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Article ; Online: Investigation of Mutated in Colorectal Cancer (MCC) Gene Family Evolution History Indicates a Putative Role in Th17/Treg Differentiation.

Kubick, Norwin / Paszkiewicz, Justyna / Bieńkowska, Irmina / Ławiński, Michał / Horbańczuk, Jarosław Olav / Sacharczuk, Mariusz / Mickael, Michel Edwar

International journal of molecular sciences

2023 Volume 24, Issue 15

Abstract: The MCC family of genes plays a role in colorectal cancer development through various immunological pathways, including the Th17/Treg axis. We have previously shown that MCC1 but not MCC2 plays a role in Treg differentiation. Our understanding of the ... ...

Abstract	The MCC family of genes plays a role in colorectal cancer development through various immunological pathways, including the Th17/Treg axis. We have previously shown that MCC1 but not MCC2 plays a role in Treg differentiation. Our understanding of the genetic divergence patterns and evolutionary history of the MCC family in relation to its function, in general, and the Th17/Treg axis, in particular, remains incomplete. In this investigation, we explored 12 species' genomes to study the phylogenetic origin, structure, and functional specificity of this family. In vertebrates, both MCC1 and MCC2 homologs have been discovered, while invertebrates have a single MCC homolog. We found MCC homologs as early as Cnidarians and Trichoplax, suggesting that the MCC family first appeared 741 million years ago (Ma), whereas MCC divergence into the MCC1 and MCC2 families occurred at 540 Ma. In general, we did not detect significant positive selection regulating MCC evolution. Our investigation, based on MCC1 structural similarity, suggests that they may play a role in the evolutionary changes in Tregs' emergence towards complexity, including the ability to utilize calcium for differentiation through the use of the EFH calcium-binding domain. We also found that the motif NPSTGE was highly conserved in MCC1, but not in MCC2. The NPSTGE motif binds KEAP1 with high affinity, suggesting an Nrf2-mediated function for MCC1. In the case of MCC2, we found that the "modifier of rudimentary" motif is highly conserved. This motif contributes to the regulation of alternative splicing. Overall, our study sheds light on how the evolution of the MCC family is connected to its function in regulating the Th17/Treg axis.
MeSH term(s)	Animals ; Humans ; Kelch-Like ECH-Associated Protein 1/genetics ; Phylogeny ; T-Lymphocytes, Regulatory ; Calcium ; NF-E2-Related Factor 2/genetics ; Colorectal Neoplasms/genetics ; Th17 Cells
Chemical Substances	Kelch-Like ECH-Associated Protein 1 ; Calcium (SY7Q814VUP) ; NF-E2-Related Factor 2
Language	English
Publishing date	2023-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241511940
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Article ; Online: Adera2.0: A Drug Repurposing Workflow for Neuroimmunological Investigations Using Neural Networks.

Lazarczyk, Marzena / Duda, Kamila / Mickael, Michel Edwar / Ak, Onurhan / Paszkiewicz, Justyna / Kowalczyk, Agnieszka / Horbańczuk, Jarosław Olav / Sacharczuk, Mariusz

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 19

Abstract: Drug repurposing in the context of neuroimmunological (NI) investigations is still in its primary stages. Drug repurposing is an important method that bypasses lengthy drug discovery procedures and focuses on discovering new usages for known medications. ...

Abstract	Drug repurposing in the context of neuroimmunological (NI) investigations is still in its primary stages. Drug repurposing is an important method that bypasses lengthy drug discovery procedures and focuses on discovering new usages for known medications. Neuroimmunological diseases, such as Alzheimer's, Parkinson's, multiple sclerosis, and depression, include various pathologies that result from the interaction between the central nervous system and the immune system. However, the repurposing of NI medications is hindered by the vast amount of information that needs mining. We previously presented Adera1.0, which was capable of text mining PubMed for answering query-based questions. However, Adera1.0 was not able to automatically identify chemical compounds within relevant sentences. To challenge the need for repurposing known medications for neuroimmunological diseases, we built a deep neural network named Adera2.0 to perform drug repurposing. The workflow uses three deep learning networks. The first network is an encoder and its main task is to embed text into matrices. The second network uses a mean squared error (MSE) loss function to predict answers in the form of embedded matrices. The third network, which constitutes the main novelty in our updated workflow, also uses a MSE loss function. Its main usage is to extract compound names from relevant sentences resulting from the previous network. To optimize the network function, we compared eight different designs. We found that a deep neural network consisting of an RNN neural network and a leaky ReLU could achieve 0.0001 loss and 67% sensitivity. Additionally, we validated Adera2.0's ability to predict NI drug usage against the DRUG Repurposing Hub database. These results establish the ability of Adera2.0 to repurpose drug candidates that can shorten the development of the drug cycle. The workflow could be download online.
MeSH term(s)	Data Mining ; Drug Discovery ; Drug Repositioning/methods ; Neural Networks, Computer ; Workflow
Language	English
Publishing date	2022-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27196453
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Article: Tick exposure and prevalence of Borrelia burgdorferi antibodies among hunters and other individuals exposed to vector ticks in eastern Poland

Pańczuk, Anna / Tokarska-Rodak, Małgorzata / Plewik, Dorota / Paszkiewicz, Justyna

Roczniki Panstwowego Zakladu Higieny

2019 Volume 70, Issue 2, Page(s) 161–168

MeSH term(s)	Adult ; Animals ; Borrelia burgdorferi/isolation & purification ; Humans ; Lyme Disease/epidemiology ; Lyme Disease/microbiology ; Male ; Middle Aged ; Occupational Exposure/statistics & numerical data ; Poland/epidemiology ; Prevalence ; Tick Bites/epidemiology ; Tick-Borne Diseases/epidemiology ; Tick-Borne Diseases/microbiology ; Ticks
Language	English
Publishing date	2019-06-19
Publishing country	Poland
Document type	Journal Article
ZDB-ID	421739-1
ISSN	0035-7715
ISSN	0035-7715
DOI	10.32394/rpzh.2019.0066
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Article ; Online: The Journey of Cancer Cells to the Brain: Challenges and Opportunities.

Łazarczyk, Marzena / Mickael, Michel Edwar / Skiba, Dominik / Kurzejamska, Ewa / Ławiński, Michał / Horbańczuk, Jarosław Olav / Radziszewski, Jakub / Fraczek, Karolina / Wolinska, Renata / Paszkiewicz, Justyna / Religa, Piotr / Sacharczuk, Mariusz

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Cancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of ... ...

Abstract	Cancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood-brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better understanding of the metastasis process to uncover novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the diverse processes that they undergo to colonize the brain. These processes include EMT, intravasation, extravasation, and infiltration of the blood-brain barrier, ending up with colonization and angiogenesis. In each phase, we focus on the pathways engaging molecules that potentially could be drug target candidates.
MeSH term(s)	Humans ; Brain Neoplasms/metabolism ; Blood-Brain Barrier/metabolism ; Signal Transduction ; Neoplasm Metastasis/pathology
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043854
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Article ; Online: Investigation of the Molecular Evolution of Treg Suppression Mechanisms Indicates a Convergent Origin.

Bhaumik, Suniti / Łazarczyk, Marzena / Kubick, Norwin / Klimovich, Pavel / Gurba, Agata / Paszkiewicz, Justyna / Teodorowicz, Patrycja / Kocki, Tomasz / Horbańczuk, Jarosław Olav / Manda, Gina / Sacharczuk, Mariusz / Mickael, Michel-Edwar

Current issues in molecular biology

2023 Volume 45, Issue 1, Page(s) 628–648

Abstract: Regulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms’ emergence ...

Abstract	Regulatory T cell (Treg) suppression of conventional T cells is a central mechanism that ensures immune system homeostasis. The exact time point of Treg emergence is still disputed. Furthermore, the time of Treg-mediated suppression mechanisms’ emergence has not been identified. It is not yet known whether Treg suppression mechanisms diverged from a single pathway or converged from several sources. We investigated the evolutionary history of Treg suppression pathways using various phylogenetic analysis tools. To ensure the conservation of function for investigated proteins, we augmented our study using nonhomology-based methods to predict protein functions among various investigated species and mined the literature for experimental evidence of functional convergence. Our results indicate that a minority of Treg suppressor mechanisms could be homologs of ancient conserved pathways. For example, CD73, an enzymatic pathway known to play an essential role in invertebrates, is highly conserved between invertebrates and vertebrates, with no evidence of positive selection (w = 0.48, p-value < 0.00001). Our findings indicate that Tregs utilize homologs of proteins that diverged in early vertebrates. However, our findings do not exclude the possibility of a more evolutionary pattern following the duplication degeneration−complementation (DDC) model. Ancestral sequence reconstruction showed that Treg suppression mechanism proteins do not belong to one family; rather, their emergence seems to follow a convergent evolutionary pattern.
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb45010042
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Zs.A 5122: Show issues

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Article: Seroprevalence of Rubella and Cytomegalia in Young Women from Biała Podlaska District.

Plewik, Dorota / Tokarska-Rodak, Małgorzata / Paszkiewicz, Justyna / Szepeluk, Adam

Polish journal of microbiology

2018 Volume 66, Issue 4, Page(s) 543–545

Abstract: The aim of this study was to analyze the seroprevalence of rubella and cytomegalia among young women. The study included 175 healthy women from the Biała Podlaska District, aged 16 to 35 years. Anti-rubella and anti-CMV IgG were determined by ELISA. 172 ( ...

