bluuebunny/crossref_metadata_2025_split huggingface dataset:
An optimized procedure for the design and evaluation of Ecotilling assays
Authors: Coassin Stefan , Brandstätter Anita , Kronenberg Florian 
Published: October 2008

Abstract

Background
Single nucleotide polymorphisms (SNPs) are the most common form of genetic variability in the human genome and play a prominent role in the heritability of phenotypes. Especially rare alleles with frequencies less than 5% may exhibit a particularly strong influence on the development of complex diseases. The detection of rare alleles by standard DNA sequencing is time-consuming and cost-intensive. Here we discuss an alternative approach for a high throughput detection of rare mutations in large population samples using Ecotilling embedded in a collection of bioinformatic analysis tools. Ecotilling originally was introduced as TILLING for the screening for rare chemically induced mutations in plants and later adopted for human samples, showing an outstanding suitability for the detection of rare alleles in humans. An actual problem in the use of Ecotilling for large mutation screening projects in humans without bioinformatic support is represented by the lack of solutions to quickly yet comprehensively evaluate each newly found variation and place it into the correct genomic context.

Results
We present an optimized strategy for the design, evaluation and interpretation of Ecotilling results by integrating several mostly freely available bioinformatic tools. A major focus of our investigations was the evaluation and meaningful economical combination of these software tools for the inference of different possible regulatory functions for each newly detected mutation.

Conclusion
Our streamlined procedure significantly facilitates the experimental design and evaluation of Ecotilling assays and strongly improves the decision process on prioritizing the newly found SNPs for further downstream analysis.
Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives
Authors: Tamplin Owen J , Kinzel Doris , Cox Brian J , Bell Christine E , Rossant Janet , Lickert Heiko 
Published: October 2008

Abstract

Background
The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined.

Results
To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and Foxa2 mutant embryos at late gastrulation stage (E7.5). We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount in situ hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm.

Conclusion
The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer and its inductive properties in an otherwise normal embryo, impacts on the molecular profile of surrounding tissues.
Genomic plasticity of the immune-related Mhc class I B region in macaque species
Authors: Bonhomme Maxime , Doxiadis Gaby GM , Heijmans Corrine MC , Vervoort Virginie , Otting Nel , Bontrop Ronald E , Crouau-Roy Brigitte 
Published: October 2008

AbstractBackgroundIn sharp contrast to humans and great apes, the expandedMhc-Bregion of rhesus and cynomolgus macaques is characterized by the presence of differential numbers and unique combinations of polymorphic class IBgenes per haplotype. The MIB microsatellite is closely linked to the single class IBgene in human and in some great apes studied. The physical map of theMhcof a heterozygous rhesus monkey provides unique material to analyze MIB andMamu-Bcopy number variation and then allows one to decipher the compound evolutionary history of this region in primate species.ResultsIn silicoresearch pinpointed 12 MIB copies (duplicons), most of which are associated with expressedB-genes that cluster in a separate clade in the phylogenetic tree. Generic primers tested on homozygous rhesus and pedigreed cynomolgus macaques allowed the identification of eight to eleven MIB copies per individual. The number of MIB copies present per haplotype varies from a minimum of three to six in cynomolgus macaques and from five to eight copies in rhesus macaques. Phylogenetic analyses highlight a strong transpecific sharing of MIB duplicons. Using the physical map, we observed that, similar to MIB duplicons, highly divergentMamu-Bgenes can be present on the same haplotype. Haplotype variation as reflected by the copy number variation of class IBloci is best explained by recombination events, which are found to occur between MIBs andMamu-B.ConclusionThe data suggest the existence of highly divergent MIB andMamu-Blineages on a given haplotype, as well as variable MIB andBcopy numbers and configurations, at least in rhesus macaque. Recombination seems to occur between MIB andMamu-Bloci, and the resulting haplotypic plasticity at the individual level may be a strategy to better cope with pathogens. Therefore, evolutionary inferences based on the multiplicated MIB loci but also other markers close toB-genes appear to be promising for the study ofB-region organization and evolution in primates.
Serological survey on immunity status against polioviruses in children and adolescents living in a border region, Apulia (Southern Italy)
Authors: Tafuri Silvio , Prato Rosa , Martinelli Domenico , Calvario Agata , Bozzi Anna , Labianca Michele , Patti Annamaria , Lopalco Pietro Luigi , Germinario Cinzia 
Published: October 2008

Abstract

Background
In 1988 the World Health Assembly adopted the goal to eradicate poliomyelitis by routine immunization using Oral Polio Vaccine (OPV). On 21 June 2002 the WHO European Region was declared polio-free. In 2008 poliomyelitis is still endemic in 4 countries (Nigeria, India, Pakistan, and Afghanistan), where 1201 new cases were registered in 2007; 107 sporadic cases were also notified in countries where poliovirus is not endemic. The aim of this work was to verify the level of antipoliomyelitis immunity status in children and adolescents in the Apulia region (south of Italy), which may be considered a border region due to its position.

