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Candida gut colonization and yeast biofilm production capacity were investigated, by means of XTT reduction assay, in Clostridioides difficile infected (CDI) patients, in non-CDI diarrheic patients, and in healthy donors in two different time periods (2013–2015 and 2018–2019 respectively). Candida gut colonization was significantly (p < 0.001) associated to C. difficile infection, and to patients infected with hypervirulent C. difficile strains bearing the tcdC deletion at nucleotide 117 (p = 0.0003). Although there was not a prevalent yeast species in CDI patients, C. albicans was the species significantly (p < 0.001) associated to both the infections sustained by the non-hypervirulent C. difficile strains and those caused by the hypervirulent strain (p = 0.001). The biofilm production by the yeasts isolated from the CDI patients and from non-CDI diarrheic patients did not differ significantly. However, a significantly (p = 0.007) higher biofilm production was observed in the Candida strains, particularly C. albicans, isolated from healthy donors compared to that of the yeasts cultured from CDI patients. Seasonal occurrence was observed in the isolation rate of CDI and non-CDI diarrheic cases (p = 0.0019), peaking in winter for CDI patients and in spring for non-CDI diarrheic patients. Furthermore, seasonality emerged in the gut colonization by Candida of CDI patients in the winter. It seems, therefore, that the reduced capacity of biofilm production by Candida strains isolated from CDI patients might have a role in the development of C. difficile infection, probably facilitating the spread of the bacteria into the gut thus amplifying their pathogenic action.
Grazia Brunetti; Alessandro Giuliani; Anna Sara Navazio; Camilla Paradisi; Flavia Raponi; Libenzio Adrian Conti; Giammarco Raponi. Candida gut colonization, yeast species distribution, and biofilm production in Clostridioides difficile infected patients: a comparison between three populations in two different time periods. Brazilian Journal of Microbiology 2021, 1 -8.
AMA StyleGrazia Brunetti, Alessandro Giuliani, Anna Sara Navazio, Camilla Paradisi, Flavia Raponi, Libenzio Adrian Conti, Giammarco Raponi. Candida gut colonization, yeast species distribution, and biofilm production in Clostridioides difficile infected patients: a comparison between three populations in two different time periods. Brazilian Journal of Microbiology. 2021; ():1-8.
Chicago/Turabian StyleGrazia Brunetti; Alessandro Giuliani; Anna Sara Navazio; Camilla Paradisi; Flavia Raponi; Libenzio Adrian Conti; Giammarco Raponi. 2021. "Candida gut colonization, yeast species distribution, and biofilm production in Clostridioides difficile infected patients: a comparison between three populations in two different time periods." Brazilian Journal of Microbiology , no. : 1-8.
The deregulation of PI3K/Akt signaling is among the most causes in inducing the acquisition of a metastatic phenotype in breast cancer cells, leading to Epithelial-Mesenchymal Transition (EMT). Inhibition of the PI3K/Akt pathway is known to be beneficial in the clinical setting. However, the activation of secondary pathways and toxicity profiles of available inhibitors, hindering optimal therapeutic results. Preliminary studies showed that myo-Inositol inhibits the PI3K/Akt pathway by exerting a pleiotropic anti-tumor action. Herein, we demonstrate that myo-Inositol triggers a prompt and profound remodeling of delineated expression pattern in triple-negative breast cancer cells (MDA-MB-231). Consequently, it inhibits metastasis and tumor progression through miR-125a-5p transcription and the subsequent inhibition of IP6K1. In contrast, hormone-responsive breast cancer cells (MCF-7) are insensitive to myo-Inositol. This is due to the persistence of MDM2 synthesis promoted by estrogen-dependent pathways. Conversely, the counteraction of estrogen effects recovered the sensitivity to myo-Inositol in the hormone-responsive model. Overall, these results identify a novel axis primed by miR-125a-5p to downregulate IP6K1 gene that inhibits metastasis. Thus, administration of myo-Inositol can activate this axis as a molecular target therapy in breast cancer.
Mirko Minini; Alice Senni; Xingkang He; Sara Proietti; Domenico Liguoro; Angela Catizone; Alessandro Giuliani; Rita Mancini; Andrea Fuso; Alessandra Cucina; Yihai Cao; Mariano Bizzarri. miR-125a-5p impairs the metastatic potential in breast cancer via IP6K1 targeting. Cancer Letters 2021, 520, 48 -56.
AMA StyleMirko Minini, Alice Senni, Xingkang He, Sara Proietti, Domenico Liguoro, Angela Catizone, Alessandro Giuliani, Rita Mancini, Andrea Fuso, Alessandra Cucina, Yihai Cao, Mariano Bizzarri. miR-125a-5p impairs the metastatic potential in breast cancer via IP6K1 targeting. Cancer Letters. 2021; 520 ():48-56.
Chicago/Turabian StyleMirko Minini; Alice Senni; Xingkang He; Sara Proietti; Domenico Liguoro; Angela Catizone; Alessandro Giuliani; Rita Mancini; Andrea Fuso; Alessandra Cucina; Yihai Cao; Mariano Bizzarri. 2021. "miR-125a-5p impairs the metastatic potential in breast cancer via IP6K1 targeting." Cancer Letters 520, no. : 48-56.
Open systems can only exist by self-organization as pulsing structures exchanging matter and energy with the outer world. This review is an attempt to reveal the organizational principles of the heterochromatin supra-intra-chromosomal network in terms of nonlinear thermodynamics. The accessibility of the linear information of the genetic code is regulated by constitutive heterochromatin (CHR) creating the positional information in a system of coordinates. These features include scale-free splitting-fusing of CHR with the boundary constraints of the nucleolus and nuclear envelope. The analysis of both the literature and our own data suggests a radial-concentric network as the main structural organization principle of CHR regulating transcriptional pulsing. The dynamic CHR network is likely created together with nucleolus-associated chromatin domains, while the alveoli of this network, including springy splicing speckles, are the pulsing transcription hubs. CHR contributes to this regulation due to the silencing position variegation effect, stickiness, and flexible rigidity determined by the positioning of nucleosomes. The whole system acts in concert with the elastic nuclear actomyosin network which also emerges by self-organization during the transcriptional pulsing process. We hypothesize that the the transcriptional pulsing, in turn, adjusts its frequency/amplitudes specified by topologically associating domains to the replication timing code that determines epigenetic differentiation memory.
Jekaterina Erenpreisa; Jekabs Krigerts; Kristine Salmina; Bogdan Gerashchenko; Talivaldis Freivalds; Reet Kurg; Ruth Winter; Matthias Krufczik; Pawel Zayakin; Michael Hausmann; Alessandro Giuliani. Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis). Cells 2021, 10, 1582 .
AMA StyleJekaterina Erenpreisa, Jekabs Krigerts, Kristine Salmina, Bogdan Gerashchenko, Talivaldis Freivalds, Reet Kurg, Ruth Winter, Matthias Krufczik, Pawel Zayakin, Michael Hausmann, Alessandro Giuliani. Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis). Cells. 2021; 10 (7):1582.
Chicago/Turabian StyleJekaterina Erenpreisa; Jekabs Krigerts; Kristine Salmina; Bogdan Gerashchenko; Talivaldis Freivalds; Reet Kurg; Ruth Winter; Matthias Krufczik; Pawel Zayakin; Michael Hausmann; Alessandro Giuliani. 2021. "Heterochromatin Networks: Topology, Dynamics, and Function (a Working Hypothesis)." Cells 10, no. 7: 1582.
The multi-level organization of nature is self-evident: proteins do interact among them to give rise to an organized metabolism, while in the same time each protein (a single node of such interaction network) is itself a network of interacting amino-acid residues allowing coordinated motion of the macromolecule and systemic effect as allosteric behavior. Similar pictures can be drawn for structure and function of cells, organs, tissues, and ecological systems. The majority of biologists are used to think that causally relevant events originate from the lower level (the molecular one) in the form of perturbations, that “climb up” the hierarchy reaching the ultimate layer of macroscopic behavior (e.g., causing a specific disease). Such causative model, stemming from the usual genotype-phenotype distinction, is not the only one. As a matter of fact, one can observe top-down, bottom-up, as well as middle-out perturbation/control trajectories. The recent complex network studies allow to go further the pure qualitative observation of the existence of both non-linear and non-bottom-up processes and to uncover the deep nature of multi-level organization. Here, taking as paradigm protein structural and interaction networks, we review some of the most relevant results dealing with between networks communication shedding light on the basic principles of complex system control and dynamics and offering a more realistic frame of causation in biology.
Vladimir N. Uversky; Alessandro Giuliani. Networks of Networks: An Essay on Multi-Level Biological Organization. Frontiers in Genetics 2021, 12, 1 .
AMA StyleVladimir N. Uversky, Alessandro Giuliani. Networks of Networks: An Essay on Multi-Level Biological Organization. Frontiers in Genetics. 2021; 12 ():1.
Chicago/Turabian StyleVladimir N. Uversky; Alessandro Giuliani. 2021. "Networks of Networks: An Essay on Multi-Level Biological Organization." Frontiers in Genetics 12, no. : 1.
Europe is experiencing a third wave of COVID-19 due to the spread of highly transmissible SARS-CoV-2 variants. A number of positive and negative factors constantly shape the rates of COVID-19 infections, hospitalization, and mortality. Among these factors, the rise in increasingly transmissible variants on one side and the effect of vaccinations on the other side create a picture deeply different from that of the first pandemic wave. Starting from the observation that in several European countries the number of COVID-19 infections in the second and third pandemic wave increased without a proportional rise in disease severity and mortality, we hypothesize the existence of an additional factor influencing SARS-CoV-2 dynamics. This factor consists of an immune defence against severe COVID-19, provided by SARS-CoV-2-specific T cells progressively developing upon natural exposure to low virus doses present in populated environments. As suggested by recent studies, low-dose viral particles entering the respiratory and intestinal tracts may be able to induce T cell memory in the absence of inflammation, potentially resulting in different degrees of immunization. In this scenario, non-pharmaceutical interventions would play a double role, one in the short term by reducing the detrimental spreading of SARS-CoV-2 particles, and one in the long term by allowing the development of a widespread (although heterogeneous and uncontrollable) form of immune protection.
Maria De Angelis; Federica Francescangeli; Rachele Rossi; Alessandro Giuliani; Ruggero De Maria; Ann Zeuner. Repeated Exposure to Subinfectious Doses of SARS-CoV-2 May Promote T Cell Immunity and Protection against Severe COVID-19. Viruses 2021, 13, 961 .
AMA StyleMaria De Angelis, Federica Francescangeli, Rachele Rossi, Alessandro Giuliani, Ruggero De Maria, Ann Zeuner. Repeated Exposure to Subinfectious Doses of SARS-CoV-2 May Promote T Cell Immunity and Protection against Severe COVID-19. Viruses. 2021; 13 (6):961.
Chicago/Turabian StyleMaria De Angelis; Federica Francescangeli; Rachele Rossi; Alessandro Giuliani; Ruggero De Maria; Ann Zeuner. 2021. "Repeated Exposure to Subinfectious Doses of SARS-CoV-2 May Promote T Cell Immunity and Protection against Severe COVID-19." Viruses 13, no. 6: 961.
Alessandro Giuliani. The statistical mechanics of life. Physics of Life Reviews 2021, 37, 100 -102.
AMA StyleAlessandro Giuliani. The statistical mechanics of life. Physics of Life Reviews. 2021; 37 ():100-102.
Chicago/Turabian StyleAlessandro Giuliani. 2021. "The statistical mechanics of life." Physics of Life Reviews 37, no. : 100-102.
Finding out how cells prepare for fate change during differentiation commitment was our task. To address if the constitutive pericentromere associated domains (PADs) may be involved, we used a model system with known transcriptome data, MCF-7 breast cancer cells treated with the ErbB3 ligand heregulin (HRG), which induces differentiation and is used in the therapy of cancer. PAD-repressive heterochromatin (H3K9me3), centromere (CENPA)-specific, and active euchromatin (H3K4me3) antibodies, qPCR, acridine-orange DNA structural test (AOT), and microscopic image analysis were applied. We found a two-step DNA unfolding, after 15-20 min and 60 min HRG treatment, respectively. This behaviour was consistent with biphasic activation of the early response genes (c-fos - fosL1/myc) and the timing of two transcriptome avalanches reported in the literature. In control, the average number of PADs negatively correlated with their size by scale-free distribution, centromere clustering in turn correlated with PAD size, both indicating that PADs may create and modulate a supra-chromosomal network by fusing and splitting a constant proportion of the constitutive heterochromatin. By 15 min HRG treatment, the bursting unravelling of PADs from the nucleolus boundary occurred, coinciding with the first step of H3K4me3 chromatin unfolding confirmed by AOT. The second step after 60 min HRG treatment was associated with transcription of long-non-coding-RNA from PADs and peaking of fosL1/c-myc response. We hypothesize that bursting of PAD clusters under a critical silencing threshold pushes first transcription avalanche, while destruction of the PAD network enables genome rewiring needed for differentiation re-patterning, mediated by early response bivalent genes.
