Reducing acetylated tau is neuroprotective in brain injury.

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.

Regulation of MicroRNA Machinery and Development by Interspecies S-Nitrosylation.

Bioactive molecules can pass between microbiota and host to influence host cellular functions. However, general principles of interspecies communication have not been discovered. We show here in C. elegans that nitric oxide derived from resident bacteria promotes widespread S-nitrosylation of the host proteome. We further show that microbiota-dependent S-nitrosylation of C. elegans Argonaute protein (ALG-1)-at a site conserved and S-nitrosylated in mammalian Argonaute 2 (AGO2)-alters its function in controlling gene expression via microRNAs. By selectively eliminating nitric oxide generation by the microbiota or S-nitrosylation in ALG-1, we reveal unforeseen effects on host development. Thus, the microbiota can shape the post-translational landscape of the host proteome to regulate microRNA activity, gene expression, and host development. Our findings suggest a general mechanism by which the microbiota may control host cellular functions, as well as a new role for gasotransmitters.

S-Nitrosylation of ß-Arrestins Biases Receptor Signaling and Confers Ligand Independence.

Most G protein-coupled receptors (GPCRs) signal through both heterotrimeric G proteins and ß-arrestins (ßarr1 and ßarr2). Although synthetic ligands can elicit biased signaling by G protein- vis-à-vis ßarr-mediated transduction, endogenous mechanisms for biasing signaling remain elusive. Here we report that S-nitrosylation of a novel site within ßarr1/2 provides a general mechanism to bias ligand-induced signaling through GPCRs by selectively inhibiting ßarr-mediated transduction. Concomitantly, S-nitrosylation endows cytosolic ßarrs with receptor-independent function. Enhanced ßarr S-nitrosylation characterizes inflammation and aging as well as human and murine heart failure. In genetically engineered mice lacking ßarr2-Cys253 S-nitrosylation, heart failure is exacerbated in association with greatly compromised ß-adrenergic chronotropy and inotropy, reflecting ßarr-biased transduction and ß-adrenergic receptor downregulation. Thus, S-nitrosylation regulates ßarr function and, thereby, biases transduction through GPCRs, demonstrating a novel role for nitric oxide in cellular signaling with potentially broad implications for patho/physiological GPCR function, including a previously unrecognized role in heart failure.

Genome-wide mapping of DNase I hypersensitive sites revealed differential chromatin accessibility and regulatory DNA elements under drought stress in rice cultivars.

Drought stress (DS) is one of the major constraints limiting yield in crop plants including rice. Gene regulation under DS is largely governed by accessibility of the transcription factors (TFs) to their cognate cis-regulatory elements (CREs). In this study, we used DNase I hypersensitive assays followed by sequencing to identify the accessible chromatin regions under DS in a drought-sensitive (IR64) and a drought-tolerant (N22) rice cultivar. Our results indicated that DNase I hypersensitive sites (DHSs) were highly enriched at transcription start sites (TSSs) and numerous DHSs were detected in the promoter regions. DHSs were concurrent with epigenetic marks and the genes harboring DHSs in their TSS and promoter regions were highly expressed. In addition, DS induced changes in DHSs (∆DHSs) in TSS and promoter regions were positively correlated with upregulation of several genes involved in drought/abiotic stress response, those encoding TFs and located within drought-associated quantitative trait loci, much preferentially in the drought-tolerant cultivar. The CREs representing the binding sites of TFs involved in DS response were detected within the ∆DHSs, suggesting differential accessibility of TFs to their cognate sites under DS in different rice cultivars, which may be further deployed for enhancing drought tolerance in rice.

Species-specific function of conserved regulators in orchestrating rice root architecture.

Shoot-borne adventitious/crown roots form a highly derived fibrous root system in grasses. The molecular mechanisms controlling their development remain largely unknown. Here, we provide a genome-wide landscape of transcriptional signatures - tightly regulated auxin response and in-depth spatio-temporal expression patterns of potential epigenetic modifiers - and transcription factors during priming and outgrowth of rice (Oryza sativa) crown root primordia. Functional analyses of rice transcription factors from WUSCHEL-RELATED HOMEOBOX and PLETHORA gene families reveal their non-redundant and species-specific roles in determining the root architecture. WOX10 and PLT1 regulate both shoot-borne crown roots and root-borne lateral roots, but PLT2 specifically controls lateral root development. PLT1 activates local auxin biosynthesis genes to promote crown root development. Interestingly, O. sativa PLT genes rescue lateral root primordia outgrowth defects of Arabidopsis plt mutants, demonstrating their conserved role in root primordia outgrowth irrespective of their developmental origin. Together, our findings unveil a molecular framework of tissue transdifferentiation during root primordia establishment, leading to the culmination of robust fibrous root architecture. This also suggests that conserved factors have evolved their transcription regulation to acquire species-specific function.

Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6Clow Monocytes while Preserving Macrophage Gene Function.

Mononuclear phagocytes are a heterogeneous family that occupy all tissues and assume numerous roles to support tissue function and systemic homeostasis. Our ability to dissect the roles of individual subsets is limited by a lack of technologies that ablate gene function within specific mononuclear phagocyte sub-populations. Using Nr4a1-dependent Ly6Clow monocytes, we present a proof-of-principle approach that addresses these limitations. Combining ChIP-seq and molecular approaches we identified a single, conserved, sub-domain within the Nr4a1 enhancer that was essential for Ly6Clow monocyte development. Mice lacking this enhancer lacked Ly6Clow monocytes but retained Nr4a1 gene expression in macrophages during steady state and in response to LPS. Because Nr4a1 regulates inflammatory gene expression and differentiation of Ly6Clow monocytes, decoupling these processes allows Ly6Clow monocytes to be studied independently.

Transcription factors KLF15 and PPARδ cooperatively orchestrate genome-wide regulation of lipid metabolism in skeletal muscle.

Skeletal muscle dynamically regulates systemic nutrient homeostasis through transcriptional adaptations to physiological cues. In response to changes in the metabolic environment (e.g., alterations in circulating glucose or lipid levels), networks of transcription factors and coregulators are recruited to specific genomic loci to fine-tune homeostatic gene regulation. Elucidating these mechanisms is of particular interest as these gene regulatory pathways can serve as potential targets to treat metabolic disease. The zinc-finger transcription factor Krüppel-like factor 15 (KLF15) is a critical regulator of metabolic homeostasis; however, its genome-wide distribution in skeletal muscle has not been previously identified. Here, we characterize the KLF15 cistrome in vivo in skeletal muscle and find that the majority of KLF15 binding is localized to distal intergenic regions and associated with genes related to circadian rhythmicity and lipid metabolism. We also identify critical interdependence between KLF15 and the nuclear receptor PPARδ in the regulation of lipid metabolic gene programs. We further demonstrate that KLF15 and PPARδ colocalize genome-wide, physically interact, and are dependent on one another to exert their transcriptional effects on target genes. These findings reveal that skeletal muscle KLF15 plays a critical role in metabolic adaptation through its direct actions on target genes and interactions with other nodal transcription factors such as PPARδ.

Spatially activated conserved auxin-transcription factor regulatory module controls de novo root organogenesis in rice.

