scholarly journals Nep1-like Proteins from Valsa mali Differentially Regulate Pathogen Virulence and Response to Abiotic Stresses

2021 ◽  
Vol 7 (10) ◽  
pp. 830
Author(s):  
Jianying Liu ◽  
Jiajun Nie ◽  
Yali Chang ◽  
Lili Huang
Keyword(s):  
Cell Death ◽  
Early Stage ◽  
Pathogenic Fungus ◽  
Strong Immune Response ◽  
Multiple Sequence ◽  
Cytotoxicity Activity ◽  
Pathogen Virulence ◽  
Apple Leaves ◽  
Its Gene ◽  
Valsa Mali

Necrosis and ethylene-inducing peptide 1(Nep1)-like protein (NLP) is well known for its cytotoxicity and immunogenicity on dicotyledonous, and it has attracted large attention due to its gene expansion and functional diversification in numerous phytopathogens. Here, two NLP family proteins, VmNLP1 and VmNLP2, were identified in the pathogenic fungus Valsa mali. We showed that VmNLP2 but not VmNLP1 induced cell death when transiently expressed in Nicotiana benthamiana. VmNLP2 was also shown to induce cell death in apple leaves via the treatment of the Escherichia coli-produced recombinant protein. VmNLP1 and VmNLP2 transcripts were drastically induced at the early stage of V. mali infection, whereas only VmNLP2 was shown to be essential for pathogen virulence. We also found that VmNLP1 and VmNLP2 are required for maintaining the integrity of cell membranes, and they differentially contribute to V. mali tolerance to salt- and osmo-stresses. Notably, multiple sequence alignment revealed that the second histidine (H) among the conserved heptapeptide (GHRHDWE) of VmNLP2 is mutated to tyrosine (Y). When this tyrosine (Y) was substituted by histidine (H), the variant displayed enhanced cytotoxicity in N. benthamiana, as well as enhanced virulence on apple leaves, suggesting that the virulence role of VmNLP2 probably correlates to its cytotoxicity activity. We further showed that the peptide among VmNLP2, called nlp25 (VmNLP2), triggered strong immune response in Arabidopsis thaliana. This work demonstrates that NLPs from V. mali involve multiple biological roles, and shed new light on how intricately complex the functions of NLP might be.

scholarly journals Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Faith L. Anderson ◽  
Katharine M. von Herrmann ◽  
Angeline S. Andrew ◽  
Yuliya I. Kuras ◽  
Alison L. Young ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Inflammasome Activation ◽  
Membrane Pore ◽  
Related Proteins ◽  
Inflammasome Activity

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD.

GROWTH INHIBITORY ACTIVITIES OF THE RHIZOME CRUDE EXTRACT OF Curcuma longa ON THE HUMAN PATHOGENIC FUNGUS Mucor circinelloides

2020 ◽  
Vol 65 (10) ◽  
pp. 82-91
Author(s):  
Phuong Nguyen Anh ◽  
Mai Le Thi Tuyet ◽  
Trung Trieu Anh
Keyword(s):  
Antifungal Activity ◽  
Crude Extract ◽  
Fungal Infections ◽  
Early Stage ◽  
Curcuma Longa ◽  
Pathogenic Fungus ◽  
Mucor Circinelloides ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Dilution Method

Mucormycosis is an uncommon but life-threatening invasive fungal infection, mostly occurs in immunocompromised patients. Lacking the appropriate antifungal drugs is one of the reasons that lead to difficulties in the management of mucormycosis. Curcuma longa has been used traditionally and widely to treat various diseases, including fungal infections. In the search for novel antifungal compounds from natural resources, we evaluated the effect of rhizome crude extract of C. longa on Mucor circinelloides – a causal agent of mucormycosis. The results of screening, using broth dilution method and agar-well diffusion method, showed that the C. longa extract exhibited promising antifungal activity against the fungus M. circinelloides. In liquid medium, C. longa extract decreased the ability of spore germination and the speed of hyphae formation of M. circinelloides decreased by up to approximately 70% and 90%, respectively. Besides, in a solid medium, the crude extract presented similar activity with amphotericin B (400 μg\mL) in decreasing the growth of M. circinelloides by nearly 77%. Moreover, the extract of C. longa also likely to induce the yeast-like type of growth of the dimorphic M. circinelloides in the early stage. These results suggest the plant could be a potential source for further study on biochemical components and the mechanism of its antifungal activity.

scholarly journals Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ling Huang ◽  
Daniel B. McClatchy ◽  
Pamela Maher ◽  
Zhibin Liang ◽  
Jolene K. Diedrich ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Model ◽  
Early Stage ◽  
Metabolic Reprogramming ◽  
Therapeutic Interventions ◽  
Amyloid Toxicity ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
Metabolomic Data ◽  
Basic Biology

Abstract Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.

scholarly journals A Genome-Wide CRISPR Activation Screen Identifies Genes Involved in Protection from Zika Virus Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 149
Author(s):  
Anna Dukhovny ◽  
Kevin Lamkiewicz ◽  
Qian Chen ◽  
Markus Fricke ◽  
Nabila Jabrane-Ferrat ◽  
...  
Keyword(s):  
Cell Death ◽  
Zika Virus ◽  
Early Stage ◽  
Specific Treatment ◽  
Febrile Illness ◽  
Neurological Complications ◽  
Host Factors ◽  
Zikv Infection ◽  
A Genome ◽  
Crispr Activation

Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated with the Guillain–Barré syndrome and other neurological complications. The vertical transmission of ZIKV can cause fetus demise, stillbirths or severe congenital abnormalities and neurological complications. There is still no vaccine or specific treatment for ZIKV infection. To identify the host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-lamda2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV infection. The activation of these genes had an effect at an early stage in the viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. These results highlighted a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death, thus substantiating CRISPR activation screens as a valid tool for identifying host factors impeding pathogen infection.

Pathway selection by chick lumbosacral motoneurons during normal development

1981 ◽  
Vol 214 (1194) ◽  
pp. 1-18 ◽  
Keyword(s):  
Cell Death ◽  
Early Stage ◽  
Spinal Nerves ◽  
Functional Connections ◽  
Hindlimb Muscles ◽  
Lateral Motor Column ◽  
Normal Period ◽  
Axon Retraction ◽  
Muscle Nerve ◽  
Specific Muscle

Pathways taken by motoneuron axons from the lumbosacral lateral motor column to individual hindlimb muscles have been characterized throughout the normal period of outgrowth and the establishment of specific functional connections in the chick embryo. Axon pathways from individual cord segments were identified after injections of horseradish peroxidase (HRP) directly into the cord. Labelled motoneuron axons were then traced through the plexus and major nerve trunks to termi­nation sites within the limb. At stages 23-24 labelled axons within spinal nerves have just reached the base of the limb and have begun to converge and form the crural and the ischiadic plexus. Even at this early stage, before periods of muscle cleavage, motoneuron cell death and muscle nerve formation, axons show no evidence of widespread random distribution within the limb. Rather, they generally maintain their anterior-posterior position as far as the base of the limb. At stages 27-30, although axons to individual muscles were found to course in discrete tracts within the plexus and nerve trunks they also changed their topographical position with respect to other axons. Axon pathways to single muscles were characterized by tracing retrogradely labelled axons back to the cord after injections of HRP into specific muscle nerves. Axons destined for a single muscle are intermingled with other axons in the spinal nerves and proximal plexus but by the distal plexus have converged to form a discrete tract which then diverges as an individual muscle nerve at more distal levels. These observations exclude models for the establishment of specific connections in which there is widespread testing of the environment with removal of projection errors by cell death and/or axon retraction. They also exclude models that require axons to maintain their topographical position with respect to each other throughout their course.

scholarly journals The Role of Pseudo-Orthocaspase (SyOC) of Synechocystis sp. PCC 6803 in Attenuating the Effect of Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Saul Lema A ◽  
Marina Klemenčič ◽  
Franziska Völlmy ◽  
Maarten Altelaar ◽  
Christiane Funk
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Building Blocks ◽  
Amino Acid Residues ◽  
Knock Out ◽  
Functional Homology ◽  
Its Gene ◽  
Pcc 6803

Caspases are proteases, best known for their involvement in the execution of apoptosis—a subtype of programmed cell death, which occurs only in animals. These proteases are composed of two structural building blocks: a proteolytically active p20 domain and a regulatory p10 domain. Although structural homologs appear in representatives of all other organisms, their functional homology, i.e., cell death depending on their proteolytical activity, is still much disputed. Additionally, pseudo-caspases and pseudo-metacaspases, in which the catalytic histidine-cysteine dyad is substituted with non-proteolytic amino acid residues, were shown to be involved in cell death programs. Here, we present the involvement of a pseudo-orthocaspase (SyOC), a prokaryotic caspase-homolog lacking the p10 domain, in oxidative stress in the model cyanobacterium Synechocystis sp. PCC 6803. To study the in vivo impact of this pseudo-protease during oxidative stress its gene expression during exposure to H2O2 was monitored by RT-qPCR. Furthermore, a knock-out mutant lacking the pseudo-orthocaspase gene was designed, and its survival and growth rates were compared to wild type cells as well as its proteome. Deletion of SyOC led to cells with a higher tolerance toward oxidative stress, suggesting that this protein may be involved in a pro-death pathway.

Long Term Effect of P188 on Meniscus Preservation Following Blunt Trauma

2012 ◽  
Author(s):  
Adam C. Abraham ◽  
Megan L. Killian ◽  
Roger C. Haut ◽  
Tammy L. Haut Donahue
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Early Stage ◽  
Subsequent Treatment ◽  
Joint Injury ◽  
Secondary Osteoarthritis ◽  
Tissue Degeneration ◽  
Long Term Effect ◽  
Tissue Matrix

Acute knee joint injury has been associated with the development and progression of secondary osteoarthritis (OA). Previous work implicates that acute damage to tissue matrix and cells of the meniscus and articular cartilage may play important roles in early-stage OA [1]. Additionally, it has been shown that articular cartilage matrix repair hinges on chondrocyte preservation [2]. Therefore, inhibition of cell death may halt tissue degeneration. Recently, the FDA-approved surfactant Poloxamer 188 (P-188) has been shown to decrease acute cell death by repair of its plasma membrane, as well as mediate p38 signaling and subsequent inflammatory and apoptotic signaling leading to a reduction in degeneration of impacted cartilage [3, 4]. Therefore, it was hypothesized that matrix glycosaminoglycans of the meniscus will be preserved in the long-term following traumatic impaction and subsequent treatment with P-188.

scholarly journals Complete Clinical Response in Stage IVB Endometrioid Endometrial Carcinoma after First-Line Pembrolizumab Therapy: Report of a Case with Isolated Loss of PMS2 Protein

2020 ◽  
Vol 13 (3) ◽  
pp. 1067-1074
Author(s):  
Jesus Paula Carvalho ◽  
Auro Del Giglio ◽  
Maria Isabel Achatz ◽  
Filomena Marino Carvalho
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Gynecological Cancer ◽  
Stage Iv ◽  
Protein Loss ◽  
First Line ◽  
Early Stage Disease ◽  
Endometrioid Endometrial Carcinoma

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.

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