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Browsing publications by Dr Carmen Martin-Ruiz.

Newcastle AuthorsTitleYearFull text
Emeritus Professor Roy Taylor
Alison Barnes
Dr Kieren Hollingsworth
Keaton Irvine
Dr Alexandra Solovyova
et al.
Aetiology of Type 2 diabetes in people with a 'normal' body mass index: testing the personal fat threshold hypothesis2023
Dr Rachael Redgrave
Dr Maria Camacho Encina
Dr Simon Tual-Chalot
Dr Omowumi Folaranmi
Dr Carmen Martin-Ruiz
et al.
The senescence-associated secretory phenotype as a biomarker for age-related myocardial remodelling and cardiovascular disease2023
Dr Paul Donaghy
Dr Simon Cockell
Dr Carmen Martin-Ruiz
Dr Jonathan Coxhead
Dr Joseph Kane
et al.
Blood mRNA expression in Alzheimer’s disease and dementia with Lewy bodies2022
Dr Antoneta Granic
Dr Carmen Martin-Ruiz
Lucy Rimmer
Dr Richard Dodds
Dr Louise Robinson
et al.
Immunosenescence profiles of lymphocyte compartments and multiple long-term conditions (multimorbidity) in very old adults: The Newcastle 85+ Study2022
Professor Heather Cordell
Dr Carmen Martin-Ruiz
Dr Louise Robinson
Emeritus Professor Thomas Kirkwood
Fotios Drenos
et al.
No Evidence That Genetic Variation at the Klotho Locus Is Associated With Longevity in Caucasians from the Newcastle 85+ Study and the UK Biobank2022
Anna Stevenson
Leolie Telford-Cooke
Dr Craig Parker
Dr Carmen Martin-Ruiz
Professor Raj Kalaria
et al.
Plasma Myeloperoxidase as a Potential Biomarker of Patient Response to Anti-Dementia Treatment in Alzheimer's Disease2022
Dr Louise Robinson
Dr Carmen Martin-Ruiz
Dr Rachel Duncan
Anaemia and physical and mental health in the very old: An individual participant data meta-analysis of four longitudinal studies of ageing2021
Dr Carmen Martin-Ruiz
L-arginine ameliorates defective autophagy in GM2 gangliosidoses by mTOR modulation2021
Dr Oliver Shannon
Ammar Ashor
Dr Filippo Scialo
Dr Gabi Saretzki
Dr Carmen Martin-Ruiz
et al.
Mediterranean diet and the hallmarks of ageing2021
Professor Heather Cordell
Dr Kristin Ayers
Dr Joanna Collerton
Dr Karen Davies
Dr Rachel Duncan
et al.
Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes (Nature Communications, (2019), 10, 1, (3669), 10.1038/s41467-019-11558-2)2021
Claire Kolenda
Dr Craig Parker
Dr Carmen Martin-Ruiz
T lymphocyte senescence is attenuated in Parkinson’s disease2021
Sarah Hakeem Hakeem
Dr Terry Aspray
Dr Andrew Kingston
Dr Carmen Martin-Ruiz
Dr Louise Robinson
et al.
The Association between 25-Hydroxyvitamin D Concentration and Telomere Length in the Very-Old: The Newcastle 85+ Study2021
Emerita Professor Carol Jagger
Dr Carmen Martin-Ruiz
The effects of single and a combination of determinants of anaemia in the very old: results from the TULIPS consortium2021
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Dr Gavin Richardson
Lilia Draganova
Dr Rachael Redgrave
et al.
CMV-independent increase in CD27−CD28+ CD8+ EMRA T cells is inversely related to mortality in octogenarians2020
Dr Antoneta Granic
Dr Carmen Martin-Ruiz
Dr Richard Dodds
Professor Dame Louise Robinson
Professor Ioakim Spyridopoulos
et al.
