Generalized MGF of Beckmann Fading with Applications to Wireless Communications Performance Analysis

The Beckmann distribution is a general multipath fading model for the received radio signal in the presence of a large number of scatterers, which can thence be modeled as a complex Gaussian random variable where both the in-phase and quadrature components have arbitrary mean and variance. However, the complicated nature of this distribution has prevented its widespread use and relatively few analytical results have been reported for this otherwise useful fading model. In this paper, we derive a closed-form expression for the generalized moment-generating function (MGF) of the signal-to-noise ratio (SNR) of Beckmann fading, which permits to circumvent the inherent analytical complexity of this model. This is a new and useful result, as it is key for evaluating several important performance metrics of different wireless communication systems and also permits to readily compute the moments of the output SNR. Thus, we obtain simple exact expressions for the energy detection performance in Beckmann fading channels, both in terms of the receiver operating characteristic (ROC) curve and of the area under ROC curve. We also analyze the outage probability in interference limited systems affected by Beckmann fading, as well as the outage probability of secrecy capacity in wiretap Beckmann fading channels. Monte Carlo simulations have been performed to validate the derived expressions.Universidad de Málaga. Campus de Excelencia Internacional. Andalucía Tech

Therapeutic potential of melatonin counteracting chemotherapy-induced toxicity in breast cancer patients: a systematic review

The purpose of this systematic review is to provide an overview of the existing knowledge on the therapeutic potential of melatonin to counteract the undesirable effects of chemotherapy in breast cancer patients. To this aim, we summarized and critically reviewed preclinical- and clinical-related evidence according to the PRISMA guidelines. Additionally, we developed an extrapolation of melatonin doses in animal studies to the human equivalent doses (HEDs) for randomized clinical trials (RCTs) with breast cancer patients. For the revision, 341 primary records were screened, which were reduced to 8 selected RCTs that met the inclusion criteria. We assembled the evidence drawn from these studies by analyzing the remaining gaps and treatment efficacy and suggested future translational research and clinical trials. Overall, the selected RCTs allow us to conclude that melatonin combined with standard chemotherapy lines would derive, at least, a better quality of life for breast cancer patients. Moreover, regular doses of 20 mg/day seemed to increase partial response and 1-year survival rates. Accordingly, this systematic review leads us to draw attention to the need for more RCTs to provide a comprehensive view of the promising actions of melatonin in breast cancer and, given the safety profile of this molecule, adequate translational doses should be established in further RCTs

Editorial: Molecular Components of Store-Operated Calcium Entry in Health and Disease

Store-Operated Calcium Entry (SOCE) is a ubiquitous Ca2+ influx mechanism first described in 1986 (Putney, 1986). This conserved mechanism results from the interaction between the tetraspanning ORAI1 channel located in plasma membrane and the unique endoplasmic reticulum (ER) Ca2+ sensor, stromal interaction molecule 1 (STIM1), via their respective intracellular domains (Roos et al., 2005; Csutora et al., 2008). Moreover, there are two homologs of ORAI1, namely ORAI2 and ORAI3, all generating SOCE with the same mechanism

The Interplay between Cytoskeleton and Calcium Dynamics

Cell motility is a complex cellular event that involves reorganization of cytoskeleton. This reorganization encompasses the transient polarization of the cell to facilitate the plasma membrane ruffling, a rearrangement of cortical actin cytoskeleton required for the development of cellular protrusions. It is known that extracellular Ca2+ influx is essential for cell migration and for the positive-feedback cycle that maintains leading-edge structures and ruffling activity. The aim of this review is to summarize our knowledge regarding the Ca2+-dependent signaling pathways, Ca2+ transporters and sensors involved in cell migration. Also, we show here reported evidences that support for a crosstalk between Ca2+ transport and the reorganization of the cytoskeleton required for cell migration. In this regard, we will analyze the role of store-operated Ca2+ entry (SOCE) as a modulator of cytoskeleton and cell migration, but also the modulation of this Ca2+ entry pathway by microtubules and the actin cytoskeleton. As a main conclusion, this review will show that data reported in the last years support a role for SOCE in shaping cytoskeleton, but at the same time, SOCE is strongly dependent on cytoskeletal proteins, in an interesting interplay between cytoskeleton and Ca2+ dynamics

Regulation of Calcium Signaling by STIM1 and ORAI1

STIM1 and ORAI1 proteins are regulators of intracellular Ca2+ mobilization. This Ca2+ mobilization is essential to shape Ca2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca2+ sensor. The transient drop of intraluminal Ca2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and activate ORAI1, a plasma membrane Ca2+ channel. Thus, the Ca2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca2+ influx mediated by these regulators

Correlation between biological responses in vitro and in vivo to Ca-doped sol-gel coatings assessed using proteomic analysis

