bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Notch responsiveness is defined by phosphoinositide 3-kinase-dependent signals
Authors: Mckenzie Grahame , Ward George , Stallwood Yvette , Briend Emmanuel , Papadia Sofia , Lennard Andrew , Turner Martin , Champion Brian , Hardingham Giles E 
Published: March 2006

AbstractBackgroundNotch plays a wide-ranging role in controlling cell fate, differentiation and development. The PI3K-Akt pathway is a similarly conserved signalling pathway which regulates processes such as differentiation, proliferation and survival. Mice with disrupted Notch and PI3K signalling show phenotypic similarities during haematopoietic cell development, suggesting functional interaction between these pathways.ResultsWe show that cellular responsiveness to Notch signals depends on the activity of the PI3K-Akt pathway in cells as diverse as CHO cells, primary T-cells and hippocampal neurons. Induction of the endogenous PI3K-Akt pathway in CHO cells (by the insulin pathway), in T-cells (via TCR activation) or in neurons (via TrKB activation) potentiates Notch-dependent responses. We propose that the PI3K-Akt pathway exerts its influence on Notch primarily via inhibition of GSK3-beta, a kinase known to phosphorylate and regulate Notch signals.ConclusionThe PI3K-Akt pathway acts as a "gain control" for Notch signal responses. Since physiological levels of intracellular Notch are often low, coincidence with PI3K-activation may be crucial for induction of Notch-dependent responses.
Multistable and multistep dynamics in neutrophil differentiation
Authors: Chang Hannah H , Oh Philmo Y , Ingber Donald E , Huang Sui 
Published: March 2006

AbstractBackgroundCell differentiation has long been theorized to represent a switch in a bistable system, and recent experimental work in micro-organisms has revealed bistable dynamics in small gene regulatory circuits. However, the dynamics of mammalian cell differentiation has not been analyzed with respect to bistability.ResultsHere we studied how HL60 promyelocytic precursor cells transition to the neutrophil cell lineage after stimulation with the differentiation inducer, dimethyl sulfoxide (DMSO). Single cell analysis of the expression kinetics of the differentiation marker CD11b (Mac-1) revealed all-or-none switch-like behavior, in contrast to the seemingly graduated change of expression when measured as a population average. Progression from the precursor to the differentiated state was detected as a discrete transition between low (CD11bLow) and high (CD11bHigh) expressor subpopulations distinguishable in a bimodal distribution. Hysteresis in the dependence of CD11b expression on DMSO dose suggests that this bimodality may reflect a bistable dynamic. But when an "unswitched" (CD11bLow) subpopulation of cells in the bistable/bimodal regime was isolated and cultured, these cells were found to differ from undifferentiated precursor cells in that they were "primed" to differentiate.ConclusionThese findings indicate that differentiation of human HL60 cells into neutrophils does not result from a simple state transition of a bistable switch as traditionally modeled. Instead, mammalian differentiation appears to be a multi-step process in a high-dimensional system, a result which is consistent with the high connectivity of the cells' complex underlying gene regulatory network.
High resolution ultrasound-guided microinjection for interventional studies of early embryonic and placental development in vivoin mice
Authors: Slevin John C , Byers Lois , Gertsenstein Marina , Qu Dawei , Mu Junwu , Sunn Nana , Kingdom John CP , Rossant Janet , Adamson S Lee 
Published: March 2006

Abstract

Background
In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5–E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure.

Results
In 40 MHz ultrasound images at E6.5, the ectoplacental cone region and proamniotic cavity could be visualized. The ectoplacental cone region was successfully targeted with 13.8 nL of a fluorescent bead suspension with few or no beads off-target in 51% of concepti microinjected at E6.5 (28/55 injected). Seventy eight percent of the embryos survived 2 to 12 days post injection (93/119), 73% (41/56) survived to term of which 68% (38/56) survived and appeared normal one week after birth. At E7.5, the amniotic and exocoelomic cavities, and ectoplacental cone region were discernable. Our success at targeting with few or no beads off-target was 90% (36/40) for the ectoplacental cone region and 81% (35/43) for the exocoelomic cavity but tended to be less, 68% (34/50), for the smaller amniotic cavity. At E11.5, beads microinjected at E7.5 into the ectoplacental cone region were found in the placental spongiotrophoblast layer, those injected into the exocoelomic cavity were found on the surface or within the placental labyrinth, and those injected into the amniotic cavity were found on the surface or within the embryo. Following microinjection at E7.5, survival one week after birth was 60% (26/43) when the amniotic cavity was the target and 66% (19/29) when the target was the ectoplacental cone region. The survival rate was similar in sham experiments, 54% (33/61), for which procedures were identical but no microinjection was performed, suggesting that surgery and manipulation of the uterus were the main causes of embryonic death.

