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BACKGROUND: Rice bean (Vigna umbellata), an underrated legume, adapts to diverse climatic conditions with the potential to support food and nutritional security worldwide. It is used as a vegetable, minor food crop and a fodder crop, being a rich source of proteins, minerals, and essential fatty acids. However, little effort has been made to decipher the genetic and molecular basis of various useful traits in this crop. Therefore, we considered three economically important traits i.e., flowering, maturity and seed weight of rice bean and identified the associated candidate genes employing an associative transcriptomics approach on 100 diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank. RESULTS: The transcriptomics-based genotyping of one-hundred diverse rice bean cultivars followed by pre-processing of genotypic data resulted in 49,271 filtered markers. The STRUCTURE, PCA and Neighbor-Joining clustering of 100 genotypes revealed three putative sub-populations. The marker-trait association analysis involving various genome-wide association study (GWAS) models revealed significant association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The transcript annotation provided information on the putative candidate genes for the considered traits. The candidate genes identified for flowering include HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A. Further, the WRKY1 and DEAD-box-RH27 were found to be associated with seed weight. Furthermore, the associations of PIF3 and pentatricopeptide-repeat-containing-gene with maturity and seed weight, and aldo-keto-reductase with flowering and maturity were revealed. CONCLUSION: This study offers insights into the genetic basis of key agronomic traits in rice bean, including flowering, maturity, and seed weight. The identified markers and associated candidate genes provide valuable resources for future exploration and targeted breeding, aiming to enhance the agronomic performance of rice bean cultivars. Notably, this research represents the first transcriptome-wide association study in pulse crop, uncovering the candidate genes for agronomically useful traits.
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Flores , Estudo de Associação Genômica Ampla , Sementes , Transcriptoma , Sementes/genética , Sementes/crescimento & desenvolvimento , Flores/genética , Flores/crescimento & desenvolvimento , Vigna/genética , Vigna/crescimento & desenvolvimento , Genes de Plantas , Genótipo , Perfilação da Expressão Gênica , Mapeamento Cromossômico , Locos de Características Quantitativas/genética , FenótipoRESUMO
Lateral roots are a major component of root system architecture, and lateral root count (LRC) positively contributes to yield under drought in chickpea. To understand the genetic regulation of LRC, a biparental mapping population derived from two chickpea accessions having contrasting LRCs was genotyped by sequencing, and phenotyped to map four major quantitative trait loci (QTLs) contributing to 13-32% of the LRC trait variation. A single- nucleotide polymorphism tightly linked to the locus contributing to highest trait variation was located on the coding region of a gene (CaWIP2), orthologous to NO TRANSMITTING TRACT/WIP domain protein 2 (NTT/WIP2) gene of Arabidopsis thaliana. A polymorphic simple sequence repeat (SSR) in the CaWIP2 promoter showed differentiation between low versus high LRC parents and mapping individuals, suggesting its utility for marker-assisted selection. CaWIP2 promoter showed strong expression in chickpea apical root meristem and lateral root primordia. Expression of CaWIP2 under its native promoter in the Arabidopsis wip2wip4wip5 mutant rescued its rootless phenotype to produce more lateral roots than the wild-type plants, and led to formation of amyloplasts in the columella. CaWIP2 expression also induced the expression of genes that regulate lateral root emergence. Our study identified a gene-based marker for LRC which will be useful for developing drought-tolerant, high-yielding chickpea varieties.
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Cicer , Locos de Características Quantitativas , Humanos , Locos de Características Quantitativas/genética , Mapeamento Cromossômico , Cicer/genética , Genótipo , Marcadores GenéticosRESUMO
India's mango productivity is hindered by many factors but more importantly due to limited understanding of the genomic complexities behind regular bearing habit. This study is the first to quantify carbohydrate fractions, protein content, and macro and micronutrient storage pools, their transportation, and contributions to regular 'Totapuri' and alternate bearer 'Bombay Green' mango varieties during the 'off' year. Deep RNA sequencing was used to assess gene expression dynamics between buds and flowers of these varieties. Differential pathway analysis showed the greatest number of differentially expressed genes in metabolic processes (1377), followed by oxido-reductase (879), hormone (80), oxidative stress (77), starvation (39), alternate bearing (8), flowering (3), meristem (3), and cellular component (2) pathways. In silico analysis showed that among 15 genes, twelve genes up-regulated in Totapuri and three in Bombay Green, confirmed by qRT-PCR. Additionally, 202 SNPs were identified in 32 alternate bearing-related genes. The study confirmed the reproductive bud's strong ability to import sugars, protein, and starch in the regular bearer variety, enhancing flowering and fruiting during off years. The mineral nutrients and biochemical constituent of the bud and leaf tissue in contrasting genotypes, showed the potential role for regular bearing in mango.
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KEY MESSAGE: In current study candidate gene (261 genes) based association mapping on 144 pigeonpea accessions for flowering time and related traits and 29 MTAs producing eight superior haplotypes were identified. In the current study, we have conducted an association analysis for flowering-associated traits in a diverse pigeonpea mini-core collection comprising 144 accessions using the SNP data of 261 flowering-related genes. In total, 13,449 SNPs were detected in the current study, which ranged from 743 (ICP10228) to 1469 (ICP6668) among the individuals. The nucleotide diversity (0.28) and Watterson estimates (0.34) reflected substantial diversity, while Tajima's D (-0.70) indicated the abundance of rare alleles in the collection. A total of 29 marker trait associations (MTAs) were identified, among which 19 were unique to days to first flowering (DOF) and/or days to fifty percent flowering (DFF), 9 to plant height (PH), and 1 to determinate (Det) growth habit using 3 years of phenotypic data. Among these MTAs, six were common to DOF and/or DFF, and four were common to DOF/DFF along with the PH, reflecting their pleiotropic action. These 29 MTAs spanned 25 genes, among which 10 genes clustered in the protein-protein network analysis, indicating their concerted involvement in floral induction. Furthermore, we identified eight haplotypes, four of which regulate late flowering, while the remaining four regulate early flowering using the MTAs. Interestingly, haplotypes conferring late flowering (H001, H002, and H008) were found to be taller, while those involved in early flowering (H003) were shorter in height. The expression pattern of these genes, as inferred from the transcriptome data, also underpinned their involvement in floral induction. The haplotypes identified will be highly useful to the pigeonpea breeding community for haplotype-based breeding.
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Cajanus , Flores , Haplótipos , Polimorfismo de Nucleotídeo Único , Flores/genética , Flores/fisiologia , Flores/crescimento & desenvolvimento , Haplótipos/genética , Cajanus/genética , Cajanus/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único/genética , Genes de Plantas/genética , Fenótipo , Regulação da Expressão Gênica de Plantas , Estudos de Associação Genética , Locos de Características Quantitativas/genéticaRESUMO
BACKGROUND: Rhizoctonia solani is a polyphagous fungal pathogen that causes diseases in crops. The fungal strains are classified into anastomosis groups (AGs); however, genomic complexity, diversification into the AGs and the evolution of pathogenicity-associated genes remain poorly understood. RESULTS: We report a recent whole-genome duplication and sequential segmental duplications in AG1-IA strains of R. solani. Transposable element (TE) clusters have caused loss of synteny in the duplicated blocks and introduced differential structural alterations in the functional domains of several pathogenicity-associated paralogous gene pairs. We demonstrate that the TE-mediated structural variations in a glycosyl hydrolase domain and a GMC oxidoreductase domain in two paralogous pairs affect the pathogenicity of R. solani. Furthermore, to investigate the association of TEs with the natural selection and evolution of pathogenicity, we sequenced the genomes of forty-two rice field isolates of R. solani AG1-IA. The genomic regions with high population mutation rates and with the lowest nucleotide diversity are enriched with TEs. Genetic diversity analysis predicted the genes that are most likely under diversifying and purifying selections. We present evidence that a smaller variant of a glucosamine phosphate N-acetyltransferase (GNAT) protein, predicted to be under purifying selection, and an LPMP_AA9 domain-containing protein, predicted to be under diversifying selection, are important for the successful pathogenesis of R. solani in rice as well as tomato. CONCLUSIONS: Our study has unravelled whole-genome duplication, TE-mediated neofunctionalization of genes and evolution of pathogenicity traits in R. solani AG1-IA. The pathogenicity-associated genes identified during the study can serve as novel targets for disease control.
