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1.
New Phytol ; 238(2): 598-611, 2023 04.
Article in English | MEDLINE | ID: mdl-36651117

ABSTRACT

Decomposition and fire are major carbon pathways in many ecosystems, yet potential linkages between these processes are poorly understood. We test whether variability in decomposability and flammability across species are related to each other and to key plant functional traits in tropical swamp forests, where habitat degradation is elevating decomposition and fire regimes. Using senesced and fresh leaves of 22 swamp tree species in Singapore, we conducted an in situ decomposition experiment and a laboratory flammability experiment. We analysed 16 leaf physical and biochemical traits as predictors of decomposability and components of flammability: combustibility, ignitability and sustainability. Decomposability and flammability were largely decoupled across species, despite some shared predictive traits such as specific leaf area (SLA). Physical traits predicted that thicker leaves with a smaller SLA and volume decomposed faster, while various cation concentrations predicted flammability components, particularly ignitability. We show that flammability and decomposability of swamp forest leaves are decoupled because flammability is mostly driven by biochemical traits, while decomposition is driven by physical traits. Our approach identifies species that are slow to decompose and burn (e.g. Calophyllum tetrapterum and Xanthophyllum flavescens), which could be planted to mitigate carbon losses in tropical swamp reforestation.


Subject(s)
Ecosystem , Wetlands , Forests , Trees/metabolism , Plants , Plant Leaves/metabolism , Carbon/metabolism
2.
Philos Trans R Soc Lond B Biol Sci ; 378(1867): 20210090, 2023 01 02.
Article in English | MEDLINE | ID: mdl-36373930

ABSTRACT

Current policy is driving renewed impetus to restore forests to return ecological function, protect species, sequester carbon and secure livelihoods. Here we assess the contribution of tree planting to ecosystem restoration in tropical and sub-tropical Asia; we synthesize evidence on mortality and growth of planted trees at 176 sites and assess structural and biodiversity recovery of co-located actively restored and naturally regenerating forest plots. Mean mortality of planted trees was 18% 1 year after planting, increasing to 44% after 5 years. Mortality varied strongly by site and was typically ca 20% higher in open areas than degraded forest, with height at planting positively affecting survival. Size-standardized growth rates were negatively related to species-level wood density in degraded forest and plantations enrichment settings. Based on community-level data from 11 landscapes, active restoration resulted in faster accumulation of tree basal area and structural properties were closer to old-growth reference sites, relative to natural regeneration, but tree species richness did not differ. High variability in outcomes across sites indicates that planting for restoration is potentially rewarding but risky and context-dependent. Restoration projects must prepare for and manage commonly occurring challenges and align with efforts to protect and reconnect remaining forest areas. The abstract of this article is available in Bahasa Indonesia in the electronic supplementary material. This article is part of the theme issue 'Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration'.


Subject(s)
Ecosystem , Tropical Climate , Biodiversity , Plants , Asia
3.
Glob Chang Biol ; 26(11): 6616-6629, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32311220

ABSTRACT

Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.


Subject(s)
Ecosystem , Microclimate , Climate Change , Snow , Temperature
4.
BMC Nephrol ; 19(1): 207, 2018 08 16.
Article in English | MEDLINE | ID: mdl-30115013

ABSTRACT

BACKGROUND: Minimal change disease (MCD) is a common cause of the nephrotic syndrome in adults with limited evidence on its treatment and prognosis. We examined the presenting characteristics, treatments, and outcomes of adult patients with MCD in our centre. METHODS: This was an observational cohort study using retrospectively-collected data. All patients who had a renal biopsy reported as MCD between 1996 and 2012 were included, and data were collected at baseline and during follow-up. Statistical analysis included Cox-regression analysis to examine which factors were associated with risk of relapse. RESULTS: Seventy-eight patients were included, and had a median age of 36 years, and were 60% male and 73% white. Median follow-up time was 72 months. 37% were in AKI at presentation, which was significantly associated with a lower serum albumin and older age. Although 10% were steroid-resistant, 98% achieved remission at a median time of 5 weeks. 61% relapsed, at a median time of 11 months, and patients had a median number of 2 relapses during follow-up. A higher eGFR was associated with an increased risk of relapse (hazard ratio 1.18 [1.03-1.36] per 10 mL/min increase in eGFR), and females were significantly more likely than males to have an early relapse. Nearly half of the cohort required an additional immunosuppressive agent on top of glucocorticoids, the most commonly used being calcineurin inhibitors. Five patients subsequently developed FSGS: these patients had a lower baseline creatinine, a higher serum albumin, a longer time to remission, and were more likely to be steroid-resistant. Follow-up renal function was generally preserved, but follow-up creatinine was higher in those who had presented with AKI, and in those who had been commenced on a RAS inhibitor after biopsy. Infection requiring admission, diabetes mellitus and venous thromboembolism developed in 14%, 12%, and 12% of patients respectively. CONCLUSIONS: Nearly all adults with MCD achieve remission, but relapses and disease- and therapy-related complications are common. In our cohort, eGFR and gender were associated with risk of relapse, and these previously undescribed associations could be explored further in future work.


