scholarly journals Extremophile – An Adaptive Strategy for Extreme Conditions and Applications

2020 ◽  
Vol 21 (2) ◽  
pp. 96-110 ◽  
Author(s):  
Isha Kohli ◽  
Naveen C. Joshi ◽  
Swati Mohapatra ◽  
Ajit Varma
Keyword(s):  
Molecular Mechanisms ◽  
Adaptive Strategy ◽  
Temperature Tolerance ◽  
Extreme Conditions ◽  
Structural Genomic ◽  
Genomic Features ◽  
The Stability ◽  
Harsh Conditions ◽  
Enhanced Stability ◽  
Extremes Of Temperature

The concurrence of microorganisms in niches that are hostile like extremes of temperature, pH, salt concentration and high pressure depends upon novel molecular mechanisms to enhance the stability of their proteins, nucleic acids, lipids and cell membranes. The structural, physiological and genomic features of extremophiles that make them capable of withstanding extremely selective environmental conditions are particularly fascinating. Highly stable enzymes exhibiting several industrial and biotechnological properties are being isolated and purified from these extremophiles. Successful gene cloning of the purified extremozymes in the mesophilic hosts has already been done. Various extremozymes such as amylase, lipase, xylanase, cellulase and protease from thermophiles, halothermophiles and psychrophiles are of industrial interests due to their enhanced stability at forbidding conditions. In this review, we made an attempt to point out the unique features of extremophiles, particularly thermophiles and psychrophiles, at the structural, genomic and proteomic levels, which allow for functionality at harsh conditions focusing on the temperature tolerance by them.

RPS24c Isoform Facilitates Tumor Angiogenesis Via Promoting the Stability of MVIH in Colorectal Cancer

2020 ◽  
Vol 20 (5) ◽  
pp. 388-395 ◽  
Author(s):  
Yue Wang ◽  
Youjun Wu ◽  
Kun Xiao ◽  
Yingjie Zhao ◽  
Gang Lv ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Protein ◽  
Real Time ◽  
Tumor Angiogenesis ◽  
Real Time Pcr ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Binding Interaction ◽  
Tubule Formation ◽  
The Stability

Background: Colorectal cancer (CRC) is the second leading cause of death worldwide, and distant metastasis is responsible for the poor prognosis in patients with advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple transcript variant encoding different isoforms have been found for this gene. Our previous studies have demonstrated that RPS24 is overexpressed in CRC. However, the mechanisms underlying the role of RPS24 in tumor development have not been fully defined. Methods: Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell lines were quantified by real-time PCR or western blotting assay. Endothelial tube formation assay was performed to determine the effect of RPS24 on tumor angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the migration and invasion ability of HUVEC were detected by transwell assay. PGK1 secretion was tested with a specific ELISA kit. Results: Here, we found that RPS24c isoform was a major contributor to tumor angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are present in both normal and CRC tissues with no statistical difference. Moreover the change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore, we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule formation, HUVEC cell proliferation and migration. Additionally, we investigated the molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA MVIH, the binding-interaction enhanced the stability of each other, thereby activated angiogenesis by inhibiting the secretion of PGK1. Conclusion: RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1 pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in CRC.

scholarly journals Improving the Stability of α-CsPbI3 Nanocrystals in Extreme Conditions Facilitated by Mn2+ Doping

ACS Omega ◽  
2021 ◽  
Author(s):  
Yu Ji ◽  
Jian-Bin Zhang ◽  
Hao-Ran Shen ◽  
Zhan Su ◽  
Hao Cui ◽  
...  
Keyword(s):  
Extreme Conditions ◽  
The Stability

scholarly journals Molecular mechanisms for microtubule length regulation by kinesin-8 and XMAP215 proteins

2014 ◽  
Vol 4 (6) ◽  
pp. 20140031 ◽  
Author(s):  
Louis Reese ◽  
Anna Melbinger ◽  
Erwin Frey
Keyword(s):  
Molecular Motors ◽  
Molecular Mechanisms ◽  
Molecular Motor ◽  
Mutual Exclusion ◽  
High Growth ◽  
Dependent Manner ◽  
Dynamic Regulation ◽  
Filament Dynamics ◽  
Length Regulation ◽  
The Stability

The cytoskeleton is regulated by a plethora of enzymes that influence the stability and dynamics of cytoskeletal filaments. How microtubules (MTs) are controlled is of particular importance for mitosis, during which dynamic MTs are responsible for proper segregation of chromosomes. Molecular motors of the kinesin-8 protein family have been shown to depolymerize MTs in a length-dependent manner, and recent experimental and theoretical evidence suggests a possible role for kinesin-8 in the dynamic regulation of MTs. However, so far the detailed molecular mechanisms of how these molecular motors interact with the growing MT tip remain elusive. Here we show that two distinct scenarios for the interactions of kinesin-8 with the MT tip lead to qualitatively different MT dynamics, including accurate length control as well as intermittent dynamics. We give a comprehensive analysis of the regimes where length regulation is possible and characterize how the stationary length depends on the biochemical rates and the bulk concentrations of the various proteins. For a neutral scenario, where MTs grow irrespective of whether the MT tip is occupied by a molecular motor, length regulation is possible only for a narrow range of biochemical rates, and, in particular, limited to small polymerization rates. By contrast, for an inhibition scenario, where the presence of a motor at the MT tip inhibits MT growth, the regime where length regulation is possible is extremely broad and includes high growth rates. These results also apply to situations where a polymerizing enzyme like XMAP215 and kinesin-8 mutually exclude each other from the MT tip. Moreover, we characterize the differences in the stochastic length dynamics between the two scenarios. While for the neutral scenario length is tightly controlled, length dynamics is intermittent for the inhibition scenario and exhibits extended periods of MT growth and shrinkage. On a broader perspective, the set of models established in this work quite generally suggest that mutual exclusion of molecules at the ends of cytoskeletal filaments is an important factor for filament dynamics and regulation.

scholarly journals Advances in 5-Aminolevulinic Acid Priming to Enhance Plant Tolerance to Abiotic Stress

2022 ◽  
Vol 23 (2) ◽  
pp. 702
Author(s):  
Shuya Tan ◽  
Jie Cao ◽  
Xinli Xia ◽  
Zhonghai Li
Keyword(s):  
Abiotic Stresses ◽  
Nitrogen Assimilation ◽  
Molecular Mechanisms ◽  
Aminolevulinic Acid ◽  
Adaptive Strategy ◽  
Forward Genetics ◽  
Plant Tolerance ◽  
Biotic And Abiotic Stresses ◽  
Defense Priming ◽  
Made In

Priming is an adaptive strategy that improves plant defenses against biotic and abiotic stresses. Stimuli from chemicals, abiotic cues, and pathogens can trigger the establishment of priming state. Priming with 5-aminolevulinic acid (ALA), a potential plant growth regulator, can enhance plant tolerance to the subsequent abiotic stresses, including salinity, drought, heat, cold, and UV-B. However, the molecular mechanisms underlying the remarkable effects of ALA priming on plant physiology remain to be elucidated. Here, we summarize recent progress made in the stress tolerance conferred by ALA priming in plants and provide the underlying molecular and physiology mechanisms of this phenomenon. Priming with ALA results in changes at the physiological, transcriptional, metabolic, and epigenetic levels, and enhances photosynthesis and antioxidant capacity, as well as nitrogen assimilation, which in turn increases the resistance of abiotic stresses. However, the signaling pathway of ALA, including receptors as well as key components, is currently unknown, which hinders the deeper understanding of the defense priming caused by ALA. In the future, there is an urgent need to reveal the molecular mechanisms by which ALA regulates plant development and enhances plant defense with the help of forward genetics, multi-omics technologies, as well as genome editing technology.

scholarly journals Extremophilic Prokaryotic Endoxylanases: Diversity, Applicability, and Molecular Insights

2021 ◽  
Vol 12 ◽  
Author(s):  
Digvijay Verma
Keyword(s):  
Molecular Mechanisms ◽  
Good Choice ◽  
Industrial Processes ◽  
Low Molecular Weight ◽  
Short Life Span ◽  
Functional Attributes ◽  
Extreme Behavior ◽  
Harsh Conditions ◽  
Free Activity ◽  
Better Than

Extremophilic endoxylanases grabbed attention in recent years due to their applicability under harsh conditions of several industrial processes. Thermophilic, alkaliphilic, and acidophilic endoxylanases found their employability in bio-bleaching of paper pulp, bioconversion of lignocellulosic biomass into xylooligosaccharides, bioethanol production, and improving the nutritious value of bread and other bakery products. Xylanases obtained from extremophilic bacteria and archaea are considered better than fungal sources for several reasons. For example, enzymatic activity under broad pH and temperature range, low molecular weight, cellulase-free activity, and longer stability under extreme conditions of prokaryotic derived xylanases make them a good choice. In addition, a short life span, easy cultivation/harvesting methods, higher yield, and rapid DNA manipulations of bacterial and archaeal cells further reduces the overall cost of the product. This review focuses on the diversity of prokaryotic endoxylanases, their characteristics, and their functional attributes. Besides, the molecular mechanisms of their extreme behavior have also been presented here.

