Concurrent infall of satellites: Collective effects changing the overall picture

A variety of new physical processes have proven to play an important role in orbital decay of a satellite galaxy embedded inside a dark matter halo but this is not fully understood. Our goal is to assess if the orbital history of a satellite remains unchanged during a concurrent sinking. For this purpose we analyze the impact that the internal structure of the satellites and their spatial distribution inside the host halo may have on the concurrent sinking process due to both mass loss and the combined effect of self-friction, which have not been studied before for concurrent sinking. We set up a set of N-body simulations that include multiple satellites, sinking simultaneously in a host halo and we compare them with models including a single satellite. The main result of our work is that the satellite's accretion history differs from the classical isolated view when we consider the collective effects. The accretion history of each satellite strongly depends on the initial configuration, the number of satellites in the halo at the time of infall and the internal properties of each satellite. We observe that compact satellites in a flat configuration fall slower than extended satellites that have lost mass, showing a non-reported behavior of self-friction. We find that such effects are maximized when satellites are located in a flat configuration. We show that in a flat configuration similar to the Vast Polar Structure, deviations in the apocenters can be of about 30% with respect to the isolated case, and up to 50% on the eccentricities. We conclude that ignoring the collective effects produced by the concurrent sinking of satellite galaxies may lead to large errors in the determination of the merger progenitors properties, making it considerably more challenging to trace back the accretion event. Timing constrains on host density profile may be modified by the effects discussed here.Comment: A&A, Forthcoming article Received: 29 March 2022 / Accepted: 26 September 2022 6 pages, 6 figure

Assessing the Hierarchical Hamiltonian Splitting Integrator for Collisionless N-body Simulations

The N-body problem has become one of the hottest topics in the fields of computational dynamics and cosmology. The large dynamical range in some astrophysical problems led to the use of adaptive time steps to integrate particle trajectories, however, the search of optimal strategies is still challenging. We quantify the performance of the hierarchical time step integrator Hamiltonian Splitting (HamSp) for collisionless multistep simulations. We compare with the constant step Leap-Frog (LeapF) integrator and the adaptive one (AKDK). Additionally, we explore the impact of different time step assigning functions. There is a computational overhead in HamSp however there are two interesting advantages: choosing a convenient time-step function may compensate and even turn around the efficiency compared with AKDK. We test both reversibility and time symmetry. The symmetrized nature of the HamSp integration is able to provide time-reversible integration for medium time scales and overall deliver better energy conservation for long integration times, and the linear and angular momentum are preserved at machine precision. We address the impact of using different integrators in astrophysical systems. We found that in most situations both AKDK and HamSp are able to correctly simulate the problems. We conclude that HamSp is an attractive and competitive alternative to AKDK, with, in some cases, faster and with better energy and momentum conservation. The use of recently discussed Bridge splitting techniques with HamSp may allow to reach considerably high efficiency.Comment: 13 pages, 16 figure

The paralogue of the intrinsically disordered nuclear protein 1 has a nuclear localization sequence that binds to human importin a3

Numerous carrier proteins intervene in protein transport from the cytoplasm to the nucleus in eukaryotic cells. One of those is importin a, with several human isoforms; among them, importin a3 (Impa3) features a particularly high flexibility. The protein NUPR1L is an intrinsically disordered protein (IDP), evolved as a paralogue of nuclear protein 1 (NUPR1), which is involved in chromatin remodeling and DNA repair. It is predicted that NUPR1L has a nuclear localization sequence (NLS) from residues Arg51 to Gln74, in order to allow for nuclear translocation. We studied in this work the ability of intact NUPR1L to bind Impa3 and its depleted species, ¿Impa3, without the importin binding domain (IBB), using fluorescence, isothermal titration calorimetry (ITC), circular dichroism (CD), nuclear magnetic resonance (NMR), and molecular docking techniques. Furthermore, the binding of the peptide matching the isolated NLS region of NUPR1L (NLS-NUPR1L) was also studied using the same methods. Our results show that NUPR1L was bound to Imp a3 with a low micromolar affinity (~5 µM). Furthermore, a similar affinity value was observed for the binding of NLS-NUPR1L. These findings indicate that the NLS region, which was unfolded in isolation in solution, was essentially responsible for the binding of NUPR1L to both importin species. This result was also confirmed by our in silico modeling. The binding reaction of NLS-NUPR1L to ¿Impa3 showed a larger affinity (i.e., lower dissociation constant) compared with that of Impa3, confirming that the IBB could act as an auto-inhibition region of Impa3. Taken together, our findings pinpoint the theoretical predictions of the NLS region in NUPR1L and, more importantly, suggest that this IDP relies on an importin for its nuclear translocation

