المؤلفون: Bender, Jeffrey M, Li, Fan, Purswani, Heena, Capretz, Taylor, Cerini, Chiara, Zabih, Sara, Hung, Long, Francis, Nicole, Chin, Steven, Pannaraj, Pia S, Aldrovandi, Grace

المصدر: The Journal of Maternal-Fetal & Neonatal Medicine. 34(20)

مصطلحات موضوعية: Paediatrics, Biomedical and Clinical Sciences, Infectious Diseases, Pediatric, Digestive Diseases, Infant Mortality, Perinatal Period - Conditions Originating in Perinatal Period, Genetics, Infection, Good Health and Well Being, Anti-Bacterial Agents, Dysbiosis, Feces, Gastrointestinal Microbiome, Humans, Infant, Infant, Newborn, Intensive Care Units, Neonatal, Bifidobacterium, Escherichia coli, FishTaco, metagenomics, mycobiome, Paediatrics and Reproductive Medicine, Obstetrics & Reproductive Medicine, Reproductive medicine, Midwifery

الوصف: IntroductionThe infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study, we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time.Materials and methodsStool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed.ResultsA total of 51 stool samples from 25 infants were analyzed: seven infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R2 = 0.044, p = .002) but later courses did not (R2 = 0.023, p = .114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray-Curtis distance 0.29 vs. 0.63, Wilcoxon p = .06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1vf4f34bTest

المؤلفون: Alecki, Célia, Chiwara, Victoria, Sanz, Lionel A, Grau, Daniel, Arias Pérez, Osvaldo, Boulier, Elodie L, Armache, Karim-Jean, Chédin, Frédéric, Francis, Nicole J

المصدر: Nature communications. 11(1)

الوصف: Polycomb Group (PcG) proteins form memory of transient transcriptional repression that is necessary for development. In Drosophila, DNA elements termed Polycomb Response Elements (PREs) recruit PcG proteins. How PcG activities are targeted to PREs to maintain repressed states only in appropriate developmental contexts has been difficult to elucidate. PcG complexes modify chromatin, but also interact with both RNA and DNA, and RNA is implicated in PcG targeting and function. Here we show that R-loops form at many PREs in Drosophila embryos, and correlate with repressive states. In vitro, both PRC1 and PRC2 can recognize R-loops and open DNA bubbles. Unexpectedly, we find that PRC2 drives formation of RNA-DNA hybrids, the key component of R-loops, from RNA and dsDNA. Our results identify R-loop formation as a feature of Drosophila PREs that can be recognized by PcG complexes, and RNA-DNA strand exchange as a PRC2 activity that could contribute to R-loop formation.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/89z509n0Test

المؤلفون: Seif, Elias¹ (AUTHOR) seif.elias@gmail.com, Francis, Nicole J.^1,2,3 (AUTHOR) nicole.francis@ircm.qc.ca

المصدر: Molecules. Jan2024, Vol. 29 Issue 2, p323. 25p.

مصطلحات موضوعية: *HISTONES, *CHROMATIN, *PHASE separation, *GENE expression, *GENETIC regulation

مستخلص: The Drosophila PRC1 complex regulates gene expression by modifying histone proteins and chromatin architecture. Two PRC1 subunits, PSC and Ph, are most implicated in chromatin architecture. In vitro, PRC1 compacts chromatin and inhibits transcription and nucleosome remodeling. The long disordered C-terminal region of PSC (PSC-CTR) is important for these activities, while Ph has little effect. In cells, Ph is important for condensate formation, long-range chromatin interactions, and gene regulation, and its polymerizing sterile alpha motif (SAM) is implicated in these activities. In vitro, truncated Ph containing the SAM and two other conserved domains (mini-Ph) undergoes phase separation with chromatin, suggesting a mechanism for SAM-dependent condensate formation in vivo. How the distinct activities of PSC and Ph on chromatin function together in PRC1 is not known. To address this question, we analyzed structures formed with large chromatin templates and PRC1 in vitro. PRC1 bridges chromatin into extensive fibrillar networks. Ph, its SAM, and SAM polymerization activity have little effect on these structures. Instead, the PSC-CTR controls their growth, and is sufficient for their formation. To understand how phase separation driven by Ph SAM intersects with the chromatin bridging activity of the PSC-CTR, we used mini-Ph to form condensates with chromatin and then challenged them with PRC1 lacking Ph (PRC1ΔPh). PRC1ΔPh converts mini-Ph chromatin condensates into clusters of small non-fusing condensates and bridged fibers. These condensates retain a high level of chromatin compaction and do not intermix. Thus, phase separation of chromatin by mini-Ph, followed by the action of the PSC-CTR, creates a unique chromatin organization with regions of high nucleosome density and extraordinary stability. We discuss how this coordinated sequential activity of two proteins found in the same complex may occur and the possible implications of stable chromatin architectures in maintaining transcription states. [ABSTRACT FROM AUTHOR]

المؤلفون: Vanzan, Ludovica, Soldati, Hadrien, Ythier, Victor, Anand, Santosh, Braun, Simon, Francis, Nicole, Murr, Rabih

المصدر: ISSN: 2041-1723 ; Nature Communications, vol. 12, no. 1 (2021) 3337.

مصطلحات موضوعية: info:eu-repo/classification/ddc/576.5, info:eu-repo/classification/ddc/590, info:eu-repo/classification/ddc/616.07

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34099689; info:eu-repo/semantics/dataset/url/https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144524Test; info:eu-repo/semantics/dataset/url/https://springernature.figshare.com/articles/dataset/Human_and_mouse_cistromes_genomic_maps_of_putative_cis-regulatory_regions_bound_by_transcription_factors/7087697Test; https://archive-ouverte.unige.ch/unige:154518Test; unige:154518

الإتاحة: https://doi.org/10.1038/s41467-021-23630-xTest
https://archive-ouverte.unige.ch/unige:154518Test

المؤلفون: Narlikar, Geeta J., Myong, Sua, Larson, Daniel, Maeshima, Kazuhiro, Francis, Nicole, Rippe, Karsten, Sabari, Benjamin, Strader, Lucia, Tjian, Robert

المصدر: Molecular Cell ; volume 81, issue 8, page 1579-1585 ; ISSN 1097-2765

مصطلحات موضوعية: Cell Biology, Molecular Biology

الإتاحة: https://doi.org/10.1016/j.molcel.2021.03.046Test
https://api.elsevier.com/content/article/PII:S1097276521002677?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1097276521002677?httpAccept=text/plainTest

المؤلفون: Francis, Nicole J., Sihou, Djamouna

المساهمون: Canadian Institutes for Health Research, Natural Sciences and Engineering Research Council of Canada

المصدر: Trends in Biochemical Sciences ; volume 46, issue 1, page 5-14 ; ISSN 0968-0004

مصطلحات موضوعية: Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1016/j.tibs.2020.08.009Test
https://api.elsevier.com/content/article/PII:S0968000420302061?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0968000420302061?httpAccept=text/plainTest

المؤلفون: Seif, Elias, Kang, Jin Joo, Sasseville, Charles, Senkovich, Olga, Kaltashov, Alexander, Boulier, Elodie L., Kapur, Ibani, Kim, Chongwoo A., Francis, Nicole J.

المساهمون: U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences

المصدر: Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Polycomb Group (PcG) proteins organize chromatin at multiple scales to regulate gene expression. A conserved Sterile Alpha Motif (SAM) in the Polycomb Repressive Complex 1 (PRC1) subunit Polyhomeotic (Ph) has been shown to play an important role in chromatin compaction and large-scale chromatin organization. Ph SAM forms helical head to tail polymers, and SAM-SAM interactions between chromatin-bound Ph/PRC1 are believed to compact chromatin and mediate long-range interactions. To understand the underlying mechanism, here we analyze the effects of Ph SAM on chromatin in vitro. We find that incubation of chromatin or DNA with a truncated Ph protein containing the SAM results in formation of concentrated, phase-separated condensates. Ph SAM-dependent condensates can recruit PRC1 from extracts and enhance PRC1 ubiquitin ligase activity towards histone H2A. We show that overexpression of Ph with an intact SAM increases ubiquitylated H2A in cells. Thus, SAM-induced phase separation, in the context of Ph, can mediate large-scale compaction of chromatin into biochemical compartments that facilitate histone modification.

