Notes

Executive Aligned Skeletal Muscular tissues Making use of Decellularized Plant-Derived Scaffolds.
Neuropathic pain (NeP) is a global cause of suffering and debilitation leading to significant morbidity and reduced quality of life. New treatments are needed to address the growing prevalence of NeP and its impact on sleep, mood and functionality. Mirogabalin besylate (mirogabalin, Tarlige) is a gabapentinoid therapy developed by Daiichi Sankyo which is approved in Japan for the treatment of postherpetic neuralgia and painful diabetic peripheral neuropathy. Mirogabalin has a potent pain-modulating effect with a unique high affinity and prolonged dissociation rate for the a2delta-1 subunit of voltage-gated calcium (Ca2+) channels (VGCCs) on the dorsal root ganglion resulting in more sustained analgesia compared with traditional gabapentinoids. Additionally, mirogabalin has a superior adverse events (AEs) profile due to a rapid dissociation from the a2delta-2 subunit of VGCCs potentially implicated in central nervous system-specific AEs. The most common AEs for mirogabalin are dizziness (approximately 8-16%), somnolence (approximately 6-24%) and headache (approximately 6-14%), with a lower incidence of constipation, nausea, diarrhea, vomiting, edema, fatigue and weight gain. Postmarketing studies are required to evaluate its analgesic durability and efficacy when combined with other antineuropathic agents such as tricyclics, duloxetine and tramadol/tapentadol. Copyright 2020 Clarivate Analytics.Parkinson's disease (PD) is an extremely common degenerative disease with a progressive course. Unfortunately, the longer patients are treated with levodopa, the more likely they are to suffer from increasingly long periods of immobility or "OFF" time. For over 30 years Kyowa Kirin Co., Ltd. (formerly Kyowa Hakko Kirin Co., Ltd.) has been researching the possibility of finding drugs that affect adenosine receptors and that can be used successfully as additional drugs in the treatment of PD. Istradefylline is an adenosine A2A receptor antagonist that significantly reduces the "OFF" time and improves the motor function of patients with PD, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) Part III, while increasing the time without troublesome dyskinesia. It was approved for use in PD in Japan in 2013 and in the United States in 2019. Copyright 2020 Clarivate Analytics.Doravirine is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) that was approved by the United States Food and Drug Administration (FDA) on August 30, 2018, for the treatment of HIV infection in adult patients. The product was also approved in the E.U. and Japan in November 2018 and January 2020, respectively. It is currently available as a single stand-alone tablet as well as part of a single-tablet regimen in a fixed-dose combination with tenofovir disoproxil and lamivudine. Similarly to other NNRTIs, doravirine exerts its antiviral effect through a noncompetitive inhibition of HIV-1 reverse transcriptase. It has a novel resistance pathway so that it retains in vitro activity against clinically relevant NNRTI viral mutations K103N, Y181C and G190A. In randomized clinical trials, doravirine was noninferior to efavirenz- and darunavir-based regimens, with fewer adverse events. Doravirine has a more favorable drug interaction profile compared with earlier NNRTIs as it neither inhibits nor induces the cytochrome P450 3A4 (CYP3A4) enzyme. Doravirine has been added to the category of Recommended Initial Regimens in Certain Clinical Situations in the United States Department of Health and Human Services Antiretroviral Guidelines for Adults and Adolescents. Copyright 2020 Clarivate Analytics.[This corrects the article DOI 10.1371/journal.pone.0228870.].The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIVmac251. Here, we demonstrate that the ALVAC-SIV/gp120/alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIVmac251 and we confirm that CD14+ classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14+ cells and/or their gene expression correlates with blood Type 1 CD4+ T helper cells, α4β7+ plasmablasts, and vaginal cytocidal NKG2A+ cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4+Ki67+CD38+ and CD4+Ki67+α4β7+ T cells, higher SIV envelope-specific IFN-γ producing cells, equivalent ADCC, and did not decrease the risk of SIVmac251 acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A+ cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.Improvements in hygiene and health management have driven significant increases in human lifespan over the last 50 years. Frustratingly however, this extension of lifespan has not been matched by equivalent improvements in late-life health, not least due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, all ageing-associated conditions exacerbated and accelerated by widespread adoption of the high calorie Western diet (HCD). Recently, evidence has begun to emerge that parasitic worm infection might protect against such ageing-associated co-morbidities, as a serendipitous side-effect of their evolution of pro-survival, anti-inflammatory mechanisms. As a novel therapeutic strategy, we have therefore investigated the potential of ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, to improve healthspan (the period of life before diseases of ageing appear) by targeting the chronic inflammation that drives metabolic dysregulation underpinningemale mice. Rather, the difference appeared to be associated with ES-62's additional ability to preferentially promote a healthier gut-metabolic tissue axis in male animals.Despite the success of antiretroviral therapy (ART) to halt viral replication and slow disease progression, this treatment is not curative and there remains an urgent need to develop approaches to clear the latent HIV reservoir. The human IL-15 superagonist N-803 (formerly ALT-803) is a promising anti-cancer biologic with potent immunostimulatory properties that has been extended into the field of HIV as a potential "shock and kill" therapeutic for HIV cure. However, the ability of N-803 to reactivate latent virus and modulate anti-viral immunity in vivo under the cover of ART remains undefined. Here, we show that in ART-suppressed, simian-human immunodeficiency virus (SHIV)SF162P3-infected rhesus macaques, subcutaneous administration of N-803 activates and mobilizes both NK cells and SHIV-specific CD8+ T cells from the peripheral blood to lymph node B cell follicles, a sanctuary site for latent virus that normally excludes such effector cells. We observed minimal activation of memory CD4+ T cells and no increase in viral RNA content in lymph node resident CD4+ T cells post N-803 administration. Accordingly, we found no difference in the number or magnitude of plasma viremia timepoints between treated and untreated animals during the N-803 administration period, and no difference in the size of the viral DNA cell-associated reservoir post N-803 treatment. These results substantiate N-803 as a potent immunotherapeutic candidate capable of activating and directing effector CD8+ T and NK cells to the B cell follicle during full ART suppression, and suggest N-803 must be paired with a bona fide latency reversing agent in vivo to facilitate immune-mediated modulation of the latent viral reservoir.[This corrects the article DOI 10.1371/journal.pone.0225391.].Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity.[This corrects the article DOI 10.1371/journal.pone.0228722.].[This corrects the article DOI 10.1371/journal.pone.0226686.].[This corrects the article DOI 10.1371/journal.pone.0228113.].The assessment of language lateralization has become widely used when planning neurosurgery close to language areas, due to individual specificities and potential influence of brain pathology. Functional magnetic resonance imaging (fMRI) allows non-invasive and quantitative assessment of language lateralization for presurgical planning using a laterality index (LI). However, the conventional method is limited by the dependence of the LI on the chosen activation threshold. To overcome this limitation, different threshold-independent LI calculations have been reported. The purpose of this study was to propose a simplified approach to threshold-independent LI calculation and compare it with three previously reported methods on the same cohort of subjects. Fifteen healthy subjects, who performed picture naming, verb generation, and word fluency tasks, were scanned. LI values were calculated for all subjects using four methods, and considering either the whole hemisphere or an atlas-defined language area. For each method, the subjects were ranked according to the calculated LI values, and the obtained rankings were compared. All LI calculation methods agreed in differentiating strong from weak lateralization on both hemispheric and regional scales (Spearman's correlation coefficients 0.59-1.00). In general, a more lateralized activation was found in the language area than in the whole hemisphere. The new method is well suited for application in the clinical practice as it is simple to implement, fast, and robust. The good agreement between LI calculation methods suggests that the choice of method is not key. Nevertheless, it should be consistent to allow a relative comparison of language lateralization between subjects.[This corrects the article DOI 10.1371/journal.pone.0228453.].
Website: