Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Using a multicultural lens to understand illnesses among Haitians living in America.

Currently, ethnic and racial minority individuals represent a large proportion of the U.S. population, and researchers expect that they will represent the majority of the population by 2050. This shift in U.S. demographics calls for a greater awareness and integration of cultural issues into the assessment and treatment of ethnically and linguistically diverse clients. This article examines the unique beliefs and manifestations of illnesses among Haitians in connection with the American Psychological Association's (APA, 2002) Multicultural Guidelines. The authors use a common culture-bound syndrome, Séizisman, to illustrate the cultural beliefs, assessment, and treatment of illnesses among Haitians. In so doing, they demonstrate how to incorporate the APA Multicultural Guidelines into treatment with clients of diverse cultural and racial backgrounds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A computational analysis of LCP methods for bilinear and concave quadratic programming

The use of a sequential linear complementarity problem (SLCP) algorithm for finding a global minimum of bilinear programming problem (BLP) or a concave quadratic program (CQP) is examined. The algorithm consists of solving a sequence of linear complementarity problems (LCP). A branch-and-bound method is also considered in this study. This algorithm is based on the reformulation of a BLP into an LCP with a linear function to minimize. Computational experience with small and medium scale BLPs and CQPs indicates that the SLCP algorithm is quite efficient in finding a global minimum (or at least a solution that is quite near the optimum), but it is, in general, unable to establish that such a solution has been found. An algorithm to find a lower-bound for the BLP can overcome this drawback in some cases. Furthermore the SLCP algorithm is shown to be robust and compares favorably with the branch-and-bound method and another alternative technique.     

汽车电子组件:一个正在发展的市场(上)

汽车中出现的电子设备和系统越来越多,而它们也是汽车功能创新的驱动力. 汽车厂商正在越来越多地使用电子系统和半导体集成电路用于汽车的各种应用,包括驾驶员信息和通信、车内娱乐电子设备、传动系和身体控制电子设备以及汽车安全和舒适设备.     

Behavioral and subjective effects of D-amphetamine and modafinil in healthy adults.

Modafinil is indicated for the management of excessive daytime sleepiness; however, recent studies have examined a broad range of potential uses. Given that clinical uses of modafinil may be expanding, this study compared modafinil and d-amphetamine effects on subjective and performance measures. Across 11 sessions, 11 healthy adults were tested after oral doses of placebo (5 sessions), modafinil (1.75 mg/kg, 3.50 mg/kg, or 7.00 mg/kg), and d-amphetamine (0.035 mg/kg, 0.070 mg/kg, 0.140 mg/kg) under double-blind, randomized conditions. Assessments of cognitive performance and subjective effects were completed before drug administration, 30 min after drug administration, and at hourly intervals after drug administration for 5 hr. Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory (ARCI) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States. d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI. Both medications significantly reduced visual analog scale ratings of feeling sleepy, and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale. Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test. Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task. These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Category Norms as a Function of Culture and Age: Comparisons of Item Responses to 105 Categories by American and Chinese Adults.

Understanding how aging influences cognition across different cultures has been hindered by a lack of standardized, cross-referenced verbal stimuli. This study introduces a database of such item-level stimuli for both younger and older adults, in China and the United States, and makes 3 distinct contributions. First, the authors specify which item categories generalize across age and/or cultural groups, rigorously quantifying differences among them. Second, they introduce novel, powerful methods to measure between-group differences in freely generated ranked data, the rank-ordered logit model and Hellinger Affinity. Finally, a broad archive of tested, cross-linguistic stimuli is now freely available to researchers: data, similarity measures, and all stimulus materials for 105 categories and 4 culture-by-age groups, comprising over 10,000 fully translated unique item responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age effects on block design: Qualitative performance features and extended-time effects.

Qualitative performance features and extended-time effects on the Block Design subtest of the Wechsler Adult Intelligence Scale—Revised (WAIS—R) were examined in 145 healthy Ss (aged 50–95 yrs). Raw scores were calculated at standard and extended time limits; error types and starting points were recorded for a subgroup of Ss. In Ss age 60 yrs and older, there was a consistent decline with age in overall scores at both time limits. Extra time allotments resulted in modest but significant increases in scores. Older and younger Ss benefited equally from the extra time, indicating that the age-related decline on this task cannot be accounted for by general age-related psychomotor slowing. Single- and multiblock rotation errors were relatively common, whereas stimulus boundedness and broken configurations were rare. Despite some potential limitations in generalizability, the results suggest that the incorporation of qualitative scoring procedures in the assessment of visuoconstructional skills may enhance understanding of normal and abnormal brain–behavior relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)