Reproductive period and preclinical cerebrospinal fluid markers for Alzheimer disease: a 25-year study

OBJECTIVE: The aim of the study was to examine the association between reproductive period, as an indicator of endogenous estrogen, and levels of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD). METHODS: A population-based sample of women from Gothenburg, Sweden was followed from 1968 to 1994 (N = 75). All women had natural menopause and were free from dementia. Information on reproductive period (age at menarche to age at menopause) was obtained from interviews from 1968 to 1980. Lumbar puncture was performed from 1992 to 1994 and CSF levels of Aβ42, Aβ40, P-tau, and T-tau were measured with immunochemical methods. Linear regression models adjusted for potential confounders were used to analyze the relationship between reproductive period and CSF biomarkers for AD. RESULTS: Longer reproductive period was associated with lower levels of Aβ42 (β = -19.2, P  = 0.01), higher levels of P-tau (β = 0.03, P  = 0.01), and lower ratio of Aβ42/Aβ40 (β = -0.02, P  = 0.01), while no association was observed for T-tau (β = 0.01, P  = 0.46). In separate analyses, examining the different components of reproductive period, earlier age at menarche was associated higher levels of P-tau (β = -0.07, P  = 0.031) and lower ratio of Aβ42/Aβ40 (β = 0.05, P  = 0.021), whereas no association was observed with Aβ42 (β = 31.1, P  = 0.11) and T-tau (β = -0.001, P  = 0.98). Furthermore, no association was observed between age at menopause and CSF biomarkers for AD. CONCLUSIONS: Our findings suggest that longer exposure to endogenous estrogen may be associated with increased levels of AD biomarkers in the preclinical phase of AD. These findings, however, need to be confirmed in larger samples. / Video Summary: http://links.lww.com/MENO/A804

Nanoscale surface topography reshapes neuronal growth in culture

International audienceNeurons are sensitive to topographical cues provided either by in vivo or in vitro environments on the micrometric scale. We have explored the role of randomly distributed silicon nanopillars on primary hippocampal neurite elongation and axonal differentiation. We observed that neurons adhere on the upper part of nanopillars with a typical distance between adhesion points of about 500 nm. These neurons produce fewer neurites, elongate faster, and differentiate an axon earlier than those grown on flat silicon surfaces. Moreover, when confronted with a differential surface topography, neurons specify an axon preferentially on nanopillars. As a whole, these results highlight the influence of the physical environment in many aspects of neuronal growth

Capturing complex tumour biology in vitro: Histological and molecular characterisation of precision cut slices

Precision-cut slices of in vivo tumours permit interrogation in vitro of heterogeneous cells from solid tumours together with their native microenvironment. They offer a low throughput but high content in vitro experimental platform. Using mouse models as surrogates for three common human solid tumours, we describe a standardised workflow for systematic comparison of tumour slice cultivation methods and a tissue microarray-based method to archive them. Cultivated slices were compared to their in vivo source tissue using immunohistochemical and transcriptional biomarkers, particularly of cellular stress. Mechanical slicing induced minimal stress. Cultivation of tumour slices required organotypic support materials and atmospheric oxygen for maintenance of integrity and was associated with significant temporal and loco-regional changes in protein expression, for example HIF-1α. We recommend adherence to the robust workflow described, with recognition of temporal-spatial changes in protein expression before interrogation of tumour slices by pharmacological or other means

Mapping the Complex Morphology of Cell Interactions with Nanowire Substrates Using FIB-SEM

Using high resolution focused ion beam scanning electron microscopy (FIB-SEM) we study the details of cell-nanostructure interactions using serial block face imaging. 3T3 Fibroblast cellular monolayers are cultured on flat glass as a control surface and on two types of nanostructured scaffold substrates made from silicon black (Nanograss) with low- and high nanowire density. After culturing for 72 hours the cells were fixed, heavy metal stained, embedded in resin, and processed with FIB-SEM block face imaging without removing the substrate. The sample preparation procedure, image acquisition and image post-processing were specifically optimised for cellular monolayers cultured on nanostructured substrates. Cells display a wide range of interactions with the nanostructures depending on the surface morphology, but also greatly varying from one cell to another on the same substrate, illustrating a wide phenotypic variability. Depending on the substrate and cell, we observe that cells could for instance: break the nanowires and engulf them, flatten the nanowires or simply reside on top of them. Given the complexity of interactions, we have categorised our observations and created an overview map. The results demonstrate that detailed nanoscale resolution images are required to begin understanding the wide variety of individual cells' interactions with a structured substrate. The map will provide a framework for light microscopy studies of such interactions indicating what modes of interactions must be considered

Multiphysics simulation explaining the behaviour of evaporation-driven nanoporous generators

Funding Information: The authors acknowledge the financial support from the Academy of Finland project 319018. L.H. and T.K. acknowledge funding from the Aalto ELEC doctoral school, and C.T. from the Vilho, Yrjö ja Kalle Väisälä Fund grant issued by the Finnish Academy of Arts and Sciences. T.K. acknowledges the support from the Walter Ahlström foundation. Further thanks go to Dr. Benjamin Wilson for the pycnometry measurements. The pycnometry was done using the Raw Materials research infrastructure by Aalto University School of Chemical Engineering, and other experimental work using the facilities and equipment of Micronova Nanofabrication Center. Finally, we acknowledge the computational resources provided by the Aalto Science-IT project. Funding Information: The authors acknowledge the financial support from the Academy of Finland project 319018. L.H. and T.K. acknowledge funding from the Aalto ELEC doctoral school, and C.T. from the Vilho, Yrj? ja Kalle V?is?l? Fund grant issued by the Finnish Academy of Arts and Sciences. T.K. acknowledges the support from the Walter Ahlstr?m foundation. Further thanks go to Dr. Benjamin Wilson for the pycnometry measurements. The pycnometry was done using the Raw Materials research infrastructure by Aalto University School of Chemical Engineering, and other experimental work using the facilities and equipment of Micronova Nanofabrication Center. Finally, we acknowledge the computational resources provided by the Aalto Science-IT project. Publisher Copyright: © 2022 The Author(s)Evaporation-induced electricity generation in porous nanomaterials has recently attracted considerable attention due to relatively high produced voltages and wide operating conditions. Here, we present a combined study of computational and experimental work exploiting finite-element method simulations to find the critical parameters influencing the performance of such generators. The simulated behaviour is found to agree with the experimental data within typical variation of the measurements. We find that the electrical power produced by the generator depends not only on the properties of the porous material, but also on the surrounding environment of the generator. Particularly, the pore size and geometry are found to have a significant influence on the output power, highlighting the importance of accurate characterization of the samples and careful control of the laboratory conditions when performing experimental work. Increasing the pore size from 5 to 20 nm improves the simulated output voltage from 0.12 to 0.47 V, while increasing the ambient humidity to 100% will prevent voltage generation completely. The obtained results can guide the future design of generators based on water evaporation induced capillary flow in a nanoporous carbon black film, leading to more efficient power production.Peer reviewe