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Duplicação Gênica , Oryza , Virulência/genética , Rhizoctonia/genética , Genômica , Elementos de DNA TransponíveisRESUMO
BACKGROUND AND AIM: Continuing Medical Education (CME) is crucial for physicians to stay current in the rapidly advancing field of medicine. A WhatsApp (WA) based community of physicians was initiated in 2016 'WhatsApp CME India Group' to facilitate learning, knowledge sharing, and discussion among physicians. Due to participant size constraints of the technology, it evolved into seven distinct WA groups, overseen by a central administrator. A survey undertaken in the group's 7th year aimed to evaluate its effectiveness in achieving its goals, measure participant engagement, and uncover the primary factors driving its usage. METHODS: The survey questionnaire was distributed to 3500 members across the 07 WhatsApp CME groups for voluntary participation. Data collected was analysed using SPSS version 24.0 (SPSS Inc., Chicago, IL, USA) and reported using descriptive statistics. RESULTS: Among the 581 survey respondents, the study found 43% of physicians use the WhatsApp academic groups for CME content, with 32% accessing their group over four times daily. The primary motivation for 77% was to discuss challenging cases and to gain knowledge updates from fellow physician (70%). Medical websites (57%), referral books (49%), and Google (43%) were other significant resources. Every participant (100%) found the WhatsApp CME India group the most beneficial resource for daily medical science updates. A significant portion (57%) of the respondents found the group valuable for real-time information exchange. Over 78% stated it kept them current with knowledge and guidelines. Notably, 94% viewed WhatsApp CME as complementary to physical conferences, not a replacement. The post-conference/webinar summaries were appreciated by 81% participants. Case discussions (31%) and update posts from fellow physicians sharing their insights and learnings (24%) were noted as activities of great academic interest. CONCLUSION: This study underscores the potential of digital platforms like WhatsApp in supplementing CME in India and potentially other comparable settings. The blend of digital and traditional resources suggests a balanced learning approach. While real-time engagement is a strength, challenges like information overload and privacy concerns require careful management. Striking a balance is crucial for ensuring content quality, structured discussions and privacy. As the digital age advances, professionals must critically assess shared information on these platforms to guarantee evidence-based and reliable knowledge dissemination. TRIAL REGISTRATION: ARK 001.
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Educação Médica Continuada , Disseminação de Informação , Aplicativos Móveis , Mídias Sociais , Humanos , Educação Médica Continuada/métodos , Inquéritos e Questionários , Disseminação de Informação/métodos , Índia , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.
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Consenso , Humanos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Complicações do Diabetes , Administração Oral , ComorbidadeRESUMO
MOTIVATION: Tea is a cross-pollinated woody perennial plant, which is why, application of conventional breeding is limited for its genetic improvement. However, lack of the genome-wide high-density SNP markers and genome-wide haplotype information has greatly hampered the utilization of tea genetic resources toward fast-track tea breeding programs. To address this challenge, we have generated a first-generation haplotype map of tea (Tea HapMap-1). Out-crossing and highly heterozygous nature of tea plants, make them more complicated for DNA-level variant discovery. RESULTS: In this study, whole genome re-sequencing data of 369 tea genotypes were used to generate 2,334,564 biallelic SNPs and 1,447,985 InDels. Around 2928.04 million paired-end reads were used with an average mapping depth of â¼0.31× per accession. Identified polymorphic sites in this study will be useful in mapping the genomic regions responsible for important traits of tea. These resources lay the foundation for future research to understand the genetic diversity within tea germplasm and utilize genes that determine tea quality. This will further facilitate the understanding of tea genome evolution and tea metabolite pathways thus, offers an effective germplasm utilization for breeding the tea varieties. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Camellia sinensis , Camellia sinensis/genética , Haplótipos , Projeto HapMap , Melhoramento Vegetal , Chá , Genoma de PlantaRESUMO
Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process. GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 in colonic epithelium. Consequently, Niacr1(-/-) mice were susceptible to development of colonic inflammation and colon cancer. Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.
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Carcinogênese/imunologia , Colite/imunologia , Colo/imunologia , Neoplasias do Colo/prevenção & controle , Células Epiteliais/imunologia , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/metabolismo , Animais , Butiratos/imunologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Colite/complicações , Colite/tratamento farmacológico , Colo/microbiologia , Colo/patologia , Neoplasias do Colo/etiologia , Células Dendríticas/imunologia , Suscetibilidade a Doenças , Células Epiteliais/efeitos dos fármacos , Interleucina-10/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota , Niacina/administração & dosagem , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia , Receptores Nicotínicos/genética , Receptores Nicotínicos/imunologia , Transdução de Sinais/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Background and objective: The prevalence rate of hyperuricemia (HU) is comparatively higher in Asian countries than in the Western regions. Patients with coexisting HU and hypertension (HTN) are at greater risk of uncontrolled HTN, metabolic syndrome, and complications. This study aims to determine the prevalence of HU in individuals with HTN from the major geographical regions across India. Materials and methods: A cross-sectional, multicentric, observational study conducted in primary and secondary care centers from urban areas across different regions in India. Primary inclusion criteria were either a history of HTN or blood pressure systolic blood pressure (SBP) ≥140 and diastolic blood pressure (DBP) ≥ 90 mm Hg. A structured Google form was circulated among the participating healthcare practitioners from various participating centers to record the demographic, clinical, and biochemical parameters of patients visiting the respective centers. The data was consolidated and analyzed using Microsoft Excel. Screening for HU among individuals with HTN was based on two criteria-(1) self-reported diagnosed history of HU or (2) based on serum uric acid (SUA) levels >7 and > 6 mg/dL for men and women, respectively. The data were analyzed and represented using GraphPad Prism version 9. Results: Among the study population from 12 participating centers across different regions in India, 1,528 individuals had HTN. The mean age of the study participants was 57.4 ± 10.5 years with a male-to-female ratio of 1:1. The total prevalence rate of HU among individuals with HTN is 22.5% (N = 345). Gender-wise analysis indicated that 51.5% (177) of the males and 48.5% (168) of the females had HU. Among the patients with HTN and HU, 75% were overweight with a body mass index (BMI) of ≥25 kg/m2. The region-wise prevalence rate HU are North-17.4% (60), South-18% (62), Central-12.2% (42), East-29.6% (102), and West-22.9% (79). Conclusion: India's overall HU prevalence rate (22.5%) was comparable to that in other Asian countries (10-30%). However, the prevalence of HU among HTN patients varies between different regions of India (12.2-29.6%). Results from the participating centers located in an urban setting indicated that the eastern region had the highest HU prevalence (29.6%) and the Central region had the lowest HU prevalence rate (12.2%). The varying prevalence rate can be attributed to the diversity in geographical factors, genetic background or (family history of HU), sociocultural habits, and metabolic perturbations. Understanding this prevalence rate diversity can help strengthen the HU prevention measures to improve quality of life. How to cite this article: Patni B, Singh AN, Singh NK, et al. Prevalence of Hyperuricemia in Indian Population with Hypertension. J Assoc Physicians India 2023;71(10):45-48.
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Hipertensão , Hiperuricemia , Humanos , Hiperuricemia/epidemiologia , Índia/epidemiologia , Hipertensão/epidemiologia , Masculino , Prevalência , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Idoso , Ácido Úrico/sangueRESUMO
Water deficit is a crucial factor causing huge loss to rice productivity. The present study aimed to develop a multiple stress tolerant genotype by pyramiding drought tolerant yield QTLs qDTY1.1 and qDTY3.1 into high yielding rice variety Samba Mahsuri Sub-1(SMS) through marker assisted pyramiding. To achieve this six introgression lines of SMS carrying qDTY1.1 (SAB) were crossed with DRR-50, an Essentially Derived Variety of SMS carrying qDTY3.1. The SAB lines are taller than SMS due to tight linkage between qDTY1.1 and wild type SD-1. Therefore, F2 generation of crosses were screened for recombinants between SD-1 and qDTY1.1. Phenotyping of 1530 F2 plants representing three F2 populations from 35 F1 hybrids, identified 305 dwarf plants. Three dwarf F2 plants along with three others carrying qDTY1.1 and qDTY3.1 were forwarded to F3 generation. From the six F3 (SABD) lines fourteen pyramided progenies were selected and forward to F4 generation. The six SABD F3 lines SABD-7, SABD-8, SABD-9, SABD-76, SABD-79 and SABD-80 along with parents were evaluated under moisture stress (MS) for various physiological parameters. Chlorophyll and relative water content were more, while canopy temperature and malonaldehyde (MDA) content were lesser in SABD lines compared to parents indicating tolerance under MS. Variance due to genotypes was highly significant for all the yield related traits except test weight. Based on seed morphology, agronomic characters and physiological parameters six superior lines SABD-9-3, SABD-9-2, SABD-9-6, SABD-9-7, SABD-76-2 and SABD-76-6 performing better under MS were identified, which could be released after multi-location evaluation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01387-5.
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MAIN CONCLUSION: The high affinity nitrate transport system is a potential target for improving nitrogen use efficiency of bread wheat growing either under optimal or limiting nitrate concentration. Nitrate uptake is one of the most important traits to take into account to improve nitrogen use efficiency in wheat (Triticum aestivum L.). In this study, we aimed to gain an insight into the regulation of NO3- -uptake and translocation systems in two contrasting wheat genotypes [K9107(K9) vs. Choti Lerma (CL)]. Different conditions, such as NO3--uptake rates, soil-types, N-free solid external media, and external NO3- levels at the seedling stage, were considered. We also studied the contribution of homeolog expression of five genes encoding two nitrate transporters in the root tissue, along with their overall transcript expression levels relative to specific external nitrate availability. We observed that K9107 had a higher 15N influx than Choti Lerma under both limiting as well as optimum external N conditions in vermiculite-perlite (i.e., N-free solid) medium, with the improved translocation efficiency in Choti Lerma. However, in different soil types, different levels of 15N-enrichment in both the genotypes were found. Our results also demonstrated that the partitioning of dry matter in root and shoot was different under these growing conditions. Moreover, K9107 showed significantly higher relative expression of TaNRT2.1 at the lowest and TaNPF6.1 and TaNPF6.2 at the highest external nitrate concentrations. We also observed genotype-specific and nitrate starvation-dependent homeolog expression bias in all five nitrate transporter genes. Our data suggest that K9107 had a higher NO3- influx capacity, involving different nitrate transporters, than Choti Lerma at the seedling stage.
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Nitratos , Triticum , Pão , Genótipo , Transportadores de Nitrato , Nitratos/metabolismo , Nitrogênio/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Solo , Triticum/genética , Triticum/metabolismoRESUMO
BACKGROUND: Pigeonpea (Cajanus cajan L.) is a photoperiod-sensitive short-day plant. Understanding the flowering-related genes is critical to developing photoperiod insensitive cultivars. METHODS: The CCT family genes were identified using 'CCT DOMAIN PROTEIN' as a keyword and localized on the chromosomes using the BLAST search option available at the LIS database. The centromeric positions were identified through BLAST search using the centromeric repeat sequence of C. cajan as a query against the chromosome-wise FASTA files downloaded from the NCBI database. The CCT family genes were classified based on additional domains and/or CCT domains. The orthologous and phylogenetic relationships were inferred using the OrthoFinder and MEGA 10.1 software, respectively. The CCT family genes' expression level in photoperiod-sensitive and insensitive genotypes was compared using RNA-seq data and qRT-PCR analysis. RESULTS: We identified 33 CCT family genes in C. cajan distributed on ten chromosomes and nine genomic scaffolds. They were classified into CMF-type, COL-type, PRR-type, and GTCC- type. The CCT family genes of legumes exhibited an extensive orthologous relationship. Glycine max showed the maximum similarity of CCT family genes with C. cajan. The expression analysis of CCT family genes using photoperiod insensitive (ICP20338) and photoperiod sensitive (MAL3) genotypes of C. cajan demonstrated that CcCCT4 and CcCCT23 are the active CONSTANS in ICP20338. In contrast, only CcCCT23 is active in MAL3. CONCLUSION: The CCT family genes in C. cajan vary considerably in structure and domain types. They are maximally similar to soybean's CCT family genes. The differential photoperiod response of pigeonpea genotypes, ICP20338 and MAL3, is possibly due to the difference in the number and types of active CONSTANS in them.
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Cajanus/metabolismo , Perfilação da Expressão Gênica/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Cajanus/genética , Mapeamento Cromossômico , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genótipo , Família Multigênica , Fotoperíodo , Filogenia , Proteínas de Plantas/química , Domínios ProteicosRESUMO
Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-d-aspartate receptor) antagonist (R,S)-ketamine exerts rapid and sustained antidepressant effects after a single dose in patients with depression, but its use is associated with undesirable side effects. Here we show that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice. These antidepressant actions are independent of NMDAR inhibition but involve early and sustained activation of AMPARs (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors). We also establish that (2R,6R)-HNK lacks ketamine-related side effects. Our data implicate a novel mechanism underlying the antidepressant properties of (R,S)-ketamine and have relevance for the development of next-generation, rapid-acting antidepressants.
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Antidepressivos/metabolismo , Antidepressivos/farmacologia , Ketamina/análogos & derivados , Ketamina/metabolismo , Animais , Antidepressivos/efeitos adversos , Feminino , Ketamina/efeitos adversos , Ketamina/farmacologia , Masculino , Camundongos , Receptores de AMPA/agonistas , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Fatores de TempoRESUMO
BACKGROUND: Deficiency of Zn is a major soil constraint in rice plant growth and yield. Edaphic factors such as Zn deficiency in soil in relation to plant performance are still poorly understood. Here, we report promising quantitative trait loci (QTL) conferring tolerance to Zn deficiency, which were identified through biparental mapping. The experiment was conducted using the 236 F7 recombinant inbred line mapping population derived from the cross of Kinandang Patong (Zn deficiency sensitive) and A69-1 (Zn deficiency tolerant). RESULTS: A total of six QTLs (qLB-2B, qLB-4B, qPM-4B, qPM-6B, qRZC-4B, qSZC-4B) on chromosomes 2, 4 and 6 were identified for environment 1, whereas five QTLs (qLB-2 N, qLB-4 N, qPM-4 N, qRZC-4 N, qSZC-4 N) on chromosomes 2 and 4 were detected for environment 2. Among these, five major (51.30, 48.70, 28.60, 56.00, 52.00 > 10 R2 ) and one minor (5.40 < 10 R2 ) QTLs for environment 1 and four major (51.48, 50.20, 53.00, 48.00 > 10 R2 ) and one minor (4.44 < 10) QTLs for environment 2 for Zn deficiency tolerance with a logarithm of odd threshold value higher than 3 were identified. The QTLs (qLB-4B, qPM-4B, qRZC-4B, qSZC-4B, qLB-4 N, qPM-4 N, qRZC-4 N, qSZC-4 N) for leaf bronzing, plant mortality root zinc concentration and shoot zinc concentration identified on chromosome 4 were found to be the most promising and highly reproducible across the locations that explained phenotypic variation from 48.00% to 56.00% with the same marker interval RM6748-RM303. CONCLUSION: The new QTLs and its linked markers identified in the present study can be utilized for Zn deficiency tolerance in elite cultivars using marker-assisted backcrossing. © 2022 Society of Chemical Industry.
