471 research outputs found

    A novel DSP zebrafish model reveals training- and drug-induced modulation of arrhythmogenic cardiomyopathy phenotypes

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    Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed “pale”, disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/β-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-β pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/β-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/β-catenin signalling cascade

    Riconnettere il tessuto di Atene Piranesi Prix de Rome et d’Athènes – 2022-23 Call internazionale di Progettazione per l’Acropoli di Atene e le adiacenze comprese nella buffer zone UNESCO

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    Reconnecting the Fabric of Athens Introduction, objectives, method Dimitris Pikionis, the architect who redesigned the paths of the Acropolis and the Philopappus, inspired us for a sentimental topography project. On its path, our urban graft introduces an ephemeral and light architecture, capable of transforming itself over time. Its pavements convey a strong message: use a collage of materials from different cultures and eras to create a timeless result. He works according to the concept of 'hiding and framing', showcasing monuments and connecting the visitor with nature and landscape. Following these principles, our routes evoke the original itineraries of the area. A paving, inspired by the work of Paul Klee, a master for Pikionis himself, makes way for citizens and visitors by dressing the colours that once adorned the monuments of ancient Greece. Intervention in the archaeological space of the Plateau is minimal. The restoration site here is intertwined with the sightseeing tour, instructing the visitor in the work in progress. Scope 1 We acted on several fronts using recurring components, 'objects' in natural materials, repeatable, adaptable, variably modular; these are pergolas, fences and pavings. Accessibility and multi-sensory enjoyment are objectives pursued here for both fenced archaeological sites and new and existing free access areas. We redefine the perimeters of some of the existing archaeological sites and extend the free ones by integrating them into the existing green system. We reopen the Panathenaic Way, now almost forgotten, rehabilitating its daily use, guiding the visitor towards the Acropolis starting from the Kerameikos and passing through the Agora. We cover the stretch connecting the Panathenaic Street with Monastiraki Square and the Kerameikos site. Between the Ancient Agora and the Pnice we envisage an intervention that extends the public spaces, particularly in the natural hollow that separates the hill of the Areopagos from the Pnice. At the esplanade on the Pnice hill, we envisage a pavement that promotes the organisation of outdoor events. At the main entrance to the site of the Acropolis we envisage two large pergolas under which new ticket booths manage the incoming flows, while a new entrance to the archaeological area of the Agora punctually widens the pedestrian street Apostolou Pavlou. In the area to the east of the Theatre of Dionysus, we propose to complement our general reconnection proposal with new pedestrian routes. Scope 2 Pursuing the general idea of 'reconnection' we redesign the main access to the Acropolis, improving the use of these spaces by adding new paving and shading elements. The entrance to the caves on the north side of the Acropolis is redesigned so that they are open and usable to the public. We revitalise the Peripatos by upgrading its paths, including by reopening the Via Panatenaica. In addition, we enhance elements such as the boundary stone of the fountain-house, the Koranic monument Thrasyllos and the adjacent Christian church. Scope 3 Regarding the plateau of the Acropolis, we want to improve the visitor experience by remaining almost 'invisible' as with the Pikionis project. We introduce vegetal elements, in particular on the Persian trench, which without occluding the views allow new shading. We rethink the organisation of the site areas, rationalising and optimising them, moving containers, screening them with vegetation and moving the most impactful ones to the old museum. The existing building thus becomes a place to support the construction site and the restoration workshop. Its roof becomes practicable, paved and with elements of potted greenery, without impairing existing views and panoramic cones, but rather creating new ones. Imagine, therefore, a continuous building site, able to fascinate and educate visitors to understand the place where the classical world originated, as well as the very idea of architecture

    Effect of Diet and Essential Oils on the Fatty Acid Composition, Oxidative Stability and Microbiological Profile of Marchigiana Burgers

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    The objective of this study is to evaluate the effects of including linseed (L) or linseed plus vitamin E (LE) in the diet of Marchigiana young bulls on the oxidative stability, color measurements, microbiological profile and fatty acid composition (FA) of burgers treated with and without a blend of essential oils (Rosmarinus officinalis and Origanum vulgare var. hirtum) (EOs). For this aim, the burgers were analysed for pH, thiobarbituric-acid-reactive substance (TBARS) content, Ferric Reducing/Antioxidant Power Assay (FRAP), vitamin E and colour measurements (L, a*, b) at 3, 6, 9, 12 days of storage: the TBARs were the highest in group L compared to C and LE after 12 days of storage (0.98, 0.73, and 0.63 mg MDA/kg, respectively). The TBARS content was also influenced by the use of EO compared to burgers not treated with EO (p < 0.05). The vitamin E content was influenced by the diet (p < 0.01), but not by the EO. The meat of the L group showed the lowest value of redness (a*) compared to C and LE (p < 0.01), while the use of EO did not affect colour parameters. The microbiological profile of the burgers showed a lower Pseudomonas count for L and LE at T0 (2.82 ± 0.30 and 2.30 ± 0.52 Log CFU/g, respectively) compared to C (3.90 ± 0.38 Log CFU/g), while the EO did not influence the microbiological profile. The FA composition was analysed at 0 and 12 days. The burgers from the LE group showed the highest value of polyunsaturated FA compared to the L and C groups (p < 0.05). Our findings suggest that the inclusion of vitamin E in a concentrate rich in polyunsaturated fatty acids is useful to limit intramuscular fat oxidation and to preserve the colour stability of burgers from young Marchigiana bulls enriched with healthy fatty acids. Moreover, linseed and vitamin E had a positive effect on microbial loads and growth dynamics, containing microbial development through time

