| 1. |
- Aleix-Mata, Gael, et al.
(författare)
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The complete mitochondrial genome of Talpa aquitania (Talpidae; Insectivora), a mole species endemic to northern Spain and southern France
- 2020
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Ingår i: Molecular Biology Reports. - : SPRINGER. - 0301-4851 .- 1573-4978. ; 47:3, s. 2397-2403
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Tidskriftsartikel (refereegranskat)abstract
- The complete mitogenome sequence of Talpa aquitania, a recently described Talpa species, was assembled using whole-genome sequencing data. It varies in length from 16,776 to 16,846 bp, contains 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, one origin of L-strand replication, and a control region. In the control region, which varied from 1320 to 1390 bp, we identified the extended termination-associated sequence (ETAS-1 and ETAS-2) and the conserved sequence blocks (CSB-1, 2, 3, B, C, D, E, F). In addition, this region includes a 10 bp tandem repeat DNA sequence, with a variable number of repeats that suggest the existence of heteroplasmy. Phylogeny reconstructions based on Maximum Likelihood, Neighbor-joining and Bayesian inference analyses yielded phylogenies with similar topologies demonstrating that T. aquitania and T. occidentalis are sister species.
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| 2. |
- Aydemir, Esra, et al.
(författare)
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Impact of silencing eEF2K expression on the malignant properties of chordoma
- 2023
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 50:4, s. 3011-3022
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Tidskriftsartikel (refereegranskat)abstract
- Background: Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. eEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the fight against cancer. Methods: In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells. Results: Silencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. Conclusion: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.
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| 3. |
- Aykutoglu, Gurkan, et al.
(författare)
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Melatonin and vitamin E alleviate homocysteine‐induced oxidative injury and apoptosis in endothelial cells
- 2020
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 1573-4978 .- 0301-4851. ; 47:7, s. 5285-5293
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Tidskriftsartikel (refereegranskat)abstract
- A relationship exists between hyperhomocysteinemia and cardiovascular diseases, although the underlying mechanisms are still incompletely defined. One possibility involves a homocysteine (Hcy)-induced increased oxidative stress. Melatonin (Mel) and vitamin E (vitE) are important anti-oxidants. The main purpose of this study was (1) to compare the effect of treatments with Mel, vitE or both, on Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs), and (2) to investigate the underlying mechanisms. Cell proliferation assay was carried out by Water Soluble Tetrazolium-1 (WST-1) assay kit. Apoptotic index was calculated by TUNEL Assay. Anti-oxidant parameters were studied by measurement of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. mRNA and protein expression levels of apoptotic and anti-apoptotic genes and proteins were studied by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting experiments respectively. The results showed that treatments with Mel, vitE or Mel + vitE suppressed Hcy-induced cell death, with a higher efficiency for the Mel and Mel + vitE treatments. Our results suggests that the mechanisms by which these anti-oxidants protected endothelial cells include the decrease in ROS and LPO levels, an increase in cell migration, the downregulation of pro-apoptotic proteins Cas 3, Cas 9, Cyt C and Bax and the upregulation of anti-apoptotic protein Bcl 2. Collectively, these results revealed the protective role of vitE and Mel against Hcy-induced cell apoptosis, which may add insight into therapeutic approaches to Hcy-induced damages.
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| 4. |
- Bavec, Aljosa, et al.
(författare)
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Role of cysteine 341 and arginine 348 of GLP-1 receptor in G-protein coupling
- 2007
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 34:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- We have demonstrated the ability of peptides derived from the third intracellular loop of GLP-1 receptor to differently modulate activity of four different types of G-proteins overexpressed in sf9 cells. In this respect, the involvement of Cys341 in inhibition of Gs and Cys341 in activation of Gs and in inhibition of Gi1, Go, and G11, respectively, indicates their potential role in discrimination between different types of G-proteins. Moreover, these two amino acids from the third intracellular loop might represent an important novel targets for covalent modification by downstream regulators in signaling through GLP-1 receptor.
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| 5. |
- Borutinskaité, Veronika, et al.
(författare)
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alpha-Dystrobrevin distribution and association with other proteins in human promyelocytic NB4 cells treated for granulocytic differentiation
- 2011
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Ingår i: MOLECULAR BIOLOGY REPORTS. - : Springer Science Business Media. - 0301-4851 .- 1573-4978. ; 38:5, s. 3001-3011
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Tidskriftsartikel (refereegranskat)abstract
- Dystrobrevins (DBs) bind directly to dystrophin and are prominent components of the dystrophin-associated protein complex (DAPC) that links the cytoskeleton to the extracellular matrix. They are involved in brain development, synapse formation and plasticity, as well as water and ion homeostasis. However, the role of DB in non-muscular cells is not clear. In this study, we show that different alpha-dystrobrevin isoforms are present in promyelocytic leukemia (NB4) cells. Only the biggest alpha-dystrobrevin isoform (DB-alpha), which can be important for its function, was expressed in the membrane fraction of NB4 cells; the other alpha-DB isoforms were found in the hydrophilic cell fractions. Employing the immunoprecipitation and mass spectrometry, we identified novel alpha-DB-interacting proteins involved in cytoskeleton reorganization (actin, tropomyosin, gelsolin, tubulin) and signal transduction process (stathmin, prohibitin, RIBA) during proliferation and differentiation of NB4 cells. Our results suggest that alpha-DB isoforms play a central role in cytoskeleton reorganization via their multiple interactions with actin and actin-associating proteins and may participate in signal transduction process during NB4 cell granulocytic differentiation via directly and non directly associated proteins.
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| 6. |
- Borutinskaite, Veronika V, et al.
(författare)
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Histone deacetylase inhibitor BML-210 induces growth inhibition and apoptosis and regulates HDAC and DAPC complex expression levels in cervical cancer cells
- 2012
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Ingår i: Molecular Biology Reports. - : Springer Verlag (Germany). - 0301-4851 .- 1573-4978. ; 39:12, s. 10179-10186
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Tidskriftsartikel (refereegranskat)abstract
- Histone deacetylase inhibitors (HDACIs) represent a new class of targeted anti-cancer agents and different other diseases, like muscular disorders. A number of studies have shown that extracellular signal-activated kinases can target chromatin-modifying complexes directly and regulate their function. The molecular connection between the dystrophin-associated protein complex (DAPC) and chromatin has been described, by showing that NO signaling regulates histone deacetylase (HDAC) activity and influences gene expression in different cell types. In present study, we investigated HDACs changes in HeLa cells undergoing growth inhibition and apoptosis, caused by HDACI BML-210 and retinoic acid (ATRA). Cell cycle analysis indicated that HeLa cell treatment with 20 and 30 mu M concentration of BML-210 increased the proportion of cells in G0/G1 phase, and caused accumulation in subG1, indicating that the cells are undergoing apoptosis. We determined down-regulation of HDAC 1-5 and 7 after treatment with BML-210. Also, we demonstrated expression of different isoforms of alpha-dystrobrevin (alpha-DB) and other components of DAPC such as syntrophin, dystrophin, beta-dystrobrevin (beta-DB) and NOS in HeLa cells after treatments. We determined changes in protein expression level of dystrophin, NOS1, alpha- and beta-DB and in subcellular localization of alpha-DB after treatments with BML-210 and ATRA. In conclusion, these results suggest that HDACI BML-210 can inhibit cell growth and induce apoptosis in cervical cancer cells, what correlates with down-regulation of HDAC class I and II and changes in the DAPC expression levels. This can be important for identifying target proteins in DAPC signaling to HDACs, as a target of pharmacological intervention for treatment of muscular dystrophies and other diseases.
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| 7. |
- Brunius, Carl, et al.
(författare)
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Expression of hepatic 3 beta-hydroxysteroid dehydrogenase and sulfotransferase 2A1 in entire and castrated male pigs
- 2012
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 39, s. 7927-7932
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the effect of surgical (SC) and immunological castration on the steroid metabolizing enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and sulfotransferase 2A1 (SULT2A1) in male pigs. Thirty-two male pigs were divided in four groups; in one group the pigs were SC before the age of 7 days, two groups were injected with Improvac(A (R)) a vaccine against gonadotropin releasing hormone (immunological castration), while the pigs in the last group remained entire males (EMs). Immunological castration was in one group performed by vaccine injection at ages 11 and 14 weeks, while the other group received injections at ages 17 and 21 weeks. Plasma, adipose and liver tissue were collected at the time of slaughter. Plasma was analyzed for concentrations of testosterone and oestradiol. The adipose tissue was analyzed for the concentration of androstenone, while the liver tissue was analyzed for mRNA and protein expression of 3 beta-HSD and SULT2A1. Independent of method, all castrated pigs showed greater mRNA and protein expression of 3 beta-HSD and lower levels of all steroids in plasma compared with EMs. Moreover, there was a strong correlation between mRNA and protein expression of 3 beta-HSD and steroid levels. The same was not valid for expression of SULT2A1. It is concluded that steroid levels can increase expression of the steroid metabolizing enzyme 3 beta-HSD and thereby influence steroid metabolism, e.g. of androstenone.
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| 8. |
- Cardona Gomez, Maria Eugenia, et al.
(författare)
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Specific properties of shRNA-mediated CCR5 downregulation that enhance the inhibition of HIV-1 infection in combination with shRNA targeting HIV-1 rev
- 2022
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Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 49, s. 11187-11192
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with RNAi against HIV-1 transcripts efficiently inhibits viral replication but induces selection of escape mutants; therefore, the CCR5 coreceptor was suggested as an additional target. Blocking viral and host transcripts improved the antiviral effect. We have used short hairpin RNA (shRNA) targeting the human CCR5 (shCCR5) or the HIV-1 rev (shRev) transcripts to demonstrate distinctive properties of anti-CCR5 shRNA: shCCR5 induced more sustained protection than shRev; partial reduction in CCR5 expression substantially decreased HIV-1 infection, and shCCR5 performed better than shRev in the mixed shRNA-treated and untreated cultures. These observations indicate that CCR5 inhibitors should be conveniently included in HIV-1 gene silencing treatment schedules when only a certain cell fraction is protected to further reduce endogenous virus in a properly ART-treated HIV-1 infected individual.
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| 9. |
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| 10. |
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| 11. |
- Dai, QQ, et al.
(författare)
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Genetic advances in Meniere Disease
- 2023
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Ingår i: Molecular biology reports. - : Springer Science and Business Media LLC. - 1573-4978 .- 0301-4851. ; 50:3, s. 2901-2908
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Tidskriftsartikel (refereegranskat)abstract
- Meniere Disease (MD) is an idiopathic inner ear disease with complex etiology and pathogenesis, which is still unclear. With the development in gene analysis technology, the genetic research of MD has attracted extensive attention, resulting in a large number of studies on the research of the relationship between human genes and MD. This paper aims to review the studies on this topic in recent years. The studies mainly focused on the genetics of familial MD and the correlation between MD and potentially related functional genes. The results of these studies have demonstrated the complexity and diversity of the pathogenesis of MD with both genetic and epigenetic alterations, suggesting that MD might be related to inflammation, immunity, aqua and ion balance in the lymphatic fluid, virus infection, metabolism, and abnormal function of nerve conduction. The finding of rare mutations in TECTA, MYO7A and OTOG genes and other genes such as CDH23, PCDH15 and ADGRV1 in the same families suggest that the integrity of the stereocilia and their interaction with the tectorial and otolithic membranes could be involved in the pathophysiology of familial MD.
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| 12. |
- Dannaeus, Karin, et al.
(författare)
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Characterization of the mouse myeloid-associated differentiation marker (myadm) gene : Promoter analysis and protein localization
- 2005
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 32:3, s. 149-157
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic differentiation is a complex process involving many genes inducing functional changes and characteristics of different cell lineages. To understand this process, it is important to identify genes involved in lineage commitment and maturation of hematopoietic progenitor cells. Recently we isolated the novel gene MYADM which is strongly up-regulated as multipotent progenitor cells differentiate towards myeloid cells. Because it is not expressed in lymphocytes, understanding the transcriptional control of MYADM could further explain differences in gene expression between myeloid and lymphoid cells. To identify regulatory elements controlling its restricted expression, we have analyzed the 5′-flanking region of the MYADM gene. The proximal promoter was found to lack both TATA and CCAAT boxes, but contained several potential binding sites for both ubiquitous and myeloid-specific transcription factors. Maximal promoter activity was contained within 800∈bp from the tentative transcription initiation site, which was reduced as portions of the 5′-end were deleted, and completely abolished when the transcription initiation site was deleted. This promoter sequence had higher activity in myeloid cells compared to B cells, and activity was enhanced during myeloid differentiation, suggesting that we have identified the MYADM core promoter. Computer predictions had suggested MYADM to encode a protein with multiple transmembrane domains. By immunofluorescence and confocal microscopy we demonstrate that the protein is localized to the nuclear envelope and to intracytoplasmic membranes, indicating that MYADM constitutes an integral membrane protein. © Springer 2005.
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| 13. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
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Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer
- 2021
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Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 48:3, s. 2429-2436
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression.
