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Artikel ; Online: Chatterboxes: the structural and functional diversity of cyclins.

Tatum, Natalie J / Endicott, Jane A

Seminars in cell & developmental biology

2020 Band 107, Seite(n) 4–20

Abstract: Proteins of the cyclin family have divergent sequences and execute diverse roles within the cell while sharing a common fold: the cyclin box domain. Structural studies of cyclins have played a key role in our characterization and understanding of ... ...

Abstract	Proteins of the cyclin family have divergent sequences and execute diverse roles within the cell while sharing a common fold: the cyclin box domain. Structural studies of cyclins have played a key role in our characterization and understanding of cellular processes that they control, though to date only ten of the 29 CDK-activating cyclins have been structurally characterized by X-ray crystallography or cryo-electron microscopy with or without their cognate kinases. In this review, we survey the available structures of human cyclins, highlighting their molecular features in the context of their cellular roles. We pay particular attention to how cyclin activity is regulated through fine control of degradation motif recognition and ubiquitination. Finally, we discuss the emergent roles of cyclins independent of their roles as cyclin-dependent protein kinase activators, demonstrating the cyclin box domain to be a versatile and generalized scaffolding domain for protein-protein interactions across the cellular machinery.
Mesh-Begriff(e)	Animals ; Cyclins/chemistry ; Cyclins/metabolism ; Humans ; Models, Molecular ; Protein Domains ; Proteolysis ; Structure-Activity Relationship ; Substrate Specificity
Chemische Substanzen	Cyclins
Sprache	Englisch
Erscheinungsdatum	2020-05-13
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2020.04.021
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in Vancomycin for Patients With Obesity.

Hughes, Maria-Stephanie A / Hughes, Jasmine H / Endicott, Jeffrey / Langton, Meagan / Ahern, John W / Keizer, Ron J

Therapeutic drug monitoring

2024

Abstract: Background: Both parametric and nonparametric methods have been proposed to support model-informed precision dosing (MIPD). However, which approach leads to better models remains uncertain. Using open-source software, these 2 statistical approaches for ... ...

Abstract	Background: Both parametric and nonparametric methods have been proposed to support model-informed precision dosing (MIPD). However, which approach leads to better models remains uncertain. Using open-source software, these 2 statistical approaches for model development were compared using the pharmacokinetics of vancomycin in a challenging subpopulation of class 3 obesity. Methods: Patients on vancomycin at the University of Vermont Medical Center from November 1, 2021, to February 14, 2023, were entered into the MIPD software. The inclusion criteria were body mass index (BMI) of at least 40 kg/m2 and 1 or more vancomycin levels. A parametric model was created using nlmixr2/NONMEM, and a nonparametric model was created using metrics. Then, a priori and a posteriori predictions were evaluated using the normalized root mean squared error (nRMSE) for precision and the mean percentage error (MPE) for bias. The parametric model was evaluated in a simulated MIPD context using an external validation dataset. Results: In total, 83 patients were included in the model development, with a median age of 56.6 years (range: 24-89 years), and a median BMI of 46.3 kg/m2 (range: 40-70.3 kg/m2). Both parametric and nonparametric models were 2-compartmental, with creatinine clearance and fat-free mass as covariates to c clearance and volume parameters, respectively. The a priori MPE and nRMSE for the parametric versus nonparametric models were -6.3% versus 2.69% and 27.2% versus 30.7%, respectively. The a posteriori MPE and RMSE were 0.16% and 0.84%, and 13.8% and 13.1%. The parametric model matched or outperformed previously published models on an external validation dataset (n = 576 patients). Conclusions: Minimal differences were found in the model structure and predictive error between the parametric and nonparametric approaches for modeling vancomycin class 3 obesity. However, the parametric model outperformed several other models, suggesting that institution-specific models may improve pharmacokinetics management.
Sprache	Englisch
Erscheinungsdatum	2024-05-10
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	424443-6
ISSN	1536-3694 ; 0163-4356
ISSN (online)	1536-3694
ISSN	0163-4356
DOI	10.1097/FTD.0000000000001214
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Crystallographic fragment screening in academic cancer drug discovery.

