A Chronic Increase in Blood-Brain Barrier Permeability Facilitates Intraneuronal Deposition of Exogenous Bloodborne Amyloid-Beta1-42 Peptide in the Brain and Leads to Alzheimer's Disease-Relevant Cognitive Changes in a Mouse Model.

Background: Increased blood-brain barrier (BBB) permeability and amyloid-β (Aβ) peptides (especially Aβ1-42) (Aβ42) have been linked to Alzheimer's disease (AD) pathogenesis, but the nature of their involvement in AD-related neuropathological changes leading to cognitive changes remains poorly understood.

Objective: To test the hypothesis that chronic extravasation of bloodborne Aβ42 peptide and brain-reactive autoantibodies and their entry into the brain parenchyma via a permeable BBB contribute to AD-related pathological changes and cognitive changes in a mouse model.

Methods: The BBB was rendered chronically permeable through repeated injections of Pertussis toxin (PT), and soluble monomeric, fluorescein isothiocyanate (FITC)-labeled or unlabeled Aβ42 was injected into the tail-vein of 10-month-old male CD1 mice at designated intervals spanning ∼3 months.

Mental health differences in medical students based on curriculum and gender.

Background: The prevalence of mental health struggles among students in medical school is widely reported; however, little is known about how it is impacted by the medical school curriculum. This study aimed to evaluate differences in anxiety, depression, and emotional exhaustion in medical students based on gender, class year, and curriculum.

Methods: An anonymous online survey consisting of questions from established, validated questionnaires about demographics, anxiety, depression, emotional exhaustion, and personal health behaviors was sent to 817 medical students who attended Rowan-Virtua School of Osteopathic Medicine during the Spring of 2021.

FDA Emergency Use Authorization-Approved Novel Coronavirus Disease 2019, Pressure-Regulated, Mechanical Ventilator Splitter That Enables Differential Compliance Multiplexing.

Infection with the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may cause viral pneumonia and acute respiratory distress syndrome (ARDS). Treatment of ARDS often requires mechanical ventilation and may take weeks for resolution. In areas with a large outbreaks, there may be shortages of ventilators available.

A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier.

Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway(s) responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier (BBB) function in schizophrenia pathogenesis. However, direct evidence demonstrating an impaired BBB function is missing.

S100B Inhibition Attenuates Intestinal Damage and Diarrhea Severity During Infection by Modulating Inflammatory Response.

The involvement of the enteric nervous system, which is a source of S100B, in () infection (CDI) is poorly understood although intestinal motility dysfunctions are known to occur following infection. Here, we investigated the role of S100B in CDI and examined the S100B signaling pathways activated in toxin A (TcdA)- and B (TcdB)-induced enteric glial cell (EGC) inflammatory response. The expression of S100B was measured in colon tissues and fecal samples of patients with and without CDI, as well as in colon tissues from -infected mice.

Calcium-Dependent Translocation of S100B Is Facilitated by Neurocalcin Delta.

S100B is a calcium-binding protein that governs calcium-mediated responses in a variety of cells-especially neuronal and glial cells. It is also extensively investigated as a potential biomarker for several disease conditions, especially neurodegenerative ones. In order to establish S100B as a viable pharmaceutical target, it is critical to understand its mechanistic role in signaling pathways and its interacting partners.

Silk fibroin-poly(lactic acid) biocomposites: Effect of protein-synthetic polymer interactions and miscibility on material properties and biological responses.

A protein-polymer blend system based on silkworm silk fibroin (SF) and polylactic acid (PLA) was systematically investigated to understand the interaction and miscibility of proteins and synthetic biocompatible polymers in the macro- and micro-meter scales, which can dramatically control the cell responses and enzyme biodegradation on the biomaterial interface. Silk fibroin, a semicrystalline protein with beta-sheet crystals, provides controllable crystal content and biodegradability; while noncrystallizable PDLLA provides hydrophobicity and thermal stability in the system. Differential scanning calorimetry (DSC) combined with scanning electron microscope (SEM) showed that the morphology of the blend films was uniform on a macroscopic scale, yet with tunable micro-phase patterns at different mixing ratios.

Tunable green graphene-silk biomaterials: Mechanism of protein-based nanocomposites.

Green graphene materials prepared by photoreduction of graphite oxide were first time blended with aqueous-based silk fibroin proteins to improve the mechanical and thermal properties of silk biomaterials, and their nanocomposite interaction mechanism was illustrated. Powder X-ray diffraction (XRD) analysis confirmed the complete exfoliation of graphite oxide to graphene in presence of focused pulses of solar radiation. By varying the concentration of graphene (0.

Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: Beneficial effects of the LpPLA inhibitor Darapladib.

Using a porcine model of diabetes mellitus and hypercholesterolaemia, we previously showed that diabetes mellitus and hypercholesterolaemia is associated with a chronic increase in blood-brain barrier permeability in the cerebral cortex, leading to selective binding of immunoglobulin G and deposition of amyloid-beta peptide in pyramidal neurons. Treatment with Darapladib (GlaxoSmithKline, SB480848), an inhibitor of lipoprotein-associated phospholipase-A2, alleviated these effects. Here, investigation of the effects of chronic diabetes mellitus and hypercholesterolaemia on the pig retina revealed a corresponding increased permeability of the blood-retina barrier coupled with a leak of plasma components into the retina, alterations in retinal architecture, selective IgG binding to neurons in the ganglion cell layer, thinning of retinal layers due to cell loss and increased glial fibrillary acidic protein expression in Müller cells, all of which were curtailed by treatment with Darapladib.

An Acute Retinal Model for Evaluating Blood Retinal Barrier Breach and Potential Drugs for Treatment.