Subject(s)
Data Analysis , Immunosuppressive Agents/therapeutic use , Nephrosis, Lipoid/diagnosis , Nephrosis, Lipoid/epidemiology , Adult , Cohort Studies , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Glomerular Filtration Rate/physiology , Humans , Immunosuppressive Agents/pharmacology , Male , Middle Aged , Nephrosis, Lipoid/therapy , Retrospective Studies , Sex Factors , Treatment Outcome , United Kingdom/epidemiology
5.
Nat Commun ; 8(1): 2239, 2017 12 21.
Article in English | MEDLINE | ID: mdl-29269852

ABSTRACT

Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture. CLEC-2 deficiency is associated with reduced numbers of podoplanin-expressing macrophages despite increased cytokine and chemokine levels in the infected peritoneum. Pharmacological inhibition of the interaction between CLEC-2 and podoplanin regulates immune cell infiltration and the inflammatory reaction during sepsis, suggesting that activation of podoplanin underlies the anti-inflammatory action of platelet CLEC-2. We suggest podoplanin-CLEC-2 as a novel anti-inflammatory axis regulating immune cell recruitment and activation in sepsis.


Subject(s)
Blood Platelets/immunology , Inflammation/immunology , Lectins, C-Type/immunology , Macrophages/immunology , Membrane Glycoproteins/immunology , Multiple Organ Failure/immunology , Sepsis/immunology , Animals , Cecum/surgery , Chemokines/immunology , Cytokines/immunology , Injections, Intraperitoneal , Kidney/immunology , Kidney/pathology , Lectins, C-Type/genetics , Ligation , Lipopolysaccharides/toxicity , Membrane Glycoproteins/genetics , Mice , Phagocytosis/immunology , Platelet Membrane Glycoproteins/genetics , Platelet Membrane Glycoproteins/immunology , Punctures , Sepsis/chemically induced
6.
Clin Kidney J ; 10(1): 16-19, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28638601

ABSTRACT

BACKGROUND: Corticosteroids are the basis of treatment for nephrotic syndrome due to minimal change disease (MCD), but 25% of patients have frequently relapsing nephrotic syndrome (FRNS) and 30% become steroid dependent. Prolonged use of conventional immunosuppressants causes significant toxicity. Rituximab (RTX) is now included in guidelines for childhood MCD. Evidence for use in adult MCD is limited. We describe a single-centre experience of RTX use in adult MCD. METHODS: Outcomes of all adult MCD patients treated with RTX for FRNS between 2008 and 2015 were retrospectively analysed. RESULTS: Thirteen patients received RTX; 11/13 had childhood-onset MCD. All had FRNS and 10 were steroid dependent. Eleven patients experienced one or more major treatment side effect from conventional therapy. At the time of RTX treatment, six patients were relapsing. All entered remission after RTX. The median length of follow-up after the first RTX treatment was 20 months (range 6-85). After RTX, the rate of relapse was reduced from 4 to 0.4/year (Wilcoxon signed rank P ≤ 0.05). Seven patients relapsed after RTX after a median of 10 months (range 1-11). All seven relapsing patients were successfully re-treated with RTX and none developed RTX-resistant nephrosis. The median number of courses of RTX per patient was 1 (range 1-5). The number of additional immunosuppressants, steroid dependency and antihypertensive agents were also reduced. At the last follow-up, two patients remained on low-dose steroids. No RTX-related adverse events were observed. CONCLUSION: RTX is safe and effective in adults with FRNS due to MCD. The median rate of relapse is significantly reduced following RTX treatment and additional immunosuppressant exposure is minimized.