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| 14. |
- Dida, Mulatu Geleta
(författare)
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Analysis of genetic diversity and population structure of oilseed crop noug (Guizotia abyssinica) accessions collected from Ethiopia
- 2023
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 501, s. 43-55
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Tidskriftsartikel (refereegranskat)abstract
- Background Noug is an Ethiopian indigenous oilseed crop cultivated primarily for its oil and various economic importance. Evaluating the extent of genetic diversity within and among populations is one of the most important steps in breeding and conservation measures. Thus, this study aimed to uncover the extent of genetic diversity and population structure of noug accessions collected from different regions of Ethiopia using microsatellite markers. Methods and results A total of 161 accessions from fourteen regions of Ethiopia, including some from Eritrea using 13 microsatellite markers were analyzed. All the 13 microsatellite markers were polymorphic and highly informative with a mean PIC value of 0.82. The analysis generated a total of 158 alleles with a mean of 12.15 per locus. The overall mean of Shannon information index and heterozygosity/gene diversity were 1.57 and 0.74, respectively suggesting the presence of higher genetic diversity across the collection regions. AMOVA revealed that 96.06% of the total genetic variation was attributed to within populations while only 3.94% was attributed to among populations. Likewise, the dendrogram clustering, PCoA, and the model-based population structure analysis didn't exactly corresponded the grouping of the genotypes according to their regions of origin. Conclusion The microsatellites used in the present study are highly informative and could be targeted for developing markers for future marker-assisted breeding. Genotypes collected from Shewa, Wollo, Gojjam, Tigray, and B/G showed a higher genetic diversity and private alleles as compared to other populations. Hence, these areas can be considered as hotspots which could help for the identification of genotypes that can be used in breeding programs as well as for the implementation of further conservation programs.
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| 15. |
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| 16. |
- Grskovic, Branka, et al.
(författare)
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DNA methylation : the future of crime scene investigation?
- 2013
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Ingår i: Molecular Biology Reports. - : Springer Netherlands. - 0301-4851 .- 1573-4978. ; 40:7, s. 4349-4360
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Tidskriftsartikel (refereegranskat)abstract
- Proper detection and subsequent analysis of biological evidence is crucial for crime scene reconstruction. The number of different criminal acts is increasing rapidly. Therefore, forensic geneticists are constantly on the battlefield, trying hard to find solutions how to solve them. One of the essential defensive lines in the fight against the invasion of crime is relying on DNA methylation. In this review, the role of DNA methylation in body fluid identification and other DNA methylation applications are discussed. Among other applications of DNA methylation, age determination of the donor of biological evidence, analysis of the parent-of-origin specific DNA methylation markers at imprinted loci for parentage testing and personal identification, differentiation between monozygotic twins due to their different DNA methylation patterns, artificial DNA detection and analyses of DNA methylation patterns in the promoter regions of circadian clock genes are the most important ones. Nevertheless, there are still a lot of open chapters in DNA methylation research that need to be closed before its final implementation in routine forensic casework.
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| 17. |
- Ignatovica, Vita, et al.
(författare)
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Single nucleotide polymorphisms of the purinergic 1 receptor are not associated with myocardial infarction in a Latvian population
- 2012
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 39:2, s. 1917-1925
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Tidskriftsartikel (refereegranskat)abstract
- The purinergic 1 receptor (P2RY1) has been implicated in development of heart disease and in individual pharmacodynamic response to anticoagulant therapies. However, the association of polymorphisms in the P2RY1 gene with myocardial infarction (MI), and its associated conditions, has yet to be reported in the literature. We evaluated seven known SNPs in P2RY1 for association with MI in a Latvian population. Seven independent parameters that are related to MI [body mass index (BMI), type 2 diabetes (T2D), angina pectoris, hypertension, hyperlipidemia, atrial fibrillation and heart failure] were investigated. No significant association with MI was observed for any of the polymorphisms. Those SNPs for which the P value was close to significance were located in coding or promoter regions. Intriguingly, carriers of the minor allele in the P2RY1 gene locus showed a tendency towards higher onset age for MI, suggesting a possible protective effect of these SNPs against MI or their contribution in progression as opposed to onset. Finally, a linkage disequilibrium (LD) plot was generated for these polymorphisms in the Latvian population. The results of this study suggest that the role of P2RY1 in individuals from Latvian population is likely to be principally involved in platelet aggregation and thromboembolic diseases, and not as a significant contributing factor to the global metabolic syndrome.
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| 18. |
- Kabir, Nuzhat N., et al.
(författare)
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Grb10 is a dual regulator of receptor tyrosine kinase signaling
- 2014
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 41:4, s. 1985-1992
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Forskningsöversikt (refereegranskat)abstract
- The adaptor protein Grb10 is a close homolog of Grb7 and Grb14. These proteins are characterized by an N-terminal proline-rich region, a Ras–GTPase binding domain, a PH domain, an SH2 domain and a BPS domain in between the PH and SH2 domains. Human Grb10 gene encodes three splice variants. These variants show differences in functionality. Grb10 associates with multiple proteins including tyrosine kinases in a tyrosine phosphorylation dependent or independent manner. Association with multiple proteins allows Grb10 to regulate different signaling pathways resulting in different biological consequences.
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| 19. |
- Kabir, Nuzhat N., et al.
(författare)
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Keratin 19 expression correlates with poor prognosis in breast cancer
- 2014
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 41:12, s. 7729-7735
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer expression profiling has been used for determining biomarkers. Using gene expression profiles of 2,400 patients we identified keratin 19 (KRT19) as a highly deregulated gene in breast cancer. KRT19 expression is independent of patient race but correlates with disease grade, and ER, PR or HER2 expression. Expression of TPD52, GATA3 and KRT18 was increased in KRT19 expressing patients. Furthermore, KRT19 expression was associated with ER up-regulation and Luminal B gene signatures, as well as a constitutive RAF1 signaling pathway. Finally, KRT19 expression correlated with poor overall survival. Taken together, our results suggest that KRT19 expression can be used as a prognostic marker.
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| 20. |
- Kajtoch, Lukasz, et al.
(författare)
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Development and characterization of microsatellite loci in the Centricnemus leucogrammus weevil
- 2012
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 39:12, s. 11131-11136
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Tidskriftsartikel (refereegranskat)abstract
- Centricnemus leucogrammus is a weevil characteristic of European xerothermic habitats and steppes. The species was probably more widespread during the Pleistocene glaciations, while its current distribution is limited to "warm-stage refugia." It may be regarded as a typical representative of flightless xerothermophilous beetles. Previous studies concentrated on its genetic variation using mitochondrial genes. Here, we identified, tested and characterized 24 polymorphic microsatellite loci with the use of 454 sequencing of microsatellite enriched genomic libraries. The new set of loci will be used in studies on the population structure of this weevil and may provide valuable information for its conservation.
