Altered neural odometry in the vertical dimension

Entorhinal grid cells integrate sensory and self-motion inputs to provide a spatial metric of a characteristic scale. One function of this metric may be to help localize the firing fields of hippocampal place cells during formation and use of the hippocampal spatial representation (“cognitive map”). Of theoretical importance is the question of how this metric, and the resulting map, is configured in 3D space. We find here that when the body plane is vertical as rats climb a wall, grid cells produce stable, almost-circular grid-cell firing fields. This contrasts with previous findings when the body was aligned horizontally during vertical exploration, suggesting a role for the body plane in orienting the plane of the grid cell map. However, in the present experiment, the fields on the wall were fewer and larger, suggesting an altered or absent odometric (distance-measuring) process. Several physiological indices of running speed in the entorhinal cortex showed reduced gain, which may explain the enlarged grid pattern. Hippocampal place fields were found to be sparser but unchanged in size/shape. Together, these observations suggest that the orientation and scale of the grid cell map, at least on a surface, are determined by an interaction between egocentric information (the body plane) and allocentric information (the gravity axis). This may be mediated by the different sensory or locomotor information available on a vertical surface and means that the resulting map has different properties on a vertical plane than a horizontal plane (i.e., is anisotropic)

Impact of the COVID-19 Shutdown on Mental Health in Appalachia by Working Status

Introduction: To slow the spread of COVID-19 in the United States, businesses shutdown in Spring 2020. Research has indicated the impact on frontline workers, yet little is known about the impact on those who were not working outside the home or switched to working remotely. Purpose: The purpose of this report is to identify the financial and healthcare issues and mental health impact of the COVID-19 shutdown on Appalachians by worker categories. Methods: An online survey was administered from May 8 – June 6, 2020 to a convenience sample of previous research participants and shared through social media networks, i.e., snowball sampling. Questions investigated mental health, financial and healthcare issues, and employment status. Survey responses were summarized by percentages overall and by working categories. Results: Of the 751 participants, 276 (42%) resided in Appalachia. After removing 17 who lost their job due to COVID-19, 59 (23%) indicated not working outside the home prior to COVID-19, whereas 111 (43%) and 89 (34%) switched to working remotely and continued working outside the home during the shutdown. Respondents were predominately Caucasian and female. Nearly a quarter of participants had lost or reduced income due to the shutdown. Approximately half missed or postponed healthcare appointments. Mental health impacts were similar across the groups, with half of the respondents reporting anxiety due to COVID-19. Implications: Further research is needed to explore health outcomes associated with missed healthcare appointments during the shutdown. Mental health support may be needed equally by those isolated at home and frontline workers

Water jet rebounds on hydrophobic surfaces : a first step to jet micro-fluidics

When a water jet impinges upon a solid surface it produces a so called hydraulic jump that everyone can observe in the sink of its kitchen. It is characterized by a thin liquid sheet bounded by a circular rise of the surface due to capillary and gravitational forces. In this phenomenon, the impact induces a geometrical transition, from the cylindrical one of the jet to the bi-dimensional one of the film. A true jet rebound on a solid surface, for which the cylindrical geometry is preserved, has never been yet observed. Here we experimentally demonstrate that a water jet can impact a solid surface without being destabilized. Depending on the incident angle of the impinging jet, its velocity and the degree of hydrophobicity of the substrate, the jet can i) bounce on the surface with a fixed reflected angle, ii) land on it and give rise to a supported jet or iii) be destabilized, emitting drops. Capillary forces are predominant at the sub-millimetric jet scale considered in this work, along with the hydrophobic nature of the substrate. The results presented in this letter raise the fundamental problem of knowing why such capillary hydraulic jump gives rise to this unexpected jet rebound phenomenon. This study furthermore offers new and promising possibilities to handle little quantity of water through "jet micro-fluidics

Accuracy of Immunofluorescence in the Diagnosis of Primary Ciliary Dyskinesia

RATIONALE The standard approach to diagnosis of primary ciliary dyskinesia (PCD) in the UK consists of assessing ciliary function by high-speed-microscopy and ultrastructure by election microscopy, but equipment and expertise is not widely available internationally. The identification of bi-allelic disease causing mutations is also diagnostic, but many disease causing genes are unknown, and testing is not widely available outside the USA. Fluorescent antibodies to ciliary proteins are used to validate research genetic studies, but diagnostic utility in this disease has not been systematically evaluated. OBJECTIVES: Determine utility of a panel of six fluorescent labelled antibodies as a diagnostic tool for PCD. METHODS: Immunofluorescent labelling of nasal brushings from a discovery cohort of 35 patients diagnosed with PCD by ciliary ultrastructure, and a diagnostic accuracy cohort of 386 patients referred with symptoms suggestive of disease. The results were compared to diagnostic outcome. MEASUREMENTS AND MAIN RESULTS: Immunofluorescence correctly identified mislocalised or absent staining in 100% of the discovery cohort. In the diagnostic cohort immunofluorescence successfully identified 22 of 25 patients with PCD and normal staining in all 252 in whom PCD was considered highly unlikely. Immunofluorescence additionally provided a result in 55% (39) of cases which were previously inconclusive. Immunofluorescence results were available within 14 days, costing $187 per sample compared to electron microscopy (27 days, cost$1452). CONCLUSIONS: Immunofluorescence is a highly specific diagnostic test for PCD, and improves the speed and availability of diagnostic testing, however, sensitivity is limited and immunofluorescence is not suitable as a stand-alone test

Mechanisms of Copper Ion Mediated Huntington's Disease Progression

Huntington's disease (HD) is caused by a dominant polyglutamine expansion within the N-terminus of huntingtin protein and results in oxidative stress, energetic insufficiency and striatal degeneration. Copper and iron are increased in the striata of HD patients, but the role of these metals in HD pathogenesis is unknown. We found, using inductively-coupled-plasma mass spectroscopy, that elevations of copper and iron found in human HD brain are reiterated in the brains of affected HD transgenic mice. Increased brain copper correlated with decreased levels of the copper export protein, amyloid precursor protein. We hypothesized that increased amounts of copper bound to low affinity sites could contribute to pro-oxidant activities and neurodegeneration. We focused on two proteins: huntingtin, because of its centrality to HD, and lactate dehydrogenase (LDH), because of its documented sensitivity to copper, necessity for normoxic brain energy metabolism and evidence for altered lactate metabolism in HD brain. The first 171 amino acids of wild-type huntingtin, and its glutamine expanded mutant form, interacted with copper, but not iron. N171 reduced Cu(2+) in vitro in a 1∶1 copper∶protein stoichiometry indicating that this fragment is very redox active. Further, copper promoted and metal chelation inhibited aggregation of cell-free huntingtin. We found decreased LDH activity, but not protein, and increased lactate levels in HD transgenic mouse brain. The LDH inhibitor oxamate resulted in neurodegeneration when delivered intra-striatially to healthy mice, indicating that LDH inhibition is relevant to neurodegeneration in HD. Our findings support a role of pro-oxidant copper-protein interactions in HD progression and offer a novel target for pharmacotherapeutics

Durrington Walls to West Amesbury by way of Stonehenge: a major transformation of the Holocene landscape

A new sequence of Holocene landscape change has been discovered through an investigation of sediment sequences, palaeosols, pollen and molluscan data discovered during the Stonehenge Riverside Project. The early post-glacial vegetational succession in the Avon valley at Durrington Walls was apparently slow and partial, with intermittent woodland modification and the opening-up of this landscape in the later Mesolithic and earlier Neolithic, though a strong element of pine lingered into the third millennium BC. There appears to have been a major hiatus around 2900 cal BC, coincident with the beginnings of demonstrable human activities at Durrington Walls, but slightly after activity started at Stonehenge. This was reflected in episodic increases in channel sedimentation and tree and shrub clearance, leading to a more open downland, with greater indications of anthropogenic activity, and an increasingly wet floodplain with sedges and alder along the river’s edge. Nonetheless, a localized woodland cover remained in the vicinity of DurringtonWalls throughout the third and second millennia BC, perhaps on the higher parts of the downs, while stable grassland, with rendzina soils, predominated on the downland slopes, and alder–hazel carr woodland and sedges continued to fringe the wet floodplain. This evidence is strongly indicative of a stable and managed landscape in Neolithic and Bronze Age times. It is not until c 800–500 cal BC that this landscape was completely cleared, except for the marshy-sedge fringe of the floodplain, and that colluvial sedimentation began in earnest associated with increased arable agriculture, a situation that continued through Roman and historic times

The role of taxonomic expertise in interpretation of metabarcoding studies

Abstract The performance of DNA metabarcoding approaches for characterizing biodiversity can be influenced by multiple factors. Here, we used morphological assessment of taxa in zooplankton samples to develop a large barcode database and to assess the congruence of taxonomic identification with metabarcoding under different conditions. We analysed taxonomic assignment of metabarcoded samples using two genetic markers (COI, 18S V1–2), two types of clustering into molecular operational taxonomic units (OTUs, ZOTUs), and three methods for taxonomic assignment (RDP Classifier, BLASTn to GenBank, BLASTn to a local barcode database). The local database includes 1042 COI and 1108 18S (SSU) barcode sequences, and we added new high-quality sequences to GenBank for both markers, including 109 contributions at the species level. The number of phyla detected and the number of taxa identified to phylum varied between a genetic marker and among the three methods used for taxonomic assignments. Blasting the metabarcodes to the local database generated multiple unique contributions to identify OTUs and ZOTUs. We argue that a multi-marker approach combined with taxonomic expertise to develop a curated, vouchered, local barcode database increases taxon detection with metabarcoding, and its potential as a tool for zooplankton biodiversity surveys

Modern Solutions for Ancient Pathogens: Direct Pathogen Sequencing for Diagnosis of Lepromatous Leprosy and Cerebral Coenurosis.

Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts