Caspase-1 activates gasdermin A in non-mammals

Gasdermins oligomerize to form pores in the cell membrane, causing regulated lytic cell death called pyroptosis. Mammals encode five gasdermins that can trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of and activate GSDMB, C, D, and E, but no endogenous activation pathways are yet known for GSDMA. Here, we perform a comprehensive evolutionary analysis of the gasdermin family. A gene duplication of GSDMA in the common ancestor of caecilian amphibians, reptiles, and birds gave rise to GSDMA-D in mammals. Uniquely in our tree, amphibian, reptile, and bird GSDMA group in a separate clade than mammal GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in the linker. We show that GSDMA from birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with the GSDMD C-terminal domain to confer the specificity of this interaction, whereas we show that bird caspase-1 uses a stereotypical tetrapeptide sequence to confer specificity for bird GSDMA. Our results reveal an evolutionarily stable association between caspase-1 and the gasdermin family, albeit a shifting one. Caspase-1 repeatedly changes its target gasdermin over evolutionary time at speciation junctures, initially cleaving GSDME in fish, then GSDMA in amphibians/reptiles/birds, and finally GSDMD in mammals

Association of Adherence to a Healthy Diet with Cognitive Decline in European and American Older Adults

Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged ≥ 55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action[SENECA], Rotterdam Study [RS], Nurses’ Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI –0.01, 0.02) in NHS, 0.00 (95% CI –0.02, 0.01) in RS, and 0.00 (95% CI –0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI –0.01, 0.01), I 2 = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity

Production of Υ(nS) mesons in Pb+Pb and pp collisions at 5.02 TeV

A measurement of the production of vector bottomonium states, Υ ( 1S ) , Υ ( 2S ) , and Υ ( 3S ) , in Pb + Pb and p p collisions at a center-of-mass energy per nucleon pair of 5.02 TeV is presented. The data correspond to integrated luminosities of 1.38 nb − 1 of Pb + Pb data collected in 2018, 0.44 nb − 1 of Pb + Pb data collected in 2015, and 0.26 fb − 1 of p p data collected in 2017 by the ATLAS detector at the Large Hadron Collider. The measurements are performed in the dimuon decay channel for transverse momentum p μ μ T < 30 GeV , absolute rapidity | y μ μ | < 1.5 , and Pb + Pb event centrality 0–80%. The production rates of the three bottomonium states in Pb + Pb collisions are compared with those in p p collisions to extract the nuclear modification factors as functions of event centrality, p μ μ T , and | y μ μ | . In addition, the suppression of the excited states relative to the ground state is studied. The results are compared with theoretical model calculations

Spin and anion dynamics on (TMTSF)2{_{2}}FSO3{_{3}}, studied by NMR

In order to characterise the electronic properties in sub-phases of (TMTSF)$_{2}$FSO$_{3}$ under pressure, $^{77}$Se, and $^{19}$F NMR Knight shift ($K)$ and relaxation rate (1/$T_{1})$ measurements were performed at ambient and 0.82 GPa pressure. The insulating phase below the metal-insulator transition (MIT) at 89 K at ambient pressure (AP) was confirmed as a nonmagnetic state with a gap of $\Delta$/$k_{B}\sim 420$ K. This MIT is strongly coupled with anion ordering. The MIT temperature decreases under pressure, and many electronic anomalies (or transitions) have been observed from transport measurements. The reduction of density of states in the metallic state by applying pressure was confirmed by the analysis of $K$ and Korringa constant (1/$T_{1}T)$. A nonmagnetic insulating transition corresponding to the MIT at AP at 89 K, was observed at $\sim$45 K at 0.82 GPa. A spin (charge) gap in the insulating state at 0.82 GPa is smaller ($\Delta$/$k_{B}\sim 90$ K) than that at AP. Key words. metal insulator transition – NMR