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<p>Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine member of the TNF family. TWEAK binds to its only known receptor, Fn14, enabling it to activate downstream signaling processes in response to tissue injury. The aim of this study was to investigate the role of TWEAK signaling in neonatal hypoxia–ischemia (HI). We found that after neonatal HI, both TWEAK and Fn14 expression were increased to a greater extent in male compared with female mice. To assess the role of TWEAK signaling after HI, the size of the injury was measured in neonatal mice genetically deficient in Fn14 and compared with their wild-type and heterozygote littermates. A significant sex difference in the Fn14 knockout (KO) animals was observed. Fn14 gene KO was beneficial in females; conversely, reducing Fn14 expression exacerbated the brain injury in male mice. Our findings indicate that the TWEAK/Fn14 pathway is critical for development of hypoxic–ischemic brain injury in immature animals. However, as the responses are different in males and females, clinical implementation depends on development of sex-specific therapies.</p

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<p>Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine member of the TNF family. TWEAK binds to its only known receptor, Fn14, enabling it to activate downstream signaling processes in response to tissue injury. The aim of this study was to investigate the role of TWEAK signaling in neonatal hypoxia–ischemia (HI). We found that after neonatal HI, both TWEAK and Fn14 expression were increased to a greater extent in male compared with female mice. To assess the role of TWEAK signaling after HI, the size of the injury was measured in neonatal mice genetically deficient in Fn14 and compared with their wild-type and heterozygote littermates. A significant sex difference in the Fn14 knockout (KO) animals was observed. Fn14 gene KO was beneficial in females; conversely, reducing Fn14 expression exacerbated the brain injury in male mice. Our findings indicate that the TWEAK/Fn14 pathway is critical for development of hypoxic–ischemic brain injury in immature animals. However, as the responses are different in males and females, clinical implementation depends on development of sex-specific therapies.</p

Additional file 3: of CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study

CDP7657 immune complex ( IC ) and aglycosyl hu5c8 IC do not induce platelet aggregation in rhesus monkey platelets both in the absence of presence of sub-aggregatory amounts of the platelet agonist (ADP). In vitro aggregation assay of rhesus monkey washed platelets. A CDP7657 IC did not aggregate rhesus monkey washed platelets in the absence (blue and red), or presence (black and green) of ADP. B Similarly, aglycosyl hu5c8 IC did not aggregate rhesus monkey washed platelets in the absence (blue and red), or presence (black and green) of ADP. (PDF 171 kb

Additional file 1: of CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study

Inhibition of secondary immune response in Cynomolgus monkeys. CDP7657 at 5 or 20 mg/kg (60 mg/kg was not evaluated in this study) was compared with hu5c8 at 20 mg/kg. Animals were administered a single dose of antibody or i.v saline. and challenged with tetanus toxoid (TT) on day 1; they then received a second dose of antibody and TT on day 30. Data are expressed as the mean anti-TT IgG titer ± standard deviation; approximately 50 % inhibition was observed at 20 mg/kg CDP7657, although this was not statistically significant. ***P <0.001 (one-way analysis of variance) compared with control; NS not significant. (PDF 66 kb