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Biomedical subjects

A H Brown

Publications and source records attributed to A H Brown.

At least 37 records · Page 2Linked to original sources

Upf1p, Nmd2p, and Upf3p are interacting components of the yeast nonsense-mediated mRNA decay pathway.

Rapid turnover of nonsense-containing mRNAs in Saccharomyces cerevisiae is dependent on Upf1p, Nmd2p, and Upf3p, the products of the UPF1, NMD2/UPF2, and UPF3 genes, respectively. We showed previously that Upf1p and Nmd2p interact and that this interaction is required for nonsense-mediated mRNA decay (F. He and A. Jacobson, Genes Dev. 9:437-454, 1995; F. He, A. H. Brown, and A. Jacobson, RNA 2:153-170, 1996). In this study we have used the yeast two-hybrid system to define other protein-protein interactions among the essential components of this decay pathway. Nmd2p-Upf3p and Upf1p-Upf3p interactions were identified, and the respective domains involved in these interactions were delineated by deletion analysis. The domains of Upf1p and Upf3p putatively involved in their mutual interaction were found to correspond to the domains on the two proteins which interact with Nmd2p, suggesting that Nmd2p bridges Upf1p and Upf3p. This conclusion was reinforced by experiments showing that: (i) deletion of NMD2 completely abolishes interactions between Upf1p and Upf3p and (ii) overexpression of full-length Nmd2p or Nmd2p fragments that retain Upf1p- and Upf3p-interacting domains promotes 10- to 200-fold enhancement of Upf1p-Nmd2p-Upf3p complex formation. These results; the observation that cells harboring either single or multiple deletions of UPF1, NMD2, and UPF3 inhibit nonsense-mediated mRNA decay to the same extent; and an analysis of the possible targets of a dominant-negative NMD2 allele indicate that Upf1p, Nmd2p, Upf3p, and at least one other factor are functionally dependent, interacting components of the yeast nonsense-mediated mRNA decay pathway.

Adaptor Proteins, Signal Transducing↗

Genotype x environment interactions in Angus, Brahman, and reciprocal cross cows and their calves grazing common bermudagrass and endophyte-infected tall fescue pastures.

Reproductive and preweaning data on 233 Angus (A), Brahman (B), and reciprocal-cross cows (AB, BA) and 455 two- and three-breed cross calves managed on common bermudagrass or endophyte-infected tall fescue were used to evaluate the interaction of forage type with individual and maternal heterosis and maternal and grandmaternal breed effects. Cows were born from 1988 to 1991 and calves from 15 Polled Hereford sires were born from 1991 to 1994. Heterosis for calving rate was similar and important on both forages (P < .01), but maternal effects were small on each forage. Maternal heterosis for birth weight differed between common bermudagrass and tall fescue (P < .10) and grandmaternal effects were evident on bermudagrass (P < .05) but not tall fescue. Forage effects were generally substantial for 205-d weight, weaning hip height, and weaning weight:height ratio (P < .01), and maternal heterosis for these traits was larger on tall fescue than on common bermudagrass (P < .01). Grandmaternal effects were in favor of Angus for 205-d weight, hip height, and weight:height ratio on common bermudagrass (P < .05) but not on tall fescue. Heterosis for 205-d weight per cow exposed was substantial on both forages (P < .01) and was numerically larger on tall fescue than on bermudagrass, but maternal effects were not significant. These results suggest more advantage for Brahman-cross cows over purebreds on endophyte-infected tall fescue than a similar comparison on common bermudagrass. They also suggest an advantage for Angus in grandmaternal effects on bermudagrass but not tall fescue.

Animals↗

Effects of frame size and time-on-feed on carcass characteristics, sensory attributes, and fatty acid profiles of steers.

Weaned British x continental crossbred steers (n = 108, 7 to 8 mo of age) of medium or large frame were used in a replicated experiment with a 2 x 4 factorial arrangement of treatments over 2 yr. Management regimens consisted of backgrounding for 150 d and finishing for 0, 30, 60, and 90 d. Carcass data were collected, and samples from the longissimus muscle were analyzed for long-chain fatty acids, cholesterol, and the percentage of fat. Duration of finishing was a source of variation for hot carcass weight, marbling, percentage of kidney, pelvic, and heart fat, fat thickness, yield and quality grades, cooking loss, flavor intensity, and stearic, oleic, and linolenic acids (P < .05). Myristic, palmitic, and margaric acids were negatively correlated (P < .05) with juiciness and with "cowy" and "painty" taste characteristics. Frame score did not influence long-chain fatty acids; however, there was a relationship between long-chain fatty acids and management regimen. Results suggest that feeding steers a finishing diet up to 90 d after backgrounding for 150 d has a positive influence on carcass characteristics without affecting cholesterol.

