The complexes L5FeIIClBPh4 and L5FeII(H2O)(BPh4)2 (L5 = N,N,N‘-tris(2-pyridylmethyl)-N‘-methyl-ethane-1,2-diamine) have been isolated. Bernal et al. (Bernal, J.; et al. J. Chem. Soc., Dalton Trans. ...1995, 3667−3675) have prepared this ligand and the corresponding complex L5FeIIClPF6. We obtained the structural data of L5FeIIClBPh4 by X-ray diffraction. It crystallizes in the orthorhombic space group P212121 with a = 17.645(7) Å, b = 16.077(6) Å, c = 13.934(5) Å, V = 3953(3) Å3, and Z = 4. It presents Fe(II)−N bond lengths close to 2.2 Å, typical of high-spin Fe(II). In solution the L5FeII(H2O)(BPh4)2 complex showed a dependence of spin state upon the nature of the solvent. It was high spin in acetone and changed to low spin in acetonitrile. This was detected by UV−vis spectroscopy and by 1H NMR. Bernal et al. (ibidem) showed that these complexes in the presence of an excess of H2O2 give a purple species, very likely the L5FeIII(OOH)2+ derivative, with spectroscopic signatures analogous to those of “activated bleomycin”. The formation of L5FeIII(OOH)2+ is confirmed here by electrospray ionization mass spectrometry. We found that a L5/Fe system gave single-strand breaks on plasmid DNA in the presence of either a reducing agent (ascorbate) and air or oxidants (H2O2, KHSO5, MMPP) at 0.1 μM concentration. The methyl group in L5 was substituted by a (CH2)5N(CH3)3 + group in order to get higher affinity with DNA. The corresponding ligand L5 + was used to prepare the complexes L5 +FeIIClY2 (Y = BPh4 -, PF6 -, ClO4 -) and L5 +FeIIBr(PF6)2. The crystal structure of L5 +FeIICl(ClO4)2 was solved. It crystallizes in the monoclinic space group P21/a with a = 14.691(2) Å, b = 13.545(2) Å, c = 17.430(2) Å, β = 93.43(1)°, V = 3462(1) Å3, and Z = 4. The Fe(II)−ligand distances are similar to those of L5FeIIClBPh4. At the relatively low concentration of 0.01 μM, L5 +FeIIBr2+ promoted DNA breaks. The reaction was not inhibited by hydroxyl radical scavengers. The reaction might involve a nondiffusible oxygen reactive species, either a coordinated hydroperoxide or a high-valent metal−oxo entity.
The growth-inhibitory effect of several newly synthesized alkyl derivatives of 3,4-bisphenylhex(3)ene was studied in four tumor cell lines and three healthy primary cell systems. A marked inhibition ...of cell proliferation was noted in the neoplastic cells but not in the primary systems. No effect on the cytoplasmic or mitotic microtubule system but an increase in the gross level of 5-methylcytosine in nuclear DNA was observed. It is speculated that the selective growth inhibition of tumor cells is due to DNA-hypermethylation.
Prioritisation of food-borne parasites in Europe, 2016 Bouwknegt, Martijn; Devleesschauwer, Brecht; Graham, Heather ...
Euro surveillance : bulletin européen sur les maladies transmissibles,
03/2018, Letnik:
23, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Background and aimsPriority setting is a challenging task for public health professionals. To support health professionals with this and in following a recommendation from the Food and Agriculture ...Organization of the United Nations (FAO) and World Health Organization (WHO), 35 European parasitologists attended a workshop from 8-12 February 2016 to rank food-borne parasites (FBP) in terms of their importance for Europe and regions within Europe.
Countries were divided into European regions according to those used by the European Society of Clinical Microbiology and Infectious Diseases. We used the same multicriteria decision analysis approach as the FAO/WHO, for comparison of results, and a modified version, for better regional representation. Twenty-five FBP were scored in subgroups, using predefined decision rules.
At the European level,
ranked first, followed by
and
. At the regional level,
ranked highest in Northern and Eastern Europe,
in South-Western and South-Eastern Europe, and
in Western Europe. Anisakidae, ranking 17th globally, appeared in each European region's top 10. In contrast,
, ranked highest globally but 10th for Europe.
FBP of importance in Europe differ from those of importance globally, requiring targeted surveillance systems, intervention measures, and preparedness planning that differ across the world and across Europe.
