scholarly journals Proline-Specific Fungal Peptidases: Genomic Analysis and Identification of Secreted DPP4 in Alkaliphilic and Alkalitolerant Fungi

2021 ◽  
Vol 7 (9) ◽  
pp. 744
Author(s):  
Nikita Alkin ◽  
Yakov Dunaevsky ◽  
Elena Elpidina ◽  
Galina Beljakova ◽  
Valeria Tereshchenkova ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Genomic Analysis ◽  
In Silico Analysis ◽  
Fungal Species ◽  
Dipeptidyl Peptidase 4 ◽  
Alkaline Conditions ◽  
Living Organisms ◽  
Taxonomic Groups ◽  
Almost All ◽  
Comparative Biochemical Analysis

Proline-specific peptidases (PSP) play a crucial role in the processing of fungal toxins, pheromones, and intracellular signaling. They are of particular interest to biotechnology, as they are able to hydrolyze proline-rich oligopeptides that give a bitter taste to food and can also cause an autoimmune celiac disease. We performed in silico analysis of PSP homologs in the genomes of 42 species of higher fungi which showed the presence of PSP homologs characteristic of various kingdoms of living organisms and belonging to different families of peptidases, including homologs of dipeptidyl peptidase 4 (DPP4) and prolyl aminopeptidase 1 found in almost all the studied fungal species. Homologs of proliniminopeptidases from the S33 family absent in humans were also found. Several studied homologs are characteristic of certain taxonomic groups of fungi. Phylogenetic analysis suggests a duplication of ancestral DPP4 into transmembrane and secreted versions, which predate the split of ascomycete and basidiomycete lineages. Comparative biochemical analysis of DPP4 in alkaliphilic and alkali-tolerant strains of fungi showed that, notwithstanding some individual features of these enzymes, in both cases, the studied DPP4 are active and stable under alkaline conditions and at high salt concentrations, which makes them viable candidates for biotechnology and bioengineering.

scholarly journals The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299
Author(s):  
Vítor Ennes-Vidal ◽  
Marta Helena Branquinha ◽  
André Luis Souza dos Santos ◽  
Claudia Masini d’Avila-Levy
Keyword(s):  
Proteolytic Activity ◽  
Current Knowledge ◽  
Current Therapy ◽  
Calcium Dependent ◽  
Administration Routes ◽  
Life Threatening ◽  
Living Organisms ◽  
Almost All ◽  
Open Question ◽  
Calpain Inhibitors

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?

Heterochrony and the Problem of Missing Links in Evolutionary Sequences

1984 ◽  
Vol 1 ◽  
pp. 84-96 ◽  
Author(s):  
Thomas W. Broadhead ◽  
Johnny A. Waters
Keyword(s):  
Natural Selection ◽  
Feature Recognition ◽  
Biological Meaning ◽  
Juvenile Stages ◽  
Transitional Forms ◽  
Living Organisms ◽  
Taxonomic Groups ◽  
Organic Change

Critics of the concept of organic change through time have demanded proof not only of “transitional forms” but of specific transitions among higher taxonomic groups. Transitional forms among species and between a species of one genus and a species of another genus have been criticized because most demonstrated ancestor-descendant transitions are considered to occur within one “kind” of organism; the “kind” concept is bereft of biological meaning.Natural selection acts upon organisms at all stages of ontogeny, and especially at larval-juvenile stages. Large shifts in the morphology of one or more features are common in groups of organisms that evolve by heterochrony. Because heterochrony involves a change in timing of the appearance or development of a particular feature, recognition of heterochrony requires a confident knowledge of ontogeny. The resulting increase in complexity (e.g. recapitulation) or decrease in complexity (e.g. paedomorphosis), well documented among living organisms, commonly excludes morphologic intermediates. Paedomorphosis is especially important in the evolution of progressively simplifying lineages and has been well documented from living plants and animals and fossil representatives of echinoderms (blastoids, crinoids), conodonts, arthropods, mollusks and vertebrates. Heterochrony characterizes the evolution of most metazoan organisms, occurs at all taxonomic levels and was probably responsible for major innovations by which higher taxonomic groups are recognized.

scholarly journals Circadian Deregulation as Possible New Player in Pollution-Induced Tissue Damage

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 116
Author(s):  
Mascia Benedusi ◽  
Elena Frigato ◽  
Cristiano Bertolucci ◽  
Giuseppe Valacchi
Keyword(s):  
Cardiovascular Diseases ◽  
Air Pollutants ◽  
Environmental Stressors ◽  
Common Mechanism ◽  
Particulate Matters ◽  
Circadian Misalignment ◽  
Pathological Conditions ◽  
Peripheral Clocks ◽  
Living Organisms ◽  
Almost All

Circadian rhythms are 24-h oscillations driven by a hypothalamic master oscillator that entrains peripheral clocks in almost all cells, tissues and organs. Circadian misalignment, triggered by industrialization and modern lifestyles, has been linked to several pathological conditions, with possible impairment of the quality or even the very existence of life. Living organisms are continuously exposed to air pollutants, and among them, ozone or particulate matters (PMs) are considered to be among the most toxic to human health. In particular, exposure to environmental stressors may result not only in pulmonary and cardiovascular diseases, but, as it has been demonstrated in the last two decades, the skin can also be affected by pollution. In this context, we hypothesize that chronodistruption can exacerbate cell vulnerability to exogenous damaging agents, and we suggest a possible common mechanism of action in deregulation of the homeostasis of the pulmonary, cardiovascular and cutaneous tissues and in its involvement in the development of pathological conditions.

scholarly journals Microbiological analysis of commonly used toothpaste samples in Bangladesh

2019 ◽  
Vol 8 (1) ◽  
pp. 38-40
Author(s):  
Mousumi Talukder ◽  
Ifra Tun Nur
Keyword(s):  
Microbiological Quality ◽  
Enteric Bacteria ◽  
Fungal Species ◽  
Microbiological Analysis ◽  
Bacillus Spp ◽  
Viable Bacteria ◽  
Dental Diseases ◽  
Almost All ◽  
Staphylococcus Spp ◽  
Great Public Health

Present study attempted to identify and enumerate microorganisms spoiling commonly used toothpaste samples. Among 7 brand of toothpaste, almost all were found to be rigorously contaminated with total viable bacteria within a range of 103 – 105 cfu/g. Proliferation of fungal species was observed up to 105 cfu/g. Prevalence of Staphylococcus spp., Pseudomonas spp. and Bacillus spp. was observed within a range of 103-105 cfu/g while Vibrio spp. were completely absent. Among the enteric bacteria, Escherichia coli and Klebsiella spp. was found in all the samples tested. Such findings highlighted a great public health risk associated with dental diseases among the users and thereby specified the importance to introduce a proper guideline in maintaining good microbiological quality for such daily usage healthcare products. Stamford Journal of Microbiology, Vol.8(1) 2018: 38-40

scholarly journals IN SILICO STUDY OF THE ANTIMICROBIAL PROFILE OF β-CITRONELLOL: POTENTIAL AS AN ANTIFUNGAL

2019 ◽  
Vol 16 (32) ◽  
pp. 894-898
Author(s):  
D. F. SILVA ◽  
H. D. NETO ◽  
M. D. L. FERREIRA ◽  
A. A. O. FILHO ◽  
E. O. LIMA
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
In Silico Analysis ◽  
Fungal Species ◽  
In Silico Study ◽  
Pass Online ◽  
Therapeutic Alternatives ◽  
Bioactivity Profile ◽  
Silico Analysis

β-citronellol (3,7-dimethyl-6-octen-1-ol) has been exhibiting a number of pharmacological effects that creates interest about its antimicrobial potential, since several substances of the monoterpene class have already demonstrated to possess activity in this profile. In addition, the emergence of fungal species resistant to current pharmacotherapy poses a serious challenge to health systems, making it necessary to search for new effective therapeutic alternatives to deal with this problem. In this study, the antimicrobial profile of β-citronellol was analyzed. The Prediction of Activity Spectra for Substances (PASS) online software was used to study the antimicrobial activity of the β-citronellol molecule by the use of in silico analysis. In contrast, an in vitro antifungal study of this monoterpene was carried out. For this purpose, the Minimum Inhibitory Concentration (MIC) was determined by the microdilution technique in 96-well plates in Saboraud Dextrose Broth/RPMI against sensitive strains of Candida albicans, and this assay was performed in duplicate. In the in silico analysis of the antimicrobial profile, it was revealed that the monoterpene β-citronellol had a diverse antimicrobial bioactivity profile. For the antifungal activity, it presented a percentage value with Pa: 58.4% (predominant) and its MIC of 128 μg/mL, which was equivalent for all strains tested. The in silico study of the β-citronellol molecule allowed us to consider that the monoterpenoid is very likely to be bioactive against agents that cause fungal infections.