Animals↗

Polysome-associated mRNAs are substrates for the nonsense-mediated mRNA decay pathway in Saccharomyces cerevisiae.

In eukaryotic cells, premature termination of translation at nonsense codons has been implicated as the cause of a variety of posttranscriptional events, including rapid mRNA decay in the cytoplasm or the nucleus, altered splice site selection, and exon skipping. In the yeast Saccharomyces cerevisiae, nonsense codons promote accelerated mRNA decay, and we sought to determine the cellular location in which this degradation occurs. In this report, we demonstrate that six different mRNAs, including nonsense-containing transcripts of the LEU2, HIS4, PGK1, and CYH2 genes, and two wild-type mRNAs (the MAT(alpha)1 and CYH2 mRNAs), were stabilized when the translation elongation inhibitor cycloheximide was added to cellular growth media. Subsequent removal of cycloheximide resulted in resumption of translation and degradation of wild-type and nonsense-containing mRNAs. A significant fraction of the CYH2 pre-mRNA that accumulated in the presence of cycloheximide was associated with polysomes, but disappeared from that fraction when decay resumed in the absence of the drug. Moreover, the abundance of the spliced and unspliced forms of the untranslated U3 snRNA was shown to be unaffected in strains harboring mutations that stabilize nonsense-containing mRNAs. Taken together, these observations indicate that nonsense-containing mRNAs in yeast are degraded within the polysome compartment of the cell.

Codon, Nonsense↗

Milk production in Angus, Brahman, and reciprocal-cross cows grazing common bermuda grass or endophyte-infected tall fescue.

Milk yield and quality were measured on 139 Angus, Brahman, and reciprocal-cross cows grazing common bermuda grass or endophyte-infected tall fescue for 4 yr to evaluate interactions of direct and maternal breed effects and heterosis for these traits with forage environment. Milk yield was estimated by method of milking machine, and milk fat, protein, and somatic cell counts were evaluated in a commercial dairy laboratory. Monthly estimates were made beginning on an average d 61 of lactation and continued monthly for six estimates in 3 yr and five estimates in 1 yr. Data were averaged over month within year, and the model included sire breed, sire in sire breed, dam breed, forage, and age averages. Somatic cell counts were transformed using natural logarithms prior to analyses. Forage effects for milk yield were dissimilar among sire breed x dam breed subclasses (P < .10), resulting in higher levels of heterosis on common bermuda grass than on tall fescue. Maternal breed effects for milk yield favored Angus on bermuda grass (P < .05) but not on tall fescue, whereas direct breed effects were similar on both forages and favored Brahman. Milk fat was reduced on tall fescue compared to bermuda grass by an average of .6% (P < .01), and direct breed effects were similar across forages and averaged 1.04% (P < .01) in favor of Brahman. Heterosis and maternal breed effects for milk fat were not important. There was little evidence of direct and maternal breed effects or heterosis for milk protein or somatic cell counts. These data suggest that heterosis for milk yield is larger on common bermuda grass than on tall fescue and that grazing endophyte-infected tall fescue is detrimental to milk fat.

Aging↗

Gravity related features of plant growth behavior studied with rotating machines.

Research in plant physiology consists mostly of studies on plant growth because almost everything a plant does is done by growing. Most aspects of plant growth are strongly influenced by the earth's gravity vector. Research on those phenomena address scientific questions specifically about how plants use gravity to guide their growth processes.

Centrifugation↗

Interaction between Nmd2p and Upf1p is required for activity but not for dominant-negative inhibition of the nonsense-mediated mRNA decay pathway in yeast.

Rapid turnover of nonsense-containing mRNAs in the yeast Saccharomyces cerevisiae is dependent on the products of the UPF1 (Upf1p), NMD2/UPF2 (Nmd2p) and UPF3 (Upf3p) genes. Mutations in each of these genes lead to the selective stabilization of mRNAs containing early nonsense mutations without affecting the decay rates of most other mRNAs. NMD2 was recently identified in a two-hybrid screen as a gene that encodes a Upf1p-interacting protein. To identify the amino acids essential to this interaction, we used two-hybrid analysis as well as missense, nonsense, and deletion mutants of NMD2, and mapped the Upf1p-interacting domain of Nmd2p to a 157-amino acid segment at its C-terminus. Mutations in this domain that disrupt interaction with Upf1p also disrupt nonsense-mediated mRNA decay. A dominant-negative deletion allele of NMD2 identified previously includes the Upf1p-interacting domain. However, mutations in the Upf1p-interacting domain do not affect dominant-negative inhibition of mRNA decay caused by this allele, suggesting interaction with yet another factor. These results, and the observation that deletion of a putative nuclear localization signal and a putative transmembrane domain also inactivate nonsense-mediated mRNA decay, suggest that Nmd2p may contain as many as four important functional domains.

Adaptor Proteins, Signal Transducing↗

Performance traits, hoof mineral composition, and hoof characteristics of bulls in a 112-day postweaning feedlot performance test.

OBJECTIVE: To evaluate relations between hoof and performance data from bulls fed in a 112-day standardized postweaning feedlot performance test. ANIMALS AND DESIGN: Breeds included were Angus (n = 20), Brangus (n = 19), Hereford (n = 31), and Simmental (n = 53). Hoof measurements, scores, and a 0.5-g hoof tissue sample were obtained from the right forefoot of bulls on days 1 and 112 of 4 tests conducted in 3 locations in Arkansas. Data were analyzed, using least squares ANOVA. The model used included an overall mean, breed, farm of origin within breed, initial age, and initial weight within breed and residual. Residual and canonical correlations of the traits studied were calculated. RESULTS: Residual correlations were found between some hoof minerals. Canonical correlations between performance traits and hoof minerals, between hoof characteristics and hoof minerals, and between hoof characteristics and performance traits were 0.62 and 0.45 (P < 0.005), 0.54 and 0.40 (P < 0.05), and 0.56 (P < 0.01) and 0.26 (P > 0.05), respectively. CONCLUSIONS: These data suggest that a relation exists between performance traits and hoof mineral composition and hoof characteristics and mineral composition. The visual scoring system for these data did not genetically separate bulls on the basis of claw quality. CLINICAL IMPLICATIONS: By selecting bulls with high claw quality, cattle producers are decreasing the chances of premature culling because of hoof laminitis. Therefore, by obtaining hoof measurements and mineral composition in a feedlot performance test, producers should have the tools to select bulls for increased lifetime performance.

Analysis of Variance↗

Nastic curvatures of wheat coleoptiles that develop in true microgravity.

Dark-grown wheat coleoptiles developed strong curvatures within 5 h of being transferred in orbit from a 1 g centrifuge to microgravity during an experiment flown on the IML-1 shuttle mission. The curving tendency was strongest in seedlings that were immature, with coleoptiles shorter than 10 mm at the time of transfer. The curvature direction was non-random, and directed away from the caryopsis (the coleptile face adjacent to the caryopsis becoming convex). The curvatures were most marked in the basal third of the coleoptiles, contrasting with phototropic responses, which occur in the apical third. We interpret these curvatures as being nastic, and related to the curvatures commonly reported to occur during clinostat rotation treatments.

Carbon Dioxide↗

Determinants of the length of stay in intensive care and in hospital after coronary artery surgery.

