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.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Development of a new ion-imprinted polymer (IIP) with Cd2+ ions based on divinylbenzene copolymers containing amidoxime groups

Polymer Bulletin - In this study, we synthesized a new ion-imprinted polymer (IIP) based on introduction of amidoxime groups in acrylonitrile, complexation with Cd2+ ions and polymerization with...     

A New Hand-Held Microsystem Architecture for Biological Analysis

This paper presents a hand-held microsystem based on new fully integrated magnetoresistive biochips for biomolecular recognition (DNA hybridization, antibody antigen interaction, etc.). Magnetoresistive chip surfaces are chemically treated, enabling the immobilization of probe biomolecules such as DNA or antibodies. Fluid handling is also integrated in the biochip. The proposed microsystem not only integrates the biochip, which is an array of 16times16 magnetoresistive sensors, but it also provides all the electronic circuitry for addressing and reading out each transducer. The proposed architecture and circuits were specifically designed for achieving a compact, programmable and portable microsystem. The microsystem also integrates a hand-held analyzer connected through a wireless channel. A prototype of the system was already developed and detection of magnetic nanoparticles was obtained. This indicates that the system may be used for magnetic label based bioassays     

Solutions to a combined problem of excessive hydrogen sulfide in biogas and struvite scaling.

The Woodman Point Wastewater Treatment Plant (WWTP) in Western Australia has experienced two separate problems causing avoidable maintenance costs: the build-up of massive struvite (MgNH4PO4. 6H2O) scaling downstream of the anaerobic digester and the formation of hydrogen sulfide (H2S) levels in the digester gas to levels that compromised gas engine operation and caused high operating costs on the gas scrubber. As both problems hang together with a chemical imbalance in the anaerobic digester, we decided to investigate whether both problems could be (feasibly and economically) addressed by a common solution (such as dosing of iron solutions to precipitate both sulfide and phosphate), or by using separate approaches. Laboratory results showed that, the hydrogen sulfide emission in digesters could be effectively and economically controlled by the addition of iron dosing. Slightly higher than the theoretical value of 1.5 mol of FeCl3 was required to precipitate 1 mol of dissolved sulfide inside the digester. Due to the high concentration of PO4(3-) in the digested sludge liquor, significantly higher iron is required for struvite precipitation. Iron dosing did not appear an economic solution for struvite control via iron phosphate formation. By taking advantage of the natural tendency of struvite formation in the digester liquid, it is possible to reduce the risk of struvite precipitation in and around the sludge-dewatering centrifuge by increasing the pH to precipitate struvite out before passing through the centrifuge. However, as the Mg2+/PO4(3-) molar ratio in digested sludge was low, by increasing the pH alone (using NaOH) the precipitation of PO4(3-) was limited by the amount of cations (Ca2+ and Mg2+) available in the sludge. Although this would reduce struvite precipitation in the centrifuge, it could not significantly reduce PO4(3-) recycling back to the plant. For long-term operation, maximum PO4(3-) reduction should be the ultimate aim to minimise PO4(3-) accumulation in the plant. Magnesium hydroxide liquid (MHL) was found to be the most cost-effective chemical to achieve this goal. It enhanced struvite precipitation from both, digested sludge and centrate to the point where more than 95% PO4(3-) reduction in the digested sludge was achieved.