Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a knock-in tauopathy model.

Missense mutations in the gene encoding the microtubule-associated protein TAU (current and approved symbol is MAPT) cause autosomal dominant forms of frontotemporal dementia. Multiple models of frontotemporal dementia based on transgenic expression of human in experimental model organisms, including , have been described. These models replicate key features of the human disease but do not faithfully recreate the genetic context of the human disorder.

An integrative systems-biology approach defines mechanisms of Alzheimer's disease neurodegeneration.

Despite years of intense investigation, the mechanisms underlying neuronal death in Alzheimer's disease, the most common neurodegenerative disorder, remain incompletely understood. To define relevant pathways, we integrated the results of an unbiased, genome-scale forward genetic screen for age-associated neurodegeneration in with human and Alzheimer's disease-associated multi-omics. We measured proteomics, phosphoproteomics, and metabolomics in models of Alzheimer's disease and identified Alzheimer's disease human genetic variants that modify expression in disease-vulnerable neurons.

Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a knock-in tauopathy model.

Missense mutations in the gene encoding the microtubule-associated protein tau cause autosomal dominant forms of frontotemporal dementia. Multiple models of frontotemporal dementia based on transgenic expression of human tau in experimental model organisms, including , have been described. These models replicate key features of the human disease, but do not faithfully recreate the genetic context of the human disorder.

Intercalation of C60 into MXene Multilayers: A Promising Approach for Enhancing the Electrochemical Properties of Electrode Materials for High-Performance Energy Storage Applications.

In this study, we report on the enhancement of the electrochemical properties of MXene by intercalating C60 nanoparticles between its layers. The aim was to increase the interlayer spacing of MXene, which has a direct effect on capacitance by allowing the electrolyte flow in the electrode. To achieve this, various concentrations of TiSiC (known as MXene) and C60 nanocomposites were prepared through a hydrothermal process under optimal conditions.

A Drosophila model relevant to chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in Drosophila, our goal was to validate a Drosophila model relevant to CRCI.

Integrative analysis reveals a conserved role for the amyloid precursor protein in proteostasis during aging.

Aβ peptides derived from the amyloid precursor protein (APP) have been strongly implicated in the pathogenesis of Alzheimer's disease. However, the normal function of APP and the importance of that role in neurodegenerative disease is less clear. We recover the Drosophila ortholog of APP, Appl, in an unbiased forward genetic screen for neurodegeneration mutants.

A model of chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in , our goal was to validate a model of CRCI.

Knowledge, attitudes, and factors associated with vegetarianism in the Saudi Population.

Background: In recent years, there has been great interest in the dietary practices of vegetarians in addition to an increasing awareness of the potential benefits of vegetarian diets. However, there are insufficient data on the spread of vegetarianism in Arab countries. The aim of this study was to investigate knowledge and attitudes about vegetarianism and associated factors in the Saudi population and to understand the reasons for its growing prevalence.

Refeeding Syndrome Awareness among Physicians of King Abdullah Medical City in Makkah, Saudi Arabia.

Background: Refeeding syndrome (RFS) is a lethal condition of metabolic disturbances that arise from the sudden switch of metabolism from a state of starvation to one of nourishment. Quick recognition would reduce health complications. Physicians who are unaware of the syndrome will not identify and treat it.

Anastasis Drives Senescence and Non-Cell Autonomous Neurodegeneration in the Astrogliopathy Alexander Disease.

Anastasis is a recently described process in which cells recover after late-stage apoptosis activation. The functional consequences of anastasis for cells and tissues are not clearly understood. Using , rat and human cells and tissues, including analyses of both males and females, we present evidence that glia undergoing anastasis in the primary astrogliopathy Alexander disease subsequently express hallmarks of senescence.

Early Surgical Intervention Improves Survival in Acute Intestinal Ischemia in the Intensive Care Unit.

The study is aimed at assessing whether the early surgical intervention improves survival in acute mesenteric ischemia with septic shock. A retrospective study design was applied to review the charts of patients admitted to the intensive care unit. The data were collected through a review of the full patient chart including physician and nursing notes, pathology reports, intraoperative findings, CT findings, and endoscopy.

Endogenous Fluorescence Tagging by CRISPR.

Fluorescent proteins have revolutionized biomedical research as they are easy to use for protein tagging, cope without fixation or permeabilization, and thus, enable live cell imaging in various models. Current methods allow easy and quick integration of fluorescent markers to endogenous genes of interest. In this review, we introduce the three central methods, zinc finger nucleases (ZFNs), transcription activator-like effectors (TALENs), and CRISPR, that have been widely used to manipulate cells or organisms.

A novel understanding of postoperative complications: In vitro study of the impact of propofol on epigenetic modifications in cholinergic genes.

Background: Propofol is a widely used anaesthetic drug with advantageous operating conditions and recovery profile. However, propofol could have long term effects on neuronal cells and is associated with post-operative delirium (POD). In this context, one of the contributing factors to the pathogenesis of POD is a reduction of cholinesterase activity.

A novel in-frame mutation in leads to Juvenile neuronal ceroid lipofuscinosis in a large Pakistani family.

Neuronal ceroid lipofuscinosis (NCLs) are the most common neurodegenerative disorders, with global incidence of 1 in 100,000 live births. NCLs affect central nervous system, primarily cerebellar and cerebral cortices. Juvenile neuronal ceroid lipofuscinosis (JNCL), also known as Batten disease, is the most common form of NCLs.

Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD.

Trends in overweight or obesity and other anthropometric indices in adults aged 18-60 years in western Saudi Arabia.

Background: The prevalence of overweight and obesity has increased considerably in Saudi Arabia in the past two decades. We conducted this study because to examine trends in weight gain with age and related anthropometric measurements in Saudi Arabia such data are limited.

Objective: To determine trends in overweight and obesity and examine anthropometric indices by age group.

Extensive nuclear sphere generation in the human Alzheimer's brain.

Nuclear spheres are protein aggregates consisting of FE65, TIP60, BLM, and other yet unknown proteins. Generation of these structures in the cellular nucleus is putatively modulated by the amyloid precursor protein (APP), either by its cleavage or its phosphorylation. Nuclear spheres were preferentially studied in cell culture models and their existence in the human brain had not been known.

Membrane tethering of APP c-terminal fragments is a prerequisite for T668 phosphorylation preventing nuclear sphere generation.

A central molecular hallmark of Alzheimer's disease (AD) is the β- and γ-secretase-mediated cleavage of the amyloid precursor protein (APP), which causes the generation of different c-terminal fragments like C99, AICD57, or AICD50 that fully or in part contain the APP transmembrane domain. In this study, we demonstrate that membrane-tethered C99 is phosphorylated by JNK3A at residue T668 (APP695 numbering) to a higher extent than AICD57, whereas AICD50 is not capable of being phosphorylated. The modification decreases the turnover of APP, while the blockade of APP cleavage increases APP phosphorylation.

Nuclear spheres modulate the expression of BEST1 and GADD45G.

Nuclear spheres are composed of FE65, TIP60, BLM and other yet unknown proteins. The amyloid precursor protein plays a central role for the generation of these highly toxic aggregates in the nucleus of cells. Thus, nuclear spheres might play a crucial role in Alzheimer's disease (AD).