Immunosenescence profiles are not associated with muscle strength, physical performance and sarcopenia risk in very old adults: The Newcastle 85+ Study2020
Professor Alan Thomas
Dr Calum Hamilton
Dr Paul Donaghy
Dr Carmen Martin-Ruiz
Dr Christopher Morris
et al.
Prospective Longitudinal Evaluation of Cytokines in mild cognitive impairment due to AD and Lewy Body Disease2020
Dr Carmen Martin-Ruiz
Professor Alison Yarnall
Dr John Boucher
Dr Rachael Lawson
Claire Kolenda
et al.
Senescence and inflammatory markers for predicting clinical progression in Parkinson's disease-the ICICLE-PD study2020
Dr Danny Chan
Dr Carmen Martin-Ruiz
Dr Gabriele Saretzki
Dr R Neely
Professor Vijay Kunadian
et al.
The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome2020
Professor Heather Cordell
Dr Joanna Collerton
Dr Karen Davies
Dr Rachel Duncan
Emerita Professor Carol Jagger
et al.
A meta-analysis of genome-wide association studies identifies multiple longevity genes2019
Professor John O'Brien
Dr Paul Donaghy
Dr Rachael Lawson
Dr Christopher Morris
Nicola Barnett
et al.
Inflammation in Mild Cognitive Impairment due to Parkinson’s disease, Lewy Body disease and Alzheimer’s disease2019
Dr Eleanor King
Dr Paul Donaghy
Dr Christopher Morris
Nicola Barnett
Kirsty Olsen
et al.
Peripheral inflammation in mild cognitive impairment with possible and probable Lewy body disease and Alzheimer’s disease2019
Dr Nuno Mendonca
Emerita Professor Carol Jagger
Dr Antoneta Granic
Dr Carmen Martin-Ruiz
Professor John Mathers
et al.
Plasma Vitamin B12, Supplementation and Mortality2019
Professor Melissa Bateson
Dr Carmen Martin-Ruiz
Gillian Pepper
Professor Thomas von Zglinicki
Professor Daniel Nettle
et al.
Smoking does not accelerate leucocyte telomere attrition: A meta-analysis of 18 longitudinal cohorts2019
Dr Carmen Martin-Ruiz
Telomere length is associated with childhood trauma in patients with severe mental disorders2019
Dr Nuno Mendonca
Emerita Professor Carol Jagger
Dr Antoneta Granic
Dr Carmen Martin-Ruiz
Professor John Mathers
et al.
Elevated total homocysteine in all participants and plasma vitamin B12 concentrations in women are associated with all-cause and cardiovascular mortality in the very old: The Newcastle 85+ Study2018
Dr Eleanor King
Professor John O'Brien
Dr Paul Donaghy
Dr Christopher Morris
Nicola Barnett
et al.
Peripheral inflammation in prodromal Alzheimer’s and Lewy body dementias2018
Dr Carmen Martin-Ruiz
Age-related gene expression changes and transcriptome wide association study of physical and cognitive aging traits in the Lothian Birth Cohort 19362017
Professor Daniel Nettle
Dr Clare Andrews
Thomas Bedford
Claire Kolenda
Dr Craig Parker
et al.
Early-life adversity accelerates cellular ageing and affects adult inflammation: Experimental evidence from the European starling2017
Dr Antoneta Granic
Dr Karen Davies
Dr Carmen Martin-Ruiz
Emerita Professor Carol Jagger
Emeritus Professor Thomas Kirkwood
et al.
Grip strength and inflammatory biomarker profiles in very old adults2017
Dr Nuno Mendonca
Dr Antoneta Granic
Professor John Mathers
Dr Carmen Martin-Ruiz
Emeritus Professor Chris Seal
et al.
Homocysteine, Tryptophan, and Cognition in the Very Old2017
Dr Nuno Mendonca
Dr Antoneta Granic
Professor John Mathers
Dr Carmen Martin-Ruiz
Emeritus Professor Chris Seal
et al.
One-Carbon Metabolism Biomarkers and Cognitive Decline in the Very Old: The Newcastle 85+ Study2017
Dr Kirsty McAleese
Dr Lauren Walker
Mary Johnson
Dr Daniel Erskine
Dr Sean Colloby
et al.
Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease2017
Professor Daniel Nettle
Dr Clare Andrews
Thomas Bedford
Annie Gott
Dr Craig Parker
et al.
Brood size moderates associations between relative size, telomere length, and immune development in European starling nestlings2016
Dr Nicola Wyatt
Dr Linda Hogarth
Dianne Turner
Dr Miranda Patterson
Dr David Jamieson
et al.
Circulating Biomarkers of Frailty Are Associated with a Poor Prognosis in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)2016
Professor Ioakim Spyridopoulos
Dr Carmen Martin-Ruiz
Professor Catharien Hilkens
Mohammad Yadegarfar
Professor John Isaacs
et al.
CMV-seropositivity and T-cell senescence predict increased cardiovascular mortality in octogenarians - results from the Newcastle 85+ study2016
Dr Nuno Mendonca
Professor John Mathers
Professor Ashley Adamson
Dr Carmen Martin-Ruiz
Emeritus Professor Chris Seal
et al.
Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The Newcastle 85+ Study2016
Dr Carmen Martin-Ruiz
Simon Cox
Professor Thomas von Zglinicki
Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 19212016
Professor Thomas Hill
Dr Antoneta Granic
Dr Karen Davies
Dr Joanna Collerton
Dr Carmen Martin-Ruiz
et al.
Serum 25-hydroxyvitamin D concentration and its determinants in the very old: The Newcastle 85+ study2016
Professor Simon Pearce
Dr Salman Razvi
Mohammad Yadegarfar
Dr Carmen Martin-Ruiz
Dr Andrew Kingston
et al.
Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+Study2016
Dr Antoneta Granic
Dr Terry Aspray
Professor Thomas Hill
Dr Karen Davies
Dr Joanna Collerton
et al.
25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study2015
Dr Joanna Collerton
Dr Carmen Martin-Ruiz
Emerita Professor Carol Jagger
Professor Thomas von Zglinicki
Emeritus Professor Thomas Kirkwood
et al.
Age-related frailty and its association with biological markers of ageing2015
Professor Vijay Kunadian
Dr Murugu Veerasamy
Dr Hannah Sinclair
Dr Jonathan Batty
Meedya Sharifpour
et al.
Association of Telomere Length and Telomerase Activity with Clinical Parameters in Older Patients Undergoing Invasive Management Of non-ST Elevation Acute Coronary Syndrome2015
Dr Carmen Martin-Ruiz
Professor Rachel Cooper
Dr Andrew Kingston
Professor Thomas von Zglinicki
Corrigendum to "Reproducibility of Telomere Length Assessment - An International Collaborative Study" [International Journal of Epidemiology 2014, doi: 10.1093/ije/dyu191]2015
Dr Yasumichi Arai
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians2015
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Is Southern blotting necessary to measure telomere length reproducibly? Authors' Response to: Commentary: The reliability of telomere length measurements2015
Jedrzej Hoffmann
Dr Evgeniya Shmeleva
Dr Stephen Boag
Dr Karel Fiser
Dr Alan Bagnall
et al.
Myocardial Ischemia and Reperfusion Leads to Transient CD8 Immune Deficiency and Accelerated Immunosenescence in CMV-Seropositive Patients2015
Dr Lauren Walker
Dr Kirsty McAleese
Professor Alan Thomas
Mary Johnson
Dr Carmen Martin-Ruiz
et al.
