imagine (Institute of molecular genetics and genetic engineering)
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Impact of genotype on neutropenia in a large cohort of Serbian patients with glycogen storage disease type Ib
No full textBackground: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. Methods: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. Results: Absolute neutrophil count (ANC) lt 1500/mm(3) was present in all 33 patients, with severe neutropenia (ANC lt 500/mm(3)) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T gt A/c.785G gt A and c.81T gt A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G gt A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. Conclusions: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI
A comparative study of liquid holding restitution of viability after oxidative stress in Ustilago maydis and Saccharomyces cerevisiae cell populations
No full textThe ability of Saccharomyces cerevisiae to reconstitute viability after strong peroxide-induced oxidative stress during liquid holding (LH) in non-nutrient medium has been compared with that of Ustilago maydis. It was found that like U. maydis, S. cerevisiae was capable of reconstituting viability through multiplication of the survivors. However, differences were observed in the pattern of their response: (i) the reconstitution of viability was slower in S. cerevisiae; (ii) before the viability was progressively increasing the treated samples of this fungus reproducibly passed through a phase of additional decrease of the surviving fraction and (iii) the final yields of viable cells attained in S. cerevisiae were below those achieved by U. maydis. The reason for the relative superiority of U. maydis is twofold: (1) early initiated and faster degradation and leakage of the intracellular biomolecules and (2) greater ability of U. maydis cells to recycle damaged and released intracellular compounds. Conceptually similar studies extended to another oxidative-stress-inducing condition, namely desiccation, indicated that the marked differences between these fungi in their patterns of the post-stress regrowth, cellular leakage and macromolecule decomposition are reproduced during LH of desiccated cells. The concordance of the findings obtained upon these two approaches was also corroborated by an analysis of the post-desiccation LH response of U. maydis mutants (adri, did4, kell and tbp1) that were previously identified as defective in post-peroxide LH restitution of viability. We discuss the findings in terms of their possible relevance to the mechanisms of the ecological and evolutionary adaptation of free-living microorganisms to fluctuating and severely inhospitable environments
Discovery and Biochemical Characterization of a Novel Polyesterase for the Degradation of Synthetic Plastics
Get PDFPlastic waste poses an enormous environmental problem as a result of soil and ocean contamination, causing the release of microplastics that end up in humans through the food web. Enzymatic degradation of plastics has emerged as an alternative to traditional recycling processes. In the present work, we used bioinfomatics tools to discover a gene coding for a putative polyester degrading enzyme (polyesterase). The gene was heterologously expressed, purified and biochemically characterized. Furthermore, its ability to degrade polyethylene terephthalate (PET) model substrates and synthetic plastics was assessed
Influence of DOAC Remove on Coagulation Assays During Thrombophilia Testing in Patients Treated with Rivaroxaban or Dabigatran
No full textBackground: Direct oral anticoagulants (DOAC) are increasingly being used as an alternative to warfarin in the treatment of venous thromboembolism. DOAC administration has a significant impact on coagulation assays. This is especially important during thrombophilia testing.
Aims: To evaluate the effect of DOAC Remove on coagulation assays during thrombophilia testing in patients treated with DOAC.
Methods: We have used samples from 20 patients treated with DOAC. Two samples of venous blood on sodium citrate were taken for each patient. One was prepared by standard method for coagulation assays, while, the second one was prepared using DOAC Remove. According to the instruction the samples were mixed gently for 5 minutes with DOAC Remove tablet, and then centrifuged 2 minutes on 2000g. The supernatant after centrifugation is used to the coagulation assays. So prepared samples were used in the thrombophilia testing.
Results: Before DOAC Remove in 10 patients treated with Rivaroxaban average APTT of 31.5s; PT 104%; LA1 51.7s; LA2 40.3s; LA- R 1.28, AT 104%, PC 104%, PS 87% and APC-R 4.1 were obtained. In Dabigatran patients APTT 40.5s, PT 104%; LA1 73.7s; LA2 53.7s; LA-R 1.37, AT 103% PC 98% and PS 82% were obtained. In relation to the APC-R test, in half of the investigated patients no result for APC-R was obtained, while, for the rest, average APC-R of 6.5 were obtained. After DOAC Remove in Rivaroxaban patients APTT 29.7s; PT 110%; LA1 37.3s; LA2 33.8s; LA- R 1.12, AT 96%, PC 102%, PS 88% and APCR 4.2 were recorded. In Dabigatran patients APTT 28.1s, PT 117%; LA 39.1s; LA2 33.8s; LA-R 1.15, AT 104%, PC 97.5%, PS 84.5% and APC-R 6.5 were recorded.
