It is notable that along the N=Z line in the nuclear chart, extremely large collectivity emerges suddenly in the mass-80 region. By applying the Monte Carlo shell model (MCSM) and the ...Hartree-Fock-Bogolyubov plus generator coordinate method (HFB+gcm), we study this problem to find the origin. On the basis that both calculations reproduce the experimental data of the N≈Z nuclei with A=64∼88, we identify the backbone from full shell-model calculations that can explain the strong prolate deformation. We find that inclusion of the 2d5/2 orbit in the model space to cooperate with 1g9/2 is the key ingredient to describe the rapid increase of collectivity from 70Se to 76Sr and to produce the observed large B(E2) values in 76Sr, 78Sr and 80Zr. The quadrupole-quadrupole (QQ) interaction acting between the quasi-SU(3) partner orbits, 1g9/2−2d5/2, is the driving force that changes the nuclear shape from oblate- to prolate-deformed. We further suggest that the quasi-SU(3) effect is particularly amplified in the N≈Z nuclei because these are the unique examples where quasi-SU(3) partner orbits can be formed, like the nuclear pairing, simultaneously in three different types: neutron-neutron (n-n), proton-proton (p-p), and neutron-proton (n-p), which respectively interact through the n-n, p-p, and n-p components of the QQ force to enhance the quadrupole collectivity coherently.
Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes ...from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14
+
cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.
The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1
. Deficiency in the LUBAC ...components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death
. In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype
. Here we show, by creating HOIL-1-deficient mice, that HOIL-1 is as essential for LUBAC function as HOIP, albeit for different reasons: whereas HOIP is the catalytically active component of LUBAC, HOIL-1 is required for LUBAC assembly, stability and optimal retention in the TNFR1 signalling complex, thereby preventing aberrant cell death. Both HOIL-1 and HOIP prevent embryonic lethality at mid-gestation by interfering with aberrant TNFR1-mediated endothelial cell death, which only partially depends on RIPK1 kinase activity. Co-deletion of caspase-8 with RIPK3 or MLKL prevents cell death in Hoil-1
(also known as Rbck1
) embryos, yet only the combined loss of caspase-8 with MLKL results in viable HOIL-1-deficient mice. Notably, triple-knockout Ripk3
Casp8
Hoil-1
embryos die at late gestation owing to haematopoietic defects that are rescued by co-deletion of RIPK1 but not MLKL. Collectively, these results demonstrate that both HOIP and HOIL-1 are essential LUBAC components and are required for embryogenesis by preventing aberrant cell death. Furthermore, they reveal that when LUBAC and caspase-8 are absent, RIPK3 prevents RIPK1 from inducing embryonic lethality by causing defects in fetal haematopoiesis.
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