scholarly journals Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis

2021 ◽  
Vol 23 (1) ◽  
pp. 310
Author(s):  
Chiara Scapoli ◽  
Nicole Ziliotto ◽  
Barbara Lunghi ◽  
Erica Menegatti ◽  
Fabrizio Salvi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Candidate Gene ◽  
Transcriptome Analysis ◽  
Jugular Vein ◽  
Low Frequency ◽  
Genome Project ◽  
Biological Processes ◽  
Gene Products ◽  
Transmission Of Disease ◽  
Disease Pathways

Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.

scholarly journals Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8357 ◽  
Author(s):  
Zhenwei Shang ◽  
Wenjing Sun ◽  
Mingming Zhang ◽  
Lidan Xu ◽  
Xueyuan Jia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Candidate Genes ◽  
Mononuclear Cells ◽  
Biological Processes ◽  
Peripheral Blood Mononuclear ◽  
Protein Protein Interaction ◽  
Microarray Expression ◽  
Disease Pathways ◽  
Combined Data

The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein–protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKBIA and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS.

scholarly journals Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 618
Author(s):  
Yue Jin ◽  
Shihao Li ◽  
Yang Yu ◽  
Chengsong Zhang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Underlying Mechanism ◽  
Biological Processes ◽  
Wild Type ◽  
Expression Levels ◽  
In The Wild ◽  
Cuticle Proteins ◽  
Apolipoprotein D ◽  
High Level ◽  
Lower Expression

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.

The 795CT polymorphism in osteopontin gene is not associated with multiple sclerosis in a Spanish population

2007 ◽  
Vol 13 (2) ◽  
pp. 250-252 ◽  
Author(s):  
A Mas ◽  
A Martínez ◽  
V De Las Heras ◽  
M Bartolomé ◽  
Eg De La Concha ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
Italian Population ◽  
Cytokine Network ◽  
Activated T Cells ◽  
Negative Finding ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is an inflammatory disease affecting the central nervous system. The dysregulation of the cytokine network is an important component of its pathogenesis. One of the cytokines produced by activated T-cells is osteopontin (OPN). OPN enhances the production of the pro-inflammatory cytokines, interleukin-12 and interferon-gamma, while reducing interleukin-10 levels. Therefore, OPN is considered a pro-inflammatory cytokine, and could play a key role in MS pathogenesis. The OPN gene contains several common polymorphisms, distributed in two main haplotypes, which may modulate its production or activity. A total of 326 MS patients and 484 healthy controls were typed for 795CT OPN polymorphism. In order to perform a familial study, 51 progenitor pairs were also included. No difference was found in the case-control or family study. This negative finding is inconsistent with a previous haplotype study in an Italian population, where the haplotype associated carried the low-frequency allele in position 795. In a Japanese population, a similar study yielded no association with this polymorphism. In conclusion, our data suggest that the 795 polymorphism does not play an etiological role per se and the haplotype structure may differ from one population to another. Multiple Sclerosis 2007; 13: 250–252. http://msj.sagepub.com

Transcriptome analysis reveals important candidate gene families related to oligosaccharides biosynthesis in Morinda officinalis

2021 ◽  
Vol 167 ◽  
pp. 1061-1071
Author(s):  
Mengyun Liu ◽  
Li Yang ◽  
Miaomiao Cai ◽  
Chong Feng ◽  
Zhimin Zhao ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Transcriptome Analysis ◽  
Gene Families

scholarly journals Annotating proteins with generalized functional linkages

2008 ◽  
Vol 105 (46) ◽  
pp. 17700-17705 ◽  
Author(s):  
Richard Llewellyn ◽  
David S. Eisenberg
Keyword(s):  
Protein Function ◽  
Biological Process ◽  
Computational Method ◽  
Majority Voting ◽  
Target Protein ◽  
Biological Processes ◽  
Gene Products ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Networks

As genome sequencing outstrips the rate of high-quality, low-throughput biochemical and genetic experimentation, accurate annotation of protein function becomes a bottleneck in the progress of the biomolecular sciences. Most gene products are now annotated by homology, in which an experimentally determined function is applied to a similar sequence. This procedure becomes error-prone between more divergent sequences and can contaminate biomolecular databases. Here, we propose a computational method of assignment of function, termed Generalized Functional Linkages (GFL), that combines nonhomology-based methods with other types of data. Functional linkages describe pairwise relationships between proteins that work together to perform a biological task. GFL provides a Bayesian framework that improves annotation by arbitrating a competition among biological process annotations to best describe the target protein. GFL addresses the unequal strengths of functional linkages among proteins, the quality of existing annotations, and the similarity among them while incorporating available knowledge about the cellular location or individual molecular function of the target protein. We demonstrate GFL with functional linkages defined by an algorithm known as zorch that quantifies connectivity in protein–protein interaction networks. Even when using proteins linked only by indirect or high-throughput interactions, GFL predicts the biological processes of many proteins in Saccharomyces cerevisiae, improving the accuracy of annotation by 20% over majority voting.

