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 corrosion of mild and stainless steel in alkaline anaerobic conditions representing the Belgian “supercontainer” concept and the Swiss L/ILW repository

Deep geological repositories for radioactive waste contain metallic materials, either used to construct disposal canisters or as low-/intermediate-level waste (L/ILW). The safety relevance of corrosion is linked to canister lifetime in the former case and gas generation in the latter. More specifically, the Belgian “supercontainer” concept envisages mild steel for the used fuel disposal canister, and in the case of the Swiss L/ILW repository, mild steels are the largest metallic waste component due to the decommissioning of civilian power-generating facilities. For these circumstances, the corrosion environment is dominated by the chemistry of cement, which is used as buffer or backfill material. The corrosion behaviour of mild steel in anoxic environments was studied through the analysis of the hydrogen end-product. Hydrogen analysis was conducted by periodically purging the cell head-space and analysing the gas using a solid-state hydrogen sensor. While this method is limited to providing only uniform corrosion rates averaged over periods of time, ranging from weeks to months, it provides excellent resolution and sensitivity. The test cell environments were matched against the anticipated Belgian high-level waste and Swiss L/ILW repository environments, and also against experiments that have been conducted by other researchers for comparative purposes. Samples were exposed to synthetic cement pore waters, representing fresh and degraded cement. In young cement waters, the formation of initial corrosion products resulted in steel wire corrosion rates of the order of µm/year, which, at 80°C rapidly declined to ∼10 nm/year. In contrast, SA516 grade 70 steel plate corroded much more slowly under similar conditions. In aged cement waters, initial corrosion rates were higher but declined faster towards a longer-term rate of ∼10 nm/year. 316L stainless steel, embedded in cementitious material, corroded at a rate of <1 nm/year at 50°C.     

Tamquam alter idem: formal similarities in a subset of reports on anti-inflammatory compounds in the years 2008–2019

Scientometrics - A literature search on the in vitro testing of anti-inflammatory compounds of natural origin revealed a considerable number of studies adopting a similar template for data...     

Development of low-alcohol isotonic beer by interrupted fermentation

Alcohol-free beer with isotonic properties is getting more popular and its production can be carried out by different production strategies; however, interrupted fermentation is still a challenge. Therefore, the objective of this study was to develop a low-alcohol isotonic beer (<0.5% v/v) by interrupted fermentation. Moreover, the major objective is to compare the developed product to commercial beverages (sports drinks, ‘Pilsen' regular beer, alcohol-free beers and low-alcohol isotonic beer). The beverages were evaluated based on pH, alcohol content (% v/v), total titratable acidity (mEq L⁻¹), osmolality (mOsmol kg⁻¹), bitterness International Bitterness Units, colour European Brewery Convention, total phenolic compounds (mg L⁻¹ gallic acid), reducing and total sugars (%) and Na and K contents (mg L⁻¹). The developed low-alcohol isotonic beer presented characteristics similar to sports drinks, with the advantage of being richer in phenolic compounds and suitable osmolality. Despite salts were added in its formulation, the grades attributed to all beers employed in the sensory evaluation, as well as the purchase intention did not present significant differences.     

How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease

Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.     

Effects of Prior Annealing on the Spark Plasma Sintering of Nanostructured Y2O3 Powders

The effects produced by annealing Y₂O₃ nanopowders on their spark plasma sintering (SPS) behavior are systematically investigated in this work. It is found that the annealed powders display higher sinterability with respect to the as‐received ones. Indeed, the maximum densification level reached from pristine powders is about 97.5%, whereas density decreases when further increasing either the sintering temperature or the dwell time. In contrast, the density of SPS products obtained from pretreated powder monotonically increases with temperature and processing time, thus leading to fully dense materials in 30 min at 1050°C and 60 MPa. Correspondingly, it is found that the annealing treatment markedly inhibits grain coarsening during SPS. Thus, dense translucent samples with grain size below 100 nm can be attained from annealed powders. On the other hand, white‐opaque specimens with significantly coarser microstructures (up to 1‐μm‐sized grains) are obtained when pristine powders are directly processed under the same sintering conditions. Furthermore, it is observed that the annealing treatment of SPS samples in air allows for graphite contamination removal, whereas no improvement in term of light transmittance is produced.     

基于小波变换的分数阶微分算法在肝脏肿瘤CT图像纹理增强中的应用

图像纹理增强过程中容易丢失平滑区域纹理细节，而分数阶微分增强虽然能够非线性保留平滑区域纹理细节，但对频率分辨率敏感。针对这个问题，提出一种基于小波变换的分数阶微分纹理增强算法，应用于平扫计算机断层扫描（CT）图像的肝脏肿瘤区域的纹理增强。首先，通过小波变换将图像感兴趣区分解成多个子带分量；其次，基于分数阶微分定义构造一个带补偿参数的分数阶微分掩膜；最后，使用该掩膜与每个高频子带分量进行卷积并利用小波逆变换重组图像感兴趣区。实验结果表明，该方法在使用较大分数阶次显著增强肿瘤区域的高频轮廓信息的同时，有效地保留了低频平滑的纹理细节：增强后的肝细胞癌区域与原区域相比，信息熵平均增加36.56%，平均梯度平均增加321.56%，平均绝对差值平均为9.287；增强后的肝血管瘤区域与原区域相比，信息熵平均增加48.77%，平均梯度平均增加511.26%，平均绝对差值平均为14.097。