scholarly journals In Silico Reconstruction of Sperm Chemotaxis

2021 ◽  
Vol 22 (17) ◽  
pp. 9104
Author(s):  
Masahiro Naruse ◽  
Midori Matsumoto
Keyword(s):  
Long Range ◽  
Sea Urchin ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Biophysical Properties ◽  
Turning Behavior ◽  
Sperm Flagellum ◽  
Sperm Chemotaxis ◽  
Experimental Findings

In echinoderms, sperm swims in random circles and turns in response to a chemoattractant. The chemoattractant evokes transient Ca2+ influx in the sperm flagellum and induces turning behavior. Recently, the molecular mechanisms and biophysical properties of this sperm response have been clarified. Based on these experimental findings, in this study, we reconstructed a sperm model in silico to demonstrate an algorithm for sperm chemotaxis. We also focused on the importance of desensitizing the chemoattractant receptor in long-range chemotaxis because sperm approach distantly located eggs, and they must sense the chemoattractant concentration over a broad range. Using parameters of the sea urchin, simulations showed that a number of sperm could reach the egg from millimeter-order distances with desensitization, indicating that we could organize a functional sperm model, and that desensitization of the receptor is essential for sperm chemotaxis. Then, we compared the model with starfish sperm, which has a different desensitization scheme and analyzed the properties of the model against various disturbances. Our approach can be applied as a novel tool in chemotaxis research.

scholarly journals TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation

2021 ◽  
Vol 7 (3) ◽  
pp. eabd4235
Author(s):  
P. Pradhan ◽  
R. Toy ◽  
N. Jhita ◽  
A. Atalis ◽  
B. Pandey ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Lipid A ◽  
Critical Role ◽  
Mouse Bone Marrow ◽  
Biophysical Properties ◽  
Gm Csf ◽  
Monophosphoryl Lipid A ◽  
Integrated Response ◽  
Particulate Carriers

Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF–driven mouse bone marrow–derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs. Mechanistically, we found that MyD88 and interferon regulatory factor 5 (IRF5) were necessary for IFN-β and IL-12p70 production, while TRIF signaling was required for the synergistic response. Both the kinetics and magnitude of downstream TRAF6 and IRF5 signaling drove the synergy. These results identify the key mechanisms of synergistic Toll-like receptor 4 (TLR4)–TLR9 co-signaling in mouse BM-APCs and underscore the critical role of signaling kinetics and biophysical properties on the integrated response to combination adjuvants.

scholarly journals Quasi-1D XY antiferromagnet Sr2Ni(SeO3)2Cl2 at Sakai-Takahashi phase diagram

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
E. S. Kozlyakova ◽  
A. V. Moskin ◽  
P. S. Berdonosov ◽  
V. V. Gapontsev ◽  
S. V. Streltsov ◽  
...  
Keyword(s):  
Phase Diagram ◽  
Long Range ◽  
Density Functional ◽  
Uniaxial Anisotropy ◽  
Exchange Interactions ◽  
Spin Liquid ◽  
Functional Theory ◽  
One Dimensional ◽  
Ordered Phases ◽  
Experimental Findings

AbstractUniform quasi-one-dimensional integer spin compounds are of interest as a potential realization of the Haldane conjecture of a gapped spin liquid. This phase, however, has to compete with magnetic anisotropy and long-range ordered phases, the implementation of which depends on the ratio of interchain J′ and intrachain J exchange interactions and both uniaxial D and rhombic E single-ion anisotropies. Strontium nickel selenite chloride, Sr2Ni(SeO3)2Cl2, is a spin-1 chain system which passes through a correlations regime at Tmax ~ 12 K to long-range order at TN = 6 K. Under external magnetic field it experiences the sequence of spin-flop at Bc1 = 9.0 T and spin-flip transitions Bc2 = 23.7 T prior to full saturation at Bsat = 31.0 T. Density functional theory provides values of the main exchange interactions and uniaxial anisotropy which corroborate the experimental findings. The values of J′/J = 0.083 and D/J = 0.357 place this compound into a hitherto unoccupied sector of the Sakai-Takahashi phase diagram.

scholarly journals Multidrug Antimicrobial Resistance and Molecular Detection of mcr-1 Gene in Salmonella Species Isolated from Chicken

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 206
Author(s):  
Md Bashir Uddin ◽  
S.M. Bayejed Hossain ◽  
Mahmudul Hasan ◽  
Mohammad Nurul Alam ◽  
Mita Debnath ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Antimicrobial Resistance ◽  
In Silico ◽  
Salmonella Enterica ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Genetic Relationships ◽  
Evolutionary Relationship ◽  
Salmonella Spp ◽  
Gram Negative

Colistin (polymyxin E) is widely used in animal and human medicine and is increasingly used as one of the last-resort antibiotics against Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant Gram-negative bacteria, resistance to this antibiotic ought to be monitored. The study was undertaken to elucidate the molecular mechanisms, genetic relationships and phenotype correlations of colistin-resistant isolates. Here, we report the detection of the mcr-1 gene in chicken-associated Salmonella isolates in Bangladesh and its in-silico functional analysis. Out of 100 samples, 82 Salmonella spp. were isolated from chicken specimens (liver, intestine). Phenotypic disc diffusion and minimum inhibitory concentration (MIC) assay using different antimicrobial agents were performed. Salmonella isolates were characterized using PCR methods targeting genus-specific invA and mcr-1 genes with validation for the functional analysis. The majority of the tested Salmonella isolates were found resistant to colistin (92.68%), ciprofloxacin (73.17%), tigecycline (62.20%) and trimethoprim/sulfamethoxazole (60.98%). When screened using PCR, five out of ten Salmonella isolates were found to carry the mcr-1 gene. One isolate was confirmed for Salmonella enterica subsp. enterica serovar Enteritidis, and other four isolates were confirmed for Salmonella enterica subsp. enterica serovar Typhimurium. Sequencing and phylogenetic analysis revealed a divergent evolutionary relationship between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, rendering them resistant to colistin. Three-dimensional homology structural analysis of MCR-1 proteins and molecular docking interactions suggested that MCR-1 and LptA share a similar substrate binding cavity, which could be validated for the functional analysis. The comprehensive molecular and in-silico analyses of the colistin resistance mcr-1 gene of Salmonella spp. of chicken origin in the present study highlight the importance of continued monitoring and surveillance for antimicrobial resistance among pathogens in food chain animals.

Macroporous resin extraction of PHNQs from Evechinus chloroticus sea urchin and their in vitro antioxidant, anti-bacterial and in silico anti-inflammatory activities

LWT ◽  
2020 ◽  
Vol 131 ◽  
pp. 109817
Author(s):  
Yakun Hou ◽  
Alan Carne ◽  
Michelle McConnell ◽  
Sonya Mros ◽  
Adnan A. Bekhit ◽  
...  
Keyword(s):  
Sea Urchin ◽  
In Silico ◽  
Macroporous Resin ◽  
Anti Inflammatory

scholarly journals Nicotine Induces Polyspermy in Sea Urchin Eggs through a Non-Cholinergic Pathway Modulating Actin Dynamics

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 63 ◽  
Author(s):  
Nunzia Limatola ◽  
Filip Vasilev ◽  
Luigia Santella ◽  
Jong Tai Chun
Keyword(s):  
Sea Urchin ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Molecular Mechanisms ◽  
Actin Dynamics ◽  
Dependent Manner ◽  
Animal Cells ◽  
Sea Urchin Eggs ◽  
Cholinergic Pathway ◽  
Dose Dependent

While alkaloids often exert unique pharmacological effects on animal cells, exposure of sea urchin eggs to nicotine causes polyspermy at fertilization in a dose-dependent manner. Here, we studied molecular mechanisms underlying the phenomenon. Although nicotine is an agonist of ionotropic acetylcholine receptors, we found that nicotine-induced polyspermy was neither mimicked by acetylcholine and carbachol nor inhibited by specific antagonists of nicotinic acetylcholine receptors. Unlike acetylcholine and carbachol, nicotine uniquely induced drastic rearrangement of egg cortical microfilaments in a dose-dependent way. Such cytoskeletal changes appeared to render the eggs more receptive to sperm, as judged by the significant alleviation of polyspermy by latrunculin-A and mycalolide-B. In addition, our fluorimetric assay provided the first evidence that nicotine directly accelerates polymerization kinetics of G-actin and attenuates depolymerization of preassembled F-actin. Furthermore, nicotine inhibited cofilin-induced disassembly of F-actin. Unexpectedly, our results suggest that effects of nicotine can also be mediated in some non-cholinergic pathways.