The global population’s increasing demand for sustainable and nutritious food sources has led to the exploration of alternative approaches in livestock production. Edible insects have emerged as a ...promising solution due to their nutritional composition, including high protein content, balanced fats, minerals, vitamins, and bioactive peptides. Biofermentation offers a viable method to enhance the nutritional value of insect feed. This study aimed to investigate the effects of feeding biofermented feeds derived from less valuable raw materials on the yield and nutritional composition of Zophobas morio larvae. The focus was on assessing fat quality, omega-3 and omega-6 fatty acids, and bioactive compounds and monitoring the larvae’s weight and length increases. Three feed types were tested: wheat bran (control), fermented wheat bran, and a mixture of fermented corn and flaxseed in a five-week period. The findings demonstrated a noteworthy (p < 0.05) elevation in polyunsaturated fatty acids, such as gamma-linolenic acid, alpha-linolenic acid, and eicosapentaenoic acid in Zophobas morio larvae fed with biofermented corn and flaxseed pomace, both pre- and postculinary treatment, as compared to the control group. The study also showed increased chelation of Cu2+ (p < 0.05) and Fe2+ (p < 0.05) between native and roasted insects in the samples without in vitro digestion, as well as increased Cyclooxygenase-1 activity (p < 0.05), indicating improved bioavailability. Additionally, culinary processing led to a reduction in polyphenol content (p < 0.05), antioxidant activity (p > 0.05) except DPPH, and peptide concentration (p < 0.05) in the samples without in vitro digestion.
Translocations of the Mixed Lineage Leukemia (MLL) gene occur in a subset (5%) of acute myeloid leukemias (AML), and in mixed phenotype acute leukemias in infancy - a disease with extremely poor ...prognosis. Animal model systems show that MLL gain of function mutations may contribute to leukemogenesis. Wild-type (wt) MLL possesses histone methyltransferase activity and functions at the level of chromatin organization by affecting the expression of specific target genes. While numerous MLL fusion proteins exert a diverse array of functions, they ultimately serve to induce transcription of specific genes. Hence, acute lymphoblastic leukemias (ALL) with MLL mutations (MLLmu) exhibit characteristic gene expression profiles including high-level expression of HOXA cluster genes. Here, we aimed to relate MLL mutational status and tumor suppressor gene (TSG) methylation/expression in acute leukemia cell lines.
Using MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification assay), methylation of 24 different TSG was analyzed in 28 MLLmu and MLLwt acute leukemia cell lines. On average, 1.8/24 TSG were methylated in MLLmu AML cells, while 6.2/24 TSG were methylated in MLLwt AML cells. Hypomethylation and expression of the TSG BEX2, IGSF4 and TIMP3 turned out to be characteristic of MLLmu AML cell lines. MLLwt AML cell lines displayed hypermethylated TSG promoters resulting in transcriptional silencing. Demethylating agents and inhibitors of histone deacetylases restored expression of BEX2, IGSF4 and TIMP3, confirming epigenetic silencing of these genes in MLLwt cells. The positive correlation between MLL translocation, TSG hypomethylation and expression suggested that MLL fusion proteins were responsible for dysregulation of TSG expression in MLLmu cells. This concept was supported by our observation that Bex2 mRNA levels in MLL-ENL transgenic mouse cell lines required expression of the MLL fusion gene.
These results suggest that the conspicuous expression of the TSG BEX2, IGSF4 and TIMP3 in MLLmu AML cell lines is the consequence of altered epigenetic properties of MLL fusion proteins.
A better understanding of events triggering chronic myeloid leukemia progression is critical for optimized clinical management of chronic myeloid leukemia (CML). We sought to validate that increased ...expression of Musashi 2 (MSI2), a post-transcription regulator, is associated with progression and prognosis. Screening of 152 patients with CML showed that MSI2 was significantly decreased among patients with CML in chronic phase (CP) at diagnosis (p < 0.0001), but found no significant difference between the normal control group and treated patients with CML in CP. Moreover MSI2 was significantly increased (p < 0.0001) in patients with advance disease (AD) CML. Furthermore, our human hematopoietic cell line data imply that MSI2 and BCR-ABL1 mRNA expression are correlated. However, these data cast a doubt on earlier reports that MSI2 effects HES1 expression via NUMB-NOTCH signaling.
