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

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Growth regulator on oat yield indicators

ABSTRACT Growth regulator in oat can reduce lodging with effects on yield indicators. The objective of the study is to define the optimum dose of growth regulator to reduce lodging in oats under different conditions of nitrogen (N) fertilization (reduced, high and very high) and the effects on yield indicators in the succession systems. In each succession system (soybean/oats and corn/oats), two experiments were conducted, one to quantify biomass yield and the other to estimate grain yield and lodging. In the four experiments, the design was randomized blocks with four replicates in 3 x 4 factorial scheme, for N-fertilizer doses (30, 90 and 150 kg ha-1) and growth regulator doses (0, 200, 400 and 600 mL ha-1), respectively. Growth regulator reduces lodging in oat plants, with the ideal doses of 500 mL ha-1 in the soybean/oat system and 400 mL ha-1 in the corn/oat system, regardless of the reduced, high and very high N doses. There is a linear reduction of biological and straw yields, and a quadratic trend in the expression of grain yield and harvest index as a function of the growth regulator doses, regardless of succession systems (soybean/oats and corn/oats)

Simulation of wheat biomass yield by thermal time, rainfall and nitrogen

ABSTRACT Wheat biomass yield focused on the production of quality silage is dependent on rainfall, temperature and nitrogen (N). The objective of the study was to validate the use of rainfall, thermal time and N as potential variables for the composition of the multiple linear regression model and simulation of wheat biomass yield for silage production under N supply conditions during the cycle, in the systems of succession. The study was conducted in 2012, 2013 and 2014, in randomized blocks with four replicates in 4 x 3 factorial, for N-fertilizer doses (0, 30, 60, 120 kg ha-1) and forms of N supply [single application (100%) in the stage V3 (third expanded leaf); split application (70%/30%) in the stages V3/V6 (third and sixth expanded leaves); split application (70%/30%) in the stages V3/E (third expanded leaf and beginning of grain filling)], respectively, in the systems soybean/wheat and maize/wheat. Rainfall and N are potential variables in the composition of the multiple linear regression model. Multiple linear regression models are efficient in the simulation of wheat biomass yield for silage under the N supply conditions during the cycle in the succession systems

Growth regulator on oat yield indicators

<div><p>ABSTRACT Growth regulator in oat can reduce lodging with effects on yield indicators. The objective of the study is to define the optimum dose of growth regulator to reduce lodging in oats under different conditions of nitrogen (N) fertilization (reduced, high and very high) and the effects on yield indicators in the succession systems. In each succession system (soybean/oats and corn/oats), two experiments were conducted, one to quantify biomass yield and the other to estimate grain yield and lodging. In the four experiments, the design was randomized blocks with four replicates in 3 x 4 factorial scheme, for N-fertilizer doses (30, 90 and 150 kg ha-1) and growth regulator doses (0, 200, 400 and 600 mL ha-1), respectively. Growth regulator reduces lodging in oat plants, with the ideal doses of 500 mL ha-1 in the soybean/oat system and 400 mL ha-1 in the corn/oat system, regardless of the reduced, high and very high N doses. There is a linear reduction of biological and straw yields, and a quadratic trend in the expression of grain yield and harvest index as a function of the growth regulator doses, regardless of succession systems (soybean/oats and corn/oats).</p></div

Simulation of wheat biomass yield by thermal time, rainfall and nitrogen

<div><p>ABSTRACT Wheat biomass yield focused on the production of quality silage is dependent on rainfall, temperature and nitrogen (N). The objective of the study was to validate the use of rainfall, thermal time and N as potential variables for the composition of the multiple linear regression model and simulation of wheat biomass yield for silage production under N supply conditions during the cycle, in the systems of succession. The study was conducted in 2012, 2013 and 2014, in randomized blocks with four replicates in 4 x 3 factorial, for N-fertilizer doses (0, 30, 60, 120 kg ha-1) and forms of N supply [single application (100%) in the stage V3 (third expanded leaf); split application (70%/30%) in the stages V3/V6 (third and sixth expanded leaves); split application (70%/30%) in the stages V3/E (third expanded leaf and beginning of grain filling)], respectively, in the systems soybean/wheat and maize/wheat. Rainfall and N are potential variables in the composition of the multiple linear regression model. Multiple linear regression models are efficient in the simulation of wheat biomass yield for silage under the N supply conditions during the cycle in the succession systems.</p></div