scholarly journals Maternal expression of the novel centrosome assembly factor Wdr8 is required for vertebrate embryonic mitosis and development

2015 ◽  
Author(s):  
Daigo Inoue ◽  
Manuel Stemmer ◽  
Thomas Thumberger ◽  
Joachim Wittbrodt ◽  
Oliver J Gruss
Keyword(s):  
Gene Knockout ◽  
The Novel ◽  
Mitotic Spindles ◽  
Centrosomal Protein ◽  
Vertebrate Embryo ◽  
Assembly Factor ◽  
Pericentriolar Material ◽  
Vertebrate Embryos ◽  
Targeted Gene Inactivation ◽  
The Stability

The assembly of the first centrosome occurs upon fertilisation when the male centrioles recruit pericentriolar material (PCM) from the egg cytoplasm. While inaccuracy in the assembly of centrosomes leads to infertility and abnormal embryogenesis, the mechanism that ensures accurate assembly in vertebrate embryos remains obscure. Here we applied a CRISPR-Cas9-mediated gene knockout to show that Wdr8, a novel centrosomal protein, is maternally essential for PCM assembly during embryonic mitoses of medaka (Oryzias latipes). Maternal/zygotic Wdr8-null (Wdr8-/-) blastomeres exhibit severe defects in PCM assembly that cause them to divide asymmetrically and develop multipolar mitotic spindles and aneuploidy. We demonstrate that Wdr8 interacts via its WD40 domains with the centriolar satellite protein SSX2IP. Strikingly, exogenously provided Wdr8 fully rescues Wdr8-/-embryos to adulthood, except in variants with mutations in the WD40 domains. This combination of targeted gene inactivation andinvivoreconstitution of the maternally essential Wdr8-SSX2IP complex reveals an essential link between maternal PCM and the stability of the zygotic genome in the early vertebrate embryo.

Novel Nanolipoidal Systems for the Management of Skin Cancer

2020 ◽  
Vol 14 (2) ◽  
pp. 108-125
Author(s):  
Apoorva Singh ◽  
Nimisha
Keyword(s):  
Skin Cancer ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
The Body ◽  
Surgical Removal ◽  
The Novel ◽  
Skin Cancers ◽  
Recent Developments ◽  
Abnormal Cells ◽  
The Stability

: Skin cancer, among the various kinds of cancers, is a type that emerges from skin due to the growth of abnormal cells. These cells are capable of spreading and invading the other parts of the body. The occurrence of non-melanoma and melanoma, which are the major types of skin cancers, has increased over the past decades. Exposure to ultraviolet radiations (UV) is the main associative cause of skin cancer. UV exposure can inactivate tumor suppressor genes while activating various oncogenes. The conventional techniques like surgical removal, chemotherapy and radiation therapy lack the potential for targeting cancer cells and harm the normal cells. However, the novel therapeutics show promising improvements in the effectiveness of treatment, survival rates and better quality of life for patients. Different methodologies are involved in the skin cancer therapeutics for delivering the active ingredients to the target sites. Nano carriers are very efficient as they have the ability to improve the stability of drugs and further enhance their penetration into the tumor cells. The recent developments and research in nanotechnology have entitled several targeting and therapeutic agents to be incorporated into nanoparticles for an enhancive treatment of skin cancer. To protect the research works in the field of nanolipoidal systems various patents have been introduced. Some of the patents acknowledge responsive liposomes for specific targeting, nanocarriers for the delivery or co-delivery of chemotherapeutics, nucleic acids as well as photosensitizers. Further recent patents on the novel delivery systems have also been included here.

Investigation of Thermochemical Hydrogen Production via the Novel Thermo-Mechanical Stabilized Iron Oxide-Zirconia Porous Structure

2013 ◽  
Author(s):  
Ayyoub M. Mehdizadeh ◽  
Kelvin Randhir ◽  
James F. Klausner ◽  
Nicholas AuYeung ◽  
Fotouh Al-Raqom ◽  
...  
Keyword(s):  
Hydrogen Production ◽  
Porous Structure ◽  
Chemical Reactivity ◽  
Thermal Reduction ◽  
The Novel ◽  
Concentrated Solar Energy ◽  
The Matrix ◽  
Unique Method ◽  
Laboratory Scale Reactor ◽  
The Stability

In this study we have developed a unique method for synthesizing very reactive water splitting materials that will remain stable at temperatures as high as 1450 °C to efficiently produce clean hydrogen from concentrated solar energy. The hydrogen production for a laboratory scale reactor using a “Thermo-mechanical Stabilized Porous Structure” (TSPS) is experimentally investigated for oxidation and thermal reduction temperatures of 1200 and 1450 °C, respectively. The stability and reactivity of a 10 g TSPS over many consecutive oxidation and thermal reduction cycles for different particle size ranges has been investigated. The novel thermo-mechanical stabilization exploits sintering and controls the geometry of the matrix of particles inside the structure in a favorable manner so that the chemical reactivity of the structure remains intact. The experimental results demonstrate that this structure yields peak hydrogen production rates of 1–2 cm3/(min.gFe3O4) during the oxidation step at 1200 °C and the 30 minute thermal reduction step at 1450 ° C without noticeable degradation over many consecutive cycles. The hydrogen production rate is one of the highest yet reported in the open literature for thermochemical looping processes using thermal reduction. This novel process has strong potential for developing an enabling technology for efficient and commercially viable solar fuel production.

