New Frontiers on ER Stress Modulation: Are TRP Channels the Leading Actors?

The endoplasmic reticulum (ER) is a dynamic structure, playing multiple roles including calcium storage, protein synthesis and lipid metabolism. During cellular stress, variations in ER homeostasis and its functioning occur. This condition is referred as ER stress and generates a cascade of signaling events termed unfolded protein response (UPR), activated as adaptative response to mitigate the ER stress condition. In this regard, calcium levels play a pivotal role in ER homeostasis and therefore in cell fate regulation since calcium signaling is implicated in a plethora of physiological processes, but also in disease conditions such as neurodegeneration, cancer and metabolic disorders. A large body of emerging evidence highlighted the functional role of TRP channels and their ability to promote cell survival or death depending on endoplasmic reticulum stress resolution, making them an attractive target. Thus, in this review we focused on the TRP channels’ correlation to UPR-mediated ER stress in disease pathogenesis, providing an overview of their implication in the activation of this cellular response.     

Binary‐offset‐carrier modulation techniques with applications in satellite navigation systems

An important aspect in designing the modulation scheme for various satellite systems, such as the modernized GPS and Galileo, is to obtain good spectral properties and suitable spectral shaping. For example, in the future satellite navigation systems, some of the main goals are: low interference with the existing GPS signals, good root‐mean‐square (RMS) bandwidth, good time resolution (in order to allow the separation between channel paths and to decrease the synchronization errors) etc. Starting from the recently proposed cosine‐ and sine‐BOC modulation families for GPS and Galileo systems, we introduce a new, generalized family, denoted here by double‐BOC (DBOC) modulation. We derive and analyze the properties of the power spectral densities (PSD) and autocorrelation functions (ACF) of the DBOC modulation with various orders, we show its relationship with BPSK, sine‐ and cosine‐BOC modulations, and we illustrate via several examples how to choose optimally the parameters of this new modulation family, according to different optimization criteria. The examples are targeting at applications such as the design of suitable modulations for Galileo open service (OS) and public regulated service (PRS) signals, but the authors believe that the DBOC concept might be useful to other satellite‐based applications, when the available bandwidth is large enough. Copyright © 2006 John Wiley & Sons, Ltd.     

Metal Triflates Incorporated in Mesoporous Catalysts for Green Synthesis of Fine Chemicals

Strong Lewis acid SnTf-MCM-41 and SnTf-UVM-7 catalysts with unimodal and bimodal pore systems were prepared in a two-step synthesis in which the triflic acid (Tf) was incorporated into previously synthesized mesoporous tin-containing silicas. The Sn incorporation inside the pore walls was carried out through the Atrane method. The SnTf-UVM-7 catalysts were prepared by aggregating nanometric mesoporous particles defining a hierarchic textural-type additional pore system. Catalysts with different Si/Sn ratios in the range 21.8–50.8 for SnTf-MCM-41 and 18.4 for SnTf-UVM-7 were found to be efficient catalysts for the acylation of aromatics and heteroaromatics. Under microwave irradiation the reaction was possible even with acetic acid. The selectivity to the desired product (o-hydroxyacetophenone for phenol) or the unfavored three-substituted five ring heterocycles was dramatically increased under these conditions. The process is green, environmentally safe, and heterogeneous.     

Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine different prognostic groups and related therapeutic treatment. Current multimodal therapeutic strategies involve surgery, chemotherapy (CHT) and radiotherapy (RT), but despite the deeper knowledge of response mechanisms underpinning CHT treatment and the technological improvements that characterize RT, local failures and recurrence frequently occur. This review sums up the RMS classification and the management of RMS patients, with special attention to RT treatment and possible radiosensitizing strategies for RMS tumors. Indeed, RMS radioresistance is a clinical problem and further studies aimed at dissecting radioresistant molecular mechanisms are needed to identify specific targets to hit, thus improving RT-induced cytotoxicity.     

CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.     

Tolerance,Adaptation, and Cell Response Elicited by Micromonospora sp. Facing Tellurite Toxicity: A Biological and Physical-Chemical Characterization

The intense use of tellurium (Te) in industrial applications, along with the improper disposal of Te-derivatives, is causing their accumulation in the environment, where oxyanion tellurite (TeO₃²⁻) is the most soluble, bioavailable, and toxic Te-species. On the other hand, tellurium is a rare metalloid element whose natural supply will end shortly with possible economic and technological effects. Thus, Te-containing waste represents the source from which Te should be recycled and recovered. Among the explored strategies, the microbial TeO₃²⁻ biotransformation into less toxic Te-species is the most appropriate concerning the circular economy. Actinomycetes are ideal candidates in environmental biotechnology. However, their exploration in TeO₃²⁻ biotransformation is scarce due to limited knowledge regarding oxyanion microbial processing. Here, this gap was filled by investigating the cell tolerance, adaptation, and response to TeO₃²⁻ of a Micromonospora strain isolated from a metal(loid)-rich environment. To this aim, an integrated biological, physical-chemical, and statistical approach combining physiological and biochemical assays with confocal or scanning electron (SEM) microscopy and Fourier-transform infrared spectroscopy in attenuated total reflectance mode (ATR-FTIR) was designed. Micromonospora cells exposed to TeO₃²⁻ under different physiological states revealed a series of striking cell responses, such as cell morphology changes, extracellular polymeric substance production, cell membrane damages and modifications, oxidative stress burst, protein aggregation and phosphorylation, and superoxide dismutase induction. These results highlight this Micromonospora strain as an asset for biotechnological purposes.     

Circulating Small EVs miRNAs as Predictors of Pathological Response to Neo-Adjuvant Therapy in Breast Cancer Patients

Neo-adjuvant therapy (NAT) is increasingly used in the clinic for the treatment of breast cancer (BC). Pathological response to NAT has been associated with improved patients’ survival; however, the current techniques employed for assessing the tumor response have significant limitations. Small EVs (sEVs)-encapsulated miRNAs have emerged as promising new biomarkers for diagnosis and prediction. Therefore, our study aims to explore the predictive value of these miRNAs for the pathological response to NAT in BC. By employing bioinformatic tools, we selected a set of miRNAs and evaluated their expression in plasma sEVs and BC biopsies. Twelve miRNAs were identified in sEVs, of which, miR-21-5p, 221-3p, 146a-5p and 26a-5p were significantly associated with the Miller–Payne (MP) pathological response to NAT. Moreover, miR-21-5p, 146a-5p, 26a-5p and miR-24-3p were independent as predictors of MP response to NAT. However, the expression of these miRNAs showed no correlation between sEVs and tissue samples, indicating that the mechanisms of miRNA sorting into sEVs still needs to be elucidated. Functional analysis of miRNA target genes and drug interactions revealed that candidate miRNAs and their targets, can be regulated by different NAT regimens. This evidence supports their role in governing the patients’ therapy response and highlights their potential use as prediction biomarkers.     

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.     

Comparison of conventional extraction under reflux conditions and microwave-assisted extraction of oil from popcorn.

Popcorn offers an environmentally friendly alternative to the commercial synthetic loose-fill packing materials. Popcorn could be used for cushioning purposes if the oil is extracted after the popping process. Conventional and microwave-assisted extraction methods were used for oil extraction from whole and ground, popped and unpopped kernels. The conventional extraction method achieved 68.5% oil recovery from whole popped kernels. However, whole unpopped kernels were not efficiently de-oiled with either of the methods. Extraction of oil from popped kernels is recommended; corn varieties with higher starch content and lower oil content should be used.