scholarly journals Conserved expression of alternative splicing variants of peroxisomal acyl-CoA oxidase 1 in vertebrates and developmental and nutritional regulation in fish

2007 ◽  
Vol 28 (3) ◽  
pp. 239-252 ◽  
Author(s):  
Sofia Morais ◽  
Anja Knoll-Gellida ◽  
Michèle André ◽  
Christophe Barthe ◽  
Patrick J. Babin
Keyword(s):  
Alternative Splicing ◽  
Early Stage ◽  
Acyl Chain ◽  
Amino Acid Sequences ◽  
Fatty Acyl Chain ◽  
Nutritional Regulation ◽  
Vertebrate Lineage ◽  
Anterior Intestine ◽  
Acyl Coa Oxidase ◽  
The Brain

The acyl-coenzyme A oxidase 1 (ACOX1) catalyzes the first, rate-limiting step in peroxisomal β-oxidation of medium to very long straight-chain fatty acids. Zebrafish ( Danio rerio) acox1 was characterized and compared with homologs from other sequenced genomes, revealing a remarkable conservation of structure in the vertebrate lineage. Strictly conserved regions of the deduced proteins included acyl-CoA oxidase and FAD binding domains, as well as a COOH-terminal peroxisomal targeting signal. Whole mount in situ hybridization showed that zebrafish acox1 transcripts were diffusely distributed in early-stage embryonic cells, then discreetly expressed in the brain and widely present in the liver and intestine at later stages. An evolutionarily conserved alternative splicing of the corresponding acox1 primary transcript was identified in teleosts and tetrapods including mammals, giving rise, after exon skipping, to two splice variants, ACOX1–3I and ACOX1–3II. Real-time quantitative RT-PCR on zebrafish adult tissues indicated high levels of both variants in the liver, anterior intestine, and to a lesser extent, in the brain. However, the ACOX1–3II transcript variant was expressed seven times more in zebrafish brain than the ACOX1–3I variant. These data suggest a tissue-specific modulation of ACOX1 activity by exchanging exon 3 duplicated isoforms containing amino acid sequences that are potentially implicated in fatty acyl chain specificity. In addition, a significant pretranslational up-regulation of zebrafish and rainbow trout ( Oncorhynchus mykiss) acox1 expression was observed in the anterior intestine after feeding. Taken together, these data indicate that ACOX1 alternative splicing isoforms play a key conserved role in the vertebrate fatty acid metabolism.

Gene expression analysis in modeling Parkinson’s disease

2020 ◽  
pp. 103-104
Author(s):  
М.М. Руденок ◽  
А.Х. Алиева ◽  
А.А. Колачева ◽  
М.В. Угрюмов ◽  
П.А. Сломинский ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Systemic Disease ◽  
Molecular Genetic ◽  
Presymptomatic Stage ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome ◽  
The Brain ◽  
Transcriptome Level

Несмотря на очевидный прогресс, достигнутый в изучении молекулярно-генетических факторов и механизмов патогенеза болезни Паркинсона (БП), в настоящее время стало ясно, что нарушения в структуре ДНК не описывают весь спектр патологических изменений, наблюдаемых при развитии заболевания. В настоящее время показано, что существенное влияние на патогенез БП могут оказывать изменения на уровне транскриптома. В работе были использованы мышиные модели досимптомной стадии БП, поздней досимптомной и ранней симптомной (РСС) стадиями БП. Для полнотранскриптомного анализа пулов РНК тканей черной субстанции и стриатума мозга мышей использовались микрочипы MouseRef-8 v2.0 Expression BeadChip Kit («Illumina», США). Полученные данные указывают на последовательное вовлечение транскриптома в патогенез БП, а также на то, что изменения на транскриптомном уровне процессов транспорта и митохондриального биогенеза могут играть важную роль в нейродегенерации при БП уже на самых ранних этапах. Parkinson’s disease (PD) is a complex systemic disease, mainly associated with the death of dopaminergic neurons. Despite the obvious progress made in the study of molecular genetic factors and mechanisms of PD pathogenesis, it has now become clear that violations in the DNA structure do not describe the entire spectrum of pathological changes observed during the development of the disease. It has now been shown that changes at the transcriptome level can have a significant effect on the pathogenesis of PD. The authors used models of the presymptomatic stage of PD with mice decapitation after 6 hours (6 h-PSS), presymptomatic stage with decapitation after 24 hours (24 h-PSS), advanced presymptomatic (Adv-PSS) and early symptomatic (ESS) stages of PD. For whole transcriptome analysis of RNA pools of the substantia nigra and mouse striatum, the MouseRef-8 v2.0 Expression BeadChip Kit microchips (Illumina, USA) were used. As a result of the analysis of whole transcriptome data, it was shown that, there are a greater number of statistically significant changes in the tissues of the brain and peripheral blood of mice with Adv-PSS and ESS models of PD compared to 6 h-PSS and 24 h-PSS models. In general, the obtained data indicate the sequential involvement of the transcriptome in the pathogenesis of PD, as well as the fact that changes at the transcriptome level of the processes of transport and mitochondrial biogenesis can play an important role in neurodegeneration in PD at an early stage.

Brain Tumor Detection via Asymmetry Quantification across Mid Sagittal Plane

2020 ◽  
Vol 13 ◽  
Author(s):  
Shoaib Amin Banday ◽  
Mohammad Khalid Pandit
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Sagittal Plane ◽  
Early Stage ◽  
Imaging Techniques ◽  
Complex Structure ◽  
Magnetic Resonance Images ◽  
Absolute Difference ◽  
Brain Hemispheres ◽  
The Brain

Introduction: Brain tumor is among the major causes of morbidity and mortality rates worldwide. According to National Brain Tumor Foundation (NBTS), the death rate has nearly increased by as much as 300% over last couple of decades. Tumors can be categorized as benign (non-cancerous) and malignant (cancerous). The type of the brain tumor significantly depends on various factors like the site of its occurrence, its shape, the age of the subject etc. On the other hand, Computer Aided Detection (CAD) has been improving significantly in recent times. The concept, design and implementation of these systems ascend from fairly simple ones to computationally intense ones. For efficient and effective diagnosis and treatment plans in brain tumor studies, it is imperative that an abnormality is detected at an early stage as it provides a little more time for medical professionals to respond. The early detection of diseases has predominantly been possible because of medical imaging techniques developed from past many decades like CT, MRI, PET, SPECT, FMRI etc. The detection of brain tumors however, has always been a challenging task because of the complex structure of the brain, diverse tumor sizes and locations in the brain. Method: This paper proposes an algorithm that can detect the brain tumors in the presence of the Radio-Frequency (RF) inhomoginiety. The algorithm utilizes the Mid Sagittal Plane as a landmark point across which the asymmetry between the two brain hemispheres is estimated using various intensity and texture based parameters. Result: The results show the efficacy of the proposed method for the detection of the brain tumors with an acceptable detection rate. Conclusion: In this paper, we have calculated three textural features from the two hemispheres of the brain viz: Contrast (CON), Entropy (ENT) and Homogeneity (HOM) and three parameters viz: Root Mean Square Error (RMSE), Correlation Co-efficient (CC), and Integral of Absolute Difference (IAD) from the intensity distribution profiles of the two brain hemispheres to predict any presence of the pathology. First a Mid Sagittal Plane (MSP) is obtained on the Magnetic Resonance Images that virtually divides brain into two bilaterally symmetric hemispheres. The block wise texture asymmetry is estimated for these hemispheres using the above 6 parameters.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

Fatty acyl chain structure, orientational order, and the lipid phase transition in Acholeplasma laidlawii B membranes. A review of recent 19F nuclear magnetic resonance studies

1984 ◽  
Vol 62 (11) ◽  
pp. 1134-1150 ◽  
Author(s):  
P. M. Macdonald ◽  
B. D. Sykes ◽  
R. N. McElhaney
Keyword(s):  
Phase Transition ◽  
Fatty Acids ◽  
Nuclear Magnetic Resonance ◽  
Acyl Chain ◽  
Orientational Order ◽  
Membrane Lipid ◽  
Fatty Acyl ◽  
Fatty Acyl Chain ◽  
Lipid Phase ◽  
Lipid Phase Transition

The orientational order parameters of monofluoropalmitic acids biosynthetically incorporated into membranes of Acholeplasma laidlawii B in the presence of a large excess of a variety of structurally diverse fatty acids have been determined via 19F nuclear magnetic resonance (19F NMR) spectroscopy. It is demonstrated that these monofluoropalmitic acids are relatively nonperturbing membrane probes based upon physical (differential scanning calorimetry), biochemical (membrane lipid analysis), and biological (growth studies) criteria. 19F NMR is shown to convey the same qualitative and quantitative picture of membrane lipid order provided by 2H-NMR techniques and to be sensitive to the structural characteristics of the membrane fatty acyl chains, as well as to the lipid phase transition. Representatives of each naturally occurring class of fatty acyl chain structures, including straight-chain saturated, methyl-branched, monounsaturated, and alicyclic-ring-substituted fatty acids, were studied and the 19F-NMR order parameters were correlated with the lipid phase transitions (determined calorimetrically). The lipid phase transition was the prime determinant of overall orientational order regardless of fatty acid structure. Effects upon orientational order attributable to specific structural substituents were discernible, but were secondary to the effects of the lipid phase transition. In the gel state, relative overall order was directly proportional to the temperature of the particular lipid phase transition. Not only the overall order, but also the order profile across the membrane was sensitive to the presence of particular structural substituents. In particular, in the gel state specific fatty acyl structures demonstrated a characteristic disordering effect in the membrane order profile. These various observations can be merged to provide a unified picture of the manner in which fatty acyl chain chemistry modulates the physical state of membrane lipids.