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| 21. |
- Kayani, Waqas Khan
(författare)
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Artemisinin and its derivatives: a promising cancer therapy
- 2020
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 47, s. 6321-6336
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Forskningsöversikt (refereegranskat)abstract
- The world is experiencing a cancer epidemic and an increase in the prevalence of the disease. Cancer remains a major killer, accounting for more than half a million deaths annually. There is a wide range of natural products that have the potential to treat this disease. One of these products is artemisinin; a natural product fromArtemisiaplant. The Nobel Prize for Medicine was awarded in 2015 for the discovery of artemisinin in recognition of the drug's efficacy. Artemisinin produces highly reactive free radicals by the breakdown of two oxygen atoms that kill cancerous cells. These cells sequester iron and accumulate as much as 1000 times in comparison with normal cells. Generally, chemotherapy is toxic to both cancerous cells and normal cells, while no significant cytotoxicity from artemisinin to normal cells has been found in more than 4000 case studies, which makes it far different than conventional chemotherapy. The pleiotropic response of artemisinin in cancer cells is responsible for growth inhibition by multiple ways including inhibition of angiogenesis, apoptosis, cell cycle arrest, disruption of cell migration, and modulation of nuclear receptor responsiveness. It is very encouraging that artemisinin and its derivatives are anticipated to be a novel class of broad-spectrum antitumor agents based on efficacy and safety. This review aims to highlight these achievements and propose potential strategies to develop artemisinin and its derivatives as a new class of cancer therapeutic agents.
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| 22. |
- Kayani, Waqas Khan
(författare)
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Biotic stress triggered small RNA and RNAi defense response in plants
- 2020
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 47, s. 5511-5522
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Forskningsöversikt (refereegranskat)abstract
- The yield of crops is largely affected by different types of biotic stresses. To minimize the damage, crop plants adapted themselves to overcome the stress conditions through gene expression reprogramming at transcriptional and post-transcriptional levels. With a better knowledge of plants' responses in adverse environments, new methodologies and strategies have been applied to develop better stress-tolerant plants. In this manner, small RNAs (micro RNA and small-interfering RNA) are reported to play a central role to combat biotic stresses in plants. Depending upon the stress stimuli, these small RNAs can up or down regulate the genes expression, that indicate their potential role in overcoming the stress. These stress-induced small RNAs may reduce the expression of the target gene(s) that might negatively influence plants' response to the adverse conditions. Contrariwise, miRNA, a class of small RNA, can downregulate its expression to upregulate the expression of the target gene(s), which might positively aid to the stress adaptation. Along with this, benefits of RNA interference (RNAi) have also been stated in functional genomic research on insects, fungi and plant pathogens. RNAi is involved in the safe transport of dsRNA to the targeted mRNA(s) in the biotic stress-causing agents (for example fungi and insects) and saves the plant from damage, which is a safer approach compared to use of chemical pesticides. The current review summarizes the role of small RNAs and the use of RNAi to save the plants from biotic stress conditions.
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| 23. |
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| 24. |
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| 25. |
- Maitra, Subhamita, et al.
(författare)
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Specific dopaminergic genetic variants influence impulsivity, cognitive deficit, and disease severity of Indian ADHD probands
- 2022
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Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 49, s. 7315-7325
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Tidskriftsartikel (refereegranskat)abstract
- Background: Impulsivity (Imp), being one of the cardinal symptoms of Attention Deficit Hyperactivity Disorder (ADHD), often leads to inappropriate responses to stimuli. Since the dopaminergic system is the primary target for pharmaceutical intervention in ADHD, we investigated the association between ADHD-related Imp and functional gene variants of the dopamine transporter (SLC6A3) and catechol-O-methyltransferase involved in dopamine clearance.Methods and results: Indo-Caucasoid families with ADHD probands (N = 217) were recruited based on the Diagnostic and Statistical Manual of Mental Disorders (DSM). Imp of the probands was assessed using the Domain Specific Imp Scale for Children and DSM. Peripheral blood was collected after obtaining informed written consent for participation, genomic DNA was isolated, and target sites were genotyped by DNA sequencing. The association of genetic variants with Imp was examined by the Quantitative trait analysis (QTA) and Analysis of variance (ANOVA). Post-Hoc analysis following QTA and ANOVA showed significant associations of rs2254408, rs2981359, and rs2239393 with different domains of Imp (P < 0.05). Various haplotypic combinations also showed statistically significant associations with Imp (P < 0.05). Multifactor dimensionality reduction models revealed strong effects of the variants on Imp. ADHD probands harboring the risk alleles exhibited a deficit in performance during cognitive assessment. Longitudinal follow-up revealed a significant association of rs2254408 with trait persistence.Conclusion: The present study indicates the influence of the studied genetic variants on ADHD-associated imp, executive deficit, and disease persistence. Thus, these variants may be helpful as predictors for the success of individual therapeutic sessions during cognitive training.
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| 26. |
- Motallebipour, Mehdi, et al.
(författare)
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Two polypyrimidine tracts in the nitric oxide synthase 2 gene : similar regulatory sequences with different properties
- 2010
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 37:4, s. 2021-2030
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Tidskriftsartikel (refereegranskat)abstract
- We reported previously that the polymorphic polypyrimidine CCTTT-microsatellite in the regulatory region of nitric oxide synthase 2 (NOS2) bound nuclear proteins in vitro. In the present work, we aimed to characterize and investigate a potential regulatory role of the CCTTT-microsatellite in NOS2 expression. Therefore, we performed gel-shift, S1-nuclease, and chromatin immunoprecipitation (ChIP) assays. In vitro experiments showed that the microsatellite formed triplex-DNA both with and without superhelical constraint. We also found that the CCTTT-microsatellite and an apparently similar CT-repeat in the first intron of NOS2 were specifically cleaved by S1-nuclease, when cloned into a supercoiled plasmid. In vitro data suggested that the CCTTT-microsatellite bound both polypyrimidine tract-binding protein (PTBP1) and heterogeneous nuclear ribonucleoprotein K (hnRNPK). On the contrary, ChIP revealed binding of PTBP1 and hnRNPK rather to the CT-repeat in the first intron than to the CCTTT-microsatellite. Enrichment for RNA polymerase II and acetylated histones H3 and H4 was also detected at the intronic site. We suggest that both PTBP1 and hnRNPK binds the single strand of the triplex-DNA formed at the CT-repeat in the first intron and that this interaction could be involved in the regulation of NOS2 expression.
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| 27. |
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| 28. |
- Nilsson, Torbjörn K., 1956-, et al.