MAIN CONCLUSION: This study reveals that the process of crown root development and auxin-induced de novo root organogenesis during in vitro plantlet regeneration share a common auxin-OsWOX10 regulatory module in rice. In the fibrous-type root system of rice, the crown roots (CR) are developed naturally from the shoot tissues. Generation of robust auxin response, followed by activation of downstream cell fate determinants and signaling pathways at the onset of crown root primordia (CRP) establishment is essential for new root initiation. During rice tissue culture, embryonic calli are induced to regenerate shoots in vitro which undergo de novo root organogenesis on an exogenous auxin-supplemented medium, but the mechanism underlying spatially restricted root organogenesis remains unknown. Here, we reveal the dynamics of progressive activation of genes involved in auxin homeostasis and signaling during initiation and outgrowth of rice crown root primordia. By comparative global dataset analysis, we identify the crown root primordia-expressed genes whose expression is also regulated by auxin signaling. In-depth spatio-temporal expression pattern analysis shows that the exogenous application of auxin induces a set of key transcription factors exclusively in the spatially positioned CRP. Further, functional analysis of rice WUSCHEL-RELATED HOMEOBOX 10 (OsWOX10) during in vitro plantlet regeneration from embryogenic calli shows that it promotes de novo root organogenesis from regenerated shoots. Expression of rice OsWOX10 also induces adventitious roots (AR) in Arabidopsis, independent of homologous endogenous Arabidopsis genes. Together, our findings reveal that a common auxin-transcription factor regulatory module is involved in root organogenesis under different conditions.

Genome-wide discovery of genetic variations between rice cultivars with contrasting drought stress response and their potential functional relevance.

Drought stress is a serious threat to rice productivity. Investigating genetic variations between drought-tolerant (DT) and drought-sensitive (DS) rice cultivars may decipher the candidate genes/regulatory regions involved in drought stress tolerance/response. In this study, whole-genome resequencing data of four DS and five DT rice cultivars were analyzed. We identified a total of approximately 4.8 million single nucleotide polymorphisms (SNPs) and 0.54 million insertions/deletions (InDels). The genetic variations (162,638 SNPs and 17,217 InDels) differentiating DS and DT rice cultivars were found to be unevenly distributed throughout the rice genome; however, they were more frequent near the transcription start and stop sites than in the genic regions. The cis-regulatory motifs representing the binding sites of stress-related transcription factors (MYB, HB, bZIP, ERF, ARR, and AREB) harboring the SNPs/InDels in the promoter regions of a few differentially expressed genes (DEGs) were identified. Importantly, many of these DEGs were located within the drought-associated quantitative trait loci. Overall, this study provides a valuable large-scale genotyping resource and facilitates the discovery of candidate genes associated with drought stress tolerance in rice.

P7C3-A20 treatment one year after TBI in mice repairs the blood-brain barrier, arrests chronic neurodegeneration, and restores cognition.

Chronic neurodegeneration in survivors of traumatic brain injury (TBI) is a major cause of morbidity, with no effective therapies to mitigate this progressive and debilitating form of nerve cell death. Here, we report that pharmacologic restoration of the blood-brain barrier (BBB), 12 mo after murine TBI, is associated with arrested axonal neurodegeneration and cognitive recovery, benefits that persisted for months after treatment cessation. Recovery was achieved by 30 d of once-daily administration of P7C3-A20, a compound that stabilizes cellular energy levels. Four months after P7C3-A20, electron microscopy revealed full repair of TBI-induced breaks in cortical and hippocampal BBB endothelium. Immunohistochemical staining identified additional benefits of P7C3-A20, including restoration of normal BBB endothelium length, increased brain capillary pericyte density, increased expression of BBB tight junction proteins, reduced brain infiltration of immunoglobulin, and attenuated neuroinflammation. These changes were accompanied by cessation of TBI-induced chronic axonal degeneration. Specificity for P7C3-A20 action on the endothelium was confirmed by protection of cultured human brain microvascular endothelial cells from hydrogen peroxide-induced cell death, as well as preservation of BBB integrity in mice after exposure to toxic levels of lipopolysaccharide. P7C3-A20 also protected mice from BBB degradation after acute TBI. Collectively, our results provide insights into the pathophysiologic mechanisms behind chronic neurodegeneration after TBI, along with a putative treatment strategy. Because TBI increases the risks of other forms of neurodegeneration involving BBB deterioration (e.g., Alzheimer's disease, Parkinson's disease, vascular dementia, chronic traumatic encephalopathy), P7C3-A20 may have widespread clinical utility in the setting of neurodegenerative conditions.

Draft genome sequence of Indian mulberry (Morus indica) provides a resource for functional and translational genomics.

Mulberry is an important crop plant for the sericulture industry. Here, we report high-quality genome sequence of a cultivated Indian mulberry (Morus indica cv K2) obtained by combining data from four different technologies, including Illumina, single-molecule real-time sequencing, chromosome conformation capture and optical mapping, with a gene completeness of 96.5%. Based on the genome sequence, we identified 49.2% of repetitive DNA and 27,435 high-confidence protein-coding genes with >90% of them supported by transcript evidence. A comparative analysis with other plant genomes identified 4.8% of species-specific genes in the M. indica genome. Transcriptome profiling revealed tissue-specific and differential expression across multiple accessions of ~4.7% and 2-5% of protein-coding genes, respectively, implicated in diverse biological processes. Whole genome resequencing of 21 accessions/species revealed ~2.5 million single nucleotide polymorphisms and ~ 0.2 million insertions/deletions. These data and results provide a comprehensive resource to accelerate the genomics research in mulberry for its improvement.

Pokkali: A Naturally Evolved Salt-Tolerant Rice Shows a Distinguished Set of lncRNAs Possibly Contributing to the Tolerant Phenotype.

Pokkali is a strong representation of how stress-tolerant genotypes have evolved due to natural selection pressure. Numerous omics-based investigations have indicated different categories of stress-related genes and proteins, possibly contributing to salinity tolerance in this wild rice. However, a comprehensive study towards understanding the role of long-noncoding RNAs (lncRNAs) in the salinity response of Pokkali has not been done to date. We have identified salt-responsive lncRNAs from contrasting rice genotypes IR64 and Pokkali. A total of 63 and 81 salinity-responsive lncRNAs were differentially expressed in IR64 and Pokkali, respectively. Molecular characterization of lncRNAs and lncRNA-miRNA-mRNA interaction networks helps to explore the role of lncRNAs in the stress response. Functional annotation revealed that identified lncRNAs modulate various cellular processes, including transcriptional regulation, ion homeostasis, and secondary metabolite production. Additionally, lncRNAs were predicted to bind stress-responsive transcription factors, namely ERF, DOF, and WRKY. In addition to salinity, expression profiling was also performed under other abiotic stresses and phytohormone treatments. A positive modulation in TCONS_00035411, TCONS_00059828, and TCONS_00096512 under both abiotic stress and phytohormone treatments could be considered as being of potential interest for the further functional characterization of IncRNA. Thus, extensive analysis of lncRNAs under various treatments helps to delineate stress tolerance mechanisms and possible cross-talk.

Natural-Product-Inspired Microwave-Assisted Synthesis of Novel Spirooxindoles as Antileishmanial Agents: Synthesis, Stereochemical Assignment, Bioevaluation, SAR, and Molecular Docking Studies.

Leishmaniasis is a neglected tropical disease, and there is an emerging need for the development of effective drugs to treat it. To identify novel compounds with antileishmanial properties, a novel series of functionalized spiro[indoline-3,2'-pyrrolidin]-2-one/spiro[indoline-3,3'-pyrrolizin]-2-one 23a-f, 24a-f, and 25a-g were prepared from natural-product-inspired pharmaceutically privileged bioactive sub-structures, i.e., isatins 20a-h, various substituted chalcones 21a-f, and 22a-c amino acids, via 1,3-dipolar cycloaddition reactions in MeOH at 80 °C using a microwave-assisted approach. Compared to traditional methods, microwave-assisted synthesis produces higher yields and better quality, and it takes less time. We report here the in vitro antileishmanial activity against Leishmania donovani and SAR studies. The analogues 24a, 24e, 24f, and 25d were found to be the most active compounds of the series and showed IC50 values of 2.43 µM, 0.96 µM, 1.62 µM, and 3.55 µM, respectively, compared to the standard reference drug Amphotericin B (IC50 = 0.060 µM). All compounds were assessed for Leishmania DNA topoisomerase type IB inhibition activity using the standard drug Camptothecin, and 24a, 24e, 24f, and 25d showed potential results. In order to further validate the experimental results and gain a deeper understanding of the binding manner of such compounds, molecular docking studies were also performed. The stereochemistry of the novel functionalized spirooxindole derivatives was confirmed by single-crystal X-ray crystallography studies.

'Candidatus Liberibacter asiaticus'-Encoded BCP Peroxiredoxin Suppresses Lipopolysaccharide-Mediated Defense Signaling and Nitrosative Stress In Planta.

The lipopolysaccharides (LPS) of gram-negative bacteria trigger a nitrosative and oxidative burst in both animals and plants during pathogen invasion. Liberibacter crescens strain BT-1 is a surrogate for functional genomic studies of the uncultured pathogenic 'Candidatus Liberibacter' spp. that are associated with severe diseases such as citrus greening and potato zebra chip. Structural determination of L. crescens LPS revealed the presence of a very long chain fatty acid modification. L. crescens LPS pretreatment suppressed growth of Xanthomonas perforans on nonhost tobacco (Nicotiana benthamiana) and X. citri subsp. citri on host orange (Citrus sinensis), confirming bioactivity of L. crescens LPS in activation of systemic acquired resistance (SAR). L. crescens LPS elicited a rapid burst of nitric oxide (NO) in suspension cultured tobacco cells. Pharmacological inhibitor assays confirmed that arginine-utilizing NO synthase (NOS) activity was the primary source of NO generation elicited by L. crescens LPS. LPS treatment also resulted in biological markers of NO-mediated SAR activation, including an increase in the glutathione pool, callose deposition, and activation of the salicylic acid and azelaic acid (AzA) signaling networks. Transient expression of 'Ca. L. asiaticus' bacterioferritin comigratory protein (BCP) peroxiredoxin in tobacco compromised AzA signaling, a prerequisite for LPS-triggered SAR. Western blot analyses revealed that 'Ca. L. asiaticus' BCP peroxiredoxin prevented peroxynitrite-mediated tyrosine nitration in tobacco. 'Ca. L. asiaticus' BCP peroxiredoxin (i) attenuates NO-mediated SAR signaling and (ii) scavenges peroxynitrite radicals, which would facilitate repetitive cycles of 'Ca. L. asiaticus' acquisition and transmission by fecund psyllids throughout the limited flush period in citrus.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Genomic landscape of prominent XDR Acinetobacter clonal complexes from Dhaka, Bangladesh.

BACKGROUND: Acinetobacter calcoaceticus-A. baumannii (ACB) complex pathogens are known for their prevalence in nosocomial infections and extensive antimicrobial resistance (AMR) capabilities. While genomic studies worldwide have elucidated the genetic context of antibiotic resistance in major international clones (ICs) of clinical Acinetobacter spp., not much information is available from Bangladesh. In this study, we analysed the AMR profiles of 63 ACB complex strains collected from Dhaka, Bangladesh. Following this, we generated draft genomes of 15 of these strains to understand the prevalence and genomic environments of AMR, virulence and mobilization associated genes in different Acinetobacter clones. RESULTS: Around 84% (n = 53) of the strains were extensively drug resistant (XDR) with two showing pan-drug resistance. Draft genomes generated for 15 strains confirmed 14 to be A. baumannii while one was A. nosocomialis. Most A. baumannii genomes fell under three clonal complexes (CCs): the globally dominant CC1 and CC2, and CC10; one strain had a novel sequence type (ST). AMR phenotype-genotype agreement was observed and the genomes contained various beta-lactamase genes including blaOXA-23 (n = 12), blaOXA-66 (n = 6), and blaNDM-1 (n = 3). All genomes displayed roughly similar virulomes, however some virulence genes such as the Acinetobactin bauA and the type IV pilus gene pilA displayed high genetic variability. CC2 strains carried highest levels of plasmidic gene content and possessed conjugative elements carrying AMR genes, virulence factors and insertion sequences. CONCLUSION: This study presents the first comparative genomic analysis of XDR clinical Acinetobacter spp. from Bangladesh. It highlights the prevalence of different classes of beta-lactamases, mobilome-derived heterogeneity in genetic architecture and virulence gene variability in prominent Acinetobacter clonal complexes in the country. The findings of this study would be valuable in understanding the genomic epidemiology of A. baumannii clones and their association with closely related pathogenic species like A. nosocomialis in Bangladesh.

