Tapping uncultured microorganisms through metagenomics for drug discovery

Natural products have been an important historical source of therapeutic agents. Microorganisms are major source of bioactive natural products, and several microbial products including antibiotics, anti-inflammatory, anti-tumour, immunosuppressants and others are currently used as therapeutic agents for human and  domestic animals. Most of these products were obtained from cultured environmental microorganisms. However, it is widely accepted that a very large majority of the microorganisms present in natural  environments are not readily cultured under laboratory conditions, and therefore are not accessible for drug  discovery. Metagenomics is a recent culture-independent approach that has been developed to access the  collective genomes of natural bacterial populations. It enables discovery of the diverse biosynthetic pathways encoded by diverse microbial assemblages that are known to be present in the environment but not-yet  cultured. Recently, several new bioactive molecules and proteins have been discovered using a metagenomic approach. This review highlights the recent methodologies, limitations, and applications of metagenomics for the discovery of new drugs. Moreover, it shows how a multidisciplinary approach combining metagenomics with other technologies can expedite and revolutionize drug discovery from diverse environmental microorganisms.Key words: Microbial diversity, metagenomics, natural products, drug discovery, microbial ecology

Interactome analysis and docking sites of MutS homologs reveal new physiological roles in arabidopsis thaliana

Due to their sedentary lifestyle, plants are constantly exposed to different stress stimuli. Stress comes in variety of forms where factors like radiation, free radicals, "replication errors, polymerase slippage", and chemical mutagens result in genotoxic or cytotoxic damage. In order to face "the base oxidation or DNA replication stress", plants have developed many sophisticated mechanisms. One of them is the DNA mismatch repair (MMR) pathway. The main part of the MMR is the MutS homologue (MSH) protein family. The genome of Arabidopsis thaliana encodes at least seven homologues of the MSH family: AtMSH1, AtMSH2, AtMSH3, AtMSH4, AtMSH5, AtMSH6, and AtMSH7. Despite their importance, the functions of AtMSH homologs have not been investigated. In this work, bioinformatics tools were used to obtain a better understanding of MSH-mediated DNA repair mechanisms in Arabidopsis thaliana and to understand the additional biological roles of AtMSH family members. In silico analysis, including phylogeny tracking, prediction of 3D structure, interactome analysis, and docking site prediction, suggested interactions with proteins were important for physiological development of A. thaliana. The MSH homologs extensively interacted with both TIL1 and TIL2 (DNA polymerase epsilon catalytic subunit), proteins involved in cell fate determination during plant embryogenesis and involved in flowering time repression. Additionally, interactions with the RECQ protein family (helicase enzymes) and proteins of nucleotide excision repair pathway were detected. Taken together, the results presented here confirm the important role of AtMSH proteins in mismatch repair and suggest important new physiological roles

Botany, nutritional value, phytochemical composition and biological activities of quinoa

Quinoa is a climate-resilient food grain crop that has gained significant importance in the last few years due to its nutritional composition, phytochemical properties and associated health benefits. Quinoa grain is enriched in amino acids, fiber, minerals, phenolics, saponins, phytosterols and vitamins. Quinoa possesses different human-health promoting biological substances and nutraceutical molecules. This review synthesizes and summarizes recent findings regarding the nutrition and phytochemical properties of quinoa grains and discusses the associated biological mechanisms. Quinoa grains and grain-based supplements are useful in treating different biological disorders of the human body. Quinoa is being promoted as an exceptionally healthy food and a gluten-free super grain. Quinoa could be used as a biomedicine due to the presence of functional compounds that may help to prevent various chronic diseases. Future research needs to explore the nutraceutical and pharmaceutical aspects of quinoa that might help to control different chronic diseases and to promote human health.King Saud University | Ref. RG-1440-05

Grasses in Semi-Arid Lowlands—Community Composition and Spatial Dynamics with Special Regard to the Influence of Edaphic Factors

