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Sympatric speciation is an important phenomenon in Evolution: a population being able to express two different phenotypes gives rise to a new species without a physical separation from the original population. In this paper, we describe a model that describes the sympatric speciation process using a population dynamics approach. Our aim is to point out some dynamical features that could be observed in a population where a sympatric speciation process is going on. Some interesting stochastic effects are discussed by means of numerical simulations. [ABSTRACT FROM AUTHOR]

Treatment with tyrosine kinase inhibitors (TKIs) has been associated with alterations in circulating thyroid hormone levels, possibly related to perturbations in peripheral thyroid hormone metabolism. In this study, we evaluated the effect of the multi-kinase inhibitor vandetanib on the expression of the three deiodinase selenoenzymes, responsible for the thyroid hormone activation (type 1 and type 2 deiodinases) or for its inactivation (type 3 deiodinase). Here, we show that the multi-kinase inhibitor vandetanib determines a strong cell-specific downregulation of type 2 deiodinase (D2) expression and a significant reduction in D2 enzymatic activity. This occurs in the diffused population of fibro/ adipogenic progenitors, which reside in different tissues -- including the muscles -- and normally express D2. Given the widespread diffusion of mesenchymal cells within the body, our results may explain at least partially the alterations in thyroid hormone levels that occur in vandetanib-treated patients. Our findings represent a step forward into the understanding of the mechanisms by which TKIs induce hypothyroidism and identify a resident cell population in which such an effect takes place. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC) is a rare thyroid tumor that frequently originates from the dedifferentiation of a well-differentiated papillary or follicular thyroid cancer. Type 2 deiodinase (D2), responsible for the activation of the thyroid hormone thyroxine into tri-iodothyronine (T3), is expressed in normal thyroid cells and its expression is strongly downregulated in papillary thyroid cancer. In skin cancer, D2 has been associated with cancer progression, dedifferentiation, and epithelial--mesenchymal transition. Here, we show that D2 is highly expressed in anaplastic compared to papillary thyroid cancer cell lines and that D2-derived T3 is required for ATC cell proliferation. D2 inhibition is associated with G1 growth arrest and induction of cell senescence, together with reduced cell migration and invasive potential. Finally, we found that mutated p5372R(R248W), frequently found in ATC, is able to induce D2 expression in transfected papillary thyroid cancer cells. Our results show that the action of D2 is crucial for ATC proliferation and invasiveness, providing a potential new therapeutic target for the treatment of ATC. [ABSTRACT FROM AUTHOR]

In this paper, we focus our investigation on providing long-term estimates of the Hamiltonian deviation computed along numerical approximations to the solutions of stochastic Hamiltonian systems, of both It\and Stratonovich types. It is well known that the expected Hamiltonian of an It Hamiltonian system with additive noise exhibits a linear drift in time [C. Chen et al., Adv. Comput. Math., 46 (2020), 27], while the Hamiltonian function is conserved along the exact flow of a Stratonovich Hamiltonian system [T. Misawa, Japan J. Indust. Appl. Math., 17 (2000), pp. 119--128; T. Misawa, Math. Probl. Eng., 2010 (2010), 384937]. Here, we focus our attention on providing modified differential equations associated to suitable discretizations for the above problems, by means of weak backward error analysis arguments [K. C. Zygalakis, SIAM J. Sci. Comput., 33 (2011), pp. 102--130]. Then, long-term estimates are provided for both It and Stratonovich Hamiltonian systems, revealing the presence of parasitic terms affecting the overall conservation accuracy. Finally, selected numerical experiments are provided to confirm the theoretical analysis. [ABSTRACT FROM AUTHOR]

In this article we address the stability of linear stochastic differential equations. In particular, we focus our attention on non-normality in stochastic differential equations. Following Higham and Mao we study a test problem for non-normal stochastic differential equations, that is stable without noise, and prove a property conjectured by Higham and Mao, that is that an exponentially small (in the dimension) noise term is able to destabilise in a mean-square sense the solution of the SDE. [ABSTRACT FROM AUTHOR]

Background: The DIO2 Thr92Ala polymorphism (rs225014), which occurs in about 15–30% of Caucasian people, determines a less efficient type 2 deiodinase (D2) enzyme. The aim of this study was to determine the impact of DIO2 Thr92Ala polymorphism on the serum thyrotropin (TSH) levels in thyroidectomized patients with hypothyroidism and to evaluate whether TSH levels and aging could be related, at pituitary level, to D2 activity. Methods: This prospective study was performed on 145 thyroid cancer patients, treated with total thyroidectomy, and undergoing radioiodine treatment after 3 weeks of levothyroxine (LT4) withdrawal. A mouse model has been used to determine D2 protein and mRNA levels in pituitary during aging. Results: Genetic analysis identified DIO2 Thr92Ala polymorphism in 56% of participants: 64/145 (44%) patients were homozygous wild type (WT) (Thr/Thr), 64 (44%) heterozygous (Thr/Ala), and 17 (12%) homozygous mutant (Ala/Ala). A significant negative relationship was observed between aging and the rise in serum TSH levels during LT4 withdrawal. However, this negative correlation found in WT was reduced in heterozygous and lost in mutant homozygous patients (Thr/Thr r = −0.45, p = 0.0002, 95% confidence interval [CI] −0.63 to −0.23; Ala/Thr r = −0.39, p = 0.0012, CI −0.60 to −0.67; and Ala/Ala r = −0.30, p = 0.2347; CI −0.70 to 0.20). Accordingly, when we compared the TSH measured in each patient to its theoretical value predicted from age, the TSH did not reach its putative target in 47% of WT patients, in 70% of Ala/Thr, and 76% of Ala/Ala carrying patients (p = 0.0036). This difference was lost in individuals older than 60 years, suggesting a decline of D2 associated with aging. The hypothesis that the pituitary D2 decreases with age was confirmed by the evidence that D2 mRNA and protein levels were lower in pituitary from old versus young mice. Conclusion: An age-related decline in TSH production in response to hypothyroidism was correlated with decreased D2 levels in pituitary. The presence of DIO2 homozygous Ala/Ala polymorphism was associated with a reduced level of TSH secretion in response to hypothyroidism, indicating a decreased pituitary sensitivity to serum thyroxine variation (Institutional Research Ethics board approval number no. 433/21). [ABSTRACT FROM AUTHOR]

In this work, we investigate the numerical conservation of characteristic properties of stochastic Hamiltonian problems driven by additive noise under time discretizations, in the spirit of stochastic geometric numerical integration. In particular, we aim to understand how Monte Carlo and multilevel Monte Carlo estimators for the expected values eventually affect the conservation properties of the numerical scheme. Specifically, our analysis is focused on the role of random number generation in the conservation of invariant laws for stochastic Hamiltonian problems under time discretization by the drift-preserving numerical scheme introduced in C. Chen, D. Cohen, R. D'Ambrosio and A. Lang, [Drift-preserving numerical integrators for stochastic Hamiltonian systems, Adv. Comput. Math. 46(2) (2020), pp. 27.] and the stochastic perturbation of a symplectic Runge–Kutta method, introduced in K. Burrage and P.M. Burrage, [Low rank Runge–Kutta methods, symplecticity and stochastic Hamiltonian problems with additive noise, J. Comput. Appl. Math. 236(16) (2012), pp. 3920–3930.]. The numerical evidence confirms the aforementioned theoretical analysis. [ABSTRACT FROM AUTHOR]