Conclusions: DOAC was practically inactivated after the addition of the DOAC Remove, which made it possible to perform analyzes for the LA and APC-R testing freely and obtain relevant results.ISTH 2020 Congress; July 12-14, 2020. Virtual Congress
Genomic profiling of thymoma using a targeted high-throughput approach
Get PDFIntroduction: Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) technology has provided novel data on their molecular pathology. Material and methods: Genomic..
Current state and prospects of biotechnology in Central and Eastern European countries. Part II: new and preaccession EU countries(CRO, RO, B&H, SRB)
No full textInnovation holds the potential for economic prosperity. Biotechnology (BT) has proved to be a viable vehicle for the development and utilization of technologies, which has brought not only advances to society, but also career opportunities to nation-states that have enabling conditions. In this review, we assess the current state of BT-related activities within selected new and preaccession EU countries (NPA) of CEE region namely Croatia, Romania, Bosnia and Herzegovina and Serbia, examining educational programs, research activity, enterprises, and the financing systems. The field of BT covers a broad area of activities, including medical, food and agriculture, aquaculture or marine, environmental, biofuels, bioinformatics, and many others. Under the European Commission (EC), member-states are to set their Research and Innovation Strategies for Smart Specialization (RIS3), to identify priorities or strengths in order to develop knowledge intensive economies. As the four countries highlighted in this review are in the early stages of implementing RIS3 or have not yet fully formulated, it presents an opportunity to learn from the successes and failures of those that have already received major structural funds from the EC. A critical point will be the ability of the public and private sectors’ actors to align, in the implementation of RIS3 as new investment instruments emerge, and to concentrate efforts on a few select target goals, rather than distribute funding widely without respect to a long-term vision
Metastatic colorectal cancer chemotherapeutic drugs alter the expression of TGF beta signaling-related miR-175p, miR-21-5p and miR-93-5p in vitro
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Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
Get PDFIn a healthy immune repertoire, there exists a fraction of polyreactive antibodies that can bind to a variety of unrelated self- and foreign antigens. Apart from naturally polyreactive antibodies, in every healthy individual, there is a fraction of antibody that can gain polyreactivity upon exposure to porphyrin cofactor heme. Molecular mechanisms and biological significance of the appearance of cryptic polyreactivity are not well understood. It is believed that heme acts as an interfacial cofactor between the antibody and the newly recognized antigens. To further test this claim and gain insight into the types of interactions involved in heme binding, we herein investigated the influence of a group of aromatic guanylhydrazone molecules on the heme-induced antibody polyreactivity. From the analysis of SAR and the results of UV-vis absorbance spectroscopy, it was concluded that the most probable mechanism by which the studied molecules inhibit heme-mediated polyreactivity of the antibody is the direct binding to heme, thus preventing heme from binding to antibody and/or antigen. The inhibitory capacity of the most potent compounds was substantially higher than that of chloroquine, a well-known heme binder. Some of the guanylhydrazone molecules were able to induce polyreactivity of the studied antibody themselves, possibly by a mechanism similar to heme. Results described here point to the conclusion that heme indeed must bind to an antibody to induce its polyreactivity, and that both pi-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes
Applications of Microbial Laccases: Patent Review of the Past Decade (2009-2019)
Get PDFThere is a high number of well characterized, commercially available laccases with different redox potentials and low substrate specificity, which in turn makes them attractive for a vast array of biotechnological applications. Laccases operate as batteries, storing electrons from individual substrate oxidation reactions to reduce molecular oxygen, releasing water as the only by-product. Due to society's increasing environmental awareness and the global intensification of bio-based economies, the biotechnological industry is also expanding. Enzymes such as laccases are seen as a better alternative for use in the wood, paper, textile, and food industries, and they are being applied as biocatalysts, biosensors, and biofuel cells. Almost 140 years from the first description of laccase, industrial implementations of these enzymes still remain scarce in comparison to their potential, which is mostly due to high production costs and the limited control of the enzymatic reaction side product(s). This review summarizes the laccase applications in the last decade, focusing on the published patents during this period