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1.
Am J Physiol Heart Circ Physiol ; 326(1): H103-H109, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37947437

RESUMO

Cardiorespiratory fitness (CRF) and the subendocardial viability ratio (SEVR) decline with age and predict future cardiovascular disease (CVD) events in a sex-dependent manner. However, the relation between CRF and SEVR in apparently healthy males and females across the age span is largely unknown. We hypothesized higher CRF is associated with greater SEVR in older females but not in males. Two-hundred sixty-two (126 M/136 F, age range 20-84 yr) participants underwent measures of CRF (maximal O2 consumption, V̇o2max) and SEVR (pulse wave analysis, PWA). A two-way analysis of variance (ANOVA) was used to examine differences in baseline characteristics between younger (<45 yr) and middle-aged and older (MA/O, ≥45 yr) males and females. Bivariate correlations assessed the relation between CRF, SEVR, and age in males and females. Partial correlations adjusted for CVD risk factors and medications. MA/O females had the lowest CRF and SEVR compared with all other groups (P < 0.05, both). SEVR was negatively correlated with age (r = -0.29) and positively correlated with CRF (r = 0.53) in females (P < 0.05, both) that persisted after controlling for CVD risk factors and medications (P < 0.05, all). SEVR was correlated with CRF in males only after adjusting for CVD risk factors and medications (r = 0.26, P < 0.05). These findings collectively demonstrate higher CRF is associated with greater SEVR in males and females after adjusting for CVD risk factors and medications, therefore highlighting subtle sex-specific nuances that warrant further investigation.NEW & NOTEWORTHY Cardiorespiratory fitness (CRF) and the subendocardial viability ratio (SEVR) are independent predictors of mortality and decline with age. However, the sex-specific relationship between CRF and SEVR with aging in adult males and females is unknown. Our findings demonstrate higher CRF is associated with greater age-related SEVR in males and females, after adjusting for traditional cardiovascular disease (CVD) risk factors and medications. However, subtle sex-related nuances exist in the relationship between SEVR and CRF that require further investigation.


Assuntos
Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Humanos , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Envelhecimento , Nível de Saúde , Perfusão/efeitos adversos
2.
Rhinology ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913328

RESUMO

BACKGROUND: The extent to which gender affects outcomes in chronic rhinosinusitis (CRS) is unclear. The objective of this study was to examine differential outcomes between genders following endoscopic sinus surgery (ESS) among CRS patients. METHODS: PubMed/Ovid, Embase and Cochrane databases were queried. Outcomes included disease burden on imaging and endoscopy, patient-reported outcome measures (PROMs) including the Sinonasal Outcome Test (SNOT-22), revision rates, and olfactory outcomes. Meta-analysis was performed using the Mantel-Haenszel method with random effects model. RESULTS: Of 4,656 articles screened, 32 (n=103,499) were included for qualitative analysis and four (n=2,602) for meta-analysis. On qualitative analysis, 19 of the 32 studies noted a significant gender difference in post-operative outcomes, with five studies favoring women and 14 favoring men. Nine of 18 studies with PROMs noted a difference between genders, all favoring men. Olfactory outcomes were mixed with studies divided on favoring men vs women. No studies noted significant gender differences of disease burden on imaging or endoscopy. Across four studies included in the meta-analysis, women had higher preoperative and post-operative SNOT-22 scores. CONCLUSION: Meta-analysis shows that women patients have worse pre and postoperative SNOT-22 scores. Postoperative gender differences are most apparent in studies that examined PROMs. Further research is needed to investigate the underlying causes and to mitigate disparities between genders.

3.
Br J Nutr ; 117(7): 951-963, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28443527

RESUMO

An experiment was conducted to determine: (1) the effect of excess maternal I supplementation on the thyroid hormone status of the ewe and her progeny; (2) potential mechanisms underpinning the failure of passive transfer associated with excess I and (3) the growing lambs' response to natural gastrointestinal infection. Twin-bearing ewes received one of two treatments (n 32/treatment group): basal diet (C) or C plus 26·6 mg of iodine/ewe per d (I), supplied as calcium iodate. Ewes were individually fed from day 119 of gestation to parturition. Progeny of I ewes had lower (P<0·01) serum IgG concentrations from 24 h to 28 d postpartum but higher serum IgG concentrations at day 70 postpartum (P<0·05). I supplementation increased the relative expression of Fc receptor, IgA, IgM high affinity and polymeric Ig receptor in the ileum of the lamb at 24 h postpartum; however, thyroid hormone receptor-ß (THRB) and ß-2-microglobulin (B2M) expression declined (P<0·05). Progeny of I ewes had higher growth rates to weaning (P<0·05) and lower faecal egg count (FEC) for Nematodirus battus (P<0·05) between weeks 6 and 10 postpartum. In conclusion, excess maternal I supplementation negatively affected the thyroid hormone status, serum IgG concentration, ileal morphology and the gene expression of THRB and B2M in the ileum and ras-related protein (RAB) RAB25 and the mucin gene (MUC) MUC1 in the duodenum of the lamb postpartum. These effects were followed by an enhancement of average daily gain and lower N. battus FEC in the pre-weaning period of I-supplemented lambs.


Assuntos
Colostro/imunologia , Suplementos Nutricionais , Imunidade Materno-Adquirida , Iodo/uso terapêutico , Fenômenos Fisiológicos da Nutrição Materna , Doenças dos Ovinos/prevenção & controle , Infecções por Strongylida/veterinária , Animais , Animais Recém-Nascidos , Colostro/química , Suplementos Nutricionais/efeitos adversos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Íleo/crescimento & desenvolvimento , Íleo/imunologia , Íleo/metabolismo , Íleo/patologia , Imunoglobulina G/análise , Imunoglobulina G/biossíntese , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Iodo/efeitos adversos , Masculino , Nematodirus/imunologia , Nematodirus/isolamento & purificação , Contagem de Ovos de Parasitas/veterinária , Gravidez , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/metabolismo , Doenças dos Ovinos/parasitologia , Carneiro Doméstico , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Infecções por Strongylida/prevenção & controle , Receptores beta dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/metabolismo , Aumento de Peso , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismo
4.
Parasite Immunol ; 38(9): 569-86, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27387842

RESUMO

Gastrointestinal nematode (GIN) infection of ruminants represents a major health and welfare challenge for livestock producers worldwide. The emergence of anthelmintic resistance in important GIN species and the associated animal welfare concerns have stimulated interest in the development of alternative and more sustainable strategies aimed at the effective management of the impact of GINs. These integrative strategies include selective breeding using genetic/genomic tools, grazing management, biological control, nutritional supplementation, vaccination and targeted selective treatment. In this review, the logic of selecting for "resistance" to GIN infection as opposed to "resilience" or "tolerance" is discussed. This is followed by a review of the potential application of immunogenomics to genetic selection for animals that have the capacity to withstand the impact of GIN infection. Advances in relevant genomic technologies are highlighted together with how these tools can be advanced to support the integration of immunogenomic information into ruminant breeding programmes.


Assuntos
Cruzamento , Resistência à Doença/genética , Enteropatias Parasitárias/veterinária , Infecções por Nematoides/veterinária , Ruminantes/parasitologia , Animais , Anti-Helmínticos/uso terapêutico , Enteropatias Parasitárias/genética , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/genética , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/parasitologia
5.
Br J Nutr ; 111(9): 1577-85, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24502994

RESUMO

In the present study, two experiments were conducted to (1) evaluate the effect of laminarin and/or fucoidan on ileal morphology, nutrient transporter gene expression and coefficient of total tract apparent digestibility (CTTAD) of nutrients and (2) determine whether laminarin inclusion could be used as an alternative to ZnO supplementation in weaned pig diets. Expt 1 was designed as a 2 × 2 factorial arrangement, comprising four dietary treatments (n 7 replicates, weaning age 24 d, live weight 6·9 kg). The dietary treatments were as follows: (1) basal diet; (2) basal diet+300 ppm laminarin; (3) basal diet+240 ppm fucoidan; (4) basal diet+300 ppm laminarin and 240 ppm fucoidan. There was an interaction between laminarin and fucoidan on the CTTAD of gross energy (GE) (P< 0·05) and the expression of sodium-glucose-linked transporter 1 (SGLT1/SLC5A1) and GLUT1/SLC2A1 and GLUT2/SLC2A2 (P< 0·05) in the ileum. The laminarin diet increased the CTTAD of GE and increased the expression of SGLT1, GLUT1 and GLUT2 compared with the basal diet. However, there was no effect of laminarin supplementation on these variables when combined with fucoidan. Expt 2 was designed as a complete randomised design (n 8 replicates/treatment, weaning age 24 d, live weight 7·0 kg), and the treatments were (1) basal diet, (2) basal diet and laminarin (300 ppm), and (3) basal diet and ZnO (3100 ppm, 0-14 d, and 2600 ppm, 15-32 d post-weaning). The laminarin diet increased average daily gain and gain:feed ratio compared with the basal diet during days 0-32 post-weaning (P< 0·01) and had an effect similar to the ZnO diet. These results demonstrate that laminarin provides a dietary means to improve gut health and growth performance post-weaning.


Assuntos
Dieta/veterinária , Digestão , Fármacos Gastrointestinais/metabolismo , Íleo/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Sus scrofa/metabolismo , Animais , Cruzamentos Genéticos , Ingestão de Energia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Regulação da Expressão Gênica no Desenvolvimento , Glucanos , Íleo/citologia , Íleo/crescimento & desenvolvimento , Mucosa Intestinal/citologia , Mucosa Intestinal/crescimento & desenvolvimento , Irlanda , Laminaria/química , Proteínas de Membrana Transportadoras/biossíntese , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Polissacarídeos/administração & dosagem , Polissacarídeos/metabolismo , Alga Marinha/química , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/microbiologia , Desmame , Aumento de Peso , Óxido de Zinco/metabolismo
6.
Br J Nutr ; 105(5): 669-77, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21251335

RESUMO

The aim of the present study was to establish the optimum inclusion level of laminarin derived from Laminaria digitata on selected microbial populations, intestinal fermentation, cytokine and mucin gene expression in the porcine ileum and colon. A total of twenty-one pigs (mean body weight 17·9 kg) were randomly assigned to one of three dietary treatments: T1 - basal (control) diet, T2 and T3 - basal diets supplemented with laminarin included at 300 and 600 parts per million (ppm), respectively. Selected intestinal bacterial populations and volatile fatty acid (VFA) concentrations were measured in the ileum and colon. Relative gene expression levels for specific cytokine and mucin genes were investigated in ileal and colonic tissue in the absence and presence of a lipopolysaccharide (LPS) challenge. There was an up-regulation of MUC2 gene expression at the 300 ppm inclusion level in the ileum. In the colon, there was a significant reduction in the enterobacteriaceae population at the 300 ppm inclusion level (P = 0·0421). Dietary supplementation of 600 ppm laminarin led to a significant increase in MUC2 (P = 0·0365) and MUC4 (P = 0·0401) expression in the colon, and in the total VFA concentration in the caecum (P = 0·0489). A significant increase was also recorded in IL-6 (P = 0·0289) and IL-8 gene expression (P = 0·0245) in LPS-challenged colonic tissue at both laminarin inclusion levels. In conclusion, dietary inclusion of 300 ppm laminarin appears to be the optimum dose in the present study due to the reduction in the enterobacteriaceae populations and enhanced IL-6 and IL-8 cytokine expression in response to an ex vivo LPS challenge.


Assuntos
Antibacterianos/farmacologia , Ácidos Graxos Voláteis/metabolismo , Interleucinas/metabolismo , Intestinos/efeitos dos fármacos , Laminaria/química , Mucinas/metabolismo , Polissacarídeos/farmacologia , Animais , Antibacterianos/administração & dosagem , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/microbiologia , Suplementos Nutricionais , Enterobacteriaceae/efeitos dos fármacos , Fermentação , Expressão Gênica/efeitos dos fármacos , Glucanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/microbiologia , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Interleucinas/genética , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Lipopolissacarídeos , Mucina-2/genética , Mucina-2/metabolismo , Mucina-4/genética , Mucina-4/metabolismo , Mucinas/genética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Polissacarídeos/administração & dosagem , Distribuição Aleatória , Suínos , Regulação para Cima , beta-Glucanas/administração & dosagem , beta-Glucanas/farmacologia
7.
Poult Sci ; 100(7): 101179, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34098504

RESUMO

Restriction in antimicrobial use in broiler chicken production is driving the exploration of alternative feed additives that will support growth through the promotion of gastrointestinal health and development. The objective of this study was to determine the effects of dietary inclusion of laminarin on growth performance, the expression of nutrient transporters, markers of inflammation and intestinal integrity in the small intestine and composition of the caecal microbiota in broiler chickens. Two-hundred-and-forty day-old male Ross 308 broiler chicks (40.64 (3.43 SD) g) were randomly assigned to: (T1) basal diet (control); (T2) basal diet + 150 ppm laminarin; (T3) basal diet + 300 ppm laminarin (5 bird/pen; 16 pens/treatment). The basal diet was supplemented with a laminarin-rich Laminaria spp. extract (65% laminarin) to achieve the two laminarin inclusion levels (150 and 300 ppm). Chick weights and feed intake was recorded weekly. After 35 days of supplementation, one bird per pen from the control and best performing (300 ppm) laminarin groups were euthanized. Duodenal, jejunal and ileal tissues were collected for gene expression analysis. Caecal digesta was collected for microbiota analysis (high-throughput sequencing and QPCR). Dietary supplementation with 300 ppm laminarin increased both final body weight (2033 vs. 1906 ± 30.4, P < 0.05) and average daily gain (62.3 vs. 58.2 ± 0.95, P < 0.05) compared to the control group and average daily feed intake (114.1 vs. 106.0 and 104.5 ± 1.77, P < 0.05) compared to all other groups. Laminarin supplementation at 300 ppm increased the relative and absolute abundance of Bifidobacterium (P < 0.05) in the caecum. Laminarin supplementation increased the expression of interleukin 17A (IL17A) in the duodenum, claudin 1 (CLDN1) and toll-like receptor 2 (TLR2) in the jejunum and IL17A, CLDN1 and SLC15A1/peptide transporter 1 (SLC15A1/PepT1) in the ileum (P < 0.05). In conclusion, supplementation with laminarin is a promising dietary strategy to enhance growth performance and 300 ppm was the optimal inclusion level with which to promote a beneficial profile of the gastrointestinal microbiota in broiler chickens.


Assuntos
Ração Animal , Galinhas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta , Suplementos Nutricionais , Glucanos , Masculino , Extratos Vegetais
8.
J Cell Biol ; 152(2): 289-300, 2001 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-11266446

RESUMO

Porin, also termed the voltage-dependent anion channel, is the most abundant protein of the mitochondrial outer membrane. The process of import and assembly of the protein is known to be dependent on the surface receptor Tom20, but the requirement for other mitochondrial proteins remains controversial. We have used mitochondria from Neurospora crassa and Saccharomyces cerevisiae to analyze the import pathway of porin. Import of porin into isolated mitochondria in which the outer membrane has been opened is inhibited despite similar levels of Tom20 as in intact mitochondria. A matrix-destined precursor and the porin precursor compete for the same translocation sites in both normal mitochondria and mitochondria whose surface receptors have been removed, suggesting that both precursors utilize the general import pore. Using an assay established to monitor the assembly of in vitro-imported porin into preexisting porin complexes we have shown that besides Tom20, the biogenesis of porin depends on the central receptor Tom22, as well as Tom5 and Tom7 of the general import pore complex (translocase of the outer mitochondrial membrane [TOM] core complex). The characterization of two new mutant alleles of the essential pore protein Tom40 demonstrates that the import of porin also requires a functional Tom40. Moreover, the porin precursor can be cross-linked to Tom20, Tom22, and Tom40 on its import pathway. We conclude that import of porin does not proceed through the action of Tom20 alone, but requires an intact outer membrane and involves at least four more subunits of the TOM machinery, including the general import pore.


Assuntos
Membranas Intracelulares/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Mitocôndrias/fisiologia , Porinas/biossíntese , Receptores de Superfície Celular , Receptores Citoplasmáticos e Nucleares , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/fisiologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Genótipo , Membranas Intracelulares/ultraestrutura , Cinética , Proteínas de Membrana/química , Mitocôndrias/ultraestrutura , Proteínas de Transporte da Membrana Mitocondrial , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Neurospora crassa/genética , Neurospora crassa/fisiologia , Neurospora crassa/ultraestrutura , Porinas/metabolismo , Transporte Proteico , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/ultraestrutura , Canais de Ânion Dependentes de Voltagem
9.
J Appl Physiol (1985) ; 127(6): 1651-1659, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622159

