bluuebunny/crossref_metadata_2025_split huggingface dataset:
How many human genes can be defined as housekeeping with current expression data?
Authors: Zhu Jiang , He Fuhong , Song Shuhui , Wang Jing , Yu Jun 
Published: April 2008

Abstract

Background
Housekeeping (HK) genes are ubiquitously expressed in all tissue/cell types and constitute a basal transcriptome for the maintenance of basic cellular functions. Partitioning transcriptomes into HK and tissue-specific (TS) genes relatively is fundamental for studying gene expression and cellular differentiation. Although many studies have aimed at large-scale and thorough categorization of human HK genes, a meaningful consensus has yet to be reached.

Results
We collected two latest gene expression datasets (both EST and microarray data) from public databases and analyzed the gene expression profiles in 18 human tissues that have been well-documented by both two data types. Benchmarked by a manually-curated HK gene collection (HK408), we demonstrated that present data from EST sampling was far from saturated, and the inadequacy has limited the gene detectability and our understanding of TS expressions. Due to a likely over-stringent threshold, microarray data showed higher false negative rate compared with EST data, leading to a significant underestimation of HK genes. Based on EST data, we found that 40.0% of the currently annotated human genes were universally expressed in at least 16 of 18 tissues, as compared to only 5.1% specifically expressed in a single tissue. Our current EST-based estimate on human HK genes ranged from 3,140 to 6,909 in number, a ten-fold increase in comparison with previous microarray-based estimates.

Conclusion
We concluded that a significant fraction of human genes, at least in the currently annotated data depositories, was broadly expressed. Our understanding of tissue-specific expression was still preliminary and required much more large-scale and high-quality transcriptomic data in future studies. The new HK gene list categorized in this study will be useful for genome-wide analyses on structural and functional features of HK genes.
Transcriptome architecture across tissues in the pig
Authors: Ferraz André LJ , Ojeda Ana , López-Béjar Manel , Fernandes Lana T , Castelló Anna , Folch Josep M , Pérez-Enciso Miguel 
Published: April 2008

AbstractBackgroundArtificial selection has resulted in animal breeds with extreme phenotypes. As an organism is made up of many different tissues and organs, each with its own genetic programme, it is pertinent to ask: How relevant is tissue in terms of total transcriptome variability? Which are the genes most distinctly expressed between tissues? Does breed or sex equally affect the transcriptome across tissues?ResultsIn order to gain insight on these issues, we conducted microarray expression profiling of 16 different tissues from four animals of two extreme pig breeds, Large White and Iberian, two males and two females. Mixed model analysis and neighbor – joining trees showed that tissues with similar developmental origin clustered closer than those with different embryonic origins. Often a sound biological interpretation was possible for overrepresented gene ontology categories within differentially expressed genes between groups of tissues. For instance, an excess of nervous system or muscle development genes were found among tissues of ectoderm or mesoderm origins, respectively. Tissue accounted for ~11 times more variability than sex or breed. Nevertheless, we were able to confidently identify genes with differential expression across tissues between breeds (33 genes) and between sexes (19 genes). The genes primarily affected by sex were overall different than those affected by breed or tissue. Interaction with tissue can be important for differentially expressed genes between breeds but not so much for genes whose expression differ between sexes.ConclusionEmbryonic development leaves an enduring footprint on the transcriptome. The interaction in gene × tissue for differentially expressed genes between breeds suggests that animal breeding has targeted differentially each tissue's transcriptome.
The Retinoic Acid Receptor-α mediates human T-cell activation and Th2 cytokine and chemokine production
Authors: Dawson Harry D , Collins Gary , Pyle Robert , Key Michael , Taub Dennis D 
Published: April 2008

AbstractBackgroundWe have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cisRA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-γ and TNF-α expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cisRA are shared with the clinically useful RAR ligand, 13-cisretinoic acid (13-cisRA), and the retinoic acid receptor-α (RAR-α)-selective agonist, AM580 but not with the RAR-β/γ ligand, 4-hydroxyphenylretinamide (4-HPR).ResultsThe increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-α-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-α-selective antagonist, RO 41–5253, inhibited these effects.ConclusionThese results strongly support a role for RAR-α engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.
Two-dimensional electrophoretic comparison of metastatic and non-metastatic human breast tumors using in vitrocultured epithelial cells derived from the cancer tissues
Authors: Vydra Jan , Selicharová Irena , Smutná Kateřina , Šanda Miloslav , Matoušková Eva , Buršíková Eva , Prchalová Markéta , Velenská Zuzana , Coufal David , Jiráček Jiří 
Published: April 2008

