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Article ; Online: Poly(dA:dT) Tracts Differentially Modulate Nucleosome Remodeling Activity of RSC and ISW1a Complexes, Exerting Tract Orientation-Dependent and -Independent Effects.

Amigo, Roberto / Raiqueo, Fernanda / Tarifeño, Estefanía / Farkas, Carlos / Gutiérrez, José L

International journal of molecular sciences

2023 Volume 24, Issue 20

Abstract: The establishment and maintenance of nucleosome-free regions (NFRs) are prominent processes within chromatin dynamics. Transcription factors, ATP-dependent chromatin remodeling complexes (CRCs) and DNA sequences are the main factors involved. ... ...

Abstract	The establishment and maintenance of nucleosome-free regions (NFRs) are prominent processes within chromatin dynamics. Transcription factors, ATP-dependent chromatin remodeling complexes (CRCs) and DNA sequences are the main factors involved. In
MeSH term(s)	Nucleosomes ; Poly dA-dT ; Chromatin/genetics ; DNA/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Chromatin Assembly and Disassembly ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Nucleosomes ; Poly dA-dT (26966-61-0) ; Chromatin ; DNA (9007-49-2) ; Saccharomyces cerevisiae Proteins
Language	English
Publishing date	2023-10-17
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/ijms242015245
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Degenerative Cervical Myelopathy induces sex-specific dysbiosis in mice.

Farkas, Carlos / Retamal-Fredes, Eduardo / Ávila, Ariel / Fehlings, Michael G / Vidal, Pia M

Frontiers in microbiology

2023 Volume 14, Page(s) 1229783

Abstract: Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord impairment in elderly populations. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel ... ...

Abstract	Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord impairment in elderly populations. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel functions, and gastrointestinal dysfunction. The gut microbiota has been recognized as an environmental factor that can modulate both the function of the central nervous system and the immune response through the microbiota-gut-brain axis. Changes in gut microbiota composition or microbiota-producing factors have been linked to the progression and development of several pathologies. However, little is known about the potential role of the gut microbiota in the pathobiology of DCM. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of DCM-induced changes in microbiota composition was assessed by 16S rRNA sequencing of the fecal samples. The immune cell composition was assessed using flow cytometry. To date, several bacterial members have been identified using BLAST against the largest collection of metagenome-derived genomes from the mouse gut. In both, female and males DCM caused gut dysbiosis compared to the sham group. However, dysbiosis was more pronounced in males than in females, and several bacterial members of the families Lachnospiraceae and Muribaculaceae were significantly altered in the DCM group. These changes were also associated with altered microbe-derived metabolic changes in propionate-, butyrate-, and lactate-producing bacterial members. Our results demonstrate that DCM causes dynamic changes over time in the gut microbiota, reducing the abundance of butyrate-producing bacteria, and lactate-producing bacteria to a lesser extent. Genome-scale metabolic modeling using gapseq successfully identified pyruvate-to-butanoate and pyruvate-to-propionate reactions involving genes such as Buk and ACH1, respectively. These results provide a better understanding of the sex-specific molecular effects of changes in the gut microbiota on DCM pathobiology.
Language	English
Publishing date	2023-10-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1229783
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Article: Deformation response of high entropy alloy nanowires

Ruestes, Carlos J. / Farkas, Diana

Journal of materials science. 2021 Oct., v. 56, no. 29

2021

Abstract: This paper reports atomistic simulation studies of tensile and compressive behavior of nanowires of a model quinary high entropy face-centered cubic (FCC) alloy. The simulations employ empirical interatomic potentials and use massively parallel molecular ...

Abstract	This paper reports atomistic simulation studies of tensile and compressive behavior of nanowires of a model quinary high entropy face-centered cubic (FCC) alloy. The simulations employ empirical interatomic potentials and use massively parallel molecular dynamics techniques at the atomistic level to study the deformation mechanisms. The studies consider pristine cylindrical nanowires oriented along various crystallographic directions. The focus is the role that local composition fluctuations in the random alloy plays in the deformation response. The deformation behavior observed for the complex random alloy is compared with a corresponding “average atom” material that has the same average properties but no local compositional fluctuations. In all cases, deformation is governed by dislocations emitted from the free surface. Twinning was also found, depending on the crystallographic orientation and loading mode. We show that for all orientations, the high entropy alloy (HEA) wires show the onset of plasticity at lower stress levels than the average atom material. However, after the onset of plasticity, the HEA presents a higher strength, mostly driven by the fact that the dislocations emitted from the surface do not glide as easily in the random alloy as they do in the average atom material.
Keywords	alloys ; deformation ; entropy ; molecular dynamics ; nanowires ; plasticity
Language	English
Dates of publication	2021-10
Size	p. 16447-16462.
Publishing place	Springer US
Document type	Article
ZDB-ID	2015305-3
ISSN	1573-4803 ; 0022-2461
ISSN (online)	1573-4803
ISSN	0022-2461
DOI	10.1007/s10853-021-06314-1
Database	NAL-Catalogue (AGRICOLA)

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Article: A Novel SARS-CoV-2 Viral Sequence Bioinformatic Pipeline Has Found Genetic Evidence That the Viral 3' Untranslated Region (UTR) Is Evolving and Generating Increased Viral Diversity.

