An Unusual 500,000 Bases Long Oscillation of Guanine and Cytosine Content in Human Chromosome 21

An oscillation with a period of around 500 kb in guanine and cytosine content (GC%) is observed in the DNA sequence of human chromosome 21. This oscillation is localized in the rightmost one-eighth region of the chromosome, from 43.5 Mb to 46.5 Mb. Five cycles of oscillation are observed in this region with six GC-rich peaks and five GC-poor valleys. The GC-poor valleys comprise regions with low density of CpG islands and, alternating between the two DNA strands, low gene density regions. Consequently, the long-range oscillation of GC% result in spacing patterns of both CpG island density, and to a lesser extent, gene densities.Comment: 15 pages (figures included), 5 figure

Magnetic-Field-Induced Antiferromagnetism in Two-Dimensional Hubbard Model: Analysis of CeRhIn5_5

We propose the mechanism for the magnetic-field-induced antiferromagnetic (AFM) state in a two-dimensional Hubbard model in the vicinity of the AFM quantum critical point (QCP), using the fluctuation-exchange (FLEX) approximation by taking the Zeeman energy due to the magnetic field $B$ into account. In the vicinity of the QCP, we find that the AFM correlation perpendicular to $B$ is enhanced, whereas that parallel to $B$ is reduced. This fact means that the finite magnetic field increases $T_N$, with the AFM order perpendicular to $B$. The increment in $T_N$ can be understood in terms of the reduction of both quantum and thermal fluctuations due to the magnetic field, which is caused by the self-energy effect within the FLEX approximation. The present study naturally explains the increment in $T_N$ in CeRhIn_5 under the magnetic field found recently.Comment: 5 page

Abelian Monopole and Center Vortex Views at the Multi-Instanton Gas

We consider full non-Abelian, Abelian and center projected lattice field configurations built up from random instanton gas configurations in the continuum. We study the instanton contribution to the $\bar{Q}Q$ force with respect to ({\it i}) instanton density dependence, ({\it ii}) Casimir scaling and ({\it iii}) whether various versions of Abelian dominance hold. We check that the dilute gas formulation for the interaction potential gives an reliable approximation only for densities small compared to the phenomenological value. We find that Casimir scaling does not hold, confirming earlier statements in the literature. We show that the lattice used to discretize the instanton gas configurations has to be sufficiently coarse ($a \approx 2\bar{\rho}$ compared with the instanton size $\bar{\rho}$) such that maximal Abelian gauge projection and center projection as well as the monopole gas contribution to the $\bar{Q}Q$ force reproduce the non-Abelian instanton-mediated force in the intermediate range of linear quasi-confinement. We demonstrate that monopole clustering also depends critically on the discretization scale confirming earlier findings based on monopole blocking.Comment: 21 pages, 22 Postscript figure

Evaluating the Need for and Effect of Percutaneous Transluminal Angioplasty on Arteriovenous Fistulas by Using Total Recirculation Rate per Dialysis Session (“Clearance Gap”)

The functioning of an arteriovenous fistula (AVF) used for vascular access during hemodialysis has been assessed mainly by dilution methods. Although these techniques indicate the immediate recirculation rate, the results obtained may not correlate with Kt/V. In contrast, the clearance gap (CL-Gap) method provides the total recirculation rate per dialysis session and correlates well with Kt/V. We assessed the correlation between Kt/V and CL-Gap as well as the change in radial artery (RA) blood flow speed in the fistula before percutaneous transluminal angioplasty (PTA) in 45 patients undergoing continuous hemodialysis. The dialysis dose during the determination of CL-Gap was 1.2 to 1.4 Kt/V. Patients with a 10% elevation or more than a 10% relative increase in CL-Gap underwent PTA (n＝45), and the values obtained for Kt/V and CL-Gap before PTA were compared with those obtained immediately afterward. The mean RA blood flow speed improved significantly (from 52.9 to 97.5cm/sec) after PTA, as did Kt/V (1.07 to 1.30) and CL-Gap (14.1% to －0.2%). A significant correlation between these differences was apparent (r＝－0.436 and p＝0.003). These findings suggest that calculating CL-Gap may be useful for determining when PTA is required and for assessing the effectiveness of PTA, toward obtaining better dialysis

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

Abelian-Projected Effective Gauge Theory of QCD with Asymptotic Freedom and Quark Confinement

We give an outline of a recent proof that the low-energy effective gauge theory exhibiting quark confinement due to magnetic monopole condensation can be derived from QCD without any specific assumption. We emphasize that the low-energy effective abelian gauge theories obtained here give the dual description of the same physics in the low-energy region. They show that the QCD vacuum is nothing but the dual (type II) superconductor.Comment: 15 pages, Latex, no figures, Talk given at YKIS'97, Non-perturbative QCD, Kyot

Abelian-Projected Effective Gauge Theory of QCD with Asymptotic Freedom and Quark Confinement

Starting from SU(2) Yang-Mills theory in 3+1 dimensions, we prove that the abelian-projected effective gauge theories are written in terms of the maximal abelian gauge field and the dual abelian gauge field interacting with monopole current. This is performed by integrating out all the remaining non-Abelian gauge field belonging to SU(2)/U(1). We show that the resulting abelian gauge theory recovers exactly the same one-loop beta function as the original Yang-Mills theory. Moreover, the dual abelian gauge field becomes massive if the monopole condensation occurs. This result supports the dual superconductor scenario for quark confinement in QCD. We give a criterion of dual superconductivity and point out that the monopole condensation can be estimated from the classical instanton configuration. Therefore there can exist the effective abelian gauge theory which shows both asymptotic freedom and quark confinement based on the dual Meissner mechanism. Inclusion of arbitrary number of fermion flavors is straightforward in this approach. Some implications to lower dimensional case will also be discussed.Comment: 39 pages, Latex, no figures, (2.2, 4.1, 4.3 are modified; 4.4, Appendices A,B,C and references are added. No change in conclusion

Synthesis of isomeric phosphoubiquitin chains reveals that phosphorylation controls deubiquitinase activity and specificity

Ubiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins for the enzymatic assembly of 20 isomeric phosphoubiquitin dimers, with different sites of isopeptide linkage and/or phosphorylation. We discover that phosphorylation of serine 20 on ubiquitin converts UBE3C from a dual-specificity E3 ligase into a ligase that primarily synthesizes K48 chains. We profile the activity of 31 deubiquitinases on the isomeric phosphoubiquitin dimers in 837 reactions, and we discover that phosphorylation at distinct sites in ubiquitin can activate or repress cleavage of a particular linkage by deubiquitinases and that phosphorylation at a single site in ubiquitin can control the specificity of deubiquitinases for distinct ubiquitin linkages

Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10⁴/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients