scholarly journals Cytoplasmic Mixing, Not Nuclear Coexistence, Can Explain Somatic Incompatibility in Basidiomycetes

2021 ◽  
Vol 9 (6) ◽  
pp. 1248
Author(s):  
Ben Auxier ◽  
Karin Scholtmeijer ◽  
Arend F. van van Peer ◽  
Johan J. P. Baars ◽  
Alfons J. M. Debets ◽  
...  
Keyword(s):  
Cell Death ◽  
Nuclear Migration ◽  
Single Type ◽  
Future Research ◽  
Life Stages ◽  
Post Translational Modification ◽  
Somatic Incompatibility ◽  
Nonself Recognition ◽  
Ascomycete Fungi ◽  
Basidiomycete Fungi

Nonself recognition leading to somatic incompatibility (SI) is commonly used by mycologists to distinguish fungal individuals. Despite this, the process remains poorly understood in basidiomycetes as all current models of SI are based on genetic and molecular research in ascomycete fungi. Ascomycete fungi are mainly found in a monokaryotic stage, with a single type of haploid nuclei, and only briefly during mating do two genomes coexist in heterokaryotic cells. The sister phylum, Basidiomycota, differs in several relevant aspects. Basidiomycete fungi have an extended heterokaryotic stage, and SI is generally observed between heterokaryons instead of between homokaryons. Additionally, considerable nuclear migration occurs during a basidiomycete mating reaction, introducing a nucleus into a resident homokaryon with cytoplasmic mixing limited to the fused or neighboring cells. To accommodate these differences, we describe a basidiomycete model for nonself recognition using post-translational modification, based on a reader-writer system as found in other organisms. This post-translational modification combined with nuclear migration allows for the coexistence of two genomes in one individual while maintaining nonself recognition during all life stages. Somewhat surprisingly, this model predicts localized cell death during mating, which is consistent with previous observations but differs from the general assumptions of basidiomycete mating. This model will help guide future research into the mechanisms behind basidiomycete nonself recognition.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

Prediction of Nitration Sites Based on FCBF Method and Stacking Ensemble Model

2021 ◽  
Vol 18 ◽  
Author(s):  
Min Liu ◽  
Lu Zhang ◽  
Xinyi Qin ◽  
Tao Huang ◽  
Ziwei Xu ◽  
...  
Keyword(s):  
Prediction Model ◽  
Protein Sequence ◽  
Cross Validation ◽  
Transplant Rejection ◽  
Sampling Technique ◽  
Single Type ◽  
Post Translational Modification ◽  
Tyrosine Residues ◽  
Under Sampling ◽  
Fusion Features

Background: Nitration is one of the important Post-Translational Modification (PTM) occurring on the tyrosine residues of proteins. The occurrence of protein tyrosine nitration under disease conditions is inevitable and represents a shift from the signal transducing physiological actions of -NO to oxidative and potentially pathogenic pathways. Abnormal protein nitration modification can lead to serious human diseases, including neurodegenerative diseases, acute respiratory distress, organ transplant rejection and lung cancer. Objective: It is necessary and important to identify the nitration sites in protein sequences. Predicting that which tyrosine residues in the protein sequence are nitrated and which are not is of great significance for the study of nitration mechanism and related diseases. Methods: In this study, a prediction model of nitration sites based on the over-under sampling strategy and the FCBF method was proposed by stacking ensemble learning and fusing multiple features. Firstly, the protein sequence sample was encoded by 2701-dimensional fusion features (PseAAC, PSSM, AAIndex, CKSAAP, Disorder). Secondly, the ranked feature set was generated by the FCBF method according to the symmetric uncertainty metric. Thirdly, in the process of model training, use the over- and under- sampling technique was used to tackle the imbalanced dataset. Finally, the Incremental Feature Selection (IFS) method was adopted to extract an optimal classifier based on 10-fold cross-validation. Results and Conclusion: Results show that the model has significant performance advantages in indicators such as MCC, Recall and F1-score, no matter in what way the comparison was conducted with other classifiers on the independent test set, or made by cross-validation with single-type feature or with fusion-features on the training set. By integrating the FCBF feature ranking methods, over- and under- sampling technique and a stacking model composed of multiple base classifiers, an effective prediction model for nitration PTM sites was build, which can achieve a better recall rate when the ratio of positive and negative samples is highly imbalanced.

