Y. Pavlov

发表

Pivotal Role of Inosine Triphosphate Pyrophosphatase in Maintaining Genome Stability and the Prevention of Apoptosis in Human Cells

M. Menezes, Xu Luo, I. Waisertreiger, 2012, PloS one.

Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast

V. I. Mayorov, I. Rogozin, T. Karpova, 2011, Biochemistry (Moscow).

Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes

G. Glazko, D. Cooper, I. Rogozin, 2019, Cancers.

From Context-Dependence of Mutations to Molecular Mechanisms of Mutagenesis

Luciano Milanesi, Igor B. Rogozin, Youri I. Pavlov, 2004, Pacific Symposium on Biocomputing.

PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.

S. Tomida, Takashi Takahashi, Siripan Limsirichaikul, 2009, Journal of biochemistry.

Precise excision of bacterial transposon Tn 5 in yeast

A. Janulaitis, Y. Chernoff, Y. Pavlov, 1988, Molecular and General Genetics MGG.

Contribution of cytosine desaminases of AID/APOBEC family to carcinogenesis

E. I. Stepchenkova, Y. Pavlov, I. Zotova, 2019, Biological Communications.

DNA polymerase η mutational signatures are found in a variety of different types of cancer

A. Panchenko, D. Cooper, S. De, 2018, Cell cycle.

In Vivo Consequences of Putative Active Site Mutations in Yeast DNA Polymerases α, ε, δ, and ζ

T. Kunkel, P. V. Shcherbakova, Y. Pavlov, 2001 .

YcbX and yiiM, two novel determinants for resistance of Escherichia coli to N‐hydroxylated base analogues

R. Schaaper, S. Kozmin, P. Leroy, 2008, Molecular microbiology.

DNA Polymerase ζ without the C-Terminus of Catalytic Subunit Rev3 Retains Characteristic Activity, but Alters Mutation Specificity of Ultraviolet Radiation in Yeast

J. Cui, Y. Pavlov, H. Siebler, 2022, Genes.

Roles of Saccharomyces cerevisiae DNA polymerases Poleta and Polzeta in response to irradiation by simulated sunlight.

T. Kunkel, E. Sage, S. Kozmin, 2003, Nucleic acids research.

A novel variant of DNA polymerase ζ, Rev3ΔC, highlights differential regulation of Pol32 as a subunit of polymerase δ versus ζ in Saccharomyces cerevisiae.

T. Tahirov, Y. Pavlov, H. Siebler, 2014, DNA repair.

DNA polymerases at the eukaryotic fork-20 years later.

P. V. Shcherbakova, Y. Pavlov, 2010, Mutation research.

Compensation for the absence of the catalytically active half of DNA polymerase ε in yeast by positively selected mutations in CDC28 gene

I. Rogozin, R. Fedorov, E. Tarakhovskaya, 2020, bioRxiv.

In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta.

T. Kunkel, P. V. Shcherbakova, Y. Pavlov, 2001, Genetics.

The genetic activity of N6-hydroxyadenine and 2-amino-N6-hydroxyadenine in Escherichia coli, Salmonella typhimurium and Saccharomyces cerevisiae.

V. Noskov, N. Khromov-Borisov, Y. Pavlov, 1991, Mutation research.

Iron-Sulfur Clusters in DNA Polymerases and Primases of Eukaryotes.

T. Tahirov, Y. Pavlov, H. Siebler, 2018, Methods in enzymology.

The 5‐aminoimidazole ribonucleotide‐carboxylase structural gene of the methylotrophic yeast Pichia methanolica: Cloning, sequencing and homology analysis

V. Noskov, V. Kulikov, Y. Chernoff, 1993, Yeast.

Transformation in the methylotrophic yeast Pichia methanolica utilizing homologous ADE1 and heterologous Saccharomyces cerevisiae ADE2 and LEU2 genes as genetic markers

V. Noskov, Y. Pavlov, Y. Pavlov, 1993, Yeast.

The C-terminal Domain of the DNA Polymerase Catalytic Subunit Regulates the Primase and Polymerase Activities of the Human DNA Polymerase α-Primase Complex*

T. Tahirov, Y. Pavlov, Yinbo Zhang, 2014, The Journal of Biological Chemistry.

Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations

H. Maki, T. Kunkel, S. Maki, 2004, BMC Biology.

Divalent ions attenuate DNA synthesis by human DNA polymerase α by changing the structure of the template/primer or by perturbing the polymerase reaction.

T. Tahirov, Y. Pavlov, Yinbo Zhang, 2016, DNA repair.

Partners in crime: Tbf1 and Vid22 promote expansions of long human telomeric repeats at an interstitial chromosome position in yeast

S. Mirkin, Alexander A. Shishkin, K. Volkov, 2022, PNAS nexus.

Mismatch Repair–Independent Increase in Spontaneous Mutagenesis in Yeast Lacking Non-Essential Subunits of DNA Polymerase ε

T. Kunkel, I. Rogozin, Z. Pursell, 2010, PLoS genetics.

The fidelity of the human leading and lagging strand DNA replication apparatus with 8-oxodeoxyguanosine triphosphate.

T. Kunkel, Y. Pavlov, D. T. Minnick, 1994, Nucleic acids research.

Evidence for Extrinsic Exonucleolytic Proofreading

T. Kunkel, Y. Pavlov, S. A. N. McElhinny, 2006, Cell cycle.

Response 1 to 'Smaller role for pol η?'

I. Rogozin, Y. Pavlov, T. Kunkel, 2001, Nature Immunology.

The human ITPA polymorphic variant P32T is destabilized by the unpacking of the hydrophobic core.

G. Borgstahl, L. Marky, Y. Pavlov, 2013, Journal of structural biology.

Correction: Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations

H. Maki, T. Kunkel, S. Maki, 2007, BMC Biology.

Activity and fidelity of human DNA polymerase (cid:2) depend on primer structure

T. Tahirov, Y. Pavlov, K. Anderson, 2018 .

Structural basis for inhibition of DNA replication by aphidicolin

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2014, Nucleic acids research.

Genome Instability in Multiple Myeloma: Facts and Factors

Y. Pavlov, A. G. Lada, I. Zotova, 2021, Cancers.

Crystal structure of the human Polϵ B-subunit in complex with the C-terminal domain of the catalytic subunit

T. Tahirov, I. Kurinov, Y. Pavlov, 2017, The Journal of Biological Chemistry.

Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome*

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2016, The Journal of Biological Chemistry.

Crystal Structure of the Human Pol α B Subunit in Complex with the C-terminal Domain of the Catalytic Subunit*

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2015, The Journal of Biological Chemistry.

X-ray structure of the complex of regulatory subunits of human DNA polymerase delta

E. Koonin, I. Rogozin, T. Tahirov, 2008, Cell cycle.

Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase η during copying of a mouse immunoglobulin κ light chain transgene

T. Kunkel, C. Rada, I. Rogozin, 2002, Proceedings of the National Academy of Sciences of the United States of America.

Comment on “A commensal strain of Staphylococcus epidermidis protects against skin neoplasia” by Nakatsuji et al.

R. Schaaper, I. Rogozin, S. Kozmin, 2019, Science Advances.

ITPA (inosine triphosphate pyrophosphatase): from surveillance of nucleotide pools to human disease and pharmacogenetics.

G. Borgstahl, Y. Pavlov, P. Simone, 2013, Mutation research.

Functional study of the P32T ITPA variant associated with drug sensitivity in humans.

G. Borgstahl, L. Marky, C. Frahm, 2009, Journal of molecular biology.

Multiple antimutagenesis mechanisms affect mutagenic activity and specificity of the base analog 6-N-hydroxylaminopurine in bacteria and yeast.

V. Noskov, K. Makarova, R. Schaaper, 1998, Mutation research.

Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase

Igor B. Rogozin, Youri I. Pavlov, Artem G. Lada, 2013, PLoS genetics.

Theoretical analysis of mutation hotspots and their DNA sequence context specificity.

I. Rogozin, Igor B Rogozin, Y. Pavlov, 2003, Mutation research.

Mechanisms of Global and Region-Specific Control of Mutagenesis

Y. Pavlov, A. G. Lada, E. Stepchenkova, 2016 .

Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools

I. Rogozin, T. Tahirov, M. Menezes, 2012, Environmental and molecular mutagenesis.

Mutator effects of overproducing DNA polymerase eta (Rad30) and its catalytically inactive variant in yeast.

T. Kunkel, Y. Pavlov, D. Nguyen, 2001, Mutation research.

Replication Protein A (RPA) Hampers the Processive Action of APOBEC3G Cytosine Deaminase on Single-Stranded DNA

G. Borgstahl, I. Rogozin, I. Waisertreiger, 2011, PloS one.

Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re-distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes

Igor B. Rogozin, Youri I. Pavlov, Artem G. Lada, 2015, PLoS genetics.

Somatic mutation hotspots correlate with DNA polymerase η error spectrum

Toshiro Matsuda, T. Kunkel, I. Rogozin, 2001, Nature Immunology.

