TIR domains of plant immune receptors are NAD+-cleaving enzymes that promote cell death

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors activate cell death and confer disease resistance by unknown mechanisms. We demonstrate that plant Toll/interleukin-1 receptor (TIR) domains of NLRs are enzymes capable of degrading nicotinamide adenine dinucleotide in its oxidized form (NAD+). Both cell death induction and NAD+ cleavage activity of plant TIR domains require known self-association interfaces and a putative catalytic glutamic acid that is conserved in both bacterial TIR NAD+-cleaving enzymes (NADases) and the mammalian SARM1 (sterile alpha and TIR motif containing 1) NADase. We identify a variant of cyclic adenosine diphosphate ribose as a biomarker of TIR enzymatic activity. TIR enzymatic activity is induced by pathogen recognition and functions upstream of the genes enhanced disease susceptibility 1 (EDS1) and N requirement gene 1 (NRG1), which encode regulators required for TIR immune function. Thus, plant TIR-NLR receptors require NADase function to transduce recognition of pathogens into a cell death response

APEX and NOEMA observations of H2S in nearby luminous galaxies and the ULIRG Mrk 231: a possible relation between dense gas properties and molecular outflows

Galaxie

A multi-model approach to X-ray pulsars: Connecting spectral and timing models to pin down the intrinsic emission characteristics of magnetized, accreting neutron stars

The emission characteristics of X-ray pulsars are governed by magnetospheric accretion within the Alfvén radius, leading to a direct coupling of accretion column properties and interactions at the magnetosphere. The complexity of the physical processes governing the formation of radiation within the accreted, strongly magnetized plasma has led to several sophisticated theoretical modelling efforts over the last decade, dedicated to either the formation of the broad band continuum, the formation of cyclotron resonance scattering features (CRSFs) or the formation of pulse profiles. While these individual approaches are powerful in themselves, they quickly reach their limits when aiming at a quantitative comparison to observational data. Too many fundamental parameters, describing the formation of the accretion columns and the systems' overall geometry are unconstrained and different models are often based on different fundamental assumptions, while everything is intertwined in the observed, highly phase-dependent spectra and energy-dependent pulse profiles. To name just one example: the (phase variable) line width of the CRSFs is highly dependent on the plasma temperature, the existence of B-field gradients (geometry) and observation angle, parameters which, in turn, drive the continuum radiation and are driven by the overall two-pole geometry for the light bending model respectively. This renders a parallel assessment of all available spectral and timing information by a compatible across-models-approach indispensable. In a collaboration of theoreticians and observers, we have been working on a model unification project over the last years, bringing together theoretical calculations of the Comptonized continuum, Monte Carlo simulations and Radiation Transfer calculations of CRSFs as well as a General Relativity (GR) light bending model for ray tracing of the incident emission pattern from both magnetic poles. The ultimate goal is to implement a unified fitting model for phase-resolved spectral and timing data analysis. We present the current status of this project

UV/IR Mixing and Anomalies in Noncommutative Gauge Theories

Using path integral method (Fujikawa's method) we calculate anomalies in noncommutative gauge theories with fermions in the bi-fundamental and adjoint representations. We find that axial and chiral gauge anomalies coming from non-planar contributions are derived in the low noncommutative momentum limit $\widetilde{p}^{\mu}(\equiv \theta^{\mu\nu}p_{\nu}) \to 0$. The adjoint chiral fermion carries no anomaly in the non-planar sector in $D=4k (k=1,2,...,)$ dimensions. It is naturally shown from the path integral method that anomalies in non-planar sector originate in UV/IR mixing.Comment: 15 pages, no figures, LaTeX, minor corrections and references adde

A Species-Wide Inventory of NLR Genes and Alleles in Arabidopsis thaliana

Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consistent with extensive balancing and positive selection, NLRs are encoded by one of the most variable gene families in plants, but the true extent of intraspecific NLR diversity has been unclear. Here, we define a nearly complete species-wide pan-NLRome in Arabidopsis thaliana based on sequence enrichment and long-read sequencing. The pan-NLRome largely saturates with approximately 40 well-chosen wild strains, with half of the pan-NLRome being present in most accessions. We chart NLR architectural diversity, identify new architectures, and quantify selective forces that act on specific NLRs and NLR domains. Our study provides a blueprint for defining pan-NLRomes. In plants, NLR proteins are important intracellular receptors with roles in innate immunity and disease resistance. This work provides a panoramic view of this diverse and complicated gene family in the model species A. thaliana and provides a foundation for the identification and functional study of disease-resistance genes in agronomically important species with complex genomes

Concerted Action of Evolutionarily Ancient and Novel SNARE Complexes in Flowering-Plant Cytokinesis

Membrane vesicles delivered to the cell-division plane fuse with one another to form the partitioning membrane during plant cytokinesis, starting in the cell center. In Arabidopsis, this requires SNARE complexes involving the cytokinesis-specific Qa-SNARE KNOLLE. However, cytokinesis still occurs in knolle mutant embryos, suggesting contributions from KNOLLE-independent SNARE complexes. Here we show that Qa-SNARE SYP132, having counterparts in lower plants, functionally overlaps with the flowering plant-specific KNOLLE. SYP132 mutation causes cytokinesis defects, knolle syp132 double mutants consist of only one or a few multi-nucleate cells, and SYP132 has the same SNARE partners as KNOLLE. SYP132 and KNOLLE also have non-overlapping functions in secretion and in cellularization of the embryo-nourishing endosperm resulting from double fertilization unique to flowering plants. Evolutionarily ancient non-specialized SNARE complexes originating in algae were thus amended by the appearance of cytokinesis-specific SNARE complexes, meeting the high demand for membrane-fusion capacity during endosperm cellularization in angiosperms. In plant cytokinesis, SNARE complexes mediate vesicle fusion for partitioning membrane formation. Park et al. show that evolutionarily ancient Qa-SNARE SYP132 functionally overlaps with flowering plant- and cytokinesis-specific Qa-SNARE KNOLLE. KNOLLE acquisition may have been due to high demand for membrane-fusion capacity during endosperm cellularization in flowering plants

Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration

Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (p_T), elliptic flow, two-particle correlations, non-statistical fluctuations, and suppression of particle production at high p_T. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted to Nuclear Physics A as a regular article; v3 has minor changes in response to referee comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer