A human brain vascular atlas reveals diverse mediators of Alzheimer's risk.

The human brain vasculature is of great medical importance: its dysfunction causes disability and death, and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders. Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment.

Exercise plasma boosts memory and dampens brain inflammation via clusterin.

Physical exercise is generally beneficial to all aspects of human and animal health, slowing cognitive ageing and neurodegeneration. The cognitive benefits of physical exercise are tied to an increased plasticity and reduced inflammation within the hippocampus, yet little is known about the factors and mechanisms that mediate these effects. Here we show that 'runner plasma', collected from voluntarily running mice and infused into sedentary mice, reduces baseline neuroinflammatory gene expression and experimentally induced brain inflammation.

Dysregulation of brain and choroid plexus cell types in severe COVID-19.

Although SARS-CoV-2 primarily targets the respiratory system, patients with and survivors of COVID-19 can suffer neurological symptoms. However, an unbiased understanding of the cellular and molecular processes that are affected in the brains of patients with COVID-19 is missing. Here we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control individuals (including 1 patient with terminal influenza) and 8 patients with COVID-19.

Ageing hallmarks exhibit organ-specific temporal signatures.

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified-such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function-these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis-or 'Mouse Ageing Cell Atlas'-which follows on from the original Tabula Muris.

Physiological blood-brain transport is impaired with age by a shift in transcytosis.

The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport.

Ultrasonic Propagation in Highly Attenuating Insulation Materials.

Experiments have been performed to demonstrate that ultrasound in the 100-400 kHz frequency range can be used to propagate signals through various types of industrial insulation. This is despite the fact that they are highly attenuating to ultrasonic signals due to scattering and viscoelastic effects. The experiments used a combination of piezocomposite transducers and pulse compression processing.

Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues.

Brain endothelial cells (BECs) are key constituents of the blood-brain barrier (BBB), protecting the brain from pathogens and restricting access of circulatory factors. Yet, because circulatory proteins have prominent age-related effects on adult neurogenesis, neuroinflammation, and cognitive function in mice, we wondered whether BECs receive and potentially relay signals between the blood and brain. Using single-cell RNA sequencing of hippocampal BECs, we discover that capillary BECs-compared with arterial and venous BECs-undergo the greatest transcriptional changes in normal aging, upregulating innate immunity and oxidative stress response pathways.

Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1.

An aged circulatory environment can activate microglia, reduce neural precursor cell activity and impair cognition in mice. We hypothesized that brain endothelial cells (BECs) mediate at least some of these effects. We observe that BECs in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of vascular cell adhesion molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions.

Papain-based Single Cell Isolation of Primary Murine Brain Endothelial Cells Using Flow Cytometry.

Brain endothelial cells (BECs) form the integral component of the blood-brain barrier (BBB) which separates the systemic milieu from the brain parenchyma and protects the brain from pathogens and circulating factors. In order to study BEC biology, it was of particular interest to establish a method that enables researchers to investigate and understand the underlying molecular mechanisms regulating their function during homeostasis, aging and disease. Furthermore, due to the heterogeneity of the cerebrovasculature and different vessel types that comprise the BBB, it is of particular interest to isolate primary BECs for single cell analysis from various subregions of the brain, such as the neurogenic and highly vascularized hippocampus and to enrich for specific vessel types.

CD22 blockade restores homeostatic microglial phagocytosis in ageing brains.

Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown.

The Effect of Boundary Conditions on Resonant Ultrasonic Spherical Chains.

The response of a resonant chain of spheres to changes in holder material and precompression is studied at ultrasonic frequencies. The system is found to be very sensitive to these parameters, with the creation of impulsive waveforms from a narrow bandwidth input seen only for certain chain lengths and holder materials. In addition, careful experiments were performed using known amounts of precompression force, using a calibrated stylus arrangement.

What does diffusion tensor imaging (DTI) tell us about cognitive networks in temporal lobe epilepsy?

Diffusion tensor imaging (DTI) has provided considerable insight into our understanding of epilepsy as a network disorder, revealing subtle alterations in white matter microstructure both proximal and distal to the epileptic focus. These white matter changes have been shown to assist with lateralizing the seizure focus, as well as delineating the location/anatomy of key white matter tracts (i.e.

My Horse Is My Therapist: The Medicalization of Pleasure among Women Equestrians.

Pink t-shirts that proclaim "My horse is my therapist" are for sale in a wide variety of horse-sport catalogues. Literature on the healing power of human-nonhuman animal encounters and the practice of a variety of animal-assisted therapy programs, such as hippotherapy and equine-facilitated therapy, show dramatic growth over the last 30 years. Less attention is paid to the role that horse-human interactions may play in more popular accountings of well-being and impairment among a sample of everyday riders.

Coded waveforms for optimised air-coupled ultrasonic nondestructive evaluation.

This paper investigates various types of coded waveforms that could be used for air-coupled ultrasound, using a pulse compression approach to signal processing. These are needed because of the low signal-to-noise ratios that are found in many air-coupled ultrasonic nondestructive evaluation measurements, due to the large acoustic mismatch between air and many solid materials. The various waveforms, including both swept-frequency signals and those with binary modulation, are described, and their performance in the presence of noise is compared.

Case-loading midwifery in New Zealand: bridging the normal/abnormal divide 'with woman'.

Objectives: to explore the way that case-loading midwives in New Zealand construct midwifery (and in so doing, the concepts of woman and childbirth). This paper illuminates the fundamental features of this construction (continuity and woman-centred care) and discusses this with regard to the role of midwives vis-à-vis normal/abnormal birth.

Design: semi-structured interviews and official publications constituted the 'text' which was analysed using a poststructural approach that was informed by theorists Foucault, Grosz and Braidotti.

The need to develop centers for environmental oncology.

The scale and scope of the cancer problem in the United States today is much greater than four decades ago when the formal war against the disease was first announced. Patterns of the disease are not fully explained by known risk factors. Much progress has been made in understanding the molecular basis of carcinogenesis, particularly the near consensus (realization) that virtually all cancers arise from an accumulation of genetic mutations and the more recent recognition of the role of inflammation and the tissue microenvironment, in particular for hormone-dependent cancers.

Characterization of cMuts in rarefied gases.

The performance of capacitive micromachined ultrasonic transducers (cMUTs) was investigated at low pressures in various gases such as air, carbon dioxide, and helium. The aim was to replicate the pressure conditions likely to meet on the surface of other planets such as Mars, where ultrasonic wind velocity measurements might be possible. It is demonstrated that cMUTs are capable of operating at low pressures, and the response to pressures below terrestrial atmospheric values is observed experimentally and compared to theoretical predictions.

High-throughput killer cell immunoglobulin-like receptor genotyping by MALDI-TOF mass spectrometry with discovery of novel alleles.

The killer cell immunoglobulin-like receptors (KIR) interact with major histocompatibility complex (MHC) class I ligands to regulate the functions of natural killer cells and T cells. Like human leukocyte antigens class I, human KIR are highly variable and correlated with infection, autoimmunity, pregnancy syndromes, and transplantation outcome. Limiting the scope of KIR analysis is the low resolution, sensitivity, and speed of the established methods of KIR typing.

Through-transmission imaging of solids in air using ultrasonic gas-jet waveguides.

An ultrasonic waveguide has been produced in air by using a gas jet. This uses the fact that a lower acoustic velocity can be produced within the jet, relative to the air surrounding it. The lower velocity is achieved by mixing carbon dioxide with air within the jet at a concentration that is a compromise between lower acoustic velocity and increasing attenuation.

Aldosterone and aldosterone antagonism in cardiovascular disease: focus on eplerenone (Inspra).

Aldosterone has long been known to mediate water and electrolyte balance by acting on mineralocorticoid receptors in the kidneys. However, recent studies have demonstrated the presence of these receptors in nonclassical locations, including the brain, blood vessels, and the heart. This finding suggests that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease.

Analysis of pesticide residues on museum objects repatriated to the Hupa tribe of California.

In the past, it was common practice for museum professionals and private collectors to apply a variety of pesticide agents to objects in their collections to preserve them from depredations by microorganisms, fungi, and other pests. The Native American Graves Repatriation and Protection Act allows federally recognized tribes to request that museums return objects taken from their ancestors. Given that poor records were kept on the treatment of individual objects, it is unknown whether specific objects are contaminated with these pesticide agents.