Bmi1 regulates memory CD4 T cell survival via repression of the Noxa gene

The maintenance of memory T cells is central to the establishment of immunological memory, although molecular details of the process are poorly understood. In the absence of the polycomb group (PcG) gene Bmi1, the number of memory CD4+ T helper (Th)1/Th2 cells was reduced significantly. Enhanced cell death of Bmi1−/− memory Th2 cells was observed both in vivo and in vitro. Among various proapoptotic genes that are regulated by Bmi1, the expression of proapoptotic BH3-only protein Noxa was increased in Bmi1−/− effector Th1/Th2 cells. The generation of memory Th2 cells was restored by the deletion of Noxa, but not by Ink4a and Arf. Direct binding of Bmi1 to the Noxa gene locus was accompanied by histone H3-K27 methylation. The recruitment of other PcG gene products and Dnmt1 to the Noxa gene was highly dependent on the expression of Bmi1. In addition, Bmi1 was required for DNA CpG methylation of the Noxa gene. Moreover, memory Th2-dependent airway inflammation was attenuated substantially in the absence of Bmi1. Thus, Bmi1 controls memory CD4+ Th1/Th2 cell survival and function through the direct repression of the Noxa gene

Demolition of Reinforced Concrete by Steam Pressure Cracking System

The authors developed an environment-friendly demolition mechanical system for a large reinforced concrete structure for an actual site. The steam pressure cracking agent (SPC, non-explosive) is a method that can safely and quickly separate concrete because it produces lesser vibration and sound than the blasting method, which uses explosives. The authors showed that the direction of cracking can be controlled by an induction hole. The principle of control is that the elastic wave of the compression stress generated from the SPC reaction changes to a tensile elastic wave at the induction hole, which initiates a crack. Furthermore, in the SPC method, a large amount of concrete powder generated by the explosion method was not produced, and there was no risk of secondary contamination by fine concrete powder. The area over which the crack propagated depends on the energy generated from the SPC. The relationship between the two is linear. For reinforced concrete, the energy of the SPC is used for both the destructive energy of the concrete and the energy of the cutting of the reinforcing steel bar, which quickly breaks with low energy. By applying an SPC to dismantle large reinforced concrete structures, controlled cracking can be achieved safely and quickly without any environmental pollution. A fracturing method using a SPC is an effective method for the decommissioning of nuclear power plants and the dismantling of concrete structures. In this report, we report a remote drilling system that can be used to remotely install loading holes and guiding holes for the SPC and perform effective controlled fracturing

Elastic Wave Property of Concrete Decomposed by Steam Pressure Cracking Agent

A steam pressure cracking (SPC) agent is a method that can dismantle concrete safely and quickly. In previous studies, the authors showed that the direction of the crack could be controlled by the tensile stress at the induction holes and not by the compressive stress at the SPC hole. We demonstrate that the compression elastic wave changes to a tensile wave when the wave is reflected at the free surface of the induction hole. We also examined the properties of the concrete by developing an elastic wave measuring system that is difficult to break down even in high-temperature, wet, and radiation environment. The elastic wave velocity change in the four concrete types was less than 4%. It was found that the standard deviation value, σ, changed four times. Therefore, it is possible to determine the deterioration of the internal structure of concrete using the standard deviation value σ, which indicates the dispersion of the elastic wave velocity

Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms

AbstractMyeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as “driver” gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%–30% of cases respectively [3]. Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs) but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6–8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2—the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators—and examined the influence of single or double mutations on HSCs (Lineage−Sca-1+c-Kit+ cells (LSKs)) by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F–LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F–LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more highly expressed in double-mutant-LSKs than in JAK2V617F–LSKs. These altered gene expressions might partly explain the mechanisms of initiation and progression of MPNs which was observed in the functional analyses [9]. Here we describe gene expression profiles deposited at the Gene Expression Omnibus (GEO) under the accession number GSE62302 including experimental methods and quality control analyses

Cutting of Diamond Substrate Using Fixed Diamond Grain Saw Wire

This study demonstrates that a single-crystal diamond substrate can be cut along designed lines using the diamond-saw-wire cutting method. We developed an original saw-wire fixed diamond-grain using a bronze solder with a high melting temperature. We created a unique product machine system with a high vacuum furnace and a bronze solder that contains a metallic compound. The diamond cutting mechanism employed in this study is based on the mild wear phenomenon, owing to the friction between the diamond surfaces. A linear relationship between the cutting length and wire feed distance was observed. The relationship can be approximated as y = 0.3622x, where y (mu m) is the cutting depth and x (km) is the wire feed distance. The life of the saw-wire was longer than that of the 6000 km wire feed distance and was tested by reciprocating an 8-m short wire at a speed, tension, and cutting force of 150 m/min, 1 N, and 0.2 N, respectively. A single crystal diamond substrate could be cut along the designed line, which was more than 2 mm long. The cutting speed was maintained constant at 0.36 mu m/km

Elastic Wave Property of Concrete Decomposed by Steam Pressure Cracking Agent

A steam pressure cracking (SPC) agent is a method that can dismantle concrete safely and quickly. In previous studies, the authors showed that the direction of the crack could be controlled by the tensile stress at the induction holes and not by the compressive stress at the SPC hole. We demonstrate that the compression elastic wave changes to a tensile wave when the wave is reflected at the free surface of the induction hole. We also examined the properties of the concrete by developing an elastic wave measuring system that is difficult to break down even in high-temperature, wet, and radiation environment. The elastic wave velocity change in the four concrete types was less than 4%. It was found that the standard deviation value, σ, changed four times. Therefore, it is possible to determine the deterioration of the internal structure of concrete using the standard deviation value σ, which indicates the dispersion of the elastic wave velocity

NONINVASIVE ESTIMATION OF CARDIAC PROPERTIES IN PATIENTS WITH HYPERTENSION USING SPECKLE TRACKING ECHOCARDIOGRAPHY: A COMPARATIVE STUDY BETWEEN GOOD AND POOR CONTROLLED HYPERTENSION

info:eu-repo/semantics/publishe

Low-Dose Intravenous Alteplase in Wake-Up Stroke

Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively. Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions

中等度狭窄の内腔狭小化への組織性状の影響：integrated backscatter intravascular ultrasoundでの評価

博士(医学)岐阜大学(Gifu University