Unraveling the Differences of the Hydrolytic Activity of Trypanosoma cruzi trans-Sialidase and Trypanosoma rangeli Sialidase: A Quantum Mechanics–Molecular Mechanics Modeling Study

Chagas’ disease, also known as American trypanosomiasis, is a lethal, chronic disease that currently affects more than 10 million people in Central and South America. The trans-sialidase from Trypanosoma cruzi (T. cruzi, TcTS) is a crucial enzyme for the survival of this parasite: sialic acids from the host are transferred to the cell surface glycoproteins of the trypanosome, thereby evading the host’s immune system. On the other hand, the sialidase of T. rangeli (TrSA), which shares 70% sequence identity with TcTS, is a strict hydrolase and shows no trans-sialidase activity. Therefore, TcTS and TrSA represent an excellent framework to understand how different catalytic activities can be achieved with extremely similar structures. By means of combined quantum mechanics–molecular mechanics (QM/MM, SCC-DFTB/Amberff99SB) calculations and umbrella sampling simulations, we investigated the hydrolysis mechanisms of TcTS and TrSA and computed the free energy profiles of these reactions. The results, together with our previous computational investigations, are able to explain the catalytic mechanism of sialidases and describe how subtle differences in the active site make TrSA a strict hydrolase and TcTS a more efficient trans-sialidase.Fil: Bueren Calabuig, Juan A.. University of Florida; Estados UnidosFil: Pierdominici Sottile, Gustavo. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roitberg, Adrián. University of Florida; Estados Unido

Impact of Ser17 phosphorylation on the conformational dynamics of the oncoprotein MDM2

MDM2 is an important oncoprotein that downregulates the activity of the tumor suppressor protein p53 via binding of its N-terminal domain to the p53 transactivation domain. The first 24 residues of the MDM2 N-terminal domain form an intrinsically disordered “lid” region that interconverts on a millisecond time scale between “open” and “closed” states in unliganded MDM2. While the former conformational state is expected to facilitate p53 binding, the latter competes in a pseudo-substrate manner with p53 for its binding site. Phosphorylation of serine 17 in the MDM2 lid region is thought to modulate the equilibrium between “open” and “closed” lid states, but contradictory findings on the favored lid conformational state upon phosphorylation have been reported. Here, the nature of the conformational states of MDM2 pSer17 and Ser17Asp variants was addressed by means of enhanced sampling molecular dynamics simulations. Detailed analyses of the computed lid conformational ensembles indicate that both lid variants stabilize a “closed” state, with respect to wild type. Nevertheless, the nature of the closed-state conformational ensembles differs significantly between the pSer17 and Ser17Asp variants. Thus, care should be applied in the interpretation of biochemical experiments that use phosphomimetic variants to model the effects of phosphorylation on the structure and dynamics of this disordered protein region

Enumeration of left braces with additive group C2×C2×C4×C4C_2\times C_2\times C_4\times C_4

We show that the number of isomorphism classes of left braces of order~$64$ with additive group isomorphic to $C_2\times C_2\times C_4\times C_4$ is $10\,326\,821$. This completes the classification of left braces of order~$64$, that turn out to fall into $15\,095\,601$ isomorphism classes.Comment: Ric. Mat., in press. 9 pages. arXiv admin note: substantial text overlap with arXiv:2210.1282

Final outcome of raptors admitted to the Tafira Wildlife Rehabilitation Center, Gran Canaria Island, Spain (2003–2013)

Disposición final de las rapaces admitidas en el Centro de Rehabilitación de Fauna Silvestre de Tafira, Gran Canaria, España (2003–2013) En este estudio se analizan los resultados de la rehabilitación de aves rapaces silvestres admitidas en el Centro de Rehabilitación de Fauna Silvestre de Tafira en la isla de Gran Canaria, España, desde 2003 hasta 2013, mediante un sistema de auditoría de la calidad basado en los índices generales y clasificados (por causa de admisión) de las cuatro categorías de disposición final, el tiempo hasta la muerte y el tiempo de permanencia como indicadores de calidad. Las categorías de disposición final fueron: eutanasia (Er) = 19,78%, mortalidad no asistida durante la hospitalización (Mr) = 22,20%, liberación (Rr) = 57,57% y cautividad permanente (Cr) = 0,46%. Teniendo en cuenta la especial vulnerabilidad de las especies de rapaces insulares y el alto índice de Rr conseguido, los resultados de este estudio ponen de relieve la importancia de los centros de rehabilitación de fauna silvestre en el tratamiento médico de las aves heridas y la consiguiente liberación de las aves rehabilitadas.Disposición final de las rapaces admitidas en el Centro de Rehabilitación de Fauna Silvestre de Tafira, Gran Canaria, España (2003–2013) En este estudio se analizan los resultados de la rehabilitación de aves rapaces silvestres admitidas en el Centro de Rehabilitación de Fauna Silvestre de Tafira en la isla de Gran Canaria, España, desde 2003 hasta 2013, mediante un sistema de auditoría de la calidad basado en los índices generales y clasificados (por causa de admisión) de las cuatro categorías de disposición final, el tiempo hasta la muerte y el tiempo de permanencia como indicadores de calidad. Las categorías de disposición final fueron: eutanasia (Er) = 19,78%, mortalidad no asistida durante la hospitalización (Mr) = 22,20%, liberación (Rr) = 57,57% y cautividad permanente (Cr) = 0,46%. Teniendo en cuenta la especial vulnerabilidad de las especies de rapaces insulares y el alto índice de Rr conseguido, los resultados de este estudio ponen de relieve la importancia de los centros de rehabilitación de fauna silvestre en el tratamiento médico de las aves heridas y la consiguiente liberación de las aves rehabilitadas.The outcomes of wild raptors admitted to the Tafira Wildlife Rehabilitation Center in Gran Canaria Island, Spain, from 2003 to 2013 were analyzed using a quality auditing system based on the crude and stratified (by causes of admission) rates of four final outcome categories, time until death and length of stay as quality indicators. The outcome categories were: euthanasia (Er = 19.78%); unassisted mortality during hospitalization (Mr = 22.20%); release (Rr = 57.57%); and permanent captivity (Cr = 0.46%). Taking into account the particular vulnerability of insular raptor species and the high Rr achieved, findings from this study emphasize the importance of wildlife rehabilitation centers for the medical management of injured raptors and the subsequent release of rehabilitated individuals into the wild

Factorizing operators on Banach function spaces through spaces of multiplication operators

In order to extend the theory of optimal domains for continuous operators on a Banach function space X(μ) over a finite measure μ, we consider operators T satisfying other type of inequalities than the one given by the continuity which occur in several well-known factorization theorems (for instance, Pisier Factorization Theorem through Lorentz spaces, pth-power factorable operators . . . ). We prove that such a T factorizes through a space of multiplication operators which can be understood in a certain sense as the optimal domain for T . Our extended optimal domain technique does not need necessarily the equivalence between μ and the measure defined by the operator T and, by using δ-rings, μ is allowed to be infinite. Classical and new examples and applications of our results are also given, including some new results on the Hardy operator and a factorization theorem through Hilbert spaces.Generalitat Valenciana TSGD-07Ministerio de Educación y Ciencia MTM2006-13000-C03-0

Tensor product representation of Kothe-Bochner spaces and their dual spaces

We provide a tensor product representation of Kothe-Bochner function spaces of vector valued integrable functions. As an application, we show that the dual space of a Kothe-Bochner function space can be understood as a space of operators satisfying a certain extension property. We apply our results in order to give an alternate representation of the dual of the Bochner spaces of p-integrable functions and to analyze some properties of the natural norms that are defined on the associated tensor products.First and third authors are supported by grant MTM201453009-P of the Ministerio de Economia y Competitividad (Spain). Second and fourth authors are supported by grant MTM2012-36740-C02-02 of the Ministerio de Economia y Competitividad (Spain).Calabuig, JM.; Jiménez Fernández, E.; Juan Blanco, MA.; Sánchez Pérez, EA. (2016). Tensor product representation of Kothe-Bochner spaces and their dual spaces. Positivity. 20(1):155-169. https://doi.org/10.1007/s11117-015-0347-3S155169201Bochner, S.: Integration von Funktionen, deren Werte die Elemente eines Vectorraumes sind. Fundamenta Mathematicae 20, 262–276 (1933)Calabuig, J.M., Delgado, O., Juan, M.A., Sánchez, E.A.: Pérez, On the Banach lattice structure of $$L^1_w$$ L w 1 of a vector measure on a $$\delta$$ δ -ring. Collect. Math. 65, 6567–85 (2014)Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364(1), 88–103 (2010)Calabuig, J.M., Gregori, P., Sánchez, E.A.: Pérez, Radon-Nikodým derivatives for vector measures belonging to Köthe function spaces. J. Math. Anal. Appl. 348, 469–479 (2008)Cerdà, J., Hudzik, H., Mastyło, M.: Geometric properties of Köthe-Bochner spaces. Math. Proc. Cambridge Philos. Soc. 120(3), 521–533 (1996)Chakraborty, N.D., Basu, S.: Spaces of p-tensor integrable functions and related Banach space properties. Real Anal. Exchange 34, 87–104 (2008)Chakraborty, N.D., Basu, S.: Integration of vector-valued functions with respect to vector measures defined on $$\delta$$ δ -rings. Ill. J. Math. 55(2), 495–508 (2011)Defant, A., Floret, K.: Tensor norms and operator ideals. North-Holland, Amsterdam (1993)Delgado, O., Juan, M.A.: Representation of Banach lattices as $$L^{1}_{w}$$ L w 1 spaces of a vector measure defined on a $$\delta -$$ δ - ring. Bull. Belgian Math. Soc. 19, 239–256 (2012)Diestel, J., Uhl, J.J.: Vector measures. Am. Math. Soc, Providence (1977)Dobrakov, I.: On integration in Banach spaces, VII. Czechoslovak Math. J. 38, 434–449 (1988)García-Raffi, L.M., Jefferies, B.: An application of bilinear integration to quantum scattering. J. Math. Anal. Appl. 415, 394–421 (2014)Gregori Huerta, P.: Espacios de medidas vectoriales. Thesis, Universidad de Valencia, ISBN:8437060591 (2005)Jefferies, B., Okada, S.: Bilinear integration in tensor products. Rocky Mt. J. Math. 28, 517–545 (1998)Lewis, D.R.: On integrability and summability in vector spaces. Ill. J. Math. 16, 294–307 (1972)Lin, P.-K.: Köthe-Bochner function spaces. Birkhauser, Boston (2004)Lindenstrauss, J., Tzafriri, L.: Classical Banach spaces II. Springer, Berlin (1979)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal Domains and integral extensions of operators acting in function spaces. Operator Theory Advances and Applications, vol. 180. Birkhäuser, Basel (2008)Pallu de La Barriére, R.: Integration of vector functions with respect to vector measures. Studia Univ. Babes-Bolyai Math. 43, 55–93 (1998)Rodríguez, J.: On integration of vector functions with respect to vector measures. Czechoslovak Math. J. 56, 805–825 (2006

Kaplan-Meier type survival curves for COVID-19: a health data based decision-making tool

Countries are recording health information on the global spread of COVID-19 using different methods, sometimes changing the rules after a few days. They are all publishing the number of new individuals infected, cured and dead, along with some supplementary data. These figures are often recorded in a non-uniform manner and do not match the standard definitions of these variables. However, in this paper we show that the Kaplan-Meier curves calculated with them could provide useful information about the dynamics of the disease in different countries. Our aim is to present a robust and simple model to show certain characteristics of the evolution of the dynamic process, showing that the differences of evolution among the countries is reflected in the corresponding Kaplan-Meier-type curves. We compare the curves obtained for the most affected countries so far, proposing possible interpretations of the properties that distinguish them.Comment: 12 pages, 6 figure

Lung tumorspheres as a drug screening platform against cancer stem cells

Treatment resistance and metastasis are linked to cancer stem cells (CSCs). This population represents a promising target, but remains unexplored in lung cancer. The main objective of this study was to characterize lung CSCs and discover new therapeutic strategies

Factorization theorems for homogeneous maps on banach function spaces and approximation of compact operators

The final publication is available at Springer via http://dx.doi.org/10.1007/s00009-014-0384-3[EN] In this paper, we characterize compact linear operators from Banach function spaces to Banach spaces by means of approximations with bounded homogeneous maps. To do so, we undertake a detailed study of such maps, proving a factorization theorem and paying special attention to the equivalent strong domination property involved. Some applications to compact maximal extensions of operators are also given.The authors thank the referee for his/her careful revision and suggestions. The first author gratefully acknowledges the support of the Ministerio de Economia y Competitividad (Spain), under Project #MTM2011-22417. The second author gratefully acknowledges the support of the Ministerio de Economia y Competitividad (Spain), under Project #MTM2012-36740-c02-02.Rueda, P.; Sánchez Pérez, EA. (2015). Factorization theorems for homogeneous maps on banach function spaces and approximation of compact operators. Mediterranean Journal of Mathematics. 12(1):89-115. https://doi.org/10.1007/s00009-014-0384-3S89115121Calabuig J.M., Delgado O., Sánchez Pérez E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364, 88–103 (2010)Defant, A.: Variants of the Maurey–Rosenthal theorem for quasi Köthe function spaces. Positivity 5, 153–175 (2001)Delgado, O., Sánchez Pérez, E.A.: Strong factorizations between couples of operators on Banach spaces, J. Conv. Anal. 20(3), 599–616 (2013)Diestel, J., Uhl, J.J.: Vector measures, Math. Surv. vol. 15, Amer. Math. Soc., Providence (1977)Fernández A., Mayoral F., Naranjo F., Sáez C., Sánchez-Pérez E.A.: Spaces of p-integrable functions with respect to a vector measure. Positivity 10, 1–16 (2006)Ferrando I., Rodríguez J.: The weak topology on L p of a vector measure. Topol. Appl. 155(13), 1439–1444 (2008)Lindenstrauss, J., Tzafriri, L.: Classical Banach Spaces, II, Springer, Berlin (1996)Maligranda L., Persson L.E.: Generalized duality of some Banach function spaces. Indag. Math. 51, 323–338 (1989)Meyer-Nieberg, P.: Banach lattices, Springer, Berlin (1991)Okada, S.: Does a compact operator admit a maximal domain for its compact linear extension? In: Vector measures, integration and related topics. Operator theory: advances and applications, Vol. 201, pp. 313–322. Birkhäuser, Basel (2009)Okada S., Ricker W.J., Rodríguez-Piazza L.: Compactness of the integration operator associated with a vector measure. Studia Math. 150(2), 133–149 (2002)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal domain and integral extension of operators acting in function spaces. Operator theory: advances and applications, 180. Birkhäuser, Basel (2008)Sánchez Pérez, E.A.: Compactness arguments for spaces of p-integrable functions with respect to a vector measure and factorization of operators through Lebesgue–Bochner spaces, Illinois J. Math. 45(3), 907–923 (2001