Meet the authors Chisae Nagiri Wataru Shihoya as well as Osamu Nureki

Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity.Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.The objectives of this study were to examine the intra and inter-operator reliability of shear wave elastography (SWE) device in quantifying the shear modulus of thoracolumbar fascia (TLF) and the device's abilities to examine the shear modulus of the TLF during upper body forward. Twenty healthy male subjects participated in this study (mean age 18.4 ± 0.7 years). Two independent operators performed the shear modulus of TLF during upper body forward using SWE, and interclass correlation coefficient (ICC) and minimum detectable change (MDC) were calculated. The shear modulus of the TLF was quantified by operator A using SWE at upper body forward 60°. The intra-operator (ICC = 0.860-0.938) and inter-operator (ICC = 0.904-0.944) reliabilities for measuring the shear modulus of the TLF with the upper body forward 0° were rated as both excellent, and the MDC was 4.71 kPa. The TLF shear modulus of upper body forward 60°was increased 45.5% (L3) and 55.0% (L4) than that of upper body forward 0°. The results indicate that the SWE is a dependable tool to quantify the shear modulus of TLF and monitor its dynamic changes. Therefore, this device can be used for biomechanical study and intervention experiments of TLF.REBa2Cu3O7-δ (REBCO, RE rare earth, such as Y and Gd) compounds have been extensively studied as a superconducting layer in coated conductors. Although ErBCO potentially has better superconducting properties than YBCO and GdBCO, little research has been made on it, especially in chemical solution deposition (CSD). In this work, ErBCO films were deposited on IBAD (ion-beam-assisted-deposition) substrates by CSD with low-fluorine solutions. The crystallization process was optimized to achieve the highest self-field critical current density (Jc) at 77 K. Commonly, for the investigation of a CSD process involving numerous process factors, one factor is changed keeping the others constant, requiring much time and cost. For more efficient investigation, this study adopted a novel design-of-experiment technique, definitive screening design (DSD), for the first time in CSD process. Two different types of solutions containing Er-propionate or Er-acetate were used to make two types of samples, Er-P and Er-A, respectively. Within the investigated range, we found that crystallization temperature, dew point, and oxygen partial pressure play a key role in Er-P, while the former two factors are significant for Er-A. DSD revealed these significant factors among six process factors with only 14 trials. Moreover, the DSD approach allowed us to create models that predict Jc accurately. These models revealed the optimum conditions giving the highest Jc values of 3.6 MA/cm2 for Er-P and 3.0 MA/cm2 for Er-A. These results indicate that DSD is an attractive approach to optimize CSD process.A detailed analysis of Geiger Mueller counter deadtime dependence on operating voltage is presented in the manuscript using four pairs of radiation sources. selleck chemicals Based on two-source method, detector deadtime is calculated for a wide range of operating voltages which revealed a peculiar relationship between the operating voltage and the detector deadtime. In the low voltage range, a distinct drop in deadtime was observed where deadtime reached a value as low as a few microseconds (22 µs for 204Tl, 26 µs for 137Cs, 9 µs for 22Na). This sharp drop in the deadtime is possibly due to reduced recombination with increasing voltage. After the lowest point, the deadtime generally increased rapidly to reach a maximum (292 µs for 204Tl, 277 µs for 137Cs, 258 µs for 22Na). This rapid increase in the deadtime is mainly due to the on-set of charge multiplication. After the maximum deadtime values, there was an exponential decrease in the deadtime reaching an asymptotic low where the manufacturer recommended voltage for operation falls.