Algebraic Properties of Riemannian Manifolds

Algebraic properties are explored for the curvature tensors of Riemannian manifolds, using the irreducible decomposition of curvature tensors. Our method provides a powerful tool to analyze the irreducible basis as well as an algorithm to determine the linear dependence of arbitrary Riemann polynomials. We completely specify 13 independent basis elements for the quartic scalars and explicitly find 13 linear relations among 26 scalar invariants. Our method provides several completely new results, including some clues to identify 23 independent basis elements from 90 quintic scalars, that are difficult to find otherwise.Comment: A few typos corrected; 40 pages (4 appendices: 16 pages). To appear in General Relativity and Gravitatio

Beclin 1 functions as a negative modulator of MLKL oligomerisation by integrating into the necrosome complex

Necroptosis is a form of regulated cell death caused by formation of the necrosome complex. However, the factors modulating this process and the systemic pathophysiological effects of necroptosis are yet to be understood. Here, we identified that Beclin 1 functions as an anti-necroptosis factor by being recruited into the necrosome complex upon treatment with TNF alpha, Smac mimetic, and pan-caspase inhibitor and by repressing MLKL oligomerisation, thus preventing the disruption of the plasma membrane. Cells ablated or knocked-out for Beclin 1 become sensitised to necroptosis in an autophagy-independent manner without affecting the necrosome formation itself. Interestingly, the recruitment of Beclin 1 into the necrosome complex is dependent on the activation and phosphorylation of MLKL. Biochemically, the coiled-coil domain (CCD) of Beclin 1 binds to the CCD of MLKL, which restrains the oligomerisation of phosphorylated MLKL. Finally, Beclin 1 depletion was found to promote necroptosis in leukaemia cells and enhance regression of xenografted-tumour upon treatment with Smac mimetics and caspase inhibitors. These results suggest that Beclin 1 functions as a negative regulator in the execution of necroptosis by suppressing MLKL oligomerisation

Dual Fistulas of Ascending Aorta and Coronary Artery to Pulmonary Artery

Coronary artery fistula to pulmonary artery is common. However, to the best of our knowledge, a case of coronary artery fistula to pulmonary artery associated with aortopulmonary fistula remains unreported. We herein report a 64-year-old female with a left anterior descending coronary artery and ascending aorta to pulmonary artery fistulas, and conduct a brief review of the literature

Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities

Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3–mediated ICAD cleavage. Overexpressed CIIA reduces H2O2- and tumor necrosis factor-α–induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1- and CAD-mediated signaling

Clinical characteristics of children with 2009 pandemic influenza A (H1N1) admitted in a single institution

PurposeThis study aims to investigate the clinical characteristics of children diagnosed with the novel influenza A (H1N1) in the winter of 2009 at a single medical institution.MethodsOut of 545 confirmed cases of influenza A (H1N1) in children, using the real time RT-PCR method at Kosin University Gospel Hospital from September to December of 2009, 149 patients and their medical records were reviewed in terms of symptoms, laboratory findings, complications and transmission within a family.ResultsMedian age of subjects was 7 years (range: 2 months-18 years). New cases increased rapidly from September to reach a peak in November, then declined rapidly. Most frequently observed symptoms were fever (96.7%), cough (73.2%), rhinorrhea (36.9%) and sore throat (31.5%). Average body temperatures on the 1st, 2nd and 3rd hospital day were 38.75±0.65℃, 38.08±0.87℃ and 37.51±0.76℃, respectively. Complete blood counts and biochemical tests performed on the first admission day showed within the reference values in most cases. Of the 82 patients with simple chest radiography, 18 (22%) had pneumonic lesions; multi-focal bronchopneumonia in eleven, single or multi-segmental lobar pneumonia in five, and diffuse interstitial pneumonia in two patients. All of the 149 patients improved from their symptoms and discharged within 9 days of admission without any late complication.ConclusionChildren with 2009 pandemic influenza A (H1N1) at our single institution displayed nonspecific symptoms and laboratory findings, resembling those of common viral respiratory illnesses, and did not appear to develop more severe disease

Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation

The underlying mechanism of necroptosis in relation to cancer is still unclear. Here, MYC, a potent oncogene, is an antinecroptotic factor that directly suppresses the formation of the RIPK1-RIPK3 complex. Gene set enrichment analyses reveal that the MYC pathway is the most prominently down-regulated signaling pathway during necroptosis. Depletion or deletion of MYC promotes the RIPK1-RIPK3 interaction, thereby stabilizing the RIPK1 and RIPK3 proteins and facilitating necroptosis. Interestingly, MYC binds to RIPK3 in the cytoplasm and inhibits the interaction between RIPK1 and RIPK3 in vitro. Furthermore, MYC-nick, a truncated form that is mainly localized in the cytoplasm, prevented TNF-induced necroptosis. Finally, down-regulation of MYC enhances necroptosis in leukemia cells and suppresses tumor growth in a xenograft model upon treatment with birinapant and emricasan. MYC-mediated suppression of necroptosis is a mechanism of necroptosis resistance in cancer, and approaches targeting MYC to induce necroptosis represent an attractive therapeutic strategy for cancer

Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter

Two major isoforms of the Runx2 gene are expressed by alternative promoter usage: Runx2 type I (Runx2-I) is derived from the proximal promoter (P2), and Runx2 type II (Runx2-II) is produced by the distal promoter (P1). Our previous results indicate that Dlx5 mediates BMP-2-induced Runx2 expression and osteoblast differentiation (Lee, M.-H., Kim, Y-J., Kim, H-J., Park, H-D., Kang, A-R., Kyung, H.-M., Sung, J-H., Wozney, J. M., Kim, H-J., and Ryoo, H-M. (2003) J. Biol. Chem. 278, 34387–34394). However, little is known of the molecular mechanisms by which Dlx5 up-regulates Runx2 expression in BMP-2 signaling. Here, Runx2-II expression was found to be specifically stimulated by BMP-2 treatment or by Dlx5 overexpression. In addition, BMP-2, Dlx5, and Runx2-II were found to be expressed in osteogenic fronts and parietal bones of the developing cranial vault and Runx2-I and Msx2 in the sutural mesenchyme. Furthermore, Runx2 P1 promoter activity was strongly stimulated by Dlx5 overexpression, whereas Runx2 P2 promoter activity was not. Runx2 P1 promoter deletion analysis indicated that the Dlx5-specific response is due to sequences between 756 and 342 bp of the P1 promoter, where three Dlx5-response elements are located. Dlx5 responsiveness to these elements was confirmed by gel mobility shift assay and site-directed mutagenesis. Moreover, Msx2 specifically suppressed the Runx2 P1 promoter, and the responsible region overlaps with that recognized by Dlx5. In summary, Dlx5 specifically transactivates the Runx2 P1 promoter, and its action on the P1 promoter is antagonized by Msx2.This work was supported by Grants 01-PJ1-PG1-01CH08-0001 and 01-PJ3-PG6- 01GN11-0002 from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

Disruption of nucleocytoplasmic trafficking as a cellular senescence driver

Senescent cells exhibit a reduced response to intrinsic and extrinsic stimuli. This diminished reaction may be explained by the disrupted transmission of nuclear signals. However, this hypothesis requires more evidence before it can be accepted as a mechanism of cellular senescence. A proteomic analysis of the cytoplasmic and nuclear fractions obtained from young and senescent cells revealed disruption of nucleocytoplasmic trafficking (NCT) as an essential feature of replicative senescence (RS) at the global level. Blocking NCT either chemically or genetically induced the acquisition of an RS-like senescence phenotype, named nuclear barrier-induced senescence (NBIS). A transcriptome analysis revealed that, among various types of cellular senescence, NBIS exhibited a gene expression pattern most similar to that of RS. Core proteomic and transcriptomic patterns common to both RS and NBIS included upregulation of the endocytosis-lysosome network and downregulation of NCT in senescent cells, patterns also observed in an aging yeast model. These results imply coordinated aging-dependent reduction in the transmission of extrinsic signals to the nucleus and in the nucleus-to-cytoplasm supply of proteins/RNAs. We further showed that the aging-associated decrease in Sp1 transcription factor expression was critical for the downregulation of NCT. Our results suggest that NBIS is a modality of cellular senescence that may represent the nature of physiological aging in eukaryotes. © 2021, The Author(s).1

The JCMT BISTRO Survey: A Spiral Magnetic Field in a Hub-filament Structure, Monoceros R2

We present and analyze observations of polarized dust emission at 850 μm toward the central 1 7 1 pc hub-filament structure of Monoceros R2 (Mon R2). The data are obtained with SCUBA-2/POL-2 on the James Clerk Maxwell Telescope (JCMT) as part of the B-fields in Star-forming Region Observations survey. The orientations of the magnetic field follow the spiral structure of Mon R2, which are well described by an axisymmetric magnetic field model. We estimate the turbulent component of the magnetic field using the angle difference between our observations and the best-fit model of the underlying large-scale mean magnetic field. This estimate is used to calculate the magnetic field strength using the Davis–Chandrasekhar–Fermi method, for which we also obtain the distribution of volume density and velocity dispersion using a column density map derived from Herschel data and the C18O (J = 3 - 2) data taken with HARP on the JCMT, respectively. We make maps of magnetic field strengths and mass-to-flux ratios, finding that magnetic field strengths vary from 0.02 to 3.64 mG with a mean value of 1.0 \ub1 0.06 mG, and the mean critical mass-to-flux ratio is 0.47 \ub1 0.02. Additionally, the mean Alfv\ue9n Mach number is 0.35 \ub1 0.01. This suggests that, in Mon R2, the magnetic fields provide resistance against large-scale gravitational collapse, and the magnetic pressure exceeds the turbulent pressure. We also investigate the properties of each filament in Mon R2. Most of the filaments are aligned along the magnetic field direction and are magnetically subcritical