Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience     

Oligodendrocytes regulate formation of nodes of Ranvier via the recognition molecule OMgp

The molecular mechanisms underlying the involvement of oligodendrocytes in formation of the nodes of Ranvier (NORs) remain poorly understood. Here we show that oligodendrocyte-myelin glycoprotein (OMgp) aggregates specifically at NORs. Nodal location of OMgp does not occur along demyelinated axons of either Shiverer or proteolipid protein (PLP) transgenic mice. Over-expression of OMgp in OLN-93 cells facilitates process outgrowth. In transgenic mice in which expression of OMgp is down-regulated, myelin thickness declines, and lateral oligodendrocyte loops at the node-paranode junction are less compacted and even join together with the opposite loops, which leads to shortened nodal gaps. Notably, each of these structural abnormalities plus modest down-regulation of expression of Na(+) channel alpha subunit result in reduced conduction velocity in the spinal cords of the mutant mice. Thus, OMgp that is derived from glia has distinct roles in regulating nodal formation and function during CNS myelination.     

Modulation of drug permeability in Chinese hamster ovary cells. Possible role for phosphorylation of surface glycoproteins.

We have previously reported that the uptake of colchicine and other drugs in Chinese hamster ovary (CHO) cells can be greatly enhanced by the addition of metabolic inhibitors such as cyanide (See, Y.P., Carlsen, S.A., Till, J.E. and Ling, V. (1974) Biochim. Biophys. Acta 373, 242-252). This has led us to postulate the presence of an active drug permeability barrier in these cells. In this paper we provide evidence for the dependence of this permeability barrier on intracellular ATP levels. Colchicine-resistant mutants of CHO cells exhibiting a reduced drug permeability, however, can maintain this drug permeability barrier at much lower ATP levels, suggesting that they possess an altered active drug permeability barrier. We have also observed a membrane-associated protein kinase-phosphoprotein phosphatase system in the isolated membranes of mutant and wild-type cells. Differences in the intrinsic protein phosphorylation patterns between the membranes of these cells have led us to conclude that the control of the drug permeability barrier may be mediated via the phosphorylation of at least two high molecular weight surface glycoproteins.     

LINC00668 Modulates SOCS5 Expression Through Competitively Sponging miR-518c-3p to Facilitate Glioma Cell Proliferation

Neurochemical Research - Glioma is a common invasive cancer with unfavorable prognosis in patients. Long non-coding RNAs (lncRNAs) exert significant functions in carcinogenesis of various cancers...     

Association between cyclooxygenase-2 gene polymorphisms and risk of periodontitis: a meta-analysis involving 5653 individuals

There ?765G > C, ?1195G > A, and 8473T > C polymorphisms in cyclooxygenase-2 (COX-2) gene polymorphisms and periodontitis risk were investigated based on published studies; however, their results could not give a conclusive result. Hence, we performed this meta-analysis of six published studies with eight case–control studies including these three polymorphisms which searched from PubMed and Web of Science up to October 15th, 2013. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between the three polymorphisms of COX-2 and periodontitis risk. The results from 2,580 periodontitis patients and 3,073 healthy controls showed that none of ?765G > C, ?1195G > A, or 8473T > C polymorphism was not associated with periodontitis susceptibility [Take ?765G > C for example: OR = 0.94, 95 % CI = (0.57–1.53) for C vs. G; OR = 2.34, 95 % CI = (0.72–7.62) for CC vs. GG; OR = 0.68, 95 % CI = (0.46–1.01) for CG vs. GG; OR = 0.81, 95 % CI = (0.52–1.27) for (CG+GG) vs. GG; OR = 2.57, 95 % CI = (0.80–8.29) for CC vs. (GG+CG)]. In subgroup analyses according to the type of periodontitis and ethnicity for ?765G > C and ?1195G > A, and deviations in Hardy–Weinberg equilibrium for ?765G > C, we only observe a boundary association between ?1195G > A polymorphism and Asian population. However, due to limitations of this meta-analysis, the results should treat with caution and we suggest the further researches should be carried out to verify our results.     

Resin gathering in neotropical resin bugs (Insecta: Hemiptera: Reduviidae): Functional and comparative morphology

Apiomerini (Reduviidae: Harpactorinae) collect plant resins with their forelegs and use these sticky substances for prey capture or maternal care. These behaviors have not been described in detail and morphological structures involved in resin gathering, transfer, and storage remain virtually undocumented. We here describe these behaviors in Apiomerus flaviventris and document the involved structures. To place them in a comparative context, we describe and document leg and abdominal structures in 14 additional species of Apiomerini that represent all but one of the 12 recent genera in the tribe. Based on these morphological data in combination with the behavioral observations on A. flaviventris, we infer behavioral and functional hypotheses for the remaining genera within the tribe Apiomerini. Setal abdominal patches for resin storage are associated with maternal care so far only documented for species of Apiomerus. Based on the occurrence of these patches in several other genera, we propose that maternal care is widespread within the tribe. Ventral abdominal glands are widespread within female Apiomerini. We propose that their products may prevent hardening of stored resins thus providing long‐term supply for egg coating. Judging from the diverse setal types and arrangements on the front legs, we predict six different behavioral patterns of resin gathering within the tribe. J. Morphol., 2011. © 2010 Wiley‐Liss, Inc.