Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.

Introduction: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures.

Methods: We included 12,369 non-demented participants from eight population-based studies.

Optoproteomics elucidates the interactome of L-type amino acid transporter 3 (LAT3).

Membrane protein interactions are crucial for diverse biological processes. We report the application of genetic code expansion in combination with photo-crosslinking chemistry, as we termed "optoproteomics", to identify proteins interacting with the human L-type membrane amino acid transporter 3 (LAT3, also known as SLC43A1). The site-specifically incorporated photo-cross-linker p-azido-L-phenylalanine (AzF), which reacts with proteins in their proximity, enabled the capture of weak and transient partners of LAT3 in living cells.

Free sialic acid storage disorder: Progress and promise.

Lysosomal free sialic acid storage disorder (FSASD) is an extremely rare, autosomal recessive, neurodegenerative, multisystemic disorder caused by defects in the lysosomal sialic acid membrane exporter SLC17A5 (sialin). SLC17A5 defects cause free sialic acid and some other acidic hexoses to accumulate in lysosomes, resulting in enlarged lysosomes in some cell types and 10-100-fold increased urinary excretion of free sialic acid. Clinical features of FSASD include coarse facial features, organomegaly, and progressive neurodegenerative symptoms with cognitive impairment, cerebellar ataxia and muscular hypotonia.

Lumbar facet cyst tuberculosis: a rare cause of cauda equina compression. Illustrative case.

Background: Spinal tuberculosis may present in atypical form to involve only the posterior spinal element with relative sparing of the anterior vertebral body and intervertebral disc. Recognition of this unusual pattern is important to avoid delay in diagnosis and treatment.

Observations: The authors report a case of a 59-year-old woman with right-sided radiculopathy and motor weakness.

Astrocytes respond to a neurotoxic Aβ fragment with state-dependent Ca alteration and multiphasic transmitter release.

Excessive amounts of amyloid β (Aβ) peptide have been suggested to dysregulate synaptic transmission in Alzheimer's disease (AD). As a major type of glial cell in the mammalian brain, astrocytes regulate neuronal function and undergo activity alterations upon Aβ exposure. Yet the mechanistic steps underlying astrocytic responses to Aβ peptide remain to be elucidated.

Maternal exposure to PM during pregnancy and asthma risk in early childhood: consideration of phases of fetal lung development.

Background: Increasingly studies suggest prenatal exposure to air pollution may increase risk of childhood asthma. Few studies have investigated exposure during specific fetal pulmonary developmental windows.

Objective: To assess associations between prenatal fine particulate matter exposure and asthma at age 4.

Time Course of Alterations in Adult Spinal Motoneuron Properties in the SOD1(G93A) Mouse Model of ALS.

Although amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease, motoneuron electrical properties are already altered during embryonic development. Motoneurons must therefore exhibit a remarkable capacity for homeostatic regulation to maintain a normal motor output for most of the life of the patient. In the present article, we demonstrate how maintaining homeostasis could come at a very high cost.

Is there hope that transpinal direct current stimulation corrects motoneuron excitability and provides neuroprotection in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of largely unknown pathophysiology, characterized by the progressive loss of motoneurons (MNs). We review data showing that in presymptomatic ALS mice, MNs display reduced intrinsic excitability and impaired level of excitatory inputs. The loss of repetitive firing specifically affects the large MNs innervating fast contracting muscle fibers, which are the most vulnerable MNs in ALS.

Suboptimal Discontinuous Current-Clamp Switching Rates Lead to Deceptive Mouse Neuronal Firing.

Intracellular recordings using sharp microelectrodes often rely on a technique called discontinuous current-clamp (DCC) to accurately record the membrane potential while injecting current through the same microelectrode. It is well known that a poor choice of DCC switching rate can lead to underestimation or overestimation of the cell potential; however, its effect on the cell firing is rarely discussed. Here, we show that suboptimal switching rates lead to an overestimation of cell excitability.

Correlative Imaging of Motoneuronal Cell Elasticity by Pump and Probe Spectroscopy.

Because of their role of information transmitter between the spinal cord and the muscle fibers, motor neurons are subject to physical stimulation and mechanical property modifications. We report on motoneuron elasticity investigated by time-resolved pump and probe spectroscopy. A dual picosecond geometry simultaneously probing the acoustic impedance mismatch at the cell-titanium transducer interface and acoustic wave propagation inside the motoneuron is presented.

Subaxial Cervical Spine Injuries: WFNS Spine Committee Recommendations.

To formulate specific guidelines for the recommendation of subaxial cervical spine injuries concerning classification, management, posttraumatic locked facets and vertebral artery injury. Computerized literature was searched on PubMed and google scholar database from 2009 to 2020. For classification, keywords "Sub Axial Cervical Spine Classification," resulting in 22 articles related to subaxial cervical spine injury classification system (SLICS) system and 11 articles related to AO (Arbeitsgemeinschaft für Osteosynthesefragen, German for "Association for the Study of Internal Fixation") Spine system.

Building neuromuscular junctions .

The neuromuscular junction (NMJ) has been the model of choice to understand the principles of communication at chemical synapses. Following groundbreaking experiments carried out over 60 years ago, many studies have focused on the molecular mechanisms underlying the development and physiology of these synapses. This Review summarizes the progress made to date towards obtaining faithful models of NMJs We provide a historical approach discussing initial experiments investigating NMJ development and function from to mice, the creation of chimeric co-cultures, approaches and co-culture methods from and derived cells, as well as the most recent developments to generate human NMJs.

DNA-Origami-Based Fluorescence Brightness Standards for Convenient and Fast Protein Counting in Live Cells.

Fluorescence microscopy has been one of the most discovery-rich methods in biology. In the digital age, the discipline is becoming increasingly quantitative. Virtually all biological laboratories have access to fluorescence microscopes, but abilities to quantify biomolecule copy numbers are limited by the complexity and sophistication associated with current quantification methods.

Infrared Excitation Induces Heating and Calcium Microdomain Hyperactivity in Cortical Astrocytes.

Unraveling how neural networks process and represent sensory information and how these cellular signals instruct behavioral output is a main goal in neuroscience. Two-photon activation of optogenetic actuators and calcium (Ca) imaging with genetically encoded indicators allow, respectively, the all-optical stimulation and readout of activity from genetically identified cell populations. However, these techniques locally expose the brain to high near-infrared light doses, raising the concern of light-induced adverse effects on the biology under study.

YIF1B mutations cause a post-natal neurodevelopmental syndrome associated with Golgi and primary cilium alterations.

Human post-natal neurodevelopmental delay is often associated with cerebral alterations that can lead, by themselves or associated with peripheral deficits, to premature death. Here, we report the clinical features of 10 patients from six independent families with mutations in the autosomal YIF1B gene encoding a ubiquitous protein involved in anterograde traffic from the endoplasmic reticulum to the cell membrane, and in Golgi apparatus morphology. The patients displayed global developmental delay, motor delay, visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy.

Cathodoluminescence Nanoscopy of 3D Plasmonic Networks.

Nanoporous metallic networks are endowed with the distinctive optical properties of strong field enhancement and spatial localization, raising the necessity to map the optical eigenmodes with high spatial resolution. In this work, we used cathodoluminescence (CL) to map the local electric fields of a three-dimensional (3D) silver network made of nanosized ligaments and holes over a broad spectral range. A multitude of neighboring hotspots at different frequencies and intensities are observed at subwavelength distances over the network.

Short-term depression and long-term plasticity together tune sensitive range of synaptic plasticity.

Synaptic efficacy is subjected to activity-dependent changes on short- and long time scales. While short-term changes decay over minutes, long-term modifications last from hours up to a lifetime and are thought to constitute the basis of learning and memory. Both plasticity mechanisms have been studied extensively but how their interaction shapes synaptic dynamics is little known.

The Effect of the COVID-19 Pandemic on People with Parkinson's Disease.

Background: The effect of the COVID-19 pandemic on people with Parkinson's disease (PD) is poorly understood.

Objective: To rapidly identify areas of need and improve care in people with PD during the COVID-19 pandemic, we deployed a survey to assess COVID-19 symptoms and the pandemic's effect among those with and without COVID-19.

Methods: People with and without PD participating in the online study Fox Insight (FI) were invited to complete a survey between April 23 and May 23, 2020.

The Impact of COVID-19 on Access to Parkinson's Disease Medication.

Background: Many countries have implemented drastic measures to fight the COVID-19 pandemic. Restrictions and diversion of resources may have negatively affected patients with Parkinson's disease (PD). Our aim was to examine whether COVID-19 had an impact on access to PD medication by region and income.

Ultra-sparse Connectivity within the Lateral Hypothalamus.

The lateral hypothalamic area (LH) is a vital controller of arousal, feeding, and metabolism [1, 2], which integrates external and internal sensory information. Whereas sensory and whole-body output properties of LH cell populations have received much interest, their intrinsic synaptic organization has remained largely unstudied. Local inhibitory and excitatory connections could help integrate and filter sensory information and mutually inhibitory connections [3] could allow coordinating activity between LH cell types, some of which have mutually exclusive behavioral effects, such as LH VGLUT2 and VGAT neurons [4-7] and orexin- (ORX) and melanin-concentrating hormone (MCH) neurons [8-10].

Retromer forms low order oligomers on supported lipid bilayers.

Retromer orchestrates the selection and export of integral membrane proteins from the endosome via retrograde and plasma membrane recycling pathways. Long-standing hypotheses regarding the retromer sorting mechanism posit that oligomeric interactions between retromer and associated accessory factors on the endosome membrane drives clustering of retromer-bound integral membrane cargo prior to its packaging into a nascent transport carrier. To test this idea, we examined interactions between components of the sorting nexin 3 (SNX3)-retromer sorting pathway using quantitative single particle fluorescence microscopy in a reconstituted system.

Amino Acids Bearing Aromatic or Heteroaromatic Substituents as a New Class of Ligands for the Lysosomal Sialic Acid Transporter Sialin.

Sialin, encoded by the gene, is a lysosomal sialic acid transporter defective in Salla disease, a rare inherited leukodystrophy. It also enables metabolic incorporation of exogenous sialic acids, leading to autoantibodies against -glycolylneuraminic acid in humans. Here, we identified a novel class of human sialin ligands by virtual screening and structure-activity relationship studies.