Publications by authors named "Pilarczyk M"

Article Synopsis
  • The connectivity enhanced structure activity relationship (ceSAR) is a new in silico method for drug discovery that combines cheminformatics with transcriptional signature analysis from the LINCS library.* -
  • ceSAR ranks drug candidates based on their similarity to known compounds and the impact on specific gene knockdowns, and then refines these ranks using molecular docking techniques and machine learning.* -
  • Benchmark tests show that ceSAR significantly reduces false positives and speeds up the drug discovery process, with successful application in finding inhibitors for the BCL2A1 target linked to melanoma and inflammation.*
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This review delves into the enzymatic processes governing the initial stages of glycerophospholipid (phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine) and triacylglycerol synthesis. The key enzymes under scrutiny include GPAT and AGPAT. Additionally, as most AGPATs exhibit LPLAT activity, enzymes participating in the Lands cycle with similar functions are also covered.

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There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here we present iLINCS ( http://ilincs.org ), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations.

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Air pollution, to which children are more susceptible than adults, can promote airway inflammation, potentially exaggerating the effects of respiratory viral infection. This study examined the association between the clinical manifestation of COVID-19 in unvaccinated pediatric patients hospitalized in Poland (n = 766) and levels of particulate matter 2.5 (PM) and benzo(a)pyrene (B(a)P) within a week before hospitalization.

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Rapid progress in proteomics and large-scale profiling of biological systems at the protein level necessitates the continued development of efficient computational tools for the analysis and interpretation of proteomics data. Here, we present the piNET server that facilitates integrated annotation, analysis and visualization of quantitative proteomics data, with emphasis on PTM networks and integration with the LINCS library of chemical and genetic perturbation signatures in order to provide further mechanistic and functional insights. The primary input for the server consists of a set of peptides or proteins, optionally with PTM sites, and their corresponding abundance values.

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The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program with the goal of generating a large-scale and comprehensive catalogue of perturbation-response signatures by utilizing a diverse collection of perturbations across many model systems and assay types. The LINCS Data Portal (LDP) has been the primary access point for the compendium of LINCS data and has been widely utilized. Here, we report the first major update of LDP (http://lincsportal.

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The vast amount of RNA-seq data deposited in Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) is still a grossly underutilized resource for biomedical research. To remove technical roadblocks for reusing these data, we have developed a web-application GREIN (GEO RNA-seq Experiments Interactive Navigator) which provides user-friendly interfaces to manipulate and analyze GEO RNA-seq data. GREIN is powered by the back-end computational pipeline for uniform processing of RNA-seq data and the large number (>6,500) of already processed datasets.

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The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies.

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The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate a diverse and extensive reference library of cell-based perturbation-response signatures, along with novel data analytics tools to improve our understanding of human diseases at the systems level. In contrast to other large-scale data generation efforts, LINCS Data and Signature Generation Centers (DSGCs) employ a wide range of assay technologies cataloging diverse cellular responses. Integration of, and unified access to LINCS data has therefore been particularly challenging.

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Background: Quantifying the response of cell lines to drugs or other perturbagens is the cornerstone of pre-clinical drug development and pharmacogenomics as well as a means to study factors that contribute to sensitivity and resistance. In dividing cells, traditional metrics derived from dose-response curves such as IC , AUC, and E , are confounded by the number of cell divisions taking place during the assay, which varies widely for biological and experimental reasons. Hafner et al.

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Aim: To investigate the impact of IL28B and gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.

Methods: We enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients.

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Introduction: An appropriate management of HBV infection is the best strategy to finally reduce the total burden of HBV infection. Mother-to-child transmission (MTCT) is responsible for more than one third of chronic HBV infections worldwide. Because HBV infection in infancy or early childhood often leads to chronic infection, appropriate prophylaxis and management of HBV in pregnancy is crucial to prevent MTCT.

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Common carp Cyprinus carpio displaying proactive or reactive stress coping styles were acclimated to two environmental regimes (low oxygen and low temperature), and selected groups were tested for response to an inflammatory challenge (Escherichia coli lipopolysaccharide, LPS). Plasma glucose and lactate levels were measured, as were selected C. carpio-specific messenger (m)RNA transcript abundance, including cortisol receptor (CR), enolase (ENO), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and interleukin-1-beta (IL1β) was measured in individual whole brain samples.