scholarly journals Calcium Signaling in Plant Programmed Cell Death

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1089
Author(s):  
Huimin Ren ◽  
Xiaohong Zhao ◽  
Wenjie Li ◽  
Jamshaid Hussain ◽  
Guoning Qi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Abiotic Stresses ◽  
Animal Studies ◽  
Future Research ◽  
Significant Progress ◽  
Biotic And Abiotic Stresses ◽  
Stress Perception ◽  
The Past

Programmed cell death (PCD) is a process intended for the maintenance of cellular homeostasis by eliminating old, damaged, or unwanted cells. In plants, PCD takes place during developmental processes and in response to biotic and abiotic stresses. In contrast to the field of animal studies, PCD is not well understood in plants. Calcium (Ca2+) is a universal cell signaling entity and regulates numerous physiological activities across all the kingdoms of life. The cytosolic increase in Ca2+ is a prerequisite for the induction of PCD in plants. Although over the past years, we have witnessed significant progress in understanding the role of Ca2+ in the regulation of PCD, it is still unclear how the upstream stress perception leads to the Ca2+ elevation and how the signal is further propagated to result in the onset of PCD. In this review article, we discuss recent advancements in the field, and compare the role of Ca2+ signaling in PCD in biotic and abiotic stresses. Moreover, we discuss the upstream and downstream components of Ca2+ signaling and its crosstalk with other signaling pathways in PCD. The review is expected to provide new insights into the role of Ca2+ signaling in PCD and to identify gaps for future research efforts.

scholarly journals Growth-factor-dependent phosphorylation of Bim in mitosis

2005 ◽  
Vol 388 (1) ◽  
pp. 185-194 ◽  
Author(s):  
Mário GRÃOS ◽  
Alexandra D. ALMEIDA ◽  
Sukalyan CHATTERJEE
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Growth Factor ◽  
Cell Fate ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Post Translational Modification ◽  
Proliferating Cells ◽  
Growth Factor Signalling ◽  
Induced Apoptosis

The regulation of survival and cell death is a key determinant of cell fate. Recent evidence shows that survival and death machineries are regulated along the cell cycle. In the present paper, we show that BimEL [a BH3 (Bcl-2 homology 3)-only member of the Bcl-2 family of proteins; Bim is Bcl-2-interacting mediator of cell death; EL is the extra-long form] is phosphorylated in mitosis. This post-translational modification is dependent on MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase) and growth factor signalling. Interestingly, FGF (fibroblast growth factor) signalling seems to play an essential role in this process, since, in the presence of serum, inhibition of FGF receptors abrogated phosphorylation of Bim in mitosis. Moreover, we have shown bFGF (basic FGF) to be sufficient to induce phosphorylation of Bim in serum-free conditions in any phase of the cell cycle, and also to significantly rescue cells from serum-deprivation-induced apoptosis. Our results show that, in mitosis, Bim is phosphorylated downstream of growth factor signalling in a MEK-dependent manner, with FGF signalling playing an important role. We suggest that phosphorylation of Bim is a decisive step for the survival of proliferating cells.

Conserved E1B-55K SUMOylation in different human adenovirus species is a potent regulator of intracellular localization

2021 ◽  
Author(s):  
Viktoria Kolbe ◽  
Wing H. Ip ◽  
Lisa Kieweg-Thompson ◽  
Judith Lang ◽  
Julia Gruhne ◽  
...  
Keyword(s):  
Cell Transformation ◽  
Intracellular Localization ◽  
Human Adenovirus ◽  
Lysine Residue ◽  
Future Research ◽  
Post Translational Modification ◽  
Cellular Effects ◽  
Sumo Conjugation ◽  
Functional Consequences ◽  
Organ Tropism

Over the past decades, studies on the biology of human adenoviruses (HAdVs) mainly focused on the HAdV prototype species C type 5 (HAdV-C5) and revealed fundamental molecular insights into mechanisms of viral replication and viral cell transformation. Recently, other HAdV species are gaining more and more attention in the field. Reports on large E1B proteins (E1B-55K) from different HAdV species showed that these multifactorial proteins possess strikingly different features along with highly conserved functions. In this work, we identified potential SUMO-conjugation motifs (SCMs) in E1B-55K proteins from HAdV species A to F. Mutational inactivation of these SCMs demonstrated that HAdV E1B-55K proteins are SUMOylated at a single lysine residue that is highly conserved among HAdV species B to E. Moreover, we provide evidence that E1B-55K SUMOylation is a potent regulator of intracellular localization and p53-mediated transcription in most HAdV species. We also identified a lysine residue at position 101 (K101), which is unique to HAdV-C5 E1B-55K and specifically regulates its SUMOylation and nucleo-cytoplasmic shuttling. Our findings reveal important new aspects on HAdV E1B-55K proteins and suggest that different E1B-55K species possess conserved SCMs while their SUMOylation has divergent cellular effects during infection. Importance E1B-55K is a multifunctional adenoviral protein and its functions are highly regulated by SUMOylation. Although functional consequences of SUMOylated HAdV-C5 E1B-55K are well studied, we lack information on the effects of SUMOylation on homologous E1B-55K proteins from other HAdV species. Here, we show that SUMOylation is a conserved post-translational modification in most of the E1B-55K proteins, similar to what we know about HAdV-C5 E1B-55K. Moreover, we identify subcellular localization and regulation of p53-dependent transcription as highly conserved SUMOylation-regulated E1B-55K functions. Thus, our results highlight how HAdV proteins might have evolved in different HAdV species with conserved domains involved in virus replication and differing alternative functions and interactions with the host cell machinery. Future research will link these differences and similarities to the diverse pathogenicity and organ tropism of the different HAdV species.

Efficacy of PD-1 or PD-L1 inhibitors and central nervous system metastases in advanced cancer: a meta-analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Minyong Peng ◽  
Shan Li ◽  
Hui Xiang ◽  
Wen Huang ◽  
Weiling Mao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Cell Death ◽  
Nervous System ◽  
Programmed Cell Death ◽  
Future Research ◽  
Significant Heterogeneity ◽  
Cns Metastases ◽  
Hazard Ratios ◽  
Significant Difference

<P>Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. <P> Objective: Assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. <P> Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. <P> Results: 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (Χ=0.06 P=0.80). <P> Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded from PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PD-L1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.</P>

scholarly journals VIB-1 Is Required for Expression of Genes Necessary for Programmed Cell Death in Neurospora crassa

2006 ◽  
Vol 5 (12) ◽  
pp. 2161-2173 ◽  
Author(s):  
Karine Dementhon ◽  
Gopal Iyer ◽  
N. Louise Glass
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Neurospora Crassa ◽  
Filamentous Fungi ◽  
Somatic Growth ◽  
Genetic Differences ◽  
Extracellular Proteases ◽  
Hyphal Fusion ◽  
Expression Of Genes ◽  
Nonself Recognition

ABSTRACT Nonself recognition during somatic growth is an essential and ubiquitous phenomenon in both prokaryotic and eukaryotic species. In filamentous fungi, nonself recognition is also important during vegetative growth. Hyphal fusion between genetically dissimilar individuals results in rejection of heterokaryon formation and in programmed cell death of the fusion compartment. In filamentous fungi, such as Neurospora crassa, nonself recognition and heterokaryon incompatibility (HI) are regulated by genetic differences at het loci. In N. crassa, mutations at the vib-1 locus suppress nonself recognition and HI mediated by genetic differences at het-c/pin-c, mat, and un-24/het-6. vib-1 is a homolog of Saccharomyces cerevisiae NDT80, which is a transcriptional activator of genes during meiosis. For this study, we determined that vib-1 encodes a nuclear protein and showed that VIB-1 localization varies during asexual reproduction and during HI. vib-1 is required for the expression of genes involved in nonself recognition and HI, including pin-c, tol, and het-6; all of these genes encode proteins containing a HET domain. vib-1 is also required for the production of downstream effectors associated with HI, including the production of extracellular proteases upon carbon and nitrogen starvation. Our data support a model in which mechanisms associated with starvation and nonself recognition/HI are interconnected. VIB-1 is a major regulator of responses to nitrogen and carbon starvation and is essential for the expression of genes involved in nonself recognition and death in N. crassa.

Flavin transferase: the maturation factor of flavin-containing oxidoreductases

2018 ◽  
Vol 46 (5) ◽  
pp. 1161-1169 ◽  
Author(s):  
Alexander V. Bogachev ◽  
Alexander A. Baykov ◽  
Yulia V. Bertsova
Keyword(s):  
Bond Formation ◽  
Covalent Bond ◽  
Target Protein ◽  
Covalent Attachment ◽  
Future Research ◽  
Post Translational Modification ◽  
Nadh:Quinone Oxidoreductase ◽  
Maturation Factor ◽  
Covalently Linked ◽  
Prevailing View

