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Biomedical subjects

Robert Reid

Publications and source records attributed to Robert Reid.

12 recordsLinked to original sources

Genome-Wide Impact of Human DBR1 Depletion on RNA Processing Networks Reveal a Connection Between Pre-mRNA Splicing, mRNA Surveillance and Stress Granule Dynamics.

The RNA lariat debranching enzyme DBR1 is essential for intron turnover and RNA metabolism, yet its broader impact on transcriptome regulation remains incompletely defined. To elucidate the consequences of DBR1 depletion, we performed transcriptome-wide RNA sequencing of DBR1-knockdown and wild-type HEK293 cells. Differential expression analysis revealed widespread perturbations in pathways linked to RNA splicing, mRNA surveillance, translational control, and stress-granule biology. Many of the most significantly altered transcripts encode splicing factors and RNA quality-control components, underscoring DBR1's influence on post-transcriptional regulation. Alternative splicing analysis showed changes across multiple event types, with exon skipping accounting for >50% of events, followed by mutually exclusive exons, alternative 5' and 3' splice sites, and retained introns, indicating that DBR1 depletion induces pervasive splicing defects. Direct spliceosome inhibition using isoginkgetin (blocks tri-snRNP recruitment) and pladienolide B (targets SF3B1) reproduced the DBR1-KD mis-splicing patterns of cell signaling genes and factors involved in RNA metabolism, supporting a functional link between DBR1 activity and alternative splicing. Notably, DBR1 knockdown revealed a subset of transcripts that are both NMD-sensitive and enriched within stress granules. Consistent with this observation, G3BP1 immunopurification and confocal microscopy further support a role for DBR1 and UPF1 in stress-granule dynamics, suggesting that these factors may participate at distinct stages to influence mRNA fate under stress conditions. Together, these findings indicate that DBR1 functions beyond lariat RNA turnover as a common regulator of RNA processing, transcriptome stability, and stress granule homeostasis, revealing intricate crosstalk between RNA splicing and RNA quality control pathways in human cells.

Humans↗

Mechanisms and control of nutrient uptake in plants.

This review is a distillation of the vast amount of physiological and molecular data on plant membrane transport, to provide a concise overview of the main processes involved in the uptake of mineral nutrients in plants. Emphasis has been placed on transport across the plasma membrane, and on the primary uptake from soil into roots, or in the case of aquatic plants, from their aqueous environment. Control of uptake has been mainly considered in terms of local effects on the rate of transport and not in terms of long-distance signaling. The general picture emerging is of a large array of membrane transporters, few of which display any strong selectivity for individual nutrients. Instead, many transporters allow low-affinity uptake of several different nutrients. These features, plus the huge number of potential transporter genes that has been revealed by sequencing of plant genomes, raise some interesting questions about their evolution and likely function.

Biological Transport↗

ADHD and stuttering: a tutorial.

UNLABELLED: The purpose of this tutorial is twofold. The first is to provide a brief description of some of the key diagnostic features of attention deficit hyperactivity disorder (ADHD) for speech-language pathologists who might not be knowledgeable about this disorder. The second purpose is to provide information and suggestions about treating children who stutter and who have been diagnosed with ADHD. Specific information is provided regarding medication used to treat ADHD symptoms as well as the minimal documented evidence of its impact on stuttering. Suggestions for educational, behavioral, and cognitive management of children who stutter and have ADHD also are discussed. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to: (1) identify diagnostic criteria for children with ADHD; (2) differentiate pharmacological, environmental, and behavioral interventions for children with ADHD; and (3) examine effective instructional techniques for children who stutter and have ADHD.

Adolescent↗

Quantitative trait loci for hypercalciuria in a rat model of kidney stone disease.

Hypercalciuria is the most common risk factor for kidney stones and has a recognized familial component. The genetic hypercalciuric stone-forming (GHS) rat is an animal model that closely resembles human idiopathic hypercalciuria, with excessive intestinal calcium absorption, increased bone resorption, and impaired renal calcium reabsorption; overexpression of the vitamin D receptor (VDR) in target tissues; and calcium nephrolithiasis. For identifying genetic loci that contribute to hypercalciuria in the GHS rat, an F2 generation of 156 rats bred from GHS female rats and normocalciuric WKY male rats was studied. The calcium excretion was six- to eightfold higher in the GHS female than in the WKY male progenitors. Selective genotyping of those F2 rats with the highest 30% and lowest 30% rates of calcium excretion was performed, scoring 98 markers with a mean interval of 23 cM across all 20 autosomes and the X chromosome. With the use of strict criteria for significance, significant linkage was found between hypercalciuria and a region of chromosome 1 at D1Rat169 (LOD, 2.91). Suggestive linkage to regions of chromosomes 4, 7, 10, and 14 was found. The proportion of phenotypic variance contributed by the region on chromosome 1, with appropriate adjustments, was estimated to be 7%. Candidate genes encoding the VDR and the calcium-sensing receptor were localized to regions on rat chromosomes 7 and 11, respectively, but the suggestive quantitative trait locus on chromosome 7 was not in the region of the VDR gene locus. Identification of genes that contribute to hypercalciuria in this animal model should prove valuable in understanding idiopathic hypercalciuria and kidney stone disease in humans.

Animals↗

Conspicuous consumption: characterizing high users of physician services in one Canadian province.

OBJECTIVES: To examine medical care use and costs, patterns of morbidity and co-morbidity, and other patient characteristics of high users of physician services in British Columbia. METHODS: This population-based study uses physician claims, hospital discharge summaries and vital statistics data linked at the level of the individual to compare characteristics of high users, other users and non-users of physician services in the Province of British Columbia, Canada. The study included all enrolled adults in the universal health care plan during fiscal year 1996/97. High users were defined as the most costly 5% of users of fee-reimbursed services. Key variables included age, sex, an ecological socio-economic status indicator and a comprehensive set of morbidity indicators, derived from the diagnoses recorded on the utilization records. RESULTS: The top 5% of users consumed a disproportionate 30% of spending on physician services. High users were overwhelmingly characterized by a significant burden of morbidity. Over 80% had at least six different types of morbidity during the study year compared with fewer than 20% of other users. High users were also much more likely to have major diagnoses that were both acute and chronic in nature. Co-morbidity involving psychosocial and chronic medical conditions was also very common. CONCLUSIONS: High users of physician services are overwhelmingly characterized by multiple and complex health problems. Policy tools based on a philosophy of deterrence such as cost-sharing are unlikely to have much impact on their costs and will likely do considerable harm.

Adolescent↗

Use of psychostimulant medication for ADHD in South Australia.

OBJECTIVE: A retrospective analysis of archival data on psychostimulant prescriptions from South Australia for the period 1990 to 2000 for 5,189 youths from birth to age 18 years was conducted. METHOD: A person-based data set was used to assess (1) rate of new prescriptions by age group, (2) demographic characteristics (age of psychostimulant start, male-to-female ratio), (3) duration of psychostimulant use, and (4) geographic variation in psychostimulant prescription. RESULTS: Four major findings were observed: (1) the rate of new prescriptions increased dramatically until 1995 but is now declining; (2) demographic characteristics and changes over time mirror those observed in the United States; (3) median duration of psychostimulant use (for a subset of 1,688 children) was approximately 2.5 years; and (4) there was a significant correlation between geographic location and prescription rate. CONCLUSIONS: The patterns of psychostimulant use in Australia closely parallel U.S. patterns. Physicians'prescribing practices may be extremely volatile. Duration of medication treatment should receive increased attention. There is pronounced geographic variability in prescription rates which may be related to socioeconomic status.

Adolescent↗

Dietary counselling for dyslipidemia in primary care: results of a randomized trial.

This study compared the effectiveness of physician advice versus dietitian advice for a fat-reduced diet, and of dietitian advice for a fat-reduced diet versus a soluble fibre-enhanced diet in patients with moderate dyslipidemia. A total of 111 men and women took part in this 26-week, three-group, randomized, clinical trial. The physician advice fat-reduced diet group (n = 38) and the dietitian advice fat-reduced diet group (n = 35) received dietary advice based on the American Heart Association (AHA) Step II guidelines. The dietitian advice soluble fibre-enhanced diet group (n = 38) consumed one-third cup per day of psyllium-containing cereal and was advised to increase soluble fibre intake to over 10 grams a day. LDL-C, TC/HDL-C ratio and body weight reductions over six months were -5.3%, -4.6%, and -1.9%, respectively, regardless of whether a physician or a dietitian provided advice, or whether advice was focused on a fat-reduced diet or a soluble fibre-enhanced diet. Both dietitians and physicians can help moderately dyslipidemic patients make clinically meaningful changes in blood lipid levels. Soluble fibre enhancement of the usual diet leads to similar reductions in LDL-C and TC/HDL-C ratio compared to interventions focused on fat reduction.

Adult↗

Stepped care approach to smoking cessation in patients hospitalized for coronary artery disease.

PURPOSE: Smoking cessation is an important goal for smokers with coronary artery disease (CAD) because it reduces cardiac morbidity and mortality. Effective interventions for cigarette smokers with CAD exist, but they often are considered to be intensive and expensive. Stepped-care interventions have been proposed as a promising way to allocate smoking cessation treatments in a cost-effective manner. Stepped care refers to the practice of initiating treatment with low-intensity intervention and then exposing treatment failures to successively more intense interventions. METHODS: To address the efficacy of this approach, 254 cigarette smokers hospitalized with CAD were provided a brief cessation intervention. The participants then were assigned randomly to either a more intensive stepped-care treatment (counseling and nicotine patch therapy) or no additional treatment. Outcomes were point-prevalent abstinence measured 3 months and 1 year after hospital discharge. RESULTS: Stepped-care treatment increased smoking cessation rates from 42% to 53% during a 3-month follow-up period (P =.05), but showed little effect at the 1-year follow-up assessment, as evidenced by a cessation rate for the minimal intervention group of 36% versus 39% for the stepped-care group (P =.36). CONCLUSIONS: A stepped-care approach to smoking cessation increased short-but not long-term point-prevalent abstinence in patients with CAD. For improvement of long-term effectiveness, refinement of the timing and content of stepped-care interventions needs to occur.

Comorbidity↗