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41.
Sydney Smith 《BMJ (Clinical research ed.)》1951,1(4707):599-607
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T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains–NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains. 相似文献
45.
Gerald Houghton 《Bulletin of mathematical biology》1969,31(2):275-293
A Lie-topology of human behavior has been generated in terms of a group of continuous transformations in multidimensional
reactivity-adaptability coordinates, connections between the conscious and unconscious surfaces being made through a finite
number of interpretive parameters. Neuroses and personality disorders are mathematically classified in terms of pure rotation
groups, while reactive depressions and reactive manias fall into the category of dilation groups. The distortions, exaggerations
and multiply-fragmented behaviors characteristic of psychoses are explained and classified by combined rotation-dilation Lie
groups that can include both real and imaginary parameters. Neurobiophysical implications of the Lie topology are mentioned
in relation to abnormal reaction formations and behavioral complexes that may be environmental or organic in origin. 相似文献
46.
Richard A. Houghton 《Global Change Biology》2020,26(5):3006-3014
The Global Carbon Project (GCP) has published global carbon budgets annually since 2007 (Canadell et al. [2007], Proc Natl Acad Sci USA, 104, 18866–18870; Raupach et al. [2007], Proc Natl Acad Sci USA, 104, 10288–10293). There are many scientists involved, but the terrestrial fluxes that appear in the budgets are not well understood by ecologists and biogeochemists outside of that community. The purpose of this paper is to make the terrestrial fluxes of carbon in those budgets more accessible to a broader community. The GCP budget is composed of annual perturbations from pre‐industrial conditions, driven by addition of carbon to the system from combustion of fossil fuels and by transfers of carbon from land to the atmosphere as a result of land use. The budget includes a term for each of the major fluxes of carbon (fossil fuels, oceans, land) as well as the rate of carbon accumulation in the atmosphere. Land is represented by two terms: one resulting from direct anthropogenic effects (Land Use, Land‐Use Change, and Forestry or land management) and one resulting from indirect anthropogenic (e.g., CO2, climate change) and natural effects. Each of these two net terrestrial fluxes of carbon, in turn, is composed of opposing gross emissions and removals (e.g., deforestation and forest regrowth). Although the GCP budgets have focused on the two net terrestrial fluxes, they have paid little attention to the gross components, which are important for a number of reasons, including understanding the potential for land management to remove CO2 from the atmosphere and understanding the processes responsible for the sink for carbon on land. In contrast to the net fluxes of carbon, which are constrained by the global carbon budget, the gross fluxes are largely unconstrained, suggesting that there is more uncertainty than commonly believed about how terrestrial carbon emissions will respond to future fossil fuel emissions and a changing climate. 相似文献
47.
Danalyn R Holmes Melissa Bredow Kathrin Thor Sydney A Pascetta Irina Sementchoukova Kristen R Siegel Cyril Zipfel Jacqueline Monaghan 《Genetics》2021,217(4)
Immune recognition in plants is governed by two major classes of receptors: pattern recognition receptors (PRRs) and nucleotide-binding leucine-rich repeat receptors (NLRs). Located at the cell surface, PRRs bind extracellular ligands originating from microbes (indicative of “non-self”) or damaged plant cells (indicative of “infected-self”), and trigger signaling cascades to protect against infection. Located intracellularly, NLRs sense pathogen-induced physiological changes and trigger localized cell death and systemic resistance. Immune responses are under tight regulation in order to maintain homeostasis and promote plant health. In a forward-genetic screen to identify regulators of PRR-mediated immune signaling, we identified a novel allele of the membrane-attack complex and perforin (MACPF)-motif containing protein CONSTITUTIVE ACTIVE DEFENSE 1 (CAD1) resulting from a missense mutation in a conserved N-terminal cysteine. We show that cad1-5 mutants display deregulated immune signaling and symptoms of autoimmunity dependent on the lipase-like protein ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), suggesting that CAD1 integrity is monitored by the plant immune system. We further demonstrate that CAD1 localizes to both the cytosol and plasma membrane using confocal microscopy and subcellular fractionation. Our results offer new insights into immune homeostasis and provide tools to further decipher the intriguing role of MACPF proteins in plants. 相似文献
48.
Sarah Findakly Vikas Daggubati Galo Garcia III Sydney A. LaStella Abrar Choudhury Cecilia Tran Amy Li Pakteema Tong Jason Q. Garcia Natasha Puri Jeremy F. Reiter Libin Xu David R. Raleigh 《The Journal of cell biology》2021,220(1)
Vertebrate Hedgehog signals are transduced through the primary cilium, a specialized lipid microdomain that is required for Smoothened activation. Cilia-associated sterol and oxysterol lipids bind to Smoothened to activate the Hedgehog pathway, but how ciliary lipids are regulated is incompletely understood. Here we identified DHCR7, an enzyme that produces cholesterol, activates the Hedgehog pathway, and localizes near the ciliary base. We found that Hedgehog stimulation negatively regulates DHCR7 activity and removes DHCR7 from the ciliary microenvironment, suggesting that DHCR7 primes cilia for Hedgehog pathway activation. In contrast, we found that Hedgehog stimulation positively regulates the oxysterol synthase CYP7A1, which accumulates near the ciliary base and produces oxysterols that promote Hedgehog signaling in response to pathway activation. Our results reveal that enzymes involved in lipid biosynthesis in the ciliary microenvironment promote Hedgehog signaling, shedding light on how ciliary lipids are established and regulated to transduce Hedgehog signals. 相似文献
49.
Natasha D. Phillips Amy Garbett Daniel Wise Sophie L. Loca Olivia Daly Lawrence E. Eagling Jonathan D. R. Houghton Peter Verhoog James Thorburn Patrick C. Collins 《Journal of fish biology》2021,99(4):1492-1496
Essential fish habitats (EFHs) are critical for fish life-history events, including spawning, breeding, feeding or growth. This study provides evidence of EFHs for the critically endangered flapper skate (Dipturus intermedius) in the waters around the Orkney Isles, Scotland, based on citizen-science observation data. The habitats of potential egg-laying sites were parametrised as >20 m depth, with boulders or exposed bedrock, in moderate current flow (0.3–2.8 knots) with low sedimentation. This information provides a significant contribution to the understanding of EFHs for flapper skate. 相似文献
50.
Abstract The ability of mature, freeze‐thawed bovine sperm to bind exogenous end‐labelled or oligo‐labelled λ Hind III DNA restriction fragments was examined. Following 30 min. incubation of bovine sperm with P32 end‐labelled λ Hind III DNA and five washes with medium, approximately 5.8 ng DNA were bound to 107 sperm. Agarose gel autoradiography revealed that all of the λ Hind III DNA bands were present following sperm washes except for the smaller 0.5 Kb and 0.125 Kb bands. Incubation of sperm with 3H oligo‐labelled λ Hind III DNA gave a much higher level of binding (138 ng/107 sperm) than that found with end‐labelled DNA. This binding was entirely eliminated by DNase I. The separation of live and dead sperm fractions on Percoll gradients revealed that more oligo‐labelled λ Hind III DNA was found to be associated with the dead sperm fraction (31.2 ng/107 sperm) rather than the live sperm fraction (2.7 ng/107 sperm). Analysis of supravital stained, light microscopic autoradiographs confirmed that oligo‐labelled λ Hind III DNA bound to dead sperm in the post‐acrosomal region of the sperm head although other minor distribution patterns were observed. 相似文献