scholarly journals In silico Analysis of Phylogeny and Virulence Genes in STEC Strains Associated with Outbreaks

2021 ◽  
Author(s):  
Mehmet Demirci ◽  
Akın Yiğin ◽  
Fadile Yıldız Zeyrek
Keyword(s):  
Foodborne Pathogens ◽  
In Silico ◽  
Virulence Genes ◽  
Genomic Analysis ◽  
In Silico Analysis ◽  
Comparative Genomic ◽  
Phylogeny Analysis ◽  
In Silico Study ◽  
The World ◽  
Different Parts

Objective: Shiga toxin-producing E. coli (STEC) strains are important foodborne pathogens. Significant outbreaks with STEC strains can be encountered, even if the geography, time or resources were different. The aim of our in silico study was to compare the virulance factors and phylogeny of STEC strains such as EDL933 and Sakai, which have been identified as an agent in important outbreaks in different parts of the world and whole genomic data were in open databases. Method: Genomic NCBI data of eight strains were included in our study, including seven different STEC strains associated with significant epidemics in different parts of the world, and one supershedder strain obtained from cattle feces. Results: According to phylogeny analysis, the most similar strain to EDL933 strain was TW14588, with 96.4% similarity. The most distant similarity was Sakai strains with 79.2%. According to the virulence genes analysis; the presence of 333 genes that constitute virulence factors under nine headings were detected. In the first STEC origin, EDL933, 45% of all virulence genes were found to be active. Adherence genes such as Ecp, Elf, Hcp and toxin genes such as clyA were active in all strains except stx genes. Conclusion: In our in silico study of comparative genomic analysis of STEC strains which are associated with outbreaks, it was determined that STEC strains used different virulence genes besides the stx gene. Indeed, they used certain virulence genes, even their sources, time and locations were different, in the pathogenesis

scholarly journals Comparative genomic analysis of Methanimicrococcus blatticola provides insights into host adaptation in archaea and the evolution of methanogenesis

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Courtney M. Thomas ◽  
Najwa Taib ◽  
Simonetta Gribaldo ◽  
Guillaume Borrel
Keyword(s):  
Gut Microbiota ◽  
Large Scale ◽  
Genomic Analysis ◽  
Host Adaptation ◽  
Comparative Genomic Analysis ◽  
Comparative Genomic ◽  
Methyl Branch ◽  
Mechanisms Of Adaptation ◽  
Hydrogenotrophic Methanogens ◽  
Almost All

AbstractOther than the Methanobacteriales and Methanomassiliicoccales, the characteristics of archaea that inhabit the animal microbiome are largely unknown. Methanimicrococcus blatticola, a member of the Methanosarcinales, currently reunites two unique features within this order: it is a colonizer of the animal digestive tract and can only reduce methyl compounds with H2 for methanogenesis, a increasingly recognized metabolism in the archaea and whose origin remains debated. To understand the origin of these characteristics, we have carried out a large-scale comparative genomic analysis. We infer the loss of more than a thousand genes in M. blatticola, by far the largest genome reduction across all Methanosarcinales. These include numerous elements for sensing the environment and adapting to more stable gut conditions, as well as a significant remodeling of the cell surface components likely involved in host and gut microbiota interactions. Several of these modifications parallel those previously observed in phylogenetically distant archaea and bacteria from the animal microbiome, suggesting large-scale convergent mechanisms of adaptation to the gut. Strikingly, M. blatticola has lost almost all genes coding for the H4MPT methyl branch of the Wood–Ljungdahl pathway (to the exception of mer), a phenomenon never reported before in any member of Class I or Class II methanogens. The loss of this pathway illustrates one of the evolutionary processes that may have led to the emergence of methyl-reducing hydrogenotrophic methanogens, possibly linked to the colonization of organic-rich environments (including the animal gut) where both methyl compounds and hydrogen are abundant.

scholarly journals BCSExplorer: a customized biosynthetic chemical space explorer with multifunctional objective function analysis

2019 ◽  
Author(s):  
Yu Tian ◽  
Ling Wu ◽  
Le Yuan ◽  
Shaozhen Ding ◽  
Fu Chen ◽  
...  
Keyword(s):  
Chemical Space ◽  
Function Analysis ◽  
Supplementary Information ◽  
Bulk Chemicals ◽  
Toxicity Analysis ◽  
Novel Method ◽  
Living Organisms ◽  
Almost All ◽  
New Generation ◽  
Rule Library

Abstract Summary The biosynthetic ability of living organisms has important applications in producing bulk chemicals, biofuels and natural products. Based on the most comprehensive biosynthesis knowledgebase, a computational system, BCSExplorer, is proposed to discover the unexplored chemical space using nature’s biosynthetic potential. BCSExplorer first integrates the most comprehensive biosynthetic reaction database with 280 000 biochemical reactions and 60 000 chemicals biosynthesized globally over the past 130 years. Second, in this study, a biosynthesis tree is computed for a starting chemical molecule based on a comprehensive biotransformation rule library covering almost all biosynthetic possibilities, in which redundant rules are removed using a new algorithm. Moreover, biosynthesis feasibility, drug-likeness and toxicity analysis of a new generation of compounds will be pursued in further studies to meet various needs. BCSExplorer represents a novel method to explore biosynthetically available chemical space. Availability and implementation BCSExplorer is available at: http://www.rxnfinder.org/bcsexplorer/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Engineering better chimeric antigen receptor T cells

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Hao Zhang ◽  
Pu Zhao ◽  
He Huang
Keyword(s):  
T Cells ◽  
Intracellular Signaling ◽  
Influence Factors ◽  
Target Antigen ◽  
Car T Cells ◽  
Car T ◽  
Underlying Mechanisms ◽  
Almost All

AbstractCD19-targeted CAR T cells therapy has shown remarkable efficacy in treatment of B cell malignancies. However, relapse of primary disease remains a major obstacle after CAR T cells therapy, and the majority of relapses present a tumor phenotype with retention of target antigen (antigen-positive relapse), which highly correlate with poor CAR T cells persistence. Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to overcome these limitations. In this review, we summarize the rapidly developing knowledge regarding the factors that influence CAR T cells in vivo persistence and the underlying mechanisms. The factors involve the CAR constructs (extracellular structures, transmembrane and intracellular signaling domains, as well as the accessory structures), activation signaling (CAR signaling and TCR engagement), methods for in vitro culture (T cells collection, purification, activation, gene transduction and cells expansion), epigenetic regulations, tumor environment, CD4/CD8 subsets, CAR T cells differentiation and exhaustion. Of note, among these influence factors, CAR T cells differentiation and exhaustion are identified as the central part due to the fact that almost all factors eventually alter the state of cells differentiation and exhaustion. Moreover, we review the potential coping strategies aiming at these limitations throughout this study.

The rmc locus does not affect plant interactions or defence-related gene expression when tomato (Solanum lycopersicum) is infected with the root fungal parasite, Rhizoctonia

2006 ◽  
Vol 33 (3) ◽  
pp. 289 ◽  
Author(s):  
Ling-Ling Gao ◽  
F. Andrew Smith ◽  
Sally E. Smith
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Arbuscular Mycorrhizal ◽  
Am Fungi ◽  
Fungal Species ◽  
Plant Interactions ◽  
Related Gene ◽  
Wild Type ◽  
Cell Layers ◽  
Almost All

A tomato mutant with reduced mycorrhizal colonisation, rmc, confers resistance to almost all arbuscular mycorrhizal (AM) fungal species tested, although there is variation in colonisation of different root cell layers by different fungi and one species of AM fungus can colonise this mutant relatively normally. These variations indicate a high degree of specificity in relation to AM colonisation. We explored the possibility of specificity or otherwise in interactions between rmc and three non-AM root-infecting fungi, Rhizoctonia solani anastomosis groups (AG) 4 and AG8, and binucleate Rhizoctonia (BNR). There were no differences between the wild type tomato 76R and rmc in the speed or extent to which these fungi infected roots or caused disease. Infection by R. solani induced high levels of defence-related gene expression in both tomato genotypes relative to non-infected plants. In contrast, with BNR the expression of these genes was not induced or induced to a much lower extent than with R. solani. The expression of defence-related genes with these two non-AM fungi was very similar in the two plant genotypes. It was different from effects observed during colonisation by AM fungi, which enhanced expression of defence-related genes in rmc compared with the wild type tomato. The specificity and molecular mechanisms of rmc in control of AM colonisation are discussed.

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