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Plant-derived protease inhibitors (PIs) are a promising defensin for crop improvement and insect pest management. Although agronomist made significant efforts in utilizing PIs for managing insect pests, the potentials of PIs are still obscured. Insect ability to compensate nutrient starvation induced by dietary PI feeding using different strategies, that is, overexpression of PI-sensitive protease, expression of PI-insensitive proteases, degradation of PI, has made this innumerable collection of PIs worthless. A practical challenge for agronomist is to identify potent PI candidates, to limit insect compensatory responses and to elucidate insect compensatory and resistance mechanisms activated upon herbivory. This knowledge could be further efficiently utilized to identify potential targets for RNAi-mediated pest control. These vital genes of insects could be functionally annotated using the advanced gene-editing technique, CRISPR/Cas9. Contemporary research is exploiting different in silico and modern molecular biology techniques to utilize PIs in controlling insect pests efficiently. This review is structured to update recent advancements in this field, along with its chronological background., (© 2018 Institute of Zoology, Chinese Academy of Sciences.)

Tuberculosis (TB) is one such disease that has become a nuisance in the world scenario and one of the most deadly diseases of the current times. The etiological agent of tuberculosis, Mycobacterium tuberculosis (M. tb) kills millions of people each year. Not only 1.7 million people worldwide are estimated to harbor M. tb in the latent form but also 5 to 15 percent of which are expected to acquire an infection during a lifetime. Though curable, a long duration of drug regimen and expense leads to low patient adherence. The emergence of multi-, extensive- and total- drug-resistant strains of M. tb further complicates the situation. Owing to high TB burden, scientists worldwide are trying to design novel therapeutics to combat this disease. Therefore, to identify new drug targets, there is a growing interest in targeting DNA repair pathways to fight this infection. Thus, this review aims to explore DNA repair and damage tolerance as an efficient target for drug development by understanding M. tb DNA repair and tolerance machinery and its regulation, its role in pathogenesis and survival, mutagenesis, and consequently, in the development of drug resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Insect neuropeptides and their associated receptors have been one of the potential targets for the pest control. The present study describes in silico models developed using natural and modified insect neuropeptides for predicting and designing new neuropeptides. Amino acid composition analysis revealed the preference of residues C, D, E, F, G, N, S, and Y in insect neuropeptides The positional residue preference analysis show that in natural neuropeptides residues like A, N, F, D, P, S, and I are preferred at N terminus and residues like L, R, P, F, N, and G are preferred at C terminus. Prediction models were developed using input features like amino acid and dipeptide composition, binary profiles and implementing different machine learning techniques. Dipeptide composition based SVM model performed best among all the models. In case of NeuroPIpred_DS1, model achieved an accuracy of 86.50% accuracy and 0.73 MCC on training dataset and 83.71% accuracy and 0.67 MCC on validation dataset whereas in case of NeuroPIpred_DS2, model achieved 97.47% accuracy and 0.95 MCC on training dataset and 97.93% accuracy and 0.96 MCC on validation dataset. In order to assist researchers, we created standalone and user friendly web server NeuroPIpred, available at ( https://webs.iiitd.edu.in/raghava/neuropipred .).

Breast cancer is too complex with various different molecular alterations involved in its pathogenesis and progression. Over the decade, we have seen a surge in the development of drugs for bimolecular targets and for the signal transduction pathways involved in the treatment line of breast cancer. These drugs, either alone or in combination with conventional treatments like chemotherapy, hormone therapy and radiotherapy, will help oncologists to get a better insight and do the needful treatment. These novel therapies bring various challenges along with them, which include the dosage selection, patient selection, schedule of treatment and weighing of clinical benefits over side effects. In this review, we highlight the recently studied target molecules that have received indications in breast carcinoma, both in the localized and in an advanced state and about their inhibitors which are in clinical development which can give the immense potential to clinical care in the near future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plants are endowed with an innate immune system, which enables them to protect themselves from pest and pathogen. The participation of pathogenesis-related (PR) proteins is one of the most crucial events of inducible plant defense response. Herein, we report the characterization of CaHaPR-4, a Helicoverpa-inducible class II PR-4 protein from chickpea. Bioinformatic analysis of CaHaPR-4 protein indicated the presence of a signal peptide, barwin domain but it lacks the chitin-binding site/hevein domain. The recombinant CaHaPR-4 is bestowed with RNase and bivalent ion-dependent DNase activity. Further, the RNA and DNA binding sites were identified and confirmed by analyzing interactions between mutated CaHaPR-4 with the altered active site and ribonuclease inhibitor, 5'ADP and DNase inhibitor, 2‑nitro‑5‑thiocyanobenzoic acid (NTCB) using 3D modeling and docking studies. Moreover, CaHaPR-4 shows antifungal activity as well as growth inhibiting properties against neonatal podborer larvae. To the best of our knowledge, this is the first report of a PR-4 showing RNase, DNase, antifungal and most importantly insect growth inhibiting properties against Helicoverpa armigera simultaneously., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Thioredoxins are small and universal proteins, which are involved in the cell redox regulation. In plants, they participate in a broad range of biochemical processes like self-incompatibility, seed germination, pathogen & pest defense and oxidative stress tolerance. The h-type of thioredoxin (Trx-h) protein represents the largest Trx family. Herein, we characterized the Helicoverpa - inducible Trx h from an important legume, Cicer arietinum, CaHaTrx-h, 'CGFS' type Trxs, which encodes for a 113 amino acids long protein and possess characteristic motifs "FLKVDVDE" and "VVDFTASWCGPCRFIAPIL" and 73% sequence identity with AtTrx-h. Homology modeling and simulation of the target showed that the extended ß-sheet regions remain stable during the simulation while the helical regions fluctuate between alpha and 3- 10 helical forms and highlights the flexibility of helix2-helix3 and terminal regions probably to accommodate an approaching protein target and facilitate their interaction. During the simulation, the structure exists in five energy minima clusters with biggest cluster size belonging to 20-25 ns time frames. PR-5 and Mannitol Dehydrogenase were nominated as potential targets and share close interaction with CaHaTrx-h via disulfide bond reduction. The study is an effort in the direction of understanding stress-related mechanisms in crop plants to overcome losses in agricultural yield., (Copyright © 2017 Elsevier B.V. All rights reserved.)