Methods
704 blood specimens from a convenience sample were collected in six laboratories. The age of subjects enrolled was 0–15 years. The immunity against poliomyelitis was evaluated by neutralizing antibody titration in tissue culture microplates.

Results
Seropositivity (neutralising antibodies titre ≥ 8) for polioviruses 1, 2 and 3 was detected in 100%, 99.8% and 99.4% of collected sera. Antibody titres were not lower in subjects who received either four doses of inactivated polio vaccine (IPV) or a sequential schedule consisting of two doses of IPV and two of oral polio vaccine than in subjects who received four doses of OPV.

Conclusion
These results confirmed current data of vaccine coverage for poliomyelitis: during the last ten years in Apulia, the coverage in 24 months old children was more than 90%. The high level of immunization found confirms the effectiveness both of the sequential schedule IPV-OPV and of the schedule all-IPV. Apulia region has to face daily arrivals of refugees and remains subject to the risk of the importation of poliovirus from endemic areas. Surveys aimed at determining anti-polio immunity in subpopulations as well as in the general population should be carried out.
Fetal age assessment based on 2nd trimester ultrasound in Africa and the effect of ethnicity
Authors: Salpou Daniel , Kiserud Torvid , Rasmussen Svein , Johnsen Synnøve Lian 
Published: October 2008

AbstractBackgroundThe African population is composed of a variety of ethnic groups, which differ considerably from each other. Some studies suggest that ethnic variation may influence dating. The aim of the present study was to establish reference values for fetal age assessment in Cameroon using two different ethnic groups (Fulani and Kirdi).MethodsThis was a prospective cross sectional study of 200 healthy pregnant women from Cameroon. The participants had regular menstrual periods and singleton uncomplicated pregnancies, and were recruited after informed consent. The head circumference (HC), outer-outer biparietal diameter (BPDoo), outer-inner biparietal diameter and femur length (FL), also called femur diaphysis length, were measured using ultrasound at 12–22 weeks of gestation. Differences in demographic factors and fetal biometry between ethnic groups were assessed by t- and Chi-square tests.ResultsCompared with Fulani women (N = 96), the Kirdi (N = 104) were 2 years older (p = 0.005), 3 cm taller (p = 0.001), 6 kg heavier (p < 0.0001), had a higher body mass index (BMI) (p = 0.001), but were not different with regard to parity. Ethnicity had no effect on BPDoo (p = 0.82), HC (p = 0.89) or FL (p = 00.24). Weight, height, maternal age and BMI had no effect on HC, BPDoo and FL (p = 0.2–0.58, 0.1–0.83, and 0.17–0.6, respectively).When comparing with relevant European charts based on similar design and statistics, we found overlapping 95% CI for BPD (Norway & UK) and a 0–4 day difference for FL and HC.ConclusionSignificant ethnic differences between mothers were not reflected in fetal biometry at second trimester. The results support the recommendation that ultrasound in practical health care can be used to assess gestational age in various populations with little risk of error due to ethnic variation.
Co-regulation analysis of closely linked genes identifies a highly recurrent gain on chromosome 17q25.3 in prostate cancer
Authors: Bermudo Raquel , Abia David , Ferrer Berta , Nayach Iracema , Benguria Alberto , Zaballos Ángel , del Rey Javier , Miró Rosa , Campo Elías , Martínez-A Carlos , Ortiz Ángel R , Fernández Pedro L , Thomson Timothy M 
Published: October 2008

AbstractBackgroundTranscriptional profiling of prostate cancer (PC) has unveiled new markers of neoplasia and allowed insights into mechanisms underlying this disease. Genomewide analyses have also identified new chromosomal abnormalities associated with PC. The combination of both classes of data for the same sample cohort might provide better criteria for identifying relevant factors involved in neoplasia. Here we describe transcriptional signatures identifying distinct normal and tumoral prostate tissue compartments, and the inference and demonstration of a new, highly recurrent copy number gain on chromosome 17q25.3.MethodsWe have applied transcriptional profiling to tumoral and non-tumoral prostate samples with relatively homogeneous epithelial representations as well as pure stromal tissue from peripheral prostate and cultured cell lines, followed by quantitative RT-PCR validations and immunohistochemical analysis. In addition, we have performedin silicocolocalization analysis of co-regulated genes and validation by fluorescent in situ hybridization (FISH).ResultsThe transcriptomic analysis has allowed us to identify signatures corresponding to non-tumoral luminal and tumoral epithelium, basal epithelial cells, and prostate stromal tissue. In addition,in silicoanalysis of co-regulated expression of physically linked genes has allowed us to predict the occurrence of a copy number gain at chromosomal region 17q25.3. This computational inference was validated by fluorescentin situhybridization, which showed gains in this region in over 65% of primary and metastatic tumoral samples.ConclusionOur approach permits to directly link gene copy number variations with transcript co-regulation in association with neoplastic states. Therefore, transcriptomic studies of carefully selected samples can unveil new diagnostic markers and transcriptional signatures highly specific of PC, and lead to the discovery of novel genomic abnormalities that may provide additional insights into the causes and mechanisms of prostate cancer.
Development and evaluation of a leadership training program for public health emergency response: results from a Chinese study
Authors: Wang Chongjian , Wei Sheng , Xiang Hao , Wu Jing , Xu Yihua , Liu Li , Nie Shaofa 
Published: October 2008

Abstract

Background
Since the 9/11 attack and severe acute respiratory syndrome (SARS), the development of qualified and able public health leaders has become a new urgency in building the infrastructure needed to address public health emergencies. Although previous studies have reported that the training of individual leaders is an important approach, the systemic and scientific training model need further improvement and development. The purpose of this study was to develop, deliver, and evaluate a participatory leadership training program for emergency response.

Methods
Forty-one public health leaders (N = 41) from five provinces completed the entire emergency preparedness training program in China. The program was evaluated by anonymous questionnaires and semi-structured interviews held prior to training, immediately post-training and 12-month after training (Follow-up).

Results
The emergency preparedness training resulted in positive shifts in knowledge, self-assessment of skills for public health leaders. More than ninety-five percent of participants reported that the training model was scientific and feasible. Moreover, the response of participants in the program to the avian influenza outbreak, as well as the planned evaluations for this leadership training program, further demonstrated both the successful approaches and methods and the positive impact of this integrated leadership training initiative.

Conclusion
The emergency preparedness training program met its aims and objectives satisfactorily, and improved the emergency capability of public health leaders. This suggests that the leadership training model was effective and feasible in improving the emergency preparedness capability.
Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis
Authors: Penolazzi Letizia , Lampronti Ilaria , Borgatti Monica , Khan Mahmud Tareq Hassan , Zennaro Margherita , Piva Roberta , Gambari Roberto 
Published: October 2008

Abstract

Background
Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of Emblica officinalis fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts.

Methods
The effects of extracts from Emblica officinalis on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of Emblica officinalis extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, in vitro effects of Emblica officinalis extracts on NF-kB transcription factor activity were determined by gel shift experiments.

Results
Extracts of Emblica officinalis were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. Emblica officinalis increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that Emblica officinalis extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that Emblica officinalis extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of Emblica officinalis on the expression levels of interleukin-6, a NF-kB specific target gene.

Conclusion
Induction of apoptosis of osteoclasts could be an important strategy both in interfering with rheumatoid arthritis complications of the bone skeleton leading to joint destruction, and preventing and reducing osteoporosis. Accordingly, we suggest the application of Emblica officinalis extracts as an alternative tool for therapy applied to bone diseases.
HOX cofactors expression and regulation in the human ovary
Authors: Ota Takayo , Asahina Haruka , Park Se-Hyung , Huang Qing , Minegishi Takashi , Auersperg Nelly , Leung Peter CK 
Published: October 2008

Abstract

Background
HOX cofactors enhance HOX binding affinities and specificities and increase HOX's unique functional activities. The expression and the regulation of HOX cofactors in human ovaries are unknown.

Methods
In this study, the expression of HOX cofactors, PBX1, PBX2, and MEIS1/2, were examined by using RT-PCR, immunofluorescence in cultured immortalized human granulosa (SVOG) cells. The distribution of these HOX cofactors in human ovaries was examined by immunohistochemistry. The effects of growth differentiation factor-9 (GDF-9) and follicle-stimulating hormone (FSH) on PBX2 in SVOG cells were investigated by western blot analysis. Binding activities of HOXA7 and PBX2 to the specific sequences in granulosa cells were determined by electrophoretic mobility shift assay (EMSA).

