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R Parker

Publications and source records attributed to R Parker.

At least 55 records · Page 3Linked to original sources
PubMed2000

Phase behavior and component partitioning in low water content amorphous carbohydrates and their potential impact on encapsulation of flavors.

The compositions at which amorphous ethanol-maltose-water mixtures exhibit liquid-liquid separation have been determined in the temperature range from 20 to 80 degrees C. At water contents below approximately 20% w/w two phases were observed, with the maltose-rich phase slightly richer in water. Partition coefficients of organic nonelectrolytes ranging in hydrophobicity from 1, 2-ethanediol and 1,2-propanediol to benzyl alcohol and propyl acetate have been measured for octanol/sorbitol, benzyl alcohol/sorbitol, and 1-butanol/sorbitol mixtures. Linear correlations were found between the log partition coefficients in the various solvent systems. Replacing water with sorbitol results in more organic partitioning into the octanol. Replacing octanol with benzyl alcohol or 1-butanol also results in more organic partitioning into the hydrophobic phase. The results establish a relationship with partition coefficients for octanol/water mixtures, which are well studied experimentally and for which predictive approaches exist. The implications of these results for flavor retention and encapsulation are discussed.

Carbohydrates↗
PubMed2000

European association of tissue banks standards for cryopreserved cardiovascular tissue banking.

The Cardiovascular Tissue Banking Standards are designed as an addition to the General Standards of the European Association of Tissue Banks to provide a minimum acceptable level for the donation, processing, storage, testing, labelling and distribution of cardiac tissue throughout Europe. The aim is that all heart valve banks in Europe should work to these Standards so that heart valves can be exchanged between countries without having to check the individual protocols of the donor processing facility. The writing of the Standards has been performed by the Heart Valve Council of EATB with input from cardiac surgeons. It is proposed that once the Standards are accepted they will form the document on which EATB may accredit tissue banks in the future and may form the basis on which National Legislation for Tissue Banking is based.

Journal Article↗
PubMed2000

Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults.

BACKGROUND: Pertussis is increasingly recognized as an important cause of cough illness in adolescents and adults. PURPOSE: To evaluate the safety and antibody response to a single dose of an adult formulation of a five component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine (aP) combined with diphtheria and tetanus toxoids (TdaP) and inactivated poliovirus vaccine (TdaP-IPV) in adolescents and adults and to assess the response to a second dose of the acellular pertussis vaccine in a subset of the adults. POPULATION AND SETTING: The study addressed 1207 healthy participants (736 adults and 466 adolescents) recruited in five Canadian communities. STUDY DESIGN: In a randomized, observer-blind, controlled clinical trial, adult participants received Td followed at a separate visit by aP, TdaP followed by IPV or TdaP-IPV; adolescents received Td-IPV followed at a separate visit by aP or TdaP-IPV. A subgroup of adults was given a booster of aP 1 month after TdaP. OUTCOME MEASURES: Antibody titers measured before and 1 month after each immunization; adverse events enumerated at 24 h, 72 h and 8 to 10 days. RESULTS: The aP vaccine given by itself was associated with adverse events less frequently than were Td, Td-IPV, TdaP or TdaP-IPV vaccines, but reaction rates did not differ significantly among the latter products. The antibody response against Bordetella pertussis antigens was vigorous in all groups, although adults given the TdaP-IPV vaccine had lower antibody titers against filamentous hemagglutinin, pertactin, diphtheria and tetanus antibodies than those given TdaP vaccine. Similarly adolescents given TdaP-IPV had lower antibody titers against pertussis toxin, filamentous hemagglutinin, fimbriae and agglutinins than those given Td-IPV and aP alone. A second dose of acellular pertussis vaccine was not associated with increased adverse events in adults but elicited increased antibody titers over that achieved by a single dose only against pertussis toxin. CONCLUSIONS: This adult formulation five component aP vaccine given as TdaP-IPV is safe and immunogenic in adolescents and adults and is a candidate vaccine for adolescent and adult immunization programs.

Adolescent↗
PubMed2000

Yeast exosome mutants accumulate 3'-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs.

