Adipocytes and micrornas crosstalk: A key tile in the mosaic of breast cancer microenvironment

Breast cancer (BC) is a disease characterized by a high grade of heterogeneity. Consequently, despite the great achievements obtained in the last decades, most of the current therapeutic regimens still fail. The identification of new molecular mechanisms that will increase the knowledge of all steps of tumor initiation and growth is mandatory in finding new clinical strategies. The BC microenvironment, consisting of endothelial cells, fibroblasts, immune cells and adipocytes, plays an essential role in regulating BC development, and recently it has gained great attention in the scientific community. In particular, adipose tissue is emerging as an important target to investigate among mammary gland components. The mechanisms underlying BC progression driven by adipocytes are predominantly unexplored, especially that involving the switch from normal adipocytes to the so-called cancer-associated adipocytes (CAAs). MicroRNAs (miRNAs), a class of gene expression modulators, have emerged as the regulators of key oncogenes and tumor suppressor genes that affect multiple pathways of the tumor microenvironment and adipose tissue. This review concerns a presentation of the role of adipocytes in breast tissue, and describes the most recent discoveries about the interplay between adipocytes and miRNAs, which collaborate in the arrangement of a pro-inflammatory and cancerous microenvironment, laying the foundations for new concepts in the prevention and treatment of BC

Exploring Tension in Hybrid Organizations in Times of Covid-19 Crisis. The Italian Benefit Corporations’ experience

The COVID-19 pandemic has caused an unprecedented social and economic crisis, not least for hybrid organisations, as they must manage the tension arising from their dual mission to create social and economic value. Building on a theoretical framework for hybrid tension, our work contextualises how tensions emerge and are managed in hybrid organisations when they are exposed to exogenous shocks. We address the following research question. How have hybrid organisations managed the tensions arising from their dual purpose during the COVID-19 crisis? Our focus is on Italian benefit corporations, which are organisations combining social and economic objectives. We conduct two focus groups with 12 Italian benefit corporations. Our findings show the emergence of four constructs that capture the responses to the COVID-19 crisis: social and/or commercial orientation; technological characterisation; internal and external stakeholder relationship; openness to changes. We explain the relationship of these constructs via a framework of performing, organising, learning, and belonging tensions

Mission, governance, and accountability of benefit corporations: Toward a commitment device for achieving commercial and social goals

Benefit corporations (BCs) are profit-with-purpose organizations regulated by a legal framework for establishing explicit commitments in terms of multi-stakeholder governance and accountability structures. We comprehensively analyze the theoretical alignment of four concepts (ownership, mission, governance, and accountability) to explain the legal rationale for BCs' unique corporate form. However, the boundaries of BC legislation are blurry, leaving them open to top-down governance arrangements and weak accountability. To explore this ambiguity, this paper investigates whether BCs implement a de facto (i.e., beyond the letter of the law) multi-stakeholder structure with governance models and downward accountability mechanisms that balance different stakeholders' interests, instead of focusing only on shareholder profits. This further highlight the soft boundaries imposed by the BC regulatory framework and suggests that more work is needed to explore the relationship between governance models that differently balance stakeholders' claims and the firm's social performance

Reversibility of airflow obstruction by hypoglossus nerve stimulation in anesthetized rabbits

Rationale: Anesthesia-induced uncoupling of upper airway dilating and inspiratory pump muscles activation may cause inspiratory flow limitation, thereby mimicking obstructive sleep apnea/hypopnea. Objectives: Determine whether inspiratory flow limitation occurs in spontaneously breathing anesthetized rabbits and whether this can be reversed by direct hypoglossal nerve stimulation and by the application of continuous positive airway pressure. Methods: Ten New Zealand White rabbits were anesthetized, instrumented, and studied supine while breathing spontaneously at ambient pressure or during the application of positive or negative airway pressure. Under each of these conditions, the effect of unilateral or bilateral hypoglossal nerve stimulation was investigated. Measurements: Inspiratory flow and tidal volume were measured together with esophageal pressure and the electromyographic activity of diaphragm, alae nasi, and genioglossus muscles. Main results: Anesthesia caused a marked increase in inspiratory resistance, snoring, and in eight rabbits, inspiratory flow limitation. Hypoglossus nerve stimulation was as effective as continuous positive airway pressure in reversing inspiratory flow limitation and snoring. Its effectiveness increased progressively as airway opening pressure was lowered, reached a maximum at -5 cm H2O, but declined markedly at lower pressures. With negative airway opening pressure, airway collapse eventually occurred during inspiration that could be prevented by hypoglossus nerve stimulation. The recruitment characteristics of hypoglossus nerve fibers was steep, and significant upper airway dilating effects already obtained with stimulus intensities 36 to 60% of maximum. Conclusion: This study supports hypoglossus nerve stimulation as a treatment option for obstructive sleep apnea

NUMERICAL EVALUATION OF THE CORROSION EFFECTS IN PRESTRESSED CONCRETE BEAMS WITHOUT SHEAR REINFORCEMENT

Corrosion of prestressed concrete structures causes size reduction of strands, degradation of mechanical properties of steel, cracking of the surrounding concrete and bond decay at steel-to-concrete interface. In this paper, a numerical approach able to take into account all the effects involved in the corrosion process by using non-linear finite element analysis (NLFEA) and membrane or shell elements modelling, is proposed. Two different strategies are adopted to model strands: the smeared and the discrete approaches. The results obtained using these latter strategies are validated by comparing NLFEA results with experimental measurements of a naturally corroded prestressed beam tested at the “Instituto de Ciencias de la Construcción Eduardo Torroja” in Madrid. Finally, pros and cons of the proposed modelling approach are critically analysed, demonstrating that considering the actual spatial corrosion distribution is necessary to predict the position where failure occurs

DNA vaccines against ErbB2+ Carcinomas: From mice to humans.

DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2+ carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities

Advances in the knowledge of the inocybe mixtilis group (Inocybaceae, Agaricomycetes), through molecular and morphological studies

Inocybe mixtilis constitutes a complex of species characterized by nodulose-angulose spores, absence of cortina and a more or less bulbous marginate stipe that is not darkening when desiccated. In order to elucidate species limits within the I. mixtilis complex, an ITS-RPB2 phylogeny was performed and interpreted using morphological and ecological characters. Six supported clades were obtained in our analyses that correspond to I. mixtilis, I. subtrivialis, and four new species to science: I. ceskae, I. johannis-stanglii, I. nothomixtilis and I. occulta. Species within this complex can be morphologically recognized through a unique combination of morphological characters, such as the spore shape, cystidial length and shape, presence and development of the velipellis and pileus colour and viscidity. Nevertheless, those characters overlap, especially among I. mixtilis, I. ceskae and I. occulta, and intermediate collections are therefore more reliably identified through ITS-sequencing. Two species, I. ceskae and I. occulta are present in both North America and Europe, while the rest are so far only known in Europe, or Europe and Asia (I. mixtilis). All species, except I. johannis-stanglii, seem to be able to establish ectomycorrhizal association both with conifers and angiosperms. Descriptions, colour illustrations and a key to all known species in the I. mixtilis group are provided