Activation induced deaminase mutational signature overlaps with CpG methylation sites in follicular lymphoma and other cancers

Subhajyoti De, Anna R. Panchenko, Igor B. Rogozin, 2016, Scientific Reports.

Roles of DNA polymerases in replication, repair, and recombination in eukaryotes.

I. Rogozin, P. V. Shcherbakova, Y. Pavlov, 2006, International review of cytology.

Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes

T. Kunkel, I. Rogozin, C. Frahm, 2005, BMC Immunology.

Computational analysis of mutation spectra

Luciano Milanesi, Igor B. Rogozin, Vladimir N. Babenko, 2003, Briefings Bioinform..

Functions of human DNA polymerases η, κ and ι suggested by their properties, including fidelity with undamaged DNA templates

T. Kunkel, K. Bebenek, Y. Pavlov, 2003 .

Double-strand breaks in DNA during somatic hypermutation of Ig genes: cause or consequence?

T. Kunkel, I. Rogozin, Y. Pavlov, 2002, Trends in immunology.

DNA Methylation, Deamination, and Translesion Synthesis Combine to Generate Footprint Mutations in Cancer Driver Genes in B-Cell Derived Lymphomas and Other Cancers

A. Panchenko, D. Cooper, I. Rogozin, 2021, Frontiers in Genetics.

Mutational signatures and mutable motifs in cancer genomes

Subhajyoti De, Anna R. Panchenko, Eugenia Poliakov, 2017, Briefings Bioinform..

Recombination Is Responsible for the Increased Recovery of Drug-Resistant Mutants with Hypermutated Genomes in Resting Yeast Diploids Expressing APOBEC Deaminases

I. Rogozin, Y. Pavlov, A. G. Lada, 2017, Front. Genet..

APOBEC4, a New Member of the AID/APOBEC Family of Polynucleotide (Deoxy)Cytidine Deaminases Predicted by Computational Analysis

E. Koonin, I. Rogozin, I. K. Jordan, 2005, Cell cycle.

Insight into the Human DNA Primase Interaction with Template-Primer*

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2015, The Journal of Biological Chemistry.

Crystal Structure of the Human Primase*

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2014, The Journal of Biological Chemistry.

Evidence for Preferential Mismatch Repair of Lagging Strand DNA Replication Errors in Yeast

T. Kunkel, Y. Pavlov, Ibrahim M. Mian, 2003, Current Biology.

The RFC2 gene encoding a subunit of replication factor C of Saccharomyces cerevisiae.

V. Noskov, S. Leem, H. Araki, 1994, Nucleic acids research.

DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer

Y. Pavlov, A. Zhuk, E. Stepchenkova, 2020, Cancers.

Measuring deaminated nucleotide surveillance enzyme ITPA activity with an ATP-releasing nucleotide chimera

E. Kool, M. Menezes, D. Ji, 2017, Nucleic acids research.

Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase

G. Glazko, L. Aravind, L. Iyer, 2007, Nature Immunology.

AID/APOBEC cytosine deaminase induces genome-wide kataegis

I. Rogozin, M. Hirano, R. Boissy, 2012, Biology Direct.

Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant

M. Menezes, I. Waisertreiger, Y. Pavlov, 2010, Journal of nucleic acids.

Base analog N6-hydroxylaminopurine mutagenesis in Escherichia coli: genetic control and molecular specificity.

T. Kunkel, R. Schaaper, A. Matsuda, 1996, Mutation research.

DNA replication fidelity with 8-oxodeoxyguanosine triphosphate.

T. Kunkel, S. Izuta, Y. Pavlov, 1994, Biochemistry.

3' -> 5' Exonucleases of DNA Polymerases ε and δ Correct Base Analog Induced DNA Replication Errors on opposite DNA Strands in Saccharomyces Cerevisiae

P. V. Shcherbakova, Y. Pavlov, 1996 .

3'-->5' exonucleases of DNA polymerases epsilon and delta correct base analog induced DNA replication errors on opposite DNA strands in Saccharomyces cerevisiae.

P. V. Shcherbakova, Y. Pavlov, 1996, Genetics.

Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase.

J. Porta, G. Borgstahl, S. Kozmin, 2006, Acta crystallographica. Section F, Structural biology and crystallization communications.

Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast

S. Kozmin, Y. Pavlov, V. Alenin, 2005, BMC Genetics.

DNA Polymerase δ and ζ Switch by Sharing Accessory Subunits of DNA Polymerase δ*

T. Tahirov, Y. Pavlov, H. Siebler, 2012, The Journal of Biological Chemistry.

Inaccurate DNA Synthesis in Cell Extracts of Yeast Producing Active Human DNA Polymerase Iota

T. Tahirov, L. Gening, T. Bessho, 2011, PloS one.

Use of yeast transformation by oligonucleotides to study DNA lesion bypass in vivo.

