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Article ; Online: BMI1 is required for melanocyte stem cell maintenance and hair pigmentation.

Wilson, Molly M / Danielian, Paul S / Salus, Griffin / Ferretti, Roberta / Whittaker, Charles A / Lees, Jacqueline A

2023 Volume 36, Issue 5, Page(s) 399–406

Abstract: The epigenetic repressor BMI1 plays an integral role in promoting the self-renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors ... ...

Abstract	The epigenetic repressor BMI1 plays an integral role in promoting the self-renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors p16
MeSH term(s)	Mice ; Animals ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Melanoma/metabolism ; Proto-Oncogene Proteins ; Skin Neoplasms/metabolism ; Stem Cells/metabolism ; Polycomb Repressive Complex 1/genetics ; Polycomb Repressive Complex 1/metabolism ; Pigmentation ; Melanocytes/metabolism ; Hair/metabolism
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; Proto-Oncogene Proteins ; Polycomb Repressive Complex 1 (EC 2.3.2.27)
Language	English
Publishing date	2023-05-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2409570-9
ISSN	1755-148X ; 1600-0749 ; 0893-5785 ; 1755-1471
ISSN (online)	1755-148X ; 1600-0749
ISSN	0893-5785 ; 1755-1471
DOI	10.1111/pcmr.13088
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Article: The environmental stress response regulates ribosome content in cell cycle-arrested

Terhorst, Allegra / Sandikci, Arzu / Whittaker, Charles A / Szórádi, Tamás / Holt, Liam J / Neurohr, Gabriel E / Amon, Angelika

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1118766

Abstract: Prolonged cell cycle arrests occur naturally in differentiated cells and in response to various stresses such as nutrient deprivation or treatment with chemotherapeutic agents. Whether and how cells survive prolonged cell cycle arrests is not clear. Here, ...

Abstract	Prolonged cell cycle arrests occur naturally in differentiated cells and in response to various stresses such as nutrient deprivation or treatment with chemotherapeutic agents. Whether and how cells survive prolonged cell cycle arrests is not clear. Here, we used
Language	English
Publishing date	2023-04-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1118766
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Article ; Online: Molecular logic of synaptic diversity between Drosophila tonic and phasic motoneurons.

Jetti, Suresh K / Crane, Andrés B / Akbergenova, Yulia / Aponte-Santiago, Nicole A / Cunningham, Karen L / Whittaker, Charles A / Littleton, J Troy

Neuron

2023 Volume 111, Issue 22, Page(s) 3554–3569.e7

Abstract: Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features are poorly understood. To identify molecular pathways that contribute to synaptic diversity, single- ... ...

Abstract	Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features are poorly understood. To identify molecular pathways that contribute to synaptic diversity, single-neuron Patch-seq RNA profiling was performed on Drosophila tonic and phasic glutamatergic motoneurons. Tonic motoneurons form weaker facilitating synapses onto single muscles, while phasic motoneurons form stronger depressing synapses onto multiple muscles. Super-resolution microscopy and in vivo imaging demonstrated that synaptic active zones in phasic motoneurons are more compact and display enhanced Ca
MeSH term(s)	Animals ; Drosophila ; Synapses/physiology ; Motor Neurons/physiology ; Signal Transduction
Language	English
Publishing date	2023-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2023.07.019
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Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Molecular Logic of Synaptic Diversity Between

Jetti, Suresh K / Crane, Andrés B / Akbergenova, Yulia / Aponte-Santiago, Nicole A / Cunningham, Karen L / Whittaker, Charles A / Littleton, J Troy

bioRxiv : the preprint server for biology

2023

Abstract: Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features is poorly understood. To identify molecular pathways that contribute to synaptic diversity, single ... ...

Abstract	Although neuronal subtypes display unique synaptic organization and function, the underlying transcriptional differences that establish these features is poorly understood. To identify molecular pathways that contribute to synaptic diversity, single neuron PatchSeq RNA profiling was performed on
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.17.524447
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Article ; Online: Unifying incidence and prevalence under a time-varying general branching process.

Pakkanen, Mikko S / Miscouridou, Xenia / Penn, Matthew J / Whittaker, Charles / Berah, Tresnia / Mishra, Swapnil / Mellan, Thomas A / Bhatt, Samir

Journal of mathematical biology

2023 Volume 87, Issue 2, Page(s) 35

Abstract: Renewal equations are a popular approach used in modelling the number of new infections, i.e., incidence, in an outbreak. We develop a stochastic model of an outbreak based on a time-varying variant of the Crump-Mode-Jagers branching process. This model ... ...