Abstract

Background
Breast carcinomas represent a heterogeneous group of tumors diverse in behavior, outcome, and response to therapy. Identification of proteins resembling the tumor biology can improve the diagnosis, prediction, treatment selection, and targeting of therapy. Since the beginning of the post-genomic era, the focus of molecular biology gradually moved from genomes to proteins and proteomes and to their functionality. Proteomics can potentially capture dynamic changes in protein expression integrating both genetic and epigenetic influences.

Methods
We prepared primary cultures of epithelial cells from 23 breast cancer tissue samples and performed comparative proteomic analysis. Seven patients developed distant metastases within three-year follow-up. These samples were included into a metastase-positive group, the others formed a metastase-negative group. Two-dimensional electrophoretical (2-DE) gels in pH range 4–7 were prepared. Spot densities in 2-DE protein maps were subjected to statistical analyses (R/maanova package) and data-mining analysis (GUHA). For identification of proteins in selected spots, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed.

Results
Three protein spots were significantly altered between the metastatic and non-metastatic groups. The correlations were proven at the 0.05 significance level. Nucleophosmin was increased in the group with metastases. The levels of 2,3-trans-enoyl-CoA isomerase and glutathione peroxidase 1 were decreased.

Conclusion
We have performed an extensive proteomic study of mammary epithelial cells from breast cancer patients. We have found differentially expressed proteins between the samples from metastase-positive and metastase-negative patient groups.
Duplicate gene expression in allopolyploid Gossypiumreveals two temporally distinct phases of expression evolution
Authors: Flagel Lex , Udall Joshua , Nettleton Dan , Wendel Jonathan 
Published: April 2008

AbstractBackgroundPolyploidy has played a prominent role in shaping the genomic architecture of the angiosperms. Through allopolyploidization, several modernGossypium(cotton) species contain two divergent, although largely redundant genomes. Owing to this redundancy, these genomes can play host to an array of evolutionary processes that act on duplicate genes.ResultsWe compared homoeolog (genes duplicated by polyploidy) contributions to the transcriptome of a natural allopolyploid and a synthetic interspecific F1hybrid, both derived from a merger between diploid species from theGossypiumA-genome and D-genome groups. Relative levels of A- and D-genome contributions to the petal transcriptome were determined for 1,383 gene pairs. This comparison permitted partitioning of homoeolog expression biases into those arising from genomic merger and those resulting from polyploidy. Within allopolyploidGossypium, approximately 24% of the genes with biased (unequal contributions from the two homoeologous copies) expression patterns are inferred to have arisen as a consequence of genomic merger, indicating that a substantial fraction of homoeolog expression biases occur instantaneously with hybridization. The remaining 76% of biased homoeologs reflect long-term evolutionary forces, such as duplicate gene neofunctionalization and subfunctionalization. Finally, we observed a greater number of genes biased toward the paternal D-genome and that expression biases have tended to increases during allopolyploid evolution.ConclusionOur results indicate that allopolyploidization entails significant homoeolog expression modulation, both immediately as a consequence of genomic merger, and secondarily as a result of long-term evolutionary transformations in duplicate gene expression.
Plasmodium falciparum-free merozoites and infected RBCs distinctly affect soluble CD40 ligand-mediated maturation of immature monocyte-derived dendritic cells
Authors: Mukherjee Paushali , Chauhan Virander Singh 
Published: April 2008

