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Abstract Preclinical methods are needed for screening potential Alzheimer’s disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. Long-term potentiation (LTP), which is a correlate of learning and memory, was induced in mature human iPSC-derived cortical neurons cultured on microelectrode arrays utilizing circuit patterns connecting two adjacent electrodes. We demonstrated an LTP system that modeled the MCI and pre-MCI stages of Alzheimer’s and validated this functional system utilizing four AD therapeutics, which was also verified utilizing patch-clamp electrophysiology. LTP was induced by tetanic electrical stimulation, and LTP maintenance was significantly reduced in the presence of Amyloid-Beta 42 (Aβ42) oligomers compared to the controls, however, co-treatment with AD therapeutics (Donepezil, Memantine, Rolipram and Saracatinib) corrected Aβ42-induced LTP impairment. The results illustrate the utility of the system as a validated platform to model MCI AD pathology, and potentially for the pre-MCI phase before significant neuronal death. This system also has the potential to become an ideal platform for high-content therapeutic screening for other neurodegenerative diseases.

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.

Microtremor seismic surveys are routinely used to provide shear wave velocities that are converted to soil stiffness site profiles. In this paper, we look to assess the feasibility of using trains as seismic sources to characterize near-surface geology, define the optimum survey parameters to collect train-induced vibrations (i.e., array location and orientation to the railway) and find how the geology affects train-induced vibration characteristics. Three-component train-induced shear wave vibrations were recorded on short (44 m) and long (115 m) linear seismic arrays, both parallel and orthogonal to the nearby railway embankment, using standard seismic refraction recording equipment. The collected data were divided into short/long array size/orientation and seismic components for each survey configuration. 1D shear wave velocity-depth profiles were also generated for all data sets. Results showed thst long linear arrays with vertical components, parallel to the railway embankment, was optimal with the greater depth ranges. The vertical component amplitude of train-induced vibrations was found to be affected by the site geology, increasing with the thickening of Quaternary deposits and having different magnitudes for trains traveling in different directions. Results showed that different apparent shear-wave velocities were obtained from different train groups and different seismic components. The passenger trains (i.e. Virgin Trains Pendolino and British Midland 319 series) generate Rayleigh waves at higher frequencies than the freight trains.

This study represents the first attempt to map the sediment thickness spatial distribution along the Andalusian coastal zone by integrating various publicly available datasets. While prior studies have presented bedform- and sediment-type syntheses, none have attempted to quantify sediment thickness at the scale and resolution performed in this study. The study area has been divided into 18 physiographic zones, and we have used BGS Groundhog Desktop v2.6 software for 3D modeling and sediment thickness model calculations. We present here the modeling workflow, model results, and the challenges that we have encountered, including discrepancies in geological maps, difficulty managing data input for grain size/consolidation, and the need for additional geological information. We have compared the modeled sediment fractions of the unconsolidated material with 4194 seabed samples distributed along the study area and found that the differences between the modeled versus the sampled emphasized the importance of incorporating river contributions, particularly from the Guadalquivir River, into the model for more accurate results. The model intermediate and final outputs and the software routines used to query the sediment thickness model are provided as publicly accessible datasets and tools. The modeled sediment thickness could contribute to making quantitative predictions of morphological change at a scale that is relevant to longer-term strategic coastal management in Andalusia. The methodology and tools used for this study are transferable to any study area.

Since the end of the last glaciation, the United Kingdom’s land surface has been altered by isostatic rebound, rising in the north and sinking in the south. Numerous studies have been published documenting the impact of isostatic rebound on relative sea levels. However, due to the difficulties in acquiring evidence to prove former sea levels, locally, these data can be sparse or absent. In this work, we explored the suitability of the passive seismic survey (PSS) method to estimate the contemporaneous beach thickness in coastal environments where there is a high impedance contrast between the beach deposits and the underlying wave-cut platform. We conducted a three-day survey at Perran Beach, Cornwall, collected 149 measurements using PSS, and interpreted the observations supported by auxiliary topographical, geological, and independent geophysical observation in the study area. The study site is a contemporaneous beach mostly composed of sand underlain by a wave-cut platform composed of igneous and sedimentary rock, therefore high impedance contrast with the sandy beach is anticipated. The elevation of the bedrock relative to the topographical elevation suggests that the bedrock elevation is −15 m ± 5 m below the present day mean sea level, which is coherent with the observation of relative sea level rise along the region of the south-west. The present study contributes to our current limited understanding of land and sea level movements by providing further subsurface information to the coastal geological archive of south-west England, a region currently in need of more data to reconstruct land- and sea-level movements.