A low-cost, easy-to-use and powerful model system is established to evaluate potential treatments that could ameliorate blood retinal barrier breach. An inflammatory factor, histamine, is demonstrated to compromise vessel integrity in the cultured retina through positive staining of IgG outside of the blood vessels. The effects of histamine itself and those of candidate drugs for potential treatments, such as lipoxin A4, are assessed using three parameters: blood vessel leakage via IgG immunostaining, activation of Müller cells via GFAP staining and change in neuronal dendrites through staining for MAP2.

Data on the identity and myristoylation state of recombinant, purified hippocalcin.

In this data article we report on the purity and post translation modification of bacterially expressed and purified recombinant hippocalcin (HPCA): a member of the neuronal calcium sensor protein family, whose functions are regulated by calcium. MALDI-TOF in source decay (ISD) analysis was used to identify both the myristoylated or non-myristoylated forms of the protein. MALDI-TOF ISD data on the identity of the protein, amino acid sequence and myristoylation efficiency are provided.

Datasets depicting mobility retardation of NCS proteins observed upon incubation with calcium, but not with magnesium, barium or strontium.

In this data article we show the specificity of the Ca(2+)-induced mobility shift in three proteins that belong to the neuronal calcium sensor (NCS) protein family: Hippocalcin, GCAP1 and GCAP2. These proteins did not display a shift in mobility in native gels when incubated with divalent cations other than Ca(2+) - such as Mg(2+), Ba(2+), and Sr(2+), even at 10× concentrations. The data is similar to that obtained with another NCS protein, neurocalcin delta (Viviano et al.

Data on the calcium-induced mobility shift of myristoylated and non-myristoylated forms of neurocalcin delta.

This data article presents the differences observed between the myristoylated and non-myristoylated forms of the neuronal calcium sensor protein, neurocalcin delta (NCALD). Analysis of the myristoylated and non-myristoylated versions of the protein by mass spectrometry provided difference in mass values consistent with addition of myristoyl group. In the presence of calcium, mobility retardation was observed upon electrophoresis of the protein in native gels.

Single-column purification of the tag-free, recombinant form of the neuronal calcium sensor protein, hippocalcin expressed in Escherichia coli.

Hippocalcin is a 193 aa protein that is a member of the neuronal calcium sensor protein family, whose functions are regulated by calcium. Mice that lack the function of this protein are compromised in the long term potentiation aspect of memory generation. Recently, mutations in the gene have been linked with dystonia in human.

Data on final calcium concentration in native gel reagents determined accurately through inductively coupled plasma measurements.

In this article we present data on the concentration of calcium as determined by Inductively Coupled Plasma (ICP) measurements. Calcium was estimated in the reagents used for native gel electrophoresis of Neuronal Calcium Sensor (NCS) proteins. NCS proteins exhibit calcium-dependent mobility shift in native gels.

Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice.

S100B is a calcium-sensor protein that impacts multiple signal transduction pathways. It is widely considered to be an important biomarker for several neuronal diseases as well as blood-brain barrier (BBB) breakdown. In this report, we demonstrate a BBB deficiency in mice that lack S100B through detection of leaked Immunoglobulin G (IgG) in the brain parenchyma.

Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures.

Among the top ten causes of death in the United States, Alzheimer's disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported.

Electrophoretic mobility shift in native gels indicates calcium-dependent structural changes of neuronal calcium sensor proteins.

In proteins of the neuronal calcium sensor (NCS) family, changes in structure as well as function are brought about by the binding of calcium. In this article, we demonstrate that these structural changes, solely due to calcium binding, can be assessed through electrophoresis in native gels. The results demonstrate that the NCS proteins undergo ligand-dependent conformational changes that are detectable in native gels as a gradual decrease in mobility with increasing calcium but not other tested divalent cations such as magnesium, strontium, and barium.

Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-β(1-42) deposition.

Previous studies have reported immunoglobulin-positive neurons in Alzheimer's disease (AD) brains, an observation indicative of blood-brain barrier (BBB) breakdown. Recently, we demonstrated the nearly ubiquitous presence of brain-reactive autoantibodies in human sera. The significance of these observations to AD pathology is unknown.

Use of osteopathic manipulative treatment to manage compensated trendelenburg gait caused by sacroiliac somatic dysfunction.

Gait dysfunctions are commonly encountered in the primary care setting. Compensated Trendelenburg gait is a gait dysfunction that was originally described in patients with weakness of ipsilateral hip abduction. This condition is thought to result from neuronal injury or myopathy.

Probing the role of aromatic residues at the secondary saccharide-binding sites of human salivary alpha-amylase in substrate hydrolysis and bacterial binding.

Human salivary alpha-amylase (HSAmy) has three distinct functions relevant to oral health: (1) hydrolysis of starch, (2) binding to hydroxyapatite (HA), and (3) binding to bacteria (e.g., viridans streptococci).

Contribution of glial cells to the development of amyloid plaques in Alzheimer's disease.

Amyloid plaques appear early during Alzheimer's disease (AD), and their development is intimately linked to activated astrocytes and microglia. Astrocytes are capable of accumulating substantial amounts of neuron-derived, amyloid beta(1-42) (Abeta42)-positive material and other neuron-specific proteins as a consequence of their debris-clearing role in response to local neurodegeneration. Immunohistochemical analyses have suggested that astrocytes overburdened with these internalized materials can eventually undergo lysis, and radial dispersal of their cytoplasmic contents, including Abeta42, can lead to the deposition of a persistent residue in the form of small, GFAP-rich, astrocytic amyloid plaques, first appearing in the molecular layer of the cerebral cortex.