Biomedical subjects

Connie M Weaver

Publications and source records attributed to Connie M Weaver.

At least 19 recordsLinked to original sources

PubMed2006

Systematic identification and functional screens of uncharacterized proteins associated with eukaryotic ribosomal complexes.

Translation regulation is a critical means by which cells control growth, division, and apoptosis. To gain further insight into translation and related processes, we performed multifaceted mass spectrometry-based proteomic screens of yeast ribosomal complexes and discovered an association of 77 uncharacterized yeast proteins with ribosomes. Immunoblotting revealed an EDTA-dependent cosedimentation with ribosomes in sucrose gradients for 11 candidate translation-machinery-associated (TMA) proteins. Tandem affinity purification linked one candidate, LSM12, to the RNA processing proteins PBP1 and PBP4. A second candidate, TMA46, interacted with RBG1, a GTPase that interacts with ribosomes. By adapting translation assays to high-throughput screening methods, we showed that null yeast strains harboring deletions for several of the TMA genes had alterations in protein synthesis rates (TMA7 and TMA19), susceptibility to drugs that inhibit translation (TMA7), translation fidelity (TMA20), and polyribosome profiles (TMA7, TMA19, and TMA20). TMA20 has significant sequence homology with the oncogene MCT-1. Expression of human MCT-1 in the Deltatma20 yeast mutant complemented translation-related defects, strongly implying that MCT-1 functions in translation-related processes. Together these findings implicate the TMA proteins and, potentially, their human homologs, in translation related processes.

Amino Acid Sequence↗

PubMed2006

Back to basics: have milk with meals.

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Adolescent↗

PubMed2006

Soy isoflavones and bone health: a double-edged sword?

Numerous publications and research studies on isoflavones have prompted a nationwide increase in the consumption of soy-based foods and supplements in the United States. Isoflavones are natural endocrine active compounds generally considered to promote health and prevent or slow the onset of certain chronic diseases such as osteoporosis. The beneficial effects of soy isoflavones on bone may, however, be life-stage specific and dependent on the estrogen receptor number and endogenous hormone milieu. Perimenopausal and early menopausal women may therefore be more receptive to the therapeutic effects of isoflavones on bone loss prior to the diminution of estrogen receptors that occurs in the postmenopausal years, whereas laboratory studies in developmental age range animals have demonstrated the potential for adverse effects following exposure to high levels of soy isoflavones. Clinical studies in developing humans that either support or refute findings in animal studies are lacking. The effects of chronic consumption of high levels of soy isoflavones at each life stage to assess risk-benefit ratios should be a high priority of research.

Animals↗

PubMed2006

Calcium retention in adolescent boys on a range of controlled calcium intakes.

BACKGROUND: National calcium requirements in the United States for boys are based on data from girls. On average, boys develop larger skeletons than do girls, yet it is unknown whether the additional skeletal accretion in boys requires additional dietary calcium intake. OBJECTIVE: The objective was to determine calcium retention in adolescent boys in response to a range of controlled intakes and to compare the intake needed for maximal retention in boys with that needed in adolescent girls studied under the same conditions. DESIGN: Thirty-one boys aged 12-15 y participated in 3-wk metabolic balance studies testing a range (700-2100 mg/d) of calcium intakes in a crossover study design with a 2-wk washout period. Calcium intake was varied by using a beverage fortified with calcium citrate malate. After a 1-wk equilibration period, calcium retention was calculated as dietary calcium intake minus the calcium excreted in the feces and urine over the following 2 wk. The dietary intake at which maximal calcium retention occurred was determined by using a nonlinear regression model. The results in boys were compared with those obtained in 35 adolescent girls previously studied under the same protocol. RESULTS: Maximal calcium retention in boys was achieved at an intake of 1140 mg/d. Calcium retention was higher (by 171 +/- 38 mg/d) in boys than in girls at all calcium intakes studied. CONCLUSION: The higher calcium retention in boys than in girls was attained through higher net calcium absorption and lower urinary excretion than in girls.

Adolescent↗

PubMed2006

Measuring calcium absorption and utilization in humans.

PURPOSE OF REVIEW: Calcium metabolism is comprised primarily of absorption, urinary excretion, endogenous secretion and bone turnover. This review evaluates recent findings relating to the role of genetic and environmental factors, especially diet, on perturbing parameters of calcium metabolism. Calcium dynamics are studied with the use of isotopic tracers. We also cover state-of-the-art methods for stable calcium isotope ratio analysis and offer insights on experimental design. RECENT FINDINGS: Some progress has been made identifying genetic and hormonal regulators of calcium absorption. Much progress has been made in understanding the role of diet on influencing calcium retention, especially with regard to dietary protein and salt. Long-held views on dietary factors thought to contribute to bone loss through urinary calcium loss have been shown to have no impact on net calcium retention because of compensatory changes in other aspects of calcium metabolism. SUMMARY: Much more work needs to be done on understanding genetic regulators of calcium metabolism. Despite recent advances in our knowledge of dietary influences on calcium metabolism, more studies are needed on the role of environmental factors, especially physical activity.

Argon↗

PubMed2005

Purifying protein complexes for mass spectrometry: applications to protein translation.

Proteins control and mediate most of the biological activities in the cell. In most cases, proteins either interact with regulatory proteins or function in large molecular assemblies to carryout biological processes. Understanding the functions of individual proteins requires the identification of these interacting proteins. With its speed and sensitivity, mass spectrometry has become the dominant method for identifying components of protein complexes. This article reviews and discusses various approaches to purify protein complexes and analyze the proteins using mass spectrometry. As examples, methods to isolate and analyze protein complexes responsible for the translation of messenger RNAs into polypeptides are described.

Cell Differentiation↗

PubMed2005

Inulin, oligofructose and bone health: experimental approaches and mechanisms.

Inulin-type fructans have been proposed to benefit mineral retention, thereby enhancing bone health. Many, but not all, experimental animal studies have shown increased mineral absorption by feeding non-digestible oligosaccharides. Possible reasons for inconsistencies are explored. A few studies have reported an enhanced bone mineral density or content. Bone health can be evaluated in chronic feeding studies with bone densitometry, bone breaking strength, bone mineral concentration and bone structure. Isotopic Ca tracers can be used to determine the point of metabolism affected by feeding a functional food ingredient. These methods and the effects of feeding inulin-type fructose are reviewed. Inulin-type fructans enhance Mg retention. Chicory long-chain inulin and oligofructose enhance femoral Ca content, bone mineral density and Ca retention through enhanced Ca absorption and suppressed bone turnover rates, but it is not bone-promoting under all conditions.

Animals↗

PubMed2005

Newer perspectives on calcium nutrition and bone quality.

It is now generally accepted that an adequate calcium intake is important for building and maintaining a skeleton that expresses quantitatively the full genetic program and reduces lifetime fracture risk. In this brief review we focus mainly on a new and growing body of evidence indicating a benefit of adequate calcium intake on qualitative features of the skeleton that, independent of the quantity of bone, themselves influence skeletal strength and fragility. Change in bone mass and size during growth are dependent on both calcium intake and exercise, with the largest differences being observed in prepubertal children who have both high exercise levels and high calcium intakes. Much of this benefit is expressed as increased bone diameter (and hence stiffness). Fracture risk peaks at about the time of puberty and is inversely related to bone mass. However, even prepubertally, children with low calcium intakes have been reported to have a fracture rate 2.7x that of their birth cohort. Bone remodeling triples from age 50 to 65 in typical women and is now recognized to have primarily a homeostatic basis. While remodeling improves bone strength by repairing acquired defects, homeostatic remodeling, while necessary to maintain blood calcium levels, contributes only structural weakness to bone. High calcium intakes in postmenopausal and older women reduce this homeostatic remodeling to approximately pre-menopausal values and improve bone strength immediately, well prior to any appreciable change in bone mass.

Adolescent↗

PubMed2005

Racial differences in calcium retention in response to dietary salt in adolescent girls.