Conclusion
Ultrasound-guided microinjection into the ectoplacental cone region at E6.5 or E7.5 and the amniotic cavity at E7.5 was achieved with a 7 day postnatal survival of ≥60%. Target accuracy of these sites and of the exocoelomic cavity at E7.5 was ≥51%. We suggest that this approach may be useful for exploring gene function during early placental and embryonic development.
Identification and targeted disruption of the mouse gene encoding ESG1 (PH34/ECAT2/DPPA5)
Authors: Amano Hisayuki , Itakura Ken , Maruyama Masayoshi , Ichisaka Tomoko , Nakagawa Masato , Yamanaka Shinya 
Published: March 2006

Abstract

Background
Embryonic stem cell-specific gene (ESG) 1, which encodes a KH-domain containing protein, is specifically expressed in early embryos, germ cells, and embryonic stem (ES) cells. Previous studies identified genomic clones containing the mouse ESG1 gene and five pseudogenes. However, their chromosomal localizations or physiological functions have not been determined.

Results
A Blast search of mouse genomic databases failed to locate the ESG1 gene. We identified several bacterial artificial clones containing the mouse ESG1 gene and an additional ESG1-like sequence with a similar gene structure from chromosome 9. The ESG1-like sequence contained a multiple critical mutations, indicating that it was a duplicated pseudogene. The 5' flanking region of the ESG1 gene, but not that of the pseudogene, exhibited strong enhancer and promoter activity in undifferentiated ES cells by luciferase reporter assay. To study the physiological functions of the ESG1 gene, we replaced this sequence in ES cells with a β-geo cassette by homologous recombination. Despite specific expression in early embryos and germ cells, ESG1
-/- mice developed normally and were fertile. We also generated ESG1
-/- ES cells both by a second independent homologous recombination and directly from blastocysts derived from heterozygous intercrosses. Northern blot and western blot analyses confirmed the absence of ESG1 in these cells. These ES cells demonstrated normal morphology, proliferation, and differentiation.

Conclusion
The mouse ESG1 gene, together with a duplicated pseudogene, is located on chromosome 9. Despite its specific expression in pluripotent cells and germ cells, ESG1 is dispensable for self-renewal of ES cells and establishment of germcells.
Generation and analysis of large-scale expressed sequence tags (ESTs) from a full-length enriched cDNA library of porcine backfat tissue
Authors: Kim Tae-Hun , Kim Nam-Soon , Lim Dajeong , Lee Kyung-Tai , Oh Jung-Hwa , Park Hye-Sook , Jang Gil-Won , Kim Hyung-Yong , Jeon Mina , Choi Bong-Hwan , Lee Hae-Young , Chung HY , Kim Heebal 
Published: March 2006

Abstract

Background
Genome research in farm animals will expand our basic knowledge of the genetic control of complex traits, and the results will be applied in the livestock industry to improve meat quality and productivity, as well as to reduce the incidence of disease. A combination of quantitative trait locus mapping and microarray analysis is a useful approach to reduce the overall effort needed to identify genes associated with quantitative traits of interest.

Results
We constructed a full-length enriched cDNA library from porcine backfat tissue. The estimated average size of the cDNA inserts was 1.7 kb, and the cDNA fullness ratio was 70%. In total, we deposited 16,110 high-quality sequences in the dbEST division of GenBank (accession numbers: DT319652-DT335761). For all the expressed sequence tags (ESTs), approximately 10.9 Mb of porcine sequence were generated with an average length of 674 bp per EST (range: 200–952 bp). Clustering and assembly of these ESTs resulted in a total of 5,008 unique sequences with 1,776 contigs (35.46%) and 3,232 singleton (65.54%) ESTs. From a total of 5,008 unique sequences, 3,154 (62.98%) were similar to other sequences, and 1,854 (37.02%) were identified as having no hit or low identity (<95%) and 60% coverage in The Institute for Genomic Research (TIGR) gene index of Sus scrofa. Gene ontology (GO) annotation of unique sequences showed that approximately 31.7, 32.3, and 30.8% were assigned molecular function, biological process, and cellular component GO terms, respectively. A total of 1,854 putative novel transcripts resulted after comparison and filtering with the TIGR SsGI; these included a large percentage of singletons (80.64%) and a small proportion of contigs (13.36%).

