Meloidogyne spp. (root-knot nematodes; RKN) are sedentary endoparasites with wide range of plant hosts. RKN negatively affect almost every crop in the world. Current management practices, though effective to some extent, are not enough to completely control the RKN. Application of certain chemicals is also being further limited in recent years due to increasing regulations and restrictions. Therefore, it is crucial to develop additional control strategies through the application of environmentally benign methods. Due to the importance of this topic, there has been much research performed around the world leading to useful outcomes and interesting findings capable of helping agriculture. Hence, it is important to have dependable resources gathering the data produced to facilitate future research. This review discusses the recent findings on the application of environmentally benign treatments to control RKN between 2015 and April 2020. A variety of biological control strategies, natural compounds, soil amendments and other emerging strategies have been included, among which, many showed promising results in RKN control in vitro and/or in vivo. The impact of biologically-based strategies on parasitic and beneficial nematodes continues to be an area of active research and new information on their efficacy will become available in the years to come. In this review, some of the mechanisms involved have been discussed and suggestions were given on maximizing the outcome of the future efforts.

/pdf/recent-advances-in-the-development-of-environmentally-benign-2wmfl5sahp.pdf

Recent Advances in the Development of Environmentally Benign Treatments to Control Root-Knot Nematodes.

Novel target for treating Alzheimer's Diseases: Crosstalk between the Nrf2 pathway and autophagy.

/pdf/bcl-2-like-protein-13-is-a-mammalian-atg32-homologue-that-59tz1ji44f.pdf

Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation

The maintenance of genome stability is essential for the cell as the integrity of genomic information guaranties reproduction of a whole organism. DNA damage occurring in response to different natural and nonnatural stimuli (errors in DNA replication, UV radiation, chemical agents, etc.) is normally detected by special cellular machinery that induces DNA repair. However, further accumulation of genetic lesions drives the activation of cell death to eliminate cells with defective genome. This particular feature is used for targeting fast-proliferating tumor cells during chemo-, radio-, and immunotherapy. Among different cell death modalities induced by DNA damage, apoptosis is the best studied. Nevertheless, nonapoptotic cell death and adaptive stress responses are also activated following genotoxic stress and play a crucial role in the outcome of anticancer therapy. Here, we provide an overview of nonapoptotic cell death pathways induced by DNA damage and discuss their interplay with cellular senescence, mitotic catastrophe, and autophagy.

The DNA-damage response and nuclear events as regulators of nonapoptotic forms of cell death

Fungal infections are an increasing threat to global public health. There are more than six million fungal species worldwide, but less than 1% are known to infect humans. Most of these fungal infections are superficial, affecting the hair, skin and nails, but some species are capable of causing life-threatening diseases. The most common of these include Cryptococcus neoformans, Aspergillus fumigatus and Candida albicans. These fungi are typically innocuous and even constitute a part of the human microbiome, but if these pathogens disseminate throughout the body, they can cause fatal infections which account for more than one million deaths worldwide each year. Thus, systemic dissemination of fungi is a critical step in the development of these deadly infections. In this review, we discuss our current understanding of how fungi disseminate from the initial infection sites to the bloodstream, how immune cells eliminate fungi from circulation and how fungi leave the blood and enter distant organs, highlighting some recent advances and offering some perspectives on future directions.

Mechanisms of fungal dissemination

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation in the nucleus, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, pretreatment with an autophagy inhibitor offsets the effects of MG132 on CHK1 and RAD51 levels. These findings imply that p62 accumulation in the nucleus in response to autophagy inhibition promotes proteasome-mediated CHK1 and RAD51 protein instability. This claim is further supported by the findings that transient expression of a p62 mutant, which is constitutively localized in the nucleus, in B cell lines with low endogenous p62 levels recaptures the effects of autophagy inhibition on CHK1 and RAD51 protein stability. These results indicate that proteasomal degradation of RAD51 and CHK1 is dependent on p62 accumulation in the nucleus. However, small hairpin RNA (shRNA)-mediated p62 depletion in EBV-transformed lymphoblastic cell lines (LCLs) had no apparent effects on the protein levels of CHK1 and RAD51, likely due to the constitutive localization of p62 in the cytoplasm and incomplete knockdown is insufficient to manifest its nuclear effects on these proteins. Rather, shRNA-mediated p62 depletion in EBV-transformed LCLs results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination, indicative of activation of RNF168-mediated DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis.

/pdf/p62-mediated-selective-autophagy-endows-virus-transformed-3psjcp3pyb.pdf

p62-mediated Selective Autophagy Endows Virus-Transformed Cells With Insusceptibility to DNA Damage Under Oxidative Stress

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that p62 is upregulated through the ROS-Keap1-NRF2 pathway, and considerable levels of p62-mediated selective autophagy are constitutively induced, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, small hairpin RNA (shRNA)-mediated p62 depletion or transient expression of p62 in B cell lines had no apparent effects on the protein levels of CHK1 and RAD51. These results indicate that p62 accumulation resulting from autophagy inhibition is prerequisite for p62-mediated proteasomal degradation of CHK1 and RAD51. Furthermore, shRNA-mediated p62 depletion in EBV-transformed lymphoblastic cell lines results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination in the nucleus, indicative of activation of RNF168-mediated DNA repair mechanisms. Finally, we have evaluated endogenous p62 and autophagy levels and their correlation with endogenous ROS and DNA damage levels in B cell population of AIDS lymphoma patients versus age-matched subjects. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis. Author Summary Reactive oxygen/nitrogen species (ROS/RNS) can induce both DNA damage response (DDR) and selective autophagy, which play crucial roles in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 links their crosstalk. However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). In this study, we provide evidence that p62-mediated selective autophagy is constitutively induced in virus-transformed cells, and that its inhibition exacerbates ROS-induced DNA damage, and promotes proteasomal degradation of CHK1 and RAD51 in a p62-dependent manner. However, rigorous autophagy induction results in accumulation of DNA repair proteins CHK1 and RAD51, and p62 degradation. Furthermore, small hairpin RNA (shRNA)-mediated p62 depletion or transient expression of p62 did not affect CHK1 and RAD51 protein levels; rather, shRNA-mediated p62 depletion activates RNF168-dependent DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy in regulation of DDR by overriding traditional DDR mechanisms in the setting of oncogenic virus latent infection, and provide a novel insight into the etiology of viral cancers.

https://www.biorxiv.org/content/biorxiv/early/2019/01/03/502823.full.pdf

Caroline Hawkins

Papers

p62-mediated Selective Autophagy Endows Virus-Transformed Cells With Insusceptibility to DNA Damage Under Oxidative Stress

p62-mediated Selective Autophagy Endows Virus-transformed Cells with Insusceptibility to DNA Damage under Oxidative Stress