How did DNA become hackable and biology personal? Tracing the self-fashioning of the DIYbio network

The DIYbio (Do-It-Yourself biology) group was established with the aim of turning biology and biotechnology into a creative practice accessible to everyone. The group is composed of graduate and post-graduate students and drop-out graduate students, but also disenfranchised researchers and professionals who see in the initiative the possibility of reviving their passion for science. Inspired by the analogy of the personal computer as a 'spokes-technology' for a free, egalitarian and decentralized society, that of the free and open-source software movement, and inspired by the image of the Victorian amateur and his home laboratory, DIYbio members organize regionally in what they call 'community laboratories,' or they practice in the comfort of their homes. Based on a series of interviews with DIYbio members, participants' observations of DIYbio's transient practices and a literary analysis of DIYbio members' use of social media, this thesis traces what I provisionally call 'the making of a personal biology.' Starting from the narrative formation the network, it then moves from the foundation of the DIYbio network in 2008 to the establishment of the first 'community laboratories', tracing the contingent orchestration of a diverse set of people, sites, tools and events, into a four-year community building effort. Due to its recent emergence in the field of Science and Technology Studies, only a limited number of research initiatives engage with the DIYbio network. Such works, mainly in the form of dissertations chapters and short articles, are analytically rich but limited in their observations, and often focus only on specific aspects of the network (Aguiton, 2010; Roosth, 2010; Delfanti, 2011; Meyer, 2012). This thesis recognizes the emergence of the DIYbio network as a cultural phenomenon in itself, and addresses the gap in the literature by tracing how DNA became hackable and biology became personal. Following Donna Haraway's effort to critically address the politics of technoscience as a practice of 'turning tropes into worlds' (1997: 59), the overarching topic of this research is how the trope of the biohacker became a world, and what type of world it became. The aim of this research is, therefore, to explore how members of the DIYbio network and biohackers define themselves, construct their identities and organize their work. This research also aims to situate the discourses and practices of DIYbio members in a context where governments and industries are intensifying their effort to make the coming century of biology into a reality

Recent advances in cardio-oncology:a report from the 'Heart Failure Association 2019 and World Congress on Acute Heart Failure 2019'

While anti-cancer therapies, including chemotherapy, immunotherapy, radiotherapy, and targeted therapy, are constantly advancing, cardiovascular toxicity has become a major challenge for cardiologists and oncologists. This has led to an increasing demand of cardio-oncology units in Europe and a growing interest of clinicians and researchers. The Heart Failure 2019 meeting of the Heart Failure Association of the European Society of Cardiology in Athens has therefore created a scientific programme that included four dedicated sessions on the topic along with several additional lectures. The major points that were discussed at the congress included the implementation and delivery of a cardio-oncology service, the collaboration among cardio-oncology experts, and the risk stratification, prevention, and early recognition of cardiotoxicity. Furthermore, sessions addressed the numerous different anti-cancer therapies associated with cardiotoxic effects and provided guidance on how to treat cancer patients who develop cardiovascular disease before, during, and after treatment

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Criticità e prospettive nella distribuzione e circolazione internazionale del cinema italiano. "Perfetti sconosciuti" e "The Place": un confronto

Il seguente lavoro ha come obiettivo analizzare le problematiche e le prospettive che caratterizzano la distribuzione e la circolazione internazionale del cinema italiano contemporaneo. Attraverso l'analisi del ruolo all'interno della filiera della distribuzione cinematografica e di come si sono evoluti i modelli di business dell'industria cinematografica americana, si effettuerà un confronto con l'industria italiana per andare ad evidenziare come l'intervento statale e la nascita del sistema distributivo delle finestre secondarie abbiano influenzato il suo sviluppo. Si andrà, poi ad esplorare la circolazione internazionale del cinema italiano dalle origini ad oggi per mettere in luce come una mancata organizzazione industriale dovuta al finanziamento pubblico, affiancata da una ricerca di cinema di qualità come unico strumento con cui contrastare il cinema commerciale americano, abbiano da un lato favorito la circolazione internazionale di un unico genere di cinema, quello d'autore che circola nei festival internazionali, dall'altro impedito al cinema più commerciale di venire esportato. Verranno anche analizzati gli unici percorsi distributivi che permettono attualmente al cinema italiano di circolare oltre i confini nazionali: oltre ai festival ci sono le co-produzioni internazionali, le piattaforme streaming e i film-format. Infine, attraverso l'analisi comparativa tra i percorsi produttivi e distributivi di Perfetti sconosciuti e The Place di Paolo Genovese, utilizzando le notizie sulle riprese, i paratesti promozionali, i dati del box office e delle admission italiani ed esteri, la loro circolazione nei canali distributivi ancillari e la loro ricezione critica, si cercheranno di evidenziare le criticità che la nostra industria presenta nella fase distributiva dei film commerciali e di individuare le eventuali prospettive che potrebbero permettere al cinema italiano di diventare effettivamente competitivo sia nel mercato domestico sia in quello internazionale

Is an FBI Agent a DIY Biologist Like Any Other? A Cultural Analysis of a Biosecurity Risk

International audienc

Quelles pratiques critiques sur le terrain des promesses scientifiques?

International audienc

Janus, or the inevitable battle between too much and too little oxygen

: Oxygen levels are key regulators of virtually every living mammalian cell, both under physiological and pathological conditions. Starting from embryonic and fetal development, through growth, onset and progression of diseases, oxygen is a subtle, although pivotal, mediator of key processes such as differentiation, proliferation, autophagy, necrosis and apoptosis. Hypoxia-driven modifications of cellular physiology are deeply investigated for the clinical and translational relevance, especially in the ischemic scenario. The mild or severe lack of oxygen is undoubtedly related to cell death although abundant evidence points at oscillating oxygen levels, instead of permanent low pO2, as the most detrimental factor. Different cell types can consume oxygen at different rates and, most interestingly, some cells can shift from low to high consumption according to the metabolic demand. Hence, we can assume that, in the intracellular compartment, oxygen tension varies from low to high levels depending on both supply and consumption. The positive balance between supply and consumption leads to a pro-oxidative environment, with some cell types facing hypoxia/hyperoxia cycles, while some others are under fairly constant oxygen tension. Within this frame, the alterations of oxygen levels (dysoxia) are critical in two paradigmatic organs, heart the brain, under physiological and pathological conditions and the interactions of oxygen with other physiologically relevant gases, such as nitric oxide, can alternatively contribute to the worsening or protection of ischemic organs. Furthermore, the effects of dysoxia is of pivotal importance for iron metabolism

A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases

: Cyclic adenosine 3',5'-monophosphate (cAMP)-elevating agents, such as β2-adrenergic receptor (β2-AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions characterized by airway constriction, inflammation, and mucus hypersecretion. However, their clinical use is limited by unwanted side effects because of unrestricted cAMP elevation in the airways and in distant organs. Here, we identified the A-kinase anchoring protein phosphoinositide 3-kinase γ (PI3Kγ) as a critical regulator of a discrete cAMP signaling microdomain activated by β2-ARs in airway structural and inflammatory cells. Displacement of the PI3Kγ-anchored pool of protein kinase A (PKA) by an inhaled, cell-permeable, PI3Kγ mimetic peptide (PI3Kγ MP) inhibited a pool of subcortical PDE4B and PDE4D and safely increased cAMP in the lungs, leading to airway smooth muscle relaxation and reduced neutrophil infiltration in a murine model of asthma. In human bronchial epithelial cells, PI3Kγ MP induced unexpected cAMP and PKA elevations restricted to the vicinity of the cystic fibrosis transmembrane conductance regulator (CFTR), the ion channel controlling mucus hydration that is mutated in cystic fibrosis (CF). PI3Kγ MP promoted the phosphorylation of wild-type CFTR on serine-737, triggering channel gating, and rescued the function of F508del-CFTR, the most prevalent CF mutant, by enhancing the effects of existing CFTR modulators. These results unveil PI3Kγ as the regulator of a β2-AR/cAMP microdomain central to smooth muscle contraction, immune cell activation, and epithelial fluid secretion in the airways, suggesting the use of a PI3Kγ MP for compartment-restricted, therapeutic cAMP elevation in chronic obstructive respiratory diseases