Abstract	The aim of this study was to analyze the seroprevalence of rubella and cytomegalia among young women. The study included 175 healthy women from the Biała Podlaska District, aged 16 to 35 years. Anti-rubella and anti-CMV IgG were determined by ELISA. 172 (98.3%) study subjects tested positive for rubella antibodies, 1 (0.6%) was seroindeterminate and 2 (1.1%) were seronegative. CMV antibodies were detected in 119 (68.0%) participants; the series included also 1 (0.6%) seroindeterminate and 55 (31.4%) seronegative women. The levels of rubella and CMV antibodies were not significantly affected by age, place of residence and educational level of the study subjects.
MeSH term(s)	Adolescent ; Adult ; Antibodies, Viral/blood ; Cytomegalovirus Infections/epidemiology ; Cytomegalovirus Infections/immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Poland/epidemiology ; Pregnancy ; Rubella/epidemiology ; Rubella/immunology ; Seroepidemiologic Studies ; Young Adult
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M ; rubella antibodies
Language	English
Publishing date	2018-01-10
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2234080-4
ISSN	2544-4646 ; 1733-1331
ISSN (online)	2544-4646
ISSN	1733-1331
DOI	10.5604/01.3001.0010.7103
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Article: Behaviour of chosen acute phase proteins in acute viral type B hepatitis as a predictive factor of further evolution of the infection.

Paszkiewicz, J

Archivum immunologiae et therapiae experimentalis

1993 Volume 41, Issue 3-4, Page(s) 267–273

Abstract: The study was aimed at the assessment of the immune system function of a large group of patients with early phase of acute viral type B hepatitis, who were subsequently follow-up in order to select those developing chronic forms of the infection. It was ... ...

Abstract	The study was aimed at the assessment of the immune system function of a large group of patients with early phase of acute viral type B hepatitis, who were subsequently follow-up in order to select those developing chronic forms of the infection. It was assumed that re-assessment of their initial immunological status with regard to further evolution of the infection would show some factors predictive of chronic active hepatitis development. Chosen immunological parameters: circulating blood lymphocyte sets and subsets, immunoglobulin concentrations, presence of non-specific immune complexes and concentrations of randomly chosen acute phase proteins (ceruloplasmin, transferrin, haptoglobin, alpha-acid glycoprotein, C3 and C4 complement components) were evaluated in 104 acute viral type B hepatitis patients, aged 18-50, on the days 8, 10, 15, 30, 40, 60, 80 and 130 of the illness. After mean of 744 days, 56 patients reported to final follow-up examination, 15 of whom presented with symptoms of chronic sequelae of acute HBV infection (elimination phase of chronic aggressive hepatitis, chronic persistent hepatitis, or integration phase of HBV infection). Behaviour of cellular immunity parameters, immunoglobulin concentrations, presence of immune complexes or non-specific antibodies, however varied in individual patients, showed no correlation predictive of chronic sequelae of the infection. Significant differences between patients who subsequently developed chronic active or chronic persistent hepatitis were found, however, with regard to all the acute phase proteins tested, most prominent in case of C3 and C4 complement components, haptoglobin, transferrin and ceruloplasmin.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH term(s)	Acute Disease ; Acute-Phase Proteins/analysis ; Adolescent ; Adult ; Complement C3/analysis ; Complement C4/analysis ; Female ; Hepatitis B/immunology ; Humans ; Male ; Middle Aged
Chemical Substances	Acute-Phase Proteins ; Complement C3 ; Complement C4
Language	English
Publishing date	1993
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	282209-x
ISSN	1661-4917 ; 0004-069X
ISSN (online)	1661-4917
ISSN	0004-069X
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Article ; Online: Double left anterior descending artery: Congenital anomaly or normal variant of coronary arteries?

Spałek, Michał / Stępień-Wałek, Alicja / Paszkiewicz, Joanna / Wożakowska-Kapłon, Beata

Cardiology journal

2017 Volume 24, Issue 4, Page(s) 445–446

MeSH term(s)	Aged ; Computed Tomography Angiography ; Coronary Angiography/methods ; Coronary Vessel Anomalies/classification ; Coronary Vessel Anomalies/diagnostic imaging ; Coronary Vessel Anomalies/therapy ; Coronary Vessels/diagnostic imaging ; Drug-Eluting Stents ; Female ; Humans ; Middle Aged ; Percutaneous Coronary Intervention/instrumentation
Language	English
Publishing date	2017
Publishing country	Poland
Document type	Case Reports ; Journal Article
ZDB-ID	2488680-4
ISSN	1897-5593 ; 1897-5593
ISSN (online)	1897-5593
ISSN	1897-5593
DOI	10.5603/CJ.2017.0090
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Book ; Online: Classification of vacuum arc breakdowns in a pulsed DC system

Saressalo, Anton / Profatilova, Iaroslava / Kyritsakis, Andreas / Paszkiewicz, Jan / Calatroni, Sergio / Wuensch, Walter / Djurabekova, Flyura

2019

Abstract: Understanding the microscopic phenomena behind vacuum arc ignition and generation is crucial for being able to control the breakdown rate, thus improving the effectiveness of many high-voltage applications where frequent breakdowns limit the operation. ... ...

Abstract	Understanding the microscopic phenomena behind vacuum arc ignition and generation is crucial for being able to control the breakdown rate, thus improving the effectiveness of many high-voltage applications where frequent breakdowns limit the operation. In this work, statistical properties of various aspects of breakdown, such as the number of pulses between breakdowns, breakdown locations, electronic waveforms and crater sizes are studied independently with almost identical Pulsed DC Systems at the University of Helsinki and in CERN. In high-gradient experiments, copper electrodes with parallel plate capacitor geometry, undergo thousands of breakdowns. The results support the classification of the events into primary and secondary breakdowns, based on the distance and number of pulses between two breakdowns. Primary events follow a power law on the log--log scale with the slope $\alpha \approx 1.33$, while the secondaries are highly dependent on the pulsing parameters. Comment: 11 pages, 12 figures
Keywords	Physics - Instrumentation and Detectors ; Condensed Matter - Materials Science
Publishing date	2019-11-11
Publishing country	us
Document type	Book ; Online
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Article: Ryzyko zakazeń zawodowych Borrelia burgdorferi u pracowników leśnictwa i rolników.

Tokarska-Rodak, Małgorzata / Plewik, Dorota / Kozioł-Montewka, Maria / Szepeluk, Adam / Paszkiewicz, Justyna

Medycyna pracy

2014 Volume 65, Issue 1, Page(s) 109–117

Abstract: Background: The aim of the work was to analyze the incidence of infection with Borrelia burgdorferi in forestry workers and farmers, major groups occupationally exposed to tick bites.: Material and methods: The study group included 275 workers (171 ... ...

Title translation	Risk of occupational infections caused by Borrelia burgdorferi among forestry workers and farmers.
Abstract	Background: The aim of the work was to analyze the incidence of infection with Borrelia burgdorferi in forestry workers and farmers, major groups occupationally exposed to tick bites. Material and methods: The study group included 275 workers (171 foresters and 104 farmers). The control group consisted of 45 people, who have not been occupationally exposed to tick bites. The screening Elisa and Wb tests for the presence of anti-Borrelia IgM/IgG antibodies were performed in all subjects of the study and control groups. Statistical analysis was performed using the Chi2 test. Results: The positive results denoting the presence of anti-Borrelia IgM/IgG antibodies were found in 55% of farmers and 28% of foresters occupationally exposed to Lyme borreliosis and coming from the area of South Podlasie Lowland and Lublin Polesie. The differences between the forestry workers and the control group (p < or = 0.00001) and between farmers and the control group (p < or = 0.001) were statistically significant. The species, such as B. spielmanii and B. bavariensis, which have not yet been reported in Poland, are significant etiologic agents of Lyme disease. Conclusion: The risk of occupational exposure to the B. burgdorferi infection is high for foresters and farmers, and the infection with spirochetes is frequently confirmed on the basis of positive results of the Wb test. The presence of specific antibodies against protein antigens of B. spielmanii and B. bavariensis suggest that these bacteria can cause Lyme disease both independently and in participation with other Borrelia species, which influences the development of the clinical manifestations of infection.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Agricultural Workers' Diseases/epidemiology ; Animals ; Antibodies, Bacterial/blood ; Borrelia burgdorferi/pathogenicity ; Causality ; Female ; Forestry ; Humans ; Incidence ; Lyme Disease/epidemiology ; Lyme Disease/microbiology ; Male ; Middle Aged ; Occupational Diseases/epidemiology ; Occupational Diseases/microbiology ; Occupational Exposure/analysis ; Occupational Exposure/statistics & numerical data ; Poland/epidemiology ; Risk Factors ; Tick Bites/epidemiology ; Tick-Borne Diseases/epidemiology ; Young Adult
Chemical Substances	Antibodies, Bacterial
Language	Polish
Publishing date	2014-05-15
Publishing country	Poland
Document type	English Abstract ; Journal Article
ZDB-ID	128739-4
ISSN	0465-5893
ISSN	0465-5893
DOI	10.13075/mp.5893.2014.017
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