Prospects of the use of beta-carotene enriched food products in the prevention and therapy of radiation injuries]

Radio-protective effectiveness of short-term (19 and 4 h before, 4 and 24 h after irradiation), long-term (3 times/week during 30 days after irradiation) and delayed (1 or 2 days after irradiation) enrichment with crystallized beta-carotene, in single doses of 0.1, 1.0 or 5.0 mg was evaluated in experimental acute external gamma-irradiation (0.029 Gy/sec) within the range of absorbed doses 9--6 Gy. The results obtained have permitted the authors to recommend the ration enriched with carotinoid for prevention and therapy of acute radiation injuries.     

Assembly of the Multi-Subunit Cytochrome bc1 Complex in the Yeast Saccharomyces cerevisiae

The cytochrome bc₁ complex is an essential component of the mitochondrial respiratory chain of the yeast Saccharomyces cerevisiae. It is composed of ten protein subunits, three of them playing an important role in electron transfer and proton pumping across the inner mitochondrial membrane. Cytochrome b, the central component of this respiratory complex, is encoded by the mitochondrial genome, whereas all the other subunits are of nuclear origin. The assembly of all these subunits into the mature and functional cytochrome bc₁ complex is therefore a complicated process which requires the participation of several chaperone proteins. It has been found that the assembly process of the mitochondrial bc₁ complex proceeds through the formation of distinct sub-complexes in an ordered sequence. Most of these sub-complexes have been thoroughly characterized, and their molecular compositions have also been defined. This study critically analyses the results obtained so far and highlights new possible areas of investigation.     

The Inhibition of the Inducible Nitric Oxide Synthase Enhances the DPSC Mineralization under LPS-Induced Inflammation

Nitric oxide (NO) is a key messenger in physiological and pathological processes in mammals. An excessive NO production is associated with pathological conditions underlying the inflammation response as a trigger. Among others, dental pulp inflammation results from the invasion of dentin by pathogenic bacteria. Vital functions of pulp mesenchymal stem cells (DPSCs, dental pulp stem cells), such as mineralization, might be affected by the inducible NOS (iNOS) upregulation. In this context, the iNOS selective inhibition can be considered an innovative therapeutic strategy to counteract inflammation and to promote the regeneration of the dentin-pulp complex. The present work aims at evaluating two acetamidines structurally related to the selective iNOS inhibitor 1400W, namely CM544 and FAB1020, in a model of LPS-stimulated primary DPSCs. Our data reveal that CM544 and even more FAB1020 are promising anti-inflammatory compounds, decreasing IL-6 secretion by enhancing CD73 expression-levels, a protein involved in innate immunity processes and thus confirming an immunomodulatory role of DPSCs. In parallel, cell mineralization potential is retained in the presence of compounds as well as VEGF secretion, and thus their angiogenetic potential. Data presented lay the ground for further investigation on the anti-inflammatory potential of acetamidines selectively targeting iNOS in a clinical context.     

Genomic Analysis Made It Possible to Identify Gene-Driver Alterations Covering the Time Window between Diagnosis of Neuroblastoma 4S and the Progression to Stage 4

Neuroblastoma (NB) is a tumor of the developing sympathetic nervous system. Despite recent advances in understanding the complexity of NB, the mechanisms that determine its regression or progression are still largely unknown. Stage 4S NB is characterized by a favorable course of disease and often by spontaneous regression, while progression to true stage 4 is a very rare event. Here, we focused on genomic analysis of an NB case that progressed from stage 4S to stage 4 with a very poor outcome. Array-comparative genomic hybridization (a-CGH) on tumor-tissue DNA, and whole-exome sequencing (WES) on exosomes DNA derived from plasma collected at the onset and at the tumor progression, pointed out relevant genetic changes that can explain this clinical worsening. The combination of a-CGH and WES data allowed for the identification iof somatic copy number aberrations and single-nucleotide variants in genes known to be responsible for aggressive NB. KLRB1, MAPK3 and FANCA genes, which were lost at the time of progression, were studied for their possible role in this event by analyzing in silico the impact of their expression on the outcome of 786 NB patients.     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Forecasting Home Sales in the Four Census Regions and the Aggregate US Economy Using Singular Spectrum Analysis

