Induction of immune response in macaque monkeys infected with simian–human immunodeficiency virus having the TNF-α gene at an early stage of infection

AbstractTNF-α has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-α against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-α gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4+ T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES and by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-α contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection

Intrusion detection and prevention system for FlexRay against spoofed frame injection

Some European original equipment manufacturers (OEMs) have adopted FlexRay as a control network that can realize the fundamental functions of a vehicle. However, studies regarding FlexRay security are scarce. We herein highlight the vulnerability of FlexRay revealed from the results of experiments conducted on real FlexRay networks. Consequently, we clarify the conditions under which attackers can masquerade as legitimate electronic control units and transmit spoofed FlexRay frames. To our knowledge, this is the first study that demonstrates a consumer vehicle being controlled by spoofing attacks in static segments. Furthermore, we discuss countermeasures against spoofing attacks on FlexRay. In particular, we discuss the intrusion detection and prevention system (IDPS), which detects spoofing attacks and mitigates the risk of malicious control of a vehicle until recovery. Furthermore, we conduct experiments to verify the feasibility of the proposed IDPSs in disabling spoofed frames

Dietitian‐supported dietary intervention leads to favorable dietary changes in patients with type 2 diabetes: A randomized controlled trial

Abstract Aims/Introduction It remains to be fully elucidated whether nutrition education by dietitians can lead to specific positive changes in the food choices of patients with diabetes. Materials and Methods A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit and the control group that received nutritional education once a year. The total energy intake, energy‐providing nutrients and 18 food groups were analyzed at baseline, and 1 and 2 years after the intervention in 87 patients. Furthermore, the relationship between the changes in hemoglobin A1c, body composition and changes in the total energy or energy‐producing nutrient intake was analyzed in 48 patients who did not use or change hypoglycemic agents during the study period. Results The total energy intake, carbohydrates, cereals, confections, nuts and seeds, and seasonings significantly decreased, and fish and shellfish intake significantly increased during the study period in the intensive intervention group, whereas these changes were not observed in the control group. The decrease in the total energy intake and carbohydrates after 2 years was significantly greater in the intensive intervention group than in the control group. The change in the total energy and carbohydrate intake showed a significant positive correlation with that in muscle mass. The multivariate analysis showed that the decrease in total energy intake was independently associated with that in muscle mass. Conclusion Dietitian‐supported intensive dietary intervention helps improve the diet of patients with type 2 diabetes

Chemokine Receptor CCR8 Is Required for Lipopolysaccharide-Triggered Cytokine Production in Mouse Peritoneal Macrophages

<div><p>Chemokine (C-C motif) receptor 8 (CCR8), the chemokine receptor for chemokine (C-C motif) ligand 1 (CCL1), is expressed in T-helper type-2 lymphocytes and peritoneal macrophages (PMφ) and is involved in various pathological conditions, including peritoneal adhesions. However, the role of CCR8 in inflammatory responses is not fully elucidated. To investigate the function of CCR8 in macrophages, we compared cytokine secretion from mouse PMφ or bone marrow-derived macrophages (BMMφ) stimulated with various Toll-like receptor (TLR) ligands in CCR8 deficient (<i>CCR8^-</i>^/-) and wild-type (WT) mice. We found that <i>CCR8^-/-</i> PMφ demonstrated attenuated secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 when stimulated with lipopolysaccharide (LPS). In particular, LPS-induced IL-10 production absolutely required CCR8. CCR8-dependent cytokine secretion was characteristic of PMφ but not BMMφ. To further investigate this result, we selected the small molecule compound R243 from a library of compounds with CCR8-antagonistic effects on CCL1-induced Ca²⁺ flux and CCL1-driven PMφ aggregation. Similar to <i>CCR8^-/-</i> PMφ, R243 attenuated secretion of TNF-α, IL-6, and most strikingly IL-10 from WT PMφ, but not BMMφ. <i>CCR8^-/-</i> PMφ and R243-treated WT PMφ both showed suppressed c-jun N-terminal kinase activity and nuclear factor-κB signaling after LPS treatment when compared with WT PMφ. A c-Jun signaling pathway inhibitor also produced an inhibitory effect on LPS-induced cytokine secretion that was similar to that of CCR8 deficiency or R243 treatment. As seen in <i>CCR8^-/-</i> mice, administration of R243 attenuated peritoneal adhesions <i>in vivo</i>. R243 also prevented hapten-induced colitis. These results are indicative of cross talk between signaling pathways downstream of CCR8 and TLR-4 that induces cytokine production by PMφ. Through use of <i>CCR8^-/-</i> mice and the new CCR8 inhibitor, R243, we identified a novel macrophage innate immune response pathway that involves a chemokine receptor.</p></div