Abstract	Renewal equations are a popular approach used in modelling the number of new infections, i.e., incidence, in an outbreak. We develop a stochastic model of an outbreak based on a time-varying variant of the Crump-Mode-Jagers branching process. This model accommodates a time-varying reproduction number and a time-varying distribution for the generation interval. We then derive renewal-like integral equations for incidence, cumulative incidence and prevalence under this model. We show that the equations for incidence and prevalence are consistent with the so-called back-calculation relationship. We analyse two particular cases of these integral equations, one that arises from a Bellman-Harris process and one that arises from an inhomogeneous Poisson process model of transmission. We also show that the incidence integral equations that arise from both of these specific models agree with the renewal equation used ubiquitously in infectious disease modelling. We present a numerical discretisation scheme to solve these equations, and use this scheme to estimate rates of transmission from serological prevalence of SARS-CoV-2 in the UK and historical incidence data on Influenza, Measles, SARS and Smallpox.
MeSH term(s)	Humans ; Incidence ; SARS-CoV-2 ; COVID-19/epidemiology ; Prevalence ; Communicable Diseases/epidemiology
Language	English
Publishing date	2023-08-01
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187101-8
ISSN	1432-1416 ; 0303-6812
ISSN (online)	1432-1416
ISSN	0303-6812
DOI	10.1007/s00285-023-01958-w
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Zs.A 1495: Show issues

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Article ; Online: The FLC Locus: A Platform for Discoveries in Epigenetics and Adaptation.

Whittaker, Charles / Dean, Caroline

Annual review of cell and developmental biology

2017 Volume 33, Page(s) 555–575

Abstract: Our understanding of the detailed molecular mechanisms underpinning adaptation is still poor. One example for which mechanistic understanding of regulation has converged with studies of life history variation is Arabidopsis thaliana FLOWERING LOCUS C ( ... ...

Abstract	Our understanding of the detailed molecular mechanisms underpinning adaptation is still poor. One example for which mechanistic understanding of regulation has converged with studies of life history variation is Arabidopsis thaliana FLOWERING LOCUS C (FLC). FLC determines the need for plants to overwinter and their ability to respond to prolonged cold in a process termed vernalization. This review highlights how molecular analysis of vernalization pathways has revealed important insight into antisense-mediated chromatin silencing mechanisms that regulate FLC. In turn, such insight has enabled molecular dissection of the diversity in vernalization across natural populations of A. thaliana. Changes in both cotranscriptional regulation and epigenetic silencing of FLC are caused by noncoding polymorphisms at FLC. The FLC locus is therefore providing important concepts for how noncoding transcription and chromatin regulation influence gene expression and how these mechanisms can vary to underpin adaptation in natural populations.
MeSH term(s)	Adaptation, Physiological/genetics ; Biological Evolution ; Epigenesis, Genetic ; Flowers/physiology ; Genetic Loci ; Plant Proteins/genetics
Chemical Substances	Plant Proteins
Language	English
Publishing date	2017-07-10
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1293750-2
ISSN	1530-8995 ; 1081-0706
ISSN (online)	1530-8995
ISSN	1081-0706
DOI	10.1146/annurev-cellbio-100616-060546
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Article ; Online: Functional Annotation Routines Used by ABRF Bioinformatics Core Facilities - Observations, Comparisons, and Considerations.

Whittaker, Charles A / Kucukural, Alper / Gates, Chris / Wilkins, Owen Michael / Bell, George W / Hutchinson, John N / Polson, Shawn W / Dragon, Julie

Journal of biomolecular techniques : JBT

2023 Volume 34, Issue 1

Abstract: The functional annotation of gene lists is a common analysis routine required for most genomics experiments, and bioinformatics core facilities must support these analyses. In contrast to methods such as the quantitation of RNA-Seq reads or differential ... ...

Abstract	The functional annotation of gene lists is a common analysis routine required for most genomics experiments, and bioinformatics core facilities must support these analyses. In contrast to methods such as the quantitation of RNA-Seq reads or differential expression analysis, our research group noted a lack of consensus in our preferred approaches to functional annotation. To investigate this observation, we selected 4 experiments that represent a range of experimental designs encountered by our cores and analyzed those data with 6 tools used by members of the Association of Biomolecular Resource Facilities (ABRF) Genomic Bioinformatics Research Group (GBIRG). To facilitate comparisons between tools, we focused on a single biological result for each experiment. These results were represented by a gene set, and we analyzed these gene sets with each tool considered in our study to map the result to the annotation categories presented by each tool. In most cases, each tool produces data that would facilitate identification of the selected biological result for each experiment. For the exceptions, Fisher's exact test parameters could be adjusted to detect the result. Because Fisher's exact test is used by many functional annotation tools, we investigated input parameters and demonstrate that, while background set size is unlikely to have a significant impact on the results, the numbers of differentially expressed genes in an annotation category and the total number of differentially expressed genes under consideration are both critical parameters that may need to be modified during analyses. In addition, we note that differences in the annotation categories tested by each tool, as well as the composition of those categories, can have a significant impact on results.
MeSH term(s)	Computational Biology/methods ; Genomics/methods ; RNA-Seq ; Molecular Sequence Annotation
Language	English
Publishing date	2023-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2116011-9
ISSN	1943-4731 ; 1943-4731
ISSN (online)	1943-4731
ISSN	1943-4731
DOI	10.7171/3fc1f5fe.0b74b9db
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Article ; Online: Autonomous circadian rhythms in the human hepatocyte regulate hepatic drug metabolism and inflammatory responses.

March, Sandra / Nerurkar, Niketa / Jain, Anisha / Andrus, Linda / Kim, Daniel / Whittaker, Charles A / Tan, Edward K W / Thiberge, Sabine / Fleming, Heather E / Mancio-Silva, Liliana / Rice, Charles M / Bhatia, Sangeeta N

Science advances

2024 Volume 10, Issue 17, Page(s) eadm9281

Abstract: Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, circadian rhythms play fundamental roles in maintaining organ homeostasis. Here, we established and characterized an in ... ...

Abstract	Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, circadian rhythms play fundamental roles in maintaining organ homeostasis. Here, we established and characterized an in vitro liver experimental system in which primary human hepatocytes display self-sustained oscillations. By generating gene expression profiles of these hepatocytes over time, we demonstrated that their transcriptional state is dynamic across 24 hours and identified a set of cycling genes with functions related to inflammation, drug metabolism, and energy homeostasis. We designed and tested a treatment protocol to minimize atorvastatin- and acetaminophen-induced hepatotoxicity. Last, we documented circadian-dependent induction of pro-inflammatory cytokines when triggered by LPS, IFN-β, or
MeSH term(s)	Humans ; Hepatocytes/metabolism ; Hepatocytes/drug effects ; Circadian Rhythm ; Inflammation/metabolism ; Liver/metabolism ; Acetaminophen/pharmacology ; Atorvastatin/pharmacology ; Cytokines/metabolism ; Inactivation, Metabolic ; Lipopolysaccharides/pharmacology ; Gene Expression Profiling ; Gene Expression Regulation ; Cells, Cultured
Chemical Substances	Acetaminophen (362O9ITL9D) ; Atorvastatin (A0JWA85V8F) ; Cytokines ; Lipopolysaccharides
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adm9281
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Article ; Online: Altered demographic profile of hospitalizations during the second COVID-19 wave in Amazonas, Brazil.

Whittaker, Charles / Ratmann, Oliver / Dye, Christopher / Sabino, Ester C / Faria, Nuno R

Lancet regional health. Americas

2021 Volume 2, Page(s) 100064

Language	English
Publishing date	2021-09-10
Publishing country	England
Document type	Journal Article
ISSN	2667-193X
ISSN (online)	2667-193X
DOI	10.1016/j.lana.2021.100064
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Article ; Online: Factors associated with variation in single-dose albendazole pharmacokinetics: A systematic review and modelling analysis.

Whittaker, Charles / Chesnais, Cédric B / Pion, Sébastien D S / Kamgno, Joseph / Walker, Martin / Basáñez, Maria-Gloria / Boussinesq, Michel

PLoS neglected tropical diseases

2022 Volume 16, Issue 10, Page(s) e0010497

Abstract: Background: Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown that the drug's pharmacologically active metabolite, albendazole sulfoxide, ...

Abstract	Background: Albendazole is an orally administered anti-parasitic medication with widespread usage in a variety of both programmatic and clinical contexts. Previous work has shown that the drug's pharmacologically active metabolite, albendazole sulfoxide, is characterised by substantial inter-individual pharmacokinetic variation. This variation might have implications for the efficacy of albendazole treatment, but current understanding of the factors associated with this variation remains incomplete. Methodology/principal findings: We carried out a systematic review to identify references containing temporally disaggregated data on the plasma concentration of albendazole and/or (its pharmacologically-active metabolite) albendazole sulfoxide following a single oral dose. These data were then integrated into a mathematical modelling framework to infer albendazole sulfoxide pharmacokinetic parameters and relate them to characteristics of the groups being treated. These characteristics included age, weight, sex, dosage, infection status, and whether patients had received a fatty meal prior to treatment or other drugs alongside albendazole. Our results highlight a number of factors systematically associated with albendazole sulfoxide pharmacokinetic variation including age, existing parasitic infection and receipt of a fatty meal. Age was significantly associated with variation in albendazole sulfoxide systemic availability and peak plasma concentration achieved; as well as the clearance rate (related to the half-life) after adjusting for variation in dosage due to differences in body weight between children and adults. Receipt of a fatty meal prior to treatment was associated with increased albendazole sulfoxide systemic availability (and by extension, peak plasma concentration and total albendazole sulfoxide exposure following the dose). Parasitic infection (particularly echinococcosis) was associated with altered pharmacokinetic parameters, with infected populations displaying distinct characteristics to uninfected ones. Conclusions/significance: These results highlight the extensive inter-individual variation that characterises albendazole sulfoxide pharmacokinetics and provide insight into some of the factors associated with this variation.
MeSH term(s)	Humans ; Adult ; Child ; Albendazole ; Anthelmintics/therapeutic use ; Echinococcosis/drug therapy ; Administration, Oral
Chemical Substances	albendazole sulfoxide (J39B52TV34) ; Albendazole (F4216019LN) ; Anthelmintics
Language	English
Publishing date	2022-10-28
Publishing country	United States
Document type	Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0010497
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