Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice

High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases.     

In Vitro Anticancer Potential of Jasione montana and Its Main Components against Human Amelanotic Melanoma Cells

Jasione montana L. (Campanulaceae) is used in traditional Belarusian herbal medicine for sleep disorders in children, but the chemical composition and biological activity have not been investigated. In this study, the activities of J. montana extracts, their fractions and main compounds were evaluated in amelanotic melanoma C32 (CRL-1585) cells and normal fibroblasts (PCS-201-012). The extracts and fractions were analyzed using liquid chromatography–photodiode array detection–electrospray ionization–mass spectrometry (LC–PDA–ESI–MS/TOF) to characterize 25 compounds. Further, three major and known constituents, luteolin (22) and its derivatives such as 7-O-glucoside (12) and 7-O-sambubioside (9) were isolated and identified. The cytotoxic activities against fibroblasts and the amelanotic melanoma cell line were determined using the fixable viability stain (FVS) assay. The influence of diethyl ether (Et₂O) fraction (JM4) and 22 on apoptosis induction was investigated using an annexin V binding assay. The obtained results showed significant cytotoxicity of JM4 and 22 with IC₅₀ values of 119.7 ± 3.2 and 95.1 ± 7.2 μg/mL, respectively. The proapoptotic potential after 22 treatment in the C32 human amelanotic melanoma cell line was comparable to that of vinblastine sulfate (VLB), detecting 29.2 ± 3.0% apoptotic cells. Moreover, 22 displayed less necrotic potential against melanoma cells than VLB. In addition, the influences of JM4 and 22 on the dysfunction of the mitochondrial membrane potential (MMP), cell cycle and activity of caspases 3, 8, 9, and 10 were established. The effects of JM4 on MMP change (74.5 ± 3.0% of the cells showed a reduced MMP) corresponded to the results obtained from the annexin V binding assay and activation of caspase-9. JM4 and 22 displayed a significant impact on caspase-9 (40.9 ± 2.4% of the cells contained active caspase-9 after JM4 treatment and 16.6 ± 0.8% after incubation with 22) and the intrinsic (mitochondrial) apoptotic pathway. Moreover, studies have shown that JM4 and 22 affect the activation of external apoptosis pathways by inducing the caspase-8 and caspase-10 cascades. Thus, activation of caspase-3 and DNA damage via external and internal apoptotic pathways were observed after treatment with JM4 and 22. The obtained results suggest that J. montana extracts could be developed as new topical preparations with potential anticancer properties due to their promising cytotoxic and proapoptotic potential.     

Geometrical setting for the classification of multilayers

We elaborate on the consequences of the factorization of the transfer matrix of any lossless multilayer in terms of three basic matrices of simple interpretation. By considering the bilinear transformation that this transfer matrix induces in the complex plane, we introduce the concept of multilayer transfer function and study its properties in the unit disk. In this geometrical setting, our factorization translates into three actions that can be viewed as the basic components for understanding the multilayer behavior. Additionally, we introduce a simple trace criterion that allows us to classify multilayers into three types with properties closely related to one (and only one) of these three basic matrices. We apply this approach to analyze some practical examples that are typical of these types of matrices.     

The organization of visual corticocortical connections in early postnatal kittens

We tested the hypothesis that, in newborn kittens, superficial layers of the extrastriate cortex receive more specific patterns of corticocortical innervation from the striate cortex than deep layers. First, we injected retrogradely transported tract-tracers at a range of depths in area 18 to label area 17. All injections were of similar tangential diameter and were in the same region of rostral area 18, where the visual field 10-20 degrees below the horizontal meridian is represented. Injections that involved only the superficial layers of area 18 labelled cells mainly in the superficial layers (future layers 2-4) of area 17, across a region that was 2-3 mm wider than the diameter of the injection site in the rostrocaudal direction. Injections that involved all layers of area 18 labelled cells in both superficial and deep layers (5 and 6) of area 17, across a region that was 6-9 mm wider than the diameter of the injection site in the rostrocaudal direction. These values demonstrate that, in neonates, the convergence of projections from area 17 to the superficial layers of area 18 is less than that to the deep layers of area 18. The lower values for convergence obtained by injecting only the superficial layers of area 18 in kittens were similar to those obtained by injecting all layers of area 18 in adult cats; the values obtained by injecting all layers of area 18 in kittens were much higher. Second, we injected the full depth of area 17 in newborn kittens with labels that travel anterogradely and retrogradely. Confirming the conclusions from the use of retrograde tracers, these focal injections produced very widespread labelling of the deep layers of area 18, but much more localized and topographically organized labelling of its superficial layers. These results indicate that there is a considerable postnatal improvement in the accuracy with which corticocortical cells in striate visual cortex target appropriate regions in extrastriate cortex, in agreement with previous findings. They also demonstrate that this change occurs mainly among those striate cortical neurons that innervate a wide region of the deep layers of extrastriate cortex at birth. The innervation of the superficial layers of extrastriate cortex is much more accurate from the outset.     