The exosome is a protein complex consisting of a variety of 3'-to-5' exonucleases that functions both in 3'-to-5' trimming of rRNA precursors and in 3'-to-5' degradation of mRNA. To determine additional exosome functions, we examined the processing of a variety of RNAs, including tRNAs, small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), RNase P, RNase MRP, and SRP RNAs, and 5S rRNAs in mutants defective in either the core components of the exosome or in other proteins required for exosome function. These experiments led to three important conclusions. First, exosome mutants accumulate 3'-extended forms of the U4 snRNA and a wide variety of snoRNAs, including snoRNAs that are independently transcribed or intron derived. This finding suggests that the exosome functions in the 3' end processing of these species. Second, in exosome mutants, transcripts for U4 snRNA and independently transcribed snoRNAs accumulate as 3'-extended polyadenylated species, suggesting that the exosome is required to process these 3'-extended transcripts. Third, processing of 5.8S rRNA, snRNA, and snoRNA by the exosome is affected by mutations of the nuclear proteins Rrp6p and Mtr4p, whereas mRNA degradation by the exosome required Ski2p and was not affected by mutations in RRP6 or MTR4. This finding suggests that the cytoplasmic and nuclear forms of the exosome represent two functionally different complexes involved in distinct 3'-to-5' processing and degradation reactions.

DEAD-box RNA Helicases↗
PubMed2000

mRNA decapping in yeast requires dissociation of the cap binding protein, eukaryotic translation initiation factor 4E.

A major pathway of eukaryotic mRNA turnover occurs by deadenylation-dependent decapping that exposes the transcript to 5'-->3' exonucleolytic degradation. A critical step in this pathway is decapping, since removal of the cap structure permits 5'-->3' exonucleolytic digestion. Based on alterations in mRNA decay rate from strains deficient in translation initiation, it has been proposed that the decapping rate is modulated by a competition between the cytoplasmic cap binding complex, which promotes translation initiation, and the decapping enzyme, Dcp1p. In order to test this model directly, we examined the functional interaction of Dcp1p and the cap binding protein, eukaryotic translation initiation factor 4E (eIF4E), in vitro. These experiments indicated that eIF4E is an inhibitor of Dcp1p in vitro due to its ability to bind the 5' cap structure. In addition, we demonstrate that in vivo a temperature-sensitive allele of eIF4E (cdc33-42) suppressed the decapping defect of a partial loss-of-function allele of DCP1. These results argue that dissociation of eIF4E from the cap structure is required before decapping. Interestingly, the temperature-sensitive allele of eIF4E does not suppress the decapping defect seen in strains lacking the decapping activators, Lsm1p and Pat1p. This indicates that these activators of decapping affect a step in mRNA turnover distinct from the competition between Dcp1 and eIF4E.

Alleles↗
PubMed2000

Function of the ski4p (Csl4p) and Ski7p proteins in 3'-to-5' degradation of mRNA.

One of two general pathways of mRNA decay in the yeast Saccharomyces cerevisiae occurs by deadenylation followed by 3'-to-5' degradation of the mRNA body. Previous results have shown that this degradation requires components of the exosome and the Ski2p, Ski3p, and Ski8p proteins, which were originally identified due to their superkiller phenotype. In this work, we demonstrate that deletion of the SKI7 gene, which encodes a putative GTPase, also causes a defect in 3'-to-5' degradation of mRNA. Deletion of SKI7, like deletion of SKI2, SKI3, or SKI8, does not affect various RNA-processing reactions of the exosome. In addition, we show that a mutation in the SKI4 gene also causes a defect in 3'-to-5' mRNA degradation. We show that the SKI4 gene is identical to the CSL4 gene, which encodes a core component of the exosome. Interestingly, the ski4-1 allele contains a point mutation resulting in a mutation in the putative RNA binding domain of the Csl4p protein. This point mutation strongly affects mRNA degradation without affecting exosome function in rRNA or snRNA processing, 5' externally transcribed spacer (ETS) degradation, or viability. In contrast, the csl4-1 allele of the same gene affects rRNA processing but not 3'-to-5' mRNA degradation. We identify csl4-1 as resulting from a partial-loss-of-function mutation in the promoter of the CSL4 gene. These data indicate that the distinct functions of the exosome can be separated genetically and suggest that the RNA binding domain of Csl4p may have a specific function in mRNA degradation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Mechanisms and control of mRNA decapping in Saccharomyces cerevisiae.

