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Diagnostic physical methods are increasingly applied to Cultural Heritage both for scientific investigations and conservation purposes. In particular, the X-ray imaging techniques of computed tomography (CT) and digital radiography (DR) are non-destructive investigation methods to study an object, being able to give information on its inner structure. In this paper, we present the results of the X-ray imaging study on an ancient Egyptian statuette (Late Period 722-30 BCE) belonging to the collection of Museo Egizio in Torino and representing an Egyptian goddess called Taweret, carved on wood and gilded with some colored details. Since few specific studies have been focused on materials and techniques used in Ancient Egypt for gilding, a detailed investigation was started in order to verify the technical features of the decoration in this sculpture. Specifically, DR and CT analyses have been performed at the Centro Conservazione e Restauro "La Venaria Reale" (CCR), with a new high resolution flat-panel detector, that allowed us to perform tomographic analysis reaching a final resolution better than the one achievable with the previous apparatus operating in the CCR.

Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome.

Red tides involving Karenia brevis expose humans to brevetoxins (PbTxs). Oral exposition triggers neurotoxic shellfish poisoning, whereas inhalation induces a respiratory syndrome and sensory disturbances. No curative treatment is available and the pathophysiology is not fully elucidated. Protease-activated receptor 2 (PAR2), cathepsin S (Cat-S) and substance P (SP) release are crucial mediators of the sensory effects of ciguatoxins (CTXs) which are PbTx analogs. This work explored the role of PAR2 and Cat-S in PbTx-1-induced sensory effects and deciphered the signaling pathway involved. We performed calcium imaging, PAR2 immunolocalization and SP release experiments in monocultured sensory neurons or co-cultured with keratinocytes treated with PbTx-1 or P-CTX-2. We demonstrated that PbTx-1-induced calcium increase and SP release involved Cat-S, PAR2 and transient receptor potential vanilloid 4 (TRPV4). The PbTx-1-induced signaling pathway included protein kinase A (PKA) and TRPV4, which are compatible with the PAR2 biased signaling induced by Cat-S. Internalization of PAR2 and protein kinase C (PKC), inositol triphosphate receptor and TRPV4 activation evoked by PbTx-1 are compatible with the PAR2 canonical signaling. Our results suggest that PbTx-1-induced sensory disturbances involve the PAR2-TRPV4 pathway. We identified PAR2, Cat-S, PKA, and PKC that are involved in TRPV4 sensitization induced by PbTx-1 in sensory neurons.

Calcium is an important second messenger that is involved in almost all cellular processes. Disruptions in the regulation of intracellular Ca2+ levels ([Ca2+]i) adversely impact normal physiological function and can contribute to various diseased conditions. STIM and Orai proteins play important roles in maintaining [Ca2+]i through store-operated Ca2+ entry (SOCE), with STIM being the primary regulatory protein that governs the function of Orai channels. STIM1 and STIM2 are single-pass ER-transmembrane proteins with their N- and C-termini located in the ER lumen and cytoplasm, respectively. The N-terminal EF-SAM domain of STIMs senses [Ca2+]ER changes, while the C-terminus mediates clustering in ER-PM junctions and gating of Orai1. ER-Ca2+ store depletion triggers activation of the STIM proteins, which involves their multimerization and clustering in ER-PM junctions, where they recruit and activate Orai1 channels. In this review, we will discuss the structure, organization, and function of EF-hand motifs and the SAM domain of STIM proteins in relation to those of other eukaryotic proteins. [ABSTRACT FROM AUTHOR]

The complex composition of cultural heritage (CH) items presents significant challenges in assessing their condition and predicting potential risks of material degradation. Typically employed diagnostic optical methods are inevitably limited by light scattering, thus restricting in-depth investigations of objects with complex structural and optical properties. To address this issue, we introduce a novel reflection-mode optoacoustic (OA) diagnostic system for non-contact and non-invasive measurements of CH, placing emphasis on the detection of ageing-related modifications in artistic media such as paints. In this direction, the sensitivity of OA measurements was proven to be up to two orders of magnitude higher than conventional absorption spectroscopy assessments. Furthermore, we have evaluated the in-depth imaging capabilities of the developed OA system, demonstrating that it can offer superior contrast levels of sketches beneath opaque paint layers compared to standard near-infrared diagnostic techniques. The current OA imaging technology may advance state-of-the-art diagnostic capabilities in CH preservation by delivering unprecedented depth-to-resolution ratios combined with exceptional optical absorption sensitivity in a non-invasive manner. These features are crucial for the early detection of material degradation and the comprehensive analysis of CH objects, facilitating the development of optimal conservation strategies to prolong their lifespan and preserve their aesthetic value. [ABSTRACT FROM AUTHOR]

This review, through the collection and comparative analysis of the most recent literature, aims to analyze the new trends in archaeometric analysis and some selected laboratory techniques aimed at determining the provenance, the physical–chemical characteristics, and the state of decay of archaeological finds of different types (ancient manuscripts, paintings, frescoes, and ceramics). In particular, the methodologies and analytical techniques relating to Raman spectroscopy, X-ray fluorescence, laser ablation, IR spectroscopy, LIBS, and Thz spectroscopy were compared and tabulated, with the aim of determining the appropriateness of each technique applied to various archaeological items. This will provide guidelines for the right conservation and restoration strategies. The work was also based on the construction of comparative tables of the consulted scientific literature and on the analysis of the research trends by using the Google Trends app. [ABSTRACT FROM AUTHOR]

Digital radiography and computed tomography are two fundamental diagnostic techniques in different fields of research, including cultural heritage studies and gemmology. The application of these physical methods of investigation has gained considerable importance as they are non-invasive techniques. The presented work has been mainly focused on micro-tomographic analysis. The project is concerned with the study of natural and cultivated pearls in order to develop an investigation methodology for the analysis, distinction and characterization of different types of pearls, some of them belonging to different precious jewels from private collections. The investigations, carried out on a total of 22 heterogeneous types of pearls, allowed us to establish their origin (natural or cultivated) or to confirm/deny if a hypothesis was already expressed, and as well to highlight the cultivation methodology used case by case. Furthermore, it was possible to ascertain how large and varied the market for cultured pearls is nowadays and how difficult is, in some particular cases, to ascertain their attribution to a certain origin. [ABSTRACT FROM AUTHOR]

The prokineticin system plays a role in hypothalamic neurons in the control of energy homeostasis. Prokineticin receptors (PKR1 and PKR2), like other G-protein-coupled receptors (GPCRs) are involved in the regulation of energy intake and expenditure and are modulated by the accessory membrane protein 2 of the melanocortin receptor (MRAP2). The aim of this work is to characterise the interaction and regulation of the non-melanocortin receptor PKR1 by MRAP2a in zebrafish (zMRAP2a) in order to use zebrafish as a model for the development of drugs targeting accessory proteins that can alter the localisation and activity of GPCRs. To this end, we first showed that zebrafish PKR1 (zPKR1) is able to interact with both zMRAP2a and human MRAP2 (hMRAP2). This interaction occurs between the N-terminal region of zPKR1 and the C-terminal domain of zMRAP2a, which shows high sequence identity with hMRAP2 and a similar propensity for dimer formation. Moreover, we demonstrated that in Chinese hamster ovary (CHO) cells, zMRAP2a or hMRAP2 are able to modulate zPKR1 activation induced by zebrafish PK2 (zPK2) resulting in an impaired ERK and STAT3 activation. [ABSTRACT FROM AUTHOR]

Contemporary murals and street art play a critical role in urban culture, serving as platforms for social activism and reflecting the vibrancy of city life. This study within the SuperStaAr project framework examines the challenge of graffiti removal while safeguarding the original synthetic paint layers. Through a detailed investigation using Q-Switch and Long Q-Switch lasers (Nd:YAG), we evaluate the effectiveness and safety of laser cleaning techniques on both unaged and artificially aged mural mock-ups. The initial findings highlight the Q-Switch and Long Q-Switch lasers as promising for removing graffiti without compromising the paint integrity. Our assessment criteria—encompassing residue presence, surface roughness, color changes, cleaning effectiveness, and pigment pickup—were validated through empirical evaluation and supported by colorimetric, micro–ATR–FTIR, and Py–GC/MS analyses. Notably, the incorporation of a passive sampling system for Py–GC/MS analysis facilitates a deeper understanding of the ablated materials without direct sampling from the artwork. This research contributes a foundational framework for the evaluation of laser cleaning in mural conservation, emphasizing the importance of tailored strategies to enhance the sustainability of urban art conservation efforts. [ABSTRACT FROM AUTHOR]

Recent progress in the realm of imaging technologies has swiftly disseminated fresh methodologies for representing objects, broadening the horizons for scholars such as art historians, archaeologists, conservators, and conservation scientists. Reflectance Transformation Imaging (RTI) and three-dimensional (3D) modeling via Structure from Motion (SfM) have rapidly gained popularity and are being employed by a wide range of users, expanding the possibilities for understanding objects of material cultural heritage from different perspectives. This paper explores the outcomes achieved through the application of these techniques to gain deeper insights into the surface of a bas-relief within a confined space. This methodology enhanced our understanding of the original sandstone surfaces of the bas-relief by integrating RTI and 3D visualization, thereby acquiring a novel investigative tool with enhanced illumination possibilities. A data fusion approach is proposed using photogrammetry to produce a Virtual RTI (V-RTI). In the case study reported in this paper, focusing on one inner wall of the chapel of Ellesiya at the Museo Egizio of Turin, V-RTI was employed to obtain useful surface information in a context where conventional RTI would have been impossible to achieve. Finally, the study compares the different techniques through direct qualitative and quantitative analysis, highlighting possible future developments from both instrumental and methodological points of view. [ABSTRACT FROM AUTHOR]

The ORAI proteins serve as crucial pore-forming subunits of calcium-release-activated calcium (CRAC) channels, pivotal in regulating downstream calcium-related signaling pathways. Dysregulated calcium homeostasis arising from mutations and post-translational modifications in ORAI can lead to immune disorders, myopathy, cardiovascular diseases, and even cancers. Small molecules targeting ORAI present an approach for calcium signaling modulation. Moreover, emerging techniques like optogenetics and optochemistry aim to offer more precise regulation of ORAI. This review focuses on the role of ORAI in cancers, providing a concise overview of their significance in the initiation and progression of cancers. Additionally, it highlights state-of-the-art techniques for ORAI channel modulation, including advanced optical tools, potent pharmacological inhibitors, and antibodies. These novel strategies offer promising avenues for the functional regulation of ORAI in research and may inspire innovative approaches to cancer therapy targeting ORAI. [ABSTRACT FROM AUTHOR]

The process of wound healing is intricate and tightly controlled, involving a number of different cellular and molecular processes. Numerous cellular functions, especially those related to wound healing, depend critically on calcium ions (Ca2+). Ca2+ channels are proteins involved in signal transduction and communication inside cells that allow calcium ions to pass through cell membranes. Key Ca2+ channel types involved in wound repair are described in this review. [ABSTRACT FROM AUTHOR]

Many essential biological processes are triggered by the proximity of molecules. Meanwhile, diverse approaches in synthetic biology, such as new biological parts or engineered cells, have opened up avenues to precisely control the proximity of molecules and eventually downstream signaling processes. This also applies to a main Ca2+ entry pathway into the cell, the so-called Ca2+ release-activated Ca2+ (CRAC) channel. CRAC channels are among other channels are essential in the immune response and are activated by receptor–ligand binding at the cell membrane. The latter initiates a signaling cascade within the cell, which finally triggers the coupling of the two key molecular components of the CRAC channel, namely the stromal interaction molecule, STIM, in the ER membrane and the plasma membrane Ca2+ ion channel, Orai. Ca2+ entry, established via STIM/Orai coupling, is essential for various immune cell functions, including cytokine release, proliferation, and cytotoxicity. In this review, we summarize the tools of synthetic biology that have been used so far to achieve precise control over the CRAC channel pathway and thus over downstream signaling events related to the immune response. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca2+ release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment. [ABSTRACT FROM AUTHOR]

Cystic Fibrosis (CF) is present due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, the most frequent variant being p.phe508del. The CFTR protein is a chloride (Cl-) channel which is defective and almost absent of cell membranes when the p.Phe508del mutation is present. The p.Phe508del-CFTR protein is retained in the endoplasmic reticulum (ER) and together with inflammation and infection triggers the Unfolded Protein Response (UPR). During the UPR, the Activating Transcription Factor 6 (ATF6) is activated with cleavage and then decreases the expression of p.Phe508del-CFTR. We have previously shown that the inhibition of the activation of ATF6 alleviates the p.Phe508del-CFTR defects in cells overexpressing the mutated protein. In the present paper, our aim was to inhibit the cleavage of ATF6, and thus its activation in a human bronchial cell line with endogenous p.Phe508del-CFTR expression and in bronchial cells from patients, to be more relevant to CF. This was achieved by inhibiting the protease MBTP1 which is responsible for the cleavage of ATF6. We show here that this inhibition leads to increased mRNA and p.Phe508del-CFTR expression and, consequently, to increased Cl-efflux. We also explain the mechanisms linked to these increases with the modulation of genes when MBTP1 is inhibited. Indeed, RT-qPCR assays show that genes such as HSPA1B, CEBPB, VIMP, PFND2, MAPK8, XBP1, INSIG1, and CALR are modulated. In conclusion, we show that the inhibition of MBTP1 has a beneficial effect in relevant models to CF and that this is due to the modulation of genes involved in the disease. [ABSTRACT FROM AUTHOR]

Apolipoprotein(a) (apo(a)) is the protein component that defines lipoprotein(a) (Lp(a)) particles and is encoded by the LPA gene. The apo(a) is extremely heterogeneous in size due to the copy number variations in the kringle-IV type 2 (KIV2) domains. In this review, we aim to discuss the role of genetics in establishing Lp(a) as a risk factor for coronary heart disease (CHD) by examining a series of molecular biology techniques aimed at identifying the best strategy for a possible application in clinical research and practice, according to the current gold standard. [ABSTRACT FROM AUTHOR]

Design has shaped the world in which we live; it has improved our lives in ways we cannot even begin to imagine. Even if design is everywhere and is the memory of the world, collections associated with it are not usually well-known as design archives which capture spatial and temporal narratives. Saving these types of archives and making them accessible to the public, using them as cultural hubs, might improve our lives thanks to visual literacy, creativity, and innovation. The Arxiu Valencià del Disseny aims to recover, preserve, protect, and disseminate the archival cultural heritage of the Valencian designers. With a collection of more than 150,000 objects, it recovers history and evolution from the applied arts and product design, but with a markedly future-oriented character through the enhancement of the collections and their dissemination thanks to an intelligent computational system featuring cutting-edge technologies in order to prove our understanding of Valencian and European design. The aim of this paper is twofold: first, we introduce the AVD project, an interdisciplinary project that has been recently funded by the Valencian Government in order to preserve and promote the heritage of design archives; second, we introduce a set of interactive tools related to the project, such as the digitisation and cataloguing of the collection, the generation of a Design Memory Archive, advanced searching, and semantically relating the digitised collection of the Arxiu Valencià del Disseny based on data interoperability across its collections and a benchmarking tool for designers. [ABSTRACT FROM AUTHOR]

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce "residual cardiovascular risk" in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage. [ABSTRACT FROM AUTHOR]

Yves Klein (1928–1962) is best known for his intensely blue monochromatic works made with International Klein Blue (IKB), a synthetic ultramarine blue pigment bound in a poly(vinyl acetate) binder. However, he also made monochromes in other colors, including red and pink, the pigments of which have never been elucidated. Analysis of one sculpture, three paintings, and one screenprint by micro-Fourier transform infrared spectroscopy (µ-FTIR), Raman and surface-enhanced Raman (SERS) spectroscopies, portable X-ray fluorescence spectroscopy (p-XRF), and scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectrometry (EDX), revealed that Klein used, knowingly or unknowingly, a variety of pink and red pigments, including Para Red, rhodamine 6G, rhodamine B, eosin Y, and alizarin lakes. The unexpected variety of pigments contrasts with his use of a single blue pigment and suggests he may not have held a singular vision of what constituted an iconic red or pink color. [ABSTRACT FROM AUTHOR]

The emergence of marine toxins such as ciguatoxins (CTXs) and tetrodotoxins (TTXs) in non-endemic regions may pose a serious food safety threat and public health concern if proper control measures are not applied. This article provides an overview of the main biorecognition molecules used for the detection of CTXs and TTXs and the different assay configurations and transduction strategies explored in the development of biosensors and other biotechnological tools for these marine toxins. The advantages and limitations of the systems based on cells, receptors, antibodies, and aptamers are described, and new challenges in marine toxin detection are identified. The validation of these smart bioanalytical systems through analysis of samples and comparison with other techniques is also rationally discussed. These tools have already been demonstrated to be useful in the detection and quantification of CTXs and TTXs, and are, therefore, highly promising for their implementation in research activities and monitoring programs. [ABSTRACT FROM AUTHOR]

Since infrared reflectography was first applied in the 1960s to visualize the underdrawings of ancient paintings, several devices and scanning techniques were successfully proposed both as prototypes and commercial instruments. In fact, because of the sensors' small dimension, typically ranging from 0.1 to 0.3 megapixels, scanning is always required. Point, line, and image scanners are all viable options to obtain an infrared image of the painting with adequate spatial resolution. This paper presents a newly developed, tailormade scanning system based on an InGaAs camera equipped with a catadioptric long-focus lens in a fixed position, enabling all movements to occur by means of a rotating mirror and precision step motors. Given the specific design of this system, as the mirror rotates, refocus of the lens is necessary and it is made possible by an autofocus system involving a laser distance meter and a motorized lens. The system proved to be lightweight, low cost, easily portable, and suitable for the examination of large-scale painting surfaces by providing high-resolution reflectograms. Furthermore, high-resolution images at different wavelengths can be obtained using band-pass filters. The in-situ analysis of a 16th-century panel painting is also discussed as a representative case study to demonstrate the effectiveness and reliability of the system described herein. [ABSTRACT FROM AUTHOR]

The exhibition "The Ladies of Art", held at the Palazzo Reale in Milan in 2021, focused on the history of women artists during the 16th and 17th centuries. As part of the exhibition, a series of diagnostic analyses have been carried out on two paintings, thanks to the collaboration of several research institutions. The considered artworks consist of two paintings on parchments, realized by Giovanna Garzoni at the Savoy Court in the 17th century. Diagnostic analyses were performed using different, complementary, and non-invasive techniques: high-resolution multiband imaging, hyperspectral imaging, optical microscopy, X-ray fluorescence, and FORS spectrometry, combined with advanced post-processing techniques, in order to map and distinguish the pigments and the underdrawing of both the paintings. This research is the first conducted on these paintings and one of the few on the entire works of this important miniaturist. The results showed an incredibly meticulous painting technique, with a detailed metal point underdrawing and painstaking brushstrokes to describe the details with a high degree of realism. Precious materials, such as gold and lapislazuli, were identified and mapped. The findings of this work represent a new contribution of knowledge, which helps to lessen the lack of information for systematic studies on the artistic production of G. Garzoni. [ABSTRACT FROM AUTHOR]

Digitalization techniques, such as photogrammetry (PG), are attracting the interest of experts in the cultural heritage field, as they enable the creation of three-dimensional virtual replicas of historical artifacts with 2D digital images. Indeed, PG allows for acquiring data regarding the overall appearance of an artifact, its geometry, and its texture. Furthermore, among several image-based techniques exploited for the conservation of works of art, multispectral imaging (MSI) finds great application in the study of the materials of historical items, taking advantage of the different responses of materials when exposed to specific wavelengths. Despite their great usefulness, PG and MSI are often used as separate tools. Integrating radiometric and geometrical data can notably expand the information carried by a 3D model. Therefore, this paper presents a novel research methodology that enables the acquisition of multispectral 3D models, combining the outcomes of PG and MSI (Visible (VIS), Ultraviolet-induced Visible Luminescence (UVL), Ultraviolet-Reflected (UVR), and Ultraviolet-Reflected False Color (UVR-FC) imaging) in a single coordinate system, using an affordable tunable set-up and open-source software. The approach has been employed for the study of two wooden artifacts from the Museo Egizio di Torino to investigate the materials present on the surface and provide information that could support the design of suitable conservation treatments. [ABSTRACT FROM AUTHOR]

Water-in-oil (w/o) nanoemulsions stabilized with amino acid surfactants (AAS) are one example of nanotechnology detergents of the "brush on, wipe off"-type for removing graffiti coatings from different sensitive surfaces. The high-pressure homogenization (HPH) process was used to obtain the nanostructured fluids (NSFs), including the non-toxic and eco-friendly components such as AAS, esterified vegetable oils, and ethyl lactate. The most effective NSF detergent was determined by response surface methodology (RSM) optimization. Afterwards, several surface properties, i.e., topography, wettability, surface free energy, and the work of water adhesion to surfaces before and after their coverage with the black graffiti paint, as well as after the removal of the paint layers by the eco-remover, were determined. It was found that the removal of graffiti with the use of the NSF detergent is more dependent on the energetic properties and microporous structure of the paint coatings than on the properties of the substrates on which the layers were deposited. The use of NSFs and knowledge of the surface properties could enable the development of versatile detergents that would remove unwanted contamination from various surfaces easily and in a controlled way. [ABSTRACT FROM AUTHOR]

This work is concerned with a multi-analytical identification of the colour palette utilised in the decoration of the cover of an Egyptian sarcophagus dated to the Late Dynastic Period and belonging to a private collection. In this study, six different points were analysed with a portable Raman spectrometer; then, in these same points, six micro-fragments were taken from the sarcophagus for laboratory analysis performed by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDXS), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and visible induced luminescence imaging (VIL). Raman spectra collected in situ showed the characteristic bands of calcite, red ochre and black carbon. SEM-EDXS analyses highlighted the presence of a copper-based pigment in the light blue, blue and black fragments; then, the ATR-FTIR spectrum of the light blue sample only displayed the peculiar bands of Egyptian blue. The latter result was confirmed by VIL analysis, which successfully identified the same pigment in blue-black fragments as well, leading to the possible authentication of the finding. Moreover, the presence of calcite, red ochre, green earth and some organic material was assessed by FTIR spectroscopy, confirming some of the results of in situ Raman analyses. Regarding organic materials, whose investigation is still ongoing, some hypotheses were made on the basis of their FTIR spectra. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for atherosclerotic cardiovascular disease (ASCVD) as they are largely determined by variations in the Lp(a) gene (LPA) locus encoding apo(a). Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, atherosclerotic lesions, endothelial function and thrombogenicity, which pathophysiologically leads to cardiovascular (CV) events. Despite this crucial role of Lp(a), its measurement lacks a globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such as statins, fibrates and ezetimibe, have a mediocre effect on Lp(a) levels, although it is not yet clear whether such treatments can affect CV events and prognosis. This narrative review aims to summarize knowledge regarding the mechanisms mediating the effect of Lp(a) on inflammation, atherosclerosis and thrombosis and discuss current diagnostic and therapeutic potentials. [ABSTRACT FROM AUTHOR]

Simple Summary: Cell fate is ultimately determined by the precisely coordinated action of the Ca2+-signaling machinery. During carcinogenesis, Ca2+ signaling is significantly remodeled due to mutations and/or ectopic expression. Here, we summarize current knowledge on how alterations in Ca2+ signaling contribute to the development of different cancer hallmarks. Emphasis is placed on the structure/function relationship of the well-studied store-operated Ca2+ channel, i.e., Orai1, and the Ca2+-activated K+ channel, i.e., SK3, alongside their individual and joint roles in cancer. This review lays out the current state of knowledge of Ca2+-signaling effectors and proteins as potential targets for the treatment of certain cancer types, with Orai1 and SK3 presented as emerging therapeutic targets. Cancer represents a major health burden worldwide. Several molecular targets have been discovered alongside treatments with positive clinical outcomes. However, the reoccurrence of cancer due to therapy resistance remains the primary cause of mortality. Endeavors in pinpointing new markers as molecular targets in cancer therapy are highly desired. The significance of the co-regulation of Ca2+-permeating and Ca2+-regulated ion channels in cancer cell development, proliferation, and migration make them promising molecular targets in cancer therapy. In particular, the co-regulation of the Orai1 and SK3 channels has been well-studied in breast and colon cancer cells, where it finally leads to an invasion-metastasis cascade. Nevertheless, many questions remain unanswered, such as which key molecular components determine and regulate their interplay. To provide a solid foundation for a better understanding of this ion channel co-regulation in cancer, we first shed light on the physiological role of Ca2+ and how this ion is linked to carcinogenesis. Then, we highlight the structure/function relationship of Orai1 and SK3, both individually and in concert, their role in the development of different types of cancer, and aspects that are not yet known in this context. [ABSTRACT FROM AUTHOR]

In this work, two historical flutes of the late eighteenth century were analysed by means of X-ray computed tomography (CT). The first one is a piccolo flute whose manufacturer is unknown, though some features could suggest an English or American origin. The second musical instrument is a baroque transverse flute, probably produced by Lorenzo Cerino, an Italian instrument maker active in Turin (Italy) in the late eighteenth century. Analyses carried out provided information on manufacturing techniques, materials and conservation state, and are suitable to plan restoration intervention. In particular, through the CT images, it was possible to observe the presence of defects, cracks, fractures and previous restorations, as well as indications of the tools used in the making of the instruments. Particular attention was directed towards extracting metrological information about the objects. In fact, this work is the first step of a study with a final aim of determining an operative protocol to enable the making of precise-sounding copies of ancient instruments starting from CT images, that can be used to plan a virtual restoration, consisting in the creation of digitally restored copies with a 3D printer. [ABSTRACT FROM AUTHOR]

Our respiratory system is exposed to toxicants and pathogens from both sides: the airways and the vasculature. While tracheal, bronchial and alveolar epithelial cells form a natural barrier in the airways, endothelial cells protect the lung from perfused toxic compounds, particulate matter and invading microorganism in the vascular system. Damages induce inflammation by our immune response and wound healing by (myo)fibroblast proliferation. Members of the transient receptor potential (TRP) superfamily of ion channel are expressed in many cells of the respiratory tract and serve multiple functions in physiology and pathophysiology. TRP expression patterns in non-neuronal cells with a focus on TRPA1, TRPC6, TRPM2, TRPM5, TRPM7, TRPV2, TRPV4 and TRPV6 channels are presented, and their roles in barrier function, immune regulation and phagocytosis are summarized. Moreover, TRP channels as future pharmacological targets in chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema are discussed. [ABSTRACT FROM AUTHOR]

Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain. Once activated, PAR2 is rapidly desensitized and internalized by phosphorylation and β-arrestin recruitment. Due to its irreversible activation mechanism, some agonists that rapidly desensitized PAR2 have been misconceived as antagonists, and this has impeded a better understanding of the pathophysiological role of PAR2. In the present study, we found that GB83, initially identified as a PAR2 antagonist, is a bona fide agonist of PAR2 that induces unique cellular signaling, distinct from trypsin and PAR2-activating peptide (AP). Activation of PAR2 by GB83 markedly elicited an increase in intracellular calcium levels and phosphorylation of MAPKs, but in a delayed and sustained manner compared to the rapid and transient signals induced by trypsin and PAR2-AP. Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization with β-arrestin. Moreover, the recovery of the localization and function of PAR2 was significantly delayed after stimulation by GB83, which may be the reason why GB83 is recognized as an antagonist of PAR2. Our results revealed that GB83 is a bona fide agonist of PAR2 that uniquely modulates PAR2-mediated cellular signaling and is a useful pharmacological tool for studying the pathophysiological role of PAR2. [ABSTRACT FROM AUTHOR]

The potential of any multi-analytical and non-invasive approach to the study of cultural heritage, both for conservation and scientific investigation purposes, is gaining increasing interest, and it was tested in this paper, focusing on the panel painting Madonna della Tenda (Musei Reali, Turin), identified as a 16th-century copy of the painting by Raffaello Sanzio. As a part of a broader diagnostic campaign carried out at the Centro Conservazione e Restauro, La Venaria Reale in Turin, Italy, the potential of the combination of X-ray radiography, pulse-compression thermography, macro X-ray fluorescence, and IR reflectography was tested to investigate the wooden support and all the preparatory phases for the realization of the painting. The results of the optical microscopy and SEM/EDS analyses on a multi-layered micro-sample were used for a precise comparison, integration, and/or confirmation of what was suggested by the non-invasive techniques. Particularly, the radiographic and thermographic techniques allowed for an in-depth study of a hole, interestingly present on the panel's back surface, detecting the trajectory of the wood grain and confirming the presence of an old wood knot, as well as of a tau-shaped element—potentially a cracked and unfilled area of the wooden support—near the hollow. The combination of radiography, macro X-ray fluorescence, Near Infrared (NIR), and Short Wave Infrared (SWIR) reflectography allowed for an inspection of the ground layer, imprimitura, engravings, and underdrawing, not only revealing interesting technical-executive aspects of the artwork realization, but also highlighting the advantages of an integrated reading of data obtained from the different analytical techniques. [ABSTRACT FROM AUTHOR]

A rare and valuable Palaeolithic wooden point, presumably belonging to a hunting weapon, was found in the Ljubljanica River in Slovenia in 2008. In order to prevent complete decay, the waterlogged wooden artefact had to undergo conservation treatment, which usually involves some expected deformations of structure and shape. To investigate these changes, a series of surface-based 3D models of the artefact were created before, during and after the conservation process. Unfortunately, the surface-based 3D models were not sufficient to understand the internal processes inside the wooden artefact (cracks, cavities, fractures). Since some of the surface-based 3D models were taken with a microtomographic scanner, we decided to create a volumetric 3D model from the available 2D tomographic images. In order to have complete control and greater flexibility in creating the volumetric 3D model than is the case with commercial software, we decided to implement our own algorithm. In fact, two algorithms were implemented for the construction of surface-based 3D models and for the construction of volumetric 3D models, using (1) unsegmented 2D images CT and (2) segmented 2D images CT. The results were positive in comparison with commercial software and new information was obtained about the actual state and causes of the deformation of the artefact. Such models could be a valuable aid in the selection of appropriate conservation and restoration methods and techniques in cultural heritage research. [ABSTRACT FROM AUTHOR]

In the last decades, high serum levels of lipoprotein(a) (Lp(a)) have been associated with increased cardiovascular disease (CVD) risk, in particular among individuals with smaller apolipoprotein(a) (apo(a)) isoforms than those with larger sizes. The aim of our analysis was to evaluate whether Lp(a) levels could predict early vascular aging, and whether smaller apo(a) isoforms had a predictive value for vascular aging different than larger apo(a) isoforms in a cohort of subjects free from CVD. We considered the data of a subset of Brisighella Heart Study (BHS) participants free from CVD (462 men and 516 women) who were clinically evaluated during the 2012 BHS population survey. Predictors of arterial stiffness, measured as carotid-femoral pulse wave velocity (cfPWV) were estimated by the application of a step-wise linear regression model. In our cohort, there were 511 subjects with small apo(a) size and 467 subjects with large apo(a) isoforms. Subjects with larger apo(a) isoform sizes had significantly lower serum levels of Lp(a). In the BHS subpopulation sample, cfPWV was predicted by age, systolic blood pressure (SBP), serum levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and sex, higher HDL-C serum levels and female sex associated with lower values of cfPWV. In subjects with smaller apo(a) isoform sizes, predictors of cfPWV were age, SBP, sex and serum levels of HDL-C, being higher HDL-C serum levels and female sex associated to lower values of cfPWV. In subjects with larger apo(a) isoform sizes, cfPWV was predicted by age, SBP, serum levels of Lp(a) and sex, with female sex associated with lower values of cfPWV. In our subpopulation sample, Lp(a) did not predict cfPWV. However, in subjects with large apo(a) isoform sizes, Lp(a) was a significant predictor of arterial stiffness. [ABSTRACT FROM AUTHOR]

Computed Tomography (CT), mostly used in the medical field, has also recently been involved in Cultural Heritage studies, thanks to its efficiency and total non-invasiveness. Due to the large variety of sizes and compositions typical of Cultural Heritage objects, different X-ray sources, detectors, and setups are necessary to meet the different needs of various case studies. Here, we focus on the use of micro-CT to explore the morphology and shape of a small, neglected bone found inside the clitoris of non-human primates (the baubellum), which we obtained by accessing two prestigious primatological collections of the American Museum of Natural History (New York, NY, USA) and the National Museum of Natural History (Washington, DC, USA). Overcoming methodological limits imposed by the absence of homologous landmarks, we combined the use of the non-invasive 3D micro-CT and a recently released landmark-free shape analysis (the alpha-shape technique) to objectively describe and quantify the shape complexity of scanned primate baubella. Micro-CT provided high-resolution results, overcoming constraints linked to museum policy about non-disruptive sampling and preserving samples for future research. Finally, it proved appropriate as post-mortem sampling had no impact on protected wild primate populations. [ABSTRACT FROM AUTHOR]

Cultural heritage preservation is a crucial topic for our society. When dealing with fine art, color is a primary feature that encompasses much information related to the artwork's conservation status and to the pigments' composition. As an alternative to more sophisticated devices, the analysis and identification of color pigments may be addressed via a digital camera, i.e., a non-invasive, inexpensive, and portable tool for studying large surfaces. In the present study, we propose a new supervised approach to camera characterization based on clustered data in order to address the homoscedasticity of the acquired data. The experimental phase is conducted on a real pictorial dataset, where pigments are grouped according to their chromatic or chemical properties. The results show that such a procedure leads to better characterization with respect to state-of-the-art methods. In addition, the present study introduces a method to deal with organic pigments in a quantitative visual approach. [ABSTRACT FROM AUTHOR]

In recent years, X-ray imaging has rapidly grown and spread beyond the medical field; today, it plays a key role in diverse research areas. Several contributions deal with new performing algorithms developed for the suppression of cone-beam artifacts in CT images [[13]] and signal retrieval from non-sinusoidal intensity modulations in X-ray and neutron interferometry [[14]], or devoted to innovative techniques, such as multiscale holotomography [[15]], rotation-free dynamic multi-angle X-ray tomography [[16]] and high-speed X-ray imaging [[17]]. 10.3390/jimaging7120263 9 Qiao Z., Shi X., Wojcik M., Assoufid L. High-Resolution Scanning Coded-Mask-Based X-ray Multi-Contrast Imaging and Tomography. [Extracted from the article]

Deletion of phenylalanine 508 (∆F508) of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channel protein is the leading cause of Cystic Fibrosis (CF). Here, we report the analysis of CFTR and ∆F508-CFTR interactomes using BioID (proximity-dependent biotin identification), a technique that can also detect transient associations. We identified 474 high-confidence CFTR proximity-interactors, 57 of which have been previously validated, with the remainder representing novel interaction space. The ∆F508 interactome, comprising 626 proximity-interactors was markedly different from its wild type counterpart, with numerous alterations in protein associations categorized in membrane trafficking and cellular stress functions. Furthermore, analysis of the ∆F508 interactome in cells treated with Orkambi identified several interactions that were altered as a result of this drug therapy. We examined two candidate CFTR proximity interactors, VAPB and NOS1AP, in functional assays designed to assess surface delivery and overall chloride efflux. VAPB depletion impacted both CFTR surface delivery and chloride efflux, whereas NOS1AP depletion only affected the latter. The wild type and ∆F508-CFTR interactomes represent rich datasets that could be further mined to reveal additional candidates for the functional rescue of ∆F508-CFTR. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is a well-recognised tool for the analysis of materials in canvas paintings. However, it can be difficult to interpret the peaks of the spectra without the additional context of the artwork such as the age, provenance, or colour. Reflectance spectrophotometry can be used to capture the colour of pigments, dyes, and lacquers, but is seldom used to complement Raman data. Additionally, reflectance spectrophotometry results can be influenced by the surface profile of the painting. To overcome these limitations, this work brings together three different analysis modalities to provide a singular, analytical map of the artwork. Raman spectroscopy was used to conduct the chemical identification of pigments, binding media, and varnish present in a synthetic painting sample. Reflectance spectrophotometry was applied to obtain colour information of the surface paint of the sample. Three-dimensional optical profilometry data was used to characterise the micro topology of the paint surface. These three data sets were spatially matched allowing the recorded spectroscopic data to be displayed with the corresponding colour and surface topography across the paint surface. [ABSTRACT FROM AUTHOR]

The Bologna Archaeological Museum, in cooperation with prestigious Italian universities, institutions, and independent scholars, recently began a vast investigation programme on a group of Egyptian coffins of Theban provenance dating to the first millennium BC, primarily the 25th–26th Dynasty (c. 746–525 BC). Herein, we present the results of the multidisciplinary investigation carried out on one of these coffins before its restoration intervention: the anthropoid wooden coffin of Un-Montu (Inv. MCABo EG1960). The integration of radiocarbon dating, wood species identification, and CT imaging enabled a deep understanding of the coffin's wooden structure. In particular, we discuss the results of the tomographic investigation performed in situ. The use of a transportable X-ray facility largely reduced the risks associated with the transfer of the large object (1.80 cm tall) out of the museum without compromising image quality. Thanks to the 3D tomographic imaging, the coffin revealed the secrets of its construction technique, from the rational use of wood to the employment of canvas (incamottatura), from the use of dowels to the assembly procedure. [ABSTRACT FROM AUTHOR]

Cystic fibrosis is a hereditary disease that mainly affects secretory organs in humans. It is caused by mutations in the gene encoding CFTR with the most common phenylalanine deletion at position 508. CFTR is an anion channel mainly conducting Cl− across the apical membranes of many different epithelial cells, the impairment of which causes dysregulation of epithelial fluid secretion and thickening of the mucus. This, in turn, leads to the dysfunction of organs such as the lungs, pancreas, kidney and liver. The CFTR protein is mainly localized in the plasma membrane; however, there is a growing body of evidence that it is also present in the intracellular organelles such as the endosomes, lysosomes, phagosomes and mitochondria. Dysfunction of the CFTR protein affects not only the ion transport across the epithelial tissues, but also has an impact on the proper functioning of the intracellular compartments. The review aims to provide a summary of the present state of knowledge regarding CFTR localization and function in intracellular compartments, the physiological role of this localization and the consequences of protein dysfunction at cellular, epithelial and organ levels. An in-depth understanding of intracellular processes involved in CFTR impairment may reveal novel opportunities in pharmacological agents of cystic fibrosis. [ABSTRACT FROM AUTHOR]

This contribution focuses on the conservation of an Egyptian wooden sculpture (Inventory Number Cat. 745) belonging to the Museo Egizio of Torino in northwest Italy. A preliminary and interdisciplinary study of constituent painting materials and their layering is here provided. It was conducted by means of a multi-technique approach starting from non-invasive multispectral analysis on the whole object, and subsequently, on selected micro-samples. In particular, visible fluorescence induced by ultraviolet radiation (UVF), infrared reflectography (IRR) and visible--induced infrared luminescence were used on the whole object. The micro-samples were analysed by means of an optical microscope with visible and UV light sources, a scanning electron microscope (SEM) with an energy-dispersive X-ray spectrometer (EDX), Fourier transform infrared (FT-IR) spectrometer, pyrolysis-gas chromatography/mass spectrometer (Py-GC/MS) and micro-particle induced X-ray emission (PIXE). The characterization of the painting materials allowed the detection of Egyptian blue and Egyptian green, and also confirmed the pertinence of the top brown layer to the original materials, which is a key point to design a suitable surface treatment. In fact, due to the water sensitiveness of the original materials, only few options were available to perform cleaning operations on this artwork. To setup the cleaning procedure, we performed several preliminary tests on mockups using dry cleaning materials, commonly used to treat reactive surfaces, and innovative highly water retentive hydrogels, which can potentially limit the mechanical action on the original surface while proving excellent cleaning results. Overall, this study has proved fundamental to increase our knowledge on ancient Egyptian artistic techniques and contribute to hypothesize the possible provenance of the artefact. It also demonstrated that polyvinyl alcohol-based retentive gels allow for the safe and efficient cleaning of extremely water sensitive painted surfaces, as those typical of ancient Egyptian artefacts. [ABSTRACT FROM AUTHOR]

We review and develop conceptual models for the bio-transfer of ciguatoxins in food chains for Platypus Bay and the Great Barrier Reef on the east coast of Australia. Platypus Bay is unique in repeatedly producing ciguateric fishes in Australia, with ciguatoxins produced by benthic dinoflagellates (Gambierdiscus spp.) growing epiphytically on free-living, benthic macroalgae. The Gambierdiscus are consumed by invertebrates living within the macroalgae, which are preyed upon by small carnivorous fishes, which are then preyed upon by Spanish mackerel (Scomberomorus commerson). We hypothesise that Gambierdiscus and/or Fukuyoa species growing on turf algae are the main source of ciguatoxins entering marine food chains to cause ciguatera on the Great Barrier Reef. The abundance of surgeonfish that feed on turf algae may act as a feedback mechanism controlling the flow of ciguatoxins through this marine food chain. If this hypothesis is broadly applicable, then a reduction in herbivory from overharvesting of herbivores could lead to increases in ciguatera by concentrating ciguatoxins through the remaining, smaller population of herbivores. Modelling the dilution of ciguatoxins by somatic growth in Spanish mackerel and coral trout (Plectropomus leopardus) revealed that growth could not significantly reduce the toxicity of fish flesh, except in young fast-growing fishes or legal-sized fishes contaminated with low levels of ciguatoxins. If Spanish mackerel along the east coast of Australia can depurate ciguatoxins, it is most likely with a half-life of ≤1-year. Our review and conceptual models can aid management and research of ciguatera in Australia, and globally. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) channels are improving their importance in different cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the perspective of personalised therapies. [ABSTRACT FROM AUTHOR]

Techinantitla building complex, in the Amanalco neighborhood of the ancient city of Teotihuacan, is famous for the iconography and quality of the mural paintings found in this site. A significant part of this heritage has been lost due to looting. In recent years, an interdisciplinary research project was developed to study the limited patrimony that was left. As part of this study, we first employed geophysical techniques to reconstruct the architectural pattern of the compound's remaining walls, where other paintings may still be found. Then, we applied a non-invasive methodology to characterize a large set of fragments recovered in the 1980s and to gain information on their pigments and manufacturing techniques. This methodology included False Color Infrared Imaging, X-ray Fluorescence and Fiber-Optics Reflectance Spectroscopy, and led to the identification of hematite, calcite, malachite, azurite and an unidentified blue pigment. The results were compared with a previous study performed on a set of Techinantitla mural paintings looted in the 1960s. A broader comparison with contemporary mural paintings from other Teotihuacan complexes shows good agreement in the materials used. These results may suggest a standardization in the making of Teotihuacan mural painting during the Xolapan period (350 to 550 AD). [ABSTRACT FROM AUTHOR]