الإتاحة: https://doi.org/10.1038/s41467-020-19435-zTest
https://www.nature.com/articles/s41467-020-19435-z.pdfTest
https://www.nature.com/articles/s41467-020-19435-zTest

المؤلفون: Kang, Jin Joo, Faubert, Denis, Boulais, Jonathan, Francis, Nicole J.

المساهمون: Canadian Institutes for Health Research, NIH

المصدر: Journal of Molecular Biology ; volume 432, issue 17, page 4856-4871 ; ISSN 0022-2836

مصطلحات موضوعية: Molecular Biology, Structural Biology

الإتاحة: https://doi.org/10.1016/j.jmb.2020.07.002Test
https://api.elsevier.com/content/article/PII:S0022283620304344?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0022283620304344?httpAccept=text/plainTest

المؤلفون: Francis, Nicole J., Kingston, Robert E., Woodcock, Christopher L.

المصدر: Science, 2004 Nov . 306(5701), 1574-1577.

الوصول الحر: https://www.jstor.org/stable/3839672Test

المؤلفون: Francis Nicole Saridin, Kimberly Ann Chew, Anthonin Reilhac, Bibek Gyanwali, Steven Gayoles Villaraza, Tomotaka Tanaka, Phillip Scheltens, Wiesje M. van der Flier, Christopher Li Hsian Chen, Saima Hilal

المساهمون: Neurology, Amsterdam Neuroscience - Neurodegeneration, APH - Personalized Medicine, APH - Methodology

المصدر: European Journal of Neurology, 29(7), 1922-1929. Wiley-Blackwell
Saridin, F N, Chew, K A, Reilhac, A, Gyanwali, B, Villaraza, S G, Tanaka, T, Scheltens, P, van der Flier, W M, Chen, C L H & Hilal, S 2022, ' Cerebrovascular disease in suspected non-Alzheimer's pathophysiology and cognitive decline over time ', European Journal of Neurology, vol. 29, no. 7, pp. 1922-1929 . https://doi.org/10.1111/ene.15337Test

مصطلحات موضوعية: Male, Amyloid beta-Peptides, Brain, Neuropsychological Tests, Magnetic Resonance Imaging, Cerebrovascular Disorders, Neurology, Alzheimer Disease, Positron-Emission Tomography, Humans, Cognitive Dysfunction, Female, Neurology (clinical), Biomarkers, Aged

الوصف: Background: The underlying cause of cognitive decline in individuals who are positive for biomarkers of neurodegeneration (N) but negative for biomarkers of amyloid-beta (A), designated as Suspected non-Alzheimer's pathophysiology (SNAP), remains unclear. We evaluate whether cerebrovascular disease (CeVD) is more prevalent in those with SNAP compared to A−N− and A+N+ individuals and whether CeVD is associated with cognitive decline over time in SNAP patients. Methods: A total of 216 individuals from a prospective memory clinic cohort (mean [SD] age, 72.7 [7.3] years, 100 women [56.5%]) were included and were diagnosed as no cognitive impairment (NCI), cognitive impairment no dementia (CIND), Alzheimer's dementia (AD) or vascular dementia (VaD). All individuals underwent clinical evaluation and neuropsychological assessment annually for up to 5 years. Carbon 11-labeled Pittsburgh Compound B ([11C]-PiB) or [18F]-flutafuranol-positron emission spectrometry imaging was performed to ascertain amyloid-beta status. Magnetic resonance imaging was performed to assess neurodegeneration as measured by medial temporal atrophy ≥2, as well as significant CeVD (sCeVD) burden, defined by cortical infarct count ≥1, Fazekas score ≥2, lacune count ≥2 or cerebral microbleed count ≥2. Results: Of the 216 individuals, 50 (23.1%) A−N+ were (SNAP), 93 (43.1%) A−N−, 36 (16.7%) A+N− and 37 (17.1%) A+N+. A+N+ individuals were significantly older, while A+N+ and SNAP individuals were more likely to have dementia. The SNAP group had a higher prevalence of sCeVD (90.0%) compared to A−N−. Moreover, SNAP individuals with sCeVD had significantly steeper decline in global cognition compared to A−N− over 5 years (p = 0.042). Conclusions: These findings suggest that CeVD is a contributing factor to cognitive decline in SNAP. Therefore, SNAP individuals should be carefully assessed and treated for CeVD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5693316d7e155f454d4ddf389a97b225Test
https://doi.org/10.1111/ene.15337Test