(författare)
-
A folate receptor alpha double-mutated haplotype 1816delC-1841A is distributed throughout Eurasia and associated with lower erythrocyte folate levels
- 2012
-
Ingår i: Molecular Biology Reports. - Dordrecht, Netherlands : Springer. - 0301-4851 .- 1573-4978. ; 39:4, s. 4471-4478
-
Tidskriftsartikel (refereegranskat)abstract
- Folate is crucial for various cellular functions. Several transport mechanisms allow folate to enter the intracellular compartment with folate receptor-alpha being the major high-affinity receptor. Rare genetic variations in exons of the FR-alpha gene, FOLR1, were recently shown to cause severe folate deficiency accompanied by neurological and other disturbances. So far, similar effects by genetic variation in noncoding parts of the FOLR1 gene have not been identified. The aim of our study was to determine biochemically the haplotype structure of two linked polymorphisms in the FOLR1 gene, 1816delC and 1841G > A, the prevalences of the mutated alleles across Eurasia, and their possible effects on physiological folate levels in vivo. For this purpose we employed allele-specific PCR and Pyrosequencing technology and performed genotyping in 738 subjects from Spain, 387 from Sweden, 952 from Estonia, and 47 from Korea. We demonstrate the presence of an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene, with the prevalence of the mutated allele being highest among Koreans (q = 0.074), lower in Estonians (q = 0.017), Spaniards (q = 0.0061), and the lowest among Swedes (q = 0.0026). Erythrocyte folate levels were studied in the Spanish population sample, where subjects carrying the double-mutated FOLR1 haplotype had significantly reduced levels by 27% (P = 0.039), adjusted for serum vitamin B-12 levels and MTHFR 677C > T genotype, while the mean serum folate levels were only 20% lower among the carriers (P = 0.11). Plasma homocysteine and cobalamin levels did not differ. Thus, we have demonstrated by molecular haplotyping an ancient double-mutated haplotype 1816delC-1841A in the FOLR1 gene, spread over the whole Eurasian continent, which may be of functional importance for uptake of folate in red blood cells.
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| 29. |
- Olmedo-Vicente, Erika, et al.
(författare)
-
Development of microsatellite markers for sister species Linum suffruticosum and Linum tenuifolium in their overlapping ranges
- 2023
-
Ingår i: Molecular Biology Reports. - 0301-4851 .- 1573-4978. ; 50:9, s. 7927-7933
-
Tidskriftsartikel (refereegranskat)abstract
- Background Microsatellite markers were developed for distylous Linum suffruticosum and tested in the monomorphic sister species Linum tenuifolium. These species are perennial herbs endemic to the western and northwestern Mediterranean, respectively, with a partially overlapping distribution area.Methods and resultsWe developed 12 microsatellite markers for L. suffruticosum using next generation sequencing, and assessed their polymorphism and genetic diversity in 152 individuals from seven natural populations. The markers displayed high polymorphism, with two to 16 alleles per locus and population, and average observed and expected heterozygosities of 0.833 and 0.692, respectively. All loci amplified successfully in the sister species L. tenuifolium, and 150 individuals from seven populations were also screened. The polymorphism exhibited was high, with two to ten alleles per locus and population, and average observed and expected heterozygosities of 0.77 and 0.62, respectively.Conclusions The microsatellite markers identified in L. suffruticosum and tested in L. tenuifolium are a powerful tool to facilitate future investigations of the population genetics, mating patterns and hybridization between both Linum species in their contact zone.
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| 30. |
- Pennanen, P., et al.
(författare)
-
Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player
- 2021
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 48, s. 1243-1254
-
Tidskriftsartikel (refereegranskat)abstract
- Little is known about the signaling pathways involved in the differentiation of human osteoclasts. The present study evaluated the roles of the Ras/PI3K/Akt/mTOR, Ras/Raf/MEK1/2/ERK1/2, calcium-PKC, and p38 signaling pathways in human osteoclast differentiation. Mononuclear cells were isolated from the peripheral blood of control persons and patients with neurofibromatosis 1 (NF1), and the cells were differentiated into osteoclasts in the presence of signaling pathway inhibitors. Osteoclast differentiation was assessed using tartrate-resistant acid phosphatase 5B. Inhibition of most signaling pathways with chemical inhibitors decreased the number of human osteoclasts and disrupted F-actin ring formation, while the inhibition of p38 resulted in an increased number of osteoclasts, which is a finding contradictory to previous murine studies. However, the p38 inhibition did not increase the bone resorption capacity of the cells. Ras-inhibitor FTS increased osteoclastogenesis in samples from control persons, but an inhibitory effect was observed in NF1 samples. Inhibition of MEK, PI3K, and mTOR reduced markedly the number of NF1-deficient osteoclasts, but no effect was observed in control samples. Western blot analyses showed that the changes in the phosphorylation of ERK1/2 correlated with the number of osteoclasts. Our results highlight the fact that osteoclastogenesis is regulated by multiple interacting signaling pathways and emphasize that murine and human findings related to osteoclastogenesis are not necessarily equivalent.
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| 31. |
- Philippou, Anastassios, et al.
(författare)
-
Expression of tissue remodelling, inflammation- and angiogenesis-related factors after eccentric exercise in humans
- 2021
-
Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 48:5, s. 4047-4054
-
Tidskriftsartikel (refereegranskat)abstract
- Eccentric exercise has been extensively used as a model to study the contraction-induced muscle damage and its consequent processes. This study aimed at examining molecular responses associated with tissue remodelling, inflammation and angiogenesis in skeletal muscle during the recovery period after eccentric exercise in humans. Ten healthy men performed 50 maximal eccentric muscle actions with the knee extensors and muscle biopsies were collected from the vastus lateralis before and 6 h, 48 h and 120 h post eccentric exercise. Real Time-PCR was utilized to investigate alterations in gene expression of various tissue remodelling-, inflammation- and angiogenesis-related factors: uPA, uPA-R, TGF-β1, MMP-9, TNF-α, IL-6, IL-8, VEGF, VEGFR-2, HIF-1a, Ang-1, Ang-2 and Tie-2. The uPA/uPA-R system exhibited a similar time-expression pattern increasing 6 h post exercise (p < 0.05), while the other tissue remodelling factors TGF-β1 and MMP-9 did not change significantly over time. Transcriptional responses of inflammatory factors TNF-α and IL-8 increased significantly and peaked 6 h post eccentric exercise (p < 0.05), while IL-6 exhibited a similar, though not statistically significant, expression profile (p > 0.05). Similarly, the expression of angiopoietin receptor Tie-2 showed an early increase only at 6 h after the completion of exercise (p < 0.05), while the other angiogenic factors failed to reach statistical significance due a high interindividual variability in the gene expression responses. The early transcriptional upregulation of tissue remodelling, inflammation- and angiogenesis-related factors post eccentric exercise may indicate the acute intramuscular activation of these processes functionally related to muscle damage-induced adaptation.
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| 32. |
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| 33. |
- Rovite, Vita, et al.
(författare)
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The role of common and rare MC4R variants and FTO polymorphisms in extreme form of obesity
- 2014
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 41:3, s. 1491-500
-
Tidskriftsartikel (refereegranskat)abstract
- Melanocortin 4 receptor (MC4R) is an important regulator of food intake and number of studies report genetic variations influencing the risk of obesity. Here we explored the role of common genetic variation from MC4R locus comparing with SNPs from gene FTO locus, as well as the frequency and functionality of rare MC4R mutations in cohort of 380 severely obese individuals (BMI > 39 kg/m(2)) and 380 lean subjects from the Genome Database of Latvian Population (LGDB). We found correlation for two SNPs-rs11642015 and rs62048402 in the fat mass and obesity-associated protein (FTO) with obesity but no association was detected for rs17782313 located in the MC4R locus in these severely obese individuals. We sequenced the whole gene MC4R coding region in all study subjects and found five previously known heterozygous non-synonymous substitutions V103I, I121T, S127L, V166I and I251L. Expression in mammalian cells showed that the S127L, V166I and double V103I/S127L mutant receptors had significantly decreased quantity at the cell surface compared to the wild type MC4R. We carried out detailed functional analysis of V166I that demonstrated that, despite low abundance in plasma membrane, the V166I variant has lower EC50 value upon αMSH activation than the wild type receptor, while the level of AGRP inhibition was decreased, implying that V166I cause hyperactive satiety signalling. Overall, this study suggest that S127L may be the most frequent functional MC4R mutation leading to the severe obesity in general population and provides new insight into the functionality of population based variants of the MC4R.
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| 34. |
- Schiller Vestergren, Anna, et al.
(författare)
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Tolbutamide hydroxylation by hepatic microsomes from Atlantic salmon (Salmo salar L.)
- 2012
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 39, s. 6867-6873
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic transformations of two substrates for human cytochrome P450 (CYP450) 2C9, tolbutamide and diclofenac, were investigated in hepatic microsomes from Atlantic salmon (Salmo salar L.). Tolbutamide hydroxylation followed Michaelis-Menten kinetics. Mean apparent Michaelis-Menten constant (K-m) and maximum reaction velocity (V-max) values for 4-hydroxytolbutamide (TBOH) formation were 0.09 +/- A 0.031 mM and 49.5 +/- A 6.03 pmol/min/mg, respectively. Addition of sulfaphenazole, an inhibitor for mammalian CYP2C9, in a range from 1 to 200 mu M decreased formation of TBOH in a concentration-dependent manner, but not to 50%. Neither fluconazole, an inhibitor of human CYP2C9, nor ketoconazole, inhibitor of CYP1A and CYP3A in fish, affected TBOH formation. In contrast ellipticine, an inhibitor of CYP1A in fish inhibited TBOH formation with the IC50 value of 12.1 mu M. The rate of TBOH formation was competitively inhibited by 100 mu M of sesamin in the incubations, but the degree of inhibition did not increase with increased sesamin concentration. Ethoxyresorufin hydroxylase (EROD) activity was inhibited by tolbutamide in a non-competitive manner (inhibition constant K-i = 218 mu M). Our data suggest that tolbutamide is metabolized by salmon microsomes with formation of TBOH. CYP1A might be involved in this reaction as suggested by decreased TBOH formation in the presence of ellipticine and decreased EROD activity in the presence of tolbutamide. Incubation of diclofenac with the microsomes yielded no metabolite formation, suggesting that salmon does not possess diclofenac-metabolizing activity.
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| 35. |
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| 36. |
- Sharma, Vinay, et al.
(författare)
-
Expression, purification, characterization and in silico analysis of newly isolated hydrocarbon degrading bleomycin resistance dioxygenase
- 2020
-
Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 47:1, s. 533-544
-
Tidskriftsartikel (refereegranskat)abstract
- In the present investigation, we report cloning, expression, purification and characterization of a novel Bleomycin Resistance Dioxygenase (BRPD). His-tagged fusion protein was purified to homogeneity using Ni-NTA affinity chromatography, yielding 1.2 mg of BRPD with specific activity of 6.25 U mg−1 from 600 ml of E. coli culture. Purified enzyme was a dimer with molecular weight ~ 26 kDa in SDS-PAGE and ~ 73 kDa in native PAGE analysis. The protein catalyzed breakdown of hydrocarbon substrates, including catechol and hydroquinone, in the presence of metal ions, as characterized via spectrophotometric analysis of the enzymatic reactions. Bleomycin binding was proven using the EMSA gel retardation assay, and the putative bleomycin binding site was further determined by in silico analysis. Molecular dynamic simulations revealed that BRPD attains octahedral configuration in the presence of Fe2+ ion, forming six co-ordinate complexes to degrade hydroquinone-like molecules. In contrary, in the presence of Zn2+ ion BRPD adopts tetrahedral configuration, which enables degradation of catechol-like molecules.
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| 37. |
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| 38. |
- Tartik, Musa
(författare)
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The priority of yeast to select among various DNA options to repair genome breaks by homologous recombination
- 2024
-
Ingår i: Molecular Biology Reports. - 1573-4978 .- 0301-4851. ; 51:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Horizontal gene transfer (HGT) is considered an important mechanism to contribute to the evolution of bacteria, plants, and animals by allowing the movement of genetic material between organisms, in difference to vertical inheritance. Thereby it can also play a significant role in spreading traits like antibiotic resistance among bacteria and virulence factors between pathogens. During the HGT, organisms take up free DNA from the environment and incorporate it into their genomes. Although HGT is known to be carried out by many organisms, there is limited information on how organisms select which genetic material for horizontal transfer. Here we have investigated the preference priority of Saccharomyces cerevisiae between different options of gene source presented under certain stress conditions to repair a double-strand break (DSB) in DNA via HR. RESULTS: Each genetic module was designed with appropriate sequences being homologous for two sides of the DSB, which is important for yeast to repair the fracture with HR. S. cerevisiae made a random selection between two heterologous T1 (44%) and T2 (56%) modules to repair DSB. Interestingly, yeast corrected the DNA break only with the T3 module (almost 100%) when the homologous T3 module was an option for the selection. It seems that S. cerevisiae tends to prefer T3 over alternatives to fix DSBs when it exists among the options. CONCLUSIONS: It seems that S. cerevisiae have a preference for priority to select a particular one under certain conditions when it has various DNA options to repair a DSB in its genome, further studies are required to support our findings.
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| 39. |
- Tavares, Ana I., et al.
(författare)
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Isolation and characterization of nine microsatellite markers for the red alga Corallina officinalis
- 2018
-
Ingår i: Molecular Biology Reports. - : Springer Nature. - 0301-4851 .- 1573-4978. ; 45:6, s. 2791-2794
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Tidskriftsartikel (refereegranskat)abstract
- We report the development of nine polymorphic microsatellite markers for Corallina officinalis (Linnaeus, 1758), a calcifying intertidal red alga and important ecosystem engineer spread along the North East Atlantic. Characterization and analysis of loci were made using 15 individuals of C. officinalis from populations in Iceland and the UK. The average number of alleles per locus was 3.78 (range 2–6) and mean of gene diversity was 0.58 (range 0.38–0.77). The set of microsatellites developed here will provide a useful molecular tool for population genetic and conservation studies.
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| 40. |
- Vallelunga, A., et al.
(författare)
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Serum miR-30c-5p is a potential biomarker for multiple system atrophy
- 2019
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 46:2, s. 1661-1666
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple system atrophy (MSA) is a neurodegenerative disease that belongs to the synucleinopathies. Clinically, there is an overlap between MSA and Parkinson's disease (PD), especially at the early disease stage. However, these two pathologies differ in terms of disease progression. Currently, no biomarker exists to differentiate MSA from PD. MicroRNAs are non-coding RNAs implicated in gene expression regulation. MiRNAs modulate cellular activity and they control a range of physiological and pathological functions. miRNAs are found in biofluids, such as blood, serum, plasma, saliva, and cerebrospinal fluid. Many groups, including ours, found that circulating miRNAs are differently expressed in blood, plasma, serum and cerebrospinal fluid of PD and MSA patients. In the present study, our primary aim was to determine if serum mir-30-5p and mir-148b-5p can be used as biomarkers for early diagnosis of PD and/or MSA. Our secondary goal was to determine if serum levels of those miRNAs can be correlated with the patients' clinical profile. Using quantitative PCR (qPCR), we evaluated expression levels of miR-30c-5p and miR148b-5p in serum samples from PD (n=56), MSA (n=49), and healthy control (n=50) subjects. We have found that miR-30c-5p is significantly upregulated in MSA if compared with PD and healthy control subjects. Moreover, serum miR-30c-5p levels correlate with disease duration in both MSA and PD. No significant difference was found in miR-148b-5p among MSA, PD and healthy control subjects. Our results suggest a possible role of serum miR-30-5p as a biomarker for diagnosis and progression of MSA.
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| 41. |
- Wagner, Liane, et al.
(författare)
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In vitro inhibition of 7-ethoxyresorufin-O-deethylase (EROD) and p-nitrophenol hydroxylase (PNPH) activities by sesamin in hepatic microsomes from two fish species
- 2013
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 40, s. 457-462
-
Tidskriftsartikel (refereegranskat)abstract
- In the present study, we investigated the effect of sesamin on CYP1A (7-ethoxyresorufin-O-deethylase, EROD) and CYP2E1-like activities (p-nitrophenol hydroxylase, PNPH) in hepatic microsomes obtained from Atlantic salmon (Salmo salar) and common carp (Cyprinus carpio). Addition of sesamin to the incubations in a concentration range from 1 to 200 mu M decreased the activities of EROD and PNPH in a concentration dependent manner. It is likely that the inhibition of EROD was mechanism-based as demonstrated by the decrease in the IC50 value from 5.9 to 3.2 mu M for A. salmon and from 7.9 to 3.0 mu M for common carp when 5 min pre-incubation step was included. Similarly, PNPH activity was inhibited by sesamin with a decrease in the IC50 values from 61.7 to 15.2 mu M for A. salmon and from 194.3 to 20.7 mu M for common carp. Thus, our results indicated that sesamin can act as a mechanism-based inhibitor of EROD and PNPH activity with similar degree of inhibition in both fish species. More importantly, the inhibition of CYP1A, in addition to being mechanism-based, was competitive with K-i value of 5.3 mu M.
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| 42. |
- Wang, H. L., et al.
(författare)
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Genetic association study of adaptor protein complex 4 with cerebral palsy in a Han Chinese population
- 2013
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 40:11, s. 6459-6467
-
Tidskriftsartikel (refereegranskat)abstract
- Adaptor protein complex 4 (AP-4) plays a key role in vesicle formation, trafficking, and sorting processes that are critical for brain development and function. AP-4 consists of four subunits encoded by the AP4E1, AP4B1, AP4M1, and AP4S1 genes. A number of studies have pointed to the involvement of AP-4-mediated vesicular trafficking pathways in the etiology of cerebral palsy (CP), the most notable of which are the causative mutations that have recently been identified in each of the AP-4 genes in different CP families. We postulated, therefore, that variations in AP-4 genes might influence an indivual's susceptibility to CP. In the present study, 16 SNPs were genotyped among 517 CP patients and 502 healthy controls from the Han Chinese population. We systematically analyzed the association of the AP4E1, AP4B1, AP4M1, and AP4S1 genes with CP on the basis of clinical characteristics. No significant associations were found between these variants and the overall risk of CP. Subgroup analysis showed that rs1217401 of AP4B1 was significantly associated with CP as a sequela of hypoxic-ischemic encephalopathy (HIE) (CP + HIE) (allele: p = 0.042151; genotype: p = 4.46 x 10(-6)). Our results indicate that the 16 variants studied in the genes of the four subunits of AP-4 have no detectable effects on the overall susceptibility to CP, but AP4B1 appears to be a susceptibility gene for CP + HIE in the Han Chinese population.
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| 43. |
- Yang, Zhen, et al.
(författare)
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Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people
- 2011
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 38:2, s. 1145-1150
-
Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies reported that GCKR rs780094 polymorphism is associated with elevated fasting serum triglyceride levels and elevated levels of C-reactive protein (CRP). There are a ample of data on the association between circulating triglyceride, CRP concentrations and risk of non-alcoholic fatty liver (NAFLD). To determine whether the GCKR rs780094 polymorphism contributes to the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis IA degrees, 90 with steatosis hepatis IIA degrees and 28 with steatosis hepatis IIIA degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. We confirmed the association of GCKR rs780094 with NAFLD in Chinese people (OR = 1.607, 95% CI 1.139-2.271, P ([dom]) = 7.2 x 10(-3)). In this study, polymorphism in GCKR rs780094 was not significantly associated with the degree of fatty infiltration of the liver. In addition, the T-allele of GCKR rs780094 was significantly associated with increasing fasting triglyceride (P ([add]) = 3.8 x 10(-4)) and CRP (P ([add]) = 2.9 x 10(-4)) concentrations after adjusting for age, gender, and BMI. The association with NAFLD remained significant after adjustment for triglyceride, while adjustment for CRP abolished the association. Genetic variation in GCKR gene rs780094 polymorphism contributes to the risk of NAFLD in Chinese people. The effect of genotype on NAFLD is probably mediated through chronic low-grade systemic inflammation rather than through dislipidemia.
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| 44. |
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| 45. |
- Zhou, Bin, et al.
