MALT1 auto-proteolysis is essential for NF-κB-dependent gene transcription in activated lymphocytes.

Mucosa-associated lymphoid tissue 1 (MALT1) controls antigen receptor-mediated signalling to nuclear factor κB (NF-κB) through both its adaptor and protease function. Upon antigen stimulation, MALT1 forms a complex with BCL10 and CARMA1, which is essential for initial IκBα phosphorylation and NF-κB nuclear translocation. Parallel induction of MALT1 protease activity serves to inactivate negative regulators of NF-κB signalling, such as A20 and RELB. Here we demonstrate a key role for auto-proteolytic MALT1 cleavage in B- and T-cell receptor signalling. MALT1 cleavage occurred after Arginine 149, between the N-terminal death domain and the first immunoglobulin-like region, and did not affect its proteolytic activity. Jurkat T cells expressing an un-cleavable MALT1-R149A mutant showed unaltered initial IκBα phosphorylation and normal nuclear accumulation of NF-κB subunits. Nevertheless, MALT1 cleavage was required for optimal activation of NF-κB reporter genes and expression of the NF-κB targets IL-2 and CSF2. Transcriptome analysis confirmed that MALT1 cleavage after R149 was required to induce NF-κB transcriptional activity in Jurkat T cells. Collectively, these data demonstrate that auto-proteolytic MALT1 cleavage controls antigen receptor-induced expression of NF-κB target genes downstream of nuclear NF-κB accumulation

A progressive refinement approach for the visualisation of implicit surfaces

Visualising implicit surfaces with the ray casting method is a slow procedure. The design cycle of a new implicit surface is, therefore, fraught with long latency times as a user must wait for the surface to be rendered before being able to decide what changes should be introduced in the next iteration. In this paper, we present an attempt at reducing the design cycle of an implicit surface modeler by introducing a progressive refinement rendering approach to the visualisation of implicit surfaces. This progressive refinement renderer provides a quick previewing facility. It first displays a low quality estimate of what the final rendering is going to be and, as the computation progresses, increases the quality of this estimate at a steady rate. The progressive refinement algorithm is based on the adaptive subdivision of the viewing frustrum into smaller cells. An estimate for the variation of the implicit function inside each cell is obtained with an affine arithmetic range estimation technique. Overall, we show that our progressive refinement approach not only provides the user with visual feedback as the rendering advances but is also capable of completing the image faster than a conventional implicit surface rendering algorithm based on ray casting

The orbit rigidity matrix of a symmetric framework

A number of recent papers have studied when symmetry causes frameworks on a graph to become infinitesimally flexible, or stressed, and when it has no impact. A number of other recent papers have studied special classes of frameworks on generically rigid graphs which are finite mechanisms. Here we introduce a new tool, the orbit matrix, which connects these two areas and provides a matrix representation for fully symmetric infinitesimal flexes, and fully symmetric stresses of symmetric frameworks. The orbit matrix is a true analog of the standard rigidity matrix for general frameworks, and its analysis gives important insights into questions about the flexibility and rigidity of classes of symmetric frameworks, in all dimensions. With this narrower focus on fully symmetric infinitesimal motions, comes the power to predict symmetry-preserving finite mechanisms - giving a simplified analysis which covers a wide range of the known mechanisms, and generalizes the classes of known mechanisms. This initial exploration of the properties of the orbit matrix also opens up a number of new questions and possible extensions of the previous results, including transfer of symmetry based results from Euclidean space to spherical, hyperbolic, and some other metrics with shared symmetry groups and underlying projective geometry.Comment: 41 pages, 12 figure

Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors

The peptidergic system is the most abundant network of ligand-receptor-mediated signaling in humans. However, the physiological roles remain elusive for numerous peptides and more than 100 G protein-coupled receptors (GPCRs). Here we report the pairing of cognate peptides and receptors. Integrating comparative genomics across 313 species and bioinformatics on all protein sequences and structures of human class A GPCRs, we identify universal characteristics that uncover additional potential peptidergic signaling systems. Using three orthogonal biochemical assays, we pair 17 proposed endogenous ligands with five orphan GPCRs that are associated with diseases, including genetic, neoplastic, nervous and reproductive system disorders. We also identify additional peptides for nine receptors with recognized ligands and pathophysiological roles. This integrated computational and multifaceted experimental approach expands the peptide-GPCR network and opens the way for studies to elucidate the roles of these signaling systems in human physiology and disease. Video Abstract: Features learned from comparative sequence and structural analyses enabled prediction of peptide ligands for orphan GPCRs that, when coupled with functional validation, expose physiologically relevant signaling systems. © 2019 The Author(s

Collisionless and hydrodynamic excitations of trapped boson-fermion mixtures

Within a scaling ansatz formalism plus Thomas-Fermi approximation, we investigate the collective excitations of a harmonically trapped boson-fermion mixture in the collisionless and hydrodynamic limit at low temperature. Both the monopole and quadrupole modes are considered in the presence of spherical as well as cylindrically symmetric traps. In the spherical traps, the frequency of monopole mode coincides in the collisionless and hydrodynamic regime, suggesting that it might be undamped in all collisional regimes. In contrast, for the quadrupole mode, the frequency differs largely in these two limits. In particular, we find that in the hydrodynamic regime the quadrupole oscillations with equal bosonic and fermionic amplitudes generate an exact eigenstate of the system, regardless of the boson-fermion interaction. This resembles the Kohn mode for the dipole excitation. We discuss in some detail the behavior of monopole and quadrupole modes as a function of boson-fermion coupling at different boson-boson interaction strength. Analytic solutions valid at weak and medium fermion-boson coupling are also derived and discussed.Comment: 29 pages + 7 figures, resubmitted to Physical Review

Resposta da produtividade de grãos e outras características agronômicas do trigo EMBRAPA-22 irrigado ao nitrogênio em cobertura

As doses e a época de aplicação do nitrogênio (N) podem influenciar as características agronômicas do trigo (Triticum aestivum L.) irrigado e, conseqüentemente, a produtividade de grãos. Neste sentido, foram instalados dois experimentos na Estação Experimental da Universidade Federal de Viçosa, localizada em Coimbra (MG), em 1995 e 1996. Os tratamentos foram constituídos pela combinação de quatro doses de N (30, 60, 90 e 120 kg ha-1), quatro formas de parcelamento (dose total aos 20 dias da emergência (DAE); ½ aos 20 + ½ aos 40 DAE; 1/3 aos 20 + 2/3 aos 40 DAE e 2/3 aos 20 + 1/3 aos 40 DAE) e uma testemunha (sem N em cobertura), dispostos em esquema fatorial 4 x 4 + 1, no delineamento em blocos casualizados com quatro repetições. A altura e o acamamento das plantas, a biomassa seca, o índice de colheita, a massa de mil grãos, o peso hectolítrico e a produtividade de grãos foram influenciados pelas doses de N. Em 1996, o número de espigas por metro quadrado e o número de perfilhos férteis por planta diminuíram, em conseqüência do acamamento precoce das plantas, enquanto o número de grãos por espiga e o número de grãos por metro quadrado aumentaram com o incremento nas doses de N. As formas de parcelamento influenciaram somente o acamamento das plantas

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions