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  1. Article ; Online: Preface to IUBMB life special issue on protein phosphorylation dedicated to Eddy Fischer.

    Newton, Alexandra C / Alessi, Dario R

    IUBMB life

    2023  Volume 75, Issue 4, Page(s) 282–283

    Language English
    Publishing date 2023-03-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 1492141-8
    ISSN 1521-6551 ; 1521-6543
    ISSN (online) 1521-6551
    ISSN 1521-6543
    DOI 10.1002/iub.2715
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  2. Article: Rubus dentatifolius (Briggs) W. C. R. Wats. and Rubus vectensis W. C. R. Wats

    Newton, A

    Watsonia. Aug 1979. v. 12 (pt.4)

    1979  

    Keywords plant taxonomy
    Language English
    Dates of publication 1979-08
    Size p. 340-341.
    Document type Article
    ZDB-ID 2474151-6
    ISSN 0043-1532
    ISSN 0043-1532
    Database NAL-Catalogue (AGRICOLA)

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  3. Article: Protein kinase C: release from quarantine by mTORC2.

    Baffi, Timothy R / Newton, Alexandra C

    Trends in biochemical sciences

    2022  Volume 47, Issue 6, Page(s) 518–530

    Abstract: Protein kinase C (PKC) isozymes are maintained in a 'ready-to-go' but 'safe' autoinhibited ...

    Abstract Protein kinase C (PKC) isozymes are maintained in a 'ready-to-go' but 'safe' autoinhibited conformation until second messenger binding unleashes an autoinhibitory pseudosubstrate to allow substrate phosphorylation. However, to gain this 'ready-to-go' conformation, PKC must be processed by a series of complex priming phosphorylations, the mechanism of which was enigmatic until now. Recent findings snapped the pieces of the phosphorylation puzzle into place to unveil a process that involves a newly described motif (TOR interaction motif, TIM), a well-described kinase [mechanistic target of rapamycin complex 2 (mTORC2)], and an often-used mechanism (autophosphorylation) to prime PKC to signal. This review highlights new insights into how phosphorylation controls PKC and discusses them in the context of common mechanisms for AGC kinase regulation by phosphorylation and autophosphorylation.
    MeSH term(s) Isoenzymes/metabolism ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Quarantine
    Chemical Substances Isoenzymes ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; Protein Kinase C (EC 2.7.11.13)
    Language English
    Publishing date 2022-03-28
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.03.003
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  4. Article ; Online: mTOR Regulation of AGC Kinases: New Twist to an Old Tail.

    Baffi, Timothy R / Newton, Alexandra C

    Molecular pharmacology

    2021  Volume 101, Issue 4, Page(s) 213–218

    Abstract: ... for catalysis, and a C-terminal tail whose phosphorylation at a site termed the hydrophobic motif stabilizes ... by the phosphoinositide-dependent kinase 1, the mechanism of phosphorylation of the C-tail hydrophobic motif has been ... controversial. For a subset of AGC kinases, which include most protein kinase C (PKC) isozymes and Akt ...

    Abstract The family of AGC kinases not only regulates cellular biology by phosphorylating substrates but is itself controlled by phosphorylation. Phosphorylation generally occurs at two conserved regions in these kinases: a loop near the entrance to the active site, termed the activation loop, that correctly aligns residues for catalysis, and a C-terminal tail whose phosphorylation at a site termed the hydrophobic motif stabilizes the active conformation. Whereas phosphorylation of the activation loop is well established to be catalyzed by the phosphoinositide-dependent kinase 1, the mechanism of phosphorylation of the C-tail hydrophobic motif has been controversial. For a subset of AGC kinases, which include most protein kinase C (PKC) isozymes and Akt, phosphorylation of the hydrophobic motif in cells was shown to depend on mTORC2 over 15 years ago, yet whether this was by direct phosphorylation or by another mechanism has remained elusive. The recent identification of a novel and evolutionarily conserved phosphorylation site on the C-tail, termed the TOR interaction motif (TIM), has finally unraveled the mystery of how mTORC2 regulates its client kinases. mTORC2 does not directly phosphorylate the hydrophobic motif; instead, it converts kinases such as PKC and Akt into a conformation that can ultimately autophosphorylate at the hydrophobic motif. Identification of the direct mTOR phosphorylation that facilitates autoregulation of the C-tail hydrophobic motif revises the activation mechanisms of mTOR-regulated AGC kinases. This new twist to an old tail opens avenues for therapeutic intervention. SIGNIFICANCE STATEMENT: The enzyme mTORC2 has been an enigmatic regulator of AGC kinases such as protein kinase C (PKC) and Akt. The recent discovery of a motif named the TOR interaction motif in the C-tail of these kinases solves the mystery: mTORC2 marks these kinases for maturity by, ultimately, facilitating autophosphorylation of another C-tail site, the hydrophobic motif.
    MeSH term(s) Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Phosphorylation/physiology ; Protein Kinase C/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances MTOR protein, human (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Protein Kinase C (EC 2.7.11.13)
    Language English
    Publishing date 2021-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/molpharm.121.000310
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  5. Article ; Online: Complex Signaling Networks Control Coxiella burnetii.

    Thomas, David R / Newton, Hayley J

    Journal of bacteriology

    2023  Volume 205, Issue 3, Page(s) e0001323

    Abstract: A recent study by S. Wachter, C. L. Larson, K. Virtaneva, K. Kanakabandi, et al. (J Bacteriol 205 ... of two-component systems in Coxiella burnetii. This research demonstrates that the zoonotic pathogen C ...

    Abstract A recent study by S. Wachter, C. L. Larson, K. Virtaneva, K. Kanakabandi, et al. (J Bacteriol 205:e00416-22, 2023, https://doi.org/10.1128/JB.00416-22) utilizes new technologies to examine the role of two-component systems in Coxiella burnetii. This research demonstrates that the zoonotic pathogen C. burnetii mediates complex transcriptional control, throughout different bacterial phases and environmental conditions, with relatively few regulatory elements.
    MeSH term(s) Humans ; Coxiella burnetii/genetics ; Gene Expression Regulation ; Q Fever/microbiology
    Language English
    Publishing date 2023-02-27
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2968-3
    ISSN 1098-5530 ; 0021-9193
    ISSN (online) 1098-5530
    ISSN 0021-9193
    DOI 10.1128/jb.00013-23
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  6. Article ; Online: Stochastic competitive release and adaptive chemotherapy.

    Park, J / Newton, P K

    Physical review. E

    2023  Volume 108, Issue 3-1, Page(s) 34407

    Abstract: ... sensitive (S), and resistant (R) populations of N cells, with a chemotherapy control parameter, C(t ... of the control parameter C∈[0,1], showing that the size of the R region increases with increasing C ... fixation probability regions of the R and S populations in the HSR trilinear phase plane as a function ...

    Abstract We develop a finite-cell model of tumor natural selection dynamics to investigate the stochastic fluctuations associated with multiple rounds of adaptive chemotherapy. The adaptive cycles are designed to avoid chemoresistance in the tumor by managing the ecological mechanism of competitive release of a resistant subpopulation. Our model is based on a three-component evolutionary game played among healthy (H), sensitive (S), and resistant (R) populations of N cells, with a chemotherapy control parameter, C(t), which we use to dynamically impose selection pressure on the sensitive subpopulation to slow tumor growth and manage competitive release of the resistant population. The adaptive chemoschedule is designed based on the deterministic (N→∞) adjusted replicator dynamical system, then implemented using the finite-cell stochastic frequency dependent Moran process model (N=10K-50K) to ascertain the cumulative effect of the stochastic fluctuations on the efficacy of the adaptive schedules over multiple rounds. We quantify the stochastic fixation probability regions of the R and S populations in the HSR trilinear phase plane as a function of the control parameter C∈[0,1], showing that the size of the R region increases with increasing C. We then implement an adaptive time-dependent schedule C(t) for the stochastic model and quantify the variances (using principal component coordinates) associated with the evolutionary cycles over multiple rounds of adaptive therapy. The variances increase subquadratically through several rounds before the evolutionary cycle begins to break down. Despite this, we show the stochastic adaptive schedules are more effective at delaying resistance than standard maximum tolerated dose and low-dose metronomic schedules. The simplified low-dimensional model provides some insights on how well multiple rounds of adaptive therapies are likely to perform over a range of tumor sizes (i.e., different values of N) if the goal is to maintain a sustained balance among competing subpopulations of cells to avoid chemoresistance via competitive release in a stochastic environment.
    MeSH term(s) Humans ; Biological Evolution ; Neoplasms/drug therapy ; Neoplasms/pathology ; Selection, Genetic ; Game Theory ; Stochastic Processes
    Language English
    Publishing date 2023-10-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2844562-4
    ISSN 2470-0053 ; 2470-0045
    ISSN (online) 2470-0053
    ISSN 2470-0045
    DOI 10.1103/PhysRevE.108.034407
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  7. Article ; Online: The importance of perinatal maternal depression as a public health problem in Africa.

    Kariuki, Symon M / Newton, Charles R J C

    The lancet. Psychiatry

    2022  Volume 9, Issue 7, Page(s) 527–528

    MeSH term(s) Africa/epidemiology ; Child ; Depression/epidemiology ; Depression, Postpartum/epidemiology ; Family ; Female ; Humans ; Infant, Newborn ; Perinatal Care ; Pregnancy ; Public Health
    Language English
    Publishing date 2022-05-19
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2215-0374
    ISSN (online) 2215-0374
    DOI 10.1016/S2215-0366(22)00197-3
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  8. Article: The association between edentulism and progress of multimorbidity over 12 years among older American adults.

    Mira, R / Newton, J T / Sabbah, W

    Community dental health

    2024  Volume 41, Issue 1, Page(s) 39–43

    Abstract: ... by summing 10 nutrients (Protein, Vitamins C, D, B12, E, Calcium, Zinc, Polyunsaturated fatty acids, Folate ...

    Abstract Objectives: To examine the relationship between edentulism and the progress of multimorbidity, and the role of nutritional intake and behaviours among older Americans.
    Methods: We used 7 waves (2006-2018) of the Health and Retirement Study, a longitudinal survey of older Americans (number included in analysis 2,224). Edentulism was assessed in 2006 and 2012. Multimorbidity was indicated by 5 self-reported conditions: diabetes, heart conditions, lung diseases, cancer, and stroke. Behavioural factors were smoking, excessive alcohol consumption, physical activity, and body mass index. Nutritional intake was calculated by summing 10 nutrients (Protein, Vitamins C, D, B12, E, Calcium, Zinc, Polyunsaturated fatty acids, Folate and ß- carotene). Multilevel models for analysis of longitudinal data were used to assess the association between change in repeated measures of multimorbidity (between 2006 and 2018) and edentulism (2006) adjusting for nutritional intake, behavioural and socioeconomic factors.
    Results: Participants who were edentate in 2006 and 2012 had higher rate-ratios (RR) for change in multimorbidity between 2006 to 2018 (RR: 1.29 and 1.28, respectively). After adjusting for socioeconomic factors, total nutrients and behavioural factors, these RR attenuated to 1.12 (95%CI: 1.06, 1.18) and 1.10 (95%CI: 1.05, 1.16), respectively. Total nutrition was negatively associated with progress of multimorbidity, but after adjusting for socioeconomic and behavioural factors the association became insignificant. Total nutrients rates in 2013 were significantly lower among those who were edentate in 2006 and 2012.
    Conclusion: There was a longitudinal association between edentulism and progress of multimorbidity. The relationship appeared to be mediated be behaviours and nutrition.
    MeSH term(s) Adult ; Humans ; Aged ; Multimorbidity ; Longitudinal Studies ; Socioeconomic Factors ; Smoking ; Body Mass Index
    Language English
    Publishing date 2024-02-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 631156-8
    ISSN 0265-539X
    ISSN 0265-539X
    DOI 10.1922/CDH_00150Mira05
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  9. Article ; Online: How are people coping with working from home during the COVID-19 pandemic?: Experiences from the Netherlands and South Korea.

    Park, So Yeon / Lee, Rachel / Newton, Caroline / Han, Gisung

    PloS one

    2024  Volume 19, Issue 4, Page(s) e0301351

    Abstract: COVID-19 has made working from home routine for many. People who have had to maintain their productivity, particularly in physically and/or socially unacceptable home-working situations, experienced one of the pandemic's disadvantages. The experience can ...

    Abstract COVID-19 has made working from home routine for many. People who have had to maintain their productivity, particularly in physically and/or socially unacceptable home-working situations, experienced one of the pandemic's disadvantages. The experience can vary substantially among individuals as well as by country. This study presents the results of a comparative study of the Netherlands and Korea. Working from home was not uncommon in the Netherlands before the pandemic; however, in Korea, employers adopted working from home from its start, and that increased rapidly. An online survey enabled us to compare the physical and social conditions of current home workspaces in both countries, to understand how well-equipped they were to support people who had to work from home. We studied the changes in productivity and physical/mental health before and during COVID-19, to learn how people coped with working from home in both countries. Contrary to expectations, Koreans showed better scores than people in the Netherlands, in terms of changes in health and productivity. This article discusses various aspects of that result, such as satisfaction with home workspace, housing type, job position and prior experience, compulsoriness, and frequency of working from home. Relieving stress and concentration appeared to be the most important dimensions of telecommuters' satisfaction with working from home environments in both countries. The results are the basis for suggesting the development of strategies for a desirable WFH environment, considering different background contexts, experiences and cultures.
    MeSH term(s) Humans ; Pandemics ; Netherlands/epidemiology ; COVID-19/epidemiology ; Republic of Korea/epidemiology ; Coping Skills
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0301351
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  10. Article ; Online: Contagious equine metritis: A 2020 vision on control of a notifiable equine disease in the United Kingdom.

    Meldrum, K C / Newton, J R

    Equine veterinary journal

    2020  Volume 52, Issue 3, Page(s) 347–348

    MeSH term(s) Animals ; Endometritis/veterinary ; Female ; Horse Diseases ; Horses ; United Kingdom
    Language English
    Publishing date 2020-04-24
    Publishing country United States
    Document type Editorial
    ZDB-ID 41606-x
    ISSN 2042-3306 ; 0425-1644
    ISSN (online) 2042-3306
    ISSN 0425-1644
    DOI 10.1111/evj.13247
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