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Oryza , Locos de Características Quantitativas , Oryza/genética , Fenótipo , Solo , ZincoRESUMO
Crop productivity in rice is harshly limited due to high concentration of salt in the soil. To understand the intricacies of the mechanism it is important to unravel the key pathways operating inside the plant cell. Emerging state-of-the art technologies have provided the tools to discover the key components inside the plant cell for salt tolerance. Among the molecular entities, transcription factors and/or other important components of sensing and signaling cascades have been the attractive targets and the role of NHX and SOS1 transporters amply described. Not only marker assisted programs but also transgenic approaches by using reverse genetic strategies (knockout or knockdown) or overexpression have been extensively used to engineer rice crop. CRISPR/Cas is an attractive paradigm and provides the feasibility for manipulating several genes simultaneously. Here, in this review we highlight some of the molecular entities that could be potentially targeted for generating rice amenable to sustain growth under high salinity conditions by employing CRISPR/Cas. We also try to address key questions for rice salt stress tolerance other than what is already known.
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Sistemas CRISPR-Cas/genética , Edição de Genes , Oryza/genética , Estresse Salino/genéticaRESUMO
Periodontitis (PD) is a common dysbiotic inflammatory disease that leads to local bone deterioration and tooth loss. PD patients experience low-grade bacteremias with oral microbes implicated in the risk of heart disease, cancer, and kidney failure. Although Th17 effectors are vital to fighting infection, functional imbalance of Th17 effectors and regulatory T cells (Tregs) promote inflammatory diseases. In this study, we investigated, in a small pilot randomized clinical trial, whether expansion of inflammatory blood myeloid dendritic cells (DCs) and conversion of Tregs to Th17 cells could be modulated with antibiotics (AB) as part of initial therapy in PD patients. PD patients were randomly assigned to either 7 d of peroral metronidazole/amoxicillin AB treatment or no AB, along with standard care debridement and chlorhexidine mouthwash. 16s ribosomal RNA analysis of keystone pathogen Porphyromonas gingivalis and its consortium members Fusobacterium nucleatum and Streptococcus gordonii confirmed the presence of all three species in the reservoirs (subgingival pockets and blood DCs) of PD patients before treatment. Of the three species, P. gingivalis was reduced in both reservoirs 4-6 wk after therapy. Further, the frequency of CD1C+CCR6+ myeloid DCs and IL-1R1 expression on IL-17A+FOXP3+CD4+ T cells in PD patients were reduced to healthy control levels. The latter led to decreased IL-1ß-stimulated Treg plasticity in PD patients and improvement in clinical measures of PD. Overall, we identified an important, albeit short-term, beneficial role of AB therapy in reducing inflammatory DCs and Treg-Th17 plasticity in humans with PD.
Assuntos
Amoxicilina/administração & dosagem , Bactérias , Infecções Bacterianas , Células Dendríticas , Metronidazol/administração & dosagem , Periodontite , Linfócitos T Reguladores , Células Th17 , Bactérias/imunologia , Bactérias/metabolismo , Infecções Bacterianas/sangue , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/patologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/sangue , Periodontite/tratamento farmacológico , Periodontite/imunologia , Periodontite/patologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/parasitologia , Linfócitos T Reguladores/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologiaRESUMO
There has been a spurt in the spread of microbial resistance to antibiotics due to indiscriminate use of antimicrobial agents in human medicine, agriculture, and animal husbandry. It has been realized that conventional antibiotic therapy would be less effective in the coming decades and more emphasis should be given for the development of novel antiinfective therapies. Cysteine rich peptides (CRPs) are broad-spectrum antimicrobial agents that modulate the innate immune system of different life forms such as bacteria, protozoans, fungi, plants, insects, and animals. These are also expressed in several plant tissues in response to invasion by pathogens, and play a crucial role in the regulation of plant growth and development. The present work explores the importance of CRPs as potent antimicrobial agents, which can supplement and/or replace the conventional antibiotics. Different plant parts of diverse plant species showed the presence of antimicrobial peptides (AMPs), which had significant structural and functional diversity. The plant-derived AMPs exhibited potent activity toward a range of plant and animal pathogens, protozoans, insects, and even against cancer cells. The cysteine-rich AMPs have opened new avenues for the use of plants as biofactories for the production of antimicrobials and can be considered as promising antimicrobial drugs in biotherapeutics.
Assuntos
Anti-Infecciosos/farmacologia , Cisteína/química , Plantas/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Sequência de Aminoácidos , Animais , Bactérias/efeitos dos fármacos , Humanos , Proteínas Citotóxicas Formadoras de Poros/química , Estrutura Secundária de ProteínaRESUMO
The NCBI database has >15 chloroplast (cp) genome sequences available for different Camellia species but none for C. assamica. There is no report of any mitochondrial (mt) genome in the Camellia genus or Theaceae family. With the strong believes that these organelle genomes can play a great tool for taxonomic and phylogenetic analysis, we successfully assembled and analyzed cp and mt genome of C. assamica. We assembled the complete mt genome of C. assamica in a single circular contig of 707,441â¯bp length comprising of a total of 66 annotated genes, including 35 protein-coding genes, 29 tRNAs and two rRNAs. The first ever cp genome of C. assamica resulted in a circular contig of 157,353â¯bp length with a typical quadripartite structure. Phylogenetic analysis based on these organelle genomes showed that C. assamica was closely related to C. sinensis and C. leptophylla. It also supports Caryophyllales as Superasterids.
Assuntos
Camellia/genética , DNA de Cloroplastos/genética , DNA Mitocondrial/genética , Genoma de Cloroplastos , Genoma Mitocondrial , Filogenia , Proteínas de Cloroplastos/genética , Proteínas Mitocondriais/genética , RNA de Cloroplastos/genética , RNA Mitocondrial/genéticaRESUMO
Deeper Rooting 1 (DRO1) gene identified from a major QTL on chromosome 9 increases the root growth angle (RGA) and thus facilitates survival under drought and hence is an excellent candidate for rice improvement. Twenty-four major Indian upland and lowland genotypes including the 'yield under drought' (DTY) QTL donors were subjected to allele mining of DRO1 (3058 bp) using four pairs of overlapping primers. A total of 216 and 52 SNPs were identified across all genotypes in the gene and coding region (756 bp) respectively with transversions 3.6 fold more common than transitions in the gene and 2.5 times in the CDS. In 251 amino acid long protein, substitutions were found in 19 positions, wherein change in position 92 was the most frequent. Based on allele mining, the 24 genotypes can be classified into 16 primary structure variants ranging from complete functional allele (Satti, IR36 and DTY 3.1 donor, IR81896-B-B-195) to truncated non-functional alleles in PMK2, IR64, IR20 and Swarna. All the DTY donors, other than IR81896-B-B-195, and most of the upland drought tolerant cultivars (Nagina 22, Vandana and Dhagaddeshi) had accumulated 6-19 SNPs and 4-8 amino acid substitutions resulting in substantial differences in their protein structure. The expression analysis revealed that all the genotypes showed upregulation under drought stress though the degree of upregulation varied among genotypes. The information on structural variations in DRO1 gene will be very useful for the breeders, especially in the light of recent breeding programmes on improving drought tolerance using several DTY donors and upland accessions. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12298-021-00950-2).