PepAnalyzer: predicting peptide properties using its sequence.

Peptides are short linear molecules consisting of amino acids that play an essential role in most biological processes. They can treat diseases by working as a vaccine or antimicrobial agent and serves as a cancer molecule to deliver the drug to the target site for the treatment of cancer. They have the potential to solve the drawbacks of current medications and can be industrially produced in large quantities at low cost. However, poor chemical and physical stability, short circulating plasma half-life, and solubility are some issues that need solutions before they can be used as therapeutics. PepAnalyzer tool is a user-friendly tool that predicts 15 different properties such as binding potential, half-life, transmembrane patterns, test tube stability, charge, isoelectric point, molecular weights, and molar extinction coefficients only using the sequence. The tool is designed using BioPython utility and has even results with standard tools, such as Expasy, EBI, Genecorner, and Geneinfinity. The tool assists students, researchers, and the pharmaceutical sector. The PepAnalyzer tool's online platform is accessible at the link: http://www.iksmbrlabdu.in/peptool .

Dynamics of Zea mays transcriptome in response to a polyphagous herbivore, Spodoptera litura.

Zea mays defense response is well-crafted according to the physical and chemical weapons utilized by their invaders during the coevolutionary period. Maize plants employ diversified defense strategies and alter the spatiotemporal distribution of several classes of defensive compounds to affect insect herbivore performance. However, only little knowledge is available about the defense orchestration of maize in response to Spodoptera litura, a voracious Noctuidae pest. In order to decipher the defense status of Zea mays (African tall variety) against S. litura, a comparative feeding bioassay was executed, which revealed reduced performance of the herbivore on maize. In order to understand the molecular mechanism behind maize tolerance against S. litura, a microarray-based genome-wide expression analysis was performed. The comparative analysis displayed 792 differentially expressed genes (DEGs), wherein 357 genes were upregulated and 435 genes were downregulated at fold change ≥ 2 and p value ≤ 0.05. The upregulated genes were identified and categorized as defense-related, oxidative stress-related, transcription regulatory genes, protein synthesis genes, phytohormone-related, and primary and secondary metabolism-related. In contrast, downregulated genes were mainly associated with plant growth and development, indicating a balance of growth and defense response and utilization of a highly evolved C-diversion response were noticed. Maize plants showed better tolerance against herbivory and maintained its fitness using a combinatorial strategy. This peculiar response of Zea mays against S. litura offers an excellent possibility of managing polyphagous pests by spicing up the plant's defensive response with tolerance mechanism.

Silicon: its ameliorative effect on plant defense against herbivory.

Plants protect themselves against pest attack utilizing both direct and indirect modes of defense. The direct mode of defense includes morphological, biochemical, and molecular barriers that affect feeding, growth, and survival of herbivores whereas the indirect mode of defense includes release of a blend of volatiles that attract natural enemies of the pests. Both of these strategies adopted by plants are reinforced if the plants are supplied with one of the most abundant metalloids, silicon (Si). Plants absorb Si as silicic acid (Si(OH)4) and accumulate it as phytoliths, which strengthens their physical defense. This deposition of Si in plant tissue is up-regulated upon pest attack. Further, Si deposited in the apoplast, suppresses pest effector molecules. Additionally, Si up-regulates the expression of defense-related genes and proteins and their activity and enhances the accumulation of secondary metabolites, boosting induced molecular and biochemical defenses. Moreover, Si plays a crucial role in phytohormone-mediated direct and indirect defense mechanisms. It is also involved in the reduction of harmful effects of oxidative stress resulting from herbivory by accelerating the scavenging process. Despite increasing evidence of its multiple roles in defense against pests, the practical implications of Si for crop protection have received less attention. Here, we highlight recent developments in Si-mediated improved plant resistance against pests and its significance for future use in crop improvement.

Molecular Modeling of Chemosensory Protein 3 from Spodoptera litura and Its Binding Property with Plant Defensive Metabolites.