Jekabs Krigerts; Kristine Salmina; Talivaldis Freivalds; Pawel Zayakin; Felikss Rumnieks; Inna Inashkina; Alessandro Giuliani; Michael Hausmann; Jekaterina Erenpreisa. Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains. Biophysical Journal 2021, 120, 711 -724.
AMA StyleJekabs Krigerts, Kristine Salmina, Talivaldis Freivalds, Pawel Zayakin, Felikss Rumnieks, Inna Inashkina, Alessandro Giuliani, Michael Hausmann, Jekaterina Erenpreisa. Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains. Biophysical Journal. 2021; 120 (4):711-724.
Chicago/Turabian StyleJekabs Krigerts; Kristine Salmina; Talivaldis Freivalds; Pawel Zayakin; Felikss Rumnieks; Inna Inashkina; Alessandro Giuliani; Michael Hausmann; Jekaterina Erenpreisa. 2021. "Differentiating cancer cells reveal early large-scale genome regulation by pericentric domains." Biophysical Journal 120, no. 4: 711-724.
To investigate through the prototype methodology as well as the interaction structures methodology which are the factors involved in the psychotherapeutic progress in the treatment of a patient with chronic diseases and somatic symptoms. 62 of the total 120 videotaped sessions were analysed by independent judges using the Psychotherapy Process Q-Set. The interaction structures as well as the extent to which each session conformed to the ideal psychodynamic, cognitive behavioural therapy (CBT) and reflective function prototypes were evaluated through multiple regression analysis, in order to test which factors were able to predict therapeutic progress. The psychotherapeutic process was characterized by moderate adherence to both psychodynamic and CBT prototypes and by greater adherence to the reflective function prototype. The therapeutic progress was better predicted by the adherence to the psychodynamic prototype. Both the psychodynamic technique and the reflective function were prominent factors in this case. Mentalization has been considered a “common factor” among different psychotherapeutic approaches, and our results highlight the importance of considering it along with specific technical aspects. Examining elements of the therapeutic process focusing on the complex interaction among these different aspects can provide helpful new insights into the process factors associated with a favourable outcome.
Pricilla Braga Laskoski; Simone Hauck; Franco Orsucci; Alessandro Giuliani; Fernanda Barcellos Serralta; Giulio de Felice. Psychodynamic Factor as Predictor of Outcome in the Treatment of a Psychosomatic Spectrum Patient. Journal of Contemporary Psychotherapy 2021, 51, 145 -153.
AMA StylePricilla Braga Laskoski, Simone Hauck, Franco Orsucci, Alessandro Giuliani, Fernanda Barcellos Serralta, Giulio de Felice. Psychodynamic Factor as Predictor of Outcome in the Treatment of a Psychosomatic Spectrum Patient. Journal of Contemporary Psychotherapy. 2021; 51 (2):145-153.
Chicago/Turabian StylePricilla Braga Laskoski; Simone Hauck; Franco Orsucci; Alessandro Giuliani; Fernanda Barcellos Serralta; Giulio de Felice. 2021. "Psychodynamic Factor as Predictor of Outcome in the Treatment of a Psychosomatic Spectrum Patient." Journal of Contemporary Psychotherapy 51, no. 2: 145-153.
Much of our understanding of critical phenomena is based on the notion of Renormalization Group (RG), but the actual determination of its fixed points is usually based on approximations and truncations, and predictions of physical quantities are often of limited accuracy. The RG fixed points can be however given a fully rigorous and non- perturbative characterization, and this is what is presented here in a model of symplectic fermions with a nonlocal (“long-range”) kinetic term depending on a parameter ε and a quartic interaction. We identify the Banach space of interactions, which the fixed point belongs to, and we determine it via a convergent approximation scheme. The Banach space is not limited to relevant interactions, but it contains all possible irrelevant terms with short-ranged kernels, decaying like a stretched exponential at large distances. As the model shares a number of features in common with ϕ4 or Ising models, the result can be used as a benchmark to test the validity of truncations and approximations in RG studies. The analysis is based on results coming from Constructive RG to which we provide a tutorial and self-contained introduction. In addition, we prove that the fixed point is analytic in ε, a somewhat surprising fact relying on the fermionic nature of the problem.
Alessandro Giuliani; Vieri Mastropietro; Slava Rychkov. Gentle introduction to rigorous Renormalization Group: a worked fermionic example. Journal of High Energy Physics 2021, 2021, 1 -112.
AMA StyleAlessandro Giuliani, Vieri Mastropietro, Slava Rychkov. Gentle introduction to rigorous Renormalization Group: a worked fermionic example. Journal of High Energy Physics. 2021; 2021 (1):1-112.
Chicago/Turabian StyleAlessandro Giuliani; Vieri Mastropietro; Slava Rychkov. 2021. "Gentle introduction to rigorous Renormalization Group: a worked fermionic example." Journal of High Energy Physics 2021, no. 1: 1-112.
We are currently facing the challenge of improving treatments for psychiatric disorders such as major depression. Notably, antidepressants have an incomplete efficacy, mostly due to our limited knowledge of their action. Here we present a theoretical framework that considers the distinction between instructive and permissive causality, which allows formalizing and disentangling the effects exerted by different therapeutic strategies commonly used in psychiatry. Instructive causality implies that an action determines a specific effect while permissive causality allows an action to take effect or not. We posit that therapeutic strategies able to improve the quality of the living environment or the ability to face it, including changes in lifestyle and psychotherapeutic interventions, rely mainly on instructive causality and thus shape the individual's ability to face the psychopathology and build resilience. By contrast, pharmacological treatments, such as selective serotonin reuptake inhibitors, act primarily through a permissive causality: they boost neural plasticity, i.e. the ability of the brain to change itself, and therefore allow for instructive interventions to produce beneficial effects or not. The combination of an instructive and a permissive action represents the most promising approach since the quality of the living environment can shape the path leading to mental health while drug treatment can increase the likelihood of achieving such a goal.
Igor Branchi; Alessandro Giuliani. Shaping therapeutic trajectories in mental health: Instructive vs. permissive causality. European Neuropsychopharmacology 2020, 43, 1 -9.
AMA StyleIgor Branchi, Alessandro Giuliani. Shaping therapeutic trajectories in mental health: Instructive vs. permissive causality. European Neuropsychopharmacology. 2020; 43 ():1-9.
Chicago/Turabian StyleIgor Branchi; Alessandro Giuliani. 2020. "Shaping therapeutic trajectories in mental health: Instructive vs. permissive causality." European Neuropsychopharmacology 43, no. : 1-9.
COVID-19 pandemic in Italy displayed a spatial distribution that made the tracking of its time course quite difficult. The most relevant anomaly was the marked spatial heterogeneity of COVID-19 diffusion. Lombardia region accounted for around 60% of fatal cases (while hosting 15% of Italian population). Moreover, 86% of fatalities concentrated in four Northern Italy regions. The ‘explosive’ outbreak of COVID-19 in Lombardia at the very beginning of pandemic fatally biased the R-like statistics routinely used to control the disease dynamics. To (at least partially) overcome this bias, we propose a new index RI = dH/dI (daily derivative ratio of H and I, given H = Healed and I = Infected), corresponding to the ratio between healed and infected patients relative daily changes. The proposed index is less flawed than R by the uncertainty related to the estimated number of infected persons and allows to follow (and possibly forecast) epidemic dynamics in a largely model-independent way. To analyze the dynamics of the epidemic, starting from the beginning of the virus spreading—when data are insufficient to make an estimate by adopting SIR model—a "sigmoidal family with delay" logistic model was introduced. That approach allowed in estimating the epidemic peak using the few data gathered even before mid-March. Based on this analysis, the peak was correctly predicted to occur by end of April. Analytical methodology of the dynamics of the epidemic we are proposing herein aims to forecast the time and intensity of the epidemic peak (forward prediction), while allowing identifying the (more likely) beginning of the epidemic (backward prediction). In addition, we established a relationship between hospitalization in intensive care units (ICU) versus deaths daily rates by avoiding the necessity to rely on precise estimates of the infected fraction of the population The joint evolution of the above parameters over time allows for a trustworthy and unbiased estimation of the dynamics of the epidemic, allowing us to clearly detect the qualitatively different character of the ‘so-called’ second wave with respect to the previous epidemic peak.
Mariano Bizzarri; Mario Di Traglia; Alessandro Giuliani; Annarita Vestri; Valeria Fedeli; Alberto Prestininzi. New statistical RI index allow to better track the dynamics of COVID-19 outbreak in Italy. Scientific Reports 2020, 10, 1 -13.
AMA StyleMariano Bizzarri, Mario Di Traglia, Alessandro Giuliani, Annarita Vestri, Valeria Fedeli, Alberto Prestininzi. New statistical RI index allow to better track the dynamics of COVID-19 outbreak in Italy. Scientific Reports. 2020; 10 (1):1-13.
Chicago/Turabian StyleMariano Bizzarri; Mario Di Traglia; Alessandro Giuliani; Annarita Vestri; Valeria Fedeli; Alberto Prestininzi. 2020. "New statistical RI index allow to better track the dynamics of COVID-19 outbreak in Italy." Scientific Reports 10, no. 1: 1-13.
Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10−16). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.
Olga V. Anatskaya; Alexander E. Vinogradov; Ninel M. Vainshelbaum; Alessandro Giuliani; Jekaterina Erenpreisa. Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer. International Journal of Molecular Sciences 2020, 21, 8759 .
AMA StyleOlga V. Anatskaya, Alexander E. Vinogradov, Ninel M. Vainshelbaum, Alessandro Giuliani, Jekaterina Erenpreisa. Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer. International Journal of Molecular Sciences. 2020; 21 (22):8759.
Chicago/Turabian StyleOlga V. Anatskaya; Alexander E. Vinogradov; Ninel M. Vainshelbaum; Alessandro Giuliani; Jekaterina Erenpreisa. 2020. "Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer." International Journal of Molecular Sciences 21, no. 22: 8759.
In this paper, we revisit and extend some mathematical aspects of Onsager’s theory of liquid crystals that have been investigated in recent years by different communities (statistical mechanics, analysis, and probability). We introduce a model of anisotropic molecules with three-dimensional orientations interacting via a Kac-type interaction. We prove that, in the limit in which the range of the interaction is sent to infinity after the thermodynamic limit, the free energy tends to the infimum of an effective energy functional à la Onsager. We then prove that, if the spherical harmonic transform of the angular interaction has a negative minimum, this effective free energy functional displays a first order phase transition as the total density of the system increases.
Clément Erignoux; Alessandro Giuliani. Nematic first order phase transition for liquid crystals in the van der Waals–Kac limit. Journal of Mathematical Physics 2020, 61, 103306 .
AMA StyleClément Erignoux, Alessandro Giuliani. Nematic first order phase transition for liquid crystals in the van der Waals–Kac limit. Journal of Mathematical Physics. 2020; 61 (10):103306.
Chicago/Turabian StyleClément Erignoux; Alessandro Giuliani. 2020. "Nematic first order phase transition for liquid crystals in the van der Waals–Kac limit." Journal of Mathematical Physics 61, no. 10: 103306.
The environment impacts human health in profound ways, yet few theories define the form of the relationship between human physiology and the environment. It is conjectured that such complex systems cannot interact directly, but rather their interaction requires the formation of an intermediary “interface.” This position contrasts with current epidemiological constructs of causation, which implicitly assume that two complex systems transfer information directly while remaining separate entities. Further, it is contended that dynamic, process‐based interfaces incorporate components from all the interacting systems but exhibit operational independence. This property has many consequences, the foremost being that characteristics of the interface cannot be fully resolved by only studying the systems involved in the interaction. The interface itself must be the subject of inquiry. Without refocusing the attention on biodynamic interfaces, how the environment impacts health cannot be discerned.
Manish Arora; Alessandro Giuliani; Paul Curtin. Biodynamic Interfaces Are Essential for Human–Environment Interactions. BioEssays 2020, 42, e2000017 .
AMA StyleManish Arora, Alessandro Giuliani, Paul Curtin. Biodynamic Interfaces Are Essential for Human–Environment Interactions. BioEssays. 2020; 42 (11):e2000017.
Chicago/Turabian StyleManish Arora; Alessandro Giuliani; Paul Curtin. 2020. "Biodynamic Interfaces Are Essential for Human–Environment Interactions." BioEssays 42, no. 11: e2000017.
The “magic” word complexity evokes a multitude of meanings that obscure its real sense. Here we try and generate a bottom-up reconstruction of the deep sense of complexity by looking at the convergence of different features shared by complex systems. We specifically focus on complexity in biology but stressing the similarities with analogous features encountered in inanimate and artefactual systems in order to track an integrative path toward a new “mainstream” of science overcoming the actual fragmentation of scientific culture.
Mariano Bizzarri; Oleg Naimark; José Nieto-Villar; Valeria Fedeli; Alessandro Giuliani. Complexity in Biological Organization: Deconstruction (and Subsequent Restating) of Key Concepts. Entropy 2020, 22, 885 .
AMA StyleMariano Bizzarri, Oleg Naimark, José Nieto-Villar, Valeria Fedeli, Alessandro Giuliani. Complexity in Biological Organization: Deconstruction (and Subsequent Restating) of Key Concepts. Entropy. 2020; 22 (8):885.
Chicago/Turabian StyleMariano Bizzarri; Oleg Naimark; José Nieto-Villar; Valeria Fedeli; Alessandro Giuliani. 2020. "Complexity in Biological Organization: Deconstruction (and Subsequent Restating) of Key Concepts." Entropy 22, no. 8: 885.
Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun PLLA) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration. In vivo efficacy was tested by implanting the drug-loaded-PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e. controls), the recovery stabilized at 21 days post lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA+Ibu+T3 rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49DPL. Glutamate release at 24 hours and 8DPL was reduced in PLLA+Ibu+T3- compared to PLLA-implanted rats, such as the estimated lesion volume at 60DPL. The myelin and 200-neurofilament-positive area-fraction was higher in PLLA+Ibu+T3 implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with ibuprofen and T3 significantly improves the endogenous regeneration, leading to an improvement of the functional locomotion outcome in the SCI.
Andrea Bighinati; Maria Letizia Focarete; Chaira Gualandi; Micaela Pannella; Alessandro Giuliani; Sarah Beggiato; Luca Ferraro; Luca Lorenzini; Luciana Giardino; Laura Calzà. Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System. Journal of Neurotrauma 2020, 37, 1708 -1719.
AMA StyleAndrea Bighinati, Maria Letizia Focarete, Chaira Gualandi, Micaela Pannella, Alessandro Giuliani, Sarah Beggiato, Luca Ferraro, Luca Lorenzini, Luciana Giardino, Laura Calzà. Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System. Journal of Neurotrauma. 2020; 37 (15):1708-1719.
Chicago/Turabian StyleAndrea Bighinati; Maria Letizia Focarete; Chaira Gualandi; Micaela Pannella; Alessandro Giuliani; Sarah Beggiato; Luca Ferraro; Luca Lorenzini; Luciana Giardino; Laura Calzà. 2020. "Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System." Journal of Neurotrauma 37, no. 15: 1708-1719.
Multiple kernel learning is a paradigm which employs a properly constructed chain of kernel functions able to simultaneously analyse different data or different representations of the same data. In this paper, we propose an hybrid classification system based on a linear combination of multiple kernels defined over multiple dissimilarity spaces. The core of the training procedure is the joint optimisation of kernel weights and representatives selection in the dissimilarity spaces. This equips the system with a two-fold knowledge discovery phase: by analysing the weights, it is possible to check which representations are more suitable for solving the classification problem, whereas the pivotal patterns selected as representatives can give further insights on the modelled system, possibly with the help of field-experts. The proposed classification system is tested on real proteomic data in order to predict proteins’ functional role starting from their folded structure: specifically, a set of eight representations are drawn from the graph-based protein folded description. The proposed multiple kernel-based system has also been benchmarked against a clustering-based classification system also able to exploit multiple dissimilarities simultaneously. Computational results show remarkable classification capabilities and the knowledge discovery analysis is in line with current biological knowledge, suggesting the reliability of the proposed system.