scholarly journals Making of fusion genes in cancer: An in-silico study of mechanism of chromosomal translocations

2018 ◽  
Author(s):  
Kiran Lalwani ◽  
Shivani Sheth ◽  
Inayatullah Sheikh ◽  
Afzal Ansari ◽  
Fulesh Kunwar ◽  
...  
Keyword(s):  
Dna Sequences ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Fusion Gene ◽  
Genetic Material ◽  
Chromosomal Translocations ◽  
In Silico Study ◽  
Clinical Consequences ◽  
The Stability ◽  
Genomic Regions

Chromosomal translocations involve exchange of genetic material between non- homologous chromosomes leading to the formation of a fusion gene with altered function. The clinical consequences of non-random and recurrent chromosomal translocations have been so well understood in carcinogenesis that they serve as diagnostic and prognostic markers and also help in therapy decisions, mainly in leukemia and lymphoma. However, the molecular mechanisms underlying these recurrent genetic exchanges are yet to be understood. Various approaches employed include the extent of the vicinity of the partner chromosomes in the nucleus, DNA sequences at the breakpoints, etc. The present study addresses the stability of DNA sequences at the breakpoint regions using in-silico approach in terms of physicochemical properties such as; AT%, flexibility, melting temperature, enthalpy, entropy, stacking energy and free energy. Changes in these properties may lead to instability of DNA which could affect gene expression in particular and genome organization in general. Our study indicates that the fusion sequences are comparatively more unstable and hence, more prone to breakage. Current study along with others could lead to developing a model for predicting breakage prone genomic regions using this novel in-silico approach.

scholarly journals Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiangyue Zhou ◽  
Youwei Li ◽  
Cameron Lenahan ◽  
Yibo Ou ◽  
Minghuan Wang ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Glymphatic System ◽  
System A ◽  
Function Recovery ◽  
The Central Nervous System ◽  
The Stability ◽  
The Brain

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

scholarly journals Dissecting Molecular Determinants of Mutational Escape Mechanisms in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Atomistic Simulations and Ensemble-Based Deep Mutational Scanning of Protein Stability and Binding Interactions

2021 ◽  
Author(s):  
Gennady Verkhivker ◽  
Steve Agajanian ◽  
Deniz Yasar Oztas ◽  
Grace Gupta
Keyword(s):  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Conformational Dynamics ◽  
Spike Protein ◽  
Atomistic Simulations ◽  
Binding Interactions ◽  
Mutational Profiling ◽  
Neutralizing Capacity ◽  
The Stability ◽  
Protein Response

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

Calcineurin regulates the stability and activity of estrogen receptor α

2021 ◽  
Vol 118 (44) ◽  
pp. e2114258118
Author(s):  
Takahiro Masaki ◽  
Makoto Habara ◽  
Yuki Sato ◽  
Takahiro Goshima ◽  
Keisuke Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
The Stability ◽  
Positive Breast Cancer

Estrogen receptor α (ER-α) mediates estrogen-dependent cancer progression and is expressed in most breast cancer cells. However, the molecular mechanisms underlying the regulation of the cellular abundance and activity of ER-α remain unclear. We here show that the protein phosphatase calcineurin regulates both ER-α stability and activity in human breast cancer cells. Calcineurin depletion or inhibition down-regulated the abundance of ER-α by promoting its polyubiquitination and degradation. Calcineurin inhibition also promoted the binding of ER-α to the E3 ubiquitin ligase E6AP, and calcineurin mediated the dephosphorylation of ER-α at Ser294 in vitro. Moreover, the ER-α (S294A) mutant was more stable and activated the expression of ER-α target genes to a greater extent compared with the wild-type protein, whereas the extents of its interaction with E6AP and polyubiquitination were attenuated. These results suggest that the phosphorylation of ER-α at Ser294 promotes its binding to E6AP and consequent degradation. Calcineurin was also found to be required for the phosphorylation of ER-α at Ser118 by mechanistic target of rapamycin complex 1 and the consequent activation of ER-α in response to β-estradiol treatment. Our study thus indicates that calcineurin controls both the stability and activity of ER-α by regulating its phosphorylation at Ser294 and Ser118. Finally, the expression of the calcineurin A–α gene (PPP3CA) was associated with poor prognosis in ER-α–positive breast cancer patients treated with tamoxifen or other endocrine therapeutic agents. Calcineurin is thus a promising target for the development of therapies for ER-α–positive breast cancer.

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