RESUMEN
Steroid hormones induce the transcription of target genes by activating nuclear receptors. Early transcriptional response to various stimuli, including hormones, involves the active catalysis of topoisomerase II (TOP2) at transcription regulatory sequences. TOP2 untangles DNAs by transiently generating double-strand breaks (DSBs), where TOP2 covalently binds to DSB ends. When TOP2 fails to rejoin, called "abortive" catalysis, the resulting DSBs are repaired by tyrosyl-DNA phosphodiesterase 2 (TDP2) and non-homologous end-joining (NHEJ). A steroid, cortisol, is the most important glucocorticoid, and dexamethasone (Dex), a synthetic glucocorticoid, is widely used for suppressing inflammation in clinics. We here revealed that clinically relevant concentrations of Dex and physiological concentrations of cortisol efficiently induce DSBs in G1 phase cells deficient in TDP2 and NHEJ. The DSB induction depends on glucocorticoid receptor (GR) and TOP2. Considering the specific role of TDP2 in removing TOP2 adducts from DSB ends, induced DSBs most likely represent stalled TOP2-DSB complexes. Inhibition of RNA polymerase II suppressed the DSBs formation only modestly in the G1 phase. We propose that cortisol and Dex frequently generate DSBs through the abortive catalysis of TOP2 at transcriptional regulatory sequences, including promoters or enhancers, where active TOP2 catalysis occurs during early transcriptional response.
Asunto(s)
Roturas del ADN de Doble Cadena , Factores de Transcripción , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/metabolismo , Glucocorticoides/farmacología , Reparación del ADN , Proteínas Nucleares/metabolismo , Hidrocortisona/farmacología , Hidrolasas Diéster Fosfóricas/genética , Hidrolasas Diéster Fosfóricas/metabolismo , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , ADN/genéticaRESUMEN
The Mre11/Rad50/Nbs1 complex initiates double-strand break repair by homologous recombination (HR). Loss of Mre11 or its nuclease activity in mouse cells is known to cause genome aberrations and cellular senescence, although the molecular basis for this phenotype is not clear. To identify the origin of these defects, we characterized Mre11-deficient (MRE11-/-) and nuclease-deficient Mre11 (MRE11-/H129N) chicken DT40 and human lymphoblast cell lines. These cells exhibit increased spontaneous chromosomal DSBs and extreme sensitivity to topoisomerase 2 poisons. The defects in Mre11 compromise the repair of etoposide-induced Top2-DNA covalent complexes, and MRE11-/- and MRE11-/H129N cells accumulate high levels of Top2 covalent conjugates even in the absence of exogenous damage. We demonstrate that both the genome instability and mortality of MRE11-/- and MRE11-/H129N cells are significantly reversed by overexpression of Tdp2, an enzyme that eliminates covalent Top2 conjugates; thus, the essential role of Mre11 nuclease activity is likely to remove these lesions.
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Antígenos de Neoplasias/genética , Roturas del ADN de Doble Cadena/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/genética , Proteínas de Unión al ADN/genética , ADN/genética , Proteínas Nucleares/genética , Reparación del ADN por Recombinación/efectos de los fármacos , Factores de Transcripción/genética , Ácido Anhídrido Hidrolasas , Animales , Antígenos de Neoplasias/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Pollos , ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismo , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/metabolismo , Etopósido/farmacología , Regulación de la Expresión Génica , Inestabilidad Genómica/efectos de los fármacos , Humanos , Linfocitos/citología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Proteína Homóloga de MRE11 , Mutación , Proteínas Nucleares/metabolismo , Hidrolasas Diéster Fosfóricas , Proteínas de Unión a Poli-ADP-Ribosa , Transducción de Señal , Inhibidores de Topoisomerasa II/farmacología , Factores de Transcripción/metabolismoRESUMEN
Nucleotide excision repair (NER) removes helix-destabilizing adducts including ultraviolet (UV) lesions, cyclobutane pyrimidine dimers (CPDs), and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). In comparison with CPDs, 6-4PPs have greater cytotoxicity and more strongly destabilizing properties of the DNA helix. It is generally believed that NER is the only DNA repair pathway that removes the UV lesions as evidenced by the previous data since no repair of UV lesions was detected in NER-deficient skin fibroblasts. Topoisomerase I (TOP1) constantly creates transient single-strand breaks (SSBs) releasing the torsional stress in genomic duplex DNA. Stalled TOP1-SSB complexes can form near DNA lesions including abasic sites and ribonucleotides embedded in chromosomal DNA. Here we show that base excision repair (BER) increases cellular tolerance to UV independently of NER in cancer cells. UV lesions irreversibly trap stable TOP1-SSB complexes near the UV damage in NER-deficient cells, and the resulting SSBs activate BER. Biochemical experiments show that 6-4PPs efficiently induce stable TOP1-SSB complexes, and the long-patch repair synthesis of BER removes 6-4PPs downstream of the SSB. Furthermore, NER-deficient cancer cell lines remove 6-4PPs within 24 h, but not CPDs, and the removal correlates with TOP1 expression. NER-deficient skin fibroblasts weakly express TOP1 and show no detectable repair of 6-4PPs. Remarkably, the ectopic expression of TOP1 in these fibroblasts led them to completely repair 6-4PPs within 24 h. In conclusion, we reveal a DNA repair pathway initiated by TOP1, which significantly contributes to cellular tolerance to UV-induced lesions particularly in malignant cancer cells overexpressing TOP1.
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Roturas del ADN de Cadena Simple/efectos de la radiación , Reparación del ADN , ADN-Topoisomerasas de Tipo I/metabolismo , Rayos Ultravioleta/efectos adversos , Sistemas CRISPR-Cas/genética , ADN Polimerasa beta/genética , ADN Polimerasa beta/metabolismo , Fibroblastos , Técnicas de Inactivación de Genes , Humanos , Células MCF-7 , Cultivo Primario de Células , Piel/citología , Piel/patología , Piel/efectos de la radiación , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/metabolismo , Xerodermia Pigmentosa/etiología , Xerodermia Pigmentosa/patología , Proteína de la Xerodermia Pigmentosa del Grupo A/genética , Proteína de la Xerodermia Pigmentosa del Grupo A/metabolismoRESUMEN
Achieving high-yield potential is always the ultimate objective of any breeding program. However, various abiotic stresses such as salinity, drought, cold, flood, and heat hampered rice productivity tremendously. Salinity is one of the most important abiotic stresses that adversely affect rice grain yield. The present investigation was undertaken to dissect new genetic loci, which are responsible for salt tolerance at the early seedling stage in rice. A bi-parental mapping population (F2:3) was developed from the cross between BRRI dhan28/Akundi, where BRRI dhan28 (BR28) is a salt-sensitive irrigated (boro) rice mega variety and Akundi is a highly salinity-tolerant Bangladeshi origin indica rice landrace that is utilized as a donor parent. We report reliable and stable QTLs for salt tolerance from a common donor (Akundi) irrespective of two different genetic backgrounds (BRRI dhan49/Akundi and BRRI dhan28/Akundi). A robust 1k-Rice Custom Amplicon (1k-RiCA) SNP marker genotyping platform was used for genome-wide analysis of this bi-parental population. After eliminating markers with high segregation distortion, 886 polymorphic SNPs built a genetic linkage map covering 1526.5 cM of whole rice genome with an average SNP density of 1.72 cM for the 12 genetic linkage groups. A total of 12 QTLs for nine different salt tolerance-related traits were identified using QGene and inclusive composite interval mapping of additive and dominant QTL (ICIM-ADD) under salt stress on seven different chromosomes. All of these 12 new QTLs were found to be unique, as no other map from the previous study has reported these QTLs in the similar chromosomal location and found them different from extensively studied Saltol, SKC1, OsSalT, and salT locus. Twenty-eight significant digenic/epistatic interactions were identified between chromosomal regions linked to or unlinked to QTLs. Akundi acts like a new alternate donor source of salt tolerance except for other usually known donors such as Nona Bokra, Pokkali, Capsule, and Hasawi used in salt tolerance genetic analysis and breeding programs worldwide, including Bangladesh. Integration of the seven novel, reliable, stable, and background independent salinity-resilient QTLs (qSES1, qSL1, qRL1, qSUR1, qSL8, qK8, qK1) reported in this investigation will expedite the cultivar development that is highly tolerant to salt stress.