Results and conclusion
In SVOG cells, PBX1, PBX2 and MEIS1/2 were expressed during cell culture. In normal human ovaries, PBX1 and MEIS1/2 were expressed in granulosa cells at essentially all stages of follicular development. These cofactors were expressed in the nuclei of the granulosa cells from the primordial to the secondary follicles, whereas beyond multilayered follicles was observed in the cytoplasm. The co-expression of PBX1 and MEIS1/2 in granulosa cells in normal human ovaries suggested that MEIS1/2 might control PBX1 sublocalization, as seen in other systems. PBX2 was not expressed or weakly expressed in the primordial follicles. From the primary follicles to the preovulatory follicles, PBX2 expression was inconsistent and the expression was found in the granulosa cell nuclei. The PBX2 expression pattern is similar to HOXA7 expression in ovarian follicular development. Furthermore, FSH down-regulated, GDF-9 did not change PBX2 expression, but co-treatment of the granulosa cells with FSH and GDF-9 up-regulated PBX2 expression. These results implicated a role for PBX2 expression in the steroidogenic activities of granulosa cells in humans. Moreover, PBX2 and HOXA7 bound together to the Pbx sequence, but not to the EMX2 promoter sequence, in SVOG cells. Our findings indicate that HOX cofactors expression in normal human ovary is temporally and spatially specific and regulated by FSH and GDF-9 in granulosa cells. HOX proteins may use different HOX cofactors, depending on DNA sequences that are specific to the granulosa cells.
Modeling the effects of drug resistant influenza virus in a pandemic
Authors: Brockmann Stefan O , Schwehm Markus , Duerr Hans-Peter , Witschi Mark , Koch Daniel , Vidondo Beatriz , Eichner Martin 
Published: October 2008

AbstractNeuraminidase inhibitors (NI) play a major role in plans to mitigate future influenza pandemics. Modeling studies suggested that a pandemic may be contained at the source by early treatment and prophylaxis with antiviral drugs. Here, we examine the influence of NI resistant influenza strains on an influenza pandemic. We extend the freely available deterministic simulation programInfluSimto incorporate importations of resistant infections and the emergence ofde novoresistance. The epidemic with the fully drug sensitive strain leads to a cumulative number of 19,500 outpatients and 258 hospitalizations, respectively, per 100,000 inhabitants. Development ofde novoresistance alone increases the total number of outpatients by about 6% and hospitalizations by about 21%. If a resistant infection is introduced into the population after three weeks, the outcome dramatically deteriorates. Wide-spread use of NI treatment makes it highly likely that the resistant strain will spread if its fitness is high. This situation is further aggravated if a resistant virus is imported into a country in the early phase of an outbreak. As NI-resistant influenza infections with high fitness and pathogenicity have just been observed, the emergence of drug resistance in treated populations and the transmission of drug resistant strains is an important public health concern for seasonal and pandemic influenza.
The incidence of acute encephalitis syndrome in Western industrialised and tropical countries
Authors: Jmor Fidan , Emsley Hedley CA , Fischer Marc , Solomon Tom , Lewthwaite Penny 
Published: October 2008

Abstract

Background
As part of efforts to control Japanese encephalitis (JE), the World Health Organization is producing a set of standards for JE surveillance, which require the identification of patients with acute encephalitis syndrome (AES). This review aims to provide information to determine what minimum annual incidence of AES should be reported to show that the surveillance programme is active.

Methods
A total of 12,436 articles were retrieved from 3 databases; these were screened by title search and duplicates removed to give 1,083 papers which were screened by abstract (or full paper if no abstract available) to give 87 papers. These 87 were reviewed and 25 papers identified which met the inclusion criteria.

Results
Case definitions and diagnostic criteria, aetiologies, study types and reliability varied among the studies reviewed. Amongst prospective studies reviewed from Western industrialised settings, the range of incidences of AES one can expect was 10.5–13.8 per 100,000 for children. For adults only, the minimum incidence from the most robust prospective study from a Western setting gave an incidence of 2.2 per 100,000. The incidence from the two prospective studies for all age groups was 6.34 and 7.4 per 100,000 from a tropical and a Western setting, respectively. However, both studies included arboviral encephalitis, which may have given higher rather than given higher] incidence levels.

Conclusion
In the most robust, prospective studies conducted in Western industrialised countries, a minimum incidence of 10.5 per 100,000 AES cases was reported for children and 2.2 per 100,000 for adults. The minimum incidence for all ages was 6.34 per 100,000 from a tropical setting. On this basis, for ease of use in protocols and for future WHO surveillance standards, a minimum incidence of 10 per 100,000 AES cases is suggested as an appropriate target for studies of children alone and 2 per 100,000 for adults and 6 per 100,000 for all age groups.