Poor correlation between the results of in vitro testing and the subsequent in vivo experiments hinders the design of biomaterials. Thus, new characterisation methods are needed. This study used proteomic and histological techniques to analyse the effects of Ca-doped biomaterials in vitro and in vivo and verify the correlation between the two systems. The sol-gel route was employed to synthesise coatings functionalised with 0.5 and 5 wt% of CaCl2. Morphology of the coatings was examined using SEM; the Ca2+ ion release from the materials was analysed by means of ICP-AES spectroscopy. The osteogenic and inflammatory responses were inspected in vitro in human osteoblasts (HOb) and TPH-1 monocytes. The in vivo experiments used a rabbit model. The nLC-MS/MS-based proteomic methods were utilised to analyse the proteins adhering to the material samples incubated with human serum or examine protein expression in the tissues close to the implants. Ca-doped biomaterials caused a remarkable increase in the adsorption of coagulation-related proteins, both in vitro (PLMN, THRB, FIBA and VTNC) and in vivo (FBLN1, G1U978). Enhanced affinity to these materials was also observed for proteins involved in inflammation (CO5, C4BPA, IGHM and KV302 in vitro; CARD6, DDOST and CD14 in vivo) and osteogenic functions (TETN, PEDF in vitro; FBN1, AHSG, MYOC in vivo). The results obtained using different techniques were well matched, with a good correlation between the in vitro and in vivo experiments. Thus, the proteomic analysis of biological responses to biomaterials in vitro is a useful tool for predicting their impact in vivo

Gut Microbiota Has a Crucial Role in the Development of Hypertension and Vascular Dysfunction in Toll-like Receptor 7-Driven Lupus Autoimmunity

Our group has investigated the involvement of gut microbiota in hypertension in a murine model of systemic lupus erythematosus induced by Toll-like receptor (TLR)-7 activation. Female BALB/c mice were randomly assigned to four experimental groups: an untreated control (CTR), a group treated with the TLR7 agonist imiquimod (IMQ), IMQ-treated with vancomycin, and IMQtreated with a cocktail of broad-spectrum antibiotics. We carried out faecal microbiota transplant (FMT) from donor CTR or IMQ mice to recipient IMQ or CTR animals, respectively. Vancomycin inhibited the increase in blood pressure; improved kidney injury, endothelial function, and oxidative stress; and reduced T helper (Th)17 infiltration in aortas from IMQ-treated mice. The rise in blood pressure and vascular complications present in IMQ mice were also observed in the CTR mice recipients of IMQ microbiota. Reduced relative populations of Sutterella and Anaerovibrio were associated with high blood pressure in our animals, which were increased after stool transplantation of healthy microbiota to IMQ mice. The reduced endothelium-dependent vasodilator responses to acetylcholine induced by IMQ microbiota were normalized after interleukin-17 neutralization. In conclusion, gut microbiota plays a role in the TLR7-driven increase in Th17 cell, endothelial dysfunction, vascular inflammation, and hypertension. The vascular changes induced by IMQ microbiota were initiated by Th17 infiltrating the vasculature.Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (MINECO) (SAF2017-84894-R, PID2020-116347RBI00)Junta de Andalucía (CTS 164, P20_00193) with funds from the European Union, and by the Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV)Instituto de Salud Carlos III (Sara Borrell Program)MINECOEuropean Union (Fondo Europeo de Desarrollo Regional, FEDER

Cranial and extracranial giant cell arteritis do not exhibit differences in the IL6 -174 G/C gene polymorphism

Since interleukin-6 (IL-6) is a pivotal proinflammatory cytokine implicated in the pathogenesis of giant cell arteritis (GCA), we aimed to determine the potential association of the functional IL6 -174 G/C polymorphism with GCA as well as if the single base change variation at the promoter region in the human IL-6 gene may account for differences in the clinical spectrum of GCA between cranial and extracranial large vessel vasculitis (LVV)-GCA

Cranial and extracranial large-vessel giant cell arteritis share a genetic pattern of interferon-gamma pathway

OBJECTIVES: Two main different clinical phenotypes of giant cell arteritis (GCA) have been described, the classic cranial pattern and the extracranial large-vessel (LV) pattern. Since interferon gamma (IFNG) has shown to be a pivotal cytokine in the pathophysiology of GCA, our aim was to evaluate for the first time the influence of IFNG and IFNG receptor 1 (IFNGR1) polymorphisms in the different clinical phenotypes of GCA. METHODS: Two IFNG polymorphisms (rs2069718 G/A and rs1861493 A/G) and one polymorphism in IFNGR1 (rs1327474 G/A) were genotyped in 191 patients with biopsy-proven cranial GCA, 109 with extracranial LV-GCA and 490 healthy controls. A comparative study was conducted between patients with cranial and extracranial LV-GCA. RESULTS: No significant differences in genotype, allele, and haplotype frequencies of IFNG polymorphisms were found between GCA patients with the classic cranial pattern and the extracranial LV-GCA pattern. Similar results were found for genotype and allele frequencies of IFNGR1 polymorphism. It was also the case when patients with extracranial LV-GCA were compared with healthy controls. CONCLUSIONS: Our results show that IFNG and IFNGR1 polymorphisms do not influence the clinical phenotype of expression of GCA. Classic cranial GCA and extracranial LV-GCA seem to share a genetic pattern of IFNG pathway