Farkas, Carlos / Mella, Andy / Turgeon, Maxime / Haigh, Jody J

Frontiers in microbiology

2021 Volume 12, Page(s) 665041

Abstract: An unprecedented amount of SARS-CoV-2 sequencing has been performed, however, novel bioinformatic tools to cope with and process these large datasets is needed. Here, we have devised a bioinformatic pipeline that inputs SARS-CoV-2 genome sequencing in ... ...

Abstract	An unprecedented amount of SARS-CoV-2 sequencing has been performed, however, novel bioinformatic tools to cope with and process these large datasets is needed. Here, we have devised a bioinformatic pipeline that inputs SARS-CoV-2 genome sequencing in FASTA/FASTQ format and outputs a single Variant Calling Format file that can be processed to obtain variant annotations and perform downstream population genetic testing. As proof of concept, we have analyzed over 229,000 SARS-CoV-2 viral sequences up until November 30, 2020. We have identified over 39,000 variants worldwide with increased polymorphisms, spanning the ORF3a gene as well as the 3' untranslated (UTR) regions, specifically in the conserved stem loop region of SARS-CoV-2 which is accumulating greater observed viral diversity relative to chance variation. Our analysis pipeline has also discovered the existence of SARS-CoV-2 hypermutation with low frequency (less than in 2% of genomes) likely arising through host immune responses and not due to sequencing errors. Among annotated non-sense variants with a population frequency over 1%, recurrent inactivation of the ORF8 gene was found. This was found to be present in the newly identified B.1.1.7 SARS-CoV-2 lineage that originated in the United Kingdom. Almost all VOC-containing genomes possess one stop codon in ORF8 gene (Q27
Language	English
Publishing date	2021-06-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.665041
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Article: Sorting Out the Risks and Benefits of the #797 Recommended Intrapartum Vancomycin Dosing Approach.

Farkas, Andras / Yassin, Arsheena

Antibiotics (Basel, Switzerland)

2022 Volume 12, Issue 1

Abstract: ... period was analyzed in this work with a two-compartment pharmacokinetic (PK) model. Monte Carlo ...

Abstract	ACOG Committee Opinion #797 proposed intrapartum vancomycin dosing guidelines in the absence of thorough evaluation of its risk versus benefit profile on the maternal and neonatal systems. The previously published serum and cord-blood concentration-time data of vancomycin given to mothers in the intrapartum period was analyzed in this work with a two-compartment pharmacokinetic (PK) model. Monte Carlo simulation was used to establish exposure for the studied population for doses of 1000 mg to 2000 mg every 8 h for gestational ages (GA) of 33 to 40 weeks and for birth times up to 4-h intervals. Probabilities of target attainment (PTA) were calculated for efficacy and toxicity indices unique to the peripartum maternal and neonatal population. Neonatal evaluations indicate uniformly high PTAs for the evaluated dosing regimens when the efficacy target is considered. On the other hand, the PTAs for potentially nephrotoxic exposure is expected to reach undesirable levels when three or more doses were to be administered. The risk is profoundly high in GA below 36 weeks and birth times beyond 20 h after the initiation of intrapartum prophylaxis and with doses greater than 1250 mg. Maternal vancomycin exposures seem reasonable up to two intrapartum doses given at 8 h intervals when the dose is kept to 1250 mg or less. Most mothers (up to 83%) who receive three or more doses of the commonly administered regimens are subjected to nephrotoxic exposures. Thus, it appears that the current recommendations by #797 for dosing of vancomycin pose considerable risk to mother and newborn alike, especially in cases with lengthy duration of preterm labor. Capping of doses at 1250 mg may be considered to minimize the need for therapeutic drug monitoring (TDM) interventions. Alternatively, and irrespective of the baseline maternal renal function, TDM for all cases requiring more than two doses of 1500 mg or higher must be assured.
Language	English
Publishing date	2022-12-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12010032
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Article: Characterization of

Farkas, Carlos / Quiroz, Aracelly / Alvarez, Claudia / Hermosilla, Viviana / Aylwin, Carlos F / Lomniczi, Alejandro / Castro, Ariel F / Hepp, Matias I / Pincheira, Roxana

Frontiers in genetics

2021 Volume 12, Page(s) 613808

Abstract: The SALL2 transcription factor, an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation. In disease, SALL2 is associated with eye, kidney, and brain disorders, but mainly is related to cancer. ... ...

Abstract	The SALL2 transcription factor, an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation. In disease, SALL2 is associated with eye, kidney, and brain disorders, but mainly is related to cancer. Some studies support a tumor suppressor role and others an oncogenic role for SALL2, which seems to depend on the cancer type. An additional consideration is tissue-dependent expression of different SALL2 isoforms. Human and mouse
Language	English
Publishing date	2021-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.613808
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Article ; Online: Complete Genome Sequence of Rhodococcus ruber R1, a Novel Strain Showing a Broad Catabolic Potential toward Lignin-Derived Aromatics.