Chemosensory perception in insects involves a broad set of chemosensory proteins (CSPs) that identify the bouquet of chemical compounds present in the external environment and regulate specific behaviors. The current study is focused on the Spodoptera litura (Fabricius) chemosensory-related protein, SlitCSP3, a midgut-expressed CSP, which demonstrates differential gene expression upon different diet intake. There is an intriguing possibility that SlitCSP3 can perceive food-derived chemical signals and modulate insect feeding behavior. We predicted the three-dimensional structure of SlitCSP3 and subsequently performed an accelerated molecular dynamics (aMD) simulation of the best-modeled structure. SlitCSP3 structure has six α-helices arranged as a prism and a hydrophobic binding pocket predominated by leucine and isoleucine. We analyzed the interaction of selected host plant metabolites with the modeled structure of SlitCSP3. Out of two predicted binding pockets in SlitCSP3, the plant-derived defensive metabolites 2-b-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1, 4-benzoxazin-3-one (DIMBOA), 6-Methoxy-2-benzoxazolinone (MBOA), and nicotine were found to interact preferably to the hydrophobic site 1, compared to site 2. The current study provides the potential role of CSPs in recognizing food-derived chemical signals, host-plant specialization, and adaptation to the varied ecosystem. Our work opens new perspectives in designing novel pest-management strategies. It can be further used in the development of CSP-based advanced biosensors.

Comparative proteome analysis of Spodoptera litura-infested Zea mays reveals a robust defense strategy targeting insect peritrophic membrane.

Herbivorous insects such as Spodoptera litura, pose a constant threat to agricultural crops. The incompetence of contemporary pest management tools and techniques stipulates unravelling of molecular dogma, that drives pest-plant interaction. From our previous observations, we inferred that despite being a voracious polyphagous herbivore, S. litura growth and adaptability is severely hampered on maize foliage diet. In this investigation we explored further and demonstrated the impact of maize diet on the insect gut peritrophic membrane (PM, a crucial membrane involved in compartmentalizing digestive events and absorption of nutrients), its structural analysis using scanning electron microscopy (SEM) revealed damaged and perforated PM. Further, this study delves into the intricate resistance mechanism adapted by Z. mays against S. litura by conducting a comparative proteome analysis. We have detected 345 differentially abundant proteins (DAPs) at p < 0.05 and fold change ≥1. The DAPs were categorized as plant defense, secondary metabolite synthesis, redox homeostasis, cytoskeleton/cell wall biosynthesis, primary metabolism, transport and molecular processes. We remarkably report differential expression of proteolysis- and defense-related proteins that have potential to target insect gut, digestion and absorption of nutrients. Our findings contribute to a deeper understanding of the molecular dynamics governing maize resistance against S. litura. Understanding of such intricate molecular dialogues at these interfaces could provide valuable information on the arms race between plants and herbivores, it may pave the way for innovative pest management strategies.

Metabolic engineering for enhanced terpenoid production: Leveraging new horizons with an old technique.

Terpenoids are a vast class of plant specialized metabolites (PSMs) manufactured by plants and are involved in their interactions with environment. In addition, they add health benefits to human nutrition and are widely used as pharmaceutically active compounds. However, native plants produce a limited amount of terpenes restricting metabolite yield of terpene-related metabolites. Exponential growth in the plant metabolome data and the requirement of alternative approaches for producing the desired amount of terpenoids, has redirected plant biotechnology research to plant metabolic engineering, which requires in-depth knowledge and precise expertise about dynamic plant metabolic pathways and cellular physiology. Metabolic engineering is an assuring tool for enhancing the concentration of terpenes by adopting specific strategies such as overexpression of the key genes associated with the biosynthesis of targeted metabolites, controlling the modulation of transcription factors, downregulation of competitive pathways (RNAi), co-expression of the biosynthetic pathway genes in heterologous system and other combinatorial approaches. Microorganisms, fast-growing host plants (such as Nicotiana benthamiana), and cell suspension/callus cultures have provided better means for producing valuable terpenoids. Manipulation in the biosynthetic pathways responsible for synthesis of terpenoids can provide opportunities to enhance the content of desired terpenoids and open up new avenues to enhance their production. This review deliberates the worth of metabolic engineering in medicinal plants to resolve issues associated with terpenoid production at a commercial scale. However, to bring the revolution through metabolic engineering, further implementation of genome editing, elucidation of metabolic pathways using omics approaches, system biology approaches, and synthetic biology tactics are essentially needed.

