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1.

Background  

Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells.  相似文献   
2.
    

Purpose

This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes.

Methods

Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration.

Results

Blood glucose concentration at different times was found to vary significantly within (p<0.0005) and between groups (p<0.0005). However, the refractive error components and ocular aberrations were not found to alter significantly over the day in either the diabetic patients or the control subjects (p>0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects.

Conclusion

This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients.  相似文献   
3.
This study examined the sexual behavior-ovarian activity relationship of the laboratory cat maintained under consistent environmental conditions. Mean (±SEM) lengths of estrus for nonovulating, mated ovulating, and human chorionic gonadotrophin (HCG)-induced ovulating queens were 5.8 ± 0.17, 6.5 ± 0.75, and 10.0 ± 0.65 days, respectively. The duration of estrus was significantly (P < 0.01) longer in HCG-treated queens in comparison to the nonovulating or mated ovulating groups. No differences were observed in the number of behavioral estrous periods detected monthly. Duration of estrus was affected by season with significantly shorter periods of estrus observed in June (P < 0.05), September (P < 0.05), October (P < 0.05), and November (P < 0.01) compared to the March, April, May, August, or December averages. Length of estrous cycle (from Day 1 of estrus to Day 1 of next estrus) was variable (range: 6–120 days); however, 49.8% of the estrous cycles were 12 to 21 days in length. Although the ovaries of queens displaying sexual receptivity always contained developing or mature foilicles, ovaries of cats showing no estrous behavior also showed patterns of follicular development and regression at 14- to 19-day intervals. These results suggest that the estrous cycle of the laboratory maintained cat varies from 2 to 3 weeks in duration and that reproductive behavioral patterns alone are not always an accurate indication of ovarian activity or duration of the reproductive cycle.  相似文献   
4.
    
Oxysterol‐binding protein (OSBP) localizes to endoplasmic reticulum (ER)‐Golgi contact sites where it transports cholesterol and phosphatidylinositol 4‐phosphate (PI‐4P), and activates lipid transport and biosynthetic activities. The PI‐4P phosphatase Sac1 cycles between the ER and Golgi apparatus where it potentially regulates OSBP activity. Here we examined whether the ER‐Golgi distribution of endogenous or ectopically expressed Sac1 influences OSBP activity. OSBP and Sac1 co‐localized at apparent ER‐Golgi contact sites in response to 25‐hydroxycholesterol (25OH), cholesterol depletion and p38 MAPK inhibitors. A Sac1 mutant that is unable to exit the ER did not localize with OSBP, suggesting that sterol perturbations cause Sac1 transport to the Golgi apparatus. Ectopic expression of Sac1 in the ER or Golgi apparatus, or Sac1 silencing, did not affect OSBP localization to ER‐Golgi contact sites, OSBP‐dependent activation of sphingomyelin synthesis, or cholesterol esterification in the ER. p38 MAPK inhibition and retention of Sac1 in the Golgi apparatus also caused OSBP phosphorylation and OSBP‐dependent activation of sphingomyelin synthesis at ER‐Golgi contacts. These results demonstrate that Sac1 expression in either the ER or Golgi apparatus has a minimal impact on the PI‐4P that regulates OSBP activity or recruitment to contact sites.   相似文献   
5.
    
The most carbon (C)‐dense ecosystems of Amazonia are areas characterized by the presence of peatlands. However, Amazonian peatland ecosystems are poorly understood and are threatened by human activities. Here, we present an investigation into long‐term ecohydrological controls on C accumulation in an Amazonian peat dome. This site is the oldest peatland yet discovered in Amazonia (peat initiation ca. 8.9 ka BP), and developed in three stages: (i) peat initiated in an abandoned river channel with open water and aquatic plants; (ii) inundated forest swamp; and (iii) raised peat dome (since ca. 3.9 ka BP). Local burning occurred at least three times in the past 4,500 years. Two phases of particularly rapid C accumulation (ca. 6.6–6.1 and ca. 4.9–3.9 ka BP), potentially resulting from increased net primary productivity, were seemingly driven by drier conditions associated with widespread drought events. The association of drought phases with major ecosystem state shifts (open water wetland–forest swamp–peat dome) suggests a potential climatic control on the developmental trajectory of this tropical peatland. A third drought phase centred on ca. 1.8–1.1 ka BP led to markedly reduced C accumulation and potentially a hiatus during the peat dome stage. Our results suggest that future droughts may lead to phases of rapid C accumulation in some inundated tropical peat swamps, although this can lead ultimately to a shift to ombrotrophy and a subsequent return to slower C accumulation. Conversely, in ombrotrophic peat domes, droughts may lead to reduced C accumulation or even net loss of peat. Increased surface wetness at our site in recent decades may reflect a shift towards a wetter climate in western Amazonia. Amazonian peatlands represent important carbon stores and habitats, and are important archives of past climatic and ecological information. They should form key foci for conservation efforts.  相似文献   
6.
7.
    
The salinisation of many coastal ecosystems is underway and is expected to continue into the future because of sea-level rise and storm intensification brought about by the changing climate. However, the response of soil microbes to increasing salinity conditions within coastal environments is poorly understood, despite their importance for nutrient cascading, carbon sequestration and wider ecosystem functioning. Here, we demonstrate deterioration in the productivity of a top-tier microbial group (testate amoebae) with increasing coastal salinity, which we show to be consistent across phylogenetic groups, salinity gradients, environment types and latitude. Our results show that microbial changes occur in the very early stages of marine inundation, presaging more radical changes in soil and ecosystem function and providing an early warning of coastal salinisation that could be used to improve coastal planning and adaptation.  相似文献   
8.
The major polypeptides of visna viruses and other lentiviruses have been isolated and shown to be closely related if not identical in radioimmunoassays. By this criterion the lentiviruses form a distinct group of retroviruses unrelated to spuma viruses, mammalian and avian retroviruses that cause tumors, and unclassified retroviruses of cattle and horses. Two sera obtained from goats immunized with Mason-Pfizer monkey virus or squirrel monkey virus reacted with visna p30. Additional data suggest that this reaction represents infection of goats with a lentivirus or a new retrovirus closely related to the lentiviruses.  相似文献   
9.
    
A series of aryl carboxamide and benzylamino dispiro 1,2,4,5-tetraoxane analogues have been designed and synthesized in a short synthetic sequence from readily available starting materials. From this series of endoperoxides, molecules with in vitro IC50s versus Plasmodium falciparum (3D7) as low as 0.84?nM were identified. Based on an assessment of blood stability and in vitro microsomal stability, N205 (10a) was selected for rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models. The results indicate that the 4-benzylamino derivatives have excellent profiles with a representative of this series, N205, an excellent starting point for further lead optimization studies.  相似文献   
10.
Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. Amino amide trioxolanes had the best combination of antimalarial and biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts.  相似文献   
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