Neuropathologically mixed Alzheimer's and Lewy body disease: burden of pathological protein aggregates differs between clinical phenotypes2015
Dr Carmen Martin-Ruiz
Dr Andrew Kingston
Professor Thomas von Zglinicki
Reproducibility of telomere length assessment: an international collaborative study2015
Dr Carmen Martin-Ruiz
Dr Andrew Kingston
Professor Thomas von Zglinicki
Reproducibility of telomere length assessment: Authors' Response to Damjan Krstajic and Ljubomir Buturovic2015
Dr Amy Anderson
Dr Carmen Martin-Ruiz
Professor Dawn Teare
RIPOSTE: a framework for improving the design and analysis of laboratory-based research2015
Dr Antoneta Granic
Professor Thomas Hill
Emeritus Professor Thomas Kirkwood
Dr Karen Davies
Dr Joanna Collerton
et al.
Serum 25-hydroxyvitamin D and cognitive decline in the very old: The Newcastle 85+ study2015
Dr Joanna Collerton
Hannah Gautrey
Sanne van Otterdijk
Dr Karen Davies
Dr Carmen Martin-Ruiz
et al.
Acquisition of aberrant DNA methylation is associated with frailty in the very old: findings from the Newcastle 85+Study2014
Laura Wiley
Dr Carmen Martin-Ruiz
Emerita Professor Carol Jagger
Mohammad Yadegarfar
Professor Thomas von Zglinicki
et al.
Gender and telomere length: Systematic review and meta-analysis2014
Dr Kristin Ayers
Professor Heather Cordell
Dr Joanna Collerton
Dr Karen Davies
Dr Carmen Martin-Ruiz
et al.
Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age2014
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Professor Avan Sayer
Inflammation, telomere length, and grip strength: a 10-year longitudinal study.2014
Laura Wiley
Deepthi Ashok
Dr Carmen Martin-Ruiz
David Talbot
Dr Joanna Collerton
et al.
Reactive Oxygen Species Production and Mitochondrial Dysfunction in White Blood Cells Are Not Valid Biomarkers of Ageing in the Very Old2014
Dr Joanna Collerton
Dr Andrew Kingston
Dr Fahad Yousaf
Dr Karen Davies
Dr Antoinette Kenny
et al.
Utility of NT-proBNP as a rule-out test for left ventricular dysfunction in very old people with limiting dyspnoea: the Newcastle 85+Study2014
Dr Antoneta Granic
Emeritus Professor Thomas Kirkwood
Dr Karen Davies
Dr Joanna Collerton
Professor Thomas Hill
et al.
25-hydroxyvitamin D and increased risk of all-cause mortality in very old women: The Newcastle 85+ study.2013
Dr Glyn Nelson
James Wordsworth
Dr Diana Jurk
Dr Conor Lawless
Dr Carmen Martin-Ruiz
et al.
A senescent cell bystander effect: senescence-induced senescence2012
Professor Mark Pearce
Dr Kay Mann
Dr Carmen Martin-Ruiz
Professor Louise Parker
Professor Martin White
et al.
Childhood Growth, IQ and Education as Predictors of White Blood Cell Telomere Length at Age 49-51 Years: The Newcastle Thousand Families Study2012
Dr Joanna Collerton
Dr Carmen Martin-Ruiz
karen Davies
Professor Mike Catt
Emerita Professor Carol Jagger
et al.
Frailty and biomarkers of inflammation, immunoscience and cellular ageing in the Newcastle 85+ Study2012
Dr Joanna Collerton
Dr Carmen Martin-Ruiz
karen Davies
Professor Catharien Hilkens
Professor John Isaacs
et al.
Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: Cross-sectional findings from the Newcastle 85+ Study2012
Jedrzej Hoffmann
Dr Karel Fiser
Dr Jolanta Weaver
Ian Dimmick
Monika Loeher
et al.
High-Throughput 13-Parameter Immunophenotyping Identifies Shifts in the Circulating T-Cell Compartment Following Reperfusion in Patients with Acute Myocardial Infarction2012
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Telomere length and aging biomarkers in 70-year-olds: the Lothian Birth Cohort 19362012
Dr Carmen Martin-Ruiz
Emerita Professor Carol Jagger
Dr Andrew Kingston
Dr Joanna Collerton
Professor Mike Catt
et al.
Assessment of a large panel of candidate biomarkers of ageing in the Newcastle 85+ study2011
Emerita Professor Carol Jagger
Dr Joanna Collerton
Dr Karen Davies
Dr Andrew Kingston
Professor Dame Louise Robinson
et al.
Capability and dependency in the Newcastle 85+ cohort study. Projections of future care needs2011
Wendy den Elzen
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Emeritus Professor Thomas Kirkwood
Telomere length and anaemia in old age: results from the Newcastle 85-plus Study* and the Leiden 85-plus Study2011
Emeritus Professor Thomas Kirkwood
Dr Carmen Martin-Ruiz
Emerita Professor Carol Jagger
Dr Joanna Collerton
Dr Andrew Kingston
et al.
Biomarkers of ageing and their relationship to disability and cognition [abstract]2010
Dr Carmen Martin-Ruiz
Dr Aurora Gomez Duran
Professor Thomas von Zglinicki
Association of mitochondrial haplogroup J and mtDNA oxidative damage in two different North Spain elderly populations2009
Chunfang Wang
Dr Diana Jurk
Mandy Maddick
Dr Glyn Nelson
Dr Carmen Martin-Ruiz
et al.
DNA damage response and cellular senescence in tissues of aging mice2009
Dr Joanna Collerton
Dr Karen Davies
Emerita Professor Carol Jagger
Dr Andrew Kingston
Professor John Bond
et al.
Health and disease in 85 year olds: Baseline findings from the Newcastle 85+ cohort study2009
Mandy Maddick
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Sustained replication in endometrium of women with endometriosis occurs without evoking a DNA damage response2009
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Dr Robin Farquharson
Endometrial telomerase shows specific expression patterns in different types of reproductive failure2008
Dr Gabriele Saretzki
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length2008
Professor Mark Pearce
Dr Jean Adams
Dr Carmen Martin-Ruiz
Professor Martin White
Professor Thomas von Zglinicki
et al.
Growth and white blood cell telomere length at age 50: the Newcastle Thousand Families Study2007
Dr Jean Adams
Dr Carmen Martin-Ruiz
Professor Mark Pearce
Professor Martin White
Professor Louise Parker
et al.
No association between socio-economic status and white blood cell telomere length2007
Dr Joao Passos
Dr Sharon Olijslagers
Dr Gabriele Saretzki
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
et al.
Premature senescence of mesothelial cells is associated with non-telomeric DNA damage2007
Dr Joanna Collerton
Dr Carmen Martin-Ruiz
Dr Antoinette Kenny
Dr Karen Davies
Professor Thomas von Zglinicki
et al.
Telomere length is associated with left ventricular function in the oldest old: The Newcastle 85+ study2007
Dr Joanna Collerton
Dr Karen Davies
Professor John Bond
Professor Martin Eccles
Emerita Professor Carol Jagger
et al.
The Newcastle 85+ study: Biological, clinical and psychosocial factors associated with healthy ageing: Study protocol2007
Jill Collerton
Dr Carmen Martin-Ruiz
Dr Karen Davies
Professor Thomas von Zglinicki
Emeritus Professor Thomas Kirkwood
et al.
White blood cell telomere length is associated with left ventricular function in the oldest old: The newcastle 85+study2007
Dr Carmen Martin-Ruiz
Dr Joao Passos
Professor Thomas von Zglinicki
Extended lifespan and long telomeres in rectal fibroblasts from late-onset ulcerative colitis patients2006
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Fat depot-specific characteristics are retained in strains derived from single human preadipocytes2006
Dr Carmen Martin-Ruiz
Dr Heather Dickinson
Barbara Keys
Dr Elise Rowan
Professor Rose Anne Kenny
et al.
