Graukeller2380

Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. check details We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes a neutralizing B-cell epitope (VP1 (140-158)) and a T-cell epitope [3A (21-35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.Neuronal survival depends on the glia, that is, on the astroglial and microglial support. Neurons die and microglia are activated not only in neurodegenerative diseases but also in physiological aging. Activated microglia, once considered harmful, express two main phenotypes the pro-inflammatory or M1, and the neuroprotective or M2. When neuroinflammation, i.e., microglial activation occurs, it is important to achieve a good M1/M2 balance, i.e., at some point M1 microglia must be skewed into M2 cells to impede chronic inflammation and to afford neuronal survival. G protein-coupled receptors in general and adenosine receptors in particular are potential targets for increasing the number of M2 cells. This article describes the mechanisms underlying microglial activation and analyzes whether these cells exposed to a first damaging event may be ready to be preconditioned to better react to exposure to more damaging events. Adenosine receptors are relevant due to their participation in preconditioning. They can also be overexpressed in activated microglial cells. The potential of adenosine receptors and complexes formed by adenosine receptors and cannabinoids as therapeutic targets to provide microglia-mediated neuroprotection is here discussed.More than one year into the novel coronavirus disease 2019 (COVID-19) pandemic, healthcare systems across the world continue to be overwhelmed with soaring daily cases. The treatment spectrum primarily includes ventilation support augmented with repurposed drugs and/or convalescent plasma transfusion (CPT) from recovered COVID-19 patients. Despite vaccine variants being recently developed and administered in several countries, challenges in global supply chain logistics limit their timely availability to the wider world population, particularly in developing countries. Given the measured success of conventional CPT in treating several infections over the past decade, recent studies have reported its effectiveness in decreasing the duration and severity of COVID-19 symptoms. In this review, we conduct a literature search of published studies investigating the use of CPT to treat COVID-19 patients from January 2020 to January 2021. The literature search identified 181 records of which 39 were included in this review. A random-effects model was used to aggregate data across studies, and mortality rates of 17 vs. 32% were estimated for the CPT and control patient groups, respectively, with an odds ratio (OR) of 0.49. The findings indicate that CPT shows potential in reducing the severity and duration of COVID-19 symptoms. However, early intervention (preferably within 3 days), recruitment of donors, and plasma potency introduce major challenges for its scaled-up implementation. Given the low number of existing randomized clinical trials (RCTs, four with a total of 319 patients), unanticipated risks to CPT recipients are highlighted and discussed. Nevertheless, CPT remains a promising COVID-19 therapeutic option that merits internationally coordinated RCTs to achieve a scientific risk-benefit consensus.In response to the increasing burden of recent health emergencies and disasters, the World Health Organization (WHO) and its partners established the WHO thematic platform for health emergency and disaster risk management research network (health EDRM RN) in 2016, with the purposes of promoting global research collaboration among various stakeholders and enhancing research activities that generate evidence to manage health risks associated with all types of emergencies and disasters. With the strong support and involvement of all WHO regional offices, the health EDRM RN now works with more than 200 global experts and partners to implement its purposes. The 1st and 2nd Core Group Meetings of the health EDRM RN were held on 17-18 October 2019 and 27 November 2020, respectively, to discuss the development of a global research agenda that the health EDRM RN will focus on facilitating, promoting, synthesizing and implementing, taking into account the emergence of the coronavirus disease 2019 (COVID-19) (health EDRM RN research agenda). A focus of the meetings was the establishment of an online platform to share information and knowledge, including the databases that the health EDRM RN accumulates (WHO health EDRM knowledge hub). This paper presents a summary of the discussion results of the meetings.Yin Yang 2 encodes a mammalian-specific transcription factor (YY2) that shares high homology in the zinc finger region with both YY1 and REX1/ZFP42, encoded by the Yin Yang 1 and Reduced Expression Protein 1/Zinc Finger Protein 42 gene, respectively. In contrast to the well-established roles of the latter two in gene regulation, X chromosome inactivation and binding to specific transposable elements (TEs), much less is known about YY2, and its presence during mouse preimplantation development has not been described. As it has been reported that