RESUMO

Carbohydrate (CHO) ingestion is an established strategy to improve endurance performance. Race fuels should not only sustain performance but also be readily digested and absorbed. Potatoes are a whole-food-based option that fulfills these criteria, yet their impact on performance remains unexamined. We investigated the effects of potato purée ingestion during prolonged cycling on subsequent performance vs. commercial CHO gel or a water-only condition. Twelve cyclists (70.7 ± 7.7 kg, 173 ± 8 cm, 31 ± 9 yr, 22 ± 5.1% body fat; means ± SD) with average peak oxygen consumption (V̇o2peak) of 60.7 ± 9.0 mL·kg-1·min-1 performed a 2-h cycling challenge (60-85% V̇o2peak) followed by a time trial (TT; 6 kJ/kg body mass) while consuming potato, gel, or water in a randomized-crossover design. The race fuels were administered with [U-13C6]glucose for an indirect estimate of gastric emptying rate. Blood samples were collected throughout the trials. Blood glucose concentrations were higher (P < 0.001) in potato and gel conditions compared with water condition. Blood lactate concentrations were higher (P = 0.001) after the TT completion in both CHO conditions compared with water condition. TT performance was improved (P = 0.032) in both potato (33.0 ± 4.5 min) and gel (33.0 ± 4.2 min) conditions compared with water condition (39.5 ± 7.9 min). Moreover, no difference was observed in TT performance between CHO conditions (P = 1.00). In conclusion, potato and gel ingestion equally sustained blood glucose concentrations and TT performance. Our results support the effective use of potatoes to support race performance for trained cyclists.NEW & NOTEWORTHY The ingestion of concentrated carbohydrate gels during prolonged exercise has been shown to promote carbohydrate availability and improve exercise performance. Our study aim was to expand and diversify race fueling menus for athletes by providing an evidence-based whole-food alternative to the routine ingestion of gels during training and competition. Our work shows that russet potato ingestion during prolonged cycling is as effective as carbohydrate gels to support exercise performance in trained athletes.


Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Carboidratos da Dieta/administração & dosagem , Solanum tuberosum , Adulto , Glicemia , Digestão , Feminino , Humanos , Masculino , Esforço Físico , Adulto Jovem
10.
Mol Cell Biol ; 18(11): 6515-24, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9774667

RESUMO

The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). We have analyzed the molecular architecture of the Tom machinery. The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. A yeast mutant lacking both Tom20 and Tom70 can still form the GIP complex when sufficient amounts of Tom22 are synthesized. Besides the essential proteins Tom22 and Tom40, the GIP complex contains three small subunits, Tom5, Tom6, and Tom7. In mutant mitochondria lacking Tom6, the interaction between Tom22 and Tom40 is destabilized, leading to the dissociation of Tom22 and the generation of a subcomplex of approximately 100K containing Tom40, Tom7, and Tom5. Tom6 is required to promote but not to maintain a stable association between Tom22 and Tom40. The following conclusions are suggested. (i) The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. (ii) Tom20 and Tom70 are not essential for the generation of the GIP complex. (iii) Tom6 functions as an assembly factor for Tom22, promoting its stable association with Tom40.


Assuntos
Adenosina Trifosfatases/química , Proteínas de Bactérias/química , Proteínas de Escherichia coli , Proteínas de Membrana/química , Proteínas de Membrana Transportadoras , Mitocôndrias/fisiologia , Proteínas de Transporte da Membrana Mitocondrial , Receptores de Superfície Celular , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/fisiologia , Proteínas de Transporte/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Canais de Translocação SEC , Proteínas SecA
11.
Mol Cell Biol ; 21(7): 2337-48, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11259583

RESUMO

The preprotein translocase of the yeast mitochondrial outer membrane (TOM) consists of the initial import receptors Tom70 and Tom20 and a approximately 400-kDa (400 K) general import pore (GIP) complex that includes the central receptor Tom22, the channel Tom40, and the three small Tom proteins Tom7, Tom6, and Tom5. We report that the GIP complex is a highly stable complex with an unusual resistance to urea and alkaline pH. Under mild conditions for mitochondrial lysis, the receptor Tom20, but not Tom70, is quantitatively associated with the GIP complex, forming a 500K to 600K TOM complex. A preprotein, stably arrested in the GIP complex, is released by urea but not high salt, indicating that ionic interactions are not essential for keeping the preprotein in the GIP complex. Under more stringent detergent conditions, however, Tom20 and all three small Tom proteins are released, while the preprotein remains in the GIP complex. Moreover, purified outer membrane vesicles devoid of translocase components of the intermembrane space and inner membrane efficiently accumulate the preprotein in the GIP complex. Together, Tom40 and Tom22 thus represent the functional core unit that stably holds accumulated preproteins. The GIP complex isolated from outer membranes exhibits characteristic TOM channel activity with two coupled conductance states, each corresponding to the activity of purified Tom40, suggesting that the complex contains two simultaneously active and coupled channel pores.


Assuntos
Canais Iônicos/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Mitocôndrias/metabolismo , Receptores Citoplasmáticos e Nucleares , Proteínas de Saccharomyces cerevisiae , Proteínas Fúngicas/metabolismo , Membranas Intracelulares/metabolismo , Proteínas de Transporte da Membrana Mitocondrial , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Saccharomyces cerevisiae , Transdução de Sinais
12.
Mol Biol Cell ; 10(7): 2461-74, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10397776

RESUMO

Two major routes of preprotein targeting into mitochondria are known. Preproteins carrying amino-terminal signals mainly use Tom20, the general import pore (GIP) complex and the Tim23-Tim17 complex. Preproteins with internal signals such as inner membrane carriers use Tom70, the GIP complex, and the special Tim pathway, involving small Tims of the intermembrane space and Tim22-Tim54 of the inner membrane. Little is known about the biogenesis and assembly of the Tim proteins of this carrier pathway. We report that import of the preprotein of Tim22 requires Tom20, although it uses the carrier Tim route. In contrast, the preprotein of Tim54 mainly uses Tom70, yet it follows the Tim23-Tim17 pathway. The positively charged amino-terminal region of Tim54 is required for membrane translocation but not for targeting to Tom70. In addition, we identify two novel homologues of the small Tim proteins and show that targeting of the small Tims follows a third new route where surface receptors are dispensable, yet Tom5 of the GIP complex is crucial. We conclude that the biogenesis of Tim proteins of the carrier pathway cannot be described by either one of the two major import routes, but involves new types of import pathways composed of various features of the hitherto known routes, including crossing over at the level of the GIP.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial , Receptores Citoplasmáticos e Nucleares , Proteínas Repressoras , Proteínas de Saccharomyces cerevisiae , Sequência de Aminoácidos , Transporte Biológico , Proteínas de Transporte/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas de Membrana/genética , Mitocôndrias/efeitos dos fármacos , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Dados de Sequência Molecular , Mutação Puntual , Receptores de Superfície Celular/metabolismo , Tripsina/metabolismo , Tripsina/farmacologia , Leveduras/genética , Leveduras/metabolismo
13.
Sci Signal ; 10(499)2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-28974650

RESUMO

Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its antitumor activity. We tested 69 anticancer drugs in combination with YK-4-279 and found that vinca alkaloids exhibited synergy with YK-4-279 in five ES cell lines. The combination of YK-4-279 and vincristine reduced tumor burden and increased survival in mice bearing ES xenografts. We determined that independent drug-induced events converged to cause this synergistic therapeutic effect. YK-4-279 rapidly induced G2-M arrest, increased the abundance of cyclin B1, and decreased EWS-FLI1-mediated generation of microtubule-associated proteins, which rendered cells more susceptible to microtubule depolymerization by vincristine. YK-4-279 reduced the expression of the EWS-FLI1 target gene encoding the ubiquitin ligase UBE2C, which, in part, contributed to the increase in cyclin B1. YK-4-279 also increased the abundance of proapoptotic isoforms of MCL1 and BCL2, presumably through inhibition of alternative splicing by EWS-FLI1, thus promoting cell death in response to vincristine. Thus, a combination of vincristine and YK-4-279 might be therapeutically effective in ES patients.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Indóis/farmacologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteína Proto-Oncogênica c-fli-1/antagonistas & inibidores , Proteína EWS de Ligação a RNA/antagonistas & inibidores , Sarcoma de Ewing/tratamento farmacológico , Vincristina/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Ciclina B1/genética , Ciclina B1/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína EWS de Ligação a RNA/genética , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patologia , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo
14.
Meat Sci ; 113: 104-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26638021