Inspection of the Cogwheel Using Virtual Instrumentation Šidiková, Michaela; Martinek, Radek; Ládrová, Martina ...
Acta Universitatis Agriculturae et Silviculturae Mendelianae Brunensis,
2019, Letnik:
67, Številka:
6
Journal Article
Recenzirano
Odprti dostop
This paper deals with use of machine vision for the needs of automated inspections based on virtual instrumentation using a visualization tool named Vision Builder for Automated Inspection (VBAI) – ...National Instruments (NI). An application for camera tests of dimensions, shapes and presence is designed in experimental parts. This work is focused on the control, detection and distribution properties of internal holes.
Increased expression of Musashi 2 (also known as MSI2), a mRNA binding protein, is reported to trigger progression of chronic myeloid leukemia (CML) from chronic phase (CP) to blast crisis (BC), ...which is frequently fatal. The data imply that MSI2 is upregulated by HOXA9 leading to disruption of the critical hematopoietic stem cell (HSC) fate decisions via the NUMB-NOTCH signaling pathway. These events lead to HSC proliferation, impaired myeloid differentiation and are associated with worse prognosis in CML and acute myeloid leukemia (Kharas, et al. Nat Med 2010; 16:903; Ito, et al. Nature 2010; 466:765). Previously, we confirmed increased MSI2 levels in CML patients in blast crisis (BC) compared with those in CP, irrespective of lymphoid or myeloid transformation (Kaeda, et al. Blood. 2011;118;supplement). To further elucidate this regulatory pathway we assessed whether HOXA9 expression correlated with increased MSI2mRNA levels and upregulation of NOTCH.
Because of the rarity of BC samples and finding MSI2 increased in lymphoid and myeloid BC CML patients, we studied lymphoid n=12 (Lymphoma:8; Myeloma:3; ALL:1) and myeloid n=12 (AML:4; CML:6; HES:1; ET:1) cells lines. We also included 29 BCR-ABL positive (e1a2: 18; e13a2: 6; e14a2: 5) diagnostic samples from acute lymphoblastic leukaemia (ALL) patients (M:18; F:11); median age 50 years (range: 26-74). We quantified MSI2 and HOXA9 mRNA transcripts by quantitative PCR and expressed the data as % ratio of the control gene, GUSβ.Western blotting of cell line protein extracts was performed to assess expression of NOTCH 1, 2, 3 receptors and delta like ligand 3.
We found MSI2 median: 7.10% (range:0.06-38.71) and HOXA9 median: 2.40% (range:0.00-51.13) expression was generally restricted to myeloid cell lines. Of the 12 lymphoid cell lines, MSI2 was only detectable in SUPB15 with 8.44%. The latter is a B-lymphocyte ALL cell line, known to express BCR-ABL e1a2 transcript. Similarly, HOXA9 median: 0.00 (range:0.00-27.0%) expression ranged from undetectable to 0.08%, among this group, apart from HD-MY-Z with 27.0%. In contrast, HOXA9 median: 0.02% (range:0.01-2.18) and MSI2 median: 3.58% (range: 1.24-22.38) transcripts were detectable in all 29 BCR-ABL positive ALL patients, irrespective of the transcript type expressed. Among the ALL samples 7 (24%) had increased MSI2 levels, i.e. >6.7% (Kaeda, et al. Blood. 2011;118;supplement) and of these 6 expressed e1a2 transcript and the other e13a2. In summary, upregulated MSI2 expression was observed in 17 (32.0%) of the 53 samples screened. But only 4 KG1, EOL1, HEL and MEG-01 (all myeloid cell lines) of the 17 also had increased HOXA9 levels. Remarkably, 5 (62%) of the 8 myeloid cell lines with increased MSI2 are known to express BCR-ABL. NOTCH1 receptor was detectable in all the lymphoid cell lines. But, NOTCH expression was highly variable in myeloid cell lines. Overall, an upregulated MSI2 mRNA expression was not reflected in the NOTCH receptor levels nor in the HOXA9levels.