AbstractFree plasmodium merozoites released from the parasitized hepatocytes and erythrocytes represent a transitory, extracellular stage in its mammalian host. In this study, we compared the effect of Plasmodium falciparum-free merozoites with infected RBCs (iRBCs) on the maturation of human monocyte-derived dendritic cells (DCs) in vitro. Phagocytosed-free merozoites prevented soluble CD40 ligand (sCD40L)-induced, phenotypic maturation of DCs and secretion of IL-12p70 but enhanced IL-10 production and primed, naive CD4+ cells to produce a high level of IL-10 compared with IFN-γ. Free merozoites augmented sCD40L-induced ERK1/2 activation, and inhibition of ERK1/2 with its inhibitor PD98059 markedly abrogated IL-10 production and rescued IL-12 production. Therefore, the molecular mechanisms by which free merozoites antagonized sCD40L-induced DC maturation appeared to involve the activation of the ERK pathway. In contrast, phagocytosed iRBCs by itself induced DCs to semi-maturation, responded to CD40 signaling by maturing and secreting increased levels of TNF-α, IL-6, and also IL-12p70, and led to a pronounced, proinflammatory response by the allogenic CD4+ T cells. iRBCs regulate CD40-induced p38MAPK. Studies using inhibitors selective for p38MAPK (SB203580) showed that p38MAPK played an essential role in the maturation and function of DCs. Our results reveal the ability of free merozoites and iRBCs to distinctly alter the sCD40L-induced DC functioning by regulating the activation of the MAPK pathway that can inactivate or exacerbate immune responses to promote their survival and the development of parasite-specific pathologies.
Treatment of Hypovitaminosis D in Infants and Toddlers
Authors: Gordon Catherine M. , Williams Avery LeBoff , Feldman Henry A. , May Jessica , Sinclair Linda , Vasquez Alex , Cox Joanne E. 
Published: April 2008

Abstract
Context: Hypovitaminosis D appears to be on the rise in young children, with implications for skeletal and overall health.
Objective: The objective of the study was to compare the safety and efficacy of vitamin D2 daily, vitamin D2 weekly, and vitamin D3 daily, combined with supplemental calcium, in raising serum 25-hydroxyvitamin D [25(OH)D] and lowering PTH concentrations.
Design: This was a 6-wk randomized controlled trial.
Setting: The study was conducted at an urban pediatric clinic in Boston.
Subjects: Forty otherwise healthy infants and toddlers with hypovitaminosis D [25(OH)D &lt; 20 ng/ml] participated in the study.
Interventions: Participants were assigned to one of three regimens: 2,000 IU oral vitamin D2 daily, 50,000 IU vitamin D2 weekly, or 2,000 IU vitamin D3 daily. Each was also prescribed elemental calcium (50 mg/kg·d). Infants received treatment for 6 wk.
Main Outcome Measures: Before and after treatment, serum measurements of 25(OH)D, PTH, calcium, and alkaline phosphatase were taken.
Results: All treatments approximately tripled the 25(OH)D concentration. Preplanned comparisons were nonsignificant: daily vitamin D2 vs. weekly vitamin D2 (12% difference in effect, P = 0.66) and daily D2 vs. daily D3 (7%, P = 0.82). The mean serum calcium change was small and similar in the three groups. There was no significant difference in PTH suppression.
Conclusions: Short-term vitamin D2 2,000 IU daily, vitamin D2 50,000 IU weekly, or vitamin D3 2,000 IU daily yield equivalent outcomes in the treatment of hypovitaminosis D among young children. Therefore, pediatric providers can individualize the treatment regimen for a given patient to ensure compliance, given that no difference in efficacy or safety was noted among these three common treatment regimens.
Role of Growth Hormone in Regulating Lipolysis, Proteolysis, and Hepatic Glucose Production during Fasting
Authors: Sakharova Alla A. , Horowitz Jeffrey F. , Surya Sowmya , Goldenberg Naila , Harber Matthew P. , Symons Kathy , Barkan Ariel 
Published: April 2008

Abstract
Context: Fasting is associated with suppressed insulin and augmented GH secretion. The involvement of each mechanism in the regulation of fuel mobilization during fasting is unknown.
Objective: To ascertain the role of GH in the regulation of the rates of lipolysis, proteolysis, and hepatic glucose production (HGP) during the physiological daily feed/fast cycle and after 2 d of complete fasting, we used a model of selective GH suppression by the administration of GHRH receptor antagonist (GHRH-A).
Design and Setting: We conducted an open label in-patient study in the General Clinical Research Center at the University of Michigan.
Participants: Six healthy, nonobese volunteers participated.
Main Outcome Measures: We assessed 24-h plasma GH concentration and rates of lipolysis, proteolysis, and HGP using stable isotope techniques after an overnight fast and after 2 d of fasting.
Results: GHRH-A suppressed plasma GH by about 65% during the fed state (P = 0.015) but did not alter the rates of lipolysis, proteolysis, or HGP. Fasting for 2 d suppressed plasma insulin concentration by about 80% and elevated plasma GH about 4-fold (both P &lt; 0.01). This was accompanied by a doubling in the rate of lipolysis, an approximately 40% increase in proteolysis, and an approximately 30% decline in HGP (all P &lt; 0.05). Preventing the fasting-induced increase in GH with GHRH-A largely abolished the increase in the rate of lipolysis. GHRH-A also augmented the fasting-induced reduction in HGP but did not alter proteolysis.
Conclusions: Endogenous GH plays a very limited metabolic role during the daily feed/fast cycle but is essential for the increased lipolytic rate found with more prolonged fasting.
The Role of Stereotactic Radiotherapy in Patients with Growth Hormone-Secreting Pituitary Adenoma
Authors: Losa Marco , Gioia Lorenzo , Picozzi Piero , Franzin Alberto , Valle Micol , Giovanelli Massimo , Mortini Pietro 
Published: April 2008

