Neurolipidomics in schizophrenia: A not so well-oiled machine.

Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive.

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity.

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates.

Membrane Lipid Replacement for reconstituting mitochondrial function and moderating cancer-related fatigue, pain and other symptoms while counteracting the adverse effects of cancer cytotoxic therapy.

Cancer-related fatigue, pain, gastrointestinal and other symptoms are among the most familiar complaints in practically every type and stage of cancer, especially metastatic cancers. Such symptoms are also related to cancer oxidative stress and the damage instigated by cancer cytotoxic therapies to cellular membranes, especially mitochondrial membranes. Cancer cytotoxic therapies (chemotherapy and radiotherapy) often cause adverse symptoms and induce patients to terminate their anti-neoplastic regimens.

Host glycosylation of immunoglobulins impairs the immune response to acute Lyme disease.

Background: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease.

Methods: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time.

Nutrigenomics of inward rectifier potassium channels.

Inwardly rectifying potassium (Kir) channels play a key role in maintaining the resting membrane potential and supporting potassium homeostasis. There are many variants of Kir channels, which are usually tetramers in which the main subunit has two trans-membrane helices attached to two N- and C-terminal cytoplasmic tails with a pore-forming loop in between that contains the selectivity filter. These channels have domains that are strongly modulated by molecules present in nutrients found in different diets, such as phosphoinositols, polyamines and Mg.

TLR9 signalling activation via direct ligation and its functional consequences in CD4 + T cells.

CpG Oligodeoxynucleotides (ODNs) are established TLR9 ligands; however, their functional responses in CD4+ T cells are believed to be independent of TLR9 and MyD88. We studied ligand-receptor interactions of ODN 2216 and TLR9 in human CD4+ T cells and assessed their consequences in terms of TLR9 signalling and cell phenotype. We demonstrated that the uptake of ODN 2216, a synthetic TLR9 agonist, is controlled by TLR9 signalling molecules and results in an increase in the expression of TLR9 signalling molecules, regulated via a feedback mechanism.

Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies.

Purpose: Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models.

The Fluid-Mosaic model of cell membranes: A brief introduction, historical features, some general principles, and its adaptation to current information.

The Fluid-Mosaic Membrane (FMM) model was originally proposed as a general, nanometer-scale representation of cell membranes (Singer and Nicolson, 1972). The FMM model was based on some general principles, such as thermodynamic considerations, intercalation of globular proteins into a lipid bilayer, independent protein and lipid dynamics, cooperativity and other characteristics. Other models had trimolecular structures or membrane globular lipoprotein units.

Microglia as Central Protagonists in the Chronic Stress Response.

Chronic stress is a major risk factor for developing psychiatric conditions. In addition to elevating the levels of stress hormones released in the body, chronic stress activates the immune system, resulting in increased levels of proinflammatory cytokines and innate immune cells in the circulation of rodents and humans. Furthermore, exposure to chronic stress alters the phenotype of microglia, a population of innate immune cells that reside in the CNS parenchyma.

Fifty Years of the Fluid-Mosaic Model of Biomembrane Structure and Organization and Its Importance in Biomedicine with Particular Emphasis on Membrane Lipid Replacement.

The Fluid-Mosaic Model has been the accepted general or basic model for biomembrane structure and organization for the last 50 years. In order to establish a basic model for biomembranes, some general principles had to be established, such as thermodynamic assumptions, various molecular interactions, component dynamics, macromolecular organization and other features. Previous researchers placed most membrane proteins on the exterior and interior surfaces of lipid bilayers to form trimolecular structures or as lipoprotein units arranged as modular sheets.

A Brief Introduction to Some Aspects of the Fluid-Mosaic Model of Cell Membrane Structure and Its Importance in Membrane Lipid Replacement.

Early cell membrane models placed most proteins external to lipid bilayers in trimolecular structures or as modular lipoprotein units. These thermodynamically untenable structures did not allow lipid lateral movements independent of membrane proteins. The Fluid-Mosaic Membrane Model accounted for these and other properties, such as membrane asymmetry, variable lateral mobilities of membrane components and their associations with dynamic complexes.

Fundamentals of Membrane Lipid Replacement: A Natural Medicine Approach to Repairing Cellular Membranes and Reducing Fatigue, Pain, and Other Symptoms While Restoring Function in Chronic Illnesses and Aging.

Membrane Lipid Replacement (MLR) uses natural membrane lipid supplements to safely replace damaged, oxidized lipids in membranes in order to restore membrane function, decrease symptoms and improve health. Oral MLR supplements contain mixtures of cell membrane glycerolphospholipids, fatty acids, and other lipids, and can be used to replace and remove damaged cellular and intracellular membrane lipids. Membrane injury, caused mainly by oxidative damage, occurs in essentially all chronic and acute medical conditions, including cancer and degenerative diseases, and in normal processes, such as aging and development.

Functional consequences of lead and mercury exposomes in the heart.