RESUMO

The MYLPF gene encodes fast myosin regulatory light chain, and is a positional and functional candidate gene for meat quality. The aim of this study was to identify associations between SNPs in the promoter region of the porcine MYLPF gene and meat quality traits. A total of 22 SNPs were identified in a population of crossbred animals (n=86) and based on minor allele frequency and proximity to the transcription start site, five SNPs were genotyped in purebred; Large White (n=98), Duroc (n=99) and Pietrain (n=98) pigs. No associations were observed in the Pietrain breed, while the Duroc breed was almost monomorphic for all SNPs. In the Large White breed SNP g-1314A>G and linked SNPS g.-871T>G, g.-566T>C, g.-403C>G were associated with ultimate pH and driploss (P<0.05). This study identified associations between MYLPF and meat quality and highlights the importance of considering the genetic background within gene-assisted selection programmes.


Assuntos
Carne/normas , Cadeias Leves de Miosina/metabolismo , Polimorfismo de Nucleotídeo Único , Tecido Adiposo/fisiologia , Animais , Feminino , Regulação da Expressão Gênica , Masculino , Cadeias Leves de Miosina/genética , Regiões Promotoras Genéticas , Suínos/genética , Suínos/fisiologia
15.
Biochim Biophys Acta ; 427(1): 337-49, 1976 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-1260006

RESUMO

Careful investigation of the influence of palmitic and lauric acid on the interaction of progesterone and testosterone with several batches of untreated and defatted bovine and human serum albumins have revealed that, by contrast with published data for studies with progesterone as well as nonsteroid ligands, there is a surprising stimulation rather than inhibition of binding, albeit with a reduction of the apparent number of binding sites in almost all instances. Furthermore, fatty acid tends to minimize or eliminate the well-known differences in affinity between bovine and human albumin for interactions with these two steroids. The values for binding affinity in the interaction of testosterone with these batches of human serum albumin are significantly higher than those previously published by us and other authors and the value for progesterone-bovine albumin interaction is not in accordance with the "polarity rule". Studies of these same interactions by ultraviolet difference spectroscopy give further evidence of the augmentation in binding but, in the case of defatted bovine albumin only, the aromatic difference troughs are indicative of tyrosine perturbation whereas refatted bovine albumin, defatted and refatted human albumin manifest tryptophan perturbation. Quantitative correlation of perturbation with level of bound steroid suggests that fatty acid alters the ratio (possibly hydrogen-bonded to non hydrogen-bonded) of two forms of bound steroid. There is also further evidence that the binding sites for testosterone and progesterone are not identical.


Assuntos
Ácidos Láuricos , Ácidos Palmíticos , Progesterona , Soroalbumina Bovina , Albumina Sérica , Testosterona , Sítios de Ligação , Humanos , Cinética , Ligação Proteica , Conformação Proteica , Espectrofotometria Ultravioleta
16.
Biochim Biophys Acta ; 543(3): 364-72, 1978 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-708793

RESUMO

Further investigation of the effect of bound testosterone on the susceptibility of human serum albumin to tryptic hydrolysis has revealed a stimulation of hydrolysis at low binding levels, becoming an inhibition at higher binding levels. The inhibition, but not the stimulation, is associated with a two-stage steroid-induced proton release phenomenon which may involve the cysteine (SH) group and tyrosine residues. Proton release is also induced by Ca2+ and ethanol. The nature of the effect and the influence of Ca2+ suggests that stimulation of hydrolysis is associated with the presence of one molecule of testosterone and inhibition with the presence of 2-5 molecules at a set of sites which are thermodynamically equivalent.


Assuntos
Albumina Sérica/metabolismo , Testosterona/farmacologia , Cálcio/farmacologia , Relação Dose-Resposta a Droga , Etanol/farmacologia , Hidrólise , Prótons , Tripsina/metabolismo , Inibidores da Tripsina
17.
Biochim Biophys Acta ; 1248(1): 75-9, 1995 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-7711059

RESUMO

We used affinity chromatography on DnaK columns to identify a mitochondrial GrpE homologue from bovine, porcine and rat liver mitochondria. The 24 kDa GrpE homologue bound specifically to the DnaK column and was not eluted with 1 M KCl but readily with 5 mM ATP. Sequence analysis of the bovine homologue (85 residues) revealed 42% positional identity to mitochondrial GrpEp from S. cerevisiae and about 30% identity to the bacterial counterparts. Thus, GrpE homologues from higher and lower eukaryotes are highly conserved.


