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Coronaviruses represent a significant class of viruses that affect both animals and humans. Their replication cycle is strongly associated with the endoplasmic reticulum (ER), which, upon virus invasion, triggers ER stress responses. The activation of the unfolded protein response (UPR) within infected cells is performed from three transmembrane receptors, IRE1, PERK, and ATF6, and results in a reduction in protein production, a boost in the ER’s ability to fold proteins properly, and the initiation of ER-associated degradation (ERAD) to remove misfolded or unfolded proteins. However, in cases of prolonged and severe ER stress, the UPR can also instigate apoptotic cell death and inflammation. Herein, we discuss the ER-triggered host responses after coronavirus infection, as well as the pharmaceutical targeting of the UPR as a potential antiviral strategy.

Background:. This study evaluates a specific breast augmentation (BA) technique in patients with pectus excavatum(PE) and its results in improving this deformity, augmenting the breasts, and correcting the concurrent breast asymmetry. Methods:. Twenty-eight patients with PE were treated from 2017 to 2021. All patients who visited our private practice were aiming to augment their breasts, correct their breast asymmetry, and improve their PE. The mean age of the patients was 25 years. In most cases, the submuscular dual-plane technique was chosen. Patients’ quality of life regarding their chest wall deformity was assessed using the Single Step Questionnaire (SSQ). Subjects’ quality of life regarding general self-esteem, psychosocial well-being, and physical function were assessed at initial screening and 24-month follow-up using the BREAST-Q V2 questionnaire. Also, patients filled out a pain-evaluating questionnaire concerning the first 5 postoperative days to determine the recovery of this specific technique. Results:. No complications were observed. The SSQ revealed high satisfaction (mean score=73) and significant (P = 0.001) improvement following the operation. The improvements regarding psychosocial well-being, sexual well-being, and satisfaction with the BREAST-Q were also equally high (P = 0.001). The pain was minimal during the first five postoperative days. This is the first prospective study that evaluates the quality of life using both the SSQ, the validated BREAST-Q, and the pain score when performing BA in patients with PE and breast asymmetry using breast silicone implants. Conclusions:. BA is a procedure that can give excellent results both regarding chest wall deformity and BA in PE patients.

Abstract Stings of certain ant species (Hymenoptera: Formicidae) can cause intense, long-lasting nociception. Here we show that the major contributors to these symptoms are venom peptides that modulate the activity of voltage-gated sodium (NaV) channels, reducing their voltage threshold for activation and inhibiting channel inactivation. These peptide toxins are likely vertebrate-selective, consistent with a primarily defensive function. They emerged early in the Formicidae lineage and may have been a pivotal factor in the expansion of ants.

When combining two conditions of reduced oxygen availability, anemia and hypoxia, human physiological responses are highly challenged to maintain arterial oxygen delivery, especially during whole-body exercise. The aim of this study was to compare the cardiorespiratory responses of mildly anemic women with those of healthy controls, while cycling in normobaric hypoxia. Two groups of young females were matched for age, weight, height, and involvement in physical activity, one with normal hemoglobin, hematocrit, and ferritin levels and another suffering from mild iron deficiency anemia (10 < (Hb) < 12 g/dL, 34 < Hct < 37%, ferritin < 15 μg/L). They cycled to exhaustion under normoxia and hypoxia (FIO2 0.21 and 0.14), and their physiological responses were compared at 40, 80, and 100% VO2max of the specific condition. The two groups differed (p < 0.05) mainly at the higher exercise intensities; the anemic participants exhibited similar heart rate but lower oxygen pulse than their control counterparts, as well as a larger drop in maximal oxygen uptake. However, they sustained maximal effort by employing the anaerobic metabolism to a larger extent, which stimulated a greater ventilatory response. It appears that iron deficiency anemia of mild severity, which is commonly observed in young athletic females, impacts physiological responses during whole-body exercise in the presence of moderate hypoxia.

The restoration of historic buildings and structures involves a wide range of scientific and technical fields. The grouting process is among an array of rehabilitation and preservation interventions and aims to homogenize the structure after the implementation of strengthening measures. The process can provide important information regarding the state of preservation of the examined structure and correlate the progress of the process with the pathology of the monument. To achieve this, the analysis of typical raw grouting data is progressively fused with additional information from the diagnostic studies, non-destructive testing, geospatial information, and from the calculation and analysis of grouting indices. The restoration project of the Katholikon of the Monastery of Panagia Varnakova in Fokida, Greece was selected as the case study, due to its large scale and the severe earthquake damage it has sustained, which has necessitated comprehensive strengthening interventions and extensive grouting. The implementation of an integrated methodological approach validated the enhanced level of co-analysis, revealing information that is not readily deduced from a typical approach. Selected sub-areas of the Katholikon are presented, demonstrating how the observed pathology can be correlated with the results of the grouting process, while incorporating 3D data, and findings from structural and non-destructive analyses.