BACKGROUND: Sodium is an important determinant of urinary calcium excretion, and race is an important determinant of calcium retention. The effect of dietary sodium on calcium retention and the influence of race have not been studied in adolescence, the life stage during which peak bone mass is accrued. OBJECTIVE: The study reported here was undertaken to compare racial differences in calcium retention as a function of dietary salt intake. DESIGN: A total of 35 adolescent girls (22 black and 13 white) participated in two 20-d metabolic summer camps, separated by 2 wk, that simulated a free-living environment. The effect of changes in dietary sodium on calcium retention was tested in a randomized-order, crossover design with 2 concentrations of sodium-1.30 g/d (57 mmol/d) and 3.86 g/d (168 mmol/d)-and a constant calcium intake of 815 mg/d (20 mmol/d). RESULTS: Both race and sodium intake significantly affected calcium retention (P < 0.01). Calcium retention was significantly greater in black girls than in white girls, regardless of dietary sodium intake (P < 0.001). The high-sodium diet significantly reduced calcium retention in both whites and blacks (P < 0.01), primarily through a decrease in net calcium absorption. Black girls excreted significantly less calcium in the urine than did white girls, regardless of diet (P < 0.05). CONCLUSIONS: Calcium retention is significantly greater in black girls than in white girls but is significantly reduced in girls of both races in response to salt loading.

Adolescent↗

PubMed2005

The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study.

BACKGROUND: Evidence suggests that soy isoflavones act as estrogen agonists and have beneficial skeletal effects, but the effects on calcium metabolism in humans are not known. OBJECTIVE: This study tested whether soybean isoflavones, soy protein, or both alter calcium metabolism in postmenopausal women. DESIGN: Calcium metabolism in 15 postmenopausal women was studied by using metabolic balance and kinetic modeling in a randomized, crossover design of three 1-mo controlled dietary interventions: soy protein isolate enriched with isoflavones (soy-plus diet), soy protein isolate devoid of isoflavones (soy-minus diet), and a casein-whey protein isolate (control diet). RESULTS: There was no significant difference between the diets in net acid excretion (P = 0.12). Urinary calcium excretion was significantly (P < 0.01) less with consumption of either of the soy diets (soy-plus diet: 85 +/- 34 mg/d; soy-minus diet: 80 +/- 34 mg/d) than with consumption of the control diet (121 +/- 63 mg/d), but fractional calcium absorption was unaffected by treatment. Endogenous fecal calcium was significantly (P < 0.01) greater with consumption of the soy-minus diet than with consumption of the other diets. Total fecal calcium excretion, bone deposition and resorption, and calcium retention were not significantly affected by the dietary regimens. CONCLUSIONS: The lower urinary calcium seen with the consumption of an isolated soy protein than with that of an isolated milk protein was not associated with improved calcium retention. This finding reinforces the importance of evaluating all aspects of calcium metabolism. Soy isoflavones did not significantly affect calcium metabolism.

Body Mass Index↗

PubMed2005

Calcium bioavailability of calcium carbonate fortified soymilk is equivalent to cow's milk in young women.

Calcium (Ca)-fortified soymilk has gained popularity in the United States. Tricalcium phosphate (TCP)-fortified soymilk was shown to have a lower Ca bioavailability than cow's milk in men. However, the most popular soymilk in the U.S. is fortified with Ca carbonate (CC) and has not been evaluated. Ca bioavailability from CC-fortified soymilk (CCSM) and TCP-fortified soymilk (TCPSM) was compared with cow's milk in young healthy women using the dual stable isotope technique. In a 3-way crossover design, 20 volunteers (23 +/- 2 y old) consumed 250 mg Ca in cow's milk, CCSM, or TCPSM along with 10 mg 44Ca after an overnight fast. Cow's milk was extrinsically labeled, whereas each fortified soymilk was intrinsically labeled with each chemical salt of 44Ca at the manufacturing facility. Another stable isotope, 43Ca, was injected i.v. 1 h after the complete consumption of cow's milk or soymilk. Fractional Ca absorption was determined from the ratios of 43Ca:42Ca and 44Ca:42Ca by inductively coupled plasma (ICP)-MS in the 24-h urine samples. A mixed linear model (SAS proc mixed) was used to compare the fractional Ca absorption among groups. Fractional Ca absorption in CCSM (0.211 +/- 0.057) did not differ from that of cow's milk (0.217 +/- 0.040), but both were higher (P < 0.05) than that of TCPSM (0.181 +/- 0.039). Our result suggests that calcium absorption is equivalent for CCSM and cow's milk at similar calcium loads.

Adult↗

PubMed2005

Sorting out bioactivity in flavonoid mixtures.