Conclusion
The sequence data generated in this study will provide valuable information for studying expression profiles using EST-based microarrays and assist in the condensation of current pig TCs into clusters representing longer stretches of cDNA sequences. The isolation of genes expressed in backfat tissue is the first step toward a better understanding of backfat tissue on a genomic basis.
Characteristics and clustering of human ribosomal protein genes
Authors: Ishii Kyota , Washio Takanori , Uechi Tamayo , Yoshihama Maki , Kenmochi Naoya , Tomita Masaru 
Published: March 2006

Abstract

Background
The ribosome is a central player in the translation system, which in mammals consists of four RNA species and 79 ribosomal proteins (RPs). The control mechanisms of gene expression and the functions of RPs are believed to be identical. Most RP genes have common promoters and were therefore assumed to have a unified gene expression control mechanism.

Results
We systematically analyzed the homogeneity and heterogeneity of RP genes on the basis of their expression profiles, promoter structures, encoded amino acid compositions, and codon compositions. The results revealed that (1) most RP genes are coordinately expressed at the mRNA level, with higher signals in the spleen, lymph node dissection (LND), and fetal brain. However, 17 genes, including the P protein genes (RPLP0, RPLP1, RPLP2), are expressed in a tissue-specific manner. (2) Most promoters have GC boxes and possible binding sites for nuclear respiratory factor 2, Yin and Yang 1, and/or activator protein 1. However, they do not have canonical TATA boxes. (3) Analysis of the amino acid composition of the encoded proteins indicated a high lysine and arginine content. (4) The major RP genes exhibit a characteristic synonymous codon composition with high rates of G or C in the third-codon position and a high content of AAG, CAG, ATC, GAG, CAC, and CTG.

Conclusion
Eleven of the RP genes are still identified as being unique and did not exhibit at least some of the above characteristics, indicating that they may have unknown functions not present in other RP genes. Furthermore, we found sequences conserved between human and mouse genes around the transcription start sites and in the intronic regions. This study suggests certain overall trends and characteristic features of human RP genes.
Computational and experimental analysis identifies Arabidopsis genes specifically expressed during early seed development
Authors: Becerra Cristian , Puigdomenech Pere , Vicient Carlos M 
Published: March 2006

Abstract

Background
Plant seeds are complex organs in which maternal tissues, embryo and endosperm, follow distinct but coordinated developmental programs. Some morphogenetic and metabolic processes are exclusively associated with seed development. The goal of this study was to explore the feasibility of incorporating the available online bioinformatics databases to discover Arabidopsis genes specifically expressed in certain organs, in our case immature seeds.

Results
A total of 11,032 EST sequences obtained from isolated immature seeds were used as the initial dataset (178 of them newly described here). A pilot study was performed using EST virtual subtraction followed by microarray data analysis, using the Genevestigator tool. These techniques led to the identification of 49 immature seed-specific genes. The findings were validated by RT-PCR analysis and in situ hybridization.

Conclusion
We conclude that the combined in silico data analysis is an effective data mining strategy for the identification of tissue-specific gene expression.
Deficits in spatial learning and motor coordination in ADAM11-deficient mice
Authors: Takahashi Eiki , Sagane Koji , Oki Tohru , Yamazaki Kazuto , Nagasu Takeshi , Kuromitsu Junro 
Published: March 2006

Abstract

Background
ADAM11 is a member of the ADAM gene family and is mainly expressed in the nervous system. It is thought to be an adhesion molecule, since it has a disintegrin-like domain related to cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM11, we generated ADAM11-deficient mice by means of gene targeting.

Results
ADAM11-deficient mice were apparently normal, and survived more than one year with no major histological abnormalities in the brain or spinal cord. Because ADAM11 is highly expressed in the hippocampus and cerebellum, we have examined ADAM11 mutant mice for learning using visual and hidden water maze tasks, and their motor coordination using a rotating rod task. Our results showed that their visual water maze task results are normal, but the hidden water maze and rotating rod task skills are impaired in ADAM11-deficient mice.

