warrant substantial attention for comprehensive HIV prevention in India.
Design and descriptive results of the "Growth, Exercise and Nutrition Epidemiological Study In preSchoolers": The GENESIS Study
Authors: Manios Yannis
Published: February 2006

Background

The Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) attempts to evaluate the food and nutrient intakes, as well as growth and development of a representative sample of Greek toddlers and preschool children. In the current work the study design, data collection procedures and some preliminary data of the GENESIS study are presented.

Methods

From April 2003 to July 2004, 1218 males and 1156 females 1 to 5 years old, stratified by parental educational level (Census 1999), were examined from 105 nurseries in five counties. Approximately 300 demographic, lifestyle, physical activity, dietary, anthropometrical and DNA variables have been recorded from the study population (children and parents).

Results

Regarding anthropometrical indices, boys were found to be taller than girls at all ages (P < 0.05) and heavier only for the age period from 1 to 3 years old (P < 0.05). No significant differences were found between genders regarding the prevalence of at risk of overweight (16.5% to 18.6% for boys and 18.5 to 20.6 % for girls) and overweight (14.0% to 18.9% for boys and 12.6% to 20.0% for girls). Additionally, boys older than 2 years of age were found to have a higher energy intake compared to girls (P < 0.05). A similar tendency was observed regarding the mean dietary intake of fat, saturated fat, carbohydrates and protein with boys exhibiting a higher intake than girls in most age groups (P < 0.05).

Conclusion

The prevalence of overweight in the current preschool population is considerably high. Future but more extensive analyses of the GENESIS data will be able to reveal the interactions of the parameters leading to this phenomenon.