Natural polyphenolic compounds, including flavonoids, which are synthesized by plants, have repeatedly been linked to multiple health benefits, but specific bioactive compounds or individualized roles have been difficult to interpret or to assign. This limitation has prevented the development of robust dietary recommendations. This paper describes a plant-cell-culture production approach that provides uniform yields of abundant natural mixtures of flavonoids from small molecules to high molecular weight oligomers and polymers. The flavonoids correspond to compounds produced in nature by the same plant genotypes; but, through elicitation tactics, the levels and the profiles of the flavonoid yield can be enhanced, and isolation from cell cultures is more rapid and streamlined than isolation from in vivo plant tissues. Introduction of (14)C sucrose to the cell-culture medium enabled the recovery and the identification of biolabeled flavonoid mixtures, which could be easily tracked in serum of rats after gavage. The biolabeled materials are now being investigated to determine tissue localization, structures of bioactive components, and the interactions between flavonoid components that contribute to bioactive potential.

Animals↗

PubMed2005

Soy isoflavones and bone health: the relationship is still unclear.

Evidence of the effect of purified soy isoflavones and soy protein isolates containing isoflavones on bone health in rats and in humans is inconsistent. Differences may be because of synergies or antagonisms among the isoflavones, threshold or biphasic dose effects, life stage of animals or human subjects, estrogen status, and environment-genetic interactions, including the ability to produce metabolites upon ingestion of isoflavones. At this time, the benefits of soy protein and isoflavones on bone health are inconclusive. This overview will summarize these discrepancies and will suggest future studies to clarify the conditions under which these dietary substances can be helpful for bones.

Bone Development↗

PubMed2005

Calcium and exercise affect the growing skeleton.

Adequate dietary calcium and bone-stimulating exercise during growth are known to affect skeletal development, but the combined effects of dietary calcium and osteogenic exercise have received scant attention. Animal research has showed a compensatory effect of impact loading on calcium-deprived bones, while various human studies have suggested compensatory, additive, or possibly synergistic effects in certain skeletal locations. Current evidence suggests that the best strategy for strong bones by the end of childhood may be either high-impact exercise with a moderate or greater calcium intake or a combination of moderate-impact exercise and adequate calcium during growth.

Adolescent↗

PubMed2005

Acute versus chronic effects of whey proteins on calcium absorption in growing rats.

The acute and chronic effects of whey proteins on calcium metabolism and bone were evaluated. In acute studies, 8-week-old male rats were gavaged with 50 mg whey protein concentrate (WPC) and 25 mg calcium. 45Ca was administered intravenously or orally. Kinetic studies were performed, and femurs were harvested. Four of seven WPCs significantly increased femur uptake of 45Ca compared with controls. One WPC at 50 mg enhanced calcium absorption over a range of calcium intakes from 35.1 +/- 9.4% to 42.4 +/- 14.0% (P < 0.01). Three of the most effective WPCs were tested further in a chronic feeding study. One hundred 3-week-old rats were randomly divided into four adequate dietary calcium (ADC; 0.4% Ca) groups (control of 20% casein and three WPC groups with 1% substitution of casein with each of three WPCs) and two low calcium (LC; 0.2% Ca) groups (control of 20% casein and one WPC group with 1% substitution of casein with one WPC). After 8 weeks, there was no effect of WPCs on femur uptake of 45Ca among ADC groups and there was no effect of WPCs on calcium retention, femur breaking force, femur bone mineral density, or total femur calcium at either dietary calcium intake. However, whole body bone mineral content (BMC) was significantly higher (P < 0.05) in the three whey protein concentrate ADC groups compared with the ADC control group. Total BMC at the proximal tibia in whey protein ADC groups was increased, as shown by peripheral quantitative computed tomography. Our results indicate that the acute calcium absorption-enhancing effect of whey proteins did not persist through long-term feeding in rats. However, the initial enhancement of calcium absorption by whey protein was sufficient to increase BMC.

Animals↗

PubMed2004

Comparative effect of soy protein, soy isoflavones, and 17beta-estradiol on bone metabolism in adult ovariectomized rats.