Our observations are consistent with MSI2 being limited to myeloid linage. However, in contrast to earlier reports our data imply that MSI2 functions via a pathway other than NOTCH signaling and is not regulated by HOXA9 alone. But the cell lines and ALL patients' data provide further evidence of correlation between MSI2 and BCR-ABL expression, suggesting they interact, directly or indirectly, to arrest cell differentiation and trigger BC. These findings, together with our reported data, show increased MSI2 levels to be an important biomarker of poor prognosis and are likely to have an impact in optimizing clinical management. It also represents a potential novel therapeutic target, especially for the BCR-ABL positive stem cells resistant to tyrosine kinase inhibitors.
Kaeda:Novartis: Research Funding. le Coutre:Novartis: Research Funding.
Abstract 365▪▪This icon denotes an abstract that is clinically relevant.
Translocations of the Mixed Lineage Leukemia (MLL) gene occur in a subset (5%) of acute myeloid leukemia (AML) and in mixed ...phenotype acute leukemia in infancy, a disease with extremely poor prognosis. Animal model systems show that MLL gain of function mutations may contribute to leukemogenesis. Wild-type MLL carries histone methyltransferase activity and affects specific target genes, such us HOXA cluster genes. While the more than three dozen MLL fusion proteins known today exert different specific functions, they finally induce transcription of individual target genes. Consequently, acute lymphoblastic leukemias (ALL) with MLL mutations (MLLmu) exhibit typical gene expression profiles including high-level expression of HOXA cluster genes. Aim of this study was to find a correlation between the MLL mutational status and tumor suppressor gene methylation/expression in acute leukemia cell lines.
Using MS-MLPA (methylation-specific multiplex ligation-dependent probe amplification assay), methylation of 24 different TSG was analyzed in 28 MLLmu and MLLwt acute leukemia cell lines. 1.8/24 TSG were methylated in MLLmu AML cells, 6.2/24 TSG were methylated in MLLwt AML cells. Hypomethylation and expression of the tumor suppressor genes (TSG) BEX2, IGSF4 and TIMP3 turned out to be characteristic of MLLmu acute myeloid leukemia (AML) cell lines. MLL wild-type (MLLwt) AML cell lines displayed hypermethylated TSG promoters resulting in transcriptional silencing. Demethylating agents and inhibitors of histone deacetylases restored expression of BEX2, IGSF4 and TIMP3 confirming epigenetic silencing of these genes in MLLwt cells. The positive correlation between MLL translocation, TSG hypomethylation and expression suggested that MLL fusion proteins were responsible for dysregulation of TSG expression in MLLmu cells. This concept was supported by our observation that Bex2 mRNA levels in MLL-ENL transgenic mouse cell lines required expression of the MLL fusion gene.
These results suggest that the conspicuous expression of the TSG BEX2, IGSF4 and TIMP3 in MLLmu AML cell lines is the consequence of altered epigenetic properties of MLL fusion proteins.
No relevant conflicts of interest to declare.
The global population’s increasing demand for sustainable and nutritious food sources has led to the exploration of alternative approaches in livestock production. Edible insects have emerged as a ...promising solution due to their nutritional composition, including high protein content, balanced fats, minerals, vitamins, and bioactive peptides. Biofermentation offers a viable method to enhance the nutritional value of insect feed. This study aimed to investigate the effects of feeding biofermented feeds derived from less valuable raw materials on the yield and nutritional composition of Zophobas morio larvae. The focus was on assessing fat quality, omega-3 and omega-6 fatty acids, and bioactive compounds and monitoring the larvae’s weight and length increases. Three feed types were tested: wheat bran (control), fermented wheat bran, and a mixture of fermented corn and flaxseed in a five-week period. The findings demonstrated a noteworthy (p < 0.05) elevation in polyunsaturated fatty acids, such as gamma-linolenic acid, alpha-linolenic acid, and eicosapentaenoic acid in Zophobas morio larvae fed with biofermented corn and flaxseed pomace, both pre- and postculinary treatment, as compared to the control group. The study also showed increased chelation of Cusup.2+ (p < 0.05) and Fesup.2+ (p < 0.05) between native and roasted insects in the samples without in vitro digestion, as well as increased Cyclooxygenase-1 activity (p < 0.05), indicating improved bioavailability. Additionally, culinary processing led to a reduction in polyphenol content (p < 0.05), antioxidant activity (p > 0.05) except DPPH, and peptide concentration (p < 0.05) in the samples without in vitro digestion.
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