7.
Glob Chang Biol ; 21(8): 3036-48, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25930662

ABSTRACT

Ecosystem carbon (C) accrual and storage can be enhanced by removing large herbivores as well as by the fertilizing effect of atmospheric nitrogen (N) deposition. These drivers are unlikely to operate independently, yet their combined effect on aboveground and belowground C storage remains largely unexplored. We sampled inside and outside 19 upland grazing exclosures, established for up to 80 years, across an N deposition gradient (5-24 kg N ha(-1) yr(-1) ) and found that herbivore removal increased aboveground plant C stocks, particularly in moss, shrubs and litter. Soil C storage increased with atmospheric N deposition, and this was moderated by the presence or absence of herbivores. In exclosures receiving above 11 kg N ha(-1) year(-1) , herbivore removal resulted in increased soil C stocks. This effect was typically greater for exclosures dominated by dwarf shrubs (Calluna vulgaris) than by grasses (Molinia caerulea). The same pattern was observed for ecosystem C storage. We used our data to predict C storage for a scenario of removing all large herbivores from UK heathlands. Predictions were made considering herbivore removal only (ignoring N deposition) and the combined effects of herbivore removal and current N deposition rates. Predictions including N deposition resulted in a smaller increase in UK heathland C storage than predictions using herbivore removal only. This finding was driven by the fact that the majority of UK heathlands receive low N deposition rates at which herbivore removal has little effect on C storage. Our findings demonstrate the crucial link between herbivory by large mammals and atmospheric N deposition, and this interaction needs to be considered in models of biogeochemical cycling.


Subject(s)
Agriculture , Carbon/analysis , Herbivory , Nitrogen/analysis , Agriculture/methods , Animals , Calluna/chemistry , Poaceae/chemistry , Soil/chemistry , United Kingdom
8.
Kidney Int ; 87(4): 807-11, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25272233

ABSTRACT

Pregnancy in patients with anti-neutrophil cytoplasm antibody-associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case review of all women who became pregnant following diagnosis. We report 15 pregnancies in 13 women resulting in 15 live births including one twin pregnancy and 13 singleton pregnancies. One patient had an unplanned pregnancy and a first trimester miscarriage while taking methotrexate. All other pregnancies were planned following a minimum of 6 months clinical remission. Eleven successful pregnancies were delivered vaginally at full term, whereas three were delivered by cesarean section. All infants were healthy with no neonatal complications on their initial health check within the first 24 h of delivery and no evidence of neonatal vasculitis. One relapse occurred during pregnancy and was successfully treated with an increased dose of azathioprine and corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. One patient developed tracheal crusting and subglottic stenosis of infective etiology in the third trimester requiring tracheal debridement post delivery. No patient had a relapse in the first 12 months postpartum. Thus, successful pregnancy outcomes can occur following planned pregnancy in women in sustained remission on non-teratogenic therapies.


Subject(s)
Granulomatosis with Polyangiitis/drug therapy , Microscopic Polyangiitis/drug therapy , Pregnancy Complications/drug therapy , Abortion, Spontaneous/chemically induced , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Inflammatory Agents/therapeutic use , Azathioprine/therapeutic use , Cesarean Section , Cyclophosphamide/therapeutic use , Female , Granulomatosis with Polyangiitis/therapy , Humans , Immunosuppressive Agents/therapeutic use , Live Birth , Methotrexate/adverse effects , Microscopic Polyangiitis/therapy , Plasma Exchange , Preconception Care , Pregnancy , Pregnancy Complications/therapy , Pregnancy, High-Risk , Pregnancy, Unplanned , Recurrence , Retrospective Studies , Term Birth , United Kingdom , Young Adult
9.
New Phytol ; 203(3): 851-62, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24841886

ABSTRACT

Root litter is the dominant soil carbon and nutrient input in many ecosystems, yet few studies have considered how root decomposition is regulated at the landscape scale and how this is mediated by land-use management practices. Large herbivores can potentially influence below-ground decomposition through changes in soil microclimate (temperature and moisture) and changes in plant species composition (root traits). To investigate such herbivore-induced changes, we quantified annual root decomposition of upland grassland species in situ across a landscape-scale livestock grazing experiment, in a common-garden experiment and in laboratory microcosms evaluating the influence of key root traits on decomposition. Livestock grazing increased soil temperatures, but this did not affect root decomposition. Grazing had no effect on soil moisture, but wetter soils retarded root decomposition. Species-specific decomposition rates were similar across all grazing treatments, and species differences were maintained in the common-garden experiment, suggesting an overriding importance of litter type. Supporting this, in microcosms, roots with lower specific root area (m(2) g(-1)) or those with higher phosphorus concentrations decomposed faster. Our results suggest that large herbivores alter below-ground carbon and nitrogen dynamics more through their effects on plant species composition and associated root traits than through effects on the soil microclimate.