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Oryza , Oryza/genética , Polimorfismo de Nucleótido Simple , Salinidad , Fitomejoramiento , Sitios de Carácter CuantitativoRESUMEN
The study was conducted to determine the genetic variants of κ-casein and ß-lactoglobulin genes in native cattle. DNA was extracted from blood samples (n = 80) collected from Babuganj, Barishal followed by PCR with gene-specific primers. Genotyping was done by RFLP with HindIII, and HaeIII restriction enzymes. Allelic and genotypic frequencies, genetic diversity, heterozygosity and Hardy-Weinberg equilibrium were estimated using the Popgen32 software. A total 80 samples were genotyped and three genotypes, namely AA, AB and BB, were detected for both the genes. In case of κ-casein gene, higher frequency was observed for AA genotype (0.73) followed by AB (0.23) and BB (0.04) genotype. A allele (0.84) was found to dominate over B allele (0.16). For ß-lactoglobulin gene, BB genotype (0.66) was found more frequently than AB (0.18) and AA (0.16) genotypes. Highest frequency was found for B (0.75) followed by A (0.25) allele. The average genetic diversity (He) was 0.38. The result indicated differences between observed (Ho) and expected (He) heterozygosity and it was out of equilibrium genetics, assumed that selection pressure was in population. To the best of our knowledge, this is the first reported study on κ-casein and ß-lactoglobulin gene variants analysis in cattle in Bangladesh.
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Caseínas , Lactoglobulinas , Alelos , Animales , Bangladesh , Caseínas/genética , Bovinos/genética , Genotipo , Lactoglobulinas/genéticaRESUMEN
The emerged novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health crisis that warrants an accurate and detailed characterization of the rapidly evolving viral genome for understanding its epidemiology, pathogenesis, and containment. Here, we explored 61,485 sequences of the nucleocapsid (N) protein, a potent diagnostic and prophylactic target, for identifying the mutations to review their roles in real-time polymerase chain reaction based diagnosis and observe consequent impacts. Compared to the Wuhan reference strain, a total of 1034 unique nucleotide mutations were identified in the mutant strains (49.15%, n = 30,221) globally. Of these mutations, 367 occupy primer binding sites including the 3'-end mismatch to the primer-pair of 11 well-characterized primer sets. Noteworthily, CDC (USA) recommended the N2 primer set contained a lower mismatch than the other primer sets. Moreover, 684 amino acid (aa) substitutions were located across 317 (75.66% of total aa) unique positions including 82, 21, and 83 of those in the RNA binding N-terminal domain (NTD), SR-rich region, and C-terminal dimerization domain, respectively. Moreover, 11 in-frame deletions, mostly (n = 10) within the highly flexible linker region, were revealed, and the rest was within the NTD region. Furthermore, we predicted the possible consequence of high-frequency mutations (≥20) and deletions on the tertiary structure of the N protein. Remarkably, we observed that a high frequency (67.94% of mutated sequences) co-occuring mutations (R203K and G204R) destabilized and decreased overall structural flexibility. The N protein of SARS-CoV-2 comprises an average of 1.2 mutations per strain compared to 4.4 and 0.4 in Middle East respiratory syndrome-related coronavirus and SARS-CoV, respectively. Despite being proposed as the alternative target to spike protein for vaccine and therapeutics, the ongoing evolution of the N protein may challenge these endeavors, thus needing further immunoinformatics analyses. Therefore, continuous monitoring is required for tracing the ongoing evolution of the SARS-CoV-2 N protein in prophylactic and diagnostic interventions.
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Proteínas de la Nucleocápside de Coronavirus/genética , SARS-CoV-2/genética , Sustitución de Aminoácidos , COVID-19/epidemiología , COVID-19/virología , Proteínas de la Nucleocápside de Coronavirus/química , Proteínas de la Nucleocápside de Coronavirus/metabolismo , Evolución Molecular , Genes Virales , Genoma Viral , Simulación de Dinámica Molecular , Mutación , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Unión Proteica , Conformación ProteicaRESUMEN
The novel coronavirus infectious disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has traumatized the whole world with the ongoing devastating pandemic. A plethora of microbial domains including viruses (other than SARS-CoV-2), bacteria, archaea and fungi have evolved together, and interact in complex molecular pathogenesis along with SARS-CoV-2. However, the involvement of other microbial co-pathogens and underlying molecular mechanisms leading to extortionate ailment in critically ill COVID-19 patients has yet not been extensively reviewed. Although, the incidence of co-infections could be up to 94.2% in laboratory-confirmed COVID-19 cases, the fate of co-infections among SARS-CoV-2 infected hosts often depends on the balance between the host's protective immunity and immunopathology. Predominantly identified co-pathogens of SARS-CoV-2 are bacteria such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Acinetobacter baumannii, Legionella pneumophila and Clamydia pneumoniae followed by viruses including influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. The cross-talk between co-pathogens (especially lung microbiomes), SARS-CoV-2 and host is an important factor that ultimately increases the difficulty of diagnosis, treatment, and prognosis of COVID-19. Simultaneously, co-infecting microbiotas may use new strategies to escape host defense mechanisms by altering both innate and adaptive immune responses to further aggravate SARS-CoV-2 pathogenesis. Better understanding of co-infections in COVID-19 is critical for the effective patient management, treatment and containment of SARS-CoV-2. This review therefore necessitates the comprehensive investigation of commonly reported microbial co-pathogens amid COVID-19, their transmission pattern along with the possible mechanism of co-infections and outcomes. Thus, identifying the possible co-pathogens and their underlying molecular mechanisms during SARS-CoV-2 pathogenesis may shed light in developing diagnostics, appropriate curative and preventive interventions for suspected SARS-CoV-2 respiratory infections in the current pandemic.
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COVID-19 , Coinfección , Enfermedades Transmisibles , Microbiota , Humanos , SARS-CoV-2RESUMEN
Although indigenous climbing perch (Anabas testudineusis) is a highly valuable species, slow growth pattern during the culture period impeding its commercial success in aquaculture. In many fish species, it has been demonstrated that incubation temperature of eggs influenced the muscle development and growth rates, which persisted throughout the subsequent larval and juvenile phases. Therefore, this study aimed to investigate whether different incubation temperature of eggs prior to hatching can stimulate the muscle development, growth, and growth-related gene expression of the slow-growing indigenous species of climbing perch. The fertilized eggs of A. testudineus from an artificial breeding program were incubated under control temperature of 24 °C (IT24), 26 °C (IT26), 28 °C (IT28), and 30 °C (IT30) in 10L glass aquaria with four replicated units for each temperature treatment. After hatching, the larvae from each incubated temperature were separately reared at ambient temperature for 10 days in aquarium, 20 days in hapas, and the next 42 days in cages, totaling 72 days post-hatching (dph). The hatching rates were found significantly (P < 0.05) higher in IT28 compared to the other incubation temperature treatments. After 72 dph, the growth performances (%length gained, %weight gained and SGR) were found to be significantly highest (P < 0.05) in the IT28, followed by the treatments IT30, IT26, and IT24, respectively. Survival rate (73 ± 1.257%) was also found to be highest in the same treatment. The rate of new muscle fiber formation was identified to be significantly highest (P < 0.05) in IT28 followed by the IT26, IT30 and IT24, respectively. The relative mRNA expression level of GHRH, IGF1, IGF2 and PRL was also significantly highest in the IT28 (P < 0.05) compared to other treatments. Results from the present study clearly suggested that 28 °C is the optimum eggs incubation temperature of the native strain of A. testudineus for its highest growth performances in captive breeding condition.
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Regulación del Desarrollo de la Expresión Génica , Músculo Esquelético/crecimiento & desarrollo , Percas , Temperatura , Cigoto/crecimiento & desarrollo , Animales , Femenino , Proteínas de Peces/genética , Hormona Liberadora de Gonadotropina/genética , Factor I del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/genética , Masculino , Músculo Esquelético/anatomía & histología , Músculo Esquelético/metabolismo , Percas/anatomía & histología , Percas/genética , Percas/crecimiento & desarrollo , Prolactina/genéticaRESUMEN
Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation. We also identified >55 heretofore-unknown protein substrates of the cysteine sulfinic acid reductase sulfiredoxin, extending its function well beyond those of 2-cysteine peroxiredoxins (2-Cys PRDX1-4) and offering new insights into the role of this unique oxidoreductase as a central mediator of reactive oxygen species-associated diseases, particularly cancer. DiaAlk therefore provides a novel tool to profile S-sulfinylated proteins and study their regulatory mechanisms in cells.
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Cisteína/análogos & derivados , Nitrógeno/química , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/química , Procesamiento Proteico-Postraduccional , Proteómica/métodos , Células A549 , Cisteína/química , Epítopos/química , Células HEK293 , Células HeLa , Humanos , Oxidación-Reducción , Estrés Oxidativo , Péptidos/química , Peroxirredoxinas , Especies Reactivas de Oxígeno/química , Proteínas Recombinantes/química , Ácidos SulfénicosRESUMEN
Identifying the sulfenylation state of stressed cells is emerging as a strategic approach for the detection of key reactive oxygen species signaling proteins. Here, we optimized an in vivo trapping method for cysteine sulfenic acids in hydrogen peroxide (H2O2) stressed plant cells using a dimedone based DYn-2 probe. We demonstrated that DYn-2 specifically detects sulfenylation events in an H2O2 dose- and time-dependent way. With mass spectrometry, we identified 226 sulfenylated proteins after H2O2 treatment of Arabidopsis cells, residing in the cytoplasm (123); plastid (68); mitochondria (14); nucleus (10); endoplasmic reticulum, Golgi and plasma membrane (7) and peroxisomes (4). Of these, 123 sulfenylated proteins have never been reported before to undergo cysteine oxidative post-translational modifications in plants. All in all, with this DYn-2 approach, we have identified new sulfenylated proteins, and gave a first glance on the locations of the sulfenomes of Arabidopsis thaliana.
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Proteínas de Arabidopsis/análisis , Arabidopsis/metabolismo , Ciclohexanonas/química , Sondas Moleculares/química , Procesamiento Proteico-Postraduccional , Ácidos Sulfénicos/metabolismo , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Avidina/química , Biotina/química , Compartimento Celular , Técnicas de Cultivo de Célula , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Anotación de Secuencia Molecular , Orgánulos/efectos de los fármacos , Orgánulos/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Proteómica/métodos , Transducción de Señal , Ácidos Sulfénicos/químicaRESUMEN
Reactive oxygen species (ROS) have been shown to be potent signaling molecules. Today, oxidation of cysteine residues is a well-recognized posttranslational protein modification, but the signaling processes steered by such oxidations are poorly understood. To gain insight into the cysteine thiol-dependent ROS signaling in Arabidopsis thaliana, we identified the hydrogen peroxide (H2O2)-dependent sulfenome: that is, proteins with at least one cysteine thiol oxidized to a sulfenic acid. By means of a genetic construct consisting of a fusion between the C-terminal domain of the yeast (Saccharomyces cerevisiae) AP-1-like (YAP1) transcription factor and a tandem affinity purification tag, we detected â¼ 100 sulfenylated proteins in Arabidopsis cell suspensions exposed to H2O2 stress. The in vivo YAP1-based trapping of sulfenylated proteins was validated by a targeted in vitro analysis of dehydroascorbate reductase2 (DHAR2). In DHAR2, the active site nucleophilic cysteine is regulated through a sulfenic acid-dependent switch, leading to S-glutathionylation, a protein modification that protects the protein against oxidative damage.
