bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of statistical significance for comparison of individual positions in multiple sequence alignments
Authors: Sadreyev Ruslan I , Grishin Nick V 
Published: August 2004

Abstract
Background
Profile-based analysis of multiple sequence alignments (MSA) allows for accurate comparison of protein families. Here, we address the problems of detecting statistically confident dissimilarities between (1) MSA position and a set of predicted residue frequencies, and (2) between two MSA positions. These problems are important for (i) evaluation and optimization of methods predicting residue occurrence at protein positions; (ii) detection of potentially misaligned regions in automatically produced alignments and their further refinement; and (iii) detection of sites that determine functional or structural specificity in two related families.

Results
For problems (1) and (2), we propose analytical estimates of P-value and apply them to the detection of significant positional dissimilarities in various experimental situations. (a) We compare structure-based predictions of residue propensities at a protein position to the actual residue frequencies in the MSA of homologs. (b) We evaluate our method by the ability to detect erroneous position matches produced by an automatic sequence aligner. (c) We compare MSA positions that correspond to residues aligned by automatic structure aligners. (d) We compare MSA positions that are aligned by high-quality manual superposition of structures. Detected dissimilarities reveal shortcomings of the automatic methods for residue frequency prediction and alignment construction. For the high-quality structural alignments, the dissimilarities suggest sites of potential functional or structural importance.

Conclusion
The proposed computational method is of significant potential value for the analysis of protein families.
Co-transcriptional folding is encoded within RNA genes
Authors: Meyer Irmtraud M , Miklós István 
Published: August 2004

Abstract
Background
Most of the existing RNA structure prediction programs fold a completely synthesized RNA molecule. However, within the cell, RNA molecules emerge sequentially during the directed process of transcription. Dedicated experiments with individual RNA molecules have shown that RNA folds while it is being transcribed and that its correct folding can also depend on the proper speed of transcription.

Methods
The main aim of this work is to study if and how co-transcriptional folding is encoded within the primary and secondary structure of RNA genes. In order to achieve this, we study the known primary and secondary structures of a comprehensive data set of 361 RNA genes as well as a set of 48 RNA sequences that are known to differ from the originally transcribed sequence units. We detect co-transcriptional folding by defining two measures of directedness which quantify the extend of asymmetry between alternative helices that lie 5' and those that lie 3' of the known helices with which they compete.

Results
We show with statistical significance that co-transcriptional folding strongly influences RNA sequences in two ways: (1) alternative helices that would compete with the formation of the functional structure during co-transcriptional folding are suppressed and (2) the formation of transient structures which may serve as guidelines for the co-transcriptional folding pathway is encouraged.

Conclusions
These findings have a number of implications for RNA secondary structure prediction methods and the detection of RNA genes.
Epidemiology of the human immunodeficiency virus in Saudi Arabia; 18-year surveillance results and prevention from an Islamic perspective
Authors: Madani Tariq A , Al-Mazrou Yagob Y , Al-Jeffri Mohammad H , Al Huzaim Naser S 
Published: August 2004

Abstract
Background
data on HIV epidemiology and preventive measures in Islamic countries is limited. This study describes the results of 18-year of HIV surveillance in Saudi Arabia (SA) and the preventive measures implemented from an Islamic perspective.

Methods
surveillance for HIV has been underway in SA since 1984. Indications for HIV testing include clinical suspicion, screening of contacts of HIV-infected patients, and routine screening of blood and organ donors, prisoners, intravenous drug users, patients with other sexually transmitted infections, and expatriates pre-employment. This is a case series descriptive study of all confirmed HIV infections diagnosed in SA from 1984 through 2001.

Results
a total of 6046 HIV infections were diagnosed, of which 1285 (21.3%) cases were Saudi citizens. Over the 18-year surveillance period the number of HIV infections diagnosed annually among Saudi citizens gradually increased and, over the period 1997–2001, it reached to 84 to 142 cases per year. The number of cases per 100,000 population varied widely between regions with a maximum of 74 cases and a minimum of 2 cases. The infection was most common in the age group 20–40 years (74.6%) and predominantly affected men (71.6%). The modes of transmission among Saudi citizens and expatriates, respectively, were as follows: heterosexual contact, 487 (37.9%) and 1352 (28.4%) cases; blood transfusion, 322 (25.0%) and 186 (3.9%) cases; perinatal transmission, 83 (6.5%) and 19 (0.4%) cases; homosexual contact, 32 (2.5%) and 38 (0.8%) cases; intravenous drug use, 17 (1.3%) and 33 (0.7%) cases; bisexual contact, 10 (0.8%) and 14 (0.3%) cases; unknown, 334 (26.0%) and 3119 (65.5%) cases. The number of HIV infections transmitted by blood or blood products transfusion declined to zero by year 2001 and all such infections occurred due to transfusions administered before 1986. At HIV diagnosis, 4502/6046 (74.5%) patients had no symptoms, 787 (13.0%) patients had non-AIDS defining manifestations, and 757 (12.5%) patients had AIDS. A total of 514/1285 (40%) Saudi patients died by year 2001.

Conclusions
the number of HIV cases in SA is limited with heterosexual contact being the main mode of transmission. From an Islamic perspective, preventive strategies include prevention of non-marital sex and intravenous drug use with encouragement of "safe sex" through legal marriage.
The oncogenic fusion protein RUNX1-CBFA2T1 supports proliferation and inhibits senescence in t(8;21)-positive leukaemic cells
Authors: Martinez Natalia , Drescher Bettina , Riehle Heidemarie , Cullmann Claire , Vornlocher Hans-Peter , Ganser Arnold , Heil Gerhard , Nordheim Alfred , Krauter Jürgen , Heidenreich Olaf 
Published: August 2004

Abstract
Background
The fusion protein RUNX1-CBFA2T1 associated with t(8;21)-positive acute myeloid leukaemia is a potent inhibitor of haematopoetic differentiation. The role of RUNX1-CBFA2T1 in leukaemic cell proliferation is less clear. We examined the consequences of siRNA-mediated RUNX1-CBFA2T1 depletion regarding proliferation and clonogenicity of t(8;21)-positive cell lines.

Methods
The t(8;21)-positive cell line Kasumi-1 was electroporated with RUNX1-CBFA2T1 or control siRNAs followed by analysis of proliferation, colony formation, cell cycle distribution, apoptosis and senescence.

Results
Electroporation of Kasumi-1 cells with RUNX1-CBFA2T1 siRNAs, but not with control siRNAs, resulted in RUNX1-CBFA2T1 suppression which lasted for at least 5 days. A single electroporation with RUNX1-CBFA2T1 siRNA severely diminished the clonogenicity of Kasumi-1 cells. Prolonged RUNX1-CBFA2T1 depletion inhibited proliferation in suspension culture and G1-S transition during the cell cycle, diminished the number of apoptotic cells, but induced cellular senescence. The addition of haematopoetic growth factors could not rescue RUNX1-CBFA2T1-depleted cells from senescence, and could only partially restore their clonogenicity.

Conclusions
RUNX1-CBFA2T1 supports the proliferation and expansion of t(8;21)-positive leukaemic cells by preventing cellular senescence. These findings suggest a central role of RUNX1-CBFA2T1 in the maintenance of the leukaemia. Therefore, RUNX1-CBFA2T1 is a promising and leukaemia-specific target for molecularly defined therapeutic approaches.
Association study of polymorphisms in the excitatory amino acid transporter 2 gene (SLC1A2) with schizophrenia
Authors: Deng Xiangdong , Shibata Hiroki , Ninomiya Hideaki , Tashiro Nobutada , Iwata Nakao , Ozaki Norio , Fukumaki Yasuyuki 
Published: August 2004

Abstract
Background
The glutamatergic dysfunction hypothesis of schizophrenia suggests that genes involved in glutametergic transmission are candidates for schizophrenic susceptibility genes. We have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. In this study we report an association study of the excitatory amino acid transporter 2 gene, SLC1A2 with schizophrenia.

Methods
We genotyped 100 Japanese schizophrenics and 100 controls recruited from the Kyushu area for 11 single nucleotide polymorphism (SNP) markers distributed in the SLC1A2 region using the direct sequencing and pyrosequencing methods, and examined allele, genotype and haplotype association with schizophrenia.The positive finding observed in the Kyushu samples was re-examined using 100 Japanese schizophrenics and 100 controls recruited from the Aichi area.

Results
We found significant differences in genotype and allele frequencies of SNP2 between cases and controls (P = 0.013 and 0.008, respectively). After Bonferroni corrections, the two significant differences disappeared. We tested haplotype associations for all possible combinations of SNP pairs. SNP2 showed significant haplotype associations with the disease (P = 9.4 × 10-5, P = 0.0052 with Bonferroni correction, at the lowest) in 8 combinations. Moreover, the significant haplotype association of SNP2-SNP7 was replicated in the cumulative analysis of our two sample sets.

Conclusion
We concluded that at least one susceptibility locus for schizophrenia is probably located within or nearby SLC1A2 in the Japanese population.
The significance of controlled conditions in lentiviral vector titration and in the use of multiplicity of infection (MOI) for predicting gene transfer events
Authors: Zhang Bing , Metharom Pat , Jullie Howard , Ellem Kay AO , Cleghorn Geoff , West Malcolm J , Wei Ming Q 
Published: August 2004

Abstract
Background
Although lentiviral vectors have been widely used for in vitro and in vivo gene therapy researches, there have been few studies systematically examining various conditions that may affect the determination of the number of viable vector particles in a vector preparation and the use of Multiplicity of Infection (MOI) as a parameter for the prediction of gene transfer events.

Methods
Lentiviral vectors encoding a marker gene were packaged and supernatants concentrated. The number of viable vector particles was determined by in vitro transduction and fluorescent microscopy and FACs analyses. Various factors that may affect the transduction process, such as vector inoculum volume, target cell number and type, vector decay, variable vector – target cell contact and adsorption periods were studied. MOI between 0–32 was assessed on commonly used cell lines as well as a new cell line.

Results
We demonstrated that the resulting values of lentiviral vector titre varied with changes of conditions in the transduction process, including inoculum volume of the vector, the type and number of target cells, vector stability and the length of period of the vector adsorption to target cells. Vector inoculum and the number of target cells determine the frequencies of gene transfer event, although not proportionally. Vector exposure time to target cells also influenced transduction results. Varying these parameters resulted in a greater than 50-fold differences in the vector titre from the same vector stock. Commonly used cell lines in vector titration were less sensitive to lentiviral vector-mediated gene transfer than a new cell line, FRL 19. Within 0–32 of MOI used transducing four different cell lines, the higher the MOI applied, the higher the efficiency of gene transfer obtained.

Conclusion
Several variables in the transduction process affected in in vitro vector titration and resulted in vastly different values from the same vector stock, thus complicating the use of MOI for predicting gene transfer events. Commonly used target cell lines underestimated vector titre. However, within a certain range of MOI, it is possible that, if strictly controlled conditions are observed in the vector titration process, including the use of a sensitive cell line, such as FRL 19 for vector titration, lentivector-mediated gene transfer events could be predicted.
Origin of Aldosterone in the Rat Heart
Authors: Gomez-Sanchez Elise P. , Ahmad Naveed , Romero Damian G. , Gomez-Sanchez Celso E. 
Published: August 2004