Particle approximation of the one dimensional Keller-Segel equation, stability and rigidity of the blow-up

We investigate a particle system which is a discrete and deterministic approximation of the one-dimensional Keller-Segel equation with a logarithmic potential. The particle system is derived from the gradient flow of the homogeneous free energy written in Lagrangian coordinates. We focus on the description of the blow-up of the particle system, namely: the number of particles involved in the first aggregate, and the limiting profile of the rescaled system. We exhibit basins of stability for which the number of particles is critical, and we prove a weak rigidity result concerning the rescaled dynamics. This work is complemented with a detailed analysis of the case where only three particles interact

Comparación de los métodos Directo y de Friedewald para la determinación de los niveles de colesterol LDL en el equino

Objective. To compare the Direct Method vs the Precipitation Friedewald Method for determing LDL cholesterol levels in the horse, specie with HDL pattern. Materials and methods. Blood Samples of 200 overnight fasted horses of different ages, breed and sex were obtained. Blood levels of LDL cholesterol were determined first by the Direct method and then by the precipitation Friedewald method. The results were analyzed using (one way ANOVA) and compared (F test <0.05). Results. There were no differences for determing LDL cholesterol levels between the Direct Method vs Friedewald Method (mean: 27.9 vs 29 mg/dl, minimal: 14 vs 11.2 mg/dl, maximal: 51 vs 54.2 mg/dl, range: 37 vs 43 mg/dl, and standard deviation: 6.4 vs 7.0 mg/dl respectively) Conclusion. According to these results both methods are recommended for determing LDL cholesterol levels in species with HDL pattern.Objetivo. Comparar el método Directo con el método de precipitación de Friedewald para la determinación de colesterol LDL en una especie con patrón metabólico HDL. Materiales y métodos. Fueron tomadas en estado de ayuno, muestras de sangre de 200 equinos de diferente edad, raza y sexo. Luego de extraer el suero, fueron determinados los niveles de colesterol LDL mediante el método directo, posteriormente fueron determinados los niveles de colesterol LDL utilizando el método de Friedewald. Los resultados fueron analizados estadísticamente mediante ANOVA de una vía. Resultados. El método directo reportó valores (mg/dl) de promedio, mínimo, máximo, rango y desviación estándar de 27.9; 14; 51; 37; 6.4 respectivamente, mediante el método de Friedewald se obtuvieron valores (mg/dl) de promedio, mínimo, máximo, rango y desviación estándar de 29; 11.2; 54.2; 43; 7.0 respectivamente. El valor de P en el test F fue mayor o igual a 0.05, por lo cual no se evidenció diferencia significativa a un nivel de confidencia del 95% entre los valores obtenidos por los dos métodos. Conclusiones. Pueden ser utilizados cualquiera de los dos métodos analizados para la determinación del colesterol LDL en especies con patrón HDL

Comparación de los métodos Directo y de Friedewald para la determinación de los niveles de colesterol LDL en el equino

Objetivo. Comparar el método Directo con el método de precipitación de Friedewald para la determinación de colesterol LDL en una especie con patrón metabólico HDL. Materiales y métodos. Fueron tomadas en estado de ayuno, muestras de sangre de 200 equinos de diferente edad, raza y sexo. Luego de extraer el suero, fueron determinados los niveles de colesterol LDL mediante el método directo, posteriormente fueron determinados los niveles de colesterol LDL utilizando el método de Friedewald. Los resultados fueron analizados estadísticamente mediante ANOVA de una vía. Resultados. El método directo reportó valores (mg/dl) de promedio, mínimo, máximo, rango y desviación estándar de 27.9; 14; 51; 37; 6.4 respectivamente, mediante el método de Friedewald se obtuvieron valores (mg/dl) de promedio, mínimo, máximo, rango y desviación estándar de 29; 11.2; 54.2; 43; 7.0 respectivamente. El valor de P en el test F fue mayor o igual a 0.05, por lo cual no se evidenció diferencia significativa a un nivel de confidencia del 95% entre los valores obtenidos por los dos métodos. Conclusiones. Pueden ser utilizados cualquiera de los dos métodos analizados para la determinación del colesterol LDL en especies con patrón HDL

Human enzyme PADI4 binds to the nuclear carrier Importin a3

PADI4 is a peptidyl-arginine deiminase (PADI) involved in the conversion of arginine to citrulline. PADI4 is present in macrophages, monocytes, granulocytes, and several cancer cells. It is the only PADI family member observed within both the nucleus and the cytoplasm. PADI4 has a predicted nuclear localization sequence (NLS) comprising residues Pro56 to Ser83, to allow for nuclear translocation. Recent predictors also suggest that the region Arg495 to Ile526 is a possible NLS. To understand how PADI4 is involved in cancer, we studied the ability of intact PADI4 to bind importin a3 (Impa3), a nuclear transport factor that plays tumor-promoting roles in several cancers, and its truncated species (¿Impa3) without the importin-binding domain (IBB), by using fluorescence, circular dichroism (CD), and isothermal titration calorimetry (ITC). Furthermore, the binding of two peptides, encompassing the first and the second NLS regions, was also studied using the same methods and molecular docking simulations. PADI4 interacted with both importin species, with affinity constants of ~1–5 µM. The isolated peptides also interacted with both importins. The molecular simulations predict that the anchoring of both peptides takes place in the major binding site of Impa3 for the NLS of cargo proteins. These findings suggest that both NLS regions were essentially responsible for the binding of PADI4 to the two importin species. Our data are discussed within the framework of a cell mechanism of nuclear transport that is crucial in cancer

A phosphorylation-induced switch in the nuclear localization sequence of the intrinsically disordered nupr1 hampers binding to importin

Several carrier proteins are involved in protein transport from the cytoplasm to the nucleus in eukaryotic cells. One of those is importin a, of which there are several human isoforms; among them, importin a3 (Impa3) has a high flexibility. The protein NUPR1, a nuclear protein involved in the cell-stress response and cell cycle regulation, is an intrinsically disordered protein (IDP) that has a nuclear localization sequence (NLS) to allow for nuclear translocation. NUPR1 does localize through the whole cell. In this work, we studied the affinity of the isolated wild-type NLS region (residues 54–74) of NUPR1 towards Impa3 and several mutants of the NLS region by using several biophysical techniques and molecular docking approaches. The NLS region of NUPR1 interacted with Impa3, opening the way to model the nuclear translocation of disordered proteins. All the isolated NLS peptides were disordered. They bound to Impa3 with low micromolar affinity (1.7–27 µM). Binding was hampered by removal of either Lys65 or Lys69 residues, indicating that positive charges were important; furthermore, binding decreased when Thr68 was phosphorylated. The peptide phosphorylated at Thr68, as well as four phospho-mimetic peptides (all containing the Thr68Glu mutation), showed the presence of a sequential NN(i, i + 1) nuclear Overhauser effect (NOE) in the 2D-1H-NMR (two-dimensional–proton NMR) spectra, indicating the presence of turn-like conformations. Thus, the phosphorylation of Thr68 modulates the binding of NUPR1 to Impa3 by a conformational, entropy-driven switch from a random-coil conformation to a turn-like structure