The process of mRNA turnover is a critical component of the regulation of gene expression. In the past few years a discrete set of pathways for the degradation of polyadenylated mRNAs in eukaryotic cells have been described. A major pathway of mRNA degradation in yeast occurs by deadenylation of the mRNA, which leads to a decapping reaction, thereby exposing the mRNA to rapid 5' to 3' exonucleolytic degradation. A critical step in this pathway is decapping, since it effectively terminates the existence of the mRNA and is the site of numerous control inputs. In this review, we discuss the properties of the decapping enzyme and how its activity is regulated to give rise to differential mRNA turnover. A key point is that decapping appears to be controlled by access of the enzyme to the cap structure in a competition with the translation initiation complex. Strikingly, several proteins required for mRNA decapping show interactions with the translation machinery and suggest possible mechanisms for the triggering of mRNA decapping.

Endoribonucleases↗
PubMed2000

Adrenalectomy reduces neuropeptide Y-induced insulin release and NPY receptor expression in the rat ventromedial hypothalamus.

Chronic central administration of neuropeptide Y (NPY) causes hyperphagia, hyperinsulinemia, and obesity, a response that is prevented by prior adrenalectomy (ADX) in rats. The basis of NPY's effect and how the acute responses to this peptide are affected by ADX remain unknown. This study investigates the role of glucocorticoids in acute NPY-stimulated food intake, acute NPY-induced insulin release, and hypothalamic NPY-receptor mRNA expression levels. NPY-induced food intake was similar in ADX and control rats after acute intracerebroventricular injection of NPY. Injection of NPY caused a significant increase in plasma insulin in control rats, but this effect was completely absent in ADX rats in which basal plasma insulin levels were also lower than controls. In addition, ADX significantly reduced the number of neurons expressing NPY receptor Y(1) and Y(5) mRNAs in the ventromedial hypothalamus (VMH), without affecting Y(1)- or Y(5)-mRNA expression in the paraventricular hypothalamus or the arcuate nucleus. These data indicate that glucocorticoids are necessary for acute NPY-mediated insulin release and suggest that the mechanisms involve glucocorticoid regulation of Y(1) and Y(5) receptors specifically within the VMH nucleus.

Adrenal Glands↗
PubMed2000

[Poverty and HIV/AIDS: anthropological and sociological aspects].

Focusing on the HIV/AIDS epidemic as a summation of several epidemics coexisting in the same space and drawing on Brazilian epidemiological data, we argue that the epidemic there shows variations already described elsewhere, such as feminization, pauperization, juvenization and interiorization, as a result of the deep inequalities characteristic of Brazilian society. We then examine the contributions of three bodies of sociological and anthropological literature related to HIV/AIDS: 1) sociological research and theory on the impact of recent global economic restructuring and social transformation, and its relationship to public health issues; 2) the cross-cultural and cross-national anthropological and sociological literature on structural factors shaping the course of the epidemic in different settings; and 3) the body of anthropological and sociological research on the synergistic effects of HIV/AIDS, social exclusion, and related social problems in pockets of extreme poverty in the large cities of core countries. We conclude that prevention policies for HIV/AIDS should deal comprehensively with diverse dimensions that determine differential vulnerabilities to the epidemic, thus requiring substantial social transformations.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Assessing the risk of falls among older inpatients.

A reduction in mobility, a poor gait, diminished mental capacity and continence problems may increase the risk of falls among older people. The consequences of falls can include physical injury such as fractures, a fear of future falls, anxiety, depression and loss of confidence. Greater disability or death may result. The use of a risk assessment tool may alert staff to the magnitude of the problem.

Accidental Falls↗
PubMed2000

SPECT brain perfusion findings in mild or moderate traumatic brain injury.

