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The multifactorial nature of cancer still classifies the disease as one of the leading causes of death worldwide. Modern medical sciences are following an interdisciplinary approach that has been fueled by the nanoscale revolution of the past years. The exploitation of high-Z materials, in combination with ionizing or non-ionizing radiation, promises to overcome restrictions in medical imaging and to augment the efficacy of current therapeutic modalities. Gold nanoparticles (AuNPs) have proven their value among the scientific community in various therapeutic and diagnostic techniques. However, the high level of multiparametric demands of AuNP experiments in combination with their biocompatibility and cytotoxicity levels remain crucial issues. Gadolinium NPs (GdNPs), have presented high biocompatibility, low cytotoxicity, and excellent hemocompatibility, and have been utilized in MRI-guided radiotherapy, photodynamic and photothermal therapy, etc. Τhe utilization of gadolinium bound to AuNPs may be a promising alternative that would reduce phenomena, such as toxicity, aggregation, etc., and could create a multimodal in vivo contrast and therapeutic agent. This review highlights multi-functionalization strategies against cancer where gold and gadolinium NPs are implicated. Their experimental applications and limitations of the past 5 years will be analyzed in the hope of enlightening the benefits and drawbacks of their proper combination.

Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by mechanical forces and play an essential role in cellular mechanotransduction. However, readouts of Piezo1 activity are mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging. Here, we introduce GenEPi, a genetically-encoded fluorescent reporter for non-invasive optical monitoring of Piezo1-dependent activity. We demonstrate that GenEPi has high spatiotemporal resolution for Piezo1-dependent stimuli from the single-cell level to that of the entire organism. GenEPi reveals transient, local mechanical stimuli in the plasma membrane of single cells, resolves repetitive contraction-triggered stimulation of beating cardiomyocytes within microtissues, and allows for robust and reliable monitoring of Piezo1-dependent activity in vivo. GenEPi will enable non-invasive optical monitoring of Piezo1 activity in mechanochemical feedback loops during development, homeostatic regulation, and disease.

In the modern working reality, the term Digital Nomad refers to professionals who work remotely via the internet and initially the phenomenon was treated simply as a modern way of life that includes continuous travel and travel away from the place of permanent residence. But since travel is a key part of nomadic life, it is now important to understand the potential of digital nomads as tourists. In a highly competitive international tourism environment, the utilization of Digital Nomads can prove to be an extremely important advantage. As this audience grows constantly, the major tourist destinations around the world are claiming their share. The growing enthusiasm of workers for travel combining work and leisure is gradually being addressed by the policies of countries that are trying to work out and amend rules on residence permits and taxation. Finally, a research on correlation coefficient is realized by the authors. According to the research findings, Nomad Tourists spend time and activities in the destination and in favor for the destination. There is a close (r = 0.62) correlation between activities and spending time in the destination. Also, from the questionnaire a number of tourist digital nomads activities are resulted, indicating that nomads participate in local activities (for example cultural activities) even if their job is offered in another place or country. From this point of view, tourist nomads participate in local development in the destination.

PurposeThe purpose of this study is, first, to determine which developments have shaped official hotel classification systems over recent years (including the impact of guest-review platforms) and second to establish the future of those systems through the eyes of the people who are actually in charge of operating them.Design/methodology/approachSemi-structured interviews were chosen as the most suitable method for approaching hotel classification system administrators. This method is in line with previous research on approaching key informants in their respective fields. Sixteen people representing 12 different official national hotel classification systems from across the world as well as one commercial hotel star rating system participated in the online interviews.FindingsThe first main conclusion is that hotel classification systems – especially voluntary ones – would not have survived the enormous impact of guest-review platforms without quickly adjusting to the ever-changing hotel industry landscape. The frequent review of classification criteria and procedures has become the main survival strategy of classification systems. The second conclusion is that system operators are strongly optimistic about the future outlook of hotel classification based on their proven flexibility to swiftly adapt to new market conditions.Originality/valueResearch about hotel classification systems is usually based on the views of the systems' users, i.e. hotels or hotel guests, whereas the present paper reflects the perspective of the systems' operators, an angle rarely analyzed in the literature.

Second-home tourism is a rapidly growing form of tourism around the world. Being an integral part of rural areas and their history, second homes are an established example of the post-productive consumption of the countryside. Τhe expansion of urbanization and the pressures of the urban way of life, as well as the search for a pleasant climate and clean environment, have contributed particularly to the development of second home tourism globally. This study intends to investigate the present, the future and the impact of second home tourism on destinations, local people and tourists. The development of second home tourism, or tourist home is, undoubtedly, a strongly evolving social phenomenon. Activated by economically developed societies and is linked to income growth, urbanization, the possibility of geographical mobility and the increase of leisure time. This phenomenon operates and intensifies, almost in parallel with tourism. Also, the study investigates the effects of second home tourism in Greece, a very popular destination for international and domestic tourism. The country has been experienced a high growth of second home tourism in the last few years.

Background Foraging for food precedes food consumption and is an important component of the overall metabolic programming that regulates feeding. Foraging is governed by central nervous system neuronal circuits but how it is influenced by diet and hormonal signals is still not well understood. Results In this study, we show that dietary cholesterol exerted suppressive effects on locomotor activity and that these effects were partially mediated by the neuropeptide Agouti-related protein (AgRP). High dietary cholesterol stimulated intestinal expression of fibroblast growth factor 15 (Fgf15), an ortholog of the human fibroblast growth factor 19 (FGF19). Intracerebroventricular infusion of FGF19 peptide reduced exploratory activity in the open field test paradigm. On the other hand, the lack of dietary cholesterol enhanced exploratory activity in the open field test, but this effect was abolished by central administration of FGF19. Conclusions Experiments in this study show that dietary cholesterol suppresses locomotor activity and foraging-like behaviors, and this regulation is in part mediated by AgRP neurons. Dietary cholesterol or the central action of FGF19 suppresses exploratory behaviors, and the anxiogenic effects of dietary cholesterol may be mediated by the effect of FGF19 in the mouse brain. This study suggests that dietary cholesterol and intestinal hormone FGF15/19 signal a satiating state to the brain, thereby suppressing foraging-like behaviors.

One of the crucial ingredients for the improvement of stellar models is the accurate knowledge of neutron capture cross-sections for the different isotopes involved in the $s$-,$r$- and $i$- processes. These measurements can shed light on existing discrepancies between observed and predicted isotopic abundances and help to constrain the physical conditions where these reactions take place along different stages of stellar evolution.In the particular case of the radioactive $^{94}$Nb, the $^{94}$Nb($n$,$γ$) cross-section could play a role in the determination of the $s$-process production of $^{94}$Mo in AGB stars, which presently cannot be reproduced by state-of-the-art stellar models. There are no previous $^{94}$Nb($n$,$γ$) experimental data for the resolved and unresolved resonance regions mainly due to the difficulties in producing high-quality samples and also due to limitations in conventional detection systems commonly used in time-of-flight experiments.Motivated by this situation, a first measurement of the $^{94}$Nb($n$,$γ$) reaction was carried out at CERN n\_TOF, thereby exploiting the high luminosity of the EAR2 area in combination with a new detection system of small-volume C6D6-detectors and a high quality $^{94}$Nb-sample. The latter was based on hyper-pure $^{93}$Nb material activated at the high-flux reactor of ILL-Grenoble. An innovative ring-configuration detection system in close geometry around the capture sample allowed us to significantly enhance the signal-to-background ratio. This set-up was supplemented with two conventional C$_{6}$D$_{6}$ detectors and a high-resolution LaCl$_{3}$(Ce)-detector, which will be employed for addressing reliably systematic effects and uncertainties.At the current status of the data analysis, 18 resonance in $^{94}$Nb+$n$ have been observed for the first time in the neutron energy range from thermal up to 10 keV., NPA-X conference proceeding

In the present work extensive multiple scattering (i.e. angular straggling) calculations were performed, implementing general–purpose Monte Carlo codes (GEANT4, MCNP6.1, FLUKA, PHITS) and selected, dedicated ion beam analysis programs (such as SRIM2013 and SIMNRA7.03), using 158.6 MeV protons impinging on a variety of thin or semi–thick, pure, single–element targets, such as carbon, aluminum, copper, tin, lead, beryllium and zinc, which are typically used as shielding materials or components in complex devices, in order to investigate all the occurring differences and similarities with respect to the experimental results obtained in the classic work of Gottschalk et al. [1] . Polystyrene was the only compound target to be examined, since it is a plastic commonly used in various applications. The obtained results are presented in graphical form, as ratios to the available experimental data from [1] for various target thicknesses and are subsequently discussed and analyzed.

Summary Background and aims The effects of ileostomy construction and colonic bypass on the general nutritional status of the patients have not yet received much attention. The aim of the present study was to assess the effect of a diverting ileostomy formation, on the nutritional intake, body composition and nutritional status biochemical markers of patients with a newly formed ileostomy. Methods This was an observational study. Patients scheduled for elective rectosigmoid resection at a surgical unit of a public university hospital, were considered for study inclusion. Patients in whom a diverting ileostomy was created were assigned to the ileostomy group (n = 41), and patients who underwent rectosigmoid resection without requiring a diverting ileostomy served as a control group (n = 37). Anthropometric characteristics, body composition, dietary intake and biochemical markers representative of nutritional status were assessed preoperatively and at 40 days postdischarge (NCT02036346). Results Anthropometric and body composition characteristics (weight, BMI and body fat percentage) significantly declined from 75 to 71.6 kg, 26.9 to 25.6 kg/m2 and 28.6 to 25.6% respectively (p = 0.001 for all) in the ileostomy group, between the preoperative stage and 40 days postdischarge from the hospital. Furthermore, a significant reduction in mean daily energy intake from 1871 to 1713 kcal/day (p = 0.046) was observed in the ileostomy group 40 days after discharge compared to preoperative assessment. No significant changes in the above measured parameters were observed in the non-ileostomy group. Conclusion Diverting ileostomy can have a negative effect on general nutritional status and dietary intake of patients, during the first postoperative period. Nutritional assessment might need to be included in the routine clinical management of this patient category to prevent weight loss and impaired energy intake.

La educción inclusiva hoy pasa unilateralmente por imbricar su práctica con las Tecnologías de la Información y la Comunicación. Sin embargo, para que esto se pueda producir las percepciones que los docentes tienen de las tecnologías van a marcar su empleo en la dinámica educativa. El objetivo principal de esta investigación es recopilar la opinión que tienen los profesores de Educación Secundaria de la localidad Atenas y Tesalónica (Grecia) sobre el empleo de las TIC en ambientes educativos inclusivos. A través de un diseño ex post facto y mediante un estudio descriptivo, inferencial y correlacional, se ha administrado un cuestionario creado ad hoc a una muestra de 377 docentes de Enseñanza Secundaria de Grecia, seleccionados a través de un muestreo de tipo incidental. El principal resultado alcanzado indica la no existencia de diferencias en sus visiones en función de la edad o del género, y que consideran que sus estudiantes están mejor formados digitalmente que ellos. Se puede concluir que, al igual que sucede en otros contextos los docentes helénicos demandan una formación clave para la utilización de las TIC en los entornos inclusivos en los que trabajan.

BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations.Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χOf 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups.These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.

In the present work extensive stopping power calculations were performed, implementing general–purpose Monte Carlo codes (GEANT4, MCNP6.1, FLUKA, PHITS) and dedicated stopping power compilations (such as SRIM2013, PSTAR/ ASTAR from NIST and ATIMA), having protons, alpha particles, 12C, 16O and 56Fe ions as beam particles, in the energy range between ~1 and ~1000 MeV/u, impinging on a variety of thin or infinitely thick, pure, single–element targets, such as aluminum, iron, copper and silicon, which are typically used as shielding materials or components in complex devices, in order to investigate all the occurring differences and similarities in the obtained results. Water was the only compound target to be examined, since it is commonly used as a close substitute for biological tissue. In all the simulations the process of multiple scattering was ignored or disabled. The obtained results are presented in graphical form, along with all the available experimental data in the studied energy range and the occurring similarities and discrepancies are discussed and analyzed.

Variants in the gene encoding ankyrin repeat and SOCS box–containing 4 ( ASB4 ) are linked to human obesity. Here, we characterized the pathways underlying the metabolic functions of ASB4. Hypothalamic Asb4 expression was suppressed by fasting in wild-type mice but not in mice deficient in AgRP , which encodes Agouti-related protein (AgRP), an appetite-stimulating hormone, suggesting that ASB4 is a negative target of AgRP. Many ASB4 neurons in the brain were adjacent to AgRP terminals, and feeding induced by AgRP neuronal activation was disrupted in Asb4 -deficient mice. Acute knockdown of Asb4 in the brain caused marked hyperphagia due to increased meal size, and Asb4 deficiency led to increased meal size and food intake at the onset of refeeding, when very large meals were consumed. Asb4 -deficient mice were resistant to the meal-terminating effects of exogenously administered calcitonin and showed decreased neuronal expression of Calcr , which encodes the calcitonin receptor. Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus in mice are involved in glucose homeostasis, and Asb4 deficiency specifically in POMC neurons resulted in glucose intolerance that was independent of obesity. Furthermore, individuals with type 2 diabetes showed reduced ASB4 abundance in the infundibular nuclei, the human equivalent of the arcuate nucleus. Together, our results indicate that ASB4 acts in the brain to improve glucose homeostasis and to induce satiety after substantial meals, particularly those after food deprivation.

ObjectivePreference for dietary fat vs. carbohydrate varies markedly across free-living individuals. It is recognized that food choice is under genetic and physiological regulation, and that the central melanocortin system is involved. However, how genetic and dietary factors interact to regulate relative macronutrient intake is not well understood.MethodsWe investigated how the choice for food rich in carbohydrate vs. fat is influenced by dietary cholesterol availability and agouti-related protein (AGRP), the orexigenic component of the central melanocortin system. We assessed how macronutrient intake and different metabolic parameters correlate with plasma AGRP in a cohort of obese humans. We also examined how both dietary cholesterol levels and inhibiting de novo cholesterol synthesis affect carbohydrate and fat intake in mice, and how dietary cholesterol deficiency during the postnatal period impacts macronutrient intake patterns in adulthood.ResultsIn obese human subjects, plasma levels of AGRP correlated inversely with consumption of carbohydrates over fats. Moreover, AgRP-deficient mice preferred to consume more calories from carbohydrates than fats, more so when each diet lacked cholesterol. Intriguingly, inhibiting cholesterol biosynthesis (simvastatin) promoted carbohydrate intake at the expense of fat without altering total caloric consumption, an effect that was remarkably absent in AgRP-deficient mice. Finally, feeding lactating C57BL/6dams and pups a cholesterol-free diet prior to weaning led the offspring to prefer fats over carbohydrates as adults, indicating that altered cholesterol metabolism early in life programs adaptive changes to macronutrient intake.ConclusionsTogether, our study illustrates a specific gene-diet interaction in modulating food choice.

Early-stage, precise disease diagnosis and treatment has been a crucial topic of scientific discussion since time immemorial. When these factors are combined with experience and scientific knowledge, they can benefit not only the patient, but also, by extension, the entire health system. The development of rapidly growing novel technologies allows for accurate diagnosis and treatment of disease. Nanomedicine can contribute to exhaled breath analysis (EBA) for disease diagnosis, providing nanomaterials and improving sensing performance and detection sensitivity. Through EBA, gas-based nano-sensors might be applied for the detection of various essential diseases, since some of their metabolic products are detectable and measurable in the exhaled breath. The design and development of innovative nanomaterial-based sensor devices for the detection of specific biomarkers in breath samples has emerged as a promising research field for the non-invasive accurate diagnosis of several diseases. EBA would be an inexpensive and widely available commercial tool that could also be used as a disease self-test kit. Thus, it could guide patients to the proper specialty, bypassing those expensive tests, resulting, hence, in earlier diagnosis, treatment, and thus a better quality of life. In this review, some of the most prevalent types of sensors used in breath-sample analysis are presented in parallel with the common diseases that might be diagnosed through EBA, highlighting the impact of incorporating new technological achievements in the clinical routine.

Secondary infections contribute significantly to covid-19 mortality but host and microbial factors driving this sequel remain poorly understood. We performed an autopsy study of 20 covid-19 cases and 14 controls from the first pandemic wave. Autopsies combined with microbial cultivation and deep RNA sequencing (RNAseq) allowed us to define major organ pathologies and specify secondary infections. Lethal covid-19 segregated into two main death causes separating cases with either dominant diffuse alveolar damage (DAD) or secondary infections of lungs. Lung microbiome changes were profound in covid-19 showing a reduced biodiversity and increased presence of prototypical bacterial and fungal pathogens in cases with secondary infections. Deep RNAseq of lung tissues distinctly mirrored death causes and cellular deconvolution stratified DAD cases into subgroups with different cellular compositions. Myeloid cells, including macrophages, and complement C1q activation were found to be strong stratifying factors suggesting a pathophysiological link possibly leading to tolerance in DAD subgroups. Moreover, several signs of immune-impairment were evident in covid-19 lungs including strong induction of inhibitory immune-checkpoints. Thus, our study highlights profound alterations of the local immunity in covid-19, wherein immune-impairment leads to reduced antimicrobial defense favoring the development of secondary infections on top of SARS-CoV-2 infection.

There has been increased interest among researchers and industry to generate insights from user-generated data and ratings on account of valuable information such as data carry and its authenticity. Numerous studies offer insight into how traditional hotel classification ratings are influenced by the information and communication technology. However, no such studies that explore the relationship between traditional hotel ratings and the largest online hotel review website, TripAdvisor, could be found. To bridge the gap, the study uses the TripAdvisor hotel rating data from Greek hotels to explore this relationship using Kruskal-Wallis H test. The results show that mean TripAdvisor ratings of hotels are in proportion to the traditional hotel classification ratings.

Inclusive education is a key tool for promoting equity in educational opportunities, that is using ICT and accessible web and non-web content to support the learning of students with disabilities in inclusive settings within compulsory education. This thesis is focusing on disability including the challenges that disabled students faced in Greece. An elaborate description of the terms Special Education and Inclusive Education is made. Additionally, ways supporting Greek special education system are also stated. In this context, challenges concerning access to software application faced by disable users are mentioned, as well as the most regularly used Assistive Technologies. Guidelines are also ponted out explaining how application, content and web-content can be made accessible to people with all types of disabilities. The study aims to determine how such familiar are Educators using ICT tools during the learning process of students with disabilities both in special and mainstream school setting, in Greece. More specifically, to define views and feelings regarding the benefits of using ICT for students with vision, speech and auditory disabilities, intellectual and cognitive disabilities, as well as physical impairments. Lastly, to investigate how much Educators are familiar with accessibility issues, applying accessibility tests and how capable Educators are to create comprehensible and navigable web and non-web content accessible by the disable. The study reveals that age and years of teaching experience in regular but also in special education play a significant role, as for the type of employment little contribution to the results and only for full-time Educators with public or private contracts.