Abstract
Context: Single-session stereotactic radiotherapy (SR) may be a potential adjuvant treatment in acromegaly.
Objective: We analyzed the safety and efficacy of SR in patients who had previously received maximal surgical debulking at our center.
Design: The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 through 2006.
Setting: The study was performed at a university hospital.
Patients: Eighty-three acromegalic patients, 52 women and 31 men, with a mean age of 42.6 ± 1.2 yr, participated in the study. The median follow-up was 69 months (interquartile range 44–107 months).
Intervention: The patients were treated with SR for residual or recurrent GH-secreting adenoma.
Main Outcome Measure: Normalization of age- and sex-adjusted IGF-I levels together with a basal GH level below 2.5 μg/liter without concomitant GH-suppressive drugs was the goal of therapy.
Results: Fifty patients (60.2%) reached the main outcome of the study. The rate of remission was 52.6% at 5 yr [95% confidence interval (CI) 40.6–64.6%]. Another 13 patients (15.7%), who were resistant to somatostatin analogs, were in remission after SR. Multivariate analysis showed that low basal GH and IGF-I levels were associated with a favorable outcome. No serious side effects occurred after SR. The 5-yr cumulative risk of new onset hypogonadism, hypothyroidism, or hypoadrenalism was 3.6% (95% CI 0–8.6%), 3.3% (95% CI 0–7.7%), and 4.9% (95% CI 0–10.4%), respectively.
Conclusion: In a highly selected group of acromegalic patients, SR treatment had good efficacy and safety. This may lead to reconsider the role of SR in the therapeutic algorithm of acromegaly.
Male Hormonal Contraception: A Double-Blind, Placebo-Controlled Study
Authors: Mommers Ellen , Kersemaekers Wendy M. , Elliesen Jörg , Kepers Marc , Apter Dan , Behre Hermann M. , Beynon Jennifer , Bouloux Pierre M. , Costantino Antonietta , Gerbershagen Hans-Peter , Grønlund Lars , Heger-Mahn Doris , Huhtaniemi Ilpo , Koldewijn Evert L. , Lange Corinna , Lindenberg Svend , Meriggiola M. Cristina , Meuleman Eric , Mulders Peter F. A. , Nieschlag Eberhard , Perheentupa Antti , Solomon Andrew , Väisälä Leena , Wu Frederick C. , Zitzmann Michael 
Published: April 2008

AbstractBackground: This study was performed to assess spermatogenesis suppression and safety of a new combination of an etonogestrel (ENG) implant combined with testosterone undecanoate (TU) injections for male contraception. This is the first large placebo-controlled study for male hormonal contraception.Design and Study Subjects: In this double-blind, multicenter study, we randomly assigned 354 healthy men to receive either a low- or high-release ENG implant sc combined with im TU injections (750 mg every 10 or 12 wk or 1000 mg every 12 wk) or placebo implant and injections. Treatment duration was 42 or 44 wk and posttreatment follow-up at least 24 wk.Results: Overall, spermatogenesis was suppressed to 1 million/ml or less at wk 16 in 89% of men, with approximately 94% in two high-release ENG groups. Suppression was maintained up to the end of the treatment period in 91% of men. For all men who completed the treatment period, 3% never achieved 1 million/ml or less. Median recovery time to a sperm concentration above 20 million/ml was 15 wk (mean 17 wk, 95% confidence interval 16–18 wk). Treatment was well tolerated. As compared with the placebo group, more men in the active treatment groups reported adverse events such as weight gain, mood changes, acne, sweating, or libido change. For both spermatogenesis suppression and safety, differences were small between the active treatment groups.Conclusions: The combination of an ENG implant with TU injections is a well-tolerated male hormonal method, providing effective and reversible suppression of spermatogenesis. Although the results are good, there is still room for improvement, possibly by adjusting the dose regimen or changing the mode of application.
Efficacy of Tamsulosin with Extracorporeal Shock Wave Lithotripsy for Passage of Renal and Ureteral Calculi
Authors: Losek Ryan L , Mauro Laurie S 
Published: April 2008