BACKGROUND: The purpose of this manuscript is to present the findings in the largest series of SPECT brain perfusion imaging reported to date for mild or moderate traumatic brain injury. PATIENTS AND METHODS: This is a retrospective evaluation of 228 SPECT brain perfusion-imaging studies of patients who suffered mild or moderate traumatic brain injury with or without loss of consciousness (LOC). All patients had no past medical history of previous brain trauma, neurological, or psychiatric diseases, HIV, alcohol or drug abuse. The patient population included 135 males and 93 females. The ages ranged from 11-88 years (mean 40.8). The most common complaints were characteristic of the postconcussion syndrome: headaches 139/228 (61%); dizziness 61/228 (27%); and memory problems 63/228 (28%). LOC status was reported to be positive in 121/228 (53%), negative in 41/228 (18%), and unknown for 63/228 (28%). RESULTS: Normal studies accounted for 52/228 (23%). For abnormal studies (176/228 or 77%) the findings were as follows: basal ganglia hypoperfusion 338 lesions (55.2%); frontal lobe hypoperfusion 146 (23.8%); temporal lobes hypoperfusion 80 (13%); parietal lobes hypoperfusion 20 (3.7%); insular and or occipital lobes hypoperfusion 28 (4.6%). Patients' symptoms correlated with the SPECT brain perfusion findings. The SPECT BPI studies in 122/228 (54%) were done early within 3 months of the date of the accident, and for the remainder, 106/228 (46%) over 3 months and less than 3 years from the date of the injury. In early imaging, 382 lesions were detected; in 92 patients (average 4.2 lesions per study) imaging after 3 months detected 230 lesions: in 84 patients (average 2.7 lesions per study). CONCLUSIONS: Basal ganglia hypoperfusion is the most common abnormality following mild or moderate traumatic brain injury (p = 0.006), and is more common in patients complaining of memory problem (p = 0.0005) and dizziness (p = 0.003). Early imaging can detect more lesions than delayed imaging (p = 0.0011). SPECT brain perfusion abnormalities can occur in the absence of LOC.

Journal Article↗
PubMed1999

The DCP2 protein is required for mRNA decapping in Saccharomyces cerevisiae and contains a functional MutT motif.

The major pathway of mRNA degradation in yeast occurs through deadenylation, decapping and subsequent 5' to 3' exonucleolytic decay of the transcript body. To identify proteins that control the activity of the decapping enzyme, which is encoded by the DCP1 gene, we isolated a high-copy suppressor of the temperature-sensitive dcp1-2 allele, termed DCP2. Overexpression of Dcp2p partially suppressed the dcp1-2 decapping defect. Moreover, the Dcp2 protein was required for the decapping of both normal mRNAs and aberrant transcripts that are degraded by the mRNA surveillance pathway. The Dcp2 protein contains a MutT motif, which is found in a class of pyrophosphatases. Mutational analyses indicated that the region of Dcp2p containing the MutT motif is necessary and sufficient for Dcp2p's function in mRNA decapping. The Dcp2p also coimmunoprecipitates with the DCP1 decapping enzyme and is required for the production of enzymatically active decapping enzyme. These results suggest that direct or indirect interaction of Dcp1p with Dcp2p is required for the production of active decapping enzyme, perhaps in a process requiring the hydrolysis of a pyrophosphate bond.

Adenosine Monophosphate↗
PubMed1999

Analysis of mRNA decay pathways in Saccharomyces cerevisiae.

The analysis of mRNA turnover often requires a knowledge of the pathway by which a particular mRNA is being degraded. In this article we describe experimental procedures that can be used to determine the mechanism of degradation for yeast transcripts. These approaches include the insertion of strong secondary structures to block exonuclease cleavage and thereby trap decay intermediates. In addition, mRNA decay pathways can be analyzed by using regulatable promoters to perform transcriptional pulse-chase experiments, thereby allowing the determination of precursor-product relationships during the mRNA decay process. Finally, the mechanism of mRNA degradation can also now be determined by using trans-acting mutations specific for distinct mRNA turnover pathways. Most importantly, the combination of these three approaches can often clearly define the mechanism(s) by which a given transcript is degraded.

Genes, Fungal↗
PubMed1999

Gestational bleeding, bacterial vaginosis, and common reproductive tract infections: risk for preterm birth and benefit of treatment.

