• Burgess Kristiansen posted an update 12 hours, 42 minutes ago

    We present the case of a 28-year-old man with a history of unexplained syncope, frequent ventricular arrhythmias, familial LMNA-related dilated cardiomyopathy (DCM) and mitral annular disjunction (MAD). We provide the first association of a novel truncating LMNA variant serving as a potential vulnerable substrate for arrhythmogenic MAD syndrome. EHop-016 nmr This could suggest a possible synergistic role between concealed genetic variants (resulting in fibrosis as a ‘substrate’ for arrhythmogenesis) and the presence of mitral annular disjunction (the ‘trigger’ with mechanical stretch initiating ventricular arrhythmias), which may provide a link between mitral valve prolapse and sudden cardiac death.The supply limitations of COVID-19 vaccines have led to the need to prioritize vaccine distribution. Obesity, diabetes, and hypertension have been associated with an increased risk of severe COVID-19 infection. Approximately half as many individuals with a cardiovascular risk factor need to be vaccinated against COVID-19 to prevent related death compared with individuals without a risk factor. Adults with body mass index ≥ 30, diabetes, or hypertension should be of a similar priority for COVID-19 vaccination to adults 10 years older with a body mass index of 20 to less then 30, no diabetes, and no hypertension.The development of CRISPR/Cas genome editing tools has revolutionized the life sciences by providing transformative applications in many biological fields, including the field of neurological disorders. Compared with previous CRISPR-Cas systems targeting DNA, a new field of RNA editing using CRISPR-Cas13 systems is gaining immense popularity. CRISPR-Cas13 is a robust, precise, versatile and safe RNA guided RNA-targeting system, which uniquely targets single-strand RNA. Recently, RNA-targeted gene editing tools have been refined by the introduction of an AAV (adeno-associated virus)-based CRISPR-Cas13 system for in vivo therapeutic cell fate conversion, which has been used to treat animal models of Parkinson’s disease. This flavor of gene editing showed promising effects on glia-to-neuron conversion in both intact and damaged mature retinas in a mouse model. Herein, we summarize the CRISPR-Cas13 system and its potential for applications in neurological diseases, focusing on the method of applying the AAV-mediated CRISPR-Cas13 system to the conversion of glia-to-neuron.Antimicrobial peptides (AMPs) are ubiquitously present small peptides, which play a critical function in the innate immune system. The defensin class of AMPs represented an evolutionarily ancient family containing cationic cysteine residue and frequently expressed in epithelial or neutrophils cells. It plays myriad functions in host innate immune responses against various infection. Defensin has a broad spectrum of antimicrobial activities, including anti-bacteria, anti-viruses (AVPs), anti-fungi, anti-cancers, and also overcoming bacterial drug resistance. In this review, we compiled the progress on defensin, particularly incorporating the mechanism of action, their application as an antiviral agent, prospects in different areas, and limitations to be solved as an antiviral peptide. Defensins were explored, in particular, their capacity to stimulate innate and adaptive immunity by trigging as anti-coronavirus (COVID-19) peptides. The present review summarised its immunomodulatory and immunoenhancing properties and predominantly focused on its promising therapeutic adjuvant choices for combat against viral infection.Current study deals with a novel multi-epitope vaccine designed in silico and its confirmation experiments for potential efficacy in BALB/c mice. Major histocompatibility complex (MHC)-binding and B-cell binding epitopes of five Toxoplasma antigens (SAG1, ROP16, GRA12, MIC4 and M2AP) were predicted. Selected epitopes were fused together using SAPGTP linker, and antigenicity, allergenicity, physico-chemical features, secondary and tertiary structures and validations were all performed via bioinformatics servers. Then, vaccine construct was cloned into pLEXSY-neo 2.1 vector. After Leishmania tarentolae transfection, live recombinant and wild parasites were subcutaneously injected into 6-8 week female BALB/c mice and immune responses were measured. Results showed that the peptide possessed 282 amino acid residues with average molecular weight of 28.06 kDa. About 90% of the peptide residues were incorporated in favored and allowed regions of the Ramachandran plot. Vaccinated mice showed remarkably elevated levels of specific antibodies (P less then 0.05) with predominance of IgG2a production. Also, a Th1 immune response with production of IFN-γ and relatively increased survival rate against intraperitoneal challenge with RH strain was demonstrated in immunized mice than control groups (P less then 0.05). Also, very low levels of IL-4 were demonstrated, which showed statistically significant association with controls (P less then 0.05). The findings clarified that multi-epitope vaccine expressed in Leishmania tarentolae induced significant immune responses against acute toxoplasmosis.Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly population and has worldwide impact. The etiology of the disease is complex and results from the confluence of multiple mechanisms ultimately leading to neuronal loss and cognitive decline. Among risk factors, aging is the most relevant and accounts for several pathogenic events that contribute to disease-specific toxic mechanisms. Accumulating evidence linked the alterations of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase playing a key role in the regulation of protein synthesis and degradation, to age-dependent cognitive decline and pathogenesis of AD. To date, growing studies demonstrated that aberrant mTOR signaling in the brain affects several pathways involved in energy metabolism, cell growth, mitochondrial function and proteostasis. Recent advances associated alterations of the mTOR pathway with the increased oxidative stress. Disruption of all these events strongly contribute to age-related cognitive decline including AD.