AbstractAldosterone has been demonstrated in the perfusate of the ex situ rat heart and heart homogenates; however, the origin of aldosterone in the heart is controversial, with some reporting a primary role for extraadrenal synthesis within the heart, and others finding that all of the aldosterone in the heart is sequestered from the circulation. In an attempt to resolve this controversy, we measured the aldosterone and corticosterone contents of plasma and hearts of rats on a normal salt (NS), low salt (LS), or high salt (HS) diet, adrenalectomized (ADX+HS), and ADX with aldosterone replacement or deoxycorticosterone excess (ADX+HS+DOC) before tissue harvest. The sodium content of the diet had no significant effect on corticosterone levels in the plasma or heart. LS significantly increased, whereas HS decreased the aldosterone content of plasma and heart compared with NS. Corticosterone levels in both plasma and heart and aldosterone levels in plasma of ADX-HS rats were undetectable in most individuals and were extremely low in very few. Although plasma aldosterone was undetectable, aldosterone was measurable in 30% of the hearts of 84 ADX+HS rats, albeit at low levels. The aldosterone and corticosterone contents of the hearts of ADX+HS+DOC were similar to those of ADX+HS, indicating that aldosterone synthase and 11β-hydroxylase, not substrate, are the limiting factors for extraadrenal synthesis of corticosteroids in the heart. In conclusion, we found that the level of aldosterone content in the healthy rat heart in vivo is significantly lower than that reported elsewhere and reflects plasma levels in intact rats.
Effect of Interferon-τ on Prostaglandin Biosynthesis, Transport, and Signaling at the Time of Maternal Recognition of Pregnancy in Cattle: Evidence of Polycrine Actions of Prostaglandin E2
Authors: Arosh J. A. , Banu S. K. , Kimmins S. , Chapdelaine P. , MacLaren L. A. , Fortier M. A. 
Published: August 2004

Abstract
Recognition and establishment of pregnancy involve several molecular and cellular interactions among the conceptus, uterus, and corpus luteum (CL). In ruminants, interferon-τ (IFNτ) of embryonic origin is recognized as the pregnancy recognition signal. Endometrial prostaglandin F2α (PGF2α) is the luteolysin, whereas PGE2 is considered a luteoprotective or luteotrophic mediator at the time of establishment of pregnancy. The interplay between IFNτ and endometrial PGs production, transport, and signaling at the time of maternal recognition of pregnancy (MRP) is not well understood. We have studied the expression of enzymes involved in metabolism of PGE2 and PGF2α, cyclooxygenase-1 (COX-1) and COX-2, PG synthases (PGES and PGFS), PG 15-dehydrogenase, and PG transporter as well as PGE2 (EP2 and EP3) and PGF2α receptors. IFNτ influences cell-specific expression of COX-2, PGFS, EP2, and EP3 in endometrium, myometrium, and CL in a spatio-temporal and tissue-specific manner, whereas it does not alter COX-1, PGES, PG 15-dehydrogenase, PG transporter, or PGF2α receptor expression in any of these tissues. In endometrium, IFNτ decreases PGFS in epithelial cells and increases EP2 in stroma. In myometrium, IFNτ decreases PGFS and increases EP2 in smooth muscle cells. In CL, IFNτ increases PGES and decreases EP3. Together, our results show that IFNτ directly or indirectly increases PGE2 biosynthesis and EP2-associated signaling in endometrium, myometrium, and CL during MRP. Thus, PGE2 may play pivotal roles in endometrial receptivity, myometrial quiescence, and luteal maintenance, indicating polycrine (endocrine, exocrine, paracrine, and autocrine) actions of PGE2 at the time of MRP. Therefore, the establishment of pregnancy may depend not only on inhibition of endometrial PGF2α, but also on increased PGE2 production in cattle.
Evaluating Sandwich Immunoassays in Microarray Format in Terms of the Ambient Analyte Regime
Authors: Saviranta Petri , Okon Ryan , Brinker Achim , Warashina Masaki , Eppinger Joerg , Geierstanger Bernhard H 
Published: August 2004

AbstractBackground: Conceptionally, antibody microarrays are simply multiplexed sandwich immunoassays in a miniaturized format. However, from the amounts of capture antibodies used, it is not apparent whether such assays are ambient analyte (Ekins. Clin Chem 1998;44:2015–30) or mass-sensing devices (Silzel et al. Clin Chem 1998;44:2036–43). We evaluated multiplexed microarray sandwich assays for 24 mouse serum proteins in these terms within the boundaries of our experimental setup and based on theoretical considerations of the law of mass action.Methods: Capture antibodies for 24 mouse serum proteins were printed on planar microarray substrates. After incubation with mixtures of purified antigens for 1 or 18 h, mixtures of biotinylated detection antibodies were used. High assay sensitivity was achieved by use of resonance-light-scattering particles for signal generation. Titration curves were generated for assay volumes of 20, 40, and 80 μL, and detection limits were calculated and compared. The assays were modeled theoretically based on the amounts of capture antibodies and the assay volumes used.Results: As predicted, experimental variations of the assay volume by up to fourfold did not appreciably affect detection. Even for the most sensitive assay, &lt;2% of the analyte molecules present in the sample were captured and generated signal at the detection limit. However, increasing the sample incubation time from 1 to 18 h on average lowered the detection limit threefold.Conclusions: In our experimental setup, all 24 sandwich microarray assays fulfill the criteria of the “ambient analyte” regime because depletion of analyte molecules from the assay volume is insignificant.
Lipid Disorders and Mutations in the APOB Gene
Authors: Whitfield Amanda J , Barrett P Hugh R , van Bockxmeer Frank M , Burnett John R 
Published: August 2004