OBJECTIVE: To examine associations between bacterial vaginosis and other prevalent lower genital tract infections and clinically recognized first-trimester bleeding; possible independent and joint effects of gestational bleeding and bacterial vaginosis or other prevalent infections on preterm birth and premature rupture of membranes; and effects of antimicrobial treatment on reducing risks of preterm birth among these women. METHODS: A secondary analysis was conducted of 1100 pregnant women enrolled in a prospective observational study that examined the effects of standardized diagnosis and treatment of lower genital tract infections to prevent preterm birth. RESULTS: Sixty percent of women with first-trimester bleeding had one or more study infections detected at the initial examination. First-trimester bleeding was associated independently with the presence of bacterial vaginosis (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0, 2.3), Trichomonas vaginalis (OR 2.3, 95% CI 1.3, 4.2), and Chlamydia trachomatis (OR 2.7, 95% CI 1.4, 5.1). Preterm birth was increased among women with first-trimester bleeding and bacterial vaginosis (relative risk [RR] 4.4, 95% CI 2.0, 9.5) and bacterial vaginosis and T vaginalis (RR 3.0, 95% CI 1.0, 8.8). Systemic antimicrobial treatment reduced the rate of preterm birth among women with bacterial vaginosis without first-trimester bleeding (RR 0.37, 95% CI 0.16, 0.88). Treatment of women with both first-trimester bleeding and bacterial vaginosis reduced preterm birth (RR 0.52, 95% CI 0.18, 1.55), but not significantly. CONCLUSION: First-trimester bleeding was increased among women with bacterial vaginosis, T vaginalis, C trachomatis, and combinations of these infections. Women with bacterial vaginosis who also experienced first-trimester bleeding were at heightened risk for preterm birth. Treatment of studied infections reduced significantly the risks of preterm birth among women without first-trimester bleeding.

Adolescent↗
PubMed1999

The cis acting sequences responsible for the differential decay of the unstable MFA2 and stable PGK1 transcripts in yeast include the context of the translational start codon.

A general pathway of mRNA turnover has been described for yeast in which the 3' poly(A) tail is first deadenylated to an oligo(A) length, leading to decapping and subsequent 5'-3' exonucleolytic decay. The unstable MFA2 mRNA and the stable PGK1 mRNAs both decay through this pathway, albeit at different rates of deadenylation and decapping. To determine the regions of the mRNAs that are responsible for these differences, we examined the decay of chimeric mRNAs derived from the 5' untranslated, coding, and 3' untranslated regions of these two mRNAs. These experiments have led to the identification of the features of these mRNAs that lead to their different stabilities. The MFA2 mRNA is unstable solely because its 3' UTR promotes the rates of deadenylation and decapping; all other features of this mRNA are neutral with respect to mRNA decay rates. The PGK1 mRNA is stable because the sequence context of the PGK1 translation start codon and the coding region function together to stabilize the transcript, whereas the PGK13' UTR is neutral with respect to decay. Importantly, changes in the PGK1 start codon context that destabilized the transcript also reduced its translational efficiency. This observation suggests that the nature of the translation initiation complex modulates the rates of mRNA decapping and decay.

3' Untranslated Regions↗
PubMed1999

mRNA surveillance in eukaryotes: kinetic proofreading of proper translation termination as assessed by mRNP domain organization?

In the last few years it has become clear that a conserved mRNA degradation system, referred to as mRNA surveillance, exists in eukaryotic cells to degrade aberrant mRNAs. This process plays an important role in checking that mRNAs have been properly synthesized and functions, at least in part, to increase the fidelity of gene expression by degrading aberrant mRNAs that, if translated, would produce truncated proteins. A critical issue is how normal and aberrant mRNAs are distinguished and how that distinction leads to differences in mRNA stability. Recent results suggest a model with three main points. First, mRNPs have a domain organization that is, in part, a reflection of the completion of nuclear pre-mRNA processing events. Second, the critical aspect of distinguishing a normal from an aberrant mRNA is the environment of the translation termination codon as determined by the organization of the mRNP domains. Third, the cell distinguishes proper from improper termination through an internal clock that is the rate of ATP hydrolysis by Upf1p. If termination is completed before ATP hydrolysis, the mRNA is protected from mRNA degradation. Conversely, if termination is slow, then ATP hydrolysis and a structural rearrangement occurs before termination is completed, which affects the fate of the terminating ribosome in a manner that fails to stabilize the mRNA. This proposed system of distinguishing normal from aberrant transcripts is similar to, but distinct from other systems of kinetic proofreading that affect the accuracy of other biogenic processes such as translation accuracy and spliceosome assembly.

3' Untranslated Regions↗