Multi-omics therapeutic perspective on ACVR1 gene: from genetic alterations to potential targeting.

Activin A receptor type I (ACVR1), a transmembrane serine/threonine kinase, belongs to the transforming growth factor-ß superfamily, which signals via phosphorylating the downstream effectors and SMAD transcription factors. Its central role in several biological processes and intracellular signaling is well known. Genetic variation in ACVR1 has been associated with a rare disease, fibrodysplasia ossificans progressive, and its somatic alteration is reported in rare cancer diffuse intrinsic pontine glioma. Furthermore, altered expression or variation of ACVR1 is associated with multiple pathologies such as polycystic ovary syndrome, congenital heart defects, diffuse idiopathic skeletal hyperostosis, posterior fossa ependymoma and other malignancies. Recent advancements have witnessed ACVR1 as a potential pharmacological target, and divergent promising approaches for its therapeutic targeting have been explored. This review highlights the structural and functional characteristics of receptor ACVR1, associated signaling pathways, genetic variants in several diseases and cancers, protein-protein interaction, gene expression, regulatory miRNA prediction and potential therapeutic targeting approaches. The comprehensive knowledge will offer new horizons and insights into future strategies harnessing its therapeutic potential.

Investigating the link between miR-34a-5p and TLR6 signaling in sepsis-induced ARDS.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are lung complications diagnosed by impaired gaseous exchanges leading to mortality. From the diverse etiologies, sepsis is a prominent contributor to ALI/ARDS. In the present study, we retrieved sepsis-induced ARDS mRNA expression profile and identified 883 differentially expressed genes (DEGs). Next, we established an ARDS-specific weighted gene co-expression network (WGCN) and picked the blue module as our hub module based on highly correlated network properties. Later we subjected all hub module DEGs to form an ARDS-specific 3-node feed-forward loop (FFL) whose highest-order subnetwork motif revealed one TF (STAT6), one miRNA (miR-34a-5p), and one mRNA (TLR6). Thereafter, we screened a natural product library and identified three lead molecules that showed promising binding affinity against TLR6. We then performed molecular dynamics simulations to evaluate the stability and binding free energy of the TLR6-lead molecule complexes. Our results suggest these lead molecules may be potential therapeutic candidates for treating sepsis-induced ALI/ARDS. In-silico studies on clinical datasets for sepsis-induced ARDS indicate a possible positive interaction between miR-34a and TLR6 and an antagonizing effect on STAT6 to promote inflammation. Also, the translational study on septic mice lungs by IHC staining reveals a hike in the expression of TLR6. We report here that miR-34a actively augments the effect of sepsis on lung epithelial cell apoptosis. This study suggests that miR-34a promotes TLR6 to heighten inflammation in sepsis-induced ALI/ARDS. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03700-1.

Monkeypox virus: phylogenomics, host-pathogen interactome and mutational cascade.

While the world is still recovering from the Covid-19 pandemic, monkeypox virus (MPXV) awaits to cause another global outbreak as a challenge to all of mankind. However, the Covid-19 pandemic has taught us a lesson to speed up the pace of viral genomic research for the implementation of preventive and treatment strategies. One of the important aspects of MPXV that needs immediate insight is its evolutionary lineage based on genomic studies. Utilizing high-quality isolates from the GISAID (Global Initiative on Sharing All Influenza Data) database, primarily sourced from Europe and North America, we employed a SNP-based whole-genome phylogeny method and identified four major clusters among 628 MPXV isolates. Our findings indicate a distinct evolutionary lineage for the first MPXV isolate, and a complex epidemiology and evolution of MPXV strains across various countries. Further analysis of the host-pathogen interaction network revealed key viral proteins, such as E3, SPI-2, K7 and CrmB, that play a significant role in regulating the network and inhibiting the host's cellular innate immune system. Our structural analysis of proteins E3 and CrmB revealed potential disruption of stability due to certain mutations. While this study identified a large number of mutations within the new outbreak clade, it also reflected that we need to move fast with the genomic analysis of newly detected strains from around the world to develop better prevention and treatment methods.

A Comprehensive Analysis of Calmodulin-Like Proteins of Glycine max Indicates Their Role in Calcium Signaling and Plant Defense Against Insect Attack.

The calcium (Ca2+) signaling is a crucial event during plant-herbivore interaction, which involves a transient change in cytosolic Ca2+ concentration, which is sensed by Ca2+-sensors, and the received message is transduced to downstream target proteins leading to appropriate defense response. Calmodulin-like proteins (CMLs) are calcium-sensing plant-specific proteins. Although CMLs have been identified in a few plants, they remained uncharacterized in leguminous crop plants. Therefore, a wide-range analysis of CMLs of soybean was performed, which identified 41 true CMLs with greater than 50% similarity with Arabidopsis CMLs. The phylogenetic study revealed their evolutionary relatedness with known CMLs. Further, the identification of conserved motifs, gene structure analysis, and identification of cis-acting elements strongly supported their identity as members of this family and their involvement in stress responses. Only a few Glycine max CMLs (GmCMLs) exhibited differential expression in different tissue types, and rest of them had minimal expression. Additionally, differential expression patterns of GmCMLs were observed during Spodoptera litura-feeding, wounding, and signaling compound treatments, indicating their role in plant defense. The three-dimensional structure prediction, identification of interactive domains, and docking with Ca2+ ions of S. litura-inducible GmCMLs, indicated their identity as calcium sensors. This study on the characterization of GmCMLs provided insights into their roles in calcium signaling and plant defense during herbivory.

Plant cytochrome P450s: Role in stress tolerance and potential applications for human welfare.

Cytochrome P450s (CYPs) are a versatile group of enzymes and one of the largest families of proteins, controlling various physiological processes via biosynthetic and detoxification pathways. CYPs perform multiple roles through a critical irreversible enzymatic reaction in which an oxygen atom is inserted within hydrophobic molecules, converting them into the reactive and hydro soluble components. During evolution, plants have acquired significantly more number of CYPs and represent about 1% of the encoded genes . CYPs are highly conserved proteins involved in growth, development and tolerance against biotic and abiotic stresses. Furthermore, CYPs reinforce plants' molecular and chemical defense mechanisms by regulating the biosynthesis of secondary metabolites, enhancing reactive oxygen species (ROS) scavenging and controlling biosynthesis and homeostasis of phytohormones, including abscisic acid (ABA) and jasmonates. Thus, they are the critical targets of metabolic engineering for enhancing plant defense against environmental stresses. Additionally, CYPs are also used as biocatalysts in the fields of pharmacology and phytoremediation. Herein, we highlight the role of CYPs in plant stress tolerance and their applications for human welfare.

Molecular Rationale of Insect-Microbes Symbiosis-From Insect Behaviour to Mechanism.

Insects nurture a panoply of microbial populations that are often obligatory and exist mutually with their hosts. Symbionts not only impact their host fitness but also shape the trajectory of their phenotype. This co-constructed niche successfully evolved long in the past to mark advanced ecological specialization. The resident microbes regulate insect nutrition by controlling their host plant specialization and immunity. It enhances the host fitness and performance by detoxifying toxins secreted by the predators and abstains them. The profound effect of a microbial population on insect physiology and behaviour is exploited to understand the host-microbial system in diverse taxa. Emergent research of insect-associated microbes has revealed their potential to modulate insect brain functions and, ultimately, control their behaviours, including social interactions. The revelation of the gut microbiota-brain axis has now unravelled insects as a cost-effective potential model to study neurodegenerative disorders and behavioural dysfunctions in humans. This article reviewed our knowledge about the insect-microbial system, an exquisite network of interactions operating between insects and microbes, its mechanistic insight that holds intricate multi-organismal systems in harmony, and its future perspectives. The demystification of molecular networks governing insect-microbial symbiosis will reveal the perplexing behaviours of insects that could be utilized in managing insect pests.

Myeloid cell leukemia 1 (MCL-1): Structural characteristics and application in cancer therapy.

Apoptosis, a major hallmark of cancer cells, regulates cellular fate and homeostasis. BCL-2 (B-cell CLL/Lymphoma 2) protein family is popularly known to mediate the intrinsic mode of apoptosis, of which MCL-1 is a crucial member. Myeloid cell leukemia 1 (MCL-1) is an anti-apoptotic oncoprotein and one of the most investigated members of the BCL-2 family. It is commonly known to be genetically altered, aberrantly overexpressed, and primarily associated with drug resistance in various human cancers. Recent advancements in the development of selective MCL-1 inhibitors and evaluating their effectiveness in cancer treatment establish its popularity as a molecular target. The overall aim is the selective induction of apoptosis in cancer cells by using a single or combination of BCL-2 family inhibitors. Delineating the precise molecular mechanisms associated with MCL-1-mediated cancer progression will certainly improve the efficacy of clinical interventions aimed at MCL-1 and hence patient survival. This review is structured to highlight the structural characteristics of MCL-1, its specific interactions with NOXA, MCL-1-regulatory microRNAs, and at the same time focus on the emerging therapeutic strategies targeting our protein of interest (MCL-1), alone or in combination with other treatments.

Pathogenesis related proteins: A defensin for plants but an allergen for humans.

Pathogenesis related (PR) proteins are defensins expressed upon biotic and abiotic stress by plants. They are also synthesized in specific plant parts such as root, stem, leaves, pollen grains and fruits. According to the current classification, there are 19 different classes of PR-Proteins, 8 out of 19 are proven to exhibit allergic reactions in human. Here, we carried out the allergenicity potential test for the remaining 11 classes of PR-Proteins using in-silico approaches. Our analysis suggests that the other 11 families also have the allergenic potential. We modelled the proteins for which our predictions suggested them to be allergens and for which the crystal structures were not available. We then predicted the B-cell epitope binding regions for all the proteins and used molecular docking approach to study the allergen-antibody interaction. Our findings suggest that all the selected proteins (belonging to 11 families of PR) analysed, can potentially be classified as allergens. We also provide evidence that the number of IgE binding-residues in the allergens is correlated with their respective binding energies with the IgE molecule. This study will be highly relevant to understand the allergenic potential of PR-Proteins to make an informed decision about the consumption of food with high degree of PR-expression.

Potential diagnostics and therapeutic approaches in COVID-19.

The most important aspect of controlling COVID-19 is its timely diagnosis. Molecular diagnostic tests target the detection of any of the following markers such as the specific region of the viral genome, certain enzyme, RNA-dependent RNA polymerase, the structural proteins such as surface spike glycoprotein, nucleocapsid protein, envelope protein, or membrane protein of SARS-CoV-2. This review highlights the underlying mechanisms, advancements, and clinical limitations for each of the diagnostic techniques authorized by the Food and Drug Administration (USA). Significance of diagnosis triaging, information on specimen collection, safety considerations while handling, transport, and storage of samples have been highlighted to make medical and research community more informed so that better clinical strategies are developed. We have discussed here the clinical manifestations and hospital outcomes along with the underlying mechanisms for several drugs administered to COVID-19 prophylaxis. In addition to favourable clinical outcomes, the challenges, and the future directions of management of COVOD-19 are highlighted. Having a comprehensive knowledge of the diagnostic approaches of SARS-CoV-2, and its pathogenesis will be of great value in designing a long-term strategy to tackle COVID-19.

Differential transcript accumulation in Cicer arietinum L. in response to a chewing insect Helicoverpa armigera and defence regulators correlate with reduced insect performance.

Monitoring transcriptional reorganization triggered in response to a particular stress is an essential first step for the functional analysis of genes involved in the process. To characterize Cicer arietinum L. defence responses against Helicoverpa armigera feeding, transcript patterns elicited by both herbivore and mechanical wounding were profiled and compared, and the application of defence regulators was assessed. A combination of approaches was employed to develop transcript profiles, including suppression subtractive hybridization (SSH), macroarray, northern blot, and cluster analysis. Of the 63 unique genes isolated, 29 genes expressed differentially when Helicoverpa feeding and wounding responses were compared. Comparative macroarray analyses revealed that most of the Helicoverpa-induced transcripts were methyl jasmonate (MeJA) and ethylene (ET) regulated. The effects of mild insect infestation and the exogenous application of signalling compounds on larval feeding behaviour were also monitored. Bioassays were performed to measure dispersal percentage and growth of larvae on elicited plants. Larvae released on elicited plants had decreased larval performance, demonstrating the central role of induced plant defence against herbivory. Similarly, wounding and exogenous application of MeJA and ET also affected larval growth and feeding behaviour. Our results demonstrated that Helicoverpa attack up-regulated large transcriptional changes and induced chickpea defence responses. Therefore, the results of this study advance the understanding of non-model plant-insect interactions on a broader scale.

Mechanistic insights into mode of action of rice allene oxide synthase on hydroxyperoxides: An intermediate step in herbivory-induced jasmonate pathway.

Various types of oxygenated fatty acids termed 'oxylipins' are involved in plant response to herbivory. Oxylipins like jasmonic acid (JA) and green leafy volatiles (GLVs) are formed by the action of enzymes like allene oxide synthase (AOS) and hydroxyperoxide lyase (HPL) respectively. In this study, we focus on AOS of Oryza sativa sb. Japonica, that interact with 9- and 13- hydroxyperoxides to produce intermediates of jasmonate pathway and compare it with rice HPL that yields GLVs. We attempt to elucidate the interaction pattern by computational docking protocols keeping the Arabidopsis AOS system as the reference model system. Both 9-hydroxyperoxide and 13-hydroxyperoxide fit into the active site of AOS completely with Phe347, Phe92, Ile463, Val345, and Asn278 being the common interacting residues. Phe347 and Phe92 were mutated with Leucine and docked again with the hydroxyperoxides. The Phe347→Leu347 mutant showed a different mode of action than AOS-hydroxyperoxide complex with Trp413 in direct bonding with the OOH group of 9-hydroxyperoxide. The loss of Lys88-OOH interaction in 13-hydroxyperoxide and loss-of-interaction of Leu347 indicated the importance of Phe347 residue in hydroxyperoxide catalysis. The second mutant Phe92→Leu92 also shows a very different interaction pattern with 13-hydroxyperoxide but not with 9-hydroxyperoxide.Therefore, it can be concluded that Phe347 is more crucial for AOS functionality than Phe92. The aromatic ring of a Phenylalanine residue is important for catalysis and its mutation affects the binding of the two ligands. Another important residue is Asn278 which is an important part of the AOS catalytic site for maintaining stability and can be compared with the Arabidopsis AOS residue Asn321. Lastly, the interaction of HPL with these two derivatives involves Leu363 residue instead of Phe347 and thus, validating the importance of Phe→Leu substitution to be the reason of different modes of action that result in completely different products from same substrates.