Flavins, cofactors of many enzymes, are often covalently linked to these enzymes; for instance, flavin adenine mononucleotide (FMN) can form a covalent bond through either its phosphate or isoalloxazine group. The prevailing view had long been that all types of covalent attachment of flavins occur as autocatalytic reactions; however, in 2013, the first flavin transferase was identified, which catalyzes phosphoester bond formation between FMN and Na+-translocating NADH:quinone oxidoreductase in certain bacteria. Later studies have indicated that this post-translational modification is widespread in prokaryotes and is even found in some eukaryotes. Flavin transferase can occur as a separate ∼40 kDa protein or as a domain within the target protein and recognizes a degenerate DgxtsAT/S motif in various target proteins. The purpose of this review was to summarize the progress already achieved by studies of the structure, mechanism, and specificity of flavin transferase and to encourage future research on this topic. Interestingly, the flavin transferase gene (apbE) is found in many bacteria that have no known target protein, suggesting the presence of yet unknown flavinylation targets.

scholarly journals Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins

2020 ◽  
Vol 28 (1) ◽  
pp. 108-122
Author(s):  
James M. Pemberton ◽  
Justin P. Pogmore ◽  
David W. Andrews
Keyword(s):  
Cell Death ◽  
Neuronal Apoptosis ◽  
Axonal Degeneration ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Axon Degeneration ◽  
Mitochondrial Outer Membrane ◽  
Future Research ◽  
System Disease ◽  
Family Protein

AbstractAxonal degeneration and neuronal cell death are fundamental processes in development and contribute to the pathology of neurological disease in adults. Both processes are regulated by BCL-2 family proteins which orchestrate the permeabilization of the mitochondrial outer membrane (MOM). MOM permeabilization (MOMP) results in the activation of pro-apoptotic molecules that commit neurons to either die or degenerate. With the success of small-molecule inhibitors targeting anti-apoptotic BCL-2 proteins for the treatment of lymphoma, we can now envision the use of inhibitors of apoptosis with exquisite selectivity for BCL-2 family protein regulation of neuronal apoptosis in the treatment of nervous system disease. Critical to this development is deciphering which subset of proteins is required for neuronal apoptosis and axon degeneration, and how these two different outcomes are separately regulated. Moreover, noncanonical BCL-2 family protein functions unrelated to the regulation of MOMP, including impacting necroptosis and other modes of cell death may reveal additional potential targets and/or confounders. This review highlights our current understanding of BCL-2 family mediated neuronal cell death and axon degeneration, while identifying future research questions to be resolved to enable regulating neuronal survival pharmacologically.

scholarly journals Effect of ocean acidification on early life stages of Atlantic herring (<i>Clupea harengus</i> L.)

2011 ◽  
Vol 8 (12) ◽  
pp. 3697-3707 ◽  
Author(s):  
A. Franke ◽  
C. Clemmesen
Keyword(s):  
Ocean Acidification ◽  
Linear Relationship ◽  
Early Life ◽  
Clupea Harengus ◽  
Control Treatment ◽  
Future Research ◽  
Atlantic Herring ◽  
Life Stages ◽  
Early Life Stages ◽  
Newly Hatched Larvae

Abstract. Due to atmospheric accumulation of anthropogenic CO2 the partial pressure of carbon dioxide (pCO2) in surface seawater increases and the pH decreases. This process known as ocean acidification might have severe effects on marine organisms and ecosystems. The present study addresses the effect of ocean acidification on early developmental stages, the most sensitive stages in life history, of the Atlantic herring (Clupea harengus L.). Eggs of the Atlantic herring were fertilized and incubated in artificially acidified seawater (pCO2 1260, 1859, 2626, 2903, 4635 μatm) and a control treatment (pCO2 480 μatm) until the main hatch of herring larvae occurred. The development of the embryos was monitored daily and newly hatched larvae were sampled to analyze their morphometrics, and their condition by measuring the RNA/DNA ratios. Elevated pCO2 neither affected the embryogenesis nor the hatch rate. Furthermore the results showed no linear relationship between pCO2 and total length, dry weight, yolk sac area and otolith area of the newly hatched larvae. For pCO2 and RNA/DNA ratio, however, a significant negative linear relationship was found. The RNA concentration at hatching was reduced at higher pCO2 levels, which could lead to a decreased protein biosynthesis. The results indicate that an increased pCO2 can affect the metabolism of herring embryos negatively. Accordingly, further somatic growth of the larvae could be reduced. This can have consequences for the larval fish, since smaller and slow growing individuals have a lower survival potential due to lower feeding success and increased predation mortality. The regulatory mechanisms necessary to compensate for effects of hypercapnia could therefore lead to lower larval survival. Since the recruitment of fish seems to be determined during the early life stages, future research on the factors influencing these stages are of great importance in fisheries science.

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