Greek waters are the recipient of several alien species, mainly through natural dispersal following invasion and establishment of non-indigenous species (NIS) in neighboring areas, making their monitoring and mitigating their effects of paramount importance. The European Union legislation framework toward alien species invasions considers risk assessments as the top of the spear for a first assessment of NIS and their potential to become invasive or not. The Union List has already included top priority species, with very few marine species. Golani’s round herring (Etrumeus golanii) is a species of round herrings in the family Dussumieriidae, a Lessepsian migrant and belonging to a group of NIS in the Mediterranean basin that are less studied. Its distribution range is mainly limited in the southeastern Mediterranean Sea, while in the Greek seas, it has not yet been observed in the north Aegean and Ionian seas, probably due to temperature and oceanographical reasons. Its presence in the basin is recorded by commercial fisheries landings in several countries (especially purse-seiners), indicating a potentially positive effect on commercial fisheries. A risk assessment of E. golanii in Greek waters was carried out in this work, based on the Risk Assessment Scheme developed by the GB Non-Native Species Secretariat (GB Non-Native Risk Assessment—GBNNRA). An overall semi-quantitative summary of risk, in terms of likelihood of events and magnitude of impacts, was facilitated for several attributors, including confidence levels for each one. The assessment highlighted a very likely possibility of introduction in the Greek seas from neighboring countries, as well as successful establishments of populations with high confidence levels. A moderate magnitude of impact regarding its further spread was deemed, while a minor one was indicated in terms of native species pressure and a minimal one in terms of economic costs and public health. Overall, E. golanii was not characterized as an invasive alien species (IAS) and local communities could benefit from its presence (commercial fisheries); however, further studies focusing on its reproduction and spawning grounds should be implemented.

The paper’s aim is to provide a synthetic and at the same time critical reading of the official theological dialogue, known as the “dialogue of truth”, between the Orthodox Church and the Catholic Church. The paper will cover the period from the dialogue’s preparation, also known as the “dialogue of charity”, to the present day. It will analyse the ecclesiological aspects of this dialogue, focusing on sacraments, church ministries, primacy, synodality, and other related issues such as “Uniatism”. The essay will provide an overall evaluation of the dialogue, examining its reception and the need for concrete criteria of unity. Also, the paper will highlight the synodal and sacramental roots of episcopacy and their significance for the unity of the Church. The article will present insights from leading theologians, such as Joseph Ratzinger and John Zizioulas, to better understand the meaning and functions of primacy in the universal Church.

The aim of this work is to present the food web models developed using the Ecopath with Ecosim (EwE) software tool to describe structure and functioning of various European marine ecosystems (eastern, central and western Mediterranean Sea; Black Sea; Bay of Biscay, Celtic Sea and Iberian coast; Baltic Sea; North Sea; English Channel, Irish Sea and west Scottish Sea; and Norwegian and Barents Seas). A total of 195 Ecopath models based on 168 scientific publications, which report original, updated and modified versions, were reviewed. Seventy models included Ecosim temporal simulations while 28 implemented Ecospace spatiotemporal dynamics. Most of the models and publications referred to the western Mediterranean Sea followed by the English Channel, Irish Sea and west Scottish Sea sub-regions. In the Mediterranean Sea, the western region had the largest number of models and publications, followed by the central and eastern regions; similar trends were observed in previous literature reviews. Most models addressed ecosystem functioning and fisheries-related hypotheses while several investigated the impact of climate change, the presence of alien species, aquaculture, chemical pollution, infrastructure, and energy production. Model complexity (i.e., number of functional groups) increased over time. Main forcing factors considered to run spatial and temporal simulations were trophic interactions, fishery, and primary production. Average scores of ecosystem indicators derived from the Ecopath summary statistics were compared. Uncertainty was also investigated based on the use of the Ecosampler plug-in and the Monte Carlo routine; only one third of the reviewed publications incorporated uncertainty analysis. Only a limited number of the models included the use of the ECOIND plug-in which provides the user with quantitative output of ecological indicators. We assert that the EwE modelling approach is a successful tool which provides a quantitative framework to analyse the structure and dynamics of ecosystems, and to evaluate the potential impacts of different management scenarios.

Abstract Background Genetic variants in the subunits of the gamma-aminobutyric acid type A (GABAA) receptors are implicated in the onset of multiple pathologic conditions including genetic epilepsy. Previous work showed that pathogenic GABAA subunits promote misfolding and inefficient assembly of the GABAA receptors, limiting receptor expression and activity at the plasma membrane. However, GABAA receptors containing variant subunits can retain activity, indicating that enhancing the folding, assembly, and trafficking of these variant receptors offers a potential opportunity to mitigate pathology associated with genetic epilepsy. Results Here, we demonstrate that pharmacologically enhancing endoplasmic reticulum (ER) proteostasis using small molecule activators of the ATF6 (Activating Transcription Factor 6) signaling arm of the unfolded protein response (UPR) increases the assembly, trafficking, and surface expression of variant GABAA receptors. These improvements are attributed to ATF6-dependent remodeling of the ER proteostasis environment, which increases protein levels of pro-folding ER proteostasis factors including the ER chaperone BiP (Immunoglobulin Binding Protein) and trafficking receptors, such as LMAN1 (Lectin Mannose-Binding 1) and enhances their interactions with GABAA receptors. Importantly, we further show that pharmacologic ATF6 activators increase the activity of GABAA receptors at the cell surface, revealing the potential for this strategy to restore receptor activity to levels that could mitigate disease pathogenesis. Conclusions These results indicate that pharmacologic ATF6 activators offer an opportunity to restore GABAA receptor activity in diseases including genetic epilepsy and point to the potential for similar pharmacologic enhancement of ER proteostasis to improve trafficking of other disease-associated variant ion channels implicated in etiologically-diverse diseases.

The use of metal compounds such as cisplatin and its derivatives as therapeutic and diagnostic agents against various diseases is well established. Although metallodrugs have been very successful clinically, low therapeutic selectivity and the potential toxicity of the metal compounds mandate the need for a continuous search for more efficient and specific treatments. Hence, the use of computer‐aided drug design (CADD), molecular modelling and theoretical studies in designing, selecting and applying potential drug candidates have become ever more necessary. Among the many computational and theoretical techniques, molecular docking and density functional theory play significant roles in predicting drug activity. Recent methodologies, within the past 5 years, that rely on these techniques to advance the adoption of potential metallodrugs are highlighted and thoroughly discussed. This is because advancements in computing power have led to the wide use of CADD approaches for drug discovery, development and analysis to shorten the time and reduce the costs associated with drug discovery. [ABSTRACT FROM AUTHOR]

I. INTRODUCTION The biggest purchase most people make in their lifetimes is a new home. (2) Over the past spring and summer, home prices have grown faster than at any [...], Alaska&apos;s Unfair and Deceptive Acts and Practices (UDAP) statute was designed to provide broad, robust protections for everyday Alaskan consumers. Astonishingly, Alaska is one of only three states that does not protect Alaskans under its UDAP statute when they fall victim to fraudulent schemes involving real property. The Alaska Supreme Court has consistently upheld this interpretation of the UDAP statute by relying on precedent from over thirty years ago. At the same time, due to the COVID-19 pandemic, everyday Alaskans are more economically vulnerable than ever before, with the atmosphere being ripe for proliferation of fraudulent real property schemes. This Note argues that the court has misapplied precedent and must therefore reevaluate the statute&apos;s application to real property transactions, especially because the statute has been amended and strengthened since the court&apos;s original rulings. If it does not, because of the sheer importance of housing in everyday life, a significant portion of the population could face devastating consequences not only to their economic wellbeing but also to their safety, security, and livelihood.

Comprehensive policy measures are needed to close the emissions gap between Nationally Determined Contributions and emissions goals of the Paris Agreement. Here the authors present a Bridge scenario that may aid in closing the emissions gap by 2030.

A high-performance Driver State Monitoring (DSM) application for the detection of driver drowsiness is presented in this paper. The popular Ensemble of Regression Trees (ERTs) machine learning method has been employed for the alignment of 68 facial landmarks. Open-source implementation of ERTs for facial shape alignment has been ported to different platforms and adapted for the acceleration of the frame processing speed using reconfigurable hardware. Reducing the frame processing latency saves time that can be used to apply frame-to-frame facial shape coherency rules. False face detection and false shape estimations can be ignored for higher robustness and accuracy in the operation of the DSM application without sacrificing the frame processing rate that can reach 65 frames per second. The sensitivity and precision in yawning recognition can reach 93% and 97%, respectively. The implementation of the employed DSM algorithm in reconfigurable hardware is challenging since the kernel arguments require large data transfers and the degree of data reuse in the computational kernel is low. Hence, unconventional hardware acceleration techniques have been employed that can also be useful for the acceleration of several other machine learning applications that require large data transfers to their kernels with low reusability.