    The prognostic impact of quitting smoking at or around diagnosis on the survival of patients with gastrointestinal cancers. A systematic literature review

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    Cigarette smoking is a strong risk factor for the occurrence of gastrointestinal cancers, and a substantial proportion of newly diagnosed patients is made up of active smokers, yet the impact of smoking cessation at or around diagnosis on the clinical course of these cancers (whose prognosis is often unfavourable) has never been summarized to date. We reviewed studies published until 30 April 2022 that investigated whether smoking cessation at or around diagnosis favourably affects the clinical course of gastrointestinal cancers patients. Six studies were included for colorectal cancer patients, which provided limited yet suggestive evidence that quitters may have longer disease-specific survival compared to continued smokers. Only one study each focused on patients with gastric or HBV-positive liver cancer (both reporting a survival advantage for quitters vs. continued smokers), while we found no eligible studies for patients with cancer at other sites within the digestive system. More research is urgently needed to expand the evidence on the topic, given the potentially major clinical implications for these patients. Moreover, health professionals should provide the necessary smoking cessation support to any smoker who is undergoing diagnostic work-up or treatment for gastrointestinal cancer

    Biological conversion of agricultural residues into microbial proteins for aquaculture using PHA-producing mixed microbial cultures

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    The current trend of increasing human population means that alternative protein sources need to be sought to avoid malnutrition. Fish is the most efficient protein-rich food, but aquaculture relies on fishmeal, whose production is environmentally unsustainable. In this study we evaluated the nutritional value of bacterial biomass produced by the biological conversion of zootechnical residues, for its use as feed in aquaculture. A bioreactor was fed with the fluid produced by the fermentation of zootechnical residues. Polyhydroxyalkanoates-producing microbial cultures were used to produce a biomass rich in proteins (61.8% of dry biomass) and amino acids, with glutamic (12.2% of total protein) and aspartic acid (8.7%) and the essential amino acids lysine (6.6%) and leucine (5.3%) being the most abundant. Feeding trials performed on Zebrafish revealed that the microbial proteins produced are a suitable alternative to the commercially available feed, with fish showing survival rates (74%) comparable to the control feed (82%), and even better results when enriched with oils and polyhydroxyalkanoates (96%). The results showed that it is possible to valorise agricultural residues into fish feed via biological conversion by polyhydroxyalkanoates-producing bacteria, while eliminating waste and producing biogas at the same time

    New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study

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    Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A twosided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in postmenopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools

    Multidisciplinary Approaches to Study Ancient Cities in a Seismic Region

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    The paper focuses on the strong connections between natural resources, environment, and urban development in the Hellenistic, Roman, and Byzantine city of Hierapolis of Phrygia (Pamukkale, Turkey). The ancient city was founded on a travertine terrace crossed by an active fault, responsible for impressive geothermal phenomena, i.e.,flowing of thermal water, emission of gases, and frequent earthquakes, while the surrounding territory offered various stone qualities (travertine, alabaster, marbles, etc.). These environmental features affected the cultural identity of Hierapolis and its urban layout, conditioning also the construction techniques and the monumentalization of the city. In recent year, a multidisciplinary research has been performed, which saw the factual integration of archaeological, geo-archaeological, and archaeometric perspectives, in order to reconstruct how the natural resources and environmental phenomena impacted on the urban history of Hierapolis and the conservation of its monuments. The main methods for the reconstruction of the ancient landscape, the tectonic context, and the cityscape are discussed

    Considerations for the Bioengineering of Advanced Cardiac In Vitro Models of Myocardial Infarction.

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    Despite the latest advances in cardiovascular biology and medicine, myocardial infarction (MI) remains one of the major causes of deaths worldwide. While reperfusion of the myocardium is critical to limit the ischemic damage typical of a MI event, it causes detrimental morphological and functional changes known as "reperfusion injury." This complex scenario is poorly represented in currently available models of ischemia/reperfusion injury, leading to a poor translation of findings from the bench to the bedside. However, more recent bioengineered in vitro models of the human heart represent more clinically relevant tools to prevent and treat MI in patients. These include 3D cultures of cardiac cells, the use of patient-derived stem cells, and 3D bioprinting technology. This review aims at highlighting the major features typical of a heart attack while comparing current in vitro, ex vivo, and in vivo models. This information has the potential to further guide in developing novel advanced in vitro cardiac models of ischemia/reperfusion injury. It may pave the way for the generation of advanced pathophysiological cardiac models with the potential to develop personalized therapies

    An Epigenetic Alphabet of Crop Adaptation to Climate Change

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    Crop adaptation to climate change is in a part attributed to epigenetic mechanisms which are related to response to abiotic and biotic stresses. Although recent studies increased our knowledge on the nature of these mechanisms, epigenetics remains under-investigated and still poorly understood in many, especially non-model, plants, Epigenetic modifications are traditionally divided into two main groups, DNA methylation and histone modifications that lead to chromatin remodeling and the regulation of genome functioning. In this review, we outline the most recent and interesting findings on crop epigenetic responses to the environmental cues that are most relevant to climate change. In addition, we discuss a speculative point of view, in which we try to decipher the "epigenetic alphabet" that underlies crop adaptation mechanisms to climate change. The understanding of these mechanisms will pave the way to new strategies to design and implement the next generation of cultivars with a broad range of tolerance/resistance to stresses as well as balanced agronomic traits, with a limited loss of (epi)genetic variability
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