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Arabidopsis/metabolismo , Metaboloma , Ácidos Sulfénicos/metabolismo , Arabidopsis/efectos de los fármacos , Proteínas de Arabidopsis/metabolismo , Cisteína/metabolismo , Glutatión/metabolismo , Peróxido de Hidrógeno/farmacología , Cinética , Metaboloma/efectos de los fármacos , Modelos Biológicos , Complejos Multiproteicos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Proteolisis/efectos de los fármacos , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
In plants, fluctuation of the redox balance by altered levels of reactive oxygen species (ROS) can affect many aspects of cellular physiology. ROS homeostasis is governed by a diversified set of antioxidant systems. Perturbation of this homeostasis leads to transient or permanent changes in the redox status and is exploited by plants in different stress signalling mechanisms. Understanding how plants sense ROS and transduce these stimuli into downstream biological responses is still a major challenge. ROS can provoke reversible and irreversible modifications to proteins that act in diverse signalling pathways. These oxidative post-translational modifications (Ox-PTMs) lead to oxidative damage and/or trigger structural alterations in these target proteins. Characterization of the effect of individual Ox-PTMs on individual proteins is the key to a better understanding of how cells interpret the oxidative signals that arise from developmental cues and stress conditions. This review focuses on ROS-mediated Ox-PTMs on cysteine (Cys) residues. The Cys side chain, with its high nucleophilic capacity, appears to be the principle target of ROS. Ox-PTMs on Cys residues participate in various signalling cascades initiated by plant stress hormones. We review the mechanistic aspects and functional consequences of Cys Ox-PTMs on specific target proteins in view of stress signalling events.
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Cisteína/metabolismo , Fenómenos Fisiológicos de las Plantas , Proteínas de Plantas/metabolismo , Procesamiento Proteico-Postraduccional , Especies Reactivas de Oxígeno/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Transducción de SeñalRESUMEN
Plants generate reactive oxygen species (ROS) as part of their metabolism and in response to various external stress factors, potentially causing significant damage to biomolecules and cell structures. During the course of evolution, plants have adapted to ROS toxicity, and use ROS as signalling messengers that activate defence responses. Cysteine (Cys) residues in proteins are one of the most sensitive targets for ROS-mediated post-translational modifications, and they have become key residues for ROS signalling studies. The reactivity of Cys residues towards ROS, and their ability to react to different oxidation states, allow them to appear at the crossroads of highly dynamic oxidative events. As such, a redox-active cysteine can be present as S-glutathionylated (-SSG), disulfide bonded (S-S), sulfenylated (-SOH), sulfinylated (-SO2H), and sulfonylated (-SO3H). The sulfenic acid (-SOH) form has been considered as part of ROS-sensing pathways, as it leads to further modifications which affect protein structure and function. Redox proteomic studies are required to understand how and why cysteines undergo oxidative post-translational modifications and to identify the ROS-sensor proteins. Here, we update current knowledge of cysteine reactivity with ROS. Further, we give an overview of proteomic techniques that have been applied to identify different redox-modified cysteines in plants. There is a particular focus on the identification of sulfenylated proteins, which have the potential to be involved in plant signal transduction.
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Cisteína/metabolismo , Fenómenos Fisiológicos de las Plantas , Proteínas de Plantas/metabolismo , Proteoma , Especies Reactivas de Oxígeno/metabolismo , Oxidación-Reducción , Transducción de SeñalRESUMEN
The structural and multiferroic properties of xNi0.24Zn0.58Cu0.18Fe2O4(NZCFO)-(1-x)Bi0.9Nd0.1Fe0.95 Sc0.05O3(BNFSO) are explored in this paper. Bi2O3 additives significantly lower the sintering temperature of the composites. The XRD analysis validates the coexistence of hexagonal perovskite BNFSO and spinel NZCFO phases. The FESEM images illustrate an almost homogeneous amalgamation of the BNFSO and NZCFO grains. The real part of initial permeability and the relative quality factor increases with NZCFO contents in the composites. The maximum permeability is observed for the composite with 80 % ferrite content. The ferroelectric BNFSO exhibits antiferromagnetic behavior and with the increase in NZCFO the saturation magnetization increases significantly. The dielectric constant confirms typical dielectric dispersion at low frequencies because of Maxwell-Wagner space charge polarization. The P-E hysteresis measurement reveals that the composite with 40 % ferrite content exhibits the highest loop area and hence a large energy storage capacity. Incorporating BNFSO and NZCFO into the composite boosts the multiferroic properties, which might be a suitable alternative to single-phase multiferroics.
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Pediococcus acidilactici is a potential probiotic bacteria isolated from diverse sources. However, strains isolated from milk, especially from raw milk of healthy cows, have not been thoroughly studied. Here, we report the draft genome sequence of P. acidilactici strains MBBL5 and MBBL7, isolated from milk samples of healthy cows.
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INTRODUCTION: Hypertension is a widespread and life-threatening condition globally, with its prevalence increasing rapidly, particularly among adults. This study aims to examine the trend in adult hypertension prevalence and associated risk factors in both urban and rural areas of Bangladesh from 2011 to 2018. METHODS: Nationally representative cross-sectional data from the Bangladesh Demographic and Health Survey was used at two time points, 2011 and 2018. In our study, we used a two-step approach for variable selection, combining traditional statistical methods ( χ 2 test) with a machine learning algorithm (Boruta algorithm).. This study also employed two different multivariate binary logistic regression models to identify the risk factors that are most closely connected to the presence of hypertension (respectively for urban and rural locations). RESULTS: According to the study, hypertension has been on the rise in Bangladesh. In 2011, over a third of adults (38.7%) in urban Bangladesh had hypertension, a number that rose by 22.6% in 2017-18. Though rural areas had a lower hypertension prevalence in 2011 (36%), it surged to 64% in 2017-18, surpassing the rate in urban areas. The results of the multivariate analysis showed that age, gender, education, wealth status, area, and survey year had a significant influence on the determinants of hypertension status in connection to place of residence. According to the odds ratio, the prevalence was significantly higher among older respondents, female respondents, wealthy families and higher-educated respondents. CONCLUSION: A large proportion of Bangladesh's adult population suffers from hypertension. A health education program is required to develop appropriate strategies, including appropriate weight control, appropriate physical activity, and healthier eating habits. Health authorities should take initiatives to spread awareness among people, particularly at an older age.
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We sequenced the genomes of Pediococcus pentosaceus strains MBBL4 and MBBL6, isolated from raw milk samples of healthy cows. The draft genomes of the MBBL4 and MBBL6 were 1,896,831 bp and 1,849,397 bp, respectively, and were fragmented into 58 and 42 contigs, with coverages of 118.2× and 128.7×, respectively.
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Oxygen homeostasis is maintained in plants and animals by O2-sensing enzymes initiating adaptive responses to low O2 (hypoxia). Recently, the O2-sensitive enzyme ADO was shown to initiate degradation of target proteins RGS4/5 and IL32 via the Cysteine/Arginine N-degron pathway. ADO functions by catalysing oxidation of N-terminal cysteine residues, but despite multiple proteins in the human proteome having an N-terminal cysteine, other endogenous ADO substrates have not yet been identified. This could be because alternative modifications of N-terminal cysteine residues, including acetylation, prevent ADO-catalysed oxidation. Here we investigate the relationship between ADO-catalysed oxidation and NatA-catalysed acetylation of a broad range of protein sequences with N-terminal cysteines. We present evidence that human NatA catalyses N-terminal cysteine acetylation in vitro and in vivo. We then show that sequences downstream of the N-terminal cysteine dictate whether this residue is oxidised or acetylated, with ADO preferring basic and aromatic amino acids and NatA preferring acidic or polar residues. In vitro, the two modifications appear to be mutually exclusive, suggesting that distinct pools of N-terminal cysteine proteins may be acetylated or oxidised. These results reveal the sequence determinants that contribute to N-terminal cysteine protein modifications, with implications for O2-dependent protein stability and the hypoxic response.
Asunto(s)
Cisteína , Oxidación-Reducción , Estabilidad Proteica , Cisteína/metabolismo , Cisteína/química , Acetilación , Humanos , Oxígeno/metabolismo , Oxígeno/química , Procesamiento Proteico-Postraduccional , Secuencia de Aminoácidos , Células HEK293RESUMEN
Frequent vaccine failure leading to recurrent outbreaks of Foot-and-Mouth Disease (FMD) in livestock populations necessitates the development of a customizable vaccine platform comprising potential antigenic determinants of circulating lineages of FMD viruses. Artificially designed, chimaeric protein-based recombinant vaccines are novel approaches to combat the phylogenetically diverse FMD Virus (FMDV) strains. Among seven recognized serotypes, only serotypes O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages of FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant proteins, procuring immunogenicity against circulating diverse genotypes of FMDV serotypes O and A. Two chimaeric proteins, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guinea pigs with a considerable antigen load of B1 and B3 followed by serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimaeric proteins strongly indicate their credibility as novel vaccine candidates for existing serotypes O and A of FMDV in Bangladesh and surrounding territories.