mouse embryonic stem cells (mESC) cannot be propagated in the absence of Yy2, the mechanistic understanding of how Yy2 contributes to mESC maintenance remains only very partially characterized. We describe Yy2 expression studies using RT-PCR and staining with a high-affinity polyclonal serum in mouse embryos and mESC. Although YY2 is expressed during preimplantation development, its presence appears dispensable for developmental progress in vitro until formation of the blastocyst. Attenuation of Yy2 levels failed to alter either Zscan4 levels in two-cell embryos or IAP and MERVL levels at later preimplantation stages. In contrast to previous claims that constitutively expressed shRNA against Yy2 in mESC prohibited the propagation of mESC in culture, we obtained colonies generated from mESC with attenuated Yy2 levels. Concomitant with a decreased number of undifferentiated colonies, Yy2-depleted mESC expressed higher levels of Zscan4 but no differences in the expression of TEs or other pluripotency markers including Sox2, Oct4, Nanog and Esrrb were observed. These results confirm the contribution of Yy2 to the maintenance of mouse embryonic stem cells and show the preimplantation expression of YY2. These functions are discussed in relation to mammalian-specific functions of YY1 and REX1.Water shortages have direct adverse effects on wheat productivity and growth worldwide, vertically and horizontally. Productivity may be promoted using water shortage-tolerant wheat genotypes. High-throughput tools have supported plant breeders in increasing the rate of stability of the genetic gain of interpretive traits for wheat productivity through multidimensional technical methods. We used 27 agrophysiological interpretive traits for grain yield (GY) of 25 bread wheat genotypes under water shortage stress conditions for two seasons. Genetic parameters and multidimensional analyses were used to identify genetic and phenotypic variations of the wheat genotypes used, combining these strategies effectively to achieve a balance. Considerable high genotypic variations were observed for 27 traits. Eleven interpretive traits related to GY had combined high heritability (h2 > 60%) and genetic gain (>20%), compared to GY, which showed moderate values both for heritability (57.60%) and genetic gain (16.89%). It warespectively. The conclusions drawn from the membership index and clustering analysis, signifying that there were clear separations between the water shortage tolerance groups, were confirmed through discriminant analysis. MANOVA indicated that there were considerable variations between the five water shortage tolerance groups. The tolerated genotypes (DHL02, DHL30, DHL26, Misr1, Pavone-76 and DHL08) can be recommended as interesting new genetic sources for water shortage-tolerant wheat breeding programs.Enterococcus faecalis (E. faecalis) is rather unsusceptible to many root canal disinfections which often cause a therapeutic problem. Therefore, the present in vitro study observed the efficiency of different endodontic antiseptics in their capability to suppress E. faecalis, especially inside dentinal tubules. Prior to any testing, root canals of extracted third human molars were inoculated with E. faecalis for 48 h. Antiseptic dressings with chloramine-T or calcium hydroxide (CaOH) for 24 h or irrigations with 1.3% sodium hypochlorite (NaOCl) were applied with n = 10 in each group. As control irrigation with normal saline was used. All treated canals were manually enlarged from size ISO 50 to 110 and the ablated dentin debris was subjected to microbial culture analysis. Bacterial colonization of the dentinal tubules up to 300 µm was verified by scanning electron microscopy and histological sample preparation. Application of crystalline chloramine-T caused total bacterial suppression inside the dentinal tubules. Dressings with CaOH showed only minor effects. Irrigation with NaOCl caused total eradication of bacteria adhering to the root canal walls, but also failed to completely suppress E. faecalis inside the dentinal tubules. The study showed that chloramine-T is of strong antiseptic activity and also efficient in suppressing E. faecalis inside dentinal tubules.Anandamide (AEA) is one of the best characterized members of the endocannabinoid family and its involvement in many pathophysiological processes has been well documented in vertebrates and invertebrates. Here, we report the biochemical and functional characterization of key elements of the endocannabinoid system in hemocytes isolated from the Mediterranean mussel Mytilus galloprovincialis. We also show the effects of exogenous AEA, as well as of capsaicin, on the cell ability to migrate and to activate the respiratory burst, upon in vitro stimulation of phagocytosis. Interestingly, our findings show that both AEA and capsaicin suppress the hemocyte response and that the use of selective antagonists of CB2 and TRPV1 receptors revert their inhibitory effects. Overall, present data support previous evidence on the presence of endocannabinoid signaling in mollusks and advance our knowledge about the evolutionary origins of this endogenous system and its role in the innate response of mollusks.