scholarly journals Comparative Genomics Reveals Insights into the Divergent Evolution of Astigmatic Mites and Household Pest Adaptations

2022 ◽  
Author(s):  
Qing Xiong ◽  
Angel Tsz-Yau Wan ◽  
Xiao-Yu Liu ◽  
Cathy Sin-Hang Fung ◽  
Xiaojun Xiao ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Serine Proteases ◽  
Drug Targets ◽  
Gene Families ◽  
House Dust Mites ◽  
Divergent Evolution ◽  
Allergy Prevention ◽  
Lytic Enzymes ◽  
Fungal Cell ◽  
Wide Range

Abstract Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing roughly 1–2% of the allergic diseases globally; however, their evolutionary origin, diverse lifestyles including reversible parasitism and quick adaptation to rather new human household environments have not been illustrated at genomic level, which hamper the allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this comparative genomics study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the divergent evolution of astigmatic mites. In the monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases (UGTs), which enriched their capacities of adapting to rapidly changing household environments. The gene diversification after tandem duplications provided plenty of genetic resources for their adaptations of sensing environmental signals, digestion, and detoxification. Whilst many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UGTs and several important fungal cell wall lytic enzymes, which enable the detoxification and associated digestive functions and provide perfect drug targets for pest control. Our comparative study sheds light on the rapid divergent evolution of astigmatic mites from the divergence of Acariformes to their diversification and provides novel insights into the genetic adaptations and even control of human household pests.

Wide-range antifungal antagonism ofPaenibacillus ehimensisIB-X-b and its dependence on chitinase and β-1,3-glucanase production

2008 ◽  
Vol 54 (7) ◽  
pp. 577-587 ◽  
Author(s):  
G. Aktuganov ◽  
A. Melentjev ◽  
N. Galimzianova ◽  
E. Khalikova ◽  
T. Korpela ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Cell Walls ◽  
Biological Control Agent ◽  
Carbon Sources ◽  
Fungal Growth ◽  
Pathogenic Fungi ◽  
Lytic Enzymes ◽  
Fungal Cell ◽  
Wide Range ◽  
Paenibacillus Ehimensis

Previously, we isolated a strain of Bacillus that had antifungal activity and produced lytic enzymes with fungicidal potential. In the present study, we identified the bacterium as Paenibacillus ehimensis and further explored its antifungal properties. In liquid co-cultivation assays, P. ehimensis IB-X-b decreased biomass production of several pathogenic fungi by 45%–75%. The inhibition was accompanied by degradation of fungal cell walls and alterations in hyphal morphology. Residual medium from cultures of P. ehimensis IB-X-b inhibited fungal growth, indicating the inhibitors were secreted into the medium. Of the 2 major lytic enzymes, chitinases were only induced by chitin-containing substrates, whereas β-1,3-glucanase showed steady levels in all carbon sources. Both purified chitinase and β-1,3-glucanase degraded cell walls of macerated fungal mycelia, whereas only the latter also degraded cell walls of intact mycelia. The results indicate synergism between the antifungal action mechanisms of these enzymes in which β-1,3-glucanase is the initiator of the cell wall hydrolysis, whereas the degradation process is reinforced by chitinases. Paenibacillus ehimensis IB-X-b has pronounced antifungal activity with a wide range of fungi and has potential as a biological control agent against plant pathogenic fungi.

Understanding Schizophrenia: Genetic Causes and Treatment

2019 ◽  
Vol 1 (1) ◽  
pp. 6-12
Author(s):  
Fatima Javeria ◽  
Shazma Altaf ◽  
Alishah Zair ◽  
Rana Khalid Iqbal
Keyword(s):  
Copy Number ◽  
Drug Targets ◽  
Disease Risk ◽  
Mental Disease ◽  
Copy Number Variants ◽  
Aminobutyric Acid ◽  
Epigenetic Mechanisms ◽  
Gamma Aminobutyric Acid ◽  
Wide Range ◽  
Severe Mental Disease

Schizophrenia is a severe mental disease. The word schizophrenia literally means split mind. There are three major categories of symptoms which include positive, negative and cognitive symptoms. The disease is characterized by symptoms of hallucination, delusions, disorganized thinking and speech. Schizophrenia is related to many other mental and psychological problems like suicide, depression, hallucinations. Including these, it is also a problem for the patient’s family and the caregiver. There is no clear reason for the disease, but with the advances in molecular genetics; certain epigenetic mechanisms are involved in the pathophysiology of the disease. Epigenetic mechanisms that are mainly involved are the DNA methylation, copy number variants. With the advent of GWAS, a wide range of SNPs is found linked with the etiology of schizophrenia. These SNPs serve as ‘hubs’; because these all are integrating with each other in causing of schizophrenia risk. Until recently, there is no treatment available to cure the disease; but anti-psychotics can reduce the disease risk by minimizing its symptoms. Dopamine, serotonin, gamma-aminobutyric acid, are the neurotransmitters which serve as drug targets in the treatment of schizophrenia. Due to the involvement of genetic and epigenetic mechanisms, drugs available are already targeting certain genes involved in the etiology of the disease.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

Comparative genomics of Bordetella pertussis and prediction of new vaccines and drug targets

2021 ◽  
pp. 1-17
Author(s):  
Andrei G. Felice ◽  
Leonardo N. Q. Santos ◽  
Ian Kolossowski ◽  
Felipe L. Zen ◽  
Leandro G. Alves ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Bordetella Pertussis ◽  
Drug Targets ◽  
New Vaccines

scholarly journals Genomic Characteristics and Comparative Genomics Analysis of Two Chinese Corynespora cassiicola Strains Causing Corynespora Leaf Fall (CLF) Disease

2021 ◽  
Vol 7 (6) ◽  
pp. 485
Author(s):  
Boxun Li ◽  
Yang Yang ◽  
Jimiao Cai ◽  
Xianbao Liu ◽  
Tao Shi ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Single Molecule ◽  
Rubber Tree ◽  
Gene Families ◽  
Gene Clusters ◽  
The Philippines ◽  
Tree Plantations ◽  
Comparative Genomic ◽  
Corynespora Cassiicola ◽  
Leaf Fall

Rubber tree Corynespora leaf fall (CLF) disease, caused by the fungus Corynespora cassiicola, is one of the most damaging diseases in rubber tree plantations in Asia and Africa, and this disease also threatens rubber nurseries and young rubber plantations in China. C. cassiicola isolates display high genetic diversity, and virulence profiles vary significantly depending on cultivar. Although one phytotoxin (cassicolin) has been identified, it cannot fully explain the diversity in pathogenicity between C. cassiicola species, and some virulent C. cassiicola strains do not contain the cassiicolin gene. In the present study, we report high-quality gapless genome sequences, obtained using short-read sequencing and single-molecule long-read sequencing, of two Chinese C. cassiicola virulent strains. Comparative genomics of gene families in these two stains and a virulent CPP strain from the Philippines showed that all three strains experienced different selective pressures, and metabolism-related gene families vary between the strains. Secreted protein analysis indicated that the quantities of secreted cell wall-degrading enzymes were correlated with pathogenesis, and the most aggressive CCP strain (cassiicolin toxin type 1) encoded 27.34% and 39.74% more secreted carbohydrate-active enzymes (CAZymes) than Chinese strains YN49 and CC01, respectively, both of which can only infect rubber tree saplings. The results of antiSMASH analysis showed that all three strains encode ~60 secondary metabolite biosynthesis gene clusters (SM BGCs). Phylogenomic and domain structure analyses of core synthesis genes, together with synteny analysis of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters, revealed diversity in the distribution of SM BGCs between strains, as well as SM polymorphisms, which may play an important role in pathogenic progress. The results expand our understanding of the C. cassiicola genome. Further comparative genomic analysis indicates that secreted CAZymes and SMs may influence pathogenicity in rubber tree plantations. The findings facilitate future exploration of the molecular pathogenic mechanism of C. cassiicola.

scholarly journals FlashPlate Scintillation Proximity Assays for Characterization and Screening of DNA Polymerase, Primase, and Helicase Activities

2001 ◽  
Vol 6 (1) ◽  
pp. 39-46 ◽  
Author(s):  
David L. Earnshaw ◽  
Andrew J. Pope
Keyword(s):  
Dna Polymerase ◽  
Drug Targets ◽  
Direct Synthesis ◽  
Enzyme Characterization ◽  
Dna Helicase ◽  
Oligonucleotide Primer ◽  
Replication Proteins ◽  
Dna Primase ◽  
Wide Range ◽  
Complementary Oligonucleotide

DNA replication proteins represent a class of extremely well-established anti-infective drug targets for which improvements in assay technology are required in order to support enzyme characterization, HTS, and structure-activity relationship studies. Replication proteins are conventionally assayed using precipitation/filtration or gelbased techniques, and are not yet all suitable for conversion into homogeneous fluorescence-based formats. We have therefore developed radiometric assays for these enzymes based upon FlashPlate technology that can be applied to a wide range of targets using a common set of reagents. This approach has allowed the rapid characterization of DNA polymerase, DNA primase, and DNA helicase activities. The resultant 96-/384-well microplate assays are suitable for primary HTS, hit selectivity determination, and/or elucidating the mechanism of action of inhibitors. In all cases, biotinylated DNA oligonucleotide substrates were tethered to streptavidin-coated scintillant-embedded FlashPlate wells. Various adaptations were employed for each enzyme activity. For DNA polymerase, a short complementary oligonucleotide primer was annealed to the longer tethered oligonucleotide, and polymerization was measured by incorporation of [3H]-dNTPs onto the growing primer 3′ end. For DNA primase, direct synthesis of short oligoribonucleotides complementary to the tethered DNA strand was measured by incorporation of [3H]-rNTPs or by subsequent polymerase extension with [3H]-dNTPs from unlabeled primers. For DNA helicase, unwinding of a [33P]-labeled oligonucleotide complementary to the tethered oligonucleotide was measured. This robust and flexible system has a number of substantial advantages over conventional assay techniques for this difficult class of enzymes.

Interaction of an annexin V homodimer (Diannexin) with phosphatidylserine on cell surfaces and consequent antithrombotic activity

2007 ◽  
Vol 97 (03) ◽  
pp. 478-486 ◽  
Author(s):  
Sandra Larkin ◽  
Jef Emeis ◽  
Anthony Allison ◽  
Frans Kuypers
Keyword(s):  
Blood Coagulation ◽  
Serine Proteases ◽  
Recombinant Dna ◽  
Anticoagulant Activity ◽  
Annexin V ◽  
Recombinant Dna Technology ◽  
Antithrombotic Activity ◽  
Human Red Blood Cells ◽  
Wide Range ◽  
Novel Drug

SummaryAnnexin V(AV), a protein with anticoagulant activity, exerts antithrombotic activity by binding to phosphatidylserine (PS), inhibiting activation of serine proteases important in blood coagulation. The potential use of this protein as an anticoagulant is limited as it rapidly passes from the blood into the kidneys due to its relatively small size (36 kDa). We used recombinant DNA technology to produce a homodimer of human AV (DAV, 73 kDa), which exceeds the renal filtration threshold, and has a 6.5-hour half-life in the rat circulation. Human red blood cells with externalized PS were used to show that DAV had a higher affinity for PS-exposing cells than AV. DAV labeling sensitively identifies PS-exposing cells, was found to be a potent inhibitor of the activity of the prothombinase complexes and inhibits the ability of secretory phospholipase A2 to hydrolyze phospholipids of PS-exposing cells, reducing the formation of mediators of blood coagulation and reperfusion injury. DAV exerts dose-dependent antithrombotic activity in ratveins. This combination of activities suggests that DAV is a valuable probe to measure PS exposure and may be efficacious as a novel drug in a wide range of clinical situations.

scholarly journals Are GPCRs Still a Source of New Targets?

