Amyloid plaques and normal ageing have differential effects on microglial Ca activity in the mouse brain.

In microglia, changes in intracellular calcium concentration ([Ca]) may regulate process motility, inflammasome activation, and phagocytosis. However, while neurons and astrocytes exhibit frequent spontaneous Ca activity, microglial Ca signals are much rarer and poorly understood. Here, we studied [Ca] changes of microglia in acute brain slices using Fluo-4-loaded cells and mice expressing GCaMP5g in microglia.

Head-to-head comparison of six warning scores to predict mortality and clinical impairment in COVID-19 patients in emergency department.

The aim was to evaluate the ability of six risk scores (4C, CURB65, SEIMC, mCHOSEN, QuickCSI, and NEWS2) to predict the outcome of patients with COVID-19 during the sixth pandemic wave in Spain. A retrospective observational study was performed to review the electronic medical records in patients ≥ 18 years of age who consulted consecutively in an emergency department with COVID-19 diagnosis throughout 2 months during the sixth pandemic wave. Clinical-epidemiological variables, comorbidities, and their respective outcomes, such as 30-day in-hospital mortality and clinical deterioration risk (a combined outcome considering: mechanical ventilation, intensive care unit admission, and/or 30-day in-hospital mortality), were calculated.

Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time.

Phagocytosis by glial cells is essential to regulate brain function during health and disease. Therapies for Alzheimer's disease (AD) have primarily focused on targeting antibodies to amyloid β (Aβ) or inhibitng enzymes that make it, and while removal of Aβ by phagocytosis is protective early in AD it remains poorly understood. Impaired phagocytic function of glial cells during later stages of AD likely contributes to worsened disease outcome, but the underlying mechanisms of how this occurs remain unknown.

Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes.

Cerebral blood flow is reduced early in the onset of Alzheimer's disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism.

GABAR isoform and subunit structural motifs determine synaptic and extrasynaptic receptor localisation.

GABA receptors (GABARs) are the principal inhibitory neurotransmitter receptors in the central nervous system. They control neuronal excitability by synaptic and tonic forms of inhibition mostly mediated by different receptor subtypes located in specific cell membrane subdomains. A consensus suggests that α1-3βγ comprise synaptic GABARs, whilst extrasynaptic α4βδ, α5βγ and αβ isoforms largely underlie tonic inhibition.

Improving Mouse Models for Dementia. Are All the Effects in Tau Mouse Models Due to Overexpression?

Mouse models of Alzheimer's disease have commonly used transgenic overexpression of genes involved in production of amyloid β ( and/or ) or Tau () with mutations that result in familial forms of dementia. We discuss possible improvements that may create full models while avoiding the problems of overexpression and report synaptic results in APPKI models. We stress use of inappropriate controls without overexpression of the normal human protein and the mismatch between the learning deficits reported in mice with plaques but no tangles and the human condition.

Ion Channels and Receptors as Determinants of Microglial Function.

Microglia provide immune surveillance of the CNS. They display diverse behaviors, including nondirectional and directed motility of their processes, phagocytosis of targets such as dying neurons or superfluous synapses, and generation of reactive oxygen species (ROS) and cytokines. Many of these functions are mediated by ion channels and cell surface receptors, the expression of which varies with the many morphological and functional states that microglial cells can adopt.

Dynamics and Embedded Internet of Things Input Shaping Control for Overhead Cranes Transporting Multibody Payloads.

Input shaping is an Optimal Control feedforward strategy whose ability to define how and when a flexible dynamical system defined by Ordinary Differential Equations (ODEs) and computer controlled would move into its operative space, without command induced unwanted dynamics, has been exhaustively demonstrated. This work examines the issue of Embedded Internet of Things (IoT) Input Shaping with regard to real time control of multibody oscillatory systems whose dynamics are better described by differential algebraic equations (DAEs). An overhead crane hanging a double link multibody payload has been appointed as a benchmark case; it is a multibody, multimode system.

Human Induced Pluripotent Stem Cells and the Modelling of Alzheimer's Disease: The Human Brain Outside the Dish.

Background: Neurodegenerative diseases like Alzheimer's Disease (AD) are a global health issue primarily in the elderly. Although AD has been investigated using primary cultures, animal models and post-mortem human brain tissues, there are currently no effective treatments.

Summary: With the advent of induced pluripotent stem cells (iPSCs) reprogrammed from fully differentiated adult cells such as skin fibroblasts, newer opportunities have arisen to study the pathophysiology of many diseases in more depth.