BACKGROUND: Patients who have coronary artery surgery normally occupy intensive care beds for less than 24 hours. Longer stays may result in under use of cardiac surgical capacity. One approach to optimise surgical throughput is prospectively to identify fast track patients--that is, those who occupy an intensive care bed for less than 24 hours. A prospective audit of patients was performed to identify fast track patients by simple clinical criteria. Total length of hospital stay was also assessed in an attempt to predict which patients were likely to have a short postoperative stay, defined as < or = 7 days. METHODS: Baseline demographic details, cardiovascular risk factors, angiographic and operative details were recorded for 431 consecutive patients who underwent coronary surgery at a regional centre over a nine month period. Outcome measures were the duration of the stay in the intensive care unit in hours and total duration of the postoperative stay in hospital in days. In addition, two groups of patients who were thought to be fast track were identified prospectively. Fast track 1 patients were identified by criteria selected by cardiovascular physicians. These were age less than 60 years, stable angina, good left ventricular function (ejection fraction > 50%), good renal function (serum creatinine < 120 mumol/l), and no obesity, diabetes, or other serious disease. Fast track 2 patients were identified by criteria defined by cardiovascular surgeons. These were male sex, age less than 65 years, good left ventricular function and no peripheral vascular disease, diabetes, or other serious disease. The efficacy of both sets of criteria in predicting outcome was tested. RESULTS: 344 (79.8%) patients were fast track. Significant factors for the prediction of fast track patients by univariate analysis (with positive predictive accuracy and sensitivity) were left ventricular ejection fraction > 50% (83%, 80%), left ventricular end diastolic pressure < 13 mm Hg (90%, 59%), creatinine less than 120 mumol/l (83%, 87%), and one or two vessel coronary disease (89%, 34%). Of the patients categorised as fast track 1 89% proved to be fast track (sensitivity 24%), however, the fast track 2 characteristics were not significant. Age, sex, obesity, diabetes, hypertension, a history of obstructive pulmonary disease and unstable angina were not predictive of the duration of intensive care stay. Multivariate analysis indicated that only left ventricular end diastolic pressure and the number of diseased coronary arteries predicted fast track patients. These criteria separated patients into three groups. Those who were good risk had one or two vessel disease and left ventricular end diastolic pressure < 13 mm Hg. They comprised 19% of the total and 93% of them were fast track. Those who were intermediate risk had either three vessel disease or left ventricular end diastolic pressure > 13 mm Hg but not both. They comprised 49% of the total and 85% of them were fast track. Those who were poor risk had both three vessel disease and left ventricular end diastolic pressure > 13 mm Hg. They comprised 32% of the total and 62% of them were fast track. The 106 (24%) patients who spent < or = 7 days in hospital after surgery were significantly younger (mean (SD) 55(8) v 58(8) years; P < 0.001) with a lower incidence of previous myocardial infarction (positive predictive accuracy 30%, sensitivity 53%), were less likely to have a history of obstructive pulmonary disease (25%, 98%), and more likely to have one or two vessel coronary disease (33%, 41%). They were more likely to have an internal mammary artery as a bypass conduit (27%, 89%) and more likely to need fewer than three distal anastomoses of the vein graft (29%, 63%). By multivariate analysis only age was significantly predictive of hospital stay. Total hospital stay could not be satisfactorily modelled on the basis of the criteria tested here. Sex, obesity, diabetes, hypertension, unstable angina, renal function, and left ventricular function were not associated with hospital stay. CONCLUSIONS-Most patients who had coronary artery surgery spent less than or equal to 24 hours in intensive care, but most spent > 7 days in hospital. The chance of a patient spending less than or equal to 24 hours in intensive care could be predicted by the number of coronary arteries diseased and the left ventricular end diastolic pressure. Poor risks patients (32%) had only a 62% chance of an intensive care unit stay of less than or equal to 24 hours. A policy of scheduling no more than one such patient for surgery per day would be simple to institute and would maximise the use of surgical capacity.

Coronary Artery Bypass↗

Gravitropic responses of the Avena coleoptile in space and on clinostats. I. Gravitropic response thresholds.

We conducted a series of gravitropic experiments on Avena coleoptiles in the weightlessness environment of Spacelab. The purpose was to test the threshold stimulus, reciprocity rule and autotropic reactions to a range of g-force stimulations of different intensities and durations The tests avoided the potentially complicating effects of earth's gravity and the interference from clinostat ambiguities. Using slow-speed centrifuges, coleoptiles received transversal accelerations in the hypogravity range between 0.l and 1.0 g over periods that ranged from 2 to 130 min. All responses that occurred in weightlessness were compared to clinostat experiments on earth using the same apparatus. Characteristic gravitropistic response patterns of Atuena were not substantially different from those observed in ground-based experiments. Gravitropic presentation times were extrapolated. The threshold at 1.0 g was less than 1 min (shortest stimulation time 2 min), in agreement with values obtained on the ground. The least stimulus tested, 0.1 g for 130 min, produced a significant response. Therefore the absolute threshold for a gravitropic response is less than 0.1 g.

Acceleration↗

Gravitropic responses of the Avena coleoptile in space and on clinostats. II. Is reciprocity valid?

Experiments were undertaken to determine if the reciprocity rule is valid for gravitropic responses of oat coleoptiles in the acceleration region below 1 g. The rule predicts that the gravitropic response should be proportional to the product of the applied acceleration and the stimulation time. Seedlings were cultivated on 1 g centrifuges and transferred to test centrifuges to apply a transverse g-stimulation. Since responses occurred in microgravity, the uncertainties about the validity of clinostat simulation of weightlessness was avoided. Plants at two stages of coleoptile development were tested. Plant responses were obtained using time-lapse video recordings that were analyzed after the flight. Stimulus intensities and durations were varied and ranged from 0.1 to 1.0 g and from 2 to 130 min, respectively. For threshold g-doses the reciprocity rule was obeyed. The threshold dose was of the order of 55 g s and 120 g s, respectively, for two groups of plants investigated. Reciprocity was studied also at bending responses which are from just above the detectable level to about 10 degrees. The validity of the rule could not be confirmed for higher g-doses, chiefly because the data were more variable. It was investigated whether the uniformity of the overall response data increased when the gravitropic dose was defined as (gm x t) with m-values different from unity. This was not the case and the reciprocity concept is, therefore, valid also in the hypogravity region. The concept of gravitropic dose, the product of the transverse acceleration and the stimulation time, is also well-defined in the acceleration region studied. With the same hardware, tests were done on earth where responses occurred on clinostats. The results did not contradict the reciprocity rule but scatter in the data was large.