scholarly journals The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Annette Brandel ◽  
Sahaja Aigal ◽  
Simon Lagies ◽  
Manuel Schlimpert ◽  
Ana Valeria Meléndez ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Plasma Membrane ◽  
Host Cell ◽  
Acyl Chain ◽  
Mass Spectrometry Analysis ◽  
Bacterial Invasion ◽  
Fatty Acyl Chain ◽  
Membrane Domain ◽  
Host Cell Membrane ◽  
Plasma Membrane Domain

AbstractThe opportunistic pathogen Pseudomonas aeruginosa has gained precedence over the years due to its ability to develop resistance to existing antibiotics, thereby necessitating alternative strategies to understand and combat the bacterium. Our previous work identified the interaction between the bacterial lectin LecA and its host cell glycosphingolipid receptor globotriaosylceramide (Gb3) as a crucial step for the engulfment of P. aeruginosa via the lipid zipper mechanism. In this study, we define the LecA-associated host cell membrane domain by pull-down and mass spectrometry analysis. We unraveled a predilection of LecA for binding to saturated, long fatty acyl chain-containing Gb3 species in the extracellular membrane leaflet and an induction of dynamic phosphatidylinositol (3,4,5)-trisphosphate (PIP3) clusters at the intracellular leaflet co-localizing with sites of LecA binding. We found flotillins and the GPI-anchored protein CD59 not only to be an integral part of the LecA-interacting membrane domain, but also majorly influencing bacterial invasion as depletion of either of these host cell proteins resulted in about 50% reduced invasiveness of the P. aeruginosa strain PAO1. In summary, we report that the LecA-Gb3 interaction at the extracellular leaflet induces the formation of a plasma membrane domain enriched in saturated Gb3 species, CD59, PIP3 and flotillin thereby facilitating efficient uptake of PAO1.

scholarly journals The Role of Ceramide Metabolism and Signaling in the Regulation of Mitophagy and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2475
Author(s):  
Megan Sheridan ◽  
Besim Ogretmen
Keyword(s):  
Cancer Therapy ◽  
Acyl Chain ◽  
Fatty Acyl ◽  
Fatty Acyl Chain ◽  
Cancer Cell Proliferation ◽  
Bioactive Lipids ◽  
Cellular Functions ◽  
Proliferation Response ◽  
Ceramide Synthases

Sphingolipids are bioactive lipids responsible for regulating diverse cellular functions such as proliferation, migration, senescence, and death. These lipids are characterized by a long-chain sphingosine backbone amide-linked to a fatty acyl chain with variable length. The length of the fatty acyl chain is determined by specific ceramide synthases, and this fatty acyl length also determines the sphingolipid’s specialized functions within the cell. One function in particular, the regulation of the selective autophagy of mitochondria, or mitophagy, is closely regulated by ceramide, a key regulatory sphingolipid. Mitophagy alterations have important implications for cancer cell proliferation, response to chemotherapeutics, and mitophagy-mediated cell death. This review will focus on the alterations of ceramide synthases in cancer and sphingolipid regulation of lethal mitophagy, concerning cancer therapy.

scholarly journals The Role of Catalase-Peroxidase Secreted by Magnaporthe oryzae During Early Infection of Rice Cells

2011 ◽  
Vol 24 (2) ◽  
pp. 163-171 ◽  
Author(s):  
Shigeru Tanabe ◽  
Naoko Ishii-Minami ◽  
Ken-Ichiro Saitoh ◽  
Yuko Otake ◽  
Hanae Kaku ◽  
...  
Keyword(s):  
Culture Filtrate ◽  
Magnaporthe Oryzae ◽  
Early Stage ◽  
Major Gene ◽  
Leaf Sheath ◽  
Epidermal Cells ◽  
Amino Acid Sequences ◽  
Conidial Suspension ◽  
Catalase Peroxidase

The biological role of a secretory catalase of the rice blast fungus Magnaporthe oryzae was studied. The internal amino acid sequences of the partially purified catalase in the culture filtrate enabled us to identify its encoding gene as a catalase-peroxidase gene, CPXB, among four putative genes for catalase or catalase-peroxidase in M. oryzae. Knockout of the gene drastically reduced the level of catalase activity in the culture filtrate and supernatant of conidial suspension (SCS), and increased the sensitivity to exogenously added H2O2 compared with control strains, suggesting that CPXB is the major gene encoding the secretory catalase and confers resistance to H2O2 in hyphae. In the mutant, the rate of appressoria that induced accumulation of H2O2 in epidermal cells of the leaf sheath increased and infection at early stages was delayed; however, the formation of lesions in the leaf blade was not affected compared with the control strain. These phenotypes were complimented by reintroducing the putative coding regions of CPXB driven by a constitutive promoter. These results suggest that CPXB plays a role in fungal defense against H2O2 accumulated in epidermal cells of rice at the early stage of infection but not in pathogenicity of M. oryzae.

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