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Article ; Online: Microbiome composition and function within the Kellet's whelk perivitelline fluid.

Daniels, Benjamin N / Nurge, Jenna / De Smet, Chanel / Sleeper, Olivia / White, Crow / Davidson, Jean M / Fidopiastis, Pat

Microbiology spectrum

2024 , Page(s) e0351423

Abstract: Microbiomes have gained significant attention in ecological research, owing to their diverse interactions and essential roles within different organismal ecosystems. Microorganisms, such as bacteria, archaea, and viruses, have profound impact on host ... ...

Abstract	Microbiomes have gained significant attention in ecological research, owing to their diverse interactions and essential roles within different organismal ecosystems. Microorganisms, such as bacteria, archaea, and viruses, have profound impact on host health, influencing digestion, metabolism, immune function, tissue development, and behavior. This study investigates the microbiome diversity and function of Kellet's whelk (
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.03514-23
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Article ; Online: De novo genome assembly and comparative genomics for the colonial ascidian Botrylloides violaceus.

Sumner, Jack T / Andrasz, Cassidy L / Johnson, Christine A / Wax, Sarah / Anderson, Paul / Keeling, Elena L / Davidson, Jean M

G3 (Bethesda, Md.)

2023 Volume 13, Issue 10

Abstract: Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation ...

Abstract	Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian, Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc. short and Oxford Nanopore Technologies long-read sequencing technologies. The resulting assembly is comprised of 831 contigs, has a total length of 121 Mbp, N50 of 1 Mbp, and a BUSCO score of 96.1%. Genome annotation identified 13 K protein-coding genes. Comparative genomic analysis with other tunicates reveals patterns of conservation and divergence within orthologous gene families even among closely related species. Characterization of the Wnt gene family, encoding signaling ligands involved in development and regeneration, reveals conserved patterns of subfamily presence and gene copy number among botryllids. This supports the use of genomic data from nonmodel organisms in the investigation of biological phenomena.
MeSH term(s)	Animals ; Urochordata/genetics ; Genomics/methods ; Genome ; Gene Dosage ; High-Throughput Nucleotide Sequencing/methods ; Molecular Sequence Annotation
Language	English
Publishing date	2023-08-09
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkad181
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Article ; Online: Genomic DNA extraction optimization and validation for genome sequencing using the marine gastropod Kellet's whelk.

Daniels, Benjamin N / Nurge, Jenna / Sleeper, Olivia / Lee, Andy / López, Cataixa / Christie, Mark R / Toonen, Robert J / White, Crow / Davidson, Jean M

PeerJ

2023 Volume 11, Page(s) e16510

Abstract: Next-generation sequencing technologies, such as Nanopore MinION, Illumina Hiseq and Novaseq, and PacBio Sequel II, hold immense potential for advancing genomic research on non-model organisms, including the vast majority of marine species. However, ... ...

Abstract	Next-generation sequencing technologies, such as Nanopore MinION, Illumina Hiseq and Novaseq, and PacBio Sequel II, hold immense potential for advancing genomic research on non-model organisms, including the vast majority of marine species. However, application of these technologies to marine invertebrate species is often impeded by challenges in extracting and purifying their genomic DNA due to high polysaccharide content and other secondary metabolites. In this study, we help resolve this issue by developing and testing DNA extraction protocols for Kellet's whelk (
MeSH term(s)	Animals ; Gastropoda/genetics ; Genome/genetics ; Genomics ; DNA/genetics ; Sequence Analysis, DNA/methods
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.16510
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Article ; Online: Reducing variability of breast cancer subtype predictors by grounding deep learning models in prior knowledge.

Anderson, Paul / Gadgil, Richa / Johnson, William A / Schwab, Ella / Davidson, Jean M

Computers in biology and medicine

2021 Volume 138, Page(s) 104850

Abstract: Deep learning neural networks have improved performance in many cancer informatics problems, including breast cancer subtype classification. However, many networks experience ... ...