Acceleration↗

Plasma characteristics of beef cattle classified as resistant or susceptible to horn flies.

Horn flies inflict economic losses on cattle producers. Therefore, the objective of this study was to identify a serological marker for cows that are innately resistant to horn flies. Plasma characteristics (optical density, cortisol, and protein pattern) were studied in beef cattle classified (cow-type) as horn fly resistant or susceptible. Cows (n = 30) of five breed groups were used in this study. Cows were bled via jugular venipuncture in May (the beginning of the horn fly season). Plasma optical density at wavelengths 200 and 464 nm was different (P < .05) between resistant and susceptible cattle. Cow-type also affected (P < .05) area percentage for proteins with running molecular weights (M(r)) of 74,000 and 54,000 daltons. Breed group affected (P < .05) optical density at wavelengths 200, 280, 320, and 464 nm and concentration of cortisol in plasma. When the ratio of area percentage for protein bands 7 and 9 (M(r) 74,000 and 54,000, respectively) was determined, cows could be categorized as horn fly resistant or susceptible. These data suggest that a serological marker for horn fly resistant cattle has been identified; however, the marker will need to be tested on a larger population of cattle.

Animals↗

Relationship of horn fly to face fly infestation in beef cattle.

Horn fly and face fly counts (n = 394) taken on 194 beef cows representing seven breed groups were used to determine the effects of horn fly and face fly counts. Breed groups included were Angus (ANI and ANII), Chianina (CA), Charolais (CH), Hereford (HH), Polled Hereford (PH), and Red Poll (RP). The breed group designated ANI consisted of small-framed cows. Total horn fly and total face fly counts were determined weekly on each cow beginning in May and ending in late October or early November in a 3-yr (1988-90) study. Face flies were not counted on the ANI and ANII breed groups in 1988. All fly counts were taken when cows were grazing Ozark upland native grass pastures with only containment fences separating breeding groups. No insecticides were used in the study. Data for analysis were the mean annual horn fly and face fly counts (averaged across weeks), spring weight and fall weights, gain/day between spring and fall weights, and skin surface area in the spring (SSAS) and fall (SSAF) for each cow. Relationships among measurements were examined by correlation and regression procedures. Horn fly count was correlated (P < .05) with face fly count, spring weight, gain/day, and SSAS (.23, .11, -.25, and .12, respectively). Correlations of horn fly count with fall weight and SSAF were non-significant. Horn fly count, breed, and the breed x horn fly count interaction were significant (P < .05) for the face fly regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

The Gravitational Plant Physiology Facility--description of equipment developed for biological research in Spacelab.

In January 1992, the NASA Shuttle mission STS 42 carried a facility designed to perform experiments on plant gravi- and photo-tropic responses. This equipment, the Gravitational Plant Physiology Facility (GPPF) was made up of a number of interconnected units mounted within a Spacelab double rack. The details of these units and the plant growth containers designed for use in GPPF are described. The equipment functioned well during the mission and returned a substantial body of time-lapse video data on plant responses to tropistic stimuli under conditions of orbital microgravity. GPPF is maintained by NASA Ames Research Center, and is flight qualifiable for future Spacelab missions.

Avena↗

Radiopharmaceutical uptake as a marker of sternal blood supply following internal mammary artery harvesting.

To evaluate the impact of internal mammary artery harvesting on sternal blood supply after open heart surgery, a conventional bone scan was performed 7 days after operation in 30 patients. After administration of 370 MBq of technetium 99 m-medronic acid complex, imaging was carried out at the level of the sternum and including the humerus as a reference. A quantitative analysis of uptake (sternum/humerus uptake index) was performed and compared in three different groups of patients: group A, ten patients who had only vein grafts or valve surgery; group B, ten patients with single internal mammary artery harvesting; and group C, ten patients with bilateral internal mammary artery harvesting. These results were compared with 24 non-surgical subjects as a control (group D). Although intervention had a significant influence in raising the uptake index of the surgical groups (A = 3.34; B = 3.09 and C = 3.48) when compared with normal subjects (D = 2.45) (P < 0.01), there was not a statistically significant difference among the three surgical groups (P > 0.05). It was concluded that the vascular supply of the sternum is not entirely dependent upon the internal mammary arteries and that mobilization of both vessels does not cause per se additional serious impact to the bone vascularization after midline sternotomy, at least beyond day 7 after operation.

Coronary Artery Bypass↗