Martin, Mathew P / Endicott, Jane A / Noble, Martin E M / Tatum, Natalie J

Methods in enzymology

2023 Band 690, Seite(n) 211–234

Abstract: Fragment-based drug discovery (FBDD) has brought several drugs to the clinic, notably to target proteins once considered to be challenging, or even undruggable. Screening in FBDD relies upon observing and/or measuring weak (millimolar-scale) binding ... ...

Abstract	Fragment-based drug discovery (FBDD) has brought several drugs to the clinic, notably to target proteins once considered to be challenging, or even undruggable. Screening in FBDD relies upon observing and/or measuring weak (millimolar-scale) binding events using biophysical techniques or crystallographic fragment screening. This latter structural approach provides no information about binding affinity but can reveal binding mode and atomic detail on protein-fragment interactions to accelerate hit-to-lead development. In recent years, high-throughput platforms have been developed at synchrotron facilities to screen thousands of fragment-soaked crystals. However, using accessible manual techniques it is possible to run informative, smaller-scale screens within an academic lab setting. This chapter describes general protocols for home laboratory-scale fragment screening, from fragment soaking through to structure solution and, where appropriate, signposts to background, protocols or alternatives elsewhere.
Mesh-Begriff(e)	Early Detection of Cancer ; Crystallography, X-Ray ; Drug Discovery/methods ; Proteins ; Drug Evaluation, Preclinical/methods ; Neoplasms
Chemische Substanzen	Proteins
Sprache	Englisch
Erscheinungsdatum	2023-07-11
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988
ISSN (online)	1557-7988
DOI	10.1016/bs.mie.2023.06.021
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Dehydrated human amnion/chorion membrane use in emergent craniectomies shows minimal dural adhesions.

Endicott, Luke / Ehresman, Jeff / Tettelbach, William / Forsyth, Allyn / Lee, Bryan S

Journal of wound care

2023 Band 32, Heft 10, Seite(n) 634–640

Abstract: Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting ... ...

Abstract	Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exploration of posterior lumbar interbody fusion operations which require entry into the epidural space. The purpose of this study was to evaluate whether or not the use of DHACM in the setting of emergent craniectomies decreased the rate of dural adhesion formation and subsequent cranioplasty complications. Patients (n=7) who underwent emergent craniectomy and intraoperative placement of DHACM were evaluated during replacement of either an autologous skull cap or a custom-made implant, at which point the degree of adhesions was qualitatively assessed. Placement of DHACM below and on top of the dura resulted in negligible adhesion being found during the defect exposure, and there were no intraoperative complications during cranioplasties. Reported estimated blood loss across the seven patients averaged 64.2ml, total operative time averaged 79.2 minutes, and time dedicated to exposing defect for bone flap placement was <3 minutes.
Mesh-Begriff(e)	Humans ; Amnion/transplantation ; Craniotomy/adverse effects ; Surgical Flaps ; Plastic Surgery Procedures ; Tissue Adhesions/surgery ; Tissue Adhesions/etiology ; Postoperative Complications/etiology ; Chorion/transplantation
Sprache	Englisch
Erscheinungsdatum	2023-10-13
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	1353951-6
ISSN	0969-0700
ISSN	0969-0700
DOI	10.12968/jowc.2023.32.10.634
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Acute Generalized Exanthematous Pustulosis.

Lee, Jinwoo / Endicott, Alyson / Shinkai, Kanade

JAMA dermatology

2021 Band 157, Heft 5, Seite(n) 589

Mesh-Begriff(e)	Acute Generalized Exanthematous Pustulosis/diagnosis ; Acute Generalized Exanthematous Pustulosis/etiology ; Acute Generalized Exanthematous Pustulosis/therapy ; Cyclosporine/therapeutic use ; Dermatologic Agents/therapeutic use ; Female ; Humans ; Middle Aged
Chemische Substanzen	Dermatologic Agents ; Cyclosporine (83HN0GTJ6D)
Sprache	Englisch
Erscheinungsdatum	2021-03-27
Erscheinungsland	United States
Dokumenttyp	Case Reports ; Journal Article
ZDB-ID	2701761-8
ISSN	2168-6084 ; 2168-6068
ISSN (online)	2168-6084
ISSN	2168-6068
DOI	10.1001/jamadermatol.2020.5187
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Structural insights into the functional diversity of the CDK-cyclin family.

Wood, Daniel J / Endicott, Jane A

Open biology

2018 Band 8, Heft 9

Abstract: Since their characterization as conserved modules that regulate progression through the eukaryotic cell cycle, cyclin-dependent protein kinases (CDKs) in higher eukaryotic cells are now also emerging as significant regulators of transcription, metabolism ...

Abstract	Since their characterization as conserved modules that regulate progression through the eukaryotic cell cycle, cyclin-dependent protein kinases (CDKs) in higher eukaryotic cells are now also emerging as significant regulators of transcription, metabolism and cell differentiation. The cyclins, though originally characterized as CDK partners, also have CDK-independent roles that include the regulation of DNA damage repair and transcriptional programmes that direct cell differentiation, apoptosis and metabolic flux. This review compares the structures of the members of the CDK and cyclin families determined by X-ray crystallography, and considers what mechanistic insights they provide to guide functional studies and distinguish CDK- and cyclin-specific activities. Aberrant CDK activity is a hallmark of a number of diseases, and structural studies can provide important insights to identify novel routes to therapy.
Mesh-Begriff(e)	Animals ; Binding Sites ; Cell Cycle ; Crystallography, X-Ray ; Cyclin-Dependent Kinases/chemistry ; Cyclin-Dependent Kinases/metabolism ; Cyclins/chemistry ; Cyclins/metabolism ; Humans ; Models, Molecular ; Multigene Family ; Protein Binding ; Protein Conformation
Chemische Substanzen	Cyclins ; Cyclin-Dependent Kinases (EC 2.7.11.22)
Sprache	Englisch
Erscheinungsdatum	2018-09-05
Erscheinungsland	England
Dokumenttyp	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.180112
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Educator Perspectives on Grief-Sensitive Training During the COVID-19 Pandemic in US Public Schools.

Lively-Endicott, Hannah R / Naimi, Kiana / Hudson, Sharon M / Schonfeld, David J

The Journal of school health

2023 Band 94, Heft 1, Seite(n) 5–13

Abstract: Background: Grief and loss are common experiences for children and adolescents, particularly during the COVID-19 pandemic. Educators feel unprepared to support grieving students due to lack of training. We studied educator experiences receiving grief- ... ...

Abstract	Background: Grief and loss are common experiences for children and adolescents, particularly during the COVID-19 pandemic. Educators feel unprepared to support grieving students due to lack of training. We studied educator experiences receiving grief-sensitive training as part of the grief-sensitive schools initiative (GSSI), which provides grief-sensitive training, online video-based and print resources, and a financial grant to schools and school districts for use in supporting grieving students. Methods: Fourteen New York and Florida educators who received GSSI training participated in small focus groups or semi-structured interviews on their experiences receiving GSSI training and supporting grieving students during the pandemic. Transcripts were analyzed using grounded-theory analysis. Results: Emergent themes included increased confidence engaging grieving students, the desire for recurring trainings, the value of receiving training from an expert on pediatric grief and loss and the opportunity to ask questions, the need for grief-sensitive training to reflect the cultural diversity of school communities, the unique losses experienced by students during the pandemic, and compassion fatigue and burnout in educators. Implications for school health policy, practice, and equity: Policymakers should recognize the effects of grief on students' learning and development and collaborate with educators to develop resources. Conclusions: Educators found GSSI training useful in supporting grieving students, particularly during the pandemic.
Mesh-Begriff(e)	Adolescent ; Humans ; Child ; Pandemics ; COVID-19/epidemiology ; Schools ; Grief ; Students
Sprache	Englisch
Erscheinungsdatum	2023-10-25
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	952835-0
ISSN	1746-1561 ; 0022-4391
ISSN (online)	1746-1561
ISSN	0022-4391
DOI	10.1111/josh.13400
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Long-lived mice with reduced growth hormone signaling have a constitutive upregulation of hepatic chaperone-mediated autophagy.

Endicott, S Joseph / Boynton, Dennis N / Beckmann, Logan J / Miller, Richard A

Autophagy

2020 Band 17, Heft 3, Seite(n) 612–625

Abstract: Chaperone-mediated autophagy (CMA) is the most selective form of lysosomal proteolysis. CMA modulates proteomic organization through selective protein degradation, with targets including metabolic enzymes, cell growth regulators, and neurodegeneration- ... ...

Abstract	Chaperone-mediated autophagy (CMA) is the most selective form of lysosomal proteolysis. CMA modulates proteomic organization through selective protein degradation, with targets including metabolic enzymes, cell growth regulators, and neurodegeneration-related proteins. CMA activity is low in
Mesh-Begriff(e)	Animals ; Chaperone-Mediated Autophagy/genetics ; Chaperone-Mediated Autophagy/physiology ; Growth Hormone/metabolism ; Liver/metabolism ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Mice, Knockout ; Signal Transduction/genetics ; Signal Transduction/physiology ; Mice
Chemische Substanzen	Growth Hormone (9002-72-6) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1)
Sprache	Englisch
Erscheinungsdatum	2020-02-12
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2020.1725378
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Emergence of Ferrichelatase Activity in a Siderophore-Binding Protein Supports an Iron Shuttle in Bacteria.

Endicott, Nathaniel P / Rivera, Gerry Sann M / Yang, Jinping / Wencewicz, Timothy A

ACS central science

2020 Band 6, Heft 4, Seite(n) 493–506

Abstract: Siderophores are small-molecule high-affinity multidentate chelators selective for ferric iron that are produced by pathogenic microbes to aid in nutrient sequestration and enhance virulence. In Gram-positive bacteria, the currently accepted paradigm in ... ...

Abstract	Siderophores are small-molecule high-affinity multidentate chelators selective for ferric iron that are produced by pathogenic microbes to aid in nutrient sequestration and enhance virulence. In Gram-positive bacteria, the currently accepted paradigm in siderophore-mediated iron acquisition is that effluxed metal-free siderophores extract ferric iron from biological sources and the resulting ferric siderophore complex undergoes diffusion-controlled association with a surface-displayed siderophore-binding protein (SBP) followed by ABC permease-mediated translocation across the cell envelope powered by ATP hydrolysis. Here we show that a more efficient paradigm is possible in Gram-positive bacteria where extracellular metal-free siderophores associate directly with
Sprache	Englisch
Erscheinungsdatum	2020-03-09
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	2374-7943
ISSN	2374-7943
DOI	10.1021/acscentsci.9b01257
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Cryo-EM structure of SKP1-SKP2-CKS1 in complex with CDK2-cyclin A-p27KIP1.

Rowland, Rhianna J / Heath, Richard / Maskell, Daniel / Thompson, Rebecca F / Ranson, Neil A / Blaza, James N / Endicott, Jane A / Noble, Martin E M / Salamina, Marco

Scientific reports

2023 Band 13, Heft 1, Seite(n) 10718

Abstract: p27KIP1 (cyclin-dependent kinase inhibitor 1B, p27) is a member of the CIP/KIP family of CDK (cyclin dependent kinase) regulators that inhibit cell cycle CDKs. p27 phosphorylation by CDK1/2, signals its recruitment to the ... ...

Abstract	p27KIP1 (cyclin-dependent kinase inhibitor 1B, p27) is a member of the CIP/KIP family of CDK (cyclin dependent kinase) regulators that inhibit cell cycle CDKs. p27 phosphorylation by CDK1/2, signals its recruitment to the SCF
Mesh-Begriff(e)	S-Phase Kinase-Associated Proteins/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Cyclin A/metabolism ; Cryoelectron Microscopy ; CDC2-CDC28 Kinases ; Cyclin-Dependent Kinases/metabolism
Chemische Substanzen	S-Phase Kinase-Associated Proteins ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; Cyclin A ; CDC2-CDC28 Kinases (EC 2.7.11.22) ; Cyclin-Dependent Kinases (EC 2.7.11.22)
Sprache	Englisch
Erscheinungsdatum	2023-07-03
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-37609-9
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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