Conclusion
Our results indicate that ADAM11 mutation does not affect cell migration and differentiation during development, but affects learning and motor coordination. Thus, ADAM11 might play an important signalling or structural role as a cell adhesion molecule at the synapse, and may thus participate in synaptic regulation underlying behavioural changes.
Epidemic infectious gastrointestinal illness aboard U.S. Navy ships deployed to the Middle East during peacetime operations – 2000–2001
Authors: Riddle Mark S , Smoak Bonnie L , Thornton Scott A , Bresee Joseph S , Faix Dennis J , Putnam Shannon D 
Published: March 2006

Abstract

Background
Infectious gastrointestinal illness (IGI) outbreaks have been reported in U.S. Navy ships and could potentially have an adverse mission impact. Studies to date have been anecdotal.

Methods
We conducted a retrospective analysis of weekly reported disease and non-battle injury health data collected in 2000 – 2001 from 44 U.S. Navy ships while sailing in the 5th Fleet (Persian Gulf and nearby seas).

Results
During this period, 11 possible IGI outbreaks were identified. Overall, we found 3.3 outbreaks per 100 ship-weeks, a mean outbreak duration of 4.4 weeks, and a mean cumulative ship population attack rate of 3.6%. Morbidity, represented by days lost due to personnel being placed on sick-in-quarters status, was higher during outbreak weeks compared to non-outbreak weeks (p = 0.002). No clear seasonal distribution was identified.

Conclusion
Explosive outbreaks due to viruses and bacteria with the potential of incapacitating large proportions of the crew raise serious concerns of mission impact and military readiness.
Hepatitis B Virus infection in HIV-positive population in Brazil: results of a survey in the state of Mato Grosso and a comparative analysis with other regions of Brazil
Authors: de Almeida Pereira Rui Alberto Roldão , Hg Mussi Aparecida Duarte , de Azevedo e Silva Vergínia Correa , Souto Francisco José Dutra 
Published: March 2006

Abstract

Background
End-stage liver disease is currently a major concern among HIV-positive individuals due to co-infection with hepatotropic virus. Hepatitis C has been pointed out as a remarkable factor for that. More recently, hepatitis B virus (HBV) infection has also been found to play a role on liver disease in this population. HIV-HBV co-infection prevalence remains largely unknown in vast areas of Brazil. The objective of the present study was to estimate the prevalence of HBV and HDV infection in HIV-infected subjects living in the state of Mato Grosso, in the Central region of Brazil, and compare it to other Brazilian studies. We also assess epidemiologic data regarding risk factors and vaccinal status.

Methods
HIV-positive individuals followed at the Central Laboratory of the Department of Public Health of Mato Grosso in the city of Cuiabá composed the sample. Participants answered a specific questionnaire and had a blood sample taken and tested for serologic markers.

Results
A thousand individuals were interviewed and tested for HBsAg, anti-HBc, anti-HBs and anti-HDV if positive for HBsAg. Measurements of CD4 and viral load for HIV-1 were also performed. Overall prevalence of HBV exposure (anti-HBc +ve) was 40.0%, and 3.7% for HBsAg. This prevalence data was similar or slightly lower than for other Brazilian regions, which ranged from 40% and 3% to 71% and 24%, respectively. Testing for anti-HDV in the 37 HBsAg positive patients was positive in only one subject. Factors that showed independent association with HBV exposure, after adjustment, were: male gender, older age groups, tattooing, and reporting more than ten sexual partners throughout life (p < 0.01). Eighty-one (27.5%) out of 291 HBV-unexposed individuals who reported vaccination were anti-HBs positive. Anti-HBs prevalence was higher among those who had higher levels of CD4 by multivariate analysis.

Conclusion
Our data showed HBV infection prevalence similar or slightly lower than that reported in other regions of Brazil. In addition, our data revealed a less important role for drug injection in the spread of HIV and HBV in Mato Grosso compared to other regions of the country. The high rate of non-vaccinated subjects among this HBV-unexposed, HIV-infected population is a matter of considerable health concern in this region. The relationship between CD4 levels and HBV vaccine response found in the present study reinforces the need of keeping health care workers alert to this issue.
Invasive fungal infections in neutropenic enterocolitis: A systematic analysis of pathogens, incidence, treatment and mortality in adult patients
Authors: Gorschlüter Marcus , Mey Ulrich , Strehl John , Schmitz Volker , Rabe Christian , Pauls Katharina , Ziske Carsten , Schmidt-Wolf Ingo GH , Glasmacher Axel 
Published: March 2006

Abstract

Background
Neutropenic enterocolitis is a life-threatening complication most frequently occurring after intensive chemotherapy in acute leukaemias. Gramnegative bacteria constitute the most important group of causative pathogens. Fungi have also been reported, but their practical relevance remains unclear. The guidelines do not address concrete treatment recommendations for fungal neutropenic enterocolitis.

Methods
Here, we conducted a metaanalysis to answer the questions: What are frequency and mortality of fungal neutropenic enterocolitis? Do frequencies and microbiological distribution of causative fungi support empirical antimycotic therapy? Do reported results of antimycotic therapy in documented fungal neutropenic enterocolitis help with the selection of appropriate drugs? Following a systematic search, we extracted and summarised all detail data from the complete literature.

Results
Among 186 articles describing patients with neutropenic enterocolitis, we found 29 reports describing 53 patients with causative fungal pathogens. We found no randomised controlled trial, no good quality cohort study and no good quality case control study on the role of antifungal treatment. The pooled frequency of fungal neutropenic enterocolitis was 6.2% calculated from all 860 reported patients and 3.4% calculated from selected representative studies only. In 94% of the patients, Candida spp. were involved. The pooled mortality rate was 81.8%. Most authors did not report or perform antifungal therapy.

Conclusion
In patients with neutropenic enterocolitis, fungal pathogens play a relevant, but secondary role compared to bacteria. Evidence concerning therapy is very poor, but epidemiological data from this study may provide helpful clues to select empiric antifungal therapy in neutropenic enterocolitis.
An outbreak of Streptococcus equi subspecies zooepidemicusassociated with consumption of fresh goat cheese
Authors: Kuusi Markku , Lahti Elina , Virolainen Anni , Hatakka Maija , Vuento Risto , Rantala Leila , Vuopio-Varkila Jaana , Seuna Eija , Karppelin Matti , Hakkinen Marjaana , Takkinen Johanna , Gindonis Veera , Siponen Kyosti , Huotari Kaisa 
Published: March 2006

Abstract

Background

Streptococcus equi subspecies zooepidemicus is a rare infection in humans associated with contact with horses or consumption of unpasteurized milk products. On October 23, 2003, the National Public Health Institute was alerted that within one week three persons had been admitted to Tampere University Central Hospital (TaYS) because of S. equi subsp. zooepidemicus septicaemia. All had consumed fresh goat cheese produced in a small-scale dairy located on a farm. We conducted an investigation to determine the source and the extent of the outbreak.

Methods
Cases were identified from the National Infectious Disease Register. Cases were persons with S. equi subsp. zooepidemicus isolated from a normally sterile site who had illness onset 15.9-31.10.2003. All cases were telephone interviewed by using a standard questionnaire and clinical information was extracted from patient charts. Environmental and food specimens included throat swabs from two persons working in the dairy, milk from goats and raw milk tank, cheeses made of unpasteurized milk, vaginal samples of goats, and borehole well water. The isolates were characterized by ribotyping and pulsed-field gel electrophoresis (PFGE).

Results
Seven persons met the case definition; six had septicaemia and one had purulent arthritis. Five were women; the median age was 70 years (range 54–93). None of the cases were immunocompromized and none died. Six cases were identified in TaYS, and one in another university hospital in southern Finland. All had eaten goat cheese produced on the implicated farm. S. equi subsp. zooepidemicus was isolated from throat swabs, fresh goat cheese, milk tank, and vaginal samples of one goat. All human and environmental strains were indistinguishable by ribotyping and PFGE.

Conclusion
The outbreak was caused by goat cheese produced from unpasteurized milk. Outbreaks caused by S. equi subsp. zooepidemicus may not be detected if streptococcal strains are only typed to the group level. S. equi subsp. zooepidemicus may be a re-emerging disease if unpasteurized milk is increasingly used for food production. Facilities using unpasteurized milk should be carefully monitored to prevent this type of outbreaks.