Identification of a candidate gene forRe, the factor determining the red leaf phenotype in ornamental kale using fine mapping and transcriptome analysis

2017 ◽  
Vol 136 (5) ◽  
pp. 738-748 ◽  
Author(s):  
Jie Ren ◽  
Wei Fu ◽  
Jiangtao Du ◽  
Ailin Hou ◽  
Zhiyong Liu ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Fine Mapping ◽  
Transcriptome Analysis ◽  
Leaf Phenotype ◽  
Ornamental Kale

scholarly journals Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study

2021 ◽  
Vol 7 (4) ◽  
pp. 205521732110615
Author(s):  
Peter Rieckmann ◽  
Robert Zivadinov ◽  
Alexey Boyko ◽  
Krzysztof Selmaj ◽  
Jessica K. Alexander ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Low Frequency ◽  
Exposure Period ◽  
Similar Efficacy ◽  
Open Label ◽  
Open Label Extension ◽  
Multiple Sclerosis Patients ◽  
Relapsing Multiple Sclerosis

Objective Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS). Methods Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered. Results Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70–0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6–0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile. Conclusions GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.

Effect of fingolimod on cardiac autonomic regulation in patients with multiple sclerosis

2015 ◽  
Vol 22 (8) ◽  
pp. 1080-1085 ◽  
Author(s):  
Sakari Simula ◽  
Tomi Laitinen ◽  
Tiina M Laitinen ◽  
Tuula Tarkiainen ◽  
Päivi Hartikainen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
High Frequency ◽  
Frequency Ratio ◽  
Low Frequency ◽  
Autonomic Regulation ◽  
Rr Interval ◽  
Cardiac Autonomic Regulation ◽  
Multiple Sclerosis Patients

Background: Fingolimod modulates sphingosine-1-phosphate receptors that are also found in cardiovascular tissue. Objective: To investigate the effects of fingolimod on cardiac autonomic regulation prospectively. Methods: Twenty-seven relapsing–remitting multiple sclerosis patients underwent 24-hour electrocardiogram recording before, at the first day of fingolimod treatment (1d) and after three months of continuous dosing (3mo). The time interval between two consecutive R-peaks (RR-interval) was measured. Cardiac autonomic regulation was assessed by the various parameters of heart rate variability. Parasympathetic stimulation prolongs the RR-interval and increases heart rate variability while the effects of sympathetic stimulation are mainly the opposite. The low frequency/high frequency ratio reflects sympathovagal balance. Results: From baseline to 1d, a prolongation of the RR-interval ( P<0.001), an increase in the values of various heart rate variability parameters ( P<0.05 to P<0.001) and a decrease in the low frequency/high frequency ratio ( P<0.05) were demonstrated. At 3mo, although the RR-interval remained longer ( P<0.01), the values of various heart rate variability parameters were lower ( P<0.01 to P<0.001) as compared to baseline. At 3mo, the low frequency/high frequency ratio ( P<0.05) was higher in men than in women although no such difference was found at baseline or at 1d. Conclusions: After an initial increase in parasympathetic regulation, continuous fingolimod dosing shifts cardiac autonomic regulation towards sympathetic predominance, especially in men. Careful follow-up of fingolimod-treated relapsing–remitting multiple sclerosis patients is warranted as sympathetic predominance associates generally with impaired outcome. ClinicalTrials.cov: NCT01704183

The Chronic Stenosis of the Internal Jugular Veins as a Cause of Multiple Sclerosis

2020 ◽  
pp. 1-6
Author(s):  
Salvatore Spagnolo ◽  
◽  
Luciano Barbato ◽  
Maria Antonietta Grasso ◽  
◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Superior Vena Cava ◽  
Jugular Vein ◽  
Superior Vena ◽  
Vena Cava ◽  
Cerebral Hypoperfusion ◽  
Jugular Veins ◽  
Venous Circulation ◽  
Clinical Pictures ◽  
The Brain

Recent perfusion-weighted imaging studies have shown that two clinical pictures characterize multiple sclerosis: intermittent focal inflammatory demyelination and diffuse progressive axonal degeneration. Their etiopathogenesis is not known. We hypothesize that a chronic obstacle to the outflow of blood from the brain can cause these two clinical pictures. We had already shown angiographically that the stenosis of the internal jugular vein causes a systemic-cerebral shunt and a reversal of the venous circulation brain and gives rise to the new circuit that directly connects the superior vena cava system to the straight sinus. This new circuit can cause the BBB to break and new plaques to form. The introduction of near-infrared spectroscopy (NIRS) in cardiac surgery has made it possible to demonstrate that obstruction of the superior vena cava is capable of causing cerebral hypoperfusion, responsible for the progressive degeneration of axons. To confirm the relationship between superior vena cava syndrome and cerebral hypoperfusion, in 35 of the152 patients with multiple sclerosis (MS) and jugular vein stenosis, operated on the plastic of jugular vein enlargement, we measured oxygen saturation in the brain. Material and Methods To measure changes in the oxygen saturation of regional brain tissue (rctSO2) before, during and after clamping the jugular veins, we applied two sensors in the left and right frontal region, and we connected them to a biosignal recorder (Invos-5100 system). Results Closing or opening the IJV produced significant changes in the rctSO2 values. Before clamping, saturations varied between 77% - 78%, while during clamping they decreased reaching values between 48% - 58% (p <0, 05). After declamping, the rctSO2 returned to its starting values. These results confirmed that obstruction of the jugular veins causes a significant reduction in rctSO2 values and cerebral hypoperfusion. Conclusions In MS patients, chronic jugular veins stenosis generates two different clinical pictures: Diffuse cerebral hypoperfusion, documented by the lowering of rctSO2. Systemic-cerebral shunt and inversion of cerebral venous circulation capable of causing a breakdown of the blood-brain barrier (BBB)

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