Collapsin response mediator protein 1 mediates Reelin signaling in cortical neuronal migration

Collapsin response mediator protein 1 ( CRMP1) is one of the CRMP family members that mediates signal transduction of axon guidance molecules. Here, we show evidence that CRMP1 is involved in Reelin ( Reln) signaling to regulate neuronal migration in the cerebral cortex. In crmp1(-/-) mice, radial migration of cortical neurons was retarded. This phenotype was not observed in the sema3A(-/-) and crmp1(+/+); sema3A(+/+) cortices. However, CRMP1 was colocalized with disabled- 1 ( Dab1), an adaptor protein in Reln signaling. In the Reln(rl/rl) cortex, CRMP1 and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower level. Loss of crmp1 in a dab1 heterozygous background led to the disruption of hippocampal lamination, a Reeler- like phenotype. In addition to axon guidance, CRMP1 regulates neuronal migration by mediating Reln signaling

Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1

Cartilage acidic protein 1 (CRTAC1) was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA) by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM) surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA

Ferrocene-Containing Pseudorotaxanes in Crystals: Aromatic Interactions with Hammett Correlation

Single crystals of pseudorotaxanes, [(FcCH2NH2CH2Ar)(DB24C8)][PF6] (DB24C8 = dibenzo[24]crown-8, Fc = Fe(C5H4)(C5H5), Ar = -C6H3-3,4-Cl2, -C6H3-3,4-F2, -C6H4-4-F, -C6H4-4-Cl, -C6H4-4-Br, -C6H3-3-F-4-Me, -C6H4-4-I) and [(FcCH2NH2CH2C6H4-4-Me)(DB24C8)][Ni(dmit)2] (dmit = 1,3-dithiole-2,4,5-dithiolate), were obtained from solutions containing DB24C8 and ferrocenylmethyl(arylmethyl)ammonium. X-ray crystallographic analyses of the pseudorotaxanes revealed that the aryl ring of the axle moiety and the catechol ring of the macrocyclic component were at close centroid distances and parallel or tilted orientation. The structures with parallel aromatic rings showed correlation of the distances between the centroids to Hammett substituent constants of the aryl groups

LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice

<div><p>Nogo receptor-1 (NgR1) and its ligands inhibit neuronal plasticity and limit functional recovery after brain damage such as ischemic stroke. We have previously shown that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated signaling. Here, we investigated whether LOTUS enhances neuronal plasticity and functional recovery after brain focal ischemia in adult mice. Focal ischemic infarcts were induced in wild-type and LOTUS-overexpressing transgenic mice via middle cerebral artery occlusion. Endogenous LOTUS expression was increased in brain and cervical spinal cord of the contralateral side of ischemia in the chronic phase after brain ischemia. LOTUS overexpression accelerated midline-crossing axonal sprouting from the contralateral side to the ipsilateral side of ischemia in the medullar reticular formation and gray matter of denervated cervical spinal cord. Importantly, LOTUS overexpression improved neurological score highly correlated with laterality ratio of corticoreticular fibers of the medulla oblongata, indicating that LOTUS overexpression may overcome the inhibitory environment induced by NgR1 signaling for damaged motor pathway reconstruction after ischemic stroke. Thus, our data suggest that LOTUS overexpression accelerates neuronal plasticity in the brainstem and cervical spinal cord after stroke and LOTUS administration is useful for future therapeutic strategies.</p></div