53 research outputs found
Synthesis and evaluation of a library of 2,5-bisdiamino-benzoquinone derivatives as probes to modulate protein-protein interactions in prions
No full textA small library combining two different benzoquinone cores with seven (L) amino acid methyl esters (alanine, Nomega-nitro-arginine, Nepsilon-BOC-lysine, isoleucine, methionine, phenylalanine and tryptophan) was prepared and tested for prion replication inhibition in ScGT1 cells. The most potent hit, 6a, displayed an EC(50) value of 0.87 microM, which is very close to that of quinacrine (0.4 microM)
A fluorescent styrylquinoline with combined therapeutic and diagnostic activities against Alzheimer's and prion diseases
No full text(E)-6-Methyl-4′-amino-2-styrylquinoline (3) is a small molecule with the proper features to potentially diagnose, deliver therapy and monitor response to therapy in protein misfolding diseases. These features include compound fluorescent emission in the NIR region and its ability to interact with both Aβ and prion fibrils, staining them with high selectivity. Styrylquinoline 3 also inhibits Aβ self-aggregation in vitro and prion replication in the submicromolar range in a cellular context. Furthermore, it is not toxic and is able to cross the blood brain barrier in vitro (PAMPA test).Peer Reviewe
Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers
No full textSeptins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions. Septin-microtubule association requires polymerizable septin octamers harboring SEPT9_i1. Although outside of the MAP-like motif, HNA mutations abrogate this association, identifying a putative regulatory domain. Removal of this domain from SEPT9_i1 sequesters septins on microtubules, promotes microtubule stability and alters actomyosin fiber distribution and tension. Thus, we identify key molecular determinants and potential regulatory roles of septin-microtubule interaction, paving the way to deciphering the mechanisms underlying septin-associated pathologies.BN/Gijsje Koenderink La
[[alternative]]The effect of vasopressin on respiratory-related hypoglossal nerve activity in rats
No full text[[abstract]]英文摘要
The purpose of the present study was to examine the influence of the arginine vasopressin (AVP) on respiratory-related hypoglossal activity in rats. The rat was anesthetized by urethane (1.2 g/kg, i.p.).Tracheotomy, and catheterization of the femoral artery and vein were performed. The animal was then paralyzed with gallamine triethiodide (5 mg/kg) and ventilated artificially. End-tidal fractional concentration of gas was maintained at normocapnia in hyperoxia. Activities of both the phrenic and hypoglossal nerves were monitored
Arginine vasopressin (AVP) was microinjected into a specific area of the ventrolateral medulla (VLM) to evaluate the response of the phrenic and the hypoglossal nerve. There were two types of response with AVP administration. In type I response, activities of the phrenic nerve (PNA) and the hypoglossal nerve (HNA) showed apnea and then recovered gradually. Mean period of apnea in response to low dose (1.5x10-8 IU) and high dose (3.0x10-8 IU) of AVP was 3.24 and 5.28 seconds respectively (p < 0.05) . Average PNA of the first neurogram after recovery from AVP treatment with low and high dose was 75.61 % and 58.21 % (p < 0.01) while HNA was 68.92 % annd 46.45 % of control. Blood pressure was unchanged. In type II response, mean period of apnea with a dosage of 3.0x10-8 IU was 4.22 seconds (p < 0.05). Average PNA of the first neurogram flowing AVP administration was 63.71 % of control whereas HNA was 80 %.These inhibitions of AVP upon PNA and HNA were attenuated by hypercapnia. Thus PNA was reduced to 85.19 % and 70.94 % of control in type I response whereas to 93.97 % of control in type II response. HNA was 88.70 % and 74.00 % of contral in type I response but to 88.99 % in type II response.
These results suggest that AVP may play a role in the modulation of respiration and upper airway patency by direct action upon the neurons in the VLM.
Onderzoek naar het reologisch gedrag van een thermotroop LCP: capillair, kegel-plaat en spleetviscosimetrie
No full textIn dit onderzoek is het reologisch gedrag van het thermotrope LCP Vectra A900 (HBA/HNA 73/27) onderzocht. Hierbij is gebruik gemaakt van drie meetmethoden, namelijk capillair, kegel-plaat en spleetviscosimetrie. Met deze drie meetmethoden is getracht de viscositeit van het gesmolten LCP over een zo breed mogelijk afschuifsnelheidsgebied te bepalen. Hierbij is gekeken of de resultaten verkregen met de drie verschillende meetmethoden met elkaar overeenstemmen…Applied SciencesScheikundige Technologie en der MateriaalkundeTechnologie van Macromoleculaire Stoffe
Reologische metingen aan het THERMOTROPE LCP HBA/HNA 73/27
No full textApplied SciencesTechnologie van Macromoleculaire Stoffe
Clustering Lifestyle Risk Behaviors among Vietnamese Adolescents and Roles of School: A Bayesian Multilevel Analysis of Global School-Based Student Health Survey 2019
No full textBackground: Adolescence is a vulnerable period for many lifestyle risk behaviors. In this study, we aimed to 1) examine a clustering pattern of lifestyle risk behaviors; 2) investigate roles of the school health promotion programs on this pattern among adolescents in Vietnam. Methods: We analyzed data of 7,541 adolescents aged 13–17 years from the 2019 nationally representative Global School-based Student Health Survey, conducted in 20 provinces and cities in Vietnam. We applied the latent class analysis to identify groups of clustering and used Bayesian 2-level logistic regressions to evaluate the correlation of school health promotion programs on these clusters. We reassessed the school effect size by incorporating different informative priors to the Bayesian models. Findings: The most frequent lifestyle risk behavior among Vietnamese adolescents was physical inactivity, followed by unhealthy diet, and sedentary behavior. Most of students had a cluster of at least two risk factors and nearly a half with at least three risk factors. Latent class analysis detected 23% males and 18% females being at higher risk of lifestyle behaviors. Consistent through different priors, high quality of health promotion programs associated with lower the odds of lifestyle risk behaviors (highest quality schools vs. lowest quality schools; males: Odds ratio (OR) = 0·67, 95% Highest Density Interval (HDI): 0·46 – 0·93; females: OR = 0·69, 95% HDI: 0·47 – 0·98). Interpretation: Our findings demonstrated the clustering of specific lifestyle risk behaviors among Vietnamese in-school adolescents. School-based interventions separated for males and females might reduce multiple health risk behaviors in adolescence. Funding: The 2019 Global School-based Student Health Survey was conducted with financial support from the World Health Organization. The authors received no funding for the data analysis, data interpretation, manuscript writing, authorship, and/or publication of this article.Full Tex
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