1,458 research outputs found

    Cardiovascular Damage in Alzheimer Disease: Autopsy Findings From the Bryan ADRC

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    Autopsy information on cardiovascular damage was investigated for pathologically confirmed Alzheimer disease (AD) patients (n = 84) and non-AD control patients (n = 60). The 51 relevant items were entered into a grade-of-membership model to describe vascular damage in AD. Five latent groups were identified ā€œI: early-onset AD,ā€ ā€œII: controls, cancer,ā€ ā€œIII: controls, extensive atherosclerosis,ā€ ā€œIV: late-onset AD, male,ā€ and ā€œV: late-onset AD, female.ā€ Expectedly, Groups IV and V had elevated APOE Ļµ4 frequency. Unexpectedly, there was limited atherosclerosis and frequent myocardial valve and ventricular damage. The findings do not indicate a strong relationship between atherosclerosis and AD, although both are associated with the APOE Ļµ4. Instead, autopsy findings of extensive atherosclerosis were associated with possible, not probable or definite AD, and premature death. They are consistent with the hypothesis that brain hypoperfusion contributes to dementia, possibly to AD pathogenesis, and raise the possibility that the APOE allele Ļµ4 contributes directly to heart valve and myocardial damage

    Structure and Magnetism of Neutral and Anionic Palladium Clusters

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    The properties of neutral and anionic Pd_N clusters were investigated with spin-density-functional calculations. The ground state structures are three-dimensional for N>3 and they are magnetic with a spin-triplet for 2<=N<=7 and a spin nonet for N=13 neutral clusters. Structural- and spin-isomers were determined and an anomalous increase of the magnetic moment with temperature is predicted for a Pd_7 ensemble. Vertical electron detachment and ionization energies were calculated and the former agree well with measured values for anionic Pd_N clusters.Comment: 5 pages, 3 figures, fig. 2 in color, accepted to Phys. Rev. Lett. (2001

    An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

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    Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool. Ā© 2013 Sejdić et al

    An influenza A virus can evolve to use human ANP32E through altering polymerase dimerization

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    Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth. We find two mutations in different subunits of the influenza polymerase that enable the mutant virus to use a novel host factor, ANP32E, an alternative family member, which is unable to support the wild type polymerase. Both mutations reside in the symmetric dimer interface between two polymerase complexes and reduce polymerase dimerization. These mutations have previously been identified as adapting influenza viruses to mice. Indeed, the evolved virus gains the ability to use suboptimal mouse ANP32 proteins and becomes more virulent in mice. We identify further mutations in the symmetric dimer interface which we predict allow influenza to adapt to use suboptimal ANP32 proteins through a similar mechanism. Overall, our results suggest a balance between asymmetric and symmetric dimers of influenza virus polymerase that is influenced by the interaction between polymerase and ANP32 host proteins
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