Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.     

琼东南盆地深水区储层分布规律

琼东南盆地深水区经历了断陷、断拗和拗陷3大构造演化和沉积充填阶段,主要发育4种沉积体系,相应地形成了4类主要储层:1)陵三段扇三角洲或滨海相砂岩储层;2)三亚、梅山组滨浅海相砂岩储层;3)三亚—莺黄组低位体储层;4)梅山组台地边缘礁滩灰岩储层。平面上,储层发育具有明显的分带性,可划分为:北部浅水陆架滨岸砂岩、三角洲砂岩储层发育带;中央坳陷低位体储层发育带;南部永乐隆起区碳酸盐岩储层发育带。深水区主要位于后2个带,每个带储层发育的控制因素不同,可以进一步划分为多个储层发育区。每个储层发育区存在多套储盖组合,每套储盖组合在多个储层区中发育。其中台地灰岩储层可能成为南部隆起区具有重要意义的勘探层系。      

Convolutional solutions of partial difference equations

A significant part of the theory of one-dimensional linear shift-invariant systems is based on the concept of weighting function (or impulse response): the output is the convolution of the weighting function with the input. This paper introduces the concept of linear translation-invariant systems and uses this notion in studying impulse response, z-transforms, and transfer functions for multidimensional systems.     

Effect of Forming Pressure on the Internal Structure of Alumina Green Bodies Examined with Immersion Liquid Technique

Green bodies prepared by compaction of alumina granules were made transparent by an immersion liquid technique, and the internal structure was characterized with an optical microscope to study the effect of forming pressure on the internal structure. Clear images obtained by the technique provide more detailed information than other existing methods for structures ranging from one to tens of micrometers. Intergranular pores were present between unfractured granules. Their sizes and concentration tended to decrease with increasing forming pressure. However, pores were clearly present even in the green body prepared at 600 MPa. A rod- and needlelike feature was also found and was concluded to correspond to a high-density region. The significance of large pores and high-density regions on processing as well as the details of the technique is discussed.     

Purification and renaturation of recombinant human lymphotoxin (tumour necrosis factor beta) expressed in Escherichia coli as inclusion bodies

High level expression of recombinant human tumour necrosis factor β (rh TNF-β) in Escherichia coli results in the formation of two portions of protein, namely soluble active protein and insoluble protein which is inactive and aggregates in the form of inclusion bodies (IBs). In this study, a procedure for purification and renaturation of rh TNF-β from inclusion bodies has been designed and verified experimentally with a product purity of more than 90% and a recovery of about 30%. The procedure includes washing of IBs with specific wash buffer (Triton X-100/EDTA/lysozyme/PMSF), their solubilization with 8 mol dm^?3 alkaline urea, purification with ion-exchange columns, refolding with renaturation buffer and finally concentration and desalination with an ultrafiltration membrane. The characteristics of the renatured protein were identical with those of purified protein from the soluble fraction as demonstrated by (1) SDS-PAGE, (2) cytotoxic activity on mouse L929 cells, (3) N-terminal amino acid sequence, and (4) gel filtration chromatography.     

Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: Externalizing and internalizing subtypes.

This study used the Multidimensional Personality Questionnaire (MPQ; A. Tellegen, in press) to identify personality-based subtypes of posttraumatic response. Cluster analyses of MPQs completed by combat veterans revealed subgroups that differed on measures relating to the externalization versus internalization of distress. The MPQ profile of the externalizing cluster was defined by low Constraint and Harmavoidance coupled with high Alienation and Aggression. Individuals in this cluster also had histories of delinquency and high rates of substance-related disorder. In comparison, the MPQ profile of the internalizing cluster was characterized by lower Positive Emotionality, Alienation, and Aggression and higher Constraint, and individuals in this cluster showed high rates of depressive disorder. These findings suggest that dispositions toward externalizing versus internalizing psychopathology may account for heterogeneity in the expression of posttraumatic responses, including patterns of comorbidity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic Architecture and Molecular,Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art,Opportunities and Challenges

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.     

Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples

The metabolic ratios lactate/pyruvate and β-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of the four metabolites in plasma and liver tissue. The procedure included an o-phenylenediamine microwave-assisted derivatization, followed by liquid-liquid extraction with ethyl acetate and silylation with bis(trimethylsilyl)trifluoroacetamide:trimethylchlorosilane 99:1. The calibration curves presented acceptable linearity, with a limit of quantification of 0.001 mM for pyruvate, β-hydroxybutyrate and acetoacetate and of 0.01 mM for lactate. The intra-day and inter-day accuracy and precision were within the European Medicines Agency’s Guideline specifications. No significant differences were observed in the slope coefficient of three-point standard metabolite-spiked curves in plasma or liver and water, and acceptable recoveries were obtained in the metabolite-spiked samples. Applicability of the method was tested in precision-cut liver rat slices and also in HepG2 cells incubated under different experimental conditions challenging the redox state. In conclusion, the validated method presented good sensitivity, specificity and reproducibility in the quantification of lactate/pyruvate and β-hydroxybutyrate/acetate metabolites and may be useful in the evaluation of in vivo redox states.     

液压气动缸筒用高精度冷拔钢管生产的回顾与展望

介绍了近年来我国液压气动缸筒用高精度冷拔钢管生产的进展及其现状，分析了影响产品尺寸精度的因素，提出了改进措施，指出了发展方向。