disturbances in brain charges

Alzheimer's disease (AD) accounts for a major statistic among the class of neurodegenerative diseases. A number of mechanisms have been identified in its pathogenesis and progression which include the amyloid beta (Aβ) aggregation, hyperphosphorylation of tau protein, oxidative stress, endoplasmic reticulum (ER) stress and apoptosis. These processes are interconnected and contribute significantly to the loss of neurons, brain mass and consequential memory loss and other cognitive difficulties. Oxidative stress in AD appears to be caused by excess of oxygen free radicals and extracellular Aβ deposits that cause local inflammatory processes and activate microglia, another possible source of reactive oxygen species (ROS)...

The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood-brain barrier (BBB) and the dense glioblastoma tissue. To achieve efficient BBB crossing and deep GBM penetration, we demonstrated a strategy of active transcellular transport of a mitochondrion-disturbing nanomedicine, GBEPPT, in the GBM tissue through mitocytosis. GBEPPT was computer-aided designed and prepared by self-assembling a conjugate of an amphiphilic block polymer and a drug podophyllotoxin (PPT). When GBEPPT was delivered to the tumor site, overexpressed γ-glutamyl transpeptidase (GGT) on the brain-blood endothelial cell or the GBM cell triggered enzymatic hydrolysis of γ-glutamylamide on GBEPPT to reverse its charge...

Lysine-based post-translational modification (PTM) such as acylation, acetylation, deamination, methylation, SUMOylation, and ubiquitination has proven to be a major regulator of gene expression, chromatin structure, protein stability, protein-protein interaction, protein degradation, and cellular localization. However, besides all the PTMs, ubiquitination stands as the second most common PTM after phosphorylation that is involved in the etiology of neurodegenerative diseases (NDDs) namely, Alzheimer's disease (AD) and Parkinson's disease (PD)...

Older adults represent the fastest growing population in the United States (US) and this portion of the population is expected to double to more than 80 million by 2050.1 Currently, older adults have more active lifestyles, therefore are at an increased risk of injury.2 Older adults currently represent 23% of trauma admissions.3 This number is projected to increase to 39% by 2050.3 In fact, over the last decade, unintentional injuries have climbed from the 9th to the 7th leading cause of death among older adults...

A 72-year-old male developed neurological symptoms such as difficulty in charging his electronic money card and making his mobile-phone call ten months before admission. On admission, neurological examination revealed extensive higher brain dysfunction such as impairment in recent memory, executive function disorders, constructional disturbance, agraphia and acalculia. Brain MRI revealed a low intensity lesion on the surface of the cerebral cortex diffusely and symmetrically on T2 *-weighted images. MRI images are consistent with superficial siderosis...

Homeostasis is crucial for cell function, and disturbances in homeostasis can lead to health disorders. Under normal conditions, intracellular pH is maintained between 7.35 and 7.45. Altered endosomal and lysosomal pH together with a general drop in brain pH are associated with the aggregation of amyloid-β-peptide (Aβ) and the development of Alzheimer's disease. Under acidic conditions, close to the Aβ isoelectric point, the absence of charges favors the formation of intermolecular contacts and promotes aggregation...

The deposition of β-amyloid (Aβ) in the brain leads to neurotoxic effects and subsequent Alzheimer's disease (AD). While AD is becoming more and more prevalent in modern society, therapeutic efforts targeting Aβ could be a promising solution. Currently, two natural products are reported to disintegrate preformed Aβ fibril in vitro. Meanwhile, the chemical driving force behind this phenomenon remains unknown. Taking cyanidin-3-O-glucoside (Cy-3G) as an example, here we studied its interaction with different Aβ polymorphs in silico...

Bipolar disorder (BP) is a lifelong psychiatric condition, which often disrupts the daily life of the patients. It is characterized by unstable and periodic mood changes, which cause patients to display unusual shifts in mood, energy, activity levels, concentration and the ability to carry out day-to-day tasks. BP is a major psychiatric condition, and it is still undertreated. The causes and neural mechanisms of bipolar disorder are unclear, and diagnosis is still mostly based on psychiatric examination, furthermore the unstable character of the disorder makes diagnosis challenging...

GRIN2B mutations are rare but often associated with patients having severe neurodevelopmental disorders with varying range of symptoms such as intellectual disability, developmental delay and epilepsy. Patient symptoms likely arise from mutations disturbing the role that the encoded NMDA receptor subunit, GluN2B, plays at neuronal connections in the developing nervous system. In this study, we investigated the cell-autonomous effects of putative gain- (GoF) and loss-of-function (LoF) missense GRIN2B mutations on excitatory synapses onto CA1 pyramidal neurons in organotypic hippocampal slices...

Photoelectrochemical (PEC) sensing has been developing quickly in recent years, while its in vivo application is still in the infancy. The complexity of biological environments poses a high challenge to the specificity and reliability of PEC sensing. We herein proposed the concept of small-molecule organic semiconductor (SMOS)-based ratiometric PEC sensing making use of the structural flexibility as well as readily tunable energy band of SMOS. Xanthene skeleton-based CyOH was prepared as a photoactive molecule, and its absorption band and corresponding PEC output can be modulated by an intramolecular charge transfer process...

The liver is the primary organ affected by cholestasis. However, the brain, skeletal muscle, heart, and kidney are also severely influenced by cholestasis/cirrhosis. However, little is known about the molecular mechanisms of organ injury in cholestasis. The current study was designed to evaluate the mitochondrial glutathione redox state as a significant index in cell death. Moreover, tissue energy charge (EC) was calculated. Rats underwent bile duct ligation (BDL) and the brain, heart, liver, kidney, and skeletal muscle mitochondria were assessed at scheduled time intervals (3, 7, 14, and 28 days after BDL)...

Alzheimer's Disease is driven by protein aggregation and is characterized by accumulation of Tau protein into neurofibrillary tangles. In healthy neurons the cellular protein quality control is successfully in charge of protein folding, which raises the question to which extent this control is disturbed in disease. Here, we describe that brain cells in Alzheimer's Disease show very specific derailment of the protein quality control network. We performed a meta-analysis on the Alzheimer's Disease Proteome database, which provides a quantitative assessment of disease-related proteome changes in six brain regions in comparison to age-matched controls...

The value of addressing trauma-related issues in psychosis with therapies such as ṇEMDR is being increasingly recognised. The hypothesis of this paper is that augmentation of EMDR with alternating bilateral photic stimulation (ABPS) is especially suited to those on the schizotypal spectrum. Not only does Alternating Bilateral Photic Stimulation (ABPS) at alpha frequencies (8-12 Hz) directly compensate EEG deficits of schizophrenia by photic driving, it also stimulates pseudo-hallucinatory visual imagery (visions) and a waking dream state...

OBJECTIVE: The risk of readmission after brain tumor resection among pediatric patients has not been defined. The authors' objective was to evaluate the readmission rates and predictors of readmission after pediatric brain tumor resection. METHODS: Nationwide Readmissions Database (NRD) data sets from 2010 to 2014 were searched for unplanned readmissions within 30 days of the discharge date after pediatric brain tumor resection. Patient demographic variables included sex, age, expected payment source (Medicaid or private insurance), and median annual household income...

We investigate the impact of solar activity changes on mortality from cardiovascular causes of death in the period 1994-2011 in the Czech Republic. This period coincides with the time of solar cycle no. 23 and the surrounding minima when there was an unusually low level of solar activity. We use long-period daily time series of numbers of deaths by cause, solar activity indices (the relative sunspot number, and the intensity of solar radio flux), geomagnetic indices (Kp-the planetary index that indicates the fluctuation rate of horizontal components of the geomagnetic field, the Auroral Electrojet, and the disturbance storm time), and physical parameters describing the ionospheric effects (the critical frequency of the ionospheric F2 layer and the content of free electrons in the ionosphere)...

The history of Neurocinema includes neuroethics, and this theme was first used in 2 films released in the 1940s in both Germany and the United States. Ich Klage An (I Accuse) is about "terminal" multiple sclerosis in a young woman and the decision to determine one's own fate. The protagonist anticipates becoming "deaf, blind, and idiotic" and asks her husband to administer a toxic drug dose, which he does. The film disturbingly suggests that the diagnosis of multiple sclerosis is tantamount to a death sentence...

The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors...

Alzheimer disease (AD) is one of the most common neurodegenerative disorders widely occurring among the elderly. The pathogenic mechanisms involved in the development of this disease are still unknown. In AD, in addition to brain, a number of peripheral tissues and cells are affected, including erythrocytes. In this study, we analyzed glycolytic energy metabolism, antioxidant status, glutathione, adenylate and proteolytic systems in erythrocytes from patients with AD and compared with those from age-matched controls and young adult controls...

Disturbance of calcium homeostasis is implicated in the normal process of aging and brain pathology prevalent in the elderly such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Previous studies demonstrated that applying a hyponatremic iso-osmotic (low-NaCl) artificial cerebrospinal fluid (ACSF) to rodent hippocampus causes extracellular calcium to rapidly decrease. Restoring normonatremia after low-NaCl treatment causes a rapid increase in extracellular calcium that overshoots baseline. This study examined the amplitude, timing, and mechanism of these surprising calcium changes...

Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms...