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.     

Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate

Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD.     

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)     

Thick-layer glycerin-containing bichromated gelatin for recording volume holograms

A thick-layer light-sensitive material consisting of glycerin-containing bichromated gelatin has been prepared and used to record real-time volume holograms with 0.44 μm helium-cadmium laser radiation. The thickness of the layers is 400–600 μm. The holographic sensitivity of the material is 1 J/cm². The highest diffraction efficiency of holograms recorded using a symmetric system with parallel beams is 32%. Pis’ma Zh. Tekh. Fiz. 23, 62–65 (April 12, 1997)     

One-dimensional diffuser based on a thick layer of dichromated gelatin

A new diffuser capable of scattering light in one direction (one-dimensional diffuser) has been developed and experimentally tested. The diffuser is formed in a thick layer of dichromated gelatin. The scattering indicatrices of the diffuser measured in two mutually perpendicular directions are presented. It is demonstrated that the indicatrix width in one direction is significantly greater than that in the perpendicular direc-tion. However, no zero-order diffraction has been observed. The proposed one-dimensional diffuser exhibits close scattering indicatrices for reading at a wavelength of 0.44 and 0.63 μm.     

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.     

Berechnung der Wirbelstromdichten und-kräfte in der Umgebung großer supraleitender Spulen für den magnetischen Einschluß bei der Kernfusion

Übersicht Um die Betriebssicherheit großer supraleitender Magnetsysteme für die Kernfusionsforschung zu gewährleisten, muß die im Magnetsystem gespeicherte Energie schnell entladen werden können. Durch die veränderlichen großvolumigen Magnetfelder werden in benachbarten leitfähigen Strukturen durch Induktion hohe Wirbelströme hervorgerufen. Durch sie treten dort elektromagnetische Kräfte. auf, die einzelne Komponenten mechanisch überlasten können. Zur Berechnung dieser Kräfte wurde eine einfache numerischanalytische Methode entwickelt, die im folgenden vorgestellt und mit Finite-Elemente-Verfahren verglichen wird.

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Calculation of eddy current densities and forces around large superconducting coils for nuclear fusion

Contents The reliable operation of the superconducting magnet systems used for the magnetic confinement in nuclear fusion research requires the ability of a fast discharge of the stored magnetic energy. The corresponding magnetic field variation gives rise to high eddy currents by inductive coupling with surrounding conductive components. The eddy current forces can lead to a mechanical overload of some of these components. A simple numerical-analytical method was developed in order to calculate these forces. This method is presented and compared with the Finite Element Method.