Lead and mercury are heavy metals that are highly toxic to life forms. There are no known physiological processes that require them, and they do not have a particular threshold concentration to produce biologic damage. They are non-biodegradable, and they slowly accumulate in the environment in a dynamic equilibrium between air, water, soil, food, and living organisms.

Pathophysiological and molecular considerations of viral and bacterial infections during maternal-fetal and -neonatal interactions of SARS-CoV-2, Zika, and Mycoplasma infectious diseases.

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe.

SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases.

The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species.

The astrocyte LAMP lights a T cell TRAIL of death.

In a recent issue of Nature, Sanmarco et al. reveal a novel mechanism by which astrocytes maintain an anti-inflammatory state in the central nervous system (CNS). IFNγ released by gut-licensed meningeal NK cells was found to induce TRAIL expression on astrocytes, causing effector T cell apoptosis.

Phase 1 study of belinostat (PXD-101) and bortezomib (Velcade, PS-341) in patients with relapsed or refractory acute leukemia and myelodysplastic syndrome.

We report the results of a phase 1 dose-escalation study of belinostat and bortezomib in adult patients with acute leukemia or MDS or CML with blast crisis. Thirty-eight patients received IV belinostat days 1-5 and 8-12 with IV bortezomib days 1, 4, 8, and 11 every 21 days. QTc prolongation was the only identified DLT.

Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases.

Neuroinflammation leads to tissue injury causing many of the clinical symptoms of Multiple Sclerosis, an autoimmune disorder of the central nervous system (CNS). While T cells, specifically T1 and T17 cells, are the ultimate effectors of this disease, dendritic cells (DCs) mediate T cell polarization, activation, etc. In our previous study, Apigenin, a natural flavonoid, has been shown to reduce EAE disease severity through amelioration of demyelination in the CNS as well as the sequestering of DCs and other myeloid cells in the periphery.

LIN28B affects gene expression at the hypothalamic-pituitary axis and serum testosterone levels.

Genome-wide association studies (GWAS) have recurrently associated sequence variation nearby LIN28B with pubertal timing, growth and disease. However, the biology linking LIN28B with these traits is still poorly understood. With our study, we sought to elucidate the mechanisms behind the LIN28B associations, with a special focus on studying LIN28B function at the hypothalamic-pituitary (HP) axis that is ultimately responsible for pubertal onset.

Combretastatin analogues in cancer biology: A prospective view.

The stilbenoid combretastatin and its derivatives are potent inhibitors of angiogenesis and cell proliferation and induce apoptosis. They disrupt cytoskeletal dynamics and modulate cell morphology, motility, and invasion. Hence they have been viewed as potential as anticancer agents.

Active immunization with tau epitope in a mouse model of tauopathy induced strong antibody response together with improvement in short memory and pSer396-tau pathology.

Abnormal tau hyperphosphorylation and its aggregation into neurofibrillary tangles are a hallmark of tauopathies, neurodegenerative disorders that include Alzheimer's disease (AD). Active and passive Tau-immunotherapy has been proposed as a therapeutic approach to AD with mixed results. One of the limitations of active immunotherapy may be associated with the mediocre immunogenicity of vaccines that are not inducing therapeutically potent titers of antibodies.

MEF-2 isoforms' (A-D) roles in development and tumorigenesis.

Myocyte enhancer factor (MEF)-2 plays a critical role in proliferation, differentiation, and development of various cell types in a tissue specific manner. Four isoforms of MEF-2 (A-D) differentially participate in controlling the cell fate during the developmental phases of cardiac, muscle, vascular, immune and skeletal systems. Through their associations with various cellular factors MEF-2 isoforms can trigger alterations in complex protein networks and modulate various stages of cellular differentiation, proliferation, survival and apoptosis.

Hepatitis C Virus Infection: Host⁻Virus Interaction and Mechanisms of Viral Persistence.

Hepatitis C (HCV) is a major cause of liver disease, in which a third of individuals with chronic HCV infections may develop liver cirrhosis. In a chronic HCV infection, host immune factors along with the actions of HCV proteins that promote viral persistence and dysregulation of the immune system have an impact on immunopathogenesis of HCV-induced hepatitis. The genome of HCV encodes a single polyprotein, which is translated and processed into structural and nonstructural proteins.

Human T cell leukemia virus type 1 and Zika virus: tale of two reemerging viruses with neuropathological sequelae of public health concern.

Human T cell leukemia virus type 1 (HTLV-1) and Zika virus (ZIKV) have been considered neglected viruses of low public health concern until recently when incidences of HTLV-1 and ZIKV were observed to be linked to serious immune-related disease and neurological complications. This review will discuss the epidemiology, genomic evolution, virus-host interactions, virulence factors, neuropathological sequelae, and current perspectives of these reemerging viruses. There are no FDA-approved therapeutics or vaccines against these viruses, and as such, it is important for clinical trials to focus on developing vaccines that can induce cell-mediated immune response to confer long-term protective immunity.