Preparation of smallest microparticles of poly-D,L-lactide by modified precipitation method: influence of the process parameters

Biodegradable microspheres such as those made of poly-D,L-lactide (PDLLA) are widely investigated delivery systems for drugs or antigens. The aim of this study was to examine experimental conditions in order to produce PDLLA microspheres with the best properties for controlled and sustained drug delivery by the modified precipitation method. For this purpose, the following parameters were varied: co-solvent (methanol or ethanol), the concentration of stabilizer polyvinyl alcohol (PVA), chloroform-to-water ratio and the speed and time of homogenization. Scanning electron microscopy (SEM) and stereological analysis were used to characterize the particles. The average size and morphology of the microspheres varied substantially with preparation conditions from 8.44-1.25 microm. Results showed that the smallest particles were obtained with methanol, 1% PVA and with 10 min of homogenization at 21,000 rpm.     

Comparison procedure of predicting the time to default in behavioural scoring

The paper deals with the problem of predicting the time to default in credit behavioural scoring. This area opens a possibility of including a dynamic component in behavioural scoring modelling which enables making decisions related to limit, collection and recovery strategies, retention and attrition, as well as providing an insight into the profitability, pricing or term structure of the loan. In this paper, we compare survival analysis and neural networks in terms of modelling and results. The neural network architecture is designed such that its output is comparable to the survival analysis output. Six neural network models were created, one for each period of default. A radial basis neural network algorithm was used to test all six models. The survival model used a Cox modelling procedure. Further, different performance measures of all models were discussed since even in highly accurate scoring models, misclassification patterns appear. A systematic comparison ‘3 + 2 + 2’ procedure is suggested to find the most effective model for a bank. Additionally, the survival analysis model is compared to neural network models according to the relative importance of different variables in predicting the time to default. Although different models can have very similar performance measures they may consist of different variables. The dataset used for the research was collected from a Croatian bank and credit customers were observed during a 12-month period. The paper emphasizes the importance of conducting a detailed comparison procedure while selecting the best model that satisfies the users’ interest.     

电源管理半导体上半年出现短缺销售不断上升,供应商疲于满足需求

据iSuppli公司,2010年上半年电源管理半导体销售收入强劲上升,出乎供应商意料,可能导致近期价格上涨.2010年第一季度,电源管理半导体销售收入达到69亿美元,比2009年第四季度的67亿美元增长2.9%.该市场在2009年第三季度曾陷入停滞,第四季度开始扩张,第一季度数据显示该市场仍在扩张.     

Protein Corona: Impact of Lymph Versus Blood in a Complex In Vitro Environment

In biological environments, the surface of nanoparticles (NPs) are modified by protein corona (PC) that determines their biological behavior. Unfortunately, in vitro tests still give different PC than in vivo tests causing in vitro–in vivo discrepancy; hence, in vitro studies are not indicative for the NPs' behavior in vivo. Here is demonstrated that PC in vitro is strongly influenced by the type of extracellular fluid (ECF), blood or lymph, by their high and low flow conditions and transitions between ECFs, and a combination of these parameters. As a result, this in vitro study approaches fluidic and dynamic variations to which NPs are exposed in vivo: different ECF that NPs encounter first in different injection routes, different transitions in‐between ECFs during circulation, and simultaneous change in the exposed flow in these transitions. The most‐abundant proteins in PCs are found to be not the most abundant in ECFs, but those having high affinity for binding to the surface of NPs. Moreover, some proteins are differently abundant in PCs at different flows, which indicate force‐promoted binding, catch bonds. These results suggest that future in vitro studies should consider more complex incubation conditions to improve the in vitro–in vivo consistency necessary for translational research.