Assuntos
Proteínas Fúngicas/isolamento & purificação , Proteínas de Choque Térmico/isolamento & purificação , Proteínas de Membrana Transportadoras , Mitocôndrias Hepáticas/metabolismo , Proteínas de Saccharomyces cerevisiae , Sequência de Aminoácidos , Animais , Bovinos , Proteínas Fúngicas/química , Proteínas de Choque Térmico/química , Proteínas de Transporte da Membrana Mitocondrial , Chaperonas Moleculares , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
18.
Int Rev Cytol ; 174: 127-93, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9161007

RESUMO

Molecular chaperones play a critical role in many cellular processes. This review concentrates on their role in targeting of proteins to the mitochondria and the subsequent folding of the imported protein. It also reviews the role of molecular chaperons in protein degradation, a process that not only regulates the turnover of proteins but also eliminates proteins that have folded incorrectly or have aggregated as a result of cell stress. Finally, the role of molecular chaperones, in particular to mitochondrial chaperonins, in disease is reviewed. In support of the endosymbiont theory on the origin of mitochondria, the chaperones of the mitochondrial compartment show a high degree of similarity to bacterial molecular chaperones. Thus, studies of protein folding in bacteria such as Escherichia coli have proved to be instructive in understanding the process in the eukaryotic cell. As in bacteria, the molecular chaperone genes of eukaryotes are activated by a variety of stresses. The regulation of stress genes involved in mitochondrial chaperone function is reviewed and major unsolved questions regarding the regulation, function, and involvement in disease of the molecular chaperones are identified.


Assuntos
Mitocôndrias/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas/metabolismo , Animais , Autoimunidade , Transporte Biológico Ativo , Citosol/metabolismo , Doença/etiologia , Escherichia coli/metabolismo , Feminino , Humanos , Membranas Intracelulares/metabolismo , Modelos Biológicos , Chaperonas Moleculares/genética , Chaperonas Moleculares/imunologia , Gravidez , Dobramento de Proteína , Proteínas/química , Ribossomos/metabolismo , Estresse Fisiológico/metabolismo
19.
Br J Biomed Sci ; 62(1): 9-14, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15816205

RESUMO

An electronic presentation of materials for a distance-learning immunology and pathology module from a postgraduate biomedical science course is evaluated. Two different electronic presentation formats for the delivery of the educational material to distance learners are assessed. Responses from users of this material highlighted a preference for a format that has a design tailored to distance learning. There was no significant difference in learning outcome between those taking the module on campus and by distance learning. This suggests that the prerequisites for entry, learning materials and direction given to the students studying by distance learning are adequate for these students to achieve the learning objectives outlined in the course. The evaluation also gave direction for areas within the (CAL) application that can be improved for future students.


Assuntos
Alergia e Imunologia/educação , Educação de Pós-Graduação em Medicina/normas , Patologia/educação , Atitude do Pessoal de Saúde , Instrução por Computador/métodos , Humanos , Aprendizagem
20.
Meat Sci ; 100: 32-40, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25306509

RESUMO

This study examines associations between SNPs in the promoter region of the fatty acid binding protein 3 (FABP3) gene and fatness traits in pure bred Large White (n=98), Duroc (n=99) and Pietrain (n=98) populations. In the Large White breed, SNP g.-634 C>A was associated a 27% increase in IMF (%) in the heterozygote (CA) and a 38% increase in the homozygote (CC) relative to the (AA) genotype in the M. semimembranosus (SM) muscle (P=0.02). While the associations observed in this breed were suggestive of significance in both the SM and in the M. longissimus thoracis et lumborum (LTL) (P=0.08), these associations no longer attained significance at thresholds adjusted for multiple testing. In conclusion, SNPs in the FABP3 promoter may contribute to IMF without influencing carcass fatness traits in pigs, however further confirmation of these associations in larger independent populations would be essential before their incorporation into breeding programmes.


Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/genética , Proteínas de Ligação a Ácido Graxo/genética , Genótipo , Carne/análise , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Animais , Cruzamento , Proteína 3 Ligante de Ácido Graxo , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Heterozigoto , Homozigoto , Humanos , Músculo Esquelético/metabolismo , Fenótipo , Suínos/genética
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