Differential requirements of MyD88 and TRIF pathways in TLR4-mediated immune responses in murine B cells

LPS stimulates the TLR4/Myeloid differentiation protein-2 (MD-2) complex and promotes a variety ofimmune responses in B cells. TLR4 has two main signaling pathways, MyD88 and Toll/IL-1R (TIR)-domain-containing adaptor-inducing interferon- (TRIF) pathways, but relatively few studies have examinedthese pathways in B cells. In this study, we investigated MyD88- or TRIF-dependent LPS responses inB cells by utilizing their knockout mice. Compared with wild-type (WT) B cells, MyD88−/−B cells weremarkedly impaired in up-regulation of CD86 and proliferation induced by lipid A moiety of LPS. TRIF−/−Bcells were also impaired in these responses compared with WT B cells, but showed better responses thanMyD88−/−B cells. Regarding class switch recombination (CSR) elicited by lipid A plus IL-4, MyD88−/−B cells showed similar patterns of CSR to WT B cells. However, TRIF−/−B cells showed the impaired inthe CSR. Compared with WT and MyD88−/−B cells, TRIF−/−B cells exhibited reduced cell division, fewerIgG1+cells per division, and decreased activation-induced cytidine deaminase (Aicda) mRNA expressionin response to lipid A plus IL-4. Finally, IgG1 production to trinitrophenyl (TNP)-LPS immunization wasimpaired in TRIF−/−mice, while MyD88−/−mice exhibited increased IgG1 production. Thus, MyD88 andTRIF pathways differently regulate TLR4-induced immune responses in B cells

Towards Generation of Visual Attention Map for Source Code

Program comprehension is a dominant process in software development and maintenance. Experts are considered to comprehend the source code efficiently by directing their gaze, or attention, to important components in it. However, reflecting the importance of components is still a remaining issue in gaze behavior analysis for source code comprehension. Here we show a conceptual framework to compare the quantified importance of source code components with the gaze behavior of programmers. We use "attention" in attention models (e.g., code2vec) as the importance indices for source code components and evaluate programmers' gaze locations based on the quantified importance. In this report, we introduce the idea of our gaze behavior analysis using the attention map, and the results of a preliminary experiment.Comment: 4 pages, 2 figures; APSIPA 2019 ACCEPTE

CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors

Adipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFβ signaling pathway. We show that adipose tissue CD206+ cells are primarily M2-like macrophages, and ablation of CD206+ M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes. Mice genetically engineered to have reduced numbers of CD206+ M2-like macrophages show a down-regulation of TGFβ signaling in adipose tissue, together with up-regulated proliferation and differentiation of adipocyte progenitors. Our findings indicate that CD206+ M2-like macrophages in adipose tissues create a microenvironment that inhibits growth and differentiation of adipocyte progenitors and, thereby, control adiposity and systemic insulin sensitivity