Ciguatera fish poisoning (CFP), the most prevalent seafood poisoning worldwide, is caused by the consumption of tropical and subtropical fish contaminated with potent neurotoxins called ciguatoxins (CTXs). Ciguatera is a complex clinical syndrome in which peripheral neurological signs predominate in the acute phase of the intoxication but also persist or reoccur long afterward. Their recognition is of particular importance in establishing the diagnosis, which is clinically-based and can be a challenge for physicians unfamiliar with CFP. To date, no specific treatment exists. Physiopathologically, the primary targets of CTXs are well identified, as are the secondary events that may contribute to CFP symptomatology. This review describes the clinical features, focusing on the sensory disturbances, and then reports on the neuronal targets and effects of CTXs, as well as the neurophysiological and histological studies that have contributed to existing knowledge of CFP neuropathophysiology at the molecular, neurocellular and nerve levels. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF), caused by biallelic inactivating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, has recently been categorized as a familial colorectal cancer (CRC) syndrome. CF patients are highly susceptible to early, aggressive colorectal tumor development. Endoscopic screening studies have revealed that by the age of forty 50% of CF patients will develop adenomas, with 25% developing aggressive advanced adenomas, some of which will have already advanced to adenocarcinomas. This enhanced risk has led to new CF colorectal cancer screening recommendations, lowering the initiation of endoscopic screening to age forty in CF patients, and to age thirty in organ transplant recipients. The enhanced risk for CRC also extends to the millions of people (more than 10 million in the US) who are heterozygous carriers of CFTR gene mutations. Further, lowered expression of CFTR is reported in sporadic CRC, where downregulation of CFTR is associated with poor survival. Mechanisms underlying the actions of CFTR as a tumor suppressor are not clearly understood. Dysregulation of Wnt/β-catenin signaling and disruption of intestinal stem cell homeostasis and intestinal barrier integrity, as well as intestinal dysbiosis, immune cell infiltration, stress responses, and intestinal inflammation have all been reported in human CF patients and in animal models. Notably, the development of new drug modalities to treat non-gastrointestinal pathologies in CF patients, especially pulmonary disease, offers hope that these drugs could be repurposed for gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Skin-derived precursor cells (SKPs) are neural crest stem cells that persist in certain adult tissues, particularly in the skin. They can generate a large type of cell in vitro, including neurons. SKPs were induced to differentiate into sensory neurons (SNs) by molecules that were previously shown to be important for the generation of SNs: purmorphamine, CHIR99021, BMP4, GDNF, BDNF, and NGF. We showed that the differentiation of SKPs induced the upregulation of neurogenins. At the end of the differentiation protocol, transcriptional analysis was performed on BRN3A and a marker of pain-sensing nerve cell PRDM12 genes: 1000 times higher for PRDM12 and 2500 times higher for BRN3A in differentiated cells than they were in undifferentiated SKPs. Using immunostaining, we showed that 65% and 80% of cells expressed peripheral neuron markers BRN3A and PERIPHERIN, respectively. Furthermore, differentiated cells expressed TRPV1, PAR2, TRPA1, substance P, CGRP, HR1. Using calcium imaging, we observed that a proportion of cells responded to histamine, SLIGKV (a specific agonist of PAR2), polygodial (a specific agonist of TRPA1), and capsaicin (a specific agonist of TRPV1). In conclusion, SKPs are able to differentiate directly into functional SNs. These differentiated cells will be very useful for further in vitro studies. [ABSTRACT FROM AUTHOR]

A range of sophisticated imaging techniques have been developed in recent years that can reveal the surface structure of cultural heritage objects with varying precision. In combination with various spectroscopic methods, they allow the study of the chemical composition of the object; thus, conclusions can be drawn about the origin of the object or its initial components, method, or time of creation, authenticity, mechanisms of degradation, and ways of further conservation. At present, different techniques can be applied to a wide range of cultural heritage objects, such as varnishes, paintings, archaeological objects, binding media, paper-based documents, parchments, marbles, frescoes, as well as various objects made of leather, fabric, stone, ceramics and glass, wood, or metal. One of the main needs in the study of cultural heritage (CH) is the transportability/portability of the research equipment, since many pieces under investigation cannot be moved to the laboratory, either because of their size, inseparability (for example, frescoes on walls, mural paintings in caves), or the threat of damage. In this work, we briefly overview the main optical- and laser-based methods used for the study of cultural heritage objects indicating the scope of their application, and we focus on the applications of non-linear microscopic methods for the investigation of a series of artifacts. We also discuss all the requirements for the construction of a prototype transportable non-linear optical system that will be used as a novel diagnostic tool for in situ studies of CH assets. The availability of such a transportable workstation will significantly improve the study and characterization of various types of CH objects and will constitute an extremely useful diagnostic tool for heritage scientists dealing with a variety of investigations. [ABSTRACT FROM AUTHOR]

Musical instruments are tools for playing music, but for some of them—made by the most important historical violin makers—the myths hide the physical artwork. Ancient violin-making Masters developed peculiar construction methods and defined aesthetic canons that are still recognizable in their musical instruments. Recently, the focus of scientific investigations has been set on the characterization of materials and methods used by the ancient violin makers by means of several scientific approaches. In this work, the merits of synchrotron radiation micro-computed tomography and optical coherence tomography (OCT) for the investigation of complex coatings systems on historical bowed string musical instruments are discussed. Five large fragments removed during past restorations from instruments produced by Jacobus Stainer, Gasparo da Salò, Giovanni Paolo Maggini, and Lorenzo Guadagnini have been considered for a non-invasive insight by tomographic techniques and the results are discussed considering previous micro-invasive investigations. The tomographic approach allows to highlight the micro-morphology of the coating systems and offers preliminary information on the methods that were employed by the ancient Masters to treat the wood and finish the musical instrument. [ABSTRACT FROM AUTHOR]