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.     

Recent Biophysical Issues About the Preparation of Solute-Filled Lipid Vesicles

Here we report some recent biophysical issues on the preparation of solute-filled lipid vesicles and their relevance to the construction of “synthetic cells.” First, we introduce the “semi-synthetic minimal cells” as the liposome-based cell-like systems, which contain a minimal number of biomolecules required to display simple and complex biological functions. Next, we focus on recent aspects related to the construction of synthetic cells. Emphasis is given to the interplay between the methods of synthetic cell preparation and the physics of solute encapsulation. We briefly introduce the notion of structural and compositional “diversity” in synthetic cell populations.     

Mitochondrial Bioenergetic,Photobiomodulation and Trigeminal Branches Nerve Damage,What’s the Connection? A Review

Background: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. Methods: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. Results and conclusions: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm² (0.07 W; 2.5 W/cm²; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm² (0.2 W; 12 J/cm²; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies.     

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)     

L'accessibilité à des traitements pour les troubles anxieux au Canada: Un commentaire.

Responds to Gauthier (see record 2004-17185-003) who commented on the two articles by Koerner et al (see record 2004-17185-001) and by Roberge et al (see record 2004-17185-002. The purpose of this response is to discuss the issue of limited availability of mental health services for anxiety disorders in Canada. From a public health perspective, the authors emphasize the importance of gathering Canadian empirical data on the organization of mental health services for anxiety disorders. Specifically more research is needed on care requirements, and the financial and structural barriers that restrict access to mental health services at the regional, provincial and national levels. The authors also discuss the role of psychologists in improving mental health care in Canada. Cost-effectiveness studies conducted in interdisciplinary practice environments could demonstrate the value added by psychology in the organization of mental health care for anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

DILIGENT: integrating digital library and Grid technologies for a new Earth observation research infrastructure

This paper introduces DILIGENT, a digital library infrastructure built by integrating digital library and Grid technologies and resources. This infrastructure allows different communities to dynamically build specialised digital libraries capable to support the entire e-Science knowledge production and consumption life-cycle by using shared computing, storage, content, and application resources. The paper presents some of the main software services that implement the DILIGENT system. Moreover, it exemplifies the provided features by presenting how the DILIGENT infrastructure is being exploited in supporting the activity of user communities working in the Earth Science Environmental sector. This work is partially funded by the European Commission in the context of the DILIGENT project, under the 2nd call of FP6 IST priority.