Marine ecosystems are constantly being threatened by contaminants produced by human activities. There is an urge to better understand their impacts on marine organisms and develop reliable tools for ...biomonitoring studies, while also assessing their potential impacts on human health. Given their position on top of food webs, sharks are particularly susceptible to bioaccumulation, making them potential sentinel species of marine contamination. The main objective of this study was to find suitable biomarkers for future marine pollution biomonitoring studies by correlating biochemical responses with tissue contaminant body burden in blue sharks (Prionace glauca), a species heavily caught and consumed by humans, while also addressing their general health. The chemical contaminants analysed comprised different persistent organic pollutants (POPs) families from polychlorinated compounds to brominated flame retardants (BFRs) and perfluorinated compounds (PFCs) and different trace and heavy metals. Concentrations of some contaminants in sharks' tissues were found to be above the legally allowed limits for human consumption. A canonical correspondence analysis (CCA) was performed and some strong associations were found between biochemical responses and contaminants' accumulation levels. DNA damage and lipid peroxidation levels, as well as the inhibition of the antioxidant enzyme glutathione peroxidase, were the main effects and consequences of contamination. The impact of contamination on these vital macromolecules underlines the suboptimal conditions of the sampled P. glauca, which can ultimately lead to the degradation of core ecological aspects, such as swimming, feeding, and reproduction. It can be concluded that P. glauca demonstrates great potential to be used as environmental sentinel and suitable biomarker candidates were identified in this work. Moreover, this study also highlights the risks that the consumption of blue shark derived products can pose to human health, which is of upmost interest as the sampled organisms were still juveniles and already presented values above regulatory limits.
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•Metals and POPs were quantified in the muscle and liver of blue sharks.•Biochemical stress responses were addressed in the same sharks.•Correlations between contaminant levels and biochemical responses were found.•Suitable biomarkers for future pollution biomonitoring studies were proposed.•Sharks presented contamination values above regulatory limits for human consumption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ca(2)(+)i signalling is a key regulatory mechanism in sperm function. In mammalian sperm the Ca(2)(+)-permeable plasma membrane ion channel CatSper is central to Ca(2)(+)i signalling, but there is ...good evidence that Ca(2)(+) stored in intracellular organelles is also functionally important. Here we briefly review the current understanding of the diversity of Ca(2)(+) stores and the mechanisms for the regulation of their activity. We then consider the evidence for the involvement of these stores in Ca(2)(+)i signalling in mammalian (primarily human) sperm, the agonists that may activate these stores and their role in control of sperm function. Finally we consider the evidence that membrane Ca(2)(+) channels and stored Ca(2)(+) may play discrete roles in the regulation of sperm activities and propose a mechanism by which these different components of the sperm Ca(2)(+)-signalling apparatus may interact to generate complex and spatially diverse Ca(2)(+)i signals.
The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a ...role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception.
Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of articulatory representations during passive listening using carefully controlled stimuli (spoken syllables) in combination with multivariate fMRI decoding. Our approach enabled us to disentangle brain responses to acoustic and articulatory speech properties. In particular, it revealed articulatory-specific brain responses of speech at multiple cortical levels, including auditory, sensorimotor, and motor regions, suggesting the representation of sensorimotor information during passive speech perception.
