N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease

N-acetyl-aspartyl-glutamate (NAAG) is the most abundant dipeptide in the brain, where it acts as a neuromodulator of glutamatergic synapses by activating presynaptic metabotropic glutamate receptor 3 (mGluR3). Recent data suggest that NAAG is selectively localized to postsynaptic dendrites in glutamatergic synapses and that it works as a retrograde neurotransmitter. NAAG is released in response to glutamate and provides the postsynaptic neuron with a feedback mechanisms to inhibit excessive glutamate signaling. A key regulator of synaptically available NAAG is rapid degradation by the extracellular enzyme glutamate carboxypeptidase II (GCPII). Increasing endogenous NAAG—for instance by inhibiting GCPII—is a promising treatment option for many brain disorders where glutamatergic excitotoxicity plays a role. The main effect of NAAG occurs through increased mGluR3 activation and thereby reduced glutamate release. In the present review, we summarize the transmitter role of NAAG and discuss the involvement of NAAG in normal brain physiology. We further present the suggested roles of NAAG in various neurological and psychiatric diseases and discuss the therapeutic potential of strategies aiming to enhance NAAG levels.     

食用核苷酸

<正> 以前,人们认为核苷酸并非人体所需的营养物质。人们普遍认为生物,包括人类在内,有能力在体内合成对于正常生长和发育所需的核苷酸。如今这个观点发生了改变。有证据表明食用核苷酸对人体起着至关重要的作用。核苷酸是一种低分子量的生物化合物,它几乎在所有的生化反应中部起着非常重要的作用。核苷酸由嘌呤或嘧啶(一种含氮碱基)组成。它们是组成脱氧核糖核酸和核糖核酸的基本物质,在细胞运动和新陈代谢过程中起着很多重要的作用,尤其在许多辅酶中它们也是ATP和其它核苷三磷酸的组成成分。     

Editorial

Though the British and Dutch approaches to disability in the construction sector exhibit common features, Britain tends towards a capabilities model compared with the Netherlands which is closer to a social model. The construction sector is considerably more regulated in the Netherlands but is in both countries highly disabling and exclusive. Sector‐specific disabling and enabling factors and policy measures were investigated in the two countries with a view to identifying which policies might facilitate labour market participation. The investigation was based on interviews using similar questionnaires with key stakeholders, firms and disabled employees and a focus group. Policy in each country addresses the nature of exclusion in different ways. The conclusion drawn is that a sector‐specific approach is needed if disability policy in Britain is to be more in tune with the social model—as apparent from the comparison with the Netherlands.     

Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy

Objective: In recent years, high-resolution magic angle spinning (HR MAS) has provided the opportunity to explore detailed biochemical composition of intact tissue. Previous studies of intact cervical biopsies with high-resolution magnetic resonance spectroscopy (MRS) have correlated well with histopathology. Lactate level in cervical cancer tissue has been found to correlate to metastatic spread. The purpose of this study was to explore the potential of the HR MAS technique as a tool for chemical characterization of cervical cancer tissue. Materials and methods: Tissue samples from the cervix were collected after hysterectomy from patients with cervical cancer (n=8) and patients with nonmalignant disease (n=8). The tissue specimens were analyzed using HR MAS MR spectroscopy combined with principal component analysis (PCA). Results: The resulting spectra showed resolution comparable with high-resolution MR spectra of extracts. Multivariate analysis confirmed that MAS spectra classified according to patient diagnosis. Conclusion: Malignant tissue of the cervix differed from nonmalignant tissue with regard to higher levels of cholines and amino acid residues and lower levels of glucose.     

Production of an Active,Human Membrane Protein in Saccharomyces cerevisiae: Full-Length FICD

The human Fic domain-containing protein (FICD) is a type II endoplasmic reticulum (ER) membrane protein that is important for the maintenance of ER proteostasis. Structural and in vitro biochemical characterisation of FICD AMPylase and deAMPylase activity have been restricted to the soluble ER-luminal domain produced in Escherichia coli. Information about potentially important features, such as structural motifs, modulator binding sites or other regulatory elements, is therefore missing for the approximately 100 N-terminal residues including the transmembrane region of FICD. Expressing and purifying the required quantity and quality of membrane proteins is demanding because of the low yields and poor stability often observed. Here, we produce full-length FICD by combining a Saccharomyces cerevisiae-based platform with green fluorescent protein (GFP) tagging to optimise the conditions for expression, solubilisation and purification. We subsequently employ these conditions to purify milligram quantities of His-tagged FICD per litre of culture, and show that the purified, detergent-solubilised membrane protein is an active deAMPylating enzyme. Our work provides a straightforward methodology for producing not only full-length FICD, but also other membrane proteins in S. cerevisiae for structural and biochemical characterisation.     

Simultaneous scheduling of parts and automated guided vehicles in an FMS environment using adaptive genetic algorithm

Automated Guided Vehicles (AGVs) are among various advanced material handling techniques that are finding increasing applications today. They can be interfaced to various other production and storage equipment and controlled through an intelligent computer control system. Both the scheduling of operations on machine centers as well as the scheduling of AGVs are essential factors contributing to the efficiency of the overall flexible manufacturing system (FMS). An increase in the performance of the FMS under consideration would be expected as a result of making the scheduling of AGVs an integral part of the overall scheduling activity. In this paper, simultaneous scheduling of parts and AGVs is done for a particular type of FMS environment by using a non-traditional optimization technique called the adaptive genetic algorithm (AGA). The problem considered here is a large variety problem (16 machines and 43 parts) and combined objective function (minimizing penalty cost and minimizing machine idle time). If the parts and AGVs are properly scheduled, then the idle time of the machining center can be minimized; as such, their utilization can be maximized. Minimizing the penalty cost for not meeting the delivery date is also considered in this work. Two contradictory objectives are to be achieved simultaneously by scheduling parts and AGVs using the adaptive genetic algorithm. The results are compared to those obtained by conventional genetic algorithm.     

Continuing education in cultural competence for community mental health practitioners.

Continuing education in cultural competence is a key strategy for enhancing provider effectiveness in working with culturally diverse clients. In the mental health field, a majority of published works address training issues related to students in graduate programs. Few articles, however, discuss specific models or methods of continuing education for practitioners working in community-based settings. The authors present a case example of an interactive workshop in cultural competence for community mental health practitioners. They discuss key modules of this workshop, including (a) cultural competence and outreach principles, (b) cultural identity and worldview, (c) stereotyping and automatic thinking, (d) dynamics of difference, and (e) application exercises. Recommendations are offered for administrators, direct care staff, trainers, and researchers who may be interested in undertaking or participating in cultural competence continuing education efforts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predictors of Use of Social Network Sites at Work ‐ A Specific Type of Cyberloafing

A total of 11,018 employees participated in a survey investigating whether demographic, personality, and work‐related variables could explain variance in attitudes towards and actual use of social network sites for personal purposes during working hours. Age was negatively related to both dependent variables. Male gender, single status, and education were positively associated with both dependent variables. Managers had negative attitudes to use, but top‐level managers reported more use than other respondents. Access to social network sites at the workplace was positively related to both dependent variables, whereas policies prohibiting showed the opposite relationship. Extraversion and Neuroticism were positively related to both dependent variables. Conscientiousness, positive challenge at work, and quantitative demands were all negatively related to both dependent variables.