Objective: To review the evidence for the safety and efficacy of adjunctive tamsulosin in enhancing the efficacy of renal and ureteral stone clearance when used with extracorporeal shock wave lithotripsy (ESWL). Data Sources: A search of MEDLINE (1950-January 2008), PubMed (1950-January 2008), and the Iowa Drug Information System (1966-January 2008) was performed using the search terms tamsulosin and extracorporeal shock wave lithotripsy. MeSH headings included lithotripsy and adrenergic α-antagonists. Additional references were found by searching bibliographic references of resulting citations. Study Selection and Data Extraction: All studies utilizing tamsulosin therapy after a single session of ESWL or after the development of steinstrasse, an accumulation of stone fragments that obstructs the ureter, were included. Data Synthesis: To date, 5 prospective studies have evaluated the efficacy of tamsulosin combined with ESWL in enhancing the passage of renal and ureteral stones. in one trial, 12-week renal stone clearance was 60% in the control group compared with 78.5% in the tamsulosin group (p = 0.037). Among trials that evaluated overall ureteral stone clearance, efficacy rates were 33.3-79.3% in the control groups compared with 66.6-96.6% in the tamsulosin groups. Reports of pain and supplemental analgesic dosing were consistently lower with tamsulosin, but data on the incidence of subsequent retreatment with ESWL or ureteroscopy was rarely reported. Adjunctive tamsulosin particularly enhanced the passage of renal stones 10-24 millimeters in diameter. Overall, tamsulosin was well tolerated. Conclusions: Overall, evidence suggests that adjunctive tamsulosin therapy combined with ESWL is safe and effective in enhancing stone clearance in patients with renal stones 10-24 millimeters in diameter. Evidence regarding ureteral stone clearance is inconclusive, although adjunctive tamsulosin has been reported to reduce painful episodes. Larger prospective trials evaluating different dosages and stone locations, as well as the ability of tamsulosin to reduce repeat ESWL or more invasive methods such as ureteroscopy should be performed.
Single Antiplatelet Therapy for Patients with Previous Gastrointestinal Bleeds
Authors: Gellatly Rochelle M , Ackman Margaret L 
Published: April 2008

Objective: To determine whether aspirin plus a proton pump inhibitor (PPI) is preferable, from a gastrointestinal bleed (GIB) risk perspective, to clopidogrel in patients who have experienced a GIB while on aspirin and who require single antiplatelet therapy for secondary prevention of cardiovascular disease. Data Sources: A literature search was conducted using EMBASE (1980–January 2008), PubMed (1966–January 2008), Google, and a manual search of the reference lists using the search terms gastrointestinal bleed, gastrointestinal hemorrhage, peptic ulcer hemorrhage, ASA, aspirin. Plavix, clopidogrel, and PPI. The search, limited to human and English studies, yielded 110 returns. Study Selection and Data Extraction: Randomized trials that compared aspirin with clopidogrel, involved patients who had previously experienced a GIB, and provided detailed information on the type and dose of drugs used were included. Studies were required to provide information on the recurrence of GIB. Data Synthesis: Two randomized trials were reviewed to assess the safety of secondary prevention of cardiovascular disease with respect to previous GIB. These noninferiority trials compared aspirin plus a PPI with clopidogrel over 12 months following confirmed healing of an aspirin-induced ulcer. In both trials, the majority of the GIB recurrences were in the clopidogrel group (8.6% vs 0.7%; difference 7.9%; 95% CI 3.4 to 12.4; p = 0.001 and 13.6% vs 0%; difference 13.6%; 95% CI 6.3 to 20.9; p = 0.0019) and the difference in recurrence rates exceeded the a priori selected upper boundary. Conclusions: Findings reported in the limited literature available support that clopidogrel is not equivalent to the combination of aspirin plus a PPI in the patient population studied. Aspirin plus a PPI would be considered clinically superior and should be used in medically managed patients who require single antiplatelet therapy but have had a prior GIB while on aspirin. Further research regarding dual antiplatelet therapy and a PPI is required.