scholarly journals TRIP6 functions in brain ciliogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shalmali Shukla ◽  
Ronny Haenold ◽  
Pavel Urbánek ◽  
Lucien Frappart ◽  
Shamci Monajembashi ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Super Resolution ◽  
Epithelial Cell Line ◽  
Lim Domain ◽  
Choroid Plexus Epithelial Cell ◽  
Interaction Sites ◽  
Assembly Factor ◽  
Pericentriolar Material ◽  
Choroid Plexus Epithelial

AbstractTRIP6, a member of the ZYXIN-family of LIM domain proteins, is a focal adhesion component. Trip6 deletion in the mouse, reported here, reveals a function in the brain: ependymal and choroid plexus epithelial cells are carrying, unexpectedly, fewer and shorter cilia, are poorly differentiated, and the mice develop hydrocephalus. TRIP6 carries numerous protein interaction domains and its functions require homodimerization. Indeed, TRIP6 disruption in vitro (in a choroid plexus epithelial cell line), via RNAi or inhibition of its homodimerization, confirms its function in ciliogenesis. Using super-resolution microscopy, we demonstrate TRIP6 localization at the pericentriolar material and along the ciliary axoneme. The requirement for homodimerization which doubles its interaction sites, its punctate localization along the axoneme, and its co-localization with other cilia components suggest a scaffold/co-transporter function for TRIP6 in cilia. Thus, this work uncovers an essential role of a LIM-domain protein assembly factor in mammalian ciliogenesis.

scholarly journals Proteome Integral Stability Alteration assay dramatically increases throughput and sensitivity in profiling factor-induced proteome changes

2018 ◽  
Author(s):  
Massimiliano Gaetani ◽  
Pierre Sabatier ◽  
Amir Ata Saei ◽  
Christian Beusch ◽  
Zhe Yang ◽  
...  
Keyword(s):  
Chemical Biology ◽  
Living Cells ◽  
Parameter Variation ◽  
The Novel ◽  
Factor Intensity ◽  
Unusual Behavior ◽  
Analysis Scheme ◽  
The Stability ◽  
Proteome Changes ◽  
Integral Stability

Various factors, including drugs as well as non-molecular influences, induce alterations in the stability of proteins in cell lysates, living cells and organisms. These alterations can be probed by applying a stability-modifying agent, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or factor intensity can be used. However, the corresponding analysis scheme has a low throughput and high cost. Additionally, since traditional data analysis employs curve fitting, proteins with unusual behavior are frequently ignored. The novel Proteome Integral Stability Alteration (PISA) assay avoids these issues altogether, increasing the analysis throughput by one to two orders of magnitude for unlimited number of parameter variation points. The consumption of the compound and biological material decreases by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.

scholarly journals A Yeast-Based Functional Assay to Study Plant N-Degron – N-Recognin Interactions

2022 ◽  
Vol 12 ◽  
Author(s):  
Aida Kozlic ◽  
Nikola Winter ◽  
Theresia Telser ◽  
Jakob Reimann ◽  
Katrin Rose ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Functional Assay ◽  
The Novel ◽  
In Planta ◽  
Amino Terminal ◽  
Weak Binding ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Proteasome ◽  
The Stability

The N-degron pathway is a branch of the ubiquitin-proteasome system where amino-terminal residues serve as degradation signals. In a synthetic biology approach, we expressed ubiquitin ligase PRT6 and ubiquitin conjugating enzyme 2 (AtUBC2) from Arabidopsis thaliana in a Saccharomyces cerevisiae strain with mutation in its endogenous N-degron pathway. The two enzymes re-constitute part of the plant N-degron pathway and were probed by monitoring the stability of co-expressed GFP-linked plant proteins starting with Arginine N-degrons. The novel assay allows for straightforward analysis, whereas in vitro interaction assays often do not allow detection of the weak binding of N-degron recognizing ubiquitin ligases to their substrates, and in planta testing is usually complex and time-consuming.