UNLABELLED: This study provided a comprehensive investigation on the effect of soy protein and soy isoflavones on both calcium and bone metabolism in virgin adult rats. The measurements included bone histology, calcium kinetic modeling, calcium balance, bone densitometry, and whole body densitometry. Results confirmed the bone-preserving effect of estrogen but did not support a bone-sparing role of soy isoflavones. INTRODUCTION: Several animal and short-term human studies have indicated that soy protein isolate enriched with isoflavones may be used as an alternative therapy to estrogen replacement therapy. However, none of the previous studies have investigated this estrogenic effect on both calcium and bone metabolism in animals or humans, which is essential in ascertaining the mode of action of isoflavones. MATERIALS AND METHODS: This study was designed to determine the effects of soy protein versus isoflavones on calcium and bone metabolism in an ovariectomized rat model. Unmated 6-month-old ovariectomized and sham-operated female Sprague-Dawley rats were randomly assigned to nine groups (16 rats/group) and pair-fed soy- or casein-based diets with or without isoflavones for 8 weeks. A reference group was administered estrogen through subcutaneous implants (20-35 pg/liter plasma). Bone densitometry, histomorphometry, and mechanical testing were used to study bone metabolism and quality. Calcium metabolism was studied using calcium tracer balance and kinetics. RESULTS: After ovariectomy, estrogen prevented bone loss in trabecular bone and suppressed formation on both trabecular and cortical bone surfaces. Isoflavones given as enriched soy protein isolate or supplements did not prevent trabecular bone loss. Combining isoflavones with estrogen had no additional benefits over estrogen alone. There were no differences in response to isoflavones caused by protein source. None of the treatments significantly affected either total Ca balance or (45)Ca absorption. However, soy protein showed significant effects on reducing urinary loss of Ca in animals, irrespective of isoflavone level, perhaps because of the lower amount of sulfur-containing amino acids in soy protein. CONCLUSION: Estrogen, but not isoflavones at the levels tested, suppressed bone remodeling in both trabecular and cortical bone after ovariectomy.

Absorption↗

PubMed2004

Inulin effects on bioavailability of soy isoflavones and their calcium absorption enhancing ability.

The effect of inulin on isoflavone absorption and the effect of isoflavones and synergy with inulin on calcium absorption in rats was investigated. Rats (n = 48) were divided into three groups and fed inulin (50 mg/g), isoflavone (8 mg/g) or inulin + isoflavone (50 mg/g + 8 mg/g) diets for 21 days. After a 2-h fast, rats were given (45)Ca orally or intraperitoneally, together with 25 mg of calcium as calcium acetate. Blood and femurs were collected 4 days later. Sera were analyzed for isoflavones using HPLC-MS, femurs for (45)Ca by beta-scintillation counting, and total femoral calcium by atomic absorption spectroscopy. Both groups fed isoflavones had similar and significantly higher weight-adjusted total femoral calcium content compared to the inulin-fed group (p < 0.0001). (45)Ca absorption was significantly higher (p < 0.01) when isoflavones were added to the diet, and serum equol was significantly lower (p < 0.01) when inulin was added to the diet containing isoflavones. We conclude that isoflavones enhance calcium absorption, without synergy from inulin, and that inulin decreases equol production.

Absorption↗

PubMed2004

Dairy intakes affect bone density in the elderly.

BACKGROUND: Race and sex differences in the effect of diet on bone mineral density (BMD) at the hip in the elderly are unknown. OBJECTIVES: This study related cross-sectional nutrient and dairy product consumption to hip BMD in white and black men and women aged >60 y and evaluated the influence of nutrient and dairy product consumption on changes in BMD in a white cohort participating in a calcium, vitamin D, or placebo trial. DESIGN: The Health Habits and History Questionnaire was used in 289 white women and 116 white men who participated in the trial and in 265 black women and 75 black men to predict total hip and femoral neck BMD or changes in BMD. RESULTS: Blacks had higher calcium intakes than did whites (700 and 654 mg/d, respectively; P = 0.0094), and men had higher calcium intakes than did women (735 and 655 mg/d, respectively; P = 0.0007). For men, the correlation between total hip BMD and dairy calcium intake after adjustment for age, race, and weight was 0.23 (P < 0.005); this relation was not significant in women (r = 0.02, P = 0.12). Similar results were found for femoral neck BMD. In the longitudinal study, calcium supplementation reduced bone loss from the total hip and femoral neck in those who consumed <1.5 servings of dairy products/d and were <72 y old. CONCLUSIONS: Cross-sectional results indicated that higher dairy product consumption is associated with greater hip BMD in men, but not in women. Calcium supplementation protected both men and women from bone loss in the longitudinal study of whites.

Age Factors↗