Editorial: Lifestyle modifications to manage migraine

Headache; Lifestyle and behavior; MigraineDolor de cabeza; Estilo de vida y comportamiento; MigrañaMal de cap; Estil de vida i comportament; MigranyaYW received research funding from the NINDS (National Institute of Neurological Disorders and Stroke), NIH (National Institutes of Health) (1K01NS124911-01). MV-P is a recipient of a Sara Borrell contract from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain (CD20/00019)

Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field

The question concerning human rights and human rightlessness: disposability and struggle in the Bhopal gas disaster

In the midst of concerns about diminishing political support for human rights, individuals and groups across the globe continue to invoke them in their diverse struggles against oppression and injustice. Yet both those concerned with the future of human rights and those who champion rights activism as essential to resistance, assume that human rights – as law, discourse and practices of rights claiming – can ameliorate rightlessness. In questioning this assumption, this article seeks also to reconceptualise rightlessness by engaging with contemporary discussions of disposability and social abandonment in an attempt to be attentive to forms of rightlessness co-emergent with the operations of global capital. Developing a heuristic analytics of rightlessness, it evaluates the relatively recent attempts to mobilise human rights as a frame for analysis and action in the campaigns for justice following the 3 December 1984 gas leak from Union Carbide Corporation’s (UCC) pesticide manufacturing plant in Bhopal, India. Informed by the complex effects of human rights in the amelioration of rightlessness, the article calls for reconstituting human rights as an optics of rightlessness

The Multifunctionality of Exosomes; from the Garbage Bin of the Cell to a Next Generation Gene and Cellular Therapy

Exosomes are packaged with a variety of cellular cargo including RNA, DNA, lipids and proteins. For several decades now there has been ongoing debate as to what extent exosomes are the garbage bin of the cell or if these entities function as a distributer of cellular cargo which acts in a meaningful mechanistic way on target cells. Are the contents of exosomes unwanted excess cellular produce or are they selective nucleic acid packaged nanoparticles used to communicate in a paracrine fashion? Overexpressed RNAs and fragments of DNA have been shown to collect into exosomes which are jettisoned from cells in response to particular stimuli to maintain homeostasis suggesting exosomes are functional trash bins of the cell. Other studies however have deciphered selective packaging of particular nucleic acids into exosomes. Nucleic acids packaged into exosomes are increasingly reported to exert transcriptional control on recipient cells, supporting the notion that exosomes may provide a role in signaling and intracellular communication. We survey the literature and conclude that exosomes are multifunctional entities, with a plethora of roles that can each be taken advantage to functionally modulate cells. We also note that the potential utility of developing exosomes as a next generation genetic therapy may in future transform cellular therapies. We also depict three models of methodologies which can be adopted by researchers intending to package nucleic acid in exosomes for developing gene and cell therapy

Improving Dynamic Performance of Automatic Generation Control of Interconnected Power System by Combing Parallel EHV AC / HV DC link

Abstract: This paper deals with load frequency control of 2 area interconnected Thermal power systems with EHVAC/HVDC links when subjected to small step load perturbations. For the present study, power system model consists of two areas thermal power plants having identical capacity. The system interconnection is considered namely (I) EHVAC transmission link only (II) EHVAC in parallel with HVDC transmission link. The HVDC link is considered to be operating in constant current control mode. To carry out the investigations, optimal AGC regulators are designed using proportionalplus-integral control strategy and implemented on the system under consideration in the wake of 1 % step load perturbation in thermal area. The system responses will be simulated in Mat lab. Responses of deviation in frequencies, deviation in tie line power and integral of area control errors are plotted. By comparing the responses of the two model developed, one by using HVDC link and another without using HVDC link, the frequency deviation and settling time is lesser than without using HVDC link. Therefore by combining the transmission line by using HVDC link provides better dynamic performances in terms of overshoot and settling time

Fibronectin glomerulopathy - A sporadic case with unusual clinical manifestation

A 22-year-old nondiabetic young Indian female presented with short history of dyspnea, anorexia, and bilateral leg swelling. Her laboratory evaluation showed severe anemia, serum creatinine of 11.89 mg/dL, nephrotic range proteinuria and microscopic hematuria with 6–8 red blood cell/high-power field. Renal biopsy showed brightly eosinophilic, periodic acid-Schiff (PAS) positive, silver negative, and fuschinophilic deposits in the mesangium extending around the capillary loops with thickening of the basement membrane. Immunohistochemistry was strongly positive for fibronectin (FN). There was no family history of renal disease. Genetic screening revealed absence of mutations in the FN1 gene. She was put on maintenance hemodialysis

G10 is a direct activator of human STING.

The cGAS/STING pathway initiates an innate immune response when DNA is detected in the cytosol. DNA bound cGAS synthesizes cyclic dinucleotides which bind and activate the adaptor STING, leading to downstream secretion of Type I interferons and other pro-inflammatory NFκB pathway cytokines. In the mouse, the STING driven innate immune response is central to immune based clearance of various tumors and this has triggered a significant effort focused on the discovery of human STING agonists for the treatment of cancer. This report uses an in vitro kinase assay to show that G10, a previously identified STING pathway activator is actually a weak but direct STING agonist and identifies other more potent leads

Stable Transcriptional Repression and Parasitism of HIV-1

Gene-based therapies represent a promising treatment for HIV-1 infection, as they offer the potential for sustained viral inhibition and reduced treatment interventions. One approach developed here involves using conditionally replicating vectors (CR-vectors). CR-vectors utilize HIV-expressed proteins to replicate and disseminate along with HIV into the budding viral particles, thereby co-infecting target cellular reservoirs. We generated and characterized several CR-vectors carrying various therapeutic payloads of non-coding RNAs targeted to HIV-1, both transcriptionally and post-transcriptionally. Both virus and vector expression was followed in cell culture systems and T cells in the presence and absence of mycophenolic acid (MPA) selection. We find here that CR-vectors functionally suppress HIV expression in a long-term stable manner and that transcriptional targeting of and epigenetic silencing of HIV can be passaged to newly infected cells by the action of the CR-vector, ultimately establishing a sustained parasitism of HIV. Our findings suggest that CR-vectors with modulatory non-coding RNAs may be a viable approach to achieving long-term sustained suppression of HIV-1, leading ultimately to a functional cure. Keywords: non-coding RNA, HIV-1, conditionally replicating lentiviral vectors, epigenetic silencing, transcriptio

Extracellular Vesicles Loaded with Long Antisense RNAs Repress Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Long antisense RNAs (asRNAs) have been observed to repress HIV and other virus expression in a manner that is refractory to viral evolution. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) disease, has a distinct ability to evolve resistance around antibody targeting, as was evident from the emergence of various SARS-CoV-2 spike antibody variants. Importantly, the effectiveness of current antivirals is waning due to the rapid emergence of new variants of concern, more recently the omicron variant. One means of avoiding the emergence of viral resistance is by using long asRNA to target SARS-CoV-2. Similar work has proven successful with HIV targeting by long asRNA. In this study, we describe a long asRNA targeting SARS-CoV-2 RNA-dependent RNA polymerase gene and the ability to deliver this RNA in extracellular vesicles (EVs) to repress virus expression. The observations presented in this study suggest that EV-delivered asRNAs are one means to targeting SARS-CoV-2 infection, which is both effective and broadly applicable as a means to control viral expression in the absence of mutation. This is the first demonstration of the use of engineered EVs to deliver long asRNA payloads for antiviral therapy.</div