Genome-wide analysis suggests the potential role of lncRNAs during seed development and seed size/weight determination in chickpea.

MAIN CONCLUSION: The integrated transcriptome data analyses suggested the plausible roles of lncRNAs during seed development in chickpea. The candidate lncRNAs associated with QTLs and those involved in miRNA-mediated seed size/weight determination in chickpea have been identified. Long non-coding RNAs (lncRNAs) are important regulators of various biological processes. Here, we identified lncRNAs at seven successive stages of seed development in small-seeded and large-seeded chickpea cultivars. In total, 4751 lncRNAs implicated in diverse biological processes were identified. Most of lncRNAs were conserved between the two cultivars, whereas only a few of them were conserved in other plants, suggesting their species-specificity. A large number of lncRNAs differentially expressed between the two chickpea cultivars associated with seed development-related processes were identified. The lncRNAs acting as precursors of miRNAs and those mimicking target protein-coding genes of miRNAs involved in seed size/weight determination, including HAIKU1, BIG SEEDS1, and SHB1, were also revealed. Further, lncRNAs located within seed size/weight associated quantitative trait loci were also detected. Overall, we present a comprehensive resource and identified candidate lncRNAs that may play important roles during seed development and seed size/weight determination in chickpea.

Recent advancements in CRISPR-Cas toolbox for imaging applications.

The imaging of chromatin, genomic loci, RNAs, and proteins is very important to study their localization, interaction, and coordinated regulation. Recently, several clustered regularly interspaced short palindromic repeats (CRISPR) based imaging methods have been established. The refurbished tool kits utilizing deactivated Cas9 (dCas9) and dCas13 have been established to develop applications of CRISPR-Cas technology beyond genome editing. Here, we review recent advancements in CRISPR-based methods that enable efficient imaging and visualization of chromatin, genomic loci, RNAs, and proteins. RNA aptamers, Pumilio, SuperNova tagging system, molecular beacons, halotag, bimolecular fluorescence complementation, RNA-guided endonuclease in situ labeling, and oligonucleotide-based imaging methods utilizing fluorescent proteins, organic dyes, or quantum dots have been developed to achieve improved fluorescence and signal-to-noise ratio for the imaging of chromatin or genomic loci. RNA-guided RNA targeting CRISPR systems (CRISPR/dCas13) and gene knock-in strategies based on CRISPR/Cas9 mediated site-specific cleavage and DNA repair mechanisms have been employed for efficient RNA and protein imaging, respectively. A few CRISPR-Cas-based methods to investigate the coordinated regulation of DNA-protein, DNA-RNA, or RNA-protein interactions for understanding chromatin dynamics, transcription, and protein function are also available. Overall, the CRISPR-based methods offer a significant improvement in elucidating chromatin organization and dynamics, RNA visualization, and protein imaging. The current and future advancements in CRISPR-based imaging techniques can revolutionize genome biology research for various applications.

Oxidant-Switched Palladium-Catalyzed Regioselective Mono- versus Bis-ortho-Aroylation of 1-Aryl-1H-indazoles with Aldehydes via C-H Bond Activation.

A highly efficient oxidant-switched palladium-catalyzed regioselective C(sp2)-H/C(sp2)-H cross-dehydrogenative coupling (CDC) for direct mono/bis-ortho-aroylation of substituted 1-phenyl-1H-indazoles 1a-j with various substituted aldehydes 3a-t via C(sp2)-H bond activation has been developed. In this study, Pd-catalyzed chelation-assisted mono- or bis-aroylation of substituted 1-phenyl-1H-indazoles depends on the type of oxidant being used for the CDC reaction. While mono-ortho-aroylation of substituted 1-phenyl-1H-indazole was obtained using dicumylperoxide (DCP) as the oxidant, the bis-ortho-aroylation product has been afforded by the use of tert-butyl hydroperoxide (TBHP). Regardless of the greater activity at the C-3 position of 1H-indazoles, the greater coordinating capacity of the N atom directed the aroylating group to the ortho position, leaving behind the nondirected metalation pathway. The Pd-catalyzed operationally simplified methodology proceeded in the presence of oxidants with either DCP or TBHP in dichloroethane as the solvent at 110 °C for 16 h, which generated a miscellaneous variety of monosubstituted o-benzoyl/acyl-1-aryl-1H-indazoles 4a-t/5a-i and bis-substituted o-benzoyl-1-aryl-1H-indazoles 6a-j in ≤88% yields. The probable mechanistic pathway involves a free radical chelation-assisted approach that could be accomplished by the addition of an in situ-generated oxidant-promoted benzoyl/acyl radical to the ortho position of 1-phenyl-1H-indazoles. A wide range of substrates, a high functional group tolerance, gram-scale synthesis, control/competitive experiments, and a variety of synthetic applications further exemplify the versatility of the developed methodology.

Genome-wide discovery of DNA polymorphisms via resequencing of chickpea cultivars with contrasting response to drought stress.

Drought stress limits plant growth, resulting in a significant yield loss in chickpea. The diversification in genome sequence and selective sweep of allele(s) in different genotypes of a crop plant may play an important role in the determination of agronomic traits, including drought stress response. We investigated, via whole genome resequencing, the DNA polymorphisms between two sets of chickpea genotypes with contrasting drought stress responses (3 drought-sensitive vs. 6 drought-tolerant). In total, 36,406 single nucleotide polymorphisms (SNPs) and 3407 insertions or deletions (InDels) differentiating drought-sensitive and drought-tolerant chickpea genotypes were identified. Interestingly, most (91%) of these DNA polymorphisms were located in chromosomes 1 and 4. The genes harboring DNA polymorphisms in their promoter and/or coding regions and exhibiting differential expression under control and/or drought stress conditions between/within the drought-sensitive and tolerant genotypes were found implicated in the stress response. Furthermore, we identified DNA polymorphisms within the cis-regulatory motifs in the promoter region of abiotic stress-related and QTL-associated genes, which might contribute to the differential expression of the candidate drought-responsive genes. In addition, we revealed the effect of nonsynonymous SNPs on mutational sensitivity and stability of the encoded proteins. Taken together, we identified DNA polymorphisms having relevance in drought stress response and revealed candidate genes to engineer drought tolerance in chickpea.

Nanoparticles as potential hallmarks of drought stress tolerance in plants.

Plants are inevitably exposed to drought stress limiting their growth and causing yield loss, thus inciting food crises across the world. Nanoparticles (NPs) are regarded as effective and promising tools for modulation of crop yield to overcome current and future constraints in sustainable agricultural production by upgrading the plant tolerance mechanism under abiotic stress conditions, including drought. NPs exhibit alleviating effects against drought stress via induction of physiological and biochemical readjustments accompanied by modulation of gene expression involved in drought response/tolerance. NPs ameliorate drought-induced reduction in carbon assimilation via increasing the photosynthetic activity. The improved root growth, upregulation of aquaporins, modification of intracellular water metabolism, accumulation of compatible solutes and ion homeostasis are the major mechanisms used by NPs to mitigate the osmotic stress caused by water deficit. NPs reduce water loss from leaves through stomatal closure due to fostered abscisic acid (ABA) accumulation and ameliorate oxidative stress damage by reducing reactive oxygen species and activating the antioxidant defense system. This review provides an evolutionary foundation regarding drought stress in plant life and summarizes the interactions between NPs and plants under drought. The subsequent impact of NPs on plant development and productivity and recent nanobiotechnological approaches to improve drought stress resilience are presented. On the whole, this review highlights the significance of NPs in dealing with the global problem of water scarcity faced by farmers.