The regeneration of articular cartilage remains a serious problem in various pathological conditions such as osteoarthritis, due to the tissue’s low self-healing capacity. The latest therapeutic approaches focus on the construction of biomaterials that induce cartilage repair. This research describes the design, synthesis, and investigation of a safe, “smart”, fibrous scaffold containing a genetically incorporated active peptide for chondrogenic induction. While possessing specific sequences and the respective mechanical properties from natural fibrous proteins, the fibers also incorporate a Transforming Growth Factor-β1 (TGF-β1)-derived peptide (YYVGRKPK) that can promote chondrogenesis. The scaffold formed stable porous networks with shear-thinning properties at 37 °C, as shown by SEM imaging and rheological characterization, and were proven to be non-toxic to human dental pulp stem cells (hDPSCs). Its chondrogenic capacity was evidenced by a strong increase in the expression of specific chondrogenesis gene markers SOX9, COL2, ACAN, TGFBR1A, and TGFBR2 in cells cultured on “scaffold-TGFβ1” for 21 days and by increased phosphorylation of intracellular signaling proteins Smad-2 and Erk-1/2. Additionally, intense staining of glycosaminoglycans was observed in these cells. According to our results, “scaffold-TGFβ1” is proposed for clinical studies as a safe, injectable treatment for cartilage degeneration.

SARS-CoV-2 ORF3a accessory protein was found to be involved in virus release, immunomodulation and exhibited a pro-apoptotic character. In order to unravel a potential ORF3a-induced apoptotic and inflammatory death mechanism, lung epithelial cells (A549) were transfected with in vitro synthesized ORF3a mRNA. The protein’s dynamic involvement as “stress factor” for the endoplasmic reticulum, causing the activation of PERK kinase and other UPR-involved proteins and therefore the upregulation of their signaling pathway executioners (ATF6, XBP-1s, PERK, phospho eIF2a, ATF4, CHOP, GADD34), has been clearly demonstrated. Furthermore, the overexpression of BAX and BH3-only pro-apoptotic protein PUMA, the upregulation of Bcl-2 family genes (BAX, BAK, BID, BAD), the reduced expression of Bcl-2 in mRNA and protein levels, and lastly, the cleavage of PARP-1 and caspase family members (caspase-3,-8 and -9) indicate that ORF3a displays its apoptotic character through the mitochondrial pathway of apoptosis. Moreover, the upregulation of NFκB, phosphorylation of p65 and IκΒα and the elevated expression of pro-inflammatory cytokines (IL-1b, IL-6, IL-8 and IL-18) in transfected cells with ORF3a mRNA indicate that this protein causes the inflammatory response through NFκB activation and therefore triggers lung injury. An intriguing finding of our study is that upon treatment of the ORF3a-transfected cells with GSK2606414, a selective PERK inhibitor, both complications (apoptosis and inflammatory response) were neutralized, and cell survival was favored, whereas treatment of transfected cells with z-VAD (a pan-caspase inhibitor) despite inhibiting cell death, could not ameliorate the inflammatory response of transfected A549 cells. Given the above, we point out that PERK kinase is a “master tactician” and its activation constitutes the main stimulus for the emergence of ORF3a apoptotic and inflammatory nature and therefore could serve as potential target for developing novel therapeutic approaches against COVID-19.

This work describes the design, preparation, and deep investigation of “intelligent nanobiomaterials” that fulfill the safety rules and aim to serve as “signal deliverers” for osteogenesis, harboring a specific peptide that promotes and enhances osteogenesis at the end of their hydrogel fibers. The de novo synthesized protein fibers, besides their mechanical properties owed to their protein constituents from elastin, silk fibroin and mussel-foot adhesive protein-1 as well as to cell-attachment peptides from extracellular matrix glycoproteins, incorporate the Bone Morphogenetic Protein-2 (BMP2) peptide (AISMLYLDEN) that, according to our studies, serves as “signal deliverer” for osteogenesis. The osteogenetic capacity of the biomaterial has been evidenced by investigating the osteogenic marker genes ALP, RUNX2, Osteocalcin, COL1A1, BMPR1A, and BMPR2, which were increased drastically in cells cultured on scaffold-BMP2 for 21 days, even in the absence of osteogenesis medium. In addition, the induction of phosphorylation of intracellular Smad-1/5 and Erk-1/2 proteins clearly supported the osteogenetic capacity of the biomaterial.

