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.     

Empirical surveys of frontier applications: a meta‐review

This contribution is the first attempt to systematically review all empirical surveys that so far have been made available in the broad field of efficiency and productivity analysis using frontier estimation methodologies. We provide a systematic bibliometric review on the many empirical surveys in the field of efficiency and productivity analysis, the most relevant concepts, areas, overlaps, and potentials to explore from its introduction to the most recent surveys. We combine the United Nations’ International Standard Industrial Classification (ISIC) taxonomy for the economic activity with the Journal of Economic Literature (JEL) classification system to classify the empirical surveys and to identify the current gaps in the literature. In addition to the most relevant/generic potential areas for applications (according to the United Nation's ISIC), this methodology provides a cluster analysis with the most relevant concepts that have been considered so far (according to the JEL codes). This overview brings an interesting guide for future work to develop the whole field.     

A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.     

Using normative ethics for building a good evaluation of research practices: towards the assessment of researcher’s virtues

This paper is an attempt of using co-citation analysis to sort out and to analyze the development and evolution of a latest hot area, open innovation from the perspective of network embedding. A dataset of 1437 records published between 1990 and 2019 is collected from Web of Science database. The empirical results show the latest hot topics in the open innovation study focus on innovation performance and value creation. In addition, we make a new interpretation of open innovation from four aspects: innovation and entrepreneurship, resource acquisition, knowledge sharing and innovation performance, then combines the importance of network embedding to the innovation and development of enterprises, and proposes the future research direction of open innovation. Our research in this paper is helpful to systematically sort out the knowledge context of open innovation, which is of great significance to the construction and development of open innovation knowledge system. The conclusions and implications in this paper will be particularly illuminating for both academic research and enterprises’ practice application.

     

FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.     

Positron Emitting Magnetic Nanoconstructs for PET/MR Imaging

Hybrid PET/MRI scanners have the potential to provide fundamental molecular, cellular, and anatomic information essential for optimizing therapeutic and surgical interventions. However, their full utilization is currently limited by the lack of truly multi‐modal contrast agents capable of exploiting the strengths of each modality. Here, we report on the development of long‐circulating positron‐emitting magnetic nanoconstructs (PEM) designed to image solid tumors for combined PET/MRI. PEMs are synthesized by a modified nano‐precipitation method mixing poly(lactic‐co‐glycolic acid) (PLGA), lipids, and polyethylene glycol (PEG) chains with 5 nm iron oxide nanoparticles (USPIOs). PEM lipids are coupled with 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) and subsequently chelated to ⁶⁴Cu. PEMs show a diameter of 140 ± 7 nm and a transversal relaxivity r₂ of 265.0 ± 10.0 (mM × s)^?1, with a r₂/r₁ ratio of 123. Using a murine xenograft model bearing human breast cancer cell line (MDA‐MB‐231), intravenously administered PEMs progressively accumulate in tumors reaching a maximum of 3.5 ± 0.25% ID/g tumor at 20 h post‐injection. Correlation of PET and MRI signals revealed non‐uniform intratumoral distribution of PEMs with focal areas of accumulation at the tumor periphery. These long‐circulating PEMs with high transversal relaxivity and tumor accumulation may allow for detailed interrogation over multiple scales in a clinically relevant setting.     

A framework for formal analysis and simulative evaluation of security attacks in wireless sensor networks

Journal of Computer Virology and Hacking Techniques - When designing Wireless Sensor Networks it is important to analyze their security risks and provide adequate solutions for protecting them from...     

Tuning light emission of PbS nanocrystals from infrared to visible range by cation exchange

Colloidal semiconductor nanocrystals, with intense and sharp-line emission between red and near-infrared spectral regions, are of great interest for optoelectronic and bio-imaging applications. The growth of an inorganic passivation layer on nanocrystal surfaces is a common strategy to improve their chemical and optical stability and their photoluminescence quantum yield. In particular, cation exchange is a suitable approach for shell growth at the expense of the nanocrystal core size. Here, the cation exchange process is used to promote the formation of a CdS passivation layer on the surface of very small PbS nanocrystals (2.3 nm in diameter), blue shifting their optical spectra and yielding luminescent and stable nanostructures emitting in the range of 700–850 nm. Structural, morphological and compositional investigation confirms the nanocrystal size contraction after the cation-exchange process, while the PbS rock-salt crystalline phase is retained. Absorption and photoluminescence spectroscopy demonstrate the growth of a passivation layer with a decrease of the PbS core size, as inferred by the blue-shift of the excitonic peaks. The surface passivation strongly increases the photoluminescence intensity and the excited state lifetime. In addition, the nanocrystals reveal increased stability against oxidation over time. Thanks to their absorption and emission spectral range and the slow recombination dynamics, such highly luminescent nano-objects can find interesting applications in sensitized photovoltaic cells and light-emitting devices.