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41.
Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction
Hohmann JG Teal TH Clifton DK Davis J Hruby VJ Han G Steiner RA 《American journal of physiology. Regulatory, integrative and comparative physiology》2000,278(1):R50-R59
Leptin serves as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to act through melanocortinergic pathways in the brain to regulate ingestive behaviors; however, whether melanocortins mediate leptin's actions on the neuroendocrine-reproductive axis is unknown. We tested this hypothesis first by determining whether the effects of leptin on feeding behavior and reproduction in the ob/ob mouse could be blocked by the melanocortin receptor (MC-R) antagonist SHU9119 and second, by examining the effects of the MC-R agonist MTII on feeding and the endocrine-reproductive system. Administered by intracerebroventricular injections, leptin inhibited food intake, raised plasma gonadotropin levels, and increased seminal vesicle weights compared with controls; SHU9119 (intracerebroventricularly) attenuated leptin's effects on food intake and body weight but did not alter leptin's stimulatory effect on the reproductive axis. MTII (intracerebroventricularly and intraperitoneally) decreased food intake and increased body temperature compared with controls but had no effect on the reproductive-endocrine axis. These results suggest that although leptin acts centrally through melanocortinergic pathways to inhibit ingestive behaviors and stimulate metabolism, leptin's activational effect on the reproductive axis is likely to be mediated by other, unknown neuroendocrine circuits. 相似文献
42.
Shimada Y Nishimura M Kakinuma S Okumoto M Shiroishi T Clifton KH Wakana S 《Radiation research》2000,154(3):293-300
Although information on the molecular pathways in radiation carcinogenesis is accumulating, the data are still relatively scanty. To find the tumor suppressor locus associated with radiation carcinogenesis, we determined the frequency and distribution of loss of heterozygosity (LOH) of X-ray-induced thymic lymphomas of B6C3F(1) mice using 58 microsatellite markers and compared the results with those for spontaneous lymphomas and N-ethylnitrosourea (ENU)-induced lymphomas. Based on the results, we describe a unique locus with frequent LOH in the centromeric region of chromosome 11 of X-ray-induced lymphomas. This locus has never been observed to be altered similarly in either ENU-induced or spontaneous lymphomas, suggesting radiation-specific molecular alteration. The LOH patterns of individual thymic lymphomas indicated that the common region of LOH was located within 1.6 cM between D11Mit62 and D11Mit204, a region syntenic to human chromosome 7p13. Linkage analysis revealed that the markers of the common LOH region were genetically linked to Ikaros (now known as Znfn1a1), a master gene of lymphopoiesis. Although the presence of radiation-associated LOH in other loci cannot be ruled out, these results suggest a novel molecular pathway in induction of thymic lymphomas by ionizing radiation. 相似文献
43.
44.
Assessing FOXO1A as a potential susceptibility locus for type 2 diabetes and obesity in American Indians
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45.
Susan J. Bartlett Ana-Maria Orbai Trisha Duncan Elaine DeLeon Victoria Ruffing Katherine Clegg-Smith Clifton O. Bingham III 《PloS one》2015,10(9)
Purpose
To evaluate the reliability and validity of 11 PROMIS measures to assess symptoms and impacts identified as important by people with rheumatoid arthritis (RA).Methods
Consecutive patients (N = 177) in an observational study completed PROMIS computer adapted tests (CATs) and a short form (SF) assessing pain, fatigue, physical function, mood, sleep, and participation. We assessed test-test reliability and internal consistency using correlation and Cronbach’s alpha. We assessed convergent validity by examining Pearson correlations between PROMIS measures and existing measures of similar domains and known groups validity by comparing scores across disease activity levels using ANOVA.Results
Participants were mostly female (82%) and white (83%) with mean (SD) age of 56 (13) years; 24% had ≤ high school, 29% had RA ≤ 5 years with 13% ≤ 2 years, and 22% were disabled. PROMIS Physical Function, Pain Interference and Fatigue instruments correlated moderately to strongly (rho’s ≥ 0.68) with corresponding PROs. Test-retest reliability ranged from .725–.883, and Cronbach’s alpha from .906–.991. A dose-response relationship with disease activity was evident in Physical Function with similar trends in other scales except Anger.Conclusions
These data provide preliminary evidence of reliability and construct validity of PROMIS CATs to assess RA symptoms and impacts, and feasibility of use in clinical care. PROMIS instruments captured the experiences of RA patients across the broad continuum of RA symptoms and function, especially at low disease activity levels. Future research is needed to evaluate performance in relevant subgroups, assess responsiveness and identify clinically meaningful changes. 相似文献46.
Hye-Kyeong Kim Mary Anne Della-Fera Dorothy B. Hausman Clifton A. Baile 《Journal of physiology and biochemistry》2010,66(3):197-203
Clenbuterol, a beta2-adrenergic receptor (β2-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice.
We hypothesized that direct actions of a β-adrenergic receptor agonist on adipocytes could trigger the observed apoptotic
effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis, adipogenesis, and lipolysis
in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with 10−9 to 10−5 M clenbuterol depending on the experiments. There was no apoptotic effect of clenbuterol both in 3T3-L1 cells and rat primary
adipocytes. Adipogenesis monitored by Oil Red O staining and AdipoRed™ assay was modestly decreased by clenbuterol treatment
(p < 0.05). In fully differentiated primary adipocytes, clenbuterol increased basal lipolysis compared with the control (p < 0.01). In summary, direct stimulation of β2-AR by clenbuterol does not cause apoptosis in adipocytes, despite a direct lipolytic stimulation and attenuation of adipogenesis. 相似文献
47.
Garret Suen Jarrod J. Scott Frank O. Aylward Sandra M. Adams Susannah G. Tringe Adrián A. Pinto-Tomás Clifton E. Foster Markus Pauly Paul J. Weimer Kerrie W. Barry Lynne A. Goodwin Pascal Bouffard Lewyn Li Jolene Osterberger Timothy T. Harkins Steven C. Slater Timothy J. Donohue Cameron R. Currie 《PLoS genetics》2010,6(9)
Herbivores can gain indirect access to recalcitrant carbon present in plant cell walls through symbiotic associations with lignocellulolytic microbes. A paradigmatic example is the leaf-cutter ant (Tribe: Attini), which uses fresh leaves to cultivate a fungus for food in specialized gardens. Using a combination of sugar composition analyses, metagenomics, and whole-genome sequencing, we reveal that the fungus garden microbiome of leaf-cutter ants is composed of a diverse community of bacteria with high plant biomass-degrading capacity. Comparison of this microbiome''s predicted carbohydrate-degrading enzyme profile with other metagenomes shows closest similarity to the bovine rumen, indicating evolutionary convergence of plant biomass degrading potential between two important herbivorous animals. Genomic and physiological characterization of two dominant bacteria in the fungus garden microbiome provides evidence of their capacity to degrade cellulose. Given the recent interest in cellulosic biofuels, understanding how large-scale and rapid plant biomass degradation occurs in a highly evolved insect herbivore is of particular relevance for bioenergy. 相似文献
48.
Bhaskar Kahali Jee‐Eun Kim Umesh Karandikar Clifton P. Bishop Ashok P. Bidwai 《Genesis (New York, N.Y. : 2000)》2010,48(1):44-55
Analysis of the retinal defects of a CK2 phosphomimetic variant of E(spl)M8 (M8S159D) and the truncated protein M8* encoded by the E(spl)D allele, suggest that the nonphosphorylated CtD “autoinhibits” repression. We have investigated this model by testing for inhibition (in “trans”) by the CtD fragment in its nonphosphorylated (M8‐CtD) and phosphomimetic (M8SD‐CtD) states. In N+ flies, ectopic M8‐CtD compromises lateral inhibition, i.e., elicits supernumerary bristles as with loss of N signaling. This antimorphic activity of M8‐CtD strongly rescues the reduced eye and/or bristle loss phenotypes that are elicited by ectopic M8SD or wild type M8. Additionally, the severely reduced eye of Nspl/Y; E(spl)D/+ flies is also rescued by M8‐CtD. Rescue is specific to the time and place, the morphogenetic furrow, where “founding” R8 photoreceptors are specified. In contrast, the phosphomimetic M8SD‐CtD that is predicted to be deficient for autoinhibition, exhibits significantly attenuated or negligible activity. These studies provide evidence that autoinhibition by the CtD regulates M8 activity in a phosphorylation‐dependent manner. genesis 48:44–55, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
49.
Bone is a composite composed mainly of organics, minerals, and water. Many researchers have studied effects such as crack velocity, density, orientation, storage media, porosity, and age on the fracture toughness (K(C), also called critical stress intensity factor) of compact bone. Most of these studies were conducted at room temperature. Considering that the body temperature of animals is greater than room temperature, and that bone has a large volumetric percentage of organics and water (generally, 55-65%), it is hypothesized that temperature has a significant effect on the fracture toughness of compact bone. Single-edge V-notched (SEVN) specimens were prepared to measure the fracture toughness of bovine femur and manatee rib in water at 0, 10, 23, 37, and 50 degrees C in four-point flexure. The fracture toughness values of bovine femur and manatee rib were found to decrease from 7.0 to 4.3MPam(1/2) and from 5.5 to 4.0MPam(1/2), respectively, as temperature increased over a temperature range of 50 degrees C. The results support the hypothesis that temperature has a significant effect on the fracture toughness of compact bone. Therefore, we suggest that study on fracture toughness of bone should be done at physiologically relevant temperatures. 相似文献
50.
Rayalam S Della-Fera MA Ambati S Boyan B Baile CA 《Biochemical and biophysical research communications》2007,364(3):450-456
Guggulsterone (GS) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] have been shown to influence adipogenesis in 3T3-L1 cells. We investigated the ability of GS and 1,25(OH)2D3, alone and in combination to inhibit adipogenesis and induce apoptosis in 3T3-L1 adipocytes. Maturing preadipocytes were treated with 1,25(OH)2D3 in combination with GS for 6 days during differentiation. GS and 1,25(OH)2D3 each inhibited lipid accumulation, but the combination potentiated the inhibition of lipid accumulation. Apoptosis was increased by 1,25(OH)2D3 while GS had no effect, but GS + 1,25(OH)2D3 increased apoptosis more than either compound alone. Furthermore, GS + 1,25(OH)2D3 caused a potentiated decrease in the expression of aP2 and farnesoid X receptor expression more than either compound alone. In addition, 1,25(OH)2D3 increased vitamin D receptor expression after 6 days, while GS had no effect. GS + 1,25(OH)2D3, however, caused a potentiated increase in the expression of VDR. These findings show that GS potentiates 1,25(OH)2D3’s anti-adipogenic and pro-apoptotic effects in maturing 3T3-L1 preadipocytes. 相似文献