This paper presents an experimental study about the use of innovative bio-based pultruded carbon-fiber-reinforced polymer (CFRP) laminates for structural strengthening. The bio-based laminates were ...produced in the framework of an applied research project (BioLam) using a resin system with 50% (wt.%) bio-based content, obtained from renewable resources. In the first part of the study, their tensile and interlaminar shear properties were characterized and compared with those of conventional oil-based CFRP laminates. In the second part of the study, the bond behavior to concrete of both types of CFRP laminates applied according to the externally bonded reinforcement (EBR) technique was assessed by means of single-lap shear tests performed on CFRP-strengthened concrete blocks; the experimental results obtained from these tests were then used in a numerical procedure to calibrate local bond vs. slip laws for both types of laminates. The final part of this study comprised four-point bending tests on full-scale EBR-CFRP-strengthened reinforced concrete (RC) beams to assess the structural efficacy of the bio-based laminates; these were benchmarked with tests performed on similar RC beams strengthened with conventional CFRP laminates. The results obtained in this study show that the (i) material properties, (ii) the bond behavior to concrete, and (iii) the structural efficacy of the developed bio-based CFRP laminates are comparable to those of their conventional counterparts, confirming their potential to be used in the strengthening of RC structures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper presents a literature review and results of an experimental study about the effects of thermal cycles on the physical and mechanical properties of pultruded glass fibre reinforced polymer ...(GFRP) profiles used in civil engineering structural applications. The GFRP profiles used in this study present similar fibre architecture, differing only in their matrix nature: unsaturated polyester and vinylester. Small-scale coupons obtained from both types of GFRP profiles were exposed to a Mediterranean range of thermal variations (−5°C to 40°C) for up to 190 cycles in a dry condition. The effects of such exposure on the physical and mechanical response of the GFRP materials were assessed and compared using the following experimental techniques: (a) dynamic mechanical analyses (DMA) to assess the viscoelastic behaviour; (b) tensile, flexural and interlaminar shear tests, to evaluate the mechanical properties; and (c) scanning electron microscopy (SEM), to monitor the potential changes in the microstructure due to the degradation (if any) caused by the thermal cycles, as well as the possible changes into the main mechanisms of fracture. After exposure to thermal cycles, the viscoelastic behaviour of the GFRP profiles presented only slight changes, indicating no significant degradation, neither in the matrix structure nor at the fibre–matrix interphase. In terms of mechanical properties, both types of GFRP materials suffered slight changes regarding tensile and interlaminar shear properties. Flexural properties were more affected, particularly the flexural modulus, especially in the first cycles, as degradation tended to stabilize for increasing cycles. The GFRP profile made of vinylester resin presented better overall performance than the one made of polyester, especially regarding the tensile properties. SEM observations of the surfaces of fracture of mechanically tested pultruded specimens showed two main mechanisms of crack propagation: cohesive rupture (matrix cracking), where the crack propagates inside the matrix, and adhesive rupture (fibre–matrix debonding), where the crack propagates at the interface fibre–matrix. Degradation of the polyester matrix caused by the thermal cycles is evidenced by extensive matrix microcracking and increased fibre–matrix debonding. The vinylester matrix resists better to such degradation as fibre–matrix debonding occurs in less extent, and matrix microcracking is scarcely present.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
This paper discusses the literature on horizontal mergers between multisided platforms and argues that the Cournot model can provide useful insights into the welfare effects of such mergers. To ...illustrate those insights, we develop a simple model in which two‐sided platforms offer a homogeneous service and compete à la Cournot, and derive the effects of “average‐marginal‐cost‐preserving” mergers on consumers on both sides of the market. We conclude with a discussion of several research avenues that could be explored to understand better the impact of horizontal mergers between multisided platforms.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This article describes the results of the WPA-WHO Global Survey of 4,887 psychiatrists in 44 countries regarding their use of diagnostic classification systems in clinical practice, and the desirable ...characteristics of a classification of mental disorders. The WHO will use these results to improve the clinical utility of the ICD classification of mental disorders through the current ICD-10 revision process. Participants indicated that the most important purposes of a classification are to facilitate communication among clinicians and to inform treatment and management. They overwhelmingly preferred a simpler system with 100 or fewer categories, and over two-thirds preferred flexible guidance to a strict criteria-based approach. Opinions were divided about how to incorporate severity and functional status, while most respondents were receptive to a system that incorporates a dimensional component. Significant minorities of psychiatrists in Latin America and Asia reported problems with the cross-cultural applicability of existing classifications. Overall, ratings of ease of use and goodness of fit for specific ICD-10 categories were fairly high, but several categories were described as having poor utility in clinical practice. This represents an important focus for the ICD revision, as does ensuring that the ICD-11 classification of mental disorders is acceptable to psychiatrists throughout the world.
A listener's interpretation of a given speech sound can vary probabilistically from moment to moment. Previous experience (i.e., the contexts in which one has encountered an ambiguous sound) can ...further influence the interpretation of speech, a phenomenon known as perceptual learning for speech. This study used multivoxel pattern analysis to query how neural patterns reflect perceptual learning, leveraging archival fMRI data from a lexically guided perceptual learning study conducted by Myers and Mesite Myers, E. B., & Mesite, L. M. Neural systems underlying perceptual adjustment to non-standard speech tokens.
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, 80–93, 2014. In that study, participants first heard ambiguous /s/–/∫/ blends in either /s/-biased lexical contexts (
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) or /∫/-biased contexts (
); subsequently, they performed a phonetic categorization task on tokens from an /asi/–/a∫i/ continuum. In the current work, a classifier was trained to distinguish between phonetic categorization trials in which participants heard unambiguous productions of /s/ and those in which they heard unambiguous productions of /∫/. The classifier was able to generalize this training to ambiguous tokens from the middle of the continuum on the basis of individual participants' trial-by-trial perception. We take these findings as evidence that perceptual learning for speech involves neural recalibration, such that the pattern of activation approximates the perceived category. Exploratory analyses showed that left parietal regions (supramarginal and angular gyri) and right temporal regions (superior, middle, and transverse temporal gyri) were most informative for categorization. Overall, our results inform an understanding of how moment-to-moment variability in speech perception is encoded in the brain.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Learning to read requires the formation of efficient neural associations between written and spoken language. Whether these associations influence the auditory cortical representation of speech ...remains unknown. Here we address this question by combining multivariate functional MRI analysis and a newly-developed 'text-based recalibration' paradigm. In this paradigm, the pairing of visual text and ambiguous speech sounds shifts (i.e. recalibrates) the perceptual interpretation of the ambiguous sounds in subsequent auditory-only trials. We show that it is possible to retrieve the text-induced perceptual interpretation from fMRI activity patterns in the posterior superior temporal cortex. Furthermore, this auditory cortical region showed significant functional connectivity with the inferior parietal lobe (IPL) during the pairing of text with ambiguous speech. Our findings indicate that reading-related audiovisual mappings can adjust the auditory cortical representation of speech in typically reading adults. Additionally, they suggest the involvement of the IPL in audiovisual and/or higher-order perceptual processes leading to this adjustment. When applied in typical and dyslexic readers of different ages, our text-based recalibration paradigm may reveal relevant aspects of perceptual learning and plasticity during successful and failing reading development.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cancer has become one of the main leading causes of morbidity and mortality worldwide. One of the critical drawbacks of current cancer therapeutics has been the lack of the target-selectivity, as ...these drugs should have an effect exclusively on cancer cells while not perturbing healthy ones. In addition, their mechanism of action should be sufficiently fast to avoid the invasion of neighbouring healthy tissues by cancer cells. The use of conventional chemotherapeutic agents and other traditional therapies, such as surgery and radiotherapy, leads to off-target interactions with serious side effects. In this respect, recently developed target-selective Antibody-Drug Conjugates (ADCs) are more effective than traditional therapies, presumably due to their modular structures that combine many chemical properties simultaneously. In particular, ADCs are made up of three different units: a highly selective Monoclonal antibody (Mab) which is developed against a tumour-associated antigen, the payload (cytotoxic agent), and the linker. The latter should be stable in circulation while allowing the release of the cytotoxic agent in target cells. The modular nature of these drugs provides a platform to manipulate and improve selectivity and the toxicity of these molecules independently from each other. This in turn leads to generation of second- and third-generation ADCs, which have been more effective than the previous ones in terms of either selectivity or toxicity or both. Development of ADCs with improved efficacy requires knowledge at the atomic level regarding the structure and dynamics of the molecule. As such, we reviewed all the most recent computational methods used to attain all-atom description of the structure, energetics and dynamics of these systems. In particular, this includes homology modelling, molecular docking and refinement, atomistic and coarse-grained molecular dynamics simulations, principal component and cross-correlation analysis. The full characterization of the structure-activity relationship devoted to ADCs is critical for antibody-drug conjugate research and development.
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