V. Noskov, S. Iwai, C. Otsuka, 2002, Mutation research.

Evolution of DNA polymerases: an inactivated polymerase-exonuclease module in Pol ε and a chimeric origin of eukaryotic polymerases from two classes of archaeal ancestors

Eugene V Koonin, Kira S Makarova, E. Koonin, 2009, Biology Direct.

Conclusion: When replication is stalled, accessory subunits of DNA Pol participate in recruitment of translesion DNA Pol . Significance: This finding provides a novel mechanism of DNA lesion bypass in eukaryotes.

T. Tahirov, Y. Pavlov, H. Siebler, 2012 .

Crystallization and preliminary crystallographic analysis of the complex of the second and third regulatory subunits of human Pol delta.

T. Tahirov, Y. Pavlov, Andrey G. Baranovskiy, 2008, Acta Crystallographica. Section F : Structural Biology and Crystallization Communications.

Yeast origins establish a strand bias for replicational mutagenesis.

C. Newlon, Y. Pavlov, T. Kunkel, 2002, Molecular cell.

A highly conserved family of inactivated archaeal B family DNA polymerases

E. Koonin, K. Makarova, I. Rogozin, 2008, Biology Direct.

Unique Error Signature of the Four-subunit Yeast DNA Polymerase ϵ*

T. Kunkel, I. Rogozin, E. Johansson, 2003, Journal of Biological Chemistry.

Base analog 6-N-hydroxylaminopurine mutagenesis in the yeast Saccharomyces cerevisiae is controlled by replicative DNA polymerases.

V. Noskov, P. V. Shcherbakova, Y. Pavlov, 1996, Mutation research.

The role of DNA polymerase alpha in the control of mutagenesis in Saccharomyces cerevisiae cells starved for nutrients.

A. Achilli, H. Lancioni, Elizabeth A. Moore, 2011, Ekologicheskaia genetika.

The exceptionally high rate of spontaneous mutations in the polymerase delta proofreading exonuclease-deficient Saccharomyces cerevisiae strain starved for adenine

A. Achilli, G. Morpurgo, E. Casalone, 2004, BMC Genetics.

Evidence that Errors Made by DNA Polymerase α are Corrected by DNA Polymerase δ

T. Kunkel, C. Frahm, Motoshi Suzuki, 2006, Current Biology.

Crystal structure of the C-terminal domain of human DNA primase large subunit

T. Tahirov, Y. Pavlov, N. Babayeva, 2011, Cell cycle.

Activity and fidelity of human DNA polymerase α depend on primer structure

K. Anderson, T. Tahirov, Y. Pavlov, 2018, The Journal of Biological Chemistry.

Saccharomyces cerevisiae DNA Polymerase δ

Carrie M. Welch, T. Kunkel, E. Johansson, 2005, Journal of Biological Chemistry.

Polymerase Sharing Accessory Subunits of DNA Switch by ζ and δ DNA Polymerase DNA and Chromosomes :

T. Tahirov, Y. Pavlov, H. Siebler, 2012 .

Deletion of the DEF1 gene does not confer UV-immutability but frequently leads to self-diploidization in yeast Saccharomyces cerevisiae.

Y. Pavlov, A. Shiriaeva, E. Stepchenkova, 2018, DNA repair.

Role of DNA polymerases in repeat-mediated genome instability.

S. Mirkin, Alexander A. Shishkin, I. Voineagu, 2012, Cell reports.

Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the LYS2 gene of yeast Saccharomyces cerevisiae.

V. Noskov, I. Rogozin, Y. Chernoff, 2001, Mutation research.

Evidence that errors made by DNA polymerase alpha are corrected by DNA polymerase delta.

T. Kunkel, S. A. Nick McElhinny, C. Frahm, 2006, Current biology : CB.

Recombinogenic Phenotype of Human Activation-Induced Cytosine Deaminase

Samuel H. Wilson, T. Kunkel, V. Poltoratsky, 2004, The Journal of Immunology.

Transposon Tn5 excision in yeast: influence of DNA polymerases alpha, delta, and epsilon and repair genes.

D. Gordenin, M. Resnick, A. Malkova, 1992, Proceedings of the National Academy of Sciences of the United States of America.

Mutagenic specificity of the base analog 6-N-hydroxylaminopurine in the URA3 gene of the yeast Saccharomyces cerevisiae.

P. V. Shcherbakova, Y. Pavlov, 1993, Mutagenesis.

Mutator alleles of yeast DNA polymerase ζ

T. Kunkel, A. Sakamoto, G. Kissling, 2007 .

High rate of starvation-associated mutagenesis in Ung− yeast caused by the overproduction of human activation-induced deaminase

A. Achilli, Y. Pavlov, N. Babudri, 2007, Current Genetics.

HIGH FIDELITY FOR BASE SUBSTITUTIONS BUT LOWER FIDELITY FOR SINGLE- AND MULTI-BASE DELETIONS*

Erik Johansson, John M. Fortune, Youri I. Pavlov, 2005 .

Mutator alleles of yeast DNA polymerase zeta.

T. Kunkel, A. Sakamoto, G. Kissling, 2007, DNA repair.

Hypersensitivity of Escherichia coli Δ(uvrB-bio) Mutants to 6-Hydroxylaminopurine and Other Base Analogs Is Due to a Defect in Molybdenum Cofactor Biosynthesis

R. Schaaper, S. Kozmin, Y. Pavlov, 2000, Journal of bacteriology.

Comment on “The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport”

T. Tahirov, L. Blanco, Y. Pavlov, 2017, Science.

Polymorphism of Saccharomyces cerevisiae Strains in DNA Metabolism Genes

Y. Pavlov, A. G. Lada, A. Zhuk, 2023, International journal of molecular sciences.

The cytidine deaminase AID exhibits similar functional properties in yeast and mammals.

I. Rogozin, Y. Pavlov, 2006, Molecular immunology.

HAM1, the gene controlling 6‐N‐hydroxylaminopurine sensitivity and mutagenesis in the yeast Saccharomyces cerevisiae

V. Noskov, S. Kozmin, H. Hayatsu, 1996, Yeast.

Overexpression of the yeast HAM1 gene prevents 6-N-hydroxylaminopurine mutagenesis in Escherichia coli.

S. Kozmin, P. Leroy, Y. Pavlov, 1998, Acta biochimica Polonica.

Evidence for interplay among yeast replicative DNA polymerases alpha, delta and epsilon from studies of exonuclease and polymerase active site mutations

H. Maki, T. Kunkel, S. Maki, 2004 .

Evaluation of methods of synchronization of cell division in yeast Saccharomyces cerevisiae

Y. Pavlov, S. Inge-Vechtomov, E. Stepchenkova, 2017, Cell and Tissue Biology.

Detection of Primary DNA Lesions by Transient Changes in Mating Behavior in Yeast Saccharomyces cerevisiae Using the Alpha-Test

E. Tarakhovskaya, Y. Pavlov, A. Shiriaeva, 2023, International journal of molecular sciences.

Functions of human DNA polymerases eta, kappa and iota suggested by their properties, including fidelity with undamaged DNA templates.

T. Kunkel, K. Bebenek, Y. Pavlov, 2003, DNA repair.

Functional study of the P32T ITPA variant associated with drug sensitivity in humans.

G. Borgstahl, L. Marky, C. Frahm, 2009, Journal of molecular biology.

Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase

G. Glazko, L. Aravind, L. Iyer, 2007, Nature Immunology.

Compensation for the absence of the catalytically active half of DNA polymerase ε in yeast by positively selected mutations in CDC28.

Stephanie R. Barbari, P. V. Shcherbakova, Y. Pavlov, 2021, Genetics.

Mutational signatures and mutable motifs in cancer genomes

A. Panchenko, D. Cooper, S. De, 2017, Briefings Bioinform..

Defect of Fe-S cluster binding by DNA polymerase δ in yeast suppresses UV-induced mutagenesis, but enhances DNA polymerase ζ - dependent spontaneous mutagenesis.

Y. Pavlov, H. Siebler, E. Stepchenkova, 2017, DNA repair.

CRISPR/Cas9 as a Mutagenic Factor

Y. Pavlov, A. Rubel, A. V. Chirinskaite, 2024, International Journal of Molecular Sciences.

JOURNAL OF STRUCTURAL BIOLOGY

Margarita C. Theodoropoulou, Fotis A. Baltoumas, S. Hamodrakas, 2004 .

Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome*

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2016, The Journal of Biological Chemistry.

Crystal Structure of the Human Pol α B Subunit in Complex with the C-terminal Domain of the Catalytic Subunit*

T. Tahirov, Y. Pavlov, Yoshiaki Suwa, 2015, The Journal of Biological Chemistry.

PCNA mono-ubiquitination and activation of translesion DNA polymerases by DNA polymerase {alpha}.

S. Tomida, Takashi Takahashi, T. Murate, 2009, Journal of biochemistry.

Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2

V. Yurchenko, Y. Pavlov, Abiel Roche-Lima, 2024, International journal of molecular sciences.