Biochemical and Biophysical characterization of the main protease, 3-chymotrypsin-like protease (3CLpro), from the novel coronavirus disease 19 (COVID-19)

2020 ◽  
Author(s):  
Juliana C. Ferreira ◽  
Wael M. Rabeh
Keyword(s):  
Antiviral Drug ◽  
Analytical Techniques ◽  
The Novel ◽  
Buffer Solution ◽  
Biophysical Characterization ◽  
Main Protease ◽  
Wide Ph Range ◽  
The Stability ◽  
Ph Range ◽  
Novel Coronavirus

Abstract Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19). An appealing antiviral drug target is the coronavirus 3C-like protease (3CLpro) that is responsible for the processing of the viral polyproteins and liberation of functional proteins essential for the maturation and infectivity of the virus. In this study, multiple thermal analytical techniques have been implemented to acquire the thermodynamic parameters of 3CLpro at different buffer conditions. 3CLpro exhibited relatively high thermodynamic stabilities over a wide pH range; however, the protease was found to be less stable in the presence of salts. Divalent metal cations reduced the thermodynamic stability of 3CLpro more than monovalent cations; however, altering the ionic strength of the buffer solution did not alter the stability of 3CLpro. Furthermore, the most stable thermal kinetic stability of 3CLpro was recorded at pH 7.5, with the highest enthalpy of activation calculated from the slope of Eyring plot. The biochemical and biophysical properties of 3CLpro explored here will improve the solubility and stability of 3CLpro for optimum conditions for the setup of an enzymatic assay for the screening of inhibitors to be used as lead candidates in the drug discovery and antiviral design for therapeutics against COVID-19.

Targeting complex plutonium oxides by combining crystal chemical reasoning with density-functional theory calculations: the quaternary plutonium oxide Cs2PuSi6O15

2020 ◽  
Vol 56 (66) ◽  
pp. 9501-9504
Author(s):  
Kristen A. Pace ◽  
Vladislav V. Klepov ◽  
Matthew S. Christian ◽  
Gregory Morrison ◽  
Travis K. Deason ◽  
...  
Keyword(s):  
Density Functional Theory ◽  
Crystal Growth ◽  
Dft Calculations ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Crystal Chemical ◽  
The Novel ◽  
Functional Theory ◽  
The Stability ◽  
Chemical Reasoning

The stability of the novel Pu(iv) silicate, Cs2PuSi6O15, was predicted from a combination of crystal chemical reasoning and DFT calculations and confirmed by its synthesis via flux crystal growth.

Study on the performance of gas foil journal bearings with bump-type shim foil

2020 ◽  
pp. 135065012096900
Author(s):  
Hongyang Hu ◽  
Ming Feng ◽  
Tianming Ren
Keyword(s):  
Dynamic Stability ◽  
Load Capacity ◽  
Practical Interest ◽  
Journal Bearings ◽  
Working Environment ◽  
Foil Thickness ◽  
The Novel ◽  
Improvement Potential ◽  
Stiffness Model ◽  
The Stability

The upscaling of turbomachinery using gas foil journal bearings (GFJBs) is limited because of their limited load capacity and dynamic stability. The improvement potential of shim foil inserted under the bump foil of such bearings is investigated in terms of better bearing performance. The arch height difference Δ hb between the shim foil and bump foil can be zero or not to attain the different effect. By considering the local hardening structural stiffness and an Initial installation clearance due to the shim foil, the static and dynamic characteristics of the novel bearing were calculated through the finite difference method (FDM) and perturbation method, respectively. In the analysis, a modified bump stiffness model considering the variable foil thickness was established, and a 2 D thick plate model was adopted for the top foil. The characteristics of novel GFJB with and without preload were compared with the traditional bearing. The results indicate that the load capacity and direct stiffness of the novel GFJB with shim foil can be increased largely, especially when there is a preload (Δ hb≠0). And the improvement is reinforced as the increment of Δ hb. Moreover, the stability threshold speed ( STS) of rotor supported by the novel GFJBs is enhanced by the preload, which means better stability. In addition, an air compressor test has also been conducted to verify the improved supporting performance of novel bearings. Based on this study it is convinced that the addition of shim foil under a GFJB's bump foil can be of practical interest in the quest of enhanced load capacity and dynamic stability. Moreover, the installation of shim foil is not affected by the working environment and could even be retrofited on the existing GFJBs.

scholarly journals Stability Analysis for Discrete-Time Stochastic Fuzzy Neural Networks with Mixed Delays

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
YaJun Li ◽  
Quanxin Zhu
Keyword(s):  
Neural Networks ◽  
Discrete Time ◽  
Sufficient Conditions ◽  
Fuzzy Neural Networks ◽  
Linear Matrix ◽  
Mixed Delays ◽  
The Novel ◽  
Free Weight ◽  
Fuzzy Neural ◽  
The Stability

This paper is concerned with the stability problem of a class of discrete-time stochastic fuzzy neural networks with mixed delays. New Lyapunov-Krasovskii functions are proposed and free weight matrices are introduced. The novel sufficient conditions for the stability of discrete-time stochastic fuzzy neural networks with mixed delays are established in terms of linear matrix inequalities (LMIs). Finally, numerical examples are given to illustrate the effectiveness and benefits of the proposed method.

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