imagine (Institute of molecular genetics and genetic engineering)
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Orally Administrated Lactiplantibacillus plantarum BGAN8-Derived EPS-AN8 Ameliorates Cd Hazards in Rats
Get PDFCadmium (Cd) is a highly toxic metal that is distributed worldwide. Exposure to it is correlated with a vast number of diseases and organism malfunctions. Exopolysaccharides (EPS) derived from Lactiplantibacillus plantarum BGAN8, EPS-AN8, previously showed great potential for the in vitro protection of intestinal cells from this metal. Here, we investigated the potential of food supplemented with EPS-AN8 to protect rats from the hazardous effects of Cd exposure. After thirty days of exposure to lower (5 ppm) and higher (50 ppm)-Cd doses, the administration of EPS-AN8 led to decreased Cd content in the kidneys, liver, and blood compared to only Cd-treated groups, whereas the fecal Cd content was strongly enriched. In addition, EPS-AN8 reversed Cd-provoked effects on the most significant parameters of oxidative stress (MDA, CAT, GST, and GSH) and inflammation (IL-1β, TNF-α, and IFN-γ) in the duodenum. Moreover, micrographs of the duodenum were in line with these findings. As the gut microbiota has an important role in maintaining homeostasis, we used 16S rRNA amplicon sequencing and investigated the effects of Cd and EPS-AN8 on one part of the microbiota presented in the duodenum. Although Cd decreased the growth of lactobacilli and mostly favored the blooming of opportunistic pathogen bacteria, parallel intake of EPS-AN8 reversed those changes. Therefore, our results imply that EPS-AN8 might be extremely noteworthy in combatting this toxic environmental pollutant
Supplementary data for the article:Marković, Z., Mišović, A., Zmejkoski, D., Zdravković, N., Kovač, J., Bajuk-Bogdanović, D., Milivojević, D., Mojsin, M., Stevanović, M., Pavlović, V.,& Todorović Marković, B.. (2023). Employing Gamma-Ray-Modified Carbon Quantum Dots to Combat a Wide Range of Bacteria. in Antibiotics, 12(5), 919. https://doi.org/10.3390/antibiotics12050919
Get PDFFigure S1. TEM micrographs a) CQD_25, b) CQD_50,c) CQD_100, and d) CQD_200 samples, respectively.Supp. data for: [https://doi.org/10.3390/antibiotics12050919
Expression profiling of ANKRD1 in rhabdomyosarcoma cell lines
Get PDFIntroduction: Rhabdomyosarcoma (RMS) is the most common soft tissue
malignancy in children and adolescents. Respecting the age
of the patients and the tumor aggressiveness, investigation
of the molecular mechanisms of RMS tumorigenesis is
essential, most notably due to the possible identification of
novel therapeutic targets. To contribute to a better
understanding of the molecular pathology of RMS, we
investigated ANKRD1 (ankyrin repeat domain 1) gene,
considered a potential RMS diagnostic marker. The
changes in its expression are related to carcinogenesis and
resistance to chemotherapy in several types of tumors.EACR 2023: Innovative Cancer Science, 12-15 June 2023, Torino, Ital
Food waste as a nutrient source for the production of biopigment in Streptomyces sp. BV365
Get PDFThe genus Streptomyces has been studied for the vast secondary metabolite
production, biological activity of crude extracts, as well as colouring properties on textile
materials [1, 2]. Streptomyces sp. BV365 is a potent producer of yellow pigments, used to
efficiently colour different natural textiles [3]. Utilization of food waste for bacterial growth
and production of pigments and antifungals [4] could contribute to conversion of waste to
valuable molecules, providing more economically acceptable and more eco-friendly
generated biotherapeutics, enzymes and pigments.KNJIGA IZVODA: 9. simpozijum Hemija i zaštita životne sredine
Kladovo, 4-7. jun 2023.