Edaphic properties have been widely shown to influence community composition and distribution. However, the degree to which edaphic factors can affect grasses in semi-arid lowlands is still little researched. We assessed the significance of nine edaphic factors to explain the distributions of 65 grass species with various ecological traits (i.e., the ecological indicator values for their preferred habitat) in the semi-arid lowlands of Pakistan. To record information on species composition and related ecological conditions, we selected 10 random sampling locations between 2020 and 2021. For each species, we determined the important value index (IVI) and looked at the primary indicator species that were identified using the indicator species analysis approach. The major genera were Setaria, Brachiaria, and Cenchrus with 6.15% species in each followed by Aristida, Panicum, and Eragrostis with 4.61% wild grass species, Bothriochloa, Bromus, Phragmites, Polypogon, Saccharum, Poa, Echinochloa, and Dactyloctenium with 3.07% species, whereas other genera had a single species each. In total, 80% of the species were native, while only 20% were introduced species. Microphylls accounted for 49.23% of the leaf size spectra of the grass flora in the study area. The other frequent traits included macrophylls (21.53%), nanophylls (20%), and leptophylls (9.23%). The major life forms were therophytes (56.92%) followed by hemicryptophytes (38.46%) and geophytes (4.61%). The results of an ordination analysis indicated that the distribution of grasses was significantly (p ≤ 0.002) influenced by several edaphic parameters, with pH having the greatest impact on species distribution. The analyses of indicator species showed that pH and EC were the most powerful and important edaphic factors for determining the composition of plant communities and indicator species. The significant indicator species in various ecosystems were Cynodon dactylon (L.) Pers. [email protected] and Leptochloa chinensis (L.) Nees (agroecosystem), Brachiaria reptans (L.) C.A. Gardner and C.E. Hubb, Dichanthium annulatum (Forssk.) Stapf, and Saccharum spontaneum L. (forest ecosystem), Cenchrus biflorus Roxb., Cenchrus ciliaris L., and Desmostachya bipinnata (L.) Stapf (urban ecosystem), Arundo donax L., Echinochloa crus-galli, and Phragmites australis (wetland ecosystem), and Saccharum spontaneum and Echinochloa crus-galli (L.) P. Beauv. (riparian ecosystem). We discovered that different species groupings had different habitat preferences and that soil pH had a significant beneficial effect on plant variety. These results provide a scientific roadmap for soil and plant restoration in semi-arid lowland habitats

Review and Measuring the Efficiency of SQL Injection Method in Preventing E-Mail Hacking

E-mail hackers use many methods in their work, in this article, most of such efficient methods are demonstrated and compared. Different methods and stages of such methods are listed here, in order to reveal such methods and to take care of them but the most common discussed method in this paper is SQL method. SQL injection is a type of security exploit in which the attacker adds SQL statements through a web application’s input fields or hidden parameters to gain access to resources or make changes to data. It is found that the SQL is an efficient way in preventing E-mail hacking and its efficiency reaches about 80%. The method of SQL injection can be considered as an efficient way comparing with other methods

Effect of Mepiquat Chloride on Phenology, Yield and Quality of Cotton as a Function of Application Time Using Different Sowing Techniques

Mepiquat chloride (MC) is a plant growth regulator used to manage the rampant vegetative growth of cotton. A two-year field experiment was conducted at the Postgraduate Agricultural Research Station, University of Agriculture, Faisalabad, Pakistan, during 2017 and 2018 to investigate the influence of MC applied at different times on phenology, morphology, lint yield and quality of cotton cultivated using different sowing techniques. MC was applied 50 days after sowing (DAS), 60 DAS and 70 DAS to cotton planted in flat fields (flat sowing), ridges (ridge sowing) and beds (bed sowing). The interactive effect of MC application time and sowing technique did not influence crop phenology, morphology, and lint yield and quality. It was revealed that the crop planted on beds took fewer days to flower (10%) as compared to that on the flat field, and the bed-sown crop produced a higher number of opened bolls (60%) and was characterized by a higher boll weight (32%) and seed cotton yield (50%) in comparison to the flat-sown crop. A late application of MC (at 70 DAS) caused a significant reduction in the time to flowering (8%), with a simultaneous increase in the number of opened bolls (60%), boll weight (32%), ginning out turn (8%) and lint yield (27%) as compared to MC application at 50 DAS. In terms of lint quality, cotton planted on beds had better fiber uniformity (8%) compared to that on the flat field, while MC applied at 70 DAS produced better fiber fineness by 27% in comparison to MC applied earlier. Overall, cotton planting on beds and MC application at 70 DAS may help improve cotton yield and fiber quality and may help in the mechanical picking of cotton

Assessment of the Impact of Different Treatments on the Technological and Antifungal Properties of Papyrus (<i>Cyperus Papyrus</i> L.) Sheets

In the present work, sheets of Papyrus (Cyperus papyrus L.), manufactured by lamination from strips pre-treated with different treatments, were evaluated for their technological and fungal infestation properties (Aspergillus flavus AFl375, A. niger Ani245 and Colletotrichum gloeosporioides Cgl311). The results showed that the highest values of tensile strength, tear strength, burst index and double-fold number were observed in papyrus sheets produced from strips treated with nano-cellulose (0.25%), dimethyl sulfoxide (DMSO 10%), Tylose (0.25%) and nano-cellulose (0.5%), with values of 98.90 N&#183;m/g, 2343.67 mN&#183;m2/g, 1162 kpa&#183;m2/g and 8.33, respectively. The percentage of brightness ranged from 49.7% (strips treated with KOH 2% + 100 mL NaClO) to 9.6% (strips treated with Eucalyptus camaldulensis bark extract 2%), while the percentage of darkness ranged from 99.86% (strips treated with Salix babylonica leaf extract 2% or E. camaldulensis bark extract 0.5%) to 67.26% (strips treated with NaOH (2%) + 100 mL NaClO). From the SEM examination, sheets produced from treated strips with extracts from P. rigida and E. camaldulensis or S. babylonica showed no growths of A. flavus and C. gloeosporioides. Additionally, other pre-treatments, such as Nano-cellulose+Tylose 0.5% (1:1 v/v) and Tylose 0.5%, were also found to have no growth of A. niger. In conclusion, strips pre-treated with nanomaterials and extracts were enhanced in terms of the technological and antifungal properties of produced Papyrus sheets, respectively

Effect of Mepiquat Chloride on Phenology, Yield and Quality of Cotton as a Function of Application Time Using Different Sowing Techniques

Mepiquat chloride (MC) is a plant growth regulator used to manage the rampant vegetative growth of cotton. A two-year field experiment was conducted at the Postgraduate Agricultural Research Station, University of Agriculture, Faisalabad, Pakistan, during 2017 and 2018 to investigate the influence of MC applied at different times on phenology, morphology, lint yield and quality of cotton cultivated using different sowing techniques. MC was applied 50 days after sowing (DAS), 60 DAS and 70 DAS to cotton planted in flat fields (flat sowing), ridges (ridge sowing) and beds (bed sowing). The interactive effect of MC application time and sowing technique did not influence crop phenology, morphology, and lint yield and quality. It was revealed that the crop planted on beds took fewer days to flower (10%) as compared to that on the flat field, and the bed-sown crop produced a higher number of opened bolls (60%) and was characterized by a higher boll weight (32%) and seed cotton yield (50%) in comparison to the flat-sown crop. A late application of MC (at 70 DAS) caused a significant reduction in the time to flowering (8%), with a simultaneous increase in the number of opened bolls (60%), boll weight (32%), ginning out turn (8%) and lint yield (27%) as compared to MC application at 50 DAS. In terms of lint quality, cotton planted on beds had better fiber uniformity (8%) compared to that on the flat field, while MC applied at 70 DAS produced better fiber fineness by 27% in comparison to MC applied earlier. Overall, cotton planting on beds and MC application at 70 DAS may help improve cotton yield and fiber quality and may help in the mechanical picking of cotton

Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation

Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 &mu;g/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (&minus;8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4&rsquo;-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy

Characterization and anti-Aspergillus flavus impact of nanoparticles synthesized by Penicillium citrinum

This work was conducted to evaluate the ability of grape molding fungus; Penicillium citrinum to synthesize silver nanoparticles (Ag NPs). The potency of biosynthesized Ag NPs was checked against the aflatoxigenic Aspergillus flavus var. columnaris, isolated from sorghum grains. Biosynthesized Ag NPs were characterized and confirmed in different ways. X ray diffraction (XRD), Energy Dispersive Spectroscopy (EDS), Transmission Electron Microscopy (TEM) and optical absorption measurements confirmed the bio-synthesis of Ag NPs. The in vitro antifungal investigation showed that biosynthesized Ag NPs were capable of inhibiting the growth of aflatoxigenic A. flavus var. columnaris. Utilization of plant pathogenic fungi in the Ag NPs biosynthesis as well as the use of bio-Ag NPs to control fungal plant diseases instead of chemicals is promising. Further work is needed to confirm the efficacy of the bio-Ag NPs against different mycotoxigenic fungi and to determine the potent applicable doses. Keywords: Nanotechnology, Seed borne, Antimicrobial agents, Aflatoxin