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As long-living apex predators, sharks tend to bioaccumulate trace metals through their diet. The distribution of Al, As, Cd, Co, Cr, Cs, Cu, Fe, Mn, Ni, Pb, V, Zn and Hg in different tissues (muscle, liver, heart, gills and gonads) of large-size (58–390 cm) sharks, some of which rare, of the eastern Mediterranean Sea was studied. Trace metals analyses in samples originating from ten different Chondrichthyes species were performed by inductively coupled plasma–mass spectrometry (ICP-MS) and Cold Vapor Atomic Absorption Spectrometry (CVAAS) for Hg. Data on trace metal levels are for the first time reported herewith for the species O. ferox and H. nakamurai. Higher median concentrations of trace metals were generally determined in the liver. The concentrations of Hg, Cs and As in the muscle increased proportionally with body length. Statistically significant differences between sexes were recorded for Hg, Cr, Ni and As (p = 0.015) in the muscle tissues of P. glauca. Muscle tissue Hg concentrations exceeded the EU maximum limit (1 μg g−1 wet weight) in 67% of the individuals sampled, with the highest concentrations detected in O. ferox and S. zygaena, whereas regarding Pb (limit 0.30 μg g−1 ww), the corresponding percentage was 15%. Arsenic concentrations were also of concern in almost all shark tissues examined.

The diversity and distribution of polychaetes in the coastal area and the EEZ of the Republic of Cyprus is presented based on both the literature records and new data acquired in a wide range of environmental monitoring programmes and research projects. A total of 585 polychaete species belonging to 49 families were reported in Cyprus waters; among them, 205 species (34%) were recorded based on the literature only, 149 (26%) were new records based on our own data, and a total of 231 spp. (40%) were recorded from both the literature and new data. A total of 51 polychaete species were identified as non-indigenous; among them, 32 were confirmed as alien species, 4 were considered cryptogenic, and 15 were considered questionable as there were doubts about their identity. The Indo-Pacific Schistomeringos loveni was reported for the first time in the Mediterranean Sea, while four species already reported in the literature, namely, Bispira melanostigma, Fimbriosthenelais longipinnis Leonnates aylaoberi, and Rhodopsis pusilla, were added to the list of non-indigenous polychaetes in the Mediterranean Sea. The current work highlights the importance of implementing environmental monitoring programmes and carrying out research surveys targeting benthic macrofauna assemblages.

Multi-story, old reinforced concrete (RC) structures with a “soft-story” on the ground floor, sustain considerable damage to the soft story during earthquakes due to the presence of masonry infills in the upper stories. Aspects of such masonry infill–RC frame interaction are briefly discussed and a particular retrofitting scheme for the soft story is studied. It consists of RC infills, added within the bays of the ground floor frames and combined with RC jacketing of the surrounding frame, aiming to avert such soft-story deficiency. The impact of such a retrofit is studied through the measured response of 1/3 scaled single-story, one-bay frames subjected to cyclic seismic-type horizontal loads. It is shown that this retrofit results in a considerable beneficial increase in stiffness, strength, and plastic energy consumption. The importance of the presence of effective steel ties connecting this RC infill with the surrounding frame is also demonstrated. In order to achieve these desired beneficial effects to such vulnerable buildings, additional design objectives are established with the aim of avoiding premature failure of the RC infill panel and/or fracture of the steel ties and to protect the surrounding RC frame from undesired local damage. A numerical methodology, which is validated by using the obtained experimental results, is shown to be capable of predicting reasonably well these important response mechanisms and can therefore be utilized for design purposes.

Cystic fibrosis (CF) is a disorder causing dysfunctional ion transport resulting in the accumulation of viscous mucus. This environment fosters a chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans, a gram-negative aerobic bacillus, has been increasingly associated with antibiotic resistance and chronic colonisation in CF. In this study, we aimed to create a reproducible model of CF infection using an artificial sputum medium (ASMDM-1) with bronchial (BEAS-2B) and macrophage (THP-1) cells to test A. xylosoxidans infection and treatment toxicity. This study was conducted in three distinct stages. First, the tolerance of BEAS-2B cell lines and two A. xylosoxidans strains against ASMDM-1 was optimised. Secondly, the cytotoxicity of combined therapy (CT) comprising N-acetylcysteine (NAC) and the antibiotics colistin or ciprofloxacin was tested on cells alone in the sputum model in both BEAS-2B and THP-1 cells. Third, the efficacy of CT was assessed in the context of a bacterial infection within the live cell/sputum model. We found that a model using 20% ASMDM-1 in both cell populations tolerated a colistin–NAC-based CT and could significantly reduce bacterial loads in vitro (~2 log10 CFU/mL compared to untreated controls). This pilot study provides the foundation to study other bacterial opportunists that infect the CF lung to observe infection and CT kinetics. This model also acts as a springboard for more complex co-culture models.

A popular water pipe system, used in many countries, is one formed by prestressed cylindrical concrete pipes (PCCP). This study used the results of an experimental investigation on ten (10) PCCP samples taken from an existing water pipeline. The objective was to investigate their bearing capacity under three-edge bending or internal hydraulic pressure loads to check the capability of specific retrofitting/strengthening schemes to upgrade this bearing capacity and thus enhance the operational period (Part A). In this part B study, the measured response of the PCCP pipes was made to validate a numerical approach aimed at numerically simulating the behavior of the original and retrofitted PCCP pipes under hydraulic internal pressure. From the obtained numerical results, it was seen that the assumed nonlinear mechanisms for the concrete volume and steel membrane were verified by comparing numerical predictions with measurements in terms of strain response of the steel membrane, damage patterns of the concrete volume, and the overall internal pressure versus radial expansion response. The numerical predictions of the bearing capacity contribution of the fully active prestress as well as the three specific jacketing schemes, including carbon fiber reinforced polymer (CFRP) or reinforced concrete (RC) jackets, were also verified from comparisons with the corresponding measured response.

For many cancer types, being undetectable from early symptoms or blood tests, or often detected at late stages, medical imaging emerges as the most efficient tool for cancer screening. MRI, ultrasound, X-rays (mammography), and X-ray CT (CT) are currently used in hospitals with variable costs. Diagnostic materials that can detect breast tumors through molecular recognition and amplify the signal at the targeting site in combination with state-of-the-art CT techniques, such as dual-energy CT, could lead to a more precise detection and assist significantly in image-guided intervention. Herein, we have developed a ligand-specific X-ray contrast agent that recognizes α5β1 integrins overexpressed in MDA-MB-231 breast cancer cells for detection of triple (−) cancer, which proliferates very aggressively. In vitro studies show binding and internalization of our nanoprobes within those cells, towards uncoated nanoparticles (NPs) and saline. In vivo studies show high retention of ~3 nm ligand-PEG-S-AuNPs in breast tumors in mice (up to 21 days) and pronounced CT detection, with statistical significance from saline and iohexol, though only 0.5 mg of metal were utilized. In addition, accumulation of ligand-specific NPs is shown in tumors with minimal presence in other organs, relative to controls. The prolonged, low-metal, NP-enhanced spectral-CT detection of triple (−) breast cancer could lead to breakthrough advances in X-ray cancer diagnostics, nanotechnology, and medicine.

A popular water pipe system used in many countries is one formed by prestressed cylindrical concrete pipes (PCCPs) formed by identical precast moduli joined together in situ. This technology was and still is quite popular in many water supply systems internationally. This technology was mainly selected at the time due to its cost-based comparative advantage. However, over the years, numerous incidents of structural failures have been reported for this type of pipeline, causing, in some cases, serious disruption of the water supply. This study summarizes the results of an experimental investigation on ten (10) PCCP specimens taken from an existing water pipeline with the objective of investigating their bearing capacity under either three-edge bending or internal hydraulic pressure loads. Moreover, there is a need to check the capability of specific retrofitting/strengthening schemes to upgrade this bearing capacity and thus enhance the operational period. Provided that the prestressing wires are fully active according to design specifications, the original specimen performed satisfactorily for the set internal hydraulic pressure limit of 8.5 bar. Specimens retrofitted with either internal or external CFRP or RC jacketing performed satisfactorily for internal hydraulic pressure levels well above this 8.5 bar limit. A critical factor is, as expected, the loss of prestress.

In cystic fibrosis (CF), mutations in the CF transmembrane conductance regulator protein reduce ionic exchange in the lung, resulting in thicker mucus, which impairs mucociliary function, airway inflammation and infection. The mucosal and nutritional environment of the CF lung is inadequately mimicked by commercially available growth media, as it lacks key components involved in microbial pathogenesis. Defining the nutritional composition of CF sputum has been a long-term goal of in vitro research into CF infections to better elucidate bacterial growth and infection pathways. This narrative review highlights the development of artificial sputum medium, from a viable in vitro method for understanding bacterial mechanisms utilised in CF lung, to uses in the development of antimicrobial treatment regimens and examination of interactions at the epithelial cell surface and interior by the addition of host cell layers. The authors collated publications based on a PubMed search using the key words: “artificial sputum media” and “cystic fibrosis”. The earliest iteration of artificial sputum media were developed in 1997. Formulations since then have been based either on published data or chemically derived from extracted sputum. Formulations contain combinations of mucin, extracellular DNA, iron, amino acids, and lipids. A valuable advantage of artificial sputum media is the ability to standardise media composition according to experimental requirements.

Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here, we show by cell-free reconstitution that binding to flat lipid membranes requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septin hexamers form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12- to 18-nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4-nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.

Today, there are excellent resources for the semantic annotation of biomedical text. These resources span from ontologies, tools for NLP, annotators, and web services. Most of these are available either in the form of open source components (i.e., MetaMap) or as web services that offer free access (i.e., Whatizit). In order to use these resources in automatic text annotation pipelines, researchers face significant technical challenges. For open-source tools, the challenges include the setting up of the computational environment, the resolution of dependencies, as well as the compilation and installation of the software. For web services, the challenge is implementing clients to undertake communication with the respective web APIs. Even resources that are available as Docker containers (i.e., NCBO annotator) require significant technical skills for installation and setup. This work deals with the task of creating ready-to-install and run Research Objects (ROs) for a large collection of components in biomedical text analysis. These components include (a) tools such as cTAKES, NOBLE Coder, MetaMap, NCBO annotator, BeCAS, and Neji; (b) ontologies from BioPortal, NCBI BioSystems, and Open Biomedical Ontologies; and (c) text corpora such as BC4GO, Mantra Gold Standard Corpus, and the COVID-19 Open Research Dataset. We make these resources available in OpenBio.eu, an open-science RO repository and workflow management system. All ROs can be searched, shared, edited, downloaded, commented on, and rated. We also demonstrate how one can easily connect these ROs to form a large variety of text annotation pipelines.

The use of hydrogen as a renewable fuel has attracted great attention in recent years. The decomposition of formic acid under mild conditions was investigated using a 2%Pd6Zn4 catalyst in a batch reactor. The results showed that the conversion of formic acid increases with reaction temperature and with the formic acid concentration. A process-simulation model was developed to predict the decomposition of formic acid using 2%Pd6Zn4 in a batch reactor. The model demonstrated very good validation with the experimental work. Further comparisons between the 2%Pd6Zn4 catalyst and a commercial Pd/C catalyst were carried out. It was found that the 2%Pd6Zn4 demonstrated significantly higher conversions when compared with the commercial catalyst.

The ultimate aim of any antimicrobial treatment is a better infection outcome for the patient. Here, we review the current state of treatment for bacterial infections in cystic fibrosis (CF) lung while also investigating potential new treatments being developed to see how they may change the dynamics of antimicrobial therapy. Treatment with antibiotics coupled with regular physical therapy has been shown to reduce exacerbations and may eradicate some strains. Therapies such as hypertonic saline and inhaled PulmozymeTM (DNase-I) improve mucus clearance, while modifier drugs, singly and more successfully in combination, re-open certain mutant forms of the cystic fibrosis transmembrane conductance regulator (CFTR) to enable ion passage. No current method, however, completely eradicates infection, mainly due to bacterial survival within biofilm aggregates. Lung transplants increase lifespan, but reinfection is a continuing problem. CFTR modifiers normalise ion transport for the affected mutations, but there is conflicting evidence on bacterial clearance. Emerging treatments combine antibiotics with novel compounds including quorum-sensing inhibitors, antioxidants, and enzymes, or with bacteriophages, aiming to disrupt the biofilm matrix and improve antibiotic access. Other treatments involve bacteriophages that target, infect and kill bacteria. These novel therapeutic approaches are showing good promise in vitro, and a few have made the leap to in vivo testing.

The practical difficulties in upgrading the structural performance of existing reinforced concrete (RC) structures is discussed, when retrofitting structural members by conventional RC jacketing. The use of retrofitting schemes employing externally applied fiber reinforcing polymer (FRP) strips attracted considerable research attention as a preferable alternative. Such retrofitting FRP schemes aiming to upgrade the shear capacity of existing RC beams have been examined in many published works employing such externally applied FRP shear reinforcing schemes without confronting the practical difficulties arising from the presence of the RC slab. Anchoring external CFRP strips aiming to shear upgrade, which is the focus here, overrides this difficulty. It is shown that effective anchoring, using either mechanical anchors such as the ones devised by the authors or CFRP anchor ropes produced by the industry, can effectively upgrade the shear capacity of an RC T-beam under-designed in shear to the desired level. A novel laboratory test set-up, devised by the authors, can be utilized to quantify the tensile capacity of CFRP stirrups with or without anchors, that can be of practical use. The predicted, according to design guidelines, upgraded shear capacity of the tested prototype RC T-beam, employing the used shear retrofitting schemes, under-estimates the measured shear capacity by 58%. This conservatism can counter-balance uncertainties arising from in situ conditions in constructing the various parts of such a shear retrofitting scheme.

The term lipophagy is used to describe the autophagic degradation of lipid droplets, the main lipid storage organelles of eukaryotic cells. Ever since its discovery in 2009, lipophagy has emerged as a significant component of lipid metabolism with important implications for organismal health. This review aims to provide a brief summary of our current knowledge on the mechanisms that are responsible for regulating lipophagy and the impact the process has under physiological and pathological conditions.

Security and privacy (SP)-related challenges constitute a significant barrier to the wider adoption of Internet of Things (IoT)/Industrial IoT (IIoT) devices and the associated novel applications and services. In this context, patterns, which are constructs encoding re-usable solutions to common problems and building blocks to architectures, can be an asset in alleviating said barrier. More specifically, patterns can be used to encode dependencies between SP properties of individual smart objects and corresponding properties of orchestrations (compositions) involving them, facilitating the design of IoT solutions that are secure and privacy-aware by design. Motivated by the above, this work presents a survey and taxonomy of SP patterns towards the creation of a usable pattern collection. The aim is to enable decomposition of higher-level properties to more specific ones, matching them to relevant patterns, while also creating a comprehensive overview of security- and privacy-related properties and sub-properties that are of interest in IoT/IIoT environments. To this end, the identified patterns are organized using a hierarchical taxonomy that allows their classification based on provided property, context, and generality, while also showing the relationships between them. The two high-level properties, Security and Privacy, are decomposed to a first layer of lower-level sub-properties such as confidentiality and anonymity. The lower layers of the taxonomy, then, include implementation-level enablers. The coverage that these patterns offer in terms of the considered properties, data states (data in transit, at rest, and in process), and platform connectivity cases (within the same IoT platform and across different IoT platforms) is also highlighted. Furthermore, pointers to extensions of the pattern collection to include additional patterns and properties, including Dependability and Interoperability, are given. Finally, to showcase the use of the presented pattern collection, a practical application is detailed, involving the pattern-driven composition of IoT/IIoT orchestrations with SP property guarantees.

Several brain diseases are characterized by abnormally strong neuronal synchrony. Coordinated Reset (CR) stimulation was computationally designed to specifically counteract abnormal neuronal synchronization processes by desynchronization. In the presence of spike-timing-dependent plasticity (STDP) this may lead to a decrease of synaptic excitatory weights and ultimately to an anti-kindling, i.e. unlearning of abnormal synaptic connectivity and abnormal neuronal synchrony. The long-lasting desynchronizing impact of CR stimulation has been verified in pre-clinical and clinical proof of concept studies. However, as yet it is unclear how to optimally choose the CR stimulation frequency, i.e. the repetition rate at which the CR stimuli are delivered. This work presents the first computational study on the dependence of the acute and long-term outcome on the CR stimulation frequency in neuronal networks with STDP. For this purpose, CR stimulation was applied with Rapidly Varying Sequences (RVS) as well as with Slowly Varying Sequences (SVS) in a wide range of stimulation frequencies and intensities. Our findings demonstrate that acute desynchronization, achieved during stimulation, does not necessarily lead to long-term desynchronization after cessation of stimulation. By comparing the long-term effects of the two different CR protocols, the RVS CR stimulation turned out to be more robust against variations of the stimulation frequency. However, SVS CR stimulation can obtain stronger anti-kindling effects. We revealed specific parameter ranges that are favorable for long-term desynchronization. For instance, RVS CR stimulation at weak intensities and with stimulation frequencies in the range of the neuronal firing rates turned out to be effective and robust, in particular, if no closed loop adaptation of stimulation parameters is (technically) available. From a clinical standpoint, this may be relevant in the context of both invasive as well as non-invasive CR stimulation.

The successive nuclear division cycles in the syncytial Drosophila embryo are accompanied by ingression and regression of plasma membrane furrows, which surround individual nuclei at the embryo periphery, playing a central role in embryo compartmentalization prior to cellularization. Here, we demonstrate that cell cycle changes in dynamin localization and activity at the plasma membrane (PM) regulate metaphase furrow formation and PM organization in the syncytial embryo. Dynamin was localized on short PM furrows during interphase, mediating endocytosis of PM components. Dynamin redistributed off ingressed PM furrows in metaphase, correlating with stabilized PM components and the associated actin regulatory machinery on long furrows. Acute inhibition of dynamin in the temperature sensitive shibire mutant embryo resulted in morphogenetic consequences in the syncytial division cycle. These included inhibition of metaphase furrow ingression, randomization of proteins normally polarized to intercap PM and disruption of the diffusion barrier separating PM domains above nuclei. Based on these findings, we propose that cell cycle changes in dynamin orchestrate recruitment of actin regulatory machinery for PM furrow dynamics during the early mitotic cycles in the Drosophila embryo.

Interoception, the sensitivity to visceral sensations, plays an important role in homeostasis and guiding motivated behaviour. It is also considered to be fundamental to self-awareness. Despite its importance, the developmental origins of interoceptive sensitivity remain unexplored. We here provide the first evidence for implicit, flexible interoceptive sensitivity in 5 month old infants using a novel behavioural measure, coupled with an established cortical index of interoceptive processing. These findings have important implications for the understanding of the early developmental stages of self-awareness, self-regulation and socio-emotional abilities.

Abstract Our current understanding of how natural genetic variation affects gene expression beyond well‐annotated coding genes is still limited. The use of deep sequencing technologies for the study of expression quantitative trait loci (eQTLs) has the potential to close this gap. Here, we generated the first recombinant strain library for fission yeast and conducted an RNA‐seq‐based QTL study of the coding, non‐coding, and antisense transcriptomes. We show that the frequency of distal effects (trans‐eQTLs) greatly exceeds the number of local effects (cis‐eQTLs) and that non‐coding RNAs are as likely to be affected by eQTLs as protein‐coding RNAs. We identified a genetic variation of swc5 that modifies the levels of 871 RNAs, with effects on both sense and antisense transcription, and show that this effect most likely goes through a compromised deposition of the histone variant H2A.Z. The strains, methods, and datasets generated here provide a rich resource for future studies.

Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 µM. No phenotype other than death was observed for compounds 1–3, 5, 6.

Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that directly target HIV-1 capsid (CA) via a novel mechanism of action. The compounds exhibit potent antiviral activity against HIV-1 laboratory strains, clinical isolates, and HIV-2, and inhibit both early and late events in the viral replication cycle. We present mechanistic studies indicating that these early and late activities result from the compound affecting viral uncoating and assembly, respectively. We show that amino acid substitutions in the N-terminal domain of HIV-1 CA are sufficient to confer resistance to this class of compounds, identifying CA as the target in infected cells. A high-resolution co-crystal structure of the compound bound to HIV-1 CA reveals a novel binding pocket in the N-terminal domain of the protein. Our data demonstrate that broad-spectrum antiviral activity can be achieved by targeting this new binding site and reveal HIV CA as a tractable drug target for HIV therapy.

Drosophila embryogenesis begins with 13 rapid nuclear divisions within a common cytoplasm. These divisions produce ~6,000 nuclei that, during the next division cycle, become encased in plasma membrane (PM) and generate the primary embryonic epithelium in the process known as cellularization. Despite the absence of PM boundaries between syncytial nuclei, the secretory membrane system is organized in functionally compartmentalized units around individual nuclei.1 We have recently used in vivo fluorescence imaging to characterize the dynamics of proteins in the PM of the embryonic syncytium. These studies revealed that the PM is polarized already before cellularization. One PM region resides above individual nuclei and has apical-like features, while PM regions lateral to nuclei have basolateral characteristics. Optical highlighting experiments showed that membrane components do not exchange between PM regions that reside above adjacent nuclei. An intact F-actin network was shown to be important for both the PM apicobasal-like polarity and the diffusion barriers within the syncytial PM. Our findings, as well as their possible implications, are further discussed in this Addendum.