Architecture of the outer arm dynein ATPase in an avian sperm flagellum, with further evidence for the B-link

1991 ◽  
Vol 98 (1) ◽  
pp. 17-26 ◽  
Author(s):  
S.A. Burgess ◽  
S.D. Dover ◽  
D.M. Woolley
Keyword(s):  
Image Enhancement ◽  
Sea Urchin ◽  
Three Dimensional ◽  
Gallus Domesticus ◽  
Replica Technique ◽  
Thin Sections ◽  
Attachment Point ◽  
Sperm Flagellum ◽  
Head Domain ◽  
20 Nm

Demembranated sperm flagella from Gallus domesticus have been prepared by the rapid-freeze, deep-etch, rotary replica technique in order to study the three-dimensional morphology of the outer dynein arm (ODA)-ATPase complex. In general, the ODAs resemble most closely those from the sea urchin Strongylocentrotus described by W. S. Sale et al. In the ‘rigor’ condition, the ODA consists of a major subunit (the head), from which a slender link extends to the adjacent B-tubule (the B-link). A smaller, intermediate subunit lies adjacent to the head, distally, and a further extension of the complex, the minor subunit, continues distally beneath the head domain of the next arm complex, where it attaches to the A-tubule. In the presence of ATP and vanadate (‘relaxed’ condition), the attachment point of the B-link to the head is shifted to a more proximal position, and the minor subunit is no longer visible. This is interpreted as resulting from a rotation of the head. These features are demonstrated stereoscopically, and from several viewpoints. Image enhancement has been used to clarify and define the repetitive features of the dynein arrays. In addition, some of the axonemes have been imaged from highly contrasted 20 nm thin sections; the detection of B-links in such sections means that these slender structures cannot be considered artefacts of the rapid-freeze, deep-etch protocol.

scholarly journals CpG island mapping of a mouse double-minute chromosome.

1993 ◽  
Vol 13 (8) ◽  
pp. 4459-4464 ◽  
Author(s):  
J L Beland ◽  
J A Longo ◽  
P J Hahn
Keyword(s):  
Cell Line ◽  
Long Range ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Single Copy ◽  
Restriction Map ◽  
Chromosomal Dna ◽  
Dhfr Gene ◽  
Range Restriction ◽  
Double Minute

The development of double-minute chromosomes (DMs) and subsequent gene amplification are important genomic alterations resulting in increased oncogene expression in a variety of tumors. The molecular mechanisms mediating the development of these acentric extrachromosomal elements have not been completely defined. To elucidate the mechanisms involved in DM formation, we have developed strategies to map amplified circular DM DNA. In this study, we present a long-range restriction map of a 980-kb DM. A cell line cloned from mouse EMT-6 cells was developed by stepwise selection for resistance to methotrexate. This cloned cell line contains multiple copies of the 980-kb DM carrying the dihydrofolate reductase (DHFR) gene. A long-range restriction map was developed in which a hypomethylated CpG-rich region near the DHFR gene served as a landmark. This strategy was combined with plasmid-like analysis of ethidium bromide-stained pulsed-field gels and indicated that a single copy of the DHFR gene was located near a hypomethylated region containing SsII and NotI sites. At least 490 kb of this DM appears to be composed of unrearranged chromosomal DNA.

scholarly journals Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis

2019 ◽  
Author(s):  
Nurbubu T. Moldogazieva ◽  
Daria S. Ostroverkhova ◽  
Nikolai N. Kuzmich ◽  
Vladimir V. Kadochnikov ◽  
Alexander A. Terentiev ◽  
...  
Keyword(s):  
Binding Sites ◽  
In Silico ◽  
Disulfide Bonds ◽  
Electrostatic Interactions ◽  
Molecular Mechanisms ◽  
3D Structure ◽  
Scoring Function ◽  
Alpha Fetoprotein ◽  
Ligand Interaction ◽  
Ligand Interactions

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔGbind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

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