JRAB/MICAL-L2 undergoes liquid–liquid phase separation to form tubular recycling endosomes

Elongated tubular endosomes play essential roles in diverse cellular functions. Multiple molecules have been implicated in tubulation of recycling endosomes, but the mechanism of endosomal tubule biogenesis has remained unclear. In this study, we found that JRAB/MICAL-L2 induces endosomal tubulation via activated Rab8A. In association with Rab8A, JRAB/MICAL-L2 adopts its closed form, which functions in the tubulation of recycling endosomes. Moreover, JRAB/MICAL-L2 induces liquid–liquid phase separation, initiating the formation of tubular recycling endosomes upon overexpression. Between its N-terminal and C-terminal globular domains, JRAB/MICAL-L2 contains an intrinsically disordered region, which contributes to the formation of JRAB/MICAL-L2 condensates. Based on our findings, we propose that JRAB/MICAL-L2 plays two sequential roles in the biogenesis of tubular recycling endosomes: first, JRAB/MICAL-L2 organizes phase separation, and then the closed form of JRAB/MICAL-L2 formed by interaction with Rab8A promotes endosomal tubulation

Multiple episodes of ice loss from the Wilkes Subglacial Basin during the Last Interglacial

The Last Interglacial (LIG: 130,000–115,000 years ago) was a period of warmer global mean temperatures and higher and more variable sea levels than the Holocene (11,700–0 years ago). Therefore, a better understanding of Antarctic ice-sheet dynamics during this interval would provide valuable insights for projecting sea-level change in future warming scenarios. Here we present a high-resolution record constraining ice-sheet changes in the Wilkes Subglacial Basin (WSB) of East Antarctica during the LIG, based on analysis of sediment provenance and an ice melt proxy in a marine sediment core retrieved from the Wilkes Land margin. Our sedimentary records, together with existing ice-core records, reveal dynamic fluctuations of the ice sheet in the WSB, with thinning, melting, and potentially retreat leading to ice loss during both early and late stages of the LIG. We suggest that such changes along the East Antarctic Ice Sheet margin may have contributed to fluctuating global sea levels during the LIG

Differentiation of murine B cells induced by chondroitin sulfate B

A two-step culture system was used to investigate the role of chondroitin sulfate (CS) B, which is mitogenic to B cells, in differentiation of B cells. Mouse spleen B cells were incubated for 3 days with CSB in the presence of interleukin (IL)-4 and IL-5. After washing, the cells were replated at 10(5) viable cells/well and recultured without CSB in the presence of IL-4 and IL-5. CSB dose-dependently increased IgM production, the greatest enhancement being 450%. Dextran sulfate had a similar effect, whereas other glycosaminoglycans, CSA, CSC, heparin and hyaluronic acid, were marginally effective. Treatment of B cells with CSB resulted in increases in the number of IgM-secreting cells and numbers of CD138-positive cells and CD45R/B220-negative cells. CSB-induced IgM production was inhibited by the protein kinase C (PKC) inhibitor GF109203X but not by the phosphatidylinositol 3-kinase (P13K) inhibitor wortmannin. These results demonstrated that CSB promoted differentiation of B cells in the presence of IL-4 and IL-5 and suggested that PKC but not P13K is crucial for CSB-induced IgM production.</p

Variants of C-C Motif Chemokine 22 (CCL22) Are Associated with Susceptibility to Atopic Dermatitis: Case-Control Studies

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD

The Successful Launch of the Fourth Epsilon Launch Vehicle and its Future Rideshare Plans

The fourth Epsilon launch vehicle conducted its first rideshare mission on January 18, 2019. It successfully delivered seven satellites to the Sun Synchronous Orbit (SSO). In order to accommodate the demands in carrying satellites with various sizes, the Epsilon Satellite Mount Structure (ESMS) and the Epsilon Small Satellite Orbital Deployer (E-SSOD) was developed. The paper first introduces features of the rideshare configuration of the Epsilon. Then, the mission design and the injection accuracy of the fourth Epsilon launch are described. Further, plans for the future rideshare opportunities are presented

Immunohistochemistry for IRTA1 and MNDA helps differentiate gastric MALT lymphoma from chronic gastritis/reactive lymphocyte hyperplasia

It is difficult to histologically differentiate extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from chronic gastritis (CG)/ reactive lymphoid hyperplasia (RLH). To determine whether immunohistochemistry for IRTA1 and MNDA can differentiate gastric MALT lymphoma from CG/RLH, we investigated 81 stomach biopsy specimens [Wotherspoon grade (WG) 1, 11 cases; WG 2, 9 cases; WG 3, 20 cases; WG 4, 31 cases; and WG 5, 10 cases]. According to a previously reported algorithm involving PCR for immunoglobulin heavy (IgH) chain locus rearrangement, all 81 cases were divided into three groups: CG/RLH (55 cases), MALT lymphoma (19 cases) groups, and IgH undetectable group (7 cases). We analyzed the CG/RLH and MALT lymphoma groups. The median percentage of IRTA1-positive cells was 0% (range 0%-90.6%) in the CG/RLH group and 43.5% (range 0%-97.6%) in the MALT lymphoma group (p < 0.0001). The median percentage of MNDA-positive cells was 32.4% (range 0%-97.6%) in the CG/RLH group and 55.1% (range 0%-97.6%) in the MALT lymphoma group (p = 0.0044). These results indicate that immunohistochemistry for IRTA1 and MNDA can help dif-ferentiate gastric MALT lymphoma from CG/RLH

Investigation of Adequate Calibration Methods for X-ray Fluorescence Core Scanning Element Count Data: A Case Study of a Marine Sediment Piston Core from the Gulf of Alaska

X-ray fluorescence (XRF) core scanner elemental count data are useful for high-resolution paleoceanographic studies. However, because several factors, such as changes in physical core properties, significantly affect element count intensities, the appropriate calibration of the count data is required. Besides, the existing approaches for calibration were not widely employed and require rigorous testing based on sediment variety. In this study, we analyzed high-resolution element intensity (cps) using a wet muddy marine sediment piston core that was collected from the northeast Gulf of Alaska and tested several approaches with ratio and log-ratio methods, and the reliability was evaluated by comparison with the concentrations that were measured by WD-XRF and an elemental analyzer. The results show that the lighter elements (Ti and K) exhibited a significantly weak relationship between raw counts measured by ITRAX and concentrations that were measured by the WD-XRF, indicating that some factors artificially influence ITRAX intensity data. The Cl intensity that is expressed as the water content in marine sediment increased significantly in the upper 202 cm by 42% and the top 25 cm by 73% as compared to the down-core (below 202 cm), which deviates the X-ray scattering and element-counts. The calibration of raw data through coherent/incoherent X-ray scattering ratio (CIR) and additive- and centered-log ratio reduces the offsets. The calibration by CIR performed best for Sr, Fe, Mn, Ti, Ca, K, and Br (0.56 &lt; R2 &lt; 0.91), and the correlation with concentration significantly increased for Ti and K of 100% and 56%, respectively. Therefore, the study suggests that the correction of raw counts through CIR is an effective approach for wet marine sediment when core physical properties have greater variability