Alessio Martino; Enrico De Santis; Alessandro Giuliani; Antonello Rizzi. Modelling and Recognition of Protein Contact Networks by Multiple Kernel Learning and Dissimilarity Representations. Entropy 2020, 22, 794 .
AMA StyleAlessio Martino, Enrico De Santis, Alessandro Giuliani, Antonello Rizzi. Modelling and Recognition of Protein Contact Networks by Multiple Kernel Learning and Dissimilarity Representations. Entropy. 2020; 22 (7):794.
Chicago/Turabian StyleAlessio Martino; Enrico De Santis; Alessandro Giuliani; Antonello Rizzi. 2020. "Modelling and Recognition of Protein Contact Networks by Multiple Kernel Learning and Dissimilarity Representations." Entropy 22, no. 7: 794.
Elucidation of the genomic mechanism that guides the cell-fate change is one of the fundamental issues of biology. We previously demonstrated that whole genome expression is coordinated by the emergence of a critical point at both the cell-population and single-cell levels through the physical principle of self-organized criticality. In this paper, we further examine the genomic mechanism that determines the cell-fate changes from embryo to cancer development. The state of the critical point, acting as the organizing center of the cell fate, determines whether the genome resides in a super- or sub-critical state. In the super-critical state, a specific stochastic perturbation can spread over the entire system through the “genome engine”, an autonomous critical-control genomic system, whereas in the sub-critical state, the perturbation remains at a local level. The cell-fate changes when the genome becomes super-critical. We provide a consistent framework to develop a time-evolutional transition theory for the biological regulation of the cell-fate change.
Masa Tsuchiya; Alessandro Giuliani; Kenichi Yoshikawa. Cell-Fate Determination from Embryo to Cancer Development: Genomic Mechanism Elucidated. International Journal of Molecular Sciences 2020, 21, 4581 .
AMA StyleMasa Tsuchiya, Alessandro Giuliani, Kenichi Yoshikawa. Cell-Fate Determination from Embryo to Cancer Development: Genomic Mechanism Elucidated. International Journal of Molecular Sciences. 2020; 21 (13):4581.
Chicago/Turabian StyleMasa Tsuchiya; Alessandro Giuliani; Kenichi Yoshikawa. 2020. "Cell-Fate Determination from Embryo to Cancer Development: Genomic Mechanism Elucidated." International Journal of Molecular Sciences 21, no. 13: 4581.
Alessandro Giuliani; Vieri Mastropietro; Fabio Lucio Toninelli. Non-integrable Dimers: Universal Fluctuations of Tilted Height Profiles. Communications in Mathematical Physics 2020, 377, 1 -77.
AMA StyleAlessandro Giuliani, Vieri Mastropietro, Fabio Lucio Toninelli. Non-integrable Dimers: Universal Fluctuations of Tilted Height Profiles. Communications in Mathematical Physics. 2020; 377 (3):1-77.
Chicago/Turabian StyleAlessandro Giuliani; Vieri Mastropietro; Fabio Lucio Toninelli. 2020. "Non-integrable Dimers: Universal Fluctuations of Tilted Height Profiles." Communications in Mathematical Physics 377, no. 3: 1-77.
SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.
Luisa Di Paola; Hamid Hadi-Alijanvand; Xingyu Song; Guang Hu; Alessandro Giuliani. The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach. Journal of Proteome Research 2020, 19, 1 .
AMA StyleLuisa Di Paola, Hamid Hadi-Alijanvand, Xingyu Song, Guang Hu, Alessandro Giuliani. The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach. Journal of Proteome Research. 2020; 19 (11):1.
Chicago/Turabian StyleLuisa Di Paola; Hamid Hadi-Alijanvand; Xingyu Song; Guang Hu; Alessandro Giuliani. 2020. "The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach." Journal of Proteome Research 19, no. 11: 1.