Telomere length predicts poststroke mortality, dementia, and cognitive decline2006
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Lymphocyte telomere dynamics and telomerase activity in inflammatory bowel disease: Effect of drugs and smoking2005
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: A population-based study2005
Professor Thomas von Zglinicki
Dr Carmen Martin-Ruiz
Telomeres as biomarkers for ageing and age-related diseases2005
Professor Thomas von Zglinicki
Dr Carmen Martin-Ruiz
Dr Gabriele Saretzki
Telomeres, cell senescence and human ageing2005
Dr Carmen Martin-Ruiz
Emeritus Professor Robert Perry
Dr Jennifer Court
Emeritus Professor Elaine Perry
Molecular analysis of nicotinic receptor expression in autism2004
Dr Jean Adams
Professor Martin White
Professor Mark Pearce
Dr Carmen Martin-Ruiz
Professor Thomas von Zglinicki
et al.
Socio-economic position, health behaviours and telomere length at age 50: a prospective cohort study2004
Dr Carmen Martin-Ruiz
Dr Gabriele Saretzki
Jessie Jeyapalan
Professor Thomas von Zglinicki
Stochastic Variation in Telomere Shortening Rate Causes Heterogeneity of Human Fibroblast Replicative Life Span2004
Dr Carmen Martin-Ruiz
Professor Allan Young
Emeritus Professor Elaine Perry
Dr Jennifer Court
Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia2003
Dr Carmen Martin-Ruiz
Dr Alison Graham
Dr Jennifer Court
Dr Evelyn Jaros
Emeritus Professor Robert Perry
et al.
Nicotinic receptor abnormalities in the cerebellar cortex in autism2002
Dr Carmen Martin-Ruiz
Dr Margaret Piggott
Dr Mark Cookson
Emeritus Professor Robert Perry
Dr Evelyn Jaros
et al.
Nicotinic receptors in the putamen of patients with dementia with Lewy bodies and Parkinson's disease: relation to changes in alpha-synuclein expression2002
Emeritus Professor Elaine Perry
Dr Carmen Martin-Ruiz
Dr Jennifer Court
Emeritus Professor Robert Perry
Cholinergic activity in autism: Abnormalities in the cerebral cortex and basal forebrain2001
Dr Jennifer Court
Dr Carmen Martin-Ruiz
Dr Margaret Piggott
Dr Michael Griffiths
Emeritus Professor Elaine Perry
et al.
Nicotinic receptor abnormalities in Alzheimer's disease2001
Emeritus Professor Elaine Perry
Dr Carmen Martin-Ruiz
Dr Jennifer Court
Nicotinic receptor subtypes in human brain related to aging and dementia2001
Dr Carmen Martin-Ruiz
Dr Margaret Piggott
Emeritus Professor David Mendelow
Dr Shahid Siddique
Emeritus Professor Robert Perry
et al.
Alpha and beta nicotinic acetylcholine receptors subunits and synaptophysin in putamen from Parkinson's disease2000
Emeritus Professor Elaine Perry
Dr Carmen Martin-Ruiz
Dr Margaret Piggott
Dr Evelyn Jaros
Emeritus Professor Robert Perry
et al.
Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases2000
Dr Carmen Martin-Ruiz
Dr Jennifer Court
Dr Margaret Piggott
Dr Clive Ballard
Professor Raj Kalaria
et al.
Nicotinic receptors in dementia of Alzheimer, lewy body and vascular types2000
Dr Carmen Martin-Ruiz
Dr Jennifer Court
Dr Elek Molnar
Emeritus Professor Elaine Perry
Alpha4 but not alpha3 nicotinic acetylcholine receptor subunits are lost from the temporal cortex in Alzheimer's disease1999
Emeritus Professor Elaine Perry
Dr Carmen Martin-Ruiz
Cholinergic component of vascular dementia1999
Dr Carmen Martin-Ruiz
Stimulation of tyrosine phosphorylation by progesterone and its 11-OH derivatives: dissection of a Ca(2+)-dependent and a Ca(2+)-independent mechanism1999