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Lipid rafts (LRs) are dynamic, sterol- and sphingolipid-enriched nanodomains involved in the regulation of cellular functions and signal transduction, that upon stimuli, via (e.g. association of raft proteins and lipids), may cluster into domains of submicron or micron scale.

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Background And Objective: The course of chronic hepatitis C in children is often mild or asymptomatic, but may lead to liver cirrhosis and neoplasm. The aim of our study was retrospective evaluation of treatment efficacy using pegylated interferon (IFN)-α2b with ribavirin in children and adolescents with chronic hepatitis C, both treatment naïve and re-treated.

Methods: The study comprised 79 patients with chronic hepatitis C ages 8 to 18 years (43 patients re-treated; 54 infected with genotype 1 hepatitis C virus and 25 with genotype 4), treated with pegylated IFN-α2b (1.

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Introduction: The paper presents the methodology and the algorithm developed to analyze sonar images focused on fish detection in small water bodies and measurement of their parameters: volume, depth and the GPS location. The final results are stored in a table and can be exported to any numerical environment for further analysis.

Material And Method: The measurement method for estimating the number of fish using the automatic robot is based on a sequential calculation of the number of occurrences of fish on the set trajectory.

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IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4.

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Background: Treatment of hepatitis C virus (HCV) infection with interferon (IFN) and ribavirin (RBV) is associated with adverse events, which may affect the patient's adherence to the treatment regimen and the treatment efficacy.

Objectives: The aim of this study was to assess the sustained viral response (SVR) and interdependence between the haematological characteristics (leukocyte count, platelet count, and haemoglobin levels) in patients with chronic hepatitis C (CHC) infection during treatment with IFN and RBV.

Patients And Methods: We conducted a retrospective cohort study of 170 children with CHC infection who completed treatment with IFN-α and RBV.

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The objective was to take a first step in the development of a process-oriented quality assurance (QA) system for monitoring and safeguarding of fish welfare at a company level. A process-oriented approach is focused on preventing hazards and involves establishment of critical steps in a process that requires careful control. The seven principles of the Hazard Analysis Critical Control Points (HACCP) concept were used as a framework to establish the QA system.

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The article discusses the merits and limitations of commercially available solid-phase microextraction (SPME) fibres and compares them with the new type of extraction coatings, in particular those containing polyethylene glycol as sorbent, as well as the methods of the preparation of the latter. It also analyses their possible application for the extraction of a broad spectrum of analytes, with particular emphasis on the sampling of polar organic compounds from different media.

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Background: This study assessed the efficacy and safety of treatment of chronic hepatitis C in children with pegylated interferon alpha and ribavirin.

Material/methods: Investigations were performed on 53 children with chronic hepatitis C, aged 8-17 years. Children were divided into 2 groups: naïve (n=29) and retreated (n=24).

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This critical review presents information on known and innovative approaches to the manufacture of fibre coatings used in solid-phase microextraction (SPME). The properties, advantages and drawbacks of the different types of commercially available SPME fibre coatings are discussed in detail, as are those of novel types of coatings and the methodologies of their preparation. The applications of fibre coatings in the solid-phase microextraction of a broad spectrum of analytes are analysed, with particular emphasis on the sampling of polar analytes from polar matrices (174 references).

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Individual common carp Cyprinus carpio were screened repeatedly for risk taking (rate of exploration of a novel, potentially dangerous environment) and for competitive ability (success in gaining access to a spatially restricted food source). Marked differences in behaviour were evident, and significant consistency in individual responses across trials was found for both risk taking and competitive ability. In addition, there was a significant positive relationship between individual performance in these two contexts, with fish that explored more quickly in the novel environment tending to be among the first to gain access to restricted food.

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A new sorption system for isolation/enrichment of polar organic analytes from aqueous samples was obtained by substantial modification of the solid-phase microextraction (SPME) probe. In this system, polar sorbents are separated from the sample by a hydrophobic membrane. The new membrane SPME (M-SPME) probe was made utilizing polyethylene glycol (PEG) (molecular weight = 20 kDa) and polydimethylsiloxane (PDMS) as the membrane material.

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Background: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges.

Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated.

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