Abstract	Deep learning neural networks have improved performance in many cancer informatics problems, including breast cancer subtype classification. However, many networks experience underspecificationwheremultiplecombinationsofparametersachievesimilarperformance, bothin training and validation. Additionally, certain parameter combinations may perform poorly when the test distribution differs from the training distribution. Embedding prior knowledge from the literature may address this issue by boosting predictive models that provide crucial, in-depth information about a given disease. Breast cancer research provides a wealth of such knowledge, particularly in the form of subtype biomarkers and genetic signatures. In this study, we draw on past research on breast cancer subtype biomarkers, label propagation, and neural graph machines to present a novel methodology for embedding knowledge into machine learning systems. We embed prior knowledge into the loss function in the form of inter-subject distances derived from a well-known published breast cancer signature. Our results show that this methodology reduces predictor variability on state-of-the-art deep learning architectures and increases predictor consistency leading to improved interpretation. We find that pathway enrichment analysis is more consistent after embedding knowledge. This novel method applies to a broad range of existing studies and predictive models. Our method moves the traditional synthesis of predictive models from an arbitrary assignment of weights to genes toward a more biologically meaningful approach of incorporating knowledge.
MeSH term(s)	Breast Neoplasms/genetics ; Deep Learning ; Female ; Humans ; Machine Learning ; Neural Networks, Computer
Language	English
Publishing date	2021-09-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2021.104850
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Article ; Online: S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.

Davidson, Jean M / Duronio, Robert J

PLoS genetics

2012 Volume 8, Issue 8, Page(s) e1002831

Abstract: Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we ... ...

Abstract	Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we genetically manipulate the single Drosophila activator E2F (E2f1) to explore the developmental requirement for S phase-coupled E2F down-regulation. Expression of an E2f1 mutant that is not destroyed during S phase drives cell cycle progression and causes apoptosis. Interestingly, this apoptosis is not exclusively the result of inappropriate cell cycle progression, because a stable E2f1 mutant that cannot function as a transcription factor or drive cell cycle progression also triggers apoptosis. This observation suggests that the inappropriate presence of E2f1 protein during S phase can trigger apoptosis by mechanisms that are independent of E2F acting directly at target genes. The ability of S phase-stabilized E2f1 to trigger apoptosis requires an interaction between E2f1 and the Drosophila pRb homolog, Rbf1, and involves induction of the pro-apoptotic gene, hid. Simultaneously blocking E2f1 destruction during S phase and inhibiting the induction of apoptosis results in tissue overgrowth and lethality. We propose that inappropriate accumulation of E2f1 protein during S phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of rapidly proliferating tissues.
MeSH term(s)	Animals ; Apoptosis/genetics ; Cell Proliferation ; DNA/biosynthesis ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; E2F1 Transcription Factor/genetics ; E2F1 Transcription Factor/metabolism ; G1 Phase/genetics ; Gene Expression Regulation, Developmental ; Homeostasis/genetics ; Larva/genetics ; Larva/metabolism ; Mutation ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Proteolysis ; Retinoblastoma Protein ; S Phase/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Drosophila Proteins ; E2F1 Transcription Factor ; HID protein, Drosophila ; Neuropeptides ; Rbf protein, Drosophila ; Retinoblastoma Protein ; Transcription Factors ; DNA (9007-49-2)
Language	English
Publishing date	2012-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1002831
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Article ; Online: SWI/SNF aberrations sensitize pancreatic cancer cells to DNA crosslinking agents.

Davidson, Jean / Shen, Zhewei / Gong, Xue / Pollack, Jonathan R

Oncotarget

2017 Volume 9, Issue 11, Page(s) 9608–9617

Abstract: While gemcitabine has been the mainstay therapy for advanced pancreatic cancer, newer combination regimens (e.g. FOLFIRINOX) have extended patient survival, though carry greater toxicity. Biomarkers are needed to better stratify patients for appropriate ... ...

Abstract	While gemcitabine has been the mainstay therapy for advanced pancreatic cancer, newer combination regimens (e.g. FOLFIRINOX) have extended patient survival, though carry greater toxicity. Biomarkers are needed to better stratify patients for appropriate therapy. Previously, we reported that one-third of pancreatic cancers harbor deletions or deleterious mutations in key subunits of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. The SWI/SNF complex mobilizes nucleosomes on DNA, and plays a key role in modulating DNA transcription and repair. Thus, we hypothesized that pancreatic cancers with SWI/SNF aberrations might exhibit compromised DNA repair, and show increased sensitivity to DNA damaging agents. Here, we studied human pancreatic cancer cell lines with deficient (or else exogenously reconstituted) SWI/SNF subunits, as well as normal pancreatic epithelial cells following SWI/SNF subunit knockdown. Cells were challenged with DNA damaging agents, including those used in current combination regimens, and then cell viability assayed. We found that pancreatic cells with SWI/SNF dysfunction showed markedly increased sensitivity to DNA damaging agents, and in particular DNA crosslinking agents (cisplatin and oxaliplatin). Assaying clearance of γH2AX confirmed that SWI/SNF dysfunction impaired DNA damage response/repair. Finally, by analyzing pancreatic cancer patient data from The Cancer Genome Atlas, we found that pancreatic cancers with SWI/SNF deficiency (subunit mutation and/or decreased expression) were associated with extended patient survival specifically when treated with platinum containing regimens. Thus, SWI/SNF dysfunction sensitizes pancreatic cancer cells to DNA crosslinking agents, and SWI/SNF mutation status may provide a useful biomarker to predict which patients are likely to benefit from platinum-containing chemotherapy regimens.
Language	English
Publishing date	2017-08-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.20033
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Article ; Online: Using Drosophila S2 cells to measure S phase-coupled protein destruction via flow cytometry.

Davidson, Jean M / Duronio, Robert J

Methods in molecular biology (Clifton, N.J.)

2011 Volume 782, Page(s) 205–219

Abstract: Cell proliferation depends on the timely synthesis and destruction of proteins at specific phases of the cell cycle. Recently it was discovered that the destruction of several key cell cycle regulatory proteins during S phase is coupled directly to DNA ... ...

Abstract	Cell proliferation depends on the timely synthesis and destruction of proteins at specific phases of the cell cycle. Recently it was discovered that the destruction of several key cell cycle regulatory proteins during S phase is coupled directly to DNA replication. These proteins harbor a motif called a PIP degron that mediates binding to chromatin bound PCNA at replication forks and recruits the CRL4(Cdt2) E3 ubiquitin ligase. These interactions comprise an elegant mechanism for coupling DNA replication with ubiquitylation and subsequent proteolysis by the 26S proteasome. Here we describe a flow cytometry-based method using Drosophila S2 cells that recapitulates S phase-specific protein proteolysis. Because of the high degree of evolutionary conservation of the PIP degron and CRL4(Cdt2) and the ease of culturing and inhibiting gene function by RNAi in S2 cells, our flow cytometric method should serve as a general tool for determining whether any eukaryotic protein is subject to replication-coupled protein destruction.
MeSH term(s)	Animals ; Cell Line ; Drosophila ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Flow Cytometry/methods ; S Phase/genetics ; S Phase/physiology ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Drosophila Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2011-08-26
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-61779-273-1_15
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Article ; Online: Geographical movement of doctors from education to training and eventual career post: UK cohort studies.

Goldacre, Michael / Davidson, Jean / Maisonneuve, Jenny / Lambert, Trevor

Journal of the Royal Society of Medicine

2013 Volume 106, Issue 3, Page(s) 96–104

Abstract: Objective: To investigate the geographical mobility of UK-trained doctors.: Design: Cohort studies conducted by postal questionnaires.: Setting: UK.: Participants: A total 31,353 UK-trained doctors in 11 cohorts defined by year of qualification, ...

Abstract	Objective: To investigate the geographical mobility of UK-trained doctors. Design: Cohort studies conducted by postal questionnaires. Setting: UK. Participants: A total 31,353 UK-trained doctors in 11 cohorts defined by year of qualification, from 1974 to 2008. Main outcome measures: Location of family home prior to medical school, location of medical school, region of first training post, region of first career post. Analysis for the UK divided into 17 standard geographical regions. Results: The response rate was 81.2% (31,353/45,061; denominators, below, depended on how far the doctors' careers had progressed). Of all respondents, 36% (11,381/31,353) attended a medical school in their home region and 48% (10,370/21,740) undertook specialty training in the same region as their medical school. Of respondents who had reached the grade of consultant or principal in general practice in the UK, 34% (4169/12,119) settled in the same region as their home before entering medical school. Of those in the UK, 70% (7643/10,887) held their first career post in the same region as either their home before medical school, or their medical school or their location of training. For 18% (1938/10,887), all four locations - family home, medical school, place of training, place of first career post - were within the same region. A higher percentage of doctors from the more recent than from the older cohorts settled in the region of their family home. Conclusion: Many doctors do not change geographical region in their successive career moves, and recent cohorts appear less inclined to do so.
MeSH term(s)	Attitude of Health Personnel ; Career Choice ; Cohort Studies ; Education, Medical, Continuing/trends ; Female ; Humans ; Male ; Physicians/statistics & numerical data ; Professional Practice Location/statistics & numerical data ; Schools, Medical/statistics & numerical data ; Surveys and Questionnaires ; United Kingdom
Language	English
Publishing date	2013-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	6731-3
ISSN	1758-1095 ; 0141-0768 ; 0035-9157
ISSN (online)	1758-1095
ISSN	0141-0768 ; 0035-9157
DOI	10.1177/0141076812472617
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Article ; Online: Doctors' age at domestic partnership and parenthood: cohort studies.

