33 research outputs found

    Multi-modal interfaces for human–robot communication in collaborative assembly

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    Nicolăescu-PlopƟor Constantin S., Zaharia Nicolae. Cercetările de la Mitoc (r. Săveni, reg. Suceava) / Les recherches de Mitoc. In: Materiale Ɵi cercetări arheologice, N°6 1959. pp. 11-23

    Early Onset Prion Disease from Octarepeat Expansion Correlates with Copper Binding Properties

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    Insertional mutations leading to expansion of the octarepeat domain of the prion protein (PrP) are directly linked to prion disease. While normal PrP has four PHGGGWGQ octapeptide segments in its flexible N-terminal domain, expanded forms may have up to nine additional octapeptide inserts. The type of prion disease segregates with the degree of expansion. With up to four extra octarepeats, the average onset age is above 60 years, whereas five to nine extra octarepeats results in an average onset age between 30 and 40 years, a difference of almost three decades. In wild-type PrP, the octarepeat domain takes up copper (Cu2+) and is considered essential for in vivo function. Work from our lab demonstrates that the copper coordination mode depends on the precise ratio of Cu2+ to protein. At low Cu2+ levels, coordination involves histidine side chains from adjacent octarepeats, whereas at high levels each repeat takes up a single copper ion through interactions with the histidine side chain and neighboring backbone amides. Here we use both octarepeat constructs and recombinant PrP to examine how copper coordination modes are influenced by octarepeat expansion. We find that there is little change in affinity or coordination mode populations for octarepeat domains with up to seven segments (three inserts). However, domains with eight or nine total repeats (four or five inserts) become energetically arrested in the multi-histidine coordination mode, as dictated by higher copper uptake capacity and also by increased binding affinity. We next pooled all published cases of human prion disease resulting from octarepeat expansion and find remarkable agreement between the sudden length-dependent change in copper coordination and onset age. Together, these findings suggest that either loss of PrP copper-dependent function or loss of copper-mediated protection against PrP polymerization makes a significant contribution to early onset prion disease

    Population genomics of speciation and admixture

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    The application of population genomics to the understanding of speciation has led to the emerging field of speciation genomics. This has brought new insight into how divergence builds up within the genome during speciation and is also revealing the extent to which species can continue to exchange genetic material despite reproductive barriers. It is also providing powerful new approaches for linking genotype to phenotype in admixed populations. In this chapter, we give an overview of some of the methods that have been used and some of the novel insights gained. We also outline some of the pitfalls of the most commonly used methods and possible problems with interpretation of the results

    Left atrial and left atrial appendage function in paroxysmal atrial fibrillation

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    Purpose: In patients with paroxysmal atrial fibrillation (PAF) little information is available about left atrial (LA) function, and there is less information about LA appendage (LAA) function, and about their relations. Methods and Results: 46 patients were selected for catheter ablation (CA) because of nonvalvular PAF. Transthoracic, tissue Doppler and transoesophageal echocardiography was performed before CA. LA volumes and volume index (LAVI) were calculated. LA function was assessed by LA filling fraction (LAFF), LA emptying fraction (LAEF), systolic fraction of pulmonary venous flow (PVSF) and late diastolic velocities of mitral annulus (Aasept , Aalat ) LAA function was assessed by peak LAA emptying flow velocity (PLAAEFV). Diastolic dysfunction (DD) was also assessed. Dilated LAVI in 32, LA dysfunction in 20, DD with elevated LV filling pressure in 19 patients was found. Aalat and Aasept correlated with LAFF (r:0.53; p<0.001 and r:0.43; p<0.05), LAEF (r:0.51; p<0.001 and r:0.63; p<0.001), PVSF (r:0.49; p<0.001 and r:0.46; p<0.005) and PLAAEFV (r:0.58; p<0.001 and r:0.45; p<0.01). Conclusions: In PAF patients Aa velocity is useful to assess LA function and correlates positively with other TTE derived LA functional parameters and LAA function by TEE derived PLAAEFV

    In vivo direct interaction of the antibiotic primycin on a Candida albicans clinical isolate and its ergosterol-less mutant

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    Interaction of primycin antibiotic with plasma membrane, and its indirect biological effects were investigated in this study. The antifungal activity of primycin against 13 human pathogenic Candida ATCC and CBS reference species and 74 other Candida albicans clinical isolates was investigated with a microdilution technique. No primycin-resistant strain was detected. Direct interaction of primycin with the plasma membrane was demonstrated for the first time by using an ergosterol-producing strain 33erg+ and its ergosterol-less mutant erg-2. In growth inhibition tests, the 33erg+ strain proved to be more sensitive to primycin than its erg-2 mutant, indicating the importance of the plasma membrane composition in primycin-induced processes. The 64 ÎŒg ml−1 (56.8 nM) primycin treatment induced an enhanced membrane fluidity and altered plasma membrane dynamics, as measured by steady-state fluorescence anisotropy applying a trimethylammonium-diphenylhexatriene (TMA-DPH) fluorescence polarization probe. The following consequences were detected. The plasma membrane of the cells lost its barrier function, and the efflux of 260-nm-absorbing materials from treated cells of both strains was 1.5–1.8 times more than that for the control. Depending on the primycin concentration, the cells exhibited unipolar budding, pseudohyphae formation, and a rough cell surface visualized by scanning electron microscopy
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