The n_TOF neutron time-of-flight facility at CERN is used for nuclear data measurements. The n_TOF Collaboration works closely with the Nuclear Reaction Data Centres (NRDC) network to disseminate the experimental data through the international EXFOR library. In addition, the Collaboration helps integrate the results in the evaluated library projects. The present contribution describes the dissemination status of n_TOF results, their impact on evaluated libraries and ongoing efforts to provide n_TOF resonance parameters in ENDF-6 format for further use by evaluation projects.

Objective: Preference for dietary fat vs. carbohydrate varies markedly across free-living individuals. It is recognized that food choice is under genetic and physiological regulation, and that the central melanocortin system is involved. However, how genetic and dietary factors interact to regulate relative macronutrient intake is not well understood. Methods: We investigated how the choice for food rich in carbohydrate vs. fat is influenced by dietary cholesterol availability and agouti-related protein (AGRP), the orexigenic component of the central melanocortin system. We assessed how macronutrient intake and different metabolic parameters correlate with plasma AGRP in a cohort of obese humans. We also examined how both dietary cholesterol levels and inhibiting de novo cholesterol synthesis affect carbohydrate and fat intake in mice, and how dietary cholesterol deficiency during the postnatal period impacts macronutrient intake patterns in adulthood. Results: In obese human subjects, plasma levels of AGRP correlated inversely with consumption of carbohydrates over fats. Moreover, AgRP-deficient mice preferred to consume more calories from carbohydrates than fats, more so when each diet lacked cholesterol. Intriguingly, inhibiting cholesterol biosynthesis (simvastatin) promoted carbohydrate intake at the expense of fat without altering total caloric consumption, an effect that was remarkably absent in AgRP-deficient mice. Finally, feeding lactating C57BL/6 dams and pups a cholesterol-free diet prior to weaning led the offspring to prefer fats over carbohydrates as adults, indicating that altered cholesterol metabolism early in life programs adaptive changes to macronutrient intake. Conclusions: Together, our study illustrates a specific gene–diet interaction in modulating food choice.

Στην παρούσα Διδακτορική Διατριβή παρουσιάζονται τα αποτελέσματα που αφορούν τη μελέτη της παρασκευής και του χαρακτηρισμού νέων σύνθετων υλικών. Τα νέα αυτά υλικά, έχουν ως βάση διάφορα οξείδια μετάλλων, τα οποία εμφανίζουν ημιαγώγιμες ιδιότητες. Η τροποποίηση των οξειδίων αυτών γίνεται με την προσθήκη οξειδίου του γραφενίου (GO), με στόχο την ενίσχυση των ιδιοτήτων τους. Η σύνθεση των τροποποιημένων υλικών μελετήθηκε, τόσο ως προς τη διαδικασία της υδροθερμικής κατεργασίας, όσο και ως προς τον καθορισμό των ιδανικών αναλογιών του GO και του οξειδίου του μετάλλου. Τα φυσικοχημικά χαρακτηριστικά των νέων αυτών υλικών μελετήθηκαν με τη χρήση διαφόρων τεχνικών, όπως η Μονοφασική Χρωματογραφία Πεδίου (ΜΧΠ), οι φασματοσκοπίες UV-Vis, Raman και δυναμική σκέδαση φωτός (DLS), καθώς επίσης με την οπτική και την ηλεκτρονική μικροσκοπία. Στο πρώτο μέρος της διατριβής αυτής, παρουσιάζονται τα αποτελέσματα τροποποιημένων υλικών με βάση το TiO2, παρουσία GO. Παρασκευάστηκαν νέα υλικά με τρεις διαφορετικές διαδικασίες υδροθερμικής επεξεργασίας, στα οποία χρησιμοποιήθηκαν διάφορες αναλογίες GO/TiO2. Οι συγκεκριμένες μέθοδοι σύνθεσης αφορούν την υδροθερμική διαδικασία μέχρι ξηρού, σε αυτόκλειστο δοχείο και υπό αναρροή (reflux). Βρέθηκε, με την τεχνική της ΜΧΠ, ότι η υδροθερμική διαδικασία υπό αναρροή δίνει το μικρότερο μέσο μέγεθος των σωματιδίων GO/TiO2, τόσο της τάξης μερικών μικρομέτρων, όσο και μερικών εκατοντάδων νανομέτρων. Επιπλέον, με την τεχνική της DLS, παρατηρήθηκε σε ορισμένες συνθέσεις και δυωνυμική κατανομή μεγεθών από τα σωματίδια GO/TiO2. Και στις τρεις διαδικασίες σύνθεσης, η επιτυχής σύνδεση των επιμέρους υλικών επιβεβαιώθηκε, τόσο με την τεχνική της φασματοσκοπίας Raman, όσο και με το TEM. Στο δεύτερο μέρος, μελετήθηκε η τροποποίηση του μεικτού οξειδίου ZrO2/Υ2Ο3 (ζιρκόνια σταθεροποιημένη με ύττρια – YSZ), με το GO. Με τη διαδικασία υδρόλυσης–πολυμερισμού (sol-gel σύνθεση), παρασκευάστηκαν τα μεικτά οξείδια 3YSZ (3 % w/w Υ2Ο3/ZrO2) και 7YSZ (7 % w/w Υ2Ο3/ZrO2). Στη συνέχεια, μέσω της υδροθερμικής διαδικασίας υπό αναρροή, παρασκευάστηκαν τα σύνθετα υλικά GO/3YSZ και GO/7YSZ. Τα υλικά που παρασκευάστηκαν χαρακτηρίστηκαν ως προς το μέγεθός τους με τις τεχνικές της ΜΧΠ και της DLS, και βρέθηκε ότι το μέγεθος των σωματιδίων εμφάνισε διωνυμικές και τριωνυμικές κατανομές, στην περιοχή πάνω και κάτω από 1 μm. Από την φασματοσκοπία Raman, βρέθηκε ότι οι μικρές περιεκτικότητες σε YSZ είναι ιδανικές για το σχηματισμό σταθερών δομών GO/YSZ, ανεξάρτητα από το ποσοστό πρόσμιξης του Υ2Ο3 στο ZrO2. Στο τρίτο και τελευταίο μέρος, μελετήθηκε η τροποποίηση του MgO παρουσία GO. Τo MgO παρασκευάστηκε με τη μέθοδο sοl-gel, ενώ για τα σύνθετα υλικά ακολουθήθηκε η υδροθερμική διαδικασία υπό αναρροή, σε διάφορες αναλογίες GO/MgO. Τα πειραματικά αποτελέσματα έδειξαν ότι στα υλικά αυτά εμφανίζονται συσσωματώματα σε πολύ μεγάλο ποσοστό και έχουν μεγάλο μέγεθος. Από την ανάλυση της μορφολογίας των υλικών, με την οπτική και ηλεκτρονική μικροσκοπία TEM, παρατηρήθηκε ανομοιογένεια στον σχηματισμό και στην κατανομή μεγέθους των σωματιδίων. Τέλος, όλα τα παραπάνω υλικά χαρακτηρίστηκαν και ως προς τις ιδιότητες που εμφανίζουν κατά την απορρόφηση ακτινοβολίας στην ορατή και υπεριώδη περιοχή του φάσματος. Παρατηρήθηκε ότι ακόμα και οι μικρότερες ποσότητες φωτοενεργούς ουσίας είναι ικανές στο να δημιουργήσουν τροποποιημένα υλικά με βελτιωμένες φωτοηλεκτρονιακές ιδιότητες, αξιοποιώντας έτσι ένα μεγάλο μέρος της ηλιακής ακτινοβολίας.

BackgroundGene panel testing has become the norm for assessing breast cancer (BC) susceptibility, but actual cancer risks conferred by genes included in panels are not established. Contrarily, deciphering the missing hereditability on BC, through identification of novel candidates, remains a challenge. We aimed to investigate the mutation prevalence and spectra in a highly selected cohort of Greek patients with BC, questioning an extensive number of genes, implicated in cancer predisposition and DNA repair, while calculating gene-specific BC risks that can ultimately lead to important associations.MethodsTo further discern BC susceptibility, a comprehensive 94-cancer gene panel was implemented in a cohort of 1382 Greek patients with BC, highly selected for strong family history and/or very young age (ResultsHerein, 31.5% of patients tested carried pathogenic variants (PVs) in 28 known, suspected or candidate BC predisposition genes. In total, 24.8% of the patients carriedBRCA1/2loss-of-function variants. An additional 6.7% carried PVs in additional genes, the vast majority of which can be offered meaningful clinical changes. Significant association to BC predisposition was observed forATM, PALB2, TP53, RAD51CandCHEK2PVs. Primarily, compared with controls,RAD51CPVs andCHEK2damaging missense variants were associated with high (ORs 6.19 (Exome Aggregation Consortium (ExAC)) and 12.6 (Fabulous Ladies Over Seventy (FLOSSIES)), p<0.01) and moderate BC risk (ORs 3.79 (ExAC) and 5.9 (FLOSSIES), p<0.01), respectively.ConclusionStudying a large and unique cohort of highly selected patients with BC, deriving from a population with founder effects, provides important insight on distinct associations, pivotal for patient management.

PALB2 loss-of-function variants play an important role in breast, pancreatic and possibly, ovarian and gastric cancer susceptibility. Their frequency can be influenced by founder effects, already described in some populations. Herein, we have assessed the possible founder effect of PALB2 c.2257C>T (p.Arg753*) truncating variant among Greek breast cancer patients, while investigating possible correlations with cancer diagnoses. Following a lead deriving from a background study of highly selected Greek breast cancer patients, a total of 2496 breast and 697 ovarian cancer patients were directly genotyped for the PALB2 c.2257C>T truncating variant. Consequently, haplotype analysis was conducted on identified carriers, using seven microsatellite markers. The prevalence of the PALB2 variant was 0.24% (6/2496) and 0.14% (1/697) among breast and ovarian cases, respectively. Family history seems to be an important factor for the variant identification, although not reaching statistical significance. Microsatellite analysis on 12 carriers revealed a common shared haplotype, spanning a chromosomal region of ~1.2 Mb; the variant was possibly introduced in the Greek population ~1600 years ago. The variant confers high breast cancer risk, as illustrated by comparison with publicly available control groups. Genetic testing for PALB2, especially for the Greek founder c.2257C>T truncating variant, should be seriously considered in Greek breast cancer cases, since such findings could assist appropriate clinical management for the patients and their families.

Gender - related issues are central factors causing refugee flows, but also act as an impediment in the unhindered settlement and integration of female refugees in their receiving country. However, the gender aspect, as explained in the intersectionality theory, is often neglected in refugee rights’ analysis. Women refugees deal with continuous hardships before and during their journey, but their quest for a better life does not stop at the arrival on the European continent. Discrimination and Gender- Based Violence follow them at their arrival also in Greece, a major hosting country. The analysis below aims in this context to showcase the risks that refugee women face before, during and after their displacement, taking as a main paradigm the case of Greece. After that the effectiveness of the response system, through the collaboration of governmental and non - governmental actors, like NGOs and civil society organizations in Greek territory is examined. This paper establishes a causality between gender and dangers or insufficiencies faced by refugees and enlightens understated aspects of this issue.

Background: Abundance calculations of a certain class of proton-rich isotopes, known as $p$ nuclei, require knowledge of the cross sections of thousands of nuclear reactions entering a reaction network. As a result, the solution of the latter relies on the predictions of the Hauser-Feshbach (HF) theory and, hence, on the reliability of the models describing the nuclear parameters entering the HF calculations, notably the optical model potential (OMP), the nuclear level density (NLD) and the $\ensuremath{\gamma}$-ray strength function ($\ensuremath{\gamma}\mathrm{SF}$).Purpose: The present work reports on a systematic study of proton capture reactions on Sr isotopes at energies relevant to the $p$ process which is responsible for the production of the $p$ nuclei at explosive stellar sites. The purpose of the work reported here is to perform a validity test of the different OMP, NLD, and $\ensuremath{\gamma}\mathrm{SF}$ models through extensive and detailed comparisons between HF calculations and experimental cross section data. This test is necessary to understand the origin of discrepancies between the $p$-nuclei abundances observed in the solar system and those predicted by the different astrophysical models, known as $p$-process models, aiming at describing the nucleosynthesis of the $p$ isotopes.Method: Cross sections were determined from $\ensuremath{\gamma}$-angular distribution measurements and from angle-integrated $\ensuremath{\gamma}$ spectra taken with the $4\ensuremath{\pi}\phantom{\rule{4pt}{0ex}}\ensuremath{\gamma}$-summing technique. Cross-section data and the resulting astrophysical $S$ factors were compared with Hauser-Feshbach calculations obtained with the latest version 1.95 of the nuclear reaction code talys using combinations of global semi-microscopic and phenomenological models of optical potentials (OMPs), nuclear level densities (NLDs), and $\ensuremath{\gamma}$-ray strength functions ($\ensuremath{\gamma}\mathrm{SFs}$).Results: Total cross sections as well as cross sections to the ground and metastable states were determined for the reactions $^{86}\mathrm{Sr}(p,\ensuremath{\gamma})^{87}\mathrm{Y}$, $^{87}\mathrm{Sr}(p,\ensuremath{\gamma})^{88}\mathrm{Y}$, and $^{88}\mathrm{Sr}(p,\ensuremath{\gamma})^{89}\mathrm{Y}$ at incident proton-beam energies from 2.5 to 3.6, 2 to 5, and 1.5 to 5 MeV, respectively.Conclusions: The experimental data reported in the present work are in very good agreement with the talys 1.95 calculations obtained with the default combination of OMP, NLD, and $\ensuremath{\gamma}\mathrm{SF}$ models. This combination is based on purely phenomenological models. A semimicroscopic proton-nucleus optical model potential was optimized at low energies leading to an equally good agreement between experimental data and theoretical calculations based solely on combinations of fully semimicroscopic models of OMP, NLD, and $\ensuremath{\gamma}\mathrm{SF}$. Our results highlight the need for a continued effort on the systematic study of proton-capture reactions to reduce the range of uncertainties arising from global nuclear models for as wide a range of relevant nuclei as possible. In this regard, new ($p,\ensuremath{\gamma}$) data at the lowest possible energies below the opening of the neutron channel are of key importance to improve global proton-nucleus optical model potentials.

During vertebrate development, cells must proliferate, move, and differentiate to form complex shapes. Elucidating the mechanisms underlying the molecular and cellular processes involved in tissue morphogenesis is essential to understanding developmental programmes. Mechanical stimuli act as a major contributor of morphogenetic processes and impact on cell behaviours to regulate tissue shape and size. Specifically, cell extrinsic physical forces are translated into biochemical signals within cells, through the process of mechanotransduction, activating multiple mechanosensitive pathways and defining cell behaviours. Physical forces generated by tissue mechanics and the extracellular matrix are crucial to orchestrate tissue patterning and cell fate specification. At the cell scale, the actomyosin network generates the cellular tension behind the tissue mechanics involved in building tissue. Thus, understanding the role of physical forces during morphogenetic processes requires the consideration of the contribution of cell intrinsic and cell extrinsic influences. The recent development of multidisciplinary approaches, as well as major advances in genetics, microscopy, and force-probing tools, have been key to push this field forward. With this review, we aim to discuss recent work on how tissue shape can be controlled by mechanical forces by focusing specifically on vertebrate organogenesis. We consider the influences of mechanical forces by discussing the cell-intrinsic forces (such as cell tension and proliferation) and cell-extrinsic forces (such as substrate stiffness and flow forces). We review recently described processes supporting the role of intratissue force generation and propagation in the context of shape emergence. Lastly, we discuss the emerging role of tissue-scale changes in tissue material properties, extrinsic forces, and shear stress on shape establishment.

Organ morphogenesis involves dynamic changes of tissue properties at the cellular scale. In addition, cells need to adapt to their mechanical environment through mechanosensitive pathways. How mechanical cues influence cell behaviors during morphogenesis, however, remains poorly understood. Here we studied the influence of mechanical forces during the formation of the atrioventricular canal (AVC) where cardiac valves develop. We show that in zebrafish the AVC forms within a zone of tissue convergence between the atrium and the ventricle which is associated with increased activation of the actomyosin meshwork and endocardial cell orientation changes. We demonstrate that tissue convergence occurs with a major reduction of endocardial cell volume triggered by mechanical forces and the mechanosensitive channels TRPP2/TRPV4. In addition, we show that the extracellular matrix component hyaluronic acid controls cell volume changes. Together, our data suggest that cell volume change is a key cellular feature activated by mechanical forces during cardiovascular morphogenesis. This work further unravels how mechanical forces and extracellular matrix can influence tissue remodeling in developing organs.

The present research investigates the official classification systems in order to find common, important sectors and criteria. Some criteria indicate the perception of certifying organizations, of countries that apply them, and of the hotel industry, as to what is important for a hotel to offer. Official classification systems state their basic principles, which differ from one system to another and not all are met at the same time. Most countries give three reasons for entering a formal rating system: consumer protection, tourism planning and marketing. The study will present the practices applied in the hotel industry, through compliance with official classification systems. It will contribute to the existing knowledge of hoteliers, institutions and organizations that create hotel certification systems, and in general to the knowledge of the tourism industry. Hotel classification systems are tools for maintaining the high quality of hotel industry. Also, τhe classification of hotels presents heterogeneity. Common points are the range of ranking categories and the marks used, but if the requirements of the criteria of each category are analyzed, very different conditions are discovered, sometimes even within the same country. Nevertheless, the introduction of a classification system for hotels is a complex matter due to the diversity of classification systems, accommodation types and the cultural, environmental and economic context in which the systems operate each time in individual countries. This study results, in a proposed model hotel classification system, which will directly contribute to reducing the risk of not meeting customers' expectations and providing hotel services more efficiently, depending on the type and category of accommodation. Effective management of customer expectations is crucial to ensuring the viability of the tourism business. The survey data were drawn from the analytical recording and processing of 39 classification systems, applied in different countries and continents. &nbsp

Astrophysical models studying the origin of the p-nuclei require knowledge of the reaction rates of photodisintegrations and capture reactions. Since experimental data at astrophysically relevant energies are limited, reaction rate calculations rely on Hauser-Feshbach (HF) theory predictions. The HF theory requires nuclear physics input such as masses, level densities, $\gamma$-ray strength functions and proton-nucleus optical potentials (pOMP). The scope of this work is to improve a global semi-microscopic pOMP at energies relevant to the p-process. This is achieved by adjusting the normalization parameters of the OMP to all available proton-capture cross sections measured at low energies. By establishing the systematic behaviour of these parameters, one expects to enhance the predictive power of the pOMP when expanding to mass regions where no data exists. The HF calculations were obtained using TALYS code. The normalization parameters for the real and imaginary central potentials ($\lambda_V$ and $\lambda_W$) were adjusted to fit the proton data in the energy range where the cross-section are independent of the other nuclear inputs. Results show that the $\lambda_V$ parameter has a strong mass dependence that can be described by a second-degree polynomial function for A $\leq$ 100 and an exponential increase for 100 < A < 162. Though variations of the $\lambda_W$ have a smaller effect on the calculations, a global increase by 50$\%$ improves the results for certain nuclei without affecting the rest of the cases. The resulting adjustment functions were obtained by fitting all suitable proton data and can be used with reasonable confidence to generate the global semi-microscopic pOMP for nuclei in the medium to heavy mass region. For better statistics, more low-energy (p,$\gamma$) cross section data are needed for heavier nuclei with mass A $>$ 100., Comment: pages 20, 12 figures

In the present work the $^{165}\mathrm{Ho}(n,2n)$ reaction was studied experimentally and theoretically for the population of the ground state (${J}^{\ensuremath{\pi}}={1}^{+}$) of the $^{164}\mathrm{Ho}$ product nucleus, as well as for the population of its isomeric state (${E}_{ex}=139.8$ keV, ${J}^{\ensuremath{\pi}}={6}^{\ensuremath{-}}$). The cross sections of both the ground and isomeric state channels were measured at energies near the reaction threshold (${E}_{th}=8.04$ MeV), at 10.1, 10.4, and 10.7 MeV, as well as at energies higher than 17 MeV, at 17.1, 18.1, 19.0, and 19.6 MeV. The adopted method was the activation technique relative to the $^{197}\mathrm{Au}(n,2n)^{196}\mathrm{Au}$ and $^{27}\mathrm{Al}(n,\ensuremath{\alpha})^{24}\mathrm{Na}$ reference reactions. The quasi-monoenergetic neutron beams for the near threshold energies were produced via the $^{2}\mathrm{H}(d,n)^{3}\mathrm{He}$ reaction, while for the neutron beams above 17 MeV the $^{3}\mathrm{H}(d,n)^{4}\mathrm{He}$ reaction was utilized. In both cases the deuteron beams were delivered by the 5.5 MV Tandem Van de Graaff accelerator of the Institute of Nuclear and Particle Physics at N.C.S.R. ``Demokritos''. Additional to the experimental study, calculations were performed using the talys code (v. 1.9). The experimental data of the present work along with the previous measurements were compared with the talys results so as to investigate the reproduction of the experimental data for the different level density models of the code.

Background: Unusual morphological variants of plasma cell myeloma are a diagnostic challenge.Case presentation: A 60 year old woman with low-back pain was diagnosed with a plasma cell myeloma in the bone marrow. Concurrently a tumour was found in the liver. The histological specimen of the liver resembled a clear cell carcinoma, but the immunophenotype revealed plasma cell myeloma.Conclusion: In tumours with an extraordinary morphology and not conclusive immunohistochemical results the use of plasma cell antibodies may lead to the correct diagnosis.

Organ morphogenesis involves dynamic changes of tissue properties while cells adapt to their mechanical environment through mechanosensitive pathways. How mechanical cues influence cell behaviors during morphogenesis remains unclear. Here, we studied the formation of the zebrafish atrioventricular canal (AVC) where cardiac valves develop. We show that the AVC forms within a zone of tissue convergence associated with the increased activation of the actomyosin meshwork and cell-orientation changes. We demonstrate that tissue convergence occurs with a reduction of cell volume triggered by mechanical forces and the mechanosensitive channel TRPP2/TRPV4. Finally, we show that the extracellular matrix component hyaluronic acid controls cell volume changes. Together, our data suggest that multiple force-sensitive signaling pathways converge to modulate cell volume. We conclude that cell volume reduction is a key cellular feature activated by mechanotransduction during cardiovascular morphogenesis. This work further identifies how mechanical forces and extracellular matrix influence tissue remodeling in developing organs.

A massive sliced Pb-target was irradiated by 20 MeV electrons and the bremsstrahlung photons produced plus the photoneutrons are applied to measure Pb 204 ( γ , n ) and Pb 204 ( n , n ′ ) reactions cross section. The radioactivity induced inside the Pb-target slices was measured using γ-spectrometry. Incidentally, the Sb 121 ( γ , n ) and ( n , γ ) besides the Sb 123 ( γ , n ) nuclear reactions were also measured, since Sb is added in lead alloys to increase their rigidity. A detailed geometry of the Pb-target has been simulated using the GEANT4 code and the initial photons and neutrons fluence at the entrance of the Pb-target was calculated. The average cross sections of photonuclear reactions on 204Pb and Sb isotopes as well neutrons inelastic reaction on 204Pb and capture on 121Sb were determined. Theoretical cross sections using the TALYS code have been simulated for all isotopes. An agreement between the experimental and simulated results appears while useful conclusions are presented regarding the nuclear parameters used in the simulations after comparison to experimental data.

An accelerator driven system has been studied by irradiation with 20 MeV electrons. Slow, intermediate and fast neutrons were measured by activation and Solid State Track Detectors. The total neutrons emitted from the target were 0.005 per electron, equally divided to slow and intermediate-fast energy regions. An agreement was presented between experimental results and simulations using the GEANT 4 code. The transmutation efficiency of 238U has been estimated as1.04 (± 0.09) × 10−7 per U-gram. Furthermore, the neutron total cross section of natPb was estimated 9.4 ± 1.8 b for fast neutrons and 6.0 ± 0.7 b for slow-intermediate neutrons.

Proper regulation of energy metabolism requires neurons in the central nervous system to respond dynamically to signals that reflect the body’s energy reserve, and one such signal is leptin. Agouti-related protein (AgRP) is a hypothalamic neuropeptide that is markedly upregulated in leptin deficiency, a condition that is associated with severe obesity, diabetes, and hepatic steatosis. Because deleting AgRP in mice does not alter energy balance, we sought to determine whether AgRP plays an indispensable role in regulating energy and hepatic lipid metabolism in the sensitized background of leptin deficiency. We generated male mice that are deficient for both leptin and AgRP [double-knockout (DKO)]. DKO mice and ob/ob littermates had similar body weights, food intake, energy expenditure, and plasma insulin levels, although DKO mice surprisingly developed heightened hyperglycemia with advancing age. Overall hepatic lipid content was reduced in young prediabetic DKO mice, but not in the older diabetic counterparts. Intriguingly, however, both young and older DKO mice had an altered zonal distribution of hepatic lipids with reduced periportal lipid deposition. Moreover, leptin stimulated, whereas AgRP inhibited, hepatic sympathetic activity. Ablating sympathetic nerves to the liver, which primarily innervate the portal regions, produced periportal lipid accumulation in wild-type mice. Collectively, our results highlight AgRP as a regulator of hepatic sympathetic activity and metabolic zonation.