To evaluate the effectiveness of current national policies in achieving global temperature targets is important but a systematic multi-model evaluation is still lacking. Here the authors identified a reduction of 3.5 GtCO2 eq of current national policies relative to a baseline scenario without climate policies by 2030 due to the increasing low carbon share of final energy and the improving final energy intensity.

Computing has undergone a significant transformation over the past two decades, shifting from a machine-based approach to a human-centric, virtually invisible service known as ubiquitous or pervasive computing. This change has been achieved by incorporating small embedded devices into a larger computational system, connected through networking and referred to as edge devices. When these devices are also connected to the Internet, they are generally named Internet-of-Thing (IoT) devices. Developing Machine Learning (ML) algorithms on these types of devices allows them to provide Artificial Intelligence (AI) inference functions such as computer vision, pattern recognition, etc. However, this capability is severely limited by the device’s resource scarcity. Embedded devices have limited computational and power resources available while they must maintain a high degree of autonomy. While there are several published studies that address the computational weakness of these small systems-mostly through optimization and compression of neural networks- they often neglect the power consumption and efficiency implications of these techniques. This study presents power efficiency experimental results from the application of well-known and proven optimization methods using a set of well-known ML models. The results are presented in a meaningful manner considering the “real world” functionality of devices and the provided results are compared with the basic “idle” power consumption of each of the selected systems. Two different systems with completely different architectures and capabilities were used providing us with results that led to interesting conclusions related to the power efficiency of each architecture.

Hematological changes are commonly observed following prolonged exposure to hypoxia and bed rest. Typically, such responses have been reported as means and standard deviations, however, investigation into the responses of individuals is insufficient. Therefore, the present study retrospectively assessed individual variation in the hematological responses to severe inactivity (bed rest) and hypoxia. The data were derived from three-bed rest projects: two 10-d (LunHab project: 8 males; FemHab project: 12 females), and one 21-d (PlanHab project: 11 males). Each project comprised a normoxic bed rest (NBR; PIO2=133mmHg) and hypoxic bed rest (HBR; PIO2=91mmHg) intervention, where the subjects were confined in the Planica facility (Rateče, Slovenia). During the HBR intervention, subjects were exposed to normobaric hypoxia equivalent to an altitude of 4,000m. NBR and HBR interventions were conducted in a random order and separated by a washout period. Blood was drawn prior to (Pre), during, and post bed rest (R1, R2, R4) to analyze the individual variation in the responses of red blood cells (RBC), erythropoietin (EPO), and reticulocytes (Rct) to bed rest and hypoxia. No significant differences were found in the mean ∆(Pre-Post) values of EPO across projects (LunHab, FemHab, and PlanHab; p>0.05), however, female EPO responses to NBR (Range - 17.39, IQR – 12.97 mIU.ml−1) and HBR (Range – 49.00, IQR – 10.91 mIU.ml−1) were larger than males (LunHab NBR Range – 4.60, IQR – 2.03; HBR Range – 7.10, IQR – 2.78; PlanHab NBR Range – 7.23, IQR – 1.37; HBR Range – 9.72, IQR – 4.91 mIU.ml−1). Bed rest duration had no impact on the heterogeneity of EPO, Rct, and RBC responses (10-d v 21-d). The resultant hematological changes that occur during NBR and HBR are not proportional to the acute EPO response. The following cascade of hematological responses to NBR and HBR suggests that the source of variability in the present data is due to mechanisms related to hypoxia as opposed to inactivity alone. Studies investigating hematological changes should structure their study design to explore these mechanistic responses and elucidate the discord between the EPO response and hematological cascade to fully assess heterogeneity.

Summary: Ants (Hymenoptera: Formicidae) are familiar inhabitants of most terrestrial environments. Although we are aware of the ability of many species to sting, knowledge of ant venom chemistry remains limited. Herein, we describe the discovery and characterization of an O-linked glycopeptide (Mg7a) as a major component of the venom of the ant Myrmecia gulosa. Electron transfer dissociation and higher-energy collisional dissociation tandem mass spectrometry were used to localize three α-N-acetylgalactosaminyl residues (α-GalNAc) present on the 63-residue peptide. To allow for functional studies, we synthesized the full-length glycosylated peptide via solid-phase peptide synthesis, combined with diselenide–selenoester ligation-deselenization chemistry. We show that Mg7a is paralytic and lethal to insects, and triggers pain behavior and inflammation in mammals, which it achieves through a membrane-targeting mode of action. Deglycosylation of Mg7a renders it insoluble in aqueous solution, suggesting a key solubilizing role of the O-glycans.