TAp73 promotes anabolism

Metabolic adaptation has emerged as a hallmark of cancer and a promising therapeutic target, as rapidly proliferating cancer cells adapt their metabolism increasing nutrient uptake and reorganizing metabolic fluxes to support biosynthesis. The transcription factor p73 belongs to the p53-family and regulates tumorigenesis via its two N-terminal isoforms, with (TAp73) or without (ΔNp73) a transactivation domain. TAp73 acts as tumor suppressor, at least partially through induction of cell cycle arrest and apoptosis and through regulation of genomic stability. Here, we sought to investigate whether TAp73 also affects metabolic profiling of cancer cells. Using high throughput metabolomics, we unveil a thorough and unexpected role for TAp73 in promoting Warburg effect and cellular metabolism. TAp73-expressing cells show increased rate of glycolysis, higher amino acid uptake and increased levels and biosynthesis of acetyl-CoA. Moreover, we report an extensive TAp73-mediated upregulation of several anabolic pathways including polyamine and synthesis of membrane phospholipids. TAp73 expression also increases cellular methyl-donor S-adenosylmethionine (SAM), possibly influencing methylation and epigenetics, and promotes arginine metabolism, suggestive of a role in extracellular matrix (ECM) modeling. In summary, our data indicate that TAp73 regulates multiple metabolic pathways that impinge on numerous cellular functions, but that, overall, converge to sustain cell growth and proliferation

Strain localization in two-dimensional lattices

Two-dimensional localized strain wave solutions of the nonlinear equation for shear waves in two-dimensional lattices are studied. The corresponding equation does not possess an invariance in one of the spatial direction while its exact plane traveling wave solution does not reflect that. However, the numerical simulation of a two-dimensional localized wave reveals a non-symmetric evolution.DFG, 405631704, Anormaler Energietransfer in kristallinen Materialien vom Standpunkt der diskreten Mechanik und der Kontinuumstheori

A lower bound on the mass of Dark Matter particles

We discuss the bounds on the mass of Dark Matter (DM) particles, coming from the analysis of DM phase-space distribution in dwarf spheroidal galaxies (dSphs). After reviewing the existing approaches, we choose two methods to derive such a bound. The first one depends on the information about the current phase space distribution of DM particles only, while the second one uses both the initial and final distributions. We discuss the recent data on dSphs as well as astronomical uncertainties in relevant parameters. As an application, we present lower bounds on the mass of DM particles, coming from various dSphs, using both methods. The model-independent bound holds for any type of fermionic DM. Stronger, model-dependent bounds are quoted for several DM models (thermal relics, non-resonantly and resonantly produced sterile neutrinos, etc.). The latter bounds rely on the assumption that baryonic feedback cannot significantly increase the maximum of a distribution function of DM particles. For the scenario in which all the DM is made of sterile neutrinos produced via non-resonant mixing with the active neutrinos (NRP) this gives m_nrp > 1.7 keV. Combining these results in their most conservative form with the X-ray bounds of DM decay lines, we conclude that the NRP scenario remains allowed in a very narrow parameter window only. This conclusion is independent of the results of the Lyman-alpha analysis. The DM model in which sterile neutrinos are resonantly produced in the presence of lepton asymmetry remains viable. Within the minimal neutrino extension of the Standard Model (the nuMSM), both mass and the mixing angle of the DM sterile neutrino are bounded from above and below, which suggests the possibility for its experimental search.Comment: 20 pages, published in JCA

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Study of ordered hadron chains with the ATLAS detector

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A search for resonances decaying into a Higgs boson and a new particle X in the XH→qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson ($H$) and a new particle ($X$) is reported, utilizing 36.1 fb$^{-1}$ of proton-proton collision data at $\sqrt{s} =$ 13 TeV collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle $X$ is assumed to decay to a pair of light quarks, and the fully hadronic final state $XH \rightarrow q\bar q'b\bar b$ is analysed. The search considers the regime of high $XH$ resonance masses, where the $X$ and $H$ bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of $XH$ mass versus $X$ mass is scanned for evidence of a signal, over a range of $XH$ resonance mass values between 1 TeV and 4 TeV, and for $X$ particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of $XH$ and $X$ masses, on the production cross-section of the $XH\rightarrow q\bar q'b\bar b$ resonance

Study of the material of the ATLAS inner detector for Run 2 of the LHC

Instituto de Física La Plat