Neutron activation technique has been applied using a proposed set of twelve thick metal foils (Au, As, Cd, In, Ir, Er, Mn, Ni, Se, Sm, W, Zn) for off-site measurements to obtain the neutron spectrum over a wide energy range (from thermal up to a few MeV) in intense neutron-gamma mixed fields such as around medical Linacs. The unfolding procedure takes into account the activation rates measured using thirteen ( n , γ ) and two ( n , p ) reactions without imposing a guess solution-spectrum. The MINUIT minimization routine unfolds a neutron spectrum that is dominated by fast neutrons (70%) peaking at 0.3 MeV, while the thermal peak corresponds to the 15% of the total neutron fluence equal to the epithermal-resonances area. The comparison of the unfolded neutron spectrum against the simulated one with the GEANT4 Monte-Carlo code shows a reasonable agreement within the measurement uncertainties. Therefore, the proposed set of activation thick-foils could be a useful tool in order to determine low flux neutrons spectrum in intense mixed field.

In general, the Pinder reaction concerns the reaction between an enolisable anhydride and an aldehyde proceeding initially through a Knoevenagel reaction followed by the ring closing process generating lactones with at least two chiral centers. These scaffolds are frequently present in natural products and synthetic bioactive molecules, hence it has attracted intense interest in organic synthesis and medicinal chemistry, particularly with respect to controlling the diastereo- and enantioselectivity. To the best of our knowledge, there has been only one attempt prior to this work towards the development of a catalytic enantioselective Pinder reaction. In our approach, we designed, synthesized, and tested dual chiral organocatalysts by combining BIMAH amines, (2-(α-(alkyl)methanamine)-1H-benzimidazoles, and a Lewis acid motif, such as squaramides, ureas and thioureas. The optimum catalyst was the derivative of isopropyl BIMAH bearing a bis(3,5-trifluoromethyl) thiourea, which afforded the Pinder products from various aromatic aldehydes with diastereomeric ratio >98:2 and enatioselectivity up to 92 ee%. Interestingly, the enantioselectivity of this catalyzed process is increased at higher concentrations and exhibits an isoinversion effect, namely an inverted "U" shaped dependency with respect to the temperature. Mechanistically, these features, point to a transition state involving an entropy-favored heterodimer interaction between a catalyst/anhydride and a catalyst/aldehyde complex when all other processes leading to this are much faster in comparison above the isoinversion temperature.

This work focuses on the influences of surfactants on the activity coefficients, γ, of methanol in binary mixtures with water, as well as on the mass transfer coefficients, kc, for the evaporation of methanol, which is a ubiquitous component in the troposphere, from mixtures of methanol with water at various surfactant's and methanol's concentrations. The technique used is the Reversed-Flow Gas Chromatography (R.F.G.C.), a version of Inverse Gas Chromatography, which allows determining both parameters by performing only one experiment for the kc parameter and two experiments for the γ parameter. The kc and γ values decrease in the presence of the three surfactants used (CTAB, SDS, TRITON X-100) at all methanol's and surfactant's concentrations. The decrease in the methanol's molar fraction, at constant number of surfactant films leads to a decrease in the kc and γ values, while the decrease in the surfactant's concentration, at constant methanol's molar fraction leads to an increase in both the kc and γ parameters. Mass transfer coefficients for the evaporation of methanol at the surfactant films, are also calculated which are approximately between 4 and 5 orders of magnitude larger than the corresponding mass transfer coefficients at the liquid films. Finally, thicknesses of the boundary layer of methanol in the mixtures of methanol with water were determined. The quantities found are compared with those given in the literature or calculated theoretically using various empirical equations. The precision of the R.F.G.C. method for measuring γ and kc parameters is approximately high (94.3-98.0%), showing that R.F.G.C. can be used with success not only for the thermodynamic study of solutions, but also for the interphase transport.

Despite that even normally functioning bicuspid aortic valves can have abnormal transvalvular-flow patterns, resulting in regional increases in wall shear stress and aortic dilatation, most often are preserved during ascending aorta replacement.

Background: The pathophysiology of COVID-19 is poorly understood but seems to be multifaceted Post-mortem examinations are a valuable tool to provide insights

Actinobacteria in the Tsukamurella genus are aerobic, high-GC, Gram-positive mycolata, considered as opportunistic pathogens and isolated from various environmental sources, including sites contaminated with oil, urban or industrial waste and pesticides. Although studies look into xenobiotic biotransformation by Tsukamurella isolates, the relevant enzymes remain uncharacterized. We investigated the arylamine N-acetyltransferase (NAT) enzyme family, known for its role in the xenobiotic metabolism of prokaryotes and eukaryotes. Xenobiotic sensitivity of Tsukamurella paurometabola type strain DSM 20162T was assessed, followed by cloning, recombinant expression and functional characterization of its single NAT homolog (TSUPD)NAT1. The bacterium appeared quite robust against chloroanilines, but more sensitive to 4-anisidine and 2-aminophenol. However, metabolic activity was not evident towards those compounds, presumably due to mechanisms protecting cells from xenobiotic entry. Of the pharmaceutical arylhydrazines tested, hydralazine was toxic, but the bacterium was less sensitive to isoniazid, a drug targeting mycolic acid biosynthesis in mycobacteria. Although (TSUPD)NAT1 protein has an atypical Cys-His-Glu (instead of the expected Cys-His-Asp) catalytic triad, it is enzymatically active, suggesting that this deviation is likely due to evolutionary adaptation potentially serving a different function. The protein was indeed found to use malonyl-CoA, instead of the archetypal acetyl-CoA, as its preferred donor substrate. Malonyl-CoA is important for microbial biosynthesis of fatty acids (including mycolic acids) and polyketide chains, and the corresponding enzymatic systems have common evolutionary histories, also linked to xenobiotic metabolism. This study adds to accummulating evidence suggesting broad phylogenetic and functional divergence of microbial NAT enzymes that goes beyond xenobiotic metabolism and merits investigation.