BOOK OF ABSTRACTS : 9th Symposium Chemistry and Environmental Protection
Kladovo, 4-7th June 202
Can Pharmacogenetic Variants in TPMT, MTHFR and SLCO1B1 Genes Be Used as Potential Markers of Outcome Prediction in Systemic Sclerosis Patients?
Get PDFSystemic sclerosis (SSc) is a rare connective tissue disorder with highest morbidity and mortality among rheumatologic diseases. Disease progression is highly heterogeneous between patients, implying a strong need for individualization of therapy. Four pharmacogenetic variants, namely TPMT rs1800460, TPMT rs1142345, MTHFR rs1801133 and SLCO1B1 rs4149056 were tested for association with severe disease outcomes in 102 patients with SSc from Serbia treated either with immunosuppressants azathioprine (AZA) and methotrexate (MTX) or with other types of medications. Genotyping was performed using PCR-RFLP and direct Sanger sequencing. R software was used for statistical analysis and development of polygenic risk score (PRS) model. Association was found between MTHFR rs1801133 and higher risk for elevated systolic pressure in all patients except those prescribed with MTX, and higher risk for kidney insufficiency in patients prescribed with other types of drugs. In patients treated with MTX, variant SLCO1B1 rs4149056 was protective against kidney insufficiency. For patients receiving MTX a trend was shown for having a higher PRS rank and elevated systolic pressure. Our results open a door wide for more extensive research on pharmacogenomics markers in patients with SSc. Altogether, pharmacogenomics markers could predict the outcome of patients with SSc and help in prevention of adverse drug reactions
Big Data in Biology: How EMBL delivers big data for biology, and some highlights of its application to human disease biology
Get PDFMolecular biology is now a leading example of a data intensive science, with both pragmatic
and theoretical challenges being raised by data volumes and dimensionality of the data.
These changes are present in both “large scale” consortia science and small scale science,
and across now a broad range of applications – from human health, through to agriculture
and ecosystems. All of molecular life science is feeling this effect. The European Molecular
Biology Laboratory (EMBL) – Europe’s only intergovernmental research organisation in
the life sciences is at the forefront of these developments performing both excellent
research and providing world leading services to enable science across Europe.
This shift in modality is creating a wealth of new opportunities and has some accompanying
challenges. In particular there is a continued need for a robust information infrastructure
for molecular biology. This ranges from the physical aspects of dealing with data volume
through to the more statistically challenging aspects of interpreting it. A particular
problem is finding causal relationships in the high level of correlative data. Genetic data
are particular useful in resolving these issues. I will present how EMBL pursues this
science and give examples from my own research that spans human genetics research
through to partnering for clinical application.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
Using AI/ML to transform molecular biology databases
Get PDFWe are living through a revolution in AI approaches, which is transforming molecular
biology and computational biology. I will discuss how the advent of high accuracy structural
models has made a large impact in our ability to completely and accurately classify protein
domains. I will also talk about how Deep Learning models such as ProtENN developed by
Google Research have expanded our ability to find distant homologues for known protein
families. I will argue that these models represent the most significant change in protein
classification in three decades. Even more recently we have seen to arrival of Large
Language Models such as ChatGPT, which may now enable us to develop high throughput
tools for annotating proteins, non-coding RNAs and families, if only we can stop them
hallucinating! I will talk about our efforts to harness these models to write accurate and
verifiable annotation at scale.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
What is life?’’: Open quantum systems approach
Get PDFRecently the quantum formalism and methodology started to be applied to modeling
of information processing in biosystems, mainly to the process of decision making and
psychological behavior (but some applications to microbiology and genetics are considered
as well). Since a living system is fundamentally open (an isolated biosystem is dead), the
theory of open quantum systems is the most powerful tool for life-modeling. In this
presentation, we turn to the famous Schrödinger book “What is life?” and reformulate his
speculations in terms of this theory. Schrödinger pointed out to order preservation as one
of the main distinguishing features of biosystems. Entropy has the tendency to increase
(Second Law of Thermodynamics for isolated classical systems and dissipation in open
classical and quantum systems). Schrödinger emphasized the ability of biosystems to beat
this tendency. We demonstrate that systems processing information in the quantumlike
way can preserve the order-structure expressed by the quantum (von Neumann or
linear) entropy. We emphasize the role of the special class of quantum dynamics and initial
states generating the camel-like graphs for entropy-evolution in the process of interaction
with a new environment E:
1) entropy (disorder) increasing in the process of adaptation to the specific features of E};
2) entropy decreasing (order increasing) resulting from adaptation;
3) the restoration of order or even its increase for limiting steady state. In the latter case
the steady state entropy can be even lower than the entropy of the initial state.
