Spatially resolved transcriptomics reveals innervation-responsive functional clusters in skeletal muscle

Striated muscle is a highly organized structure composed of well-defined anatomical domains with integrated but distinct assignments. So far, the lack of a direct correlation between tissue architecture and gene expression has limited our understanding of how each unit responds to physio-pathologic contexts. Here, we show how the combined use of spatially resolved transcriptomics and immunofluorescence can bridge this gap by enabling the unbiased identification of such domains and the characterization of their response to external perturbations. Using a spatiotemporal analysis, we follow changes in the transcriptome of specific domains in muscle in a model of denervation. Furthermore, our approach enables us to identify the spatial distribution and nerve dependence of atrophic signaling pathway and polyamine metabolism to glycolytic fibers. Indeed, we demonstrate that perturbations of polyamine pathway can affect muscle function. Our dataset serves as a resource for future studies of the mechanisms underlying skeletal muscle homeostasis and innervation

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring

Continuing the construction of the city

In recent years, above and beyond both specific and varying professional opportunities, the dimensions of urban design are, more than anything, what has polarized our common research. By urban design we do not necessarily mean large-scale. Our core interest is the urban nature of design. Whether the work major or minor, our interest is the ability of the new job to relate to and interface with its real and physical surroundings, its ability to be a link in a chain of events in which it is basically the continuation

LICEO FARNESINA. Nuovi spazi didattici.

Il contributo riguarda la presentazione/illustrazione del Progetto di RDM Studio (PV. Dell'Aira, P. Misino, M. Ruggieri, P. Troiano) al Concorso Internazionale "Liceo Farnesina". L’obiettivo principale contenuto nel Bando Concorsuale, riguardava la fattibilità in 2 fasi, dovuta a specifiche necessità finanziarie. Il progetto trae la sua organizzazione morfologica da tale requisito, conformando il plesso scolastico come edificio "bino", attraverso due volumetrie tra loro interconnesse, strutturalmente indipendenti e realizzabili in successione consentendo un'eventuale cantierizzazione "in esercizio"

Riqualificazione del Lungomare di Fregene

Il progetto di Riqualificazione del Lungomare di Fregene, vincitore dell'omonimo Concorso Internazionale, bandito nel 2006, dal Comune di Fiumicino (RM), si sviluppa sia sul piano stradale che su una piastra attrezzata rialzata, ove trovano alloggio destinazioni commerciali e infrastrutture di servizio. Un articolato progetto di suolo, unito all'installazione di molteplici utilities, restituisce qualità urbana e architettonica a un waterfront, che da tempo versa in un avanzato stato di degrado. Il saggio di presentazione ne illustra gli sviluppi attraverso testi, schizzi, disegni tecnici, schede e diagrammi funzionali. Un capitolo importante di questo intervento è rappresentato dal tema della mobilità. Nel progetto, infatti, si giustappongono, organizzandosi in virtuose complementarietà, i percorsi pedonali, i carrabili e i ciclabili dell’intera fascia lungomare. Nello specifico l’area viene dotata di una pista ciclabile, di una circolazione veicolare ad anello (con senso unico di marcia e dissuasori di velocità), di parcheggi in linea su tutto il tratto lungomare e di una strada pedo-carrabile dedicata esclusivamente all’accesso veicolare di emergenza e allo spazio di manovra per i gli ospiti degli stabilimenti balneari. Particolare attenzione è stata posta alla regolamentazione e messa in sicurezza degli accessi carrabili e pedonali agli arenili, che vengono conservati e salvaguardati. L'estensivo miglioramento e la dotazione infrastrutturale prevista dal progetto garantiscono l’attivazione di un servizio di trasporto pubblico urbano, oggi non possibile a causa delle condizioni di degrado in cui versa sia l’arteria stradale principale longitudinale che quelle di collegamento trasversale

Preliminary selection of non-target Lepidoptera species for ecological risk assessment of Bt canola in Sicily

It is essential to assess the environmental risk that Bt canola resistant to Lepidopteran pests may hold and to study its effect on species assemblages that fulfil a variety of ecosystem functions. Environmental risk assessment can be improved through the use of an ecological model which can be applied to a specific environment, so that local species can be classified functionally and prioritized to identify potential test species. Several other Lepidoptera species are also directly exposed to Bt toxin. In this paper an ecological approach was followed for selection of non-target Lepidoptera species for ecological risk assessment of Bt canola in Sicily, using data collected over a one-year period on Lepidoptera biodiversity on different habitats. Non-target Lepidoptera most likely to be affected were identified and prioritized for future testing and inclusion in risk assessments. Through use of the selection matrix, knowledge gaps were identified for future research and guidance for the design of ecologically realistic experiments

Phenotypic and molecular diversity in a collection of ‘Pomodoro di Sorrento’ Italian tomato landrace

The ‘Pomodoro di Sorrento’, originating from Southern Italy, represents one of the most important andremunerative Italian tomato landraces for “fresh market”. Despite its outstanding organoleptic and nutri-tional qualities scanty information still exists on the structural variation of this traditional tomato. Herewe report the evaluation of ten accessions of the ‘Pomodoro di Sorrento’ tomato at phenotypic and molec-ular levels in order to provide a basis to unequivocally distinguish them from those belonging to the othermost famous similar landraces grown in Italy. Morphological characterization based on 13 descriptorshighlighted the presence of a significant level of variation for puffiness, green color and green shoulderof unripe fruits, allowing distinguishing two ‘Sorrento’ morphotypes. Genome-wide SNP genotyping wascarried out using the ILLUMINA Infinium tomato array and revealed a genetically well defined structureof the ‘Sorrento’ landrace with respect to the other multilocular landraces most widespread in Italy. Inparticular, 1450 SNPs resulted polymorphic among 20 tested genotypes, and one clearly distinguishes the‘Sorrento’ from other similar landraces. Finally, resistance assay to Verticillium wilt allowed the identifi-cation of promising ‘Sorrento’ accessions. Interestingly two markers localized into the Ve2 gene showeda strong association with the resistance/susceptibility trait. Taken as whole, our results provide a descrip-tion of ‘Pomodoro di Sorrento’ landrace diversity, which provide useful information for its utilization inbreeding programs as well as for its direct use in quality markets

Mechanical behavior of infrapatellar fat pad of patients affected by osteoarthritis

The infrapatellar fat pad (IFP) is an adipose tissue present in the knee that lies between the patella, femur, meniscus and tibia, filling the space between these structures. IFP facilitates the distribution of the synovial fluid and may act to absorb impulsive actions generated through the joint. IFP in osteoarthritis (OA) pathology undergoes structural changes characterized by inflammation, hypertrophy and fibrosis. The aim of the present study is to analyze the mechanical behavior of the IFP in patients affected by end-stage OA. A specific test fixture was designed and indentation tests were performed on IFP specimens harvested from OA patients who underwent total knee arthroplasty. Experiments allowed to assess the typical features of mechanical response, such as non-linear stress–strain behavior and time-dependent effects. Results from mechanical experimentations were implemented within the framework of a visco-hyperelastic constitutive theory, with the aim to provide data for computational modelling of OA IFP role in knee mechanics. Initial and final indentation stiffness were calculated for all subjects and statistical results reveled that OA IFP mechanics was not significantly influenced by gender, BMI and sample preparation. OA IFP mechanical behavior was also compared to that of other adipose tissues. OA IFP appeared to be a stiffer adipose tissue compared to subcutaneous, visceral adipose tissues and heel fat pads. It is reasonable that fibrosis induces a modification of the tissue destabilizing the normal distribution of forces in the joint during movement, causing a worsening of the disease

Doxorubicin-Induced TrkAIII Activation: A Selection Mechanism for Resistant Dormant Neuroblastoma Cells

Patients with advanced neuroblastoma (NB) receive multimodal clinical therapy, including the potent anthracycline chemotherapy drug doxorubicin (Dox). The acquisition of Dox resistance, however, is a major barrier to a sustained response and leads to a poor prognosis in advanced disease states, reinforcing the need to identify and inhibit Dox resistance mechanisms. In this context, we report on the identification and inhibition of a novel Dox resistance mechanism. This mechanism is characterized by the Dox-induced activation of the oncogenic TrkAIII alternative splice variant, resulting in increased Dox resistance, and is blocked by lestaurtinib, entrectinib, and crizotinib tyrosine kinase and LY294002 IP3-K inhibitors. Using time lapse live cell imaging, conventional and co-immunoprecipitation Western blots, RT-PCR, and inhibitor studies, we report that the Dox-induced TrkAIII activation correlates with proliferation inhibition and is CDK1- and Ca2+-uniporter-independent. It is mediated by ryanodine receptors; involves Ca2+-dependent interactions between TrkAIII, calmodulin and Hsp90; requires oxygen and oxidation; occurs within assembled ERGICs; and does not occur with fully spliced TrkA. The inhibitory effects of lestaurtinib, entrectinib, crizotinib, and LY294002 on the Dox-induced TrkAIII and Akt phosphorylation and resistance confirm roles for TrkAIII and IP3-K consistent with Dox-induced, TrkAIII-mediated pro-survival IP3K/Akt signaling. This mechanism has the potential to select resistant dormant TrkAIII-expressing NB cells, supporting the use of Trk inhibitors during Dox therapy in TrkAIII-expressing NBs

Nutraceutical Preventative and Therapeutic Potential in Neuroblastoma: From Pregnancy to Early Childhood

Neuroblastoma (NB) is a highly malignant embryonic extracranial solid tumor that arises from sympathoadrenal neuroblasts of neural crest origin. In addition to genetic factors, NB has been linked to maternal exposure to a variety of substances during pregnancy. Recent interest in the potential of nutrients to prevent cancer and reduce malignancy has resulted in the identification of several nutraceuticals including resveratrol, curcumin, and molecular components of garlic, which together with certain vitamins may help to prevent NB development. As NBs arise during fetal development and progress during early childhood, specific NB inhibiting nutraceuticals and vitamins could enhance the preventative influence of maternal nutrition and breast feeding on the development and early progression of NB. In this article, we review NB inhibitory nutraceuticals and vitamins, their mechanisms of action and expound their potential as maternal nutritional supplements to reduce NB development and progression during fetal growth and early childhood, whilst at the same time enhancing maternal, fetal, and infant health