Accurate forecasts of home sales can provide valuable information for not only, policy makers, but also financial institutions and real estate professionals. Given this, our analysis compares the ability of two different versions of singular spectrum analysis (SSA) methods, namely recurrent SSA (RSSA) and vector SSA (VSSA), in univariate (UV) and multivariate (MV) frameworks, in forecasting seasonally unadjusted home sales for the aggregate US economy and its four census regions (Northeast, Midwest, South and West). We compare the performance of the SSA-based models with classical and Bayesian variants of the autoregressive (AR) and vector AR models. Using an out-of-sample period of 1979:8–2014:6, given an in-sample period of 1973:1–1979:7, we find that the UVVSSA is the best performing model for the aggregate US home sales, while the MV versions of the RSSA is the outright favorite in forecasting home sales for all the four census regions. Our results highlight the superiority of the nonparametric approach of the SSA, which in turn, allows us to handle any statistical process: linear or nonlinear, stationary or non-stationary, Gaussian or non-Gaussian.     

Delay and link utilization aware routing protocol for wireless multimedia sensor networks

Wireless Multimedia Sensor Networks (WMSNs) consist of networks of interconnected devices involved in retrieving multimedia content, such as, video, audio, acoustic, and scalar data, from the environment. The goal of these networks is optimized delivery of multimedia content based on quality of service (QoS) parameters, such as delay, jitter and distortion. In multimedia communications each packet has strict playout deadlines, thus late arriving packets and lost packets are treated equally. It is a challenging task to guarantee soft delay deadlines along with energy minimization, in resource constrained, high data rate WMSNs. Conventional layered approach does not provide optimal solution for guaranteeing soft delay deadlines due to the large amount of overhead involved at each layer. Cross layer approach is fast gaining popularity, due to its ability to exploit the interdependence between different layers, to guarantee QoS constraints like latency, distortion, reliability, throughput and error rate. The paper presents a channel utilization and delay aware routing (CUDAR) protocol for WMSNs. This protocol is based on a cross-layer approach, which provides soft end-to-end delay guarantees along with efficient utilization of resources. Extensive simulation analysis of CUDAR shows that it provides better delay guarantees than existing protocols and consequently reduces jitter and distortion in WMSN communication.     

Microbial communities and malt quality of durum wheat used in brewing

Durum wheat (Triticum durum Desf.) has potential as an adjunct in brewing given its agronomic, chemical and technological properties. The aim of this work were to identify the cultivable microflora and evaluate the technological quality of the durum wheat variety ‘Senatore Cappelli’ grown and used by a craft brewery in Sardinia, Italy. The isolated bacterial strains were mainly rhizospheric (Kocuria rizophila, Microbacterium aerolatum and Bacillus pumilus) and associated with the microbiota of wheat (Staphylococcus spp.). None have been reported previously as spoilage species in brewing. The dominant yeast genera were Cryptococcus spp. and Rhodotorula spp., followed by Saccharomyces cerevisiae. The dominant filamentous fungus genera were Alternaria and Rhizopus. Low levels of mycotoxigenic Fusarium spp., Aspergillus spp. and Penicillium spp. were isolated. However, the levels of deoxynivalenol, T2‐HT2, fumonisin, aflatoxin and ochratoxin detected in the malt and grain were below the thresholds defined by European law. Malt obtained from raw grain showed interesting technological properties, but required specific malting parameters different from those of common wheat and barley. These data suggest that the use of locally grown durum wheat in brewing can increase sustainability and reduce costs, while reinforcing the link with the terroir and promoting reduced mycotoxin levels. © 2019 The Institute of Brewing & Distilling