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)     

Mobile Device Security Using Transient Authentication

Mobile devices are vulnerable to theft and loss due to their small size and the characteristics of their common usage environment. Since they allow users to work while away from their desk, they are most useful in public locations and while traveling. Unfortunately, this is also where they are most at risk. Existing schemes for securing data either do not protect the device after it is stolen or require bothersome reauthentication. Transient Authentication lifts the burden of authentication from the user by use of a wearable token that constantly attests to the user's presence. When the user departs, the token and device lose contact and the device secures itself. We show how to leverage this authentication framework to secure all the memory and storage locations on a device into which secrets may creep. Our evaluation shows this is done without inconveniencing the user, while imposing a minimal performance overhead     

Resistance to Fracture of a Partially Stabilized Zirconia/β-Alumina Composite

Partially stabilized zirconia (PSZ) /β-alumina composites exhibit extensive non-elastic deformation during fracture. Repeated loading/stable fracture/unloading experiments were performed on chevron-notched four-point-bend specimens of the composite and pure PSZ. The energy consumption during the propagation of long cracks in the composite (∼500 J/m²) is 1 order of magnitude larger than for PSZ (∼50 J/m²). Breaking strengths of 127 MPa were obtained with a Weibull modulus of 43.     

Dynamics of photosynthetic pigments in an Andean lake in Colombia

Guatavita Lake is a small, sheltered tropical high mountain lake located in the Colombian Andes, with a closed watershed and a maximum depth of 25 m. It is the freshwater source for human consumption in nearby small towns, as well as being a site of cultural value for the country, as it was a sacred place to indigenous peoples until about five centuries ago. As the structure and function of this aquatic ecosystem is poorly understood, this study provides initial knowledge on its phytoplankton biomass dynamics, which should be useful in designing efficient management plans with environmental baseline information for similar lakes elsewhere. Physical and chemical data, and photosynthetic pigment concentrations, were measured for the period November 1999–November 2000 at the central vertical axis of Guatavita Lake. The vertical profile of the chlorophyll‐a concentration was closely related to the dissolved inorganic nitrogen concentrations and the thermal stratification characteristics. The maximum chlorophyll‐a concentration in the metalimnion was recorded for the thermal stratification period (November 1999–June 2000). Deepening of the maximum chlorophyll‐a concentration began in February, continuing to June, when it reached its lowest value at the 15 m depth. The phytoplankton biomass values showed an increment within the entire water column at the beginning of the mixing period (July). The relation between the metalimnetic peak of chlorophyll‐a and the dissolved inorganic nitrogen concentration suggests the growth of the phytoplankton community is limited mainly by the availability of nitrogen.     

Glass-ionomer cements in restorative dentistry

This article reviews the current status and future prospects for glass-ionomer materials. These materials are of two chemical types: the older, self-hardening cements, which set by an acid-base neutralization reaction to give relatively brittle materials; and the newer, resin-modified cements, which set partly by polymerization and partly by neutralization. Compared with the self-hardening cements, the latter materials have improved esthetics, improved resistance to moisture, and greater toughness. Both types of glass-ionomer cement bond well to enamel and dentin and release a clinically useful amount of fluoride. They have been used in a variety of applications: as liners or bases, for luting of stainless steel crowns, for Class V restorations in permanent teeth, and for Class II and Class III restorations in primary teeth. The resin-modified glass-ionomers are particularly promising for these latter uses, although it is too early to be sure whether their long-term durability is sufficient. Self-hardening glass-ionomer materials are likely to retain specific niches of clinical application, including in their metal-reinforced and cermet-containing forms.     

Relationship of a dystrophin-associated glycoprotein to junctional acetylcholine receptor clusters in rat skeletal muscle

The relationship of a member of the transmembrane dystrophin-associated glycoprotein (DAG) complex to acetylcholine receptors (AChRs) was investigated using immunofluorescence techniques at rat neuromuscular junctions (NMJs) viewed en face. These results were compared with those from a similar previous study of dystrophin and an autosomal homologue (utrophin or dystrophin-related protein, DRP) (Bewick et al. Neuro Report 1992; 3: 857-860). The region of highest 43 K DAG (43DAG) labelling projected beyond the AChRs by approximately 0.3 microns, as does that for dystrophin. By contrast DRP labelling precisely co-localizes with the AChRs. These results suggest that at the NMJ, the region of high 43DAG concentration encompasses the area of highest intensity labelling for both DRP and dystrophin.