RNA interference (RNAi) based methods are being developed for pest management. A few products for control of coleopteran pests are expected to be commercialized soon. However, variability in RNAi efficiency among insects is preventing the widespread use of this technology. In this study, we conducted research to identify reasons for variability in RNAi efficiency among thirty-seven (37) insects belonging to five orders. Studies on double-stranded RNA (dsRNA) degradation by dsRNases and processing of labeled dsRNA to siRNA showed that both dsRNA degradation and processing are variable among insects belonging to different orders as well as among different insect species within the same order. We identified homologs of key RNAi genes in the genomes of some of these insects and studied their domain architecture. These data suggest that dsRNA digestion by dsRNases and its processing to siRNAs in the cells are among the major factors contributing to differential RNAi efficiency reported among insects.

Receptor tyrosine kinases (RTK) are important cell signaling molecules that influence many cellular processes. Receptor tyrosine kinase such as orphan receptor 1 (Ror1), a surface antigen, is a member of the RTK family of Ror, which plays a crucial role in cancers that have high-grade histology. As Ror1 has been implicated to be a potential target for cancer therapy, we selected this protein for further investigation. The secondary and tertiary structure of this protein was determined, which revealed that this protein contained three β-sheets, seven α-helices, and coils. The prediction of the active site revealed its cage-like function that opens for ligand entry and then closes for interacting with the ligands. Optimized ligands from the database were virtually screened to obtain the most efficient and potent ones. The screened ligands were evaluated for their therapeutic usefulness. Furthermore, the ligands that passed the test were docked to the target protein resulting in a few ligands with high score, which were analyzed further. The highest scoring ligand, Beta-1, 2,3,4,6-Penta-O-Galloyl-D-Glucopyranose was reported to be a naturally occurring tannin. This in silico approach indicates the potential of this molecule for advancing a further step in cancer treatment.

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: To study the correlation between the volume of the spleen and hematological parameters, splenic vein diameter, portal pressure before shunt, portal pressure after shunt, reduction of portal pressure and grade of esophageal varices in patients with extrahepatic portal vein obstruction (EHPVO)., Methods: Twenty-four patients with EHPVO who underwent splenectomy with leino-renal shunt during a period of 2 years were prospectively analyzed. Splenic volumes were measured from CT scans using appropriate volumetry software. In order to standardize the difference in the size of the patients, the splenic volume was expressed as a ratio, the splenic volume index, between the actual volume as measured on the CT scan and the surface area of the body. The splenic vein diameter was measured on the CT portogram and confirmed during surgery using a caliper. The grade of esophageal varices was determined during esophageal endoscopy using the Japanese Research Society for Portal Hypertension classification. The portal pressure was measured by cannulating a venous tributary of the gastro-epiploic arcade and using a pressure transducer., Results: The splenic volume, expressed as splenic volume index, ranged from 362.15 to 1,849.51 ml/m² (mean 929.23 ± 409.02). Larger splenic volumes were associated with lower hemoglobin and platelet counts and significantly lower total leukocyte counts (p = 0.0003). The portal pressures reduced remarkably following the splenectomy and leino-renal shunt; mean post-shunt pressure 20 ± 6.63 mmHg from mean pre-shunt pressure of 34.33 ± 6.21 mmHg (mean percentage reduction 43.37 ± 16.02%). There was no statistically significant correlation between splenic volume and any of the hemodynamic parameters except a weak correlation with splenic vein diameter. There was no correlation between the splenic vein diameter and the pre-shunt portal pressure; however, there was a statistically significant correlation between the splenic vein diameter and the percentage of post-shunt portal pressure reduction (p = 0.0494)., Conclusion: Splenic volume has a weak correlation with splenic vein diameter, but does not correlate with portal pressure or the grade of varix. Splenic vein diameter has a statistically significant correlation with the percentage of portal pressure reduction following a leino-renal shunt. There is a statistically significant negative correlation between the splenic volume and the total leukocyte count.

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.