2013 ◽  
Vol 18 (9) ◽  
pp. 947-966 ◽  
Author(s):  
Stephen L. Garland
Keyword(s):  
Drug Targets ◽  
Protein Complexes ◽  
X Ray Crystallography ◽  
Peptide Family ◽  
Wide Range ◽  
The Family ◽  
Receptor Pharmacology ◽  
Technical Advances ◽  
Allosteric Mechanisms ◽  
G Protein Coupled

G-protein–coupled receptors (GPCRs) still offer enormous scope for new therapeutic targets. Currently marketed agents are dominated by those with activity at aminergic receptors and yet they account for only ~10% of the family. Progress up until now with other subfamilies, notably orphans, Family A/peptide, Family A/lipid, Family B, Family C, and Family F, has been, at best, patchy. This may be attributable to the heterogeneous nature of GPCRs, their endogenous ligands, and consequently their binding sites. Our appreciation of receptor similarity has arguably been too simplistic, and screening collections have not necessarily been well suited to identifying leads in new areas. Despite the relative shortage of high-quality tool molecules in a number of cases, there is an emerging, and increasingly substantial, body of evidence associating many as yet “undrugged” receptors with a very wide range of diseases. Significant advances in our understanding of receptor pharmacology and technical advances in screening, protein X-ray crystallography, and ligand design methods are paving the way for new successes in the area. Exploitation of allosteric mechanisms; alternative signaling pathways such as G12/13, Gβγ, and β-arrestin; the discovery of “biased” ligands; and the emergence of GPCR-protein complexes as potential drug targets offer scope for new and much improved drugs.

scholarly journals Glucosylceramide Plays a Role in Fungal Germination, Lipid Raft Organization and Biofilm Adhesion of the Pathogenic Fungus Scedosporium aurantiacum

2020 ◽  
Vol 6 (4) ◽  
pp. 345
Author(s):  
Victor Pereira Rochetti ◽  
Rodrigo Rollin-Pinheiro ◽  
Evely Bertulino de Oliveira ◽  
Mariana Ingrid Dutra da Silva Xisto ◽  
Eliana Barreto-Bergter
Keyword(s):  
Cell Surface ◽  
Pathogenic Fungus ◽  
Clinical Manifestations ◽  
Tube Length ◽  
Total Biomass ◽  
Fungal Cell ◽  
Germ Tube Length ◽  
Wide Range ◽  
Fluorescent Stain ◽  
Altered Lipid

Infections caused by Scedosporium species present a wide range of clinical manifestations, from superficial to disseminated, especially in immunocompromised patients. Glucosylceramides (GlcCer) are glycosphingolipids found on the fungal cell surface and play an important role in growth and pathogenicity processes in different fungi. The present study aimed to evaluate the structure of GlcCer and its role during growth in two S. aurantiacum isolates. Purified GlcCer from both isolates were obtained and its chemical structure identified by mass spectrometry. Using ELISA and immunofluorescence techniques it was observed that germination and NaOH-treatment of conidia favor GlcCer exposure. Monoclonal anti-GlcCer antibody reduced germination when cultivated with the inhibitor of melanin synthesis tricyclazole and also reduced germ tube length of conidia, both cultivated or not with tricyclazole. It was also demonstrated that anti-GlcCer altered lipid rafts organization, as shown by using the fluorescent stain filipin, but did not affect the susceptibility of the cell surface to damaging agents. Anti-GlcCer reduced total biomass and viability in biofilms formed on polystyrene plates. In the presence of anti-GlcCer, germinated S. aurantiacum conidia and biofilms could not adhere to polystyrene with the same efficacy as control cells. These results highlight the relevance of GlcCer in growth processes of S. aurantiacum.

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