Such quantum entropy dynamics is illustrated by graphs obtained via numerical simulation
for quantum master equation. For simplicity of modelling we consider only quantum
Markov dynamics. But the real dynamics of biosystems’ states is non-Markovean.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
From multifunctionality to polypathogenicity with intrinsic disorder
Get PDFIntrinsically disordered proteins (IDPs) lack stable tertiary and/or secondary structure
under physiological conditions in vitro. IDPs are characterized by an astonishing multilevel
spatiotemporal heterogeneity, with their mosaic structure representing a complex
combination of foldons, inducible foldons, morphing inducible foldons, non-foldons, semifoldons,
and unfoldons.
IDPs are highly abundant in nature and have functional repertoire that is very
broad and complements functions of ordered proteins. Often, IDPs are involved in
regulation, signaling and control pathways, commonly acting as hubs in protein-protein
interaction networks. Intrinsic disorder is an important constituent of the proteoform
concept, representing one of the important means of functional diversification of the
proteinaceous products of a gene. Functions of IDPs may arise from specific disordered
forms, from inter-conversion of disordered forms, or from order ←→ disorder transitions.
The choice between these conformations is determined by the peculiarities of the
protein environment, and many IDPs possess an exceptional ability to differently fold in a
template-dependent manner. As a result, many IDPs are capable of conducting multiple
functions, with such multifunctionality being linked to their spatiotemporal heterogeneity.
Therefore, a correlation between protein structure and function represents a “protein
structure–function continuum”, where a given protein exists as a dynamic conformational
ensemble containing multiple proteoforms characterized by diverse structural features
and miscellaneous functions.
IDPs are tightly controlled in the norm by various genetic and non-genetic mechanisms.
Alteration in regulation of this disordered regulators are often detrimental to a cell, and
many IDPs are associated with a variety of human diseases, such as cancer, cardiovascular
disease, amyloidoses, neurodegenerative diseases, diabetes and others. Furthermore,
many IDPs are multipathogenic, being associated with the origination and development
of a number of different diseases. Therefore, there is a though-provoking interconnection
between intrinsic disorder, cell signaling, and human diseases, with polypathogenicity of
the involved proteins being linked to their structural plasticity and multifunctionality.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
Persistence of plasmids targeted by CRISPR interference in bacterial populations
Get PDFCRISPR-Cas systems provide prokaryotes with an RNA-guided defense against foreign
mobile genetic elements (MGEs) such as plasmids and viruses. A common mechanism by
which MGEs avoid interference by CRISPR consists of acquisition of escape mutations in
regions targeted by CRISPR. Here, using microbiological, live microscopy and microfluidics
analyses we demonstrate that plasmids can persist for multiple generations in some
Escherichia coli cell lineages at conditions of continuous targeting by the type I-E CRISPRCas
system. We used mathematical modeling to show how plasmid persistence in a
subpopulation of cells mounting CRISPR interference is achieved due to the stochastic
nature of CRISPR interference and plasmid replication events. We hypothesize that the
observed complex dynamics provides bacterial populations with long-term benefits due
to continuous maintenance of mobile genetic elements in some cells, which leads to
diversification of phenotypes in the entire community and allows rapid changes in the
population structure to meet the demands of a changing environment.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202