36 research outputs found

    Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

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    A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

    HIV and COVID-19: two pandemics with significant (but different) central nervous system complications

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    Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions

    Can music lessons increase the performance of preschool children in IQ tests?

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    The impact of music on human cognition has a\ud distinguished history as a research topic in psychology. The\ud focus of the present study was on investigating the effects\ud of music instruction on the cognitive development of preschool\ud children. From a sample of 154 preschool children\ud of Tehran kindergartens, 60 children aged between 5 and 6\ud were randomly assigned to two groups, one receiving\ud music lessons and the other (matched for sex, age and\ud mother’s educational level) not taking part in any music\ud classes. Children were tested before the start of the course\ud of music lessons and at its end with 4 subtests of the\ud Tehran-Stanford-Binet Intelligence Scale (TSB). The\ud experimental group participated in twelve 75-min weekly\ud music lessons. Statistical analysis showed significant IQ\ud increase in participants receiving music lessons, specifically\ud on the TSB verbal reasoning and short-term memory\ud subtests. The numerical and visual/abstract reasoning\ud abilities did not differ for the two groups after lessons.\ud These data support studies that found similar skills\ud enhancements in preschool children, despite vast\ud differences in the setting in which the instruction occurred.\ud These findings appear to be consistent with some neuroimaging\ud and neurological observations which are discussed\ud in the paper

    Artificial and natural silk materials have high mechanical property variability regardless of sample size.

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    Silk fibres attract great interest in materials science for their biological and mechanical properties. Hitherto, the mechanical properties of the silk fibres have been explored mainly by tensile tests, which provide information on their strength, Young's modulus, strain at break and toughness modulus. Several hypotheses have been based on these data, but the intrinsic and often overlooked variability of natural and artificial silk fibres makes it challenging to identify trends and correlations. In this work, we determined the mechanical properties of Bombyx mori cocoon and degummed silk, native spider silk, and artificial spider silk, and compared them with classical commercial carbon fibres using large sample sizes (from 10 to 100 fibres, in total 200 specimens per fibre type). The results confirm a substantial variability of the mechanical properties of silk fibres compared to commercial carbon fibres, as the relative standard deviation for strength and strain at break is 10-50%. Moreover, the variability does not decrease significantly when the number of tested fibres is increased, which was surprising considering the low variability frequently reported for silk fibres in the literature. Based on this, we prove that tensile testing of 10 fibres per type is representative of a silk fibre population. Finally, we show that the ideal shape of the stress-strain curve for spider silk, characterized by a pronounced exponential stiffening regime, occurs in only 25% of all tested spider silk fibres
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