(författare)
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PNAS-4 expression and its relationship to p53 in colorectal cancer
- 2012
-
Ingår i: Molecular Biology Reports. - : Springer Verlag (Germany). - 0301-4851 .- 1573-4978. ; 39:1, s. 243-249
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Tidskriftsartikel (refereegranskat)abstract
- PNAS-4 is a novel pro-apoptotic protein activated during the early response to DNA damage; however, the molecular mechanisms and pathways regulating PNAS-4 expression in tumors are not well understood. We hypothesized that PNAS-4 is a p53 down-stream target gene and designed this study. We searched online for putative p53-binding sites in the entire PNAS-4 gene and did not find any corresponding information. In HCT116 colon cancer cells, after being transfected with small interfering RNA to silence p53, the expressions of PNAS-4 and other known p53 target gene (Apaf1, Bax, Fas and Dr5) were determined by real-time PCR. We found that PNAS-4 was up-regulated while Apaf1, Bax, Fas and Dr5 were down-regulated. We then examined the expression of PNAS-4 and p53 mutation in colorectal cancer patients. PNAS-4 expressed both in colorectal cancers and normal tissues, but compared with paired control, PNAS-4 was up-regulated in cancers (P = 0.018). PNAS-4 overexpression ratios were correlated to the p53 mutant status (P = 0.001). The mean PNAS-4 expression levels of p53 mutant homozygote group and heterozygote group were higher than that of p53 wild type group (P = 0.013). The expression ratios of PNAS-4 (every sample in relative to its paired normal mucosa) were different between negative lymph node metastasis (66% up-regulated, 34% down-regulated) and positive metastasis (42% up-regulated, 58% down-regulated). Taken together, these findings suggested that PNAS-4 was not a p53 target, but overexpression of PNAS-4 was correlated to p53 inactivity in colorectal cancer.
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| 46. |
- Zhou, Ying, et al.
(författare)
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The effects and possible mechanism of action of apolipoprotein M on the growth of breast cancer cells
- 2022
-
Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 49:2, s. 1171-1179
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Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate the effects and mechanism of action of apolipoprotein M (ApoM) on the growth of breast cancer (BC) cells. Methods and results: Bioinformatics, cell experiments and animal experiments were used to verify the effect of ApoM on breast cancer cell lines and breast tumor growth in vivo. ApoM expression was significantly reduced in BC tissues, and patients with lower ApoM mRNA expression had a poorer prognosis (P < 0.0001). Besides, ApoM can partially inhibit the proliferative, migratory and invasive processes of BC cells. In vivo, the difference between ApoM-OE and NC groups was no significant. The level of vitamin D receptor (VDR) protein in MDA-MB-231 cells was increased by overexpression of ApoM (P < 0.05), while in MCF-7 cells, VDR levels decreased (P < 0.05). Conclusions: ApoM can partially inhibit the growth of BC cells. VDR may play a role, but is not the main pathway.
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| 47. |
- Andrén, Daniela, Associate Professor, 1968-
(författare)
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Valuing Depression Using the Well-Being Valuation Approach
- 2023
-
Ingår i: Journal of Happiness Studies. - : Springer. - 1389-4978 .- 1573-7780. ; 24:1, s. 107-140
-
Tidskriftsartikel (refereegranskat)abstract
- The continuously dramatic rise of the number of people suffering from depression is attracting an increasing demand for effective ways of preventing depression. Besides the need for new interventions, there is also a continuous call for a more robust framework for economic evaluation of public interventions. Taking into account people's preferences for public goods is not straightforward to quantify, and therefore, in addition to designing a new technique for valuing nonmarket goods and services, it is equally important to use valuation methods that are not yet established as traditional. One less commonly used method to assess the cost of depression in monetary terms is the well-being valuation method or the life satisfaction approach, which requires answers to only a few questions that are significantly less time demanding for the respondents than more traditional approaches. We added a well-being question to a contingent valuation web-survey that describes hypothetical interventions aimed to prevent depression in Sweden and estimated that the loss in life satisfaction for individuals who experienced depression varies between approximately 350 and 45,000 euros per year. The monetary compensation would be, on average, higher for individuals who experienced own depression than for those who know someone near, family or friend, who experienced depression, for men than for women, and for middle-aged than for younger and older individuals, respectively.
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| 48. |
- Backman, Ylva
(författare)
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Circles of Happiness: Students’ Perceptions of Bidirectional Crossovers of Subjective Well-Being
- 2016
-
Ingår i: Journal of Happiness Studies. - : Springer. - 1389-4978 .- 1573-7780. ; 17:4, s. 1547-1563
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Tidskriftsartikel (refereegranskat)abstract
- The mental well-being of the world’s adolescents has decreased in the last 20–30 years. Such a trend is visible also in Sweden, a country otherwise considered a positive example in terms of child well-being. In Sweden, students in lower secondary school are especially exposed. From a salutogenic orientation, this study qualitatively explored 200 Swedish students’ (grades 5–9) perceptions of the role of happiness in school. Students perceived happiness as both promoting and being promoted by five aspects: learning, school engagement, appreciation of subjects or lesson content, others’ happiness, and prosocial behavior. Hence, five perceived bidirectional crossovers of subjective well-being were found. These were compared to the findings of previous research about the determinants and effects of happiness. The students’ perceptions both add new direction for future research and align in several respects with decades of earlier research.
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| 49. |
- Baranowska-Rataj, Anna, 1980-, et al.
(författare)
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Does lone motherhood decrease women’s happiness? : evidence from qualitative and quantitative research
- 2014
-
Ingår i: Journal of Happiness Studies. - : Springer Netherlands. - 1389-4978 .- 1573-7780. ; 15:6, s. 1457-1477
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Tidskriftsartikel (refereegranskat)abstract
- This paper contributes to the discussion on the effects of single motherhood on happiness. We use a mixed-method approach. First, based on in-depth interviews with mothers who gave birth while single, we explore mechanisms through which children may influence mothers’ happiness. In a second step, we analyze panel survey data to quantify this influence. Our results leave no doubt that, while raising a child outside of marriage poses many challenges, parenthood has some positive influence on a lone mother’s life.Our qualitative evidence shows that children are a central point in an unmarried woman’s life, and that many life decisions are taken with consideration of the child’s welfare, including escaping from pathological relationships. Our quantitative evidence shows that, although the general level of happiness among unmarried women is lower than among their married counterparts, raising a child does not have a negative impact on their happiness.
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| 50. |
- Baranowska-Rataj, Anna
(författare)
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What would your parents say? : the impact of cohabitation among young people on their relationships with their parents
- 2014
-
Ingår i: Journal of Happiness Studies. - : Springer Berlin/Heidelberg. - 1389-4978 .- 1573-7780. ; 15:6, s. 1313-1332
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Tidskriftsartikel (refereegranskat)abstract
- Most European countries have seen a retreat from marriage, which is increasingly preceded or replaced by cohabitation. A question that arises in light of this trend is how the diffusion of non-marital cohabitation may affect the quality of family relations. This article investigates how cohabitation among young people affects their level of satisfaction with their relationship with their parents. We analyse data from the recently released Generation and Gender Survey for Poland, a country with a limited degree of social acceptance of cohabitation, a high degree of attachment to the institution of marriage, and a familialistic culture. Since young adults who choose to cohabit are a rather specific group, we use statistical methods that allow us to control for both the observed and the unobserved characteristics of cohabiters. We find that young people who cohabited in their first union rated their level of satisfaction with their parental relationship lower than their peers who were married. Thus, at least in the context of a country where informal partnerships are not yet fully socially accepted or institutionally supported, the role of cohabitation in intergenerational relations may not be neutral.
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