Goldacre, Michael J / Davidson, Jean M / Lambert, Trevor W

Journal of the Royal Society of Medicine

2012 Volume 105, Issue 9, Page(s) 390–399

Abstract: Objective: To report on doctors' family formation. Design Cohort studies using structured questionnaires. Setting UK. Participants Doctors who qualified in 1988, 1993, 1996, 1999, 2000 and 2002 were followed up.: Main outcome measures: Living with ... ...

Abstract	Objective: To report on doctors' family formation. Design Cohort studies using structured questionnaires. Setting UK. Participants Doctors who qualified in 1988, 1993, 1996, 1999, 2000 and 2002 were followed up. Main outcome measures: Living with spouse or partner; and doctors' age when first child was born. Results: The response to surveys including questions about domestic circumstances was 89.8% (20,717/23,077 doctors). The main outcomes - living with spouse or partner, and parenthood - varied according to age at qualification. Using the modal ages of 23-24 years at qualification, by the age of 24-25 (i.e. in their first year of medical work) a much smaller percentage of doctors than the general population was living with spouse or partner. By the age of 33, 75% of both women and men doctors were living with spouse or partner, compared with 68% of women and 61% of men aged 33 in the general population. By the age of 24-25, 2% of women doctors and 41% of women in the general population had a child; but women doctors caught up with the general population, in this respect, in their 30s. The specialty with the highest percentage of women doctors who, aged 35, had children was general practice (74%); the lowest was surgery (41%). Conclusions: Doctors are more likely than other people to live with a spouse or partner, and to have children, albeit typically at later ages. Differences between specialties in rates of motherhood may indicate sacrifice by some women of family in favour of career.
MeSH term(s)	Adult ; Age Factors ; Cohort Studies ; Family ; Female ; Humans ; Male ; Medicine/statistics & numerical data ; Parenting ; Physicians/statistics & numerical data ; Spouses/statistics & numerical data ; Surveys and Questionnaires ; United Kingdom ; Young Adult
Language	English
Publishing date	2012-09-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6731-3
ISSN	1758-1095 ; 0141-0768 ; 0035-9157
ISSN (online)	1758-1095
ISSN	0141-0768 ; 0035-9157
DOI	10.1258/jrsm.2012.120016
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Article ; Online: Endoreplication: polyploidy with purpose.

Lee, Hyun O / Davidson, Jean M / Duronio, Robert J

Genes & development

2009 Volume 23, Issue 21, Page(s) 2461–2477

Abstract: A great many cell types are necessary for the myriad capabilities of complex, multicellular organisms. One interesting aspect of this diversity of cell type is that many cells in diploid organisms are polyploid. This is called endopolyploidy and arises ... ...

Abstract	A great many cell types are necessary for the myriad capabilities of complex, multicellular organisms. One interesting aspect of this diversity of cell type is that many cells in diploid organisms are polyploid. This is called endopolyploidy and arises from cell cycles that are often characterized as "variant," but in fact are widespread throughout nature. Endopolyploidy is essential for normal development and physiology in many different organisms. Here we review how both plants and animals use variations of the cell cycle, termed collectively as endoreplication, resulting in polyploid cells that support specific aspects of development. In addition, we discuss briefly how endoreplication occurs in response to certain physiological stresses, and how it may contribute to the development of cancer. Finally, we describe the molecular mechanisms that support the onset and progression of endoreplication.
MeSH term(s)	Animals ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cell Differentiation ; Cell Proliferation ; DNA Replication/genetics ; DNA Replication/physiology ; Humans ; Neoplasms/pathology ; Plant Cells ; Plant Development ; Polyploidy ; Stress, Physiological/physiology
Language	English
Publishing date	2009-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.1829209
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