Farkas, Carlos / Donoso, Raúl A / Melis-Arcos, Felipe / Gárate-Castro, Carla / Pérez-Pantoja, Danilo

Microbiology resource announcements

2020 Volume 9, Issue 2

Abstract: Rhodococcus ... ...

Abstract	Rhodococcus ruber
Language	English
Publishing date	2020-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/MRA.00905-19
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Article ; Online: annotate_my_genomes: an easy-to-use pipeline to improve genome annotation and uncover neglected genes by hybrid RNA sequencing.

Farkas, Carlos / Recabal, Antonia / Mella, Andy / Candia-Herrera, Daniel / Olivero, Maryori González / Haigh, Jody Jonathan / Tarifeño-Saldivia, Estefanía / Caprile, Teresa

GigaScience

2022 Volume 11

Abstract: Background: The advancement of hybrid sequencing technologies is increasingly expanding genome assemblies that are often annotated using hybrid sequencing transcriptomics, leading to improved genome characterization and the identification of novel genes ...

Abstract	Background: The advancement of hybrid sequencing technologies is increasingly expanding genome assemblies that are often annotated using hybrid sequencing transcriptomics, leading to improved genome characterization and the identification of novel genes and isoforms in a wide variety of organisms. Results: We developed an easy-to-use genome-guided transcriptome annotation pipeline that uses assembled transcripts from hybrid sequencing data as input and distinguishes between coding and long non-coding RNAs by integration of several bioinformatic approaches, including gene reconciliation with previous annotations in GTF format. We demonstrated the efficiency of this approach by correctly assembling and annotating all exons from the chicken SCO-spondin gene (containing more than 105 exons), including the identification of missing genes in the chicken reference annotations by homology assignments. Conclusions: Our method helps to improve the current transcriptome annotation of the chicken brain. Our pipeline, implemented on Anaconda/Nextflow and Docker is an easy-to-use package that can be applied to a broad range of species, tissues, and research areas helping to improve and reconcile current annotations. The code and datasets are publicly available at https://github.com/cfarkas/annotate_my_genomes.
MeSH term(s)	Sequence Analysis, RNA
Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2708999-X
ISSN	2047-217X ; 2047-217X
ISSN (online)	2047-217X
ISSN	2047-217X
DOI	10.1093/gigascience/giac099
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Article: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions.

Farkas, Carlos / Fuentes-Villalobos, Francisco / Garrido, Jose Luis / Haigh, Jody / Barría, María Inés

PeerJ

2020 Volume 8, Page(s) e9255

Abstract: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA ... ...

Abstract	Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (
Keywords	covid19
Language	English
Publishing date	2020-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.9255
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Article ; Online: Large-scale population analysis of SARS-CoV2 whole genome sequences reveals host-mediated viral evolution with emergence of mutations in the viral Spike protein associated with elevated mortality rates

Farkas, Carlos / Mella, Andy / Haigh, Jody J

medRxiv

Abstract: Abstract Background We aimed to further characterize and analyze in depth intra-host variation and founder variants of SARS-CoV-2 worldwide up until August 2020, by examining in excess of 94,000 SARS-CoV-2 viral sequences in order to understand SARS-CoV- ... ...

Abstract	Abstract Background We aimed to further characterize and analyze in depth intra-host variation and founder variants of SARS-CoV-2 worldwide up until August 2020, by examining in excess of 94,000 SARS-CoV-2 viral sequences in order to understand SARS-CoV-2 variant evolution, how these variants arose and identify any increased mortality associated with these variants. Methods and Findings We combined worldwide sequencing data from GISAID and Sequence Read Archive (SRA) repositories and discovered SARS-CoV-2 hypermutation occurring in less than 2% of COVID19 patients, likely caused by host mechanisms involved APOBEC3G complexes and intra-host microdiversity. Most of this intra-host variation occurring in SARS-CoV-2 are predicted to change viral proteins with defined variant signatures, demonstrating that SARS-CoV-2 can be actively shaped by the host immune system to varying degrees. At the global population level, several SARS-CoV-2 proteins such as Nsp2, 3C-like proteinase, ORF3a and ORF8 are under active evolution, as evidenced by their increased πN/πS ratios per geographical region. Importantly, two emergent variants: V1176F in co-occurrence with D614G mutation in the viral Spike protein, and S477N, located in the Receptor Binding Domain (RBD) of the Spike protein, are associated with high fatality rates and are increasingly spreading throughout the world. The S477N variant arose quickly in Australia and experimental data support that this variant increases Spike protein fitness and its binding to ACE2. Conclusions SARS-CoV-2 is evolving non-randomly, and human hosts shape emergent variants with positive fitness that can easily spread into the population. We propose that V1776F and S477N variants occurring in the Spike protein are two novel mutations occurring in SARS-CoV-2 and may pose significant public health concerns in the future.
Keywords	covid19
Language	English
Publishing date	2020-10-27
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.10.23.20218511
Database	COVID19

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