AbstractBackground: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human lipoprotein metabolism. Two forms of apoB are produced from the APOB gene by a unique posttranscriptional editing process: apoB-48, which is required for chylomicron production in the small intestine, and apoB-100, required for VLDL production in the liver. In addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles.Content: The study of monogenic dyslipidemias has revealed important aspects of metabolic pathways. In this review, we discuss the regulation of apoB metabolism and examine how APOB gene defects can lead to both hypo- and hypercholesterolemia. The key clinical, metabolic, and genetic features of familial hypobetalipoproteinemia and familial ligand-defective apoB-100 are described.Summary: Missense mutations in the LDL-receptor-binding domain of apoB cause familial ligand-defective apoB-100, characterized by hypercholesterolemia and premature coronary artery disease. Other mutations in APOB can cause familial hypobetalipoproteinemia, characterized by hypocholesterolemia and resistance to atherosclerosis. These naturally occurring mutations reveal key domains in apoB and demonstrate how monogenic dyslipidemias can provide insight into biologically important mechanisms.
Alternative Routes of Drug Administration—Advantages and Disadvantages (Subject Review)
Authors:   Committee on Drugs
Published: August 2004

This Policy Statement was retired May 2011.During the past 20 years, advances in drug formulations and innovative routes of administration have been made. Our understanding of drug transport across tissues has increased. These changes have often resulted in improved patient adherence to the therapeutic regimen and pharmacologic response. The administration of drugs by transdermal or transmucosal routes offers the advantage of being relatively painless.12 Also, the potential for greater flexibility in a variety of clinical situations exists, often precluding the need to establish intravenous access, which is a particular benefit for children.This statement focuses on the advantages and disadvantages of alternative routes of drug administration. Issues of particular importance in the care of pediatric patients, especially factors that could lead to drug-related toxicity or adverse responses, are emphasized.
Seven Days of Erythromycin Estolate Is as Effective as Fourteen Days for the Treatment of Bordetella pertussis Infections
Authors: Halperin Scott A. , Bortolussi R. , Langley Joanne M. , Miller Barbara , Eastwood Brian J. 
Published: August 2004

Objective and Methods. Although 14 days of erythromycin is recommended for the treatment ofBordetella pertussis infection, there have been no prospective controlled studies to support the contention that this long course of therapy is required to eradicate the microorganism from the nasopharynx or to prevent bacteriological relapse. We randomly allocated children and adults with culture-positive community-acquired pertussis to either 7 or 14 days of erythromycin estolate treatment (40 mg/kg/d; maximum dose 1 g/d). Nasopharyngeal aspirate cultures were obtained by study nurses during home visits before and at the end of treatment, and 1 week after the completion of treatment. B pertussis-specific antibodies were measured before treatment and 1 month later. Information about clinical symptoms, adverse reactions, and compliance were collected at each scheduled contact.
Results and Conclusions. A total of 168 participants were eligible for analysis (74 treated for 7 days and 94 treated for 14 days). Bacteriological persistence (positive end of therapy culture) occurred once in each group, and bacteriological relapse (positive culture 1 week after completion of treatment) occurred in one participant treated for 7 days. The overall failure rate (persistence plus relapse) of 2.70% in the 7-day group was not different than the rate of 1.06% in the 14-day group. The study had a power of 99.99% at the 5% level to detect a difference in failure rates of 10% and a power of 80% to detect a difference of 5%. We conclude that 7 days of erythromycin estolate is as effective as 14 days for the eradication ofB pertussis.