Subject(s)
Herbivory/physiology , Plant Roots/physiology , Poaceae/physiology , Quantitative Trait, Heritable , Animals , Carbon/analysis , Humidity , Livestock , Microclimate , Nitrogen/analysis , Plant Roots/anatomy & histology , Scotland , Soil/chemistry , Species Specificity , Temperature
10.
New Phytol ; 198(1): 222-231, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23356534

ABSTRACT

Parasitic plants have major impacts on plant community structure through their direct negative influence on host productivity and competitive ability. However, the possibility that these parasites may also have indirect impacts on community structure (via the mechanism of nutrient-rich litter input) while long hypothesized, has remained unsupported until now. Using the hemiparasite Rhinanthus minor, we established experimental grassland mesocosms to quantify the impacts of Rhinanthus litter and parasitism across two soil fertility levels. We measured the biomass and tissue nutrient concentration of three functional groups within these communities to determine their physiological response to resource abstraction and litter input by the parasite. We show that Rhinanthus alters the biomass and nutrient status of co-occurring plants with contrasting effects on different functional groups via the mechanism of nutrient-rich litter input. Critically, in the case of grass and total community biomass, this partially negates biomass reductions caused directly by parasitism. This demonstrates that the influence of parasitic plant litter on plant community structure can be of equal importance to the much-reported direct impacts of parasitism. We must consider both positive indirect (litter) and negative direct (parasitism) impacts of parasitic plants to understand their role in structuring plant communities.


Subject(s)
Biomass , Ecosystem , Orobanchaceae/physiology , Analysis of Variance , Nitrogen/metabolism , Orobanchaceae/metabolism , Phosphorus/metabolism , Soil , United Kingdom
11.
Nephrol Dial Transplant ; 27(6): 2149-55, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22555252

ABSTRACT

Pericytes are cells of mesenchymal origin that are intimately involved in the development and stabilization of vascular networks. Novel studies of their role in inflammation have identified that pericytes are not only major contributors to the activated matrix depositing myofibroblast populations seen in progressive renal fibrosis but perhaps even more importantly, the detachment of renal pericytes from the vasculature contributes to the microvasculature rarefaction and subsequent hypoxia associated with chronic kidney disease. In this review, our current understanding of the functioning of renal pericytes will be considered and set in the context of the wider literature that is currently available on this neglected population of cells.


Subject(s)
Kidney Diseases/pathology , Kidney/pathology , Pericytes/pathology , Animals , Humans , Microvessels
12.
Pediatr Rheumatol Online J ; 9: 12, 2011 Jun 19.
Article in English | MEDLINE | ID: mdl-21682926

ABSTRACT

BACKGROUND: Primary systemic vasculitis presenting in childhood is an uncommon but serious condition. As these patients transfer to adult clinics for continuing care, defining long term outcomes with emphasis on disease and treatment- related morbidity and mortality is important. The aim of this study is to describe the long- term clinical course of paediatric patients with ANCA vasculitis. METHODS: The adult patients in our vasculitis clinics who had presented in childhood, with a follow up time of greater than 10 years were included. We also reviewed the literature for articles describing the clinical outcome of paediatric patients with ANCA vasculitis. RESULTS: We describe the clinical course of 8 adults who presented in childhood with ANCA vasculitis. 7 patients had Wegener's granulomatosis and 1 had microscopic polyangiitis. The median age at presentation was 11.5 years, and follow up time ranged form 11 to 30 years. Induction therapy for all patients was steroids and/or cyclophosphamide. Maintenance therapy was with azathioprine or mycophenolate mofetil. Biological agents were used in 3 patients for relapsed disease in adulthood only.Seven patients achieved complete remission. All patients experienced disease relapse, with a median of 4 episodes. Kidney function was generally well preserved, with median eGFR 76 ml/min. Only one patient developed end-stage renal failure and one patient died after 25 years of disease. Treatment-related morbidity rates were high; 7 suffered from infections, 4 were infertile, 2 had skeletal complications, and 1 developed malignancy. CONCLUSION: Close long- term follow up of paediatric patients with ANCA vasculitis is imperative, as this patient cohort is likely to live long enough to develop significant treatment and disease- related morbidities. Prospective cohort studies with novel therapies including paediatric patients are crucial to help us determine the best approach to managing this complex group of patients. In addition, although not yet observed in our series, late cardiovascular morbidity remains a major longer-term potential concern for adult survivors of paediatric vasculitis.

13.
Kidney Int ; 80(2): 199-207, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21490589

ABSTRACT

Stromal fibroblasts are the primary cells of the kidney that produce fibrotic matrix. CD248 is a stromal marker expressed on fibroblasts and pericytes within the human kidney. Here, we tested whether CD248 expression in the kidney colocalizes with fibrosis and if it is associated with known determinants of chronic kidney disease (CKD). CD248 expression was located and quantified in situ by immunohistochemistry in kidney biopsies from 93 patients with IgA nephropathy and compared with 22 archived biopsies encompassing normal kidney tissue as control. In normal kidney tissue, CD248 was expressed by resident pericytes, stromal fibroblasts, and was upregulated in human CKD. The expression was linked to known determinants of renal progression. This relationship was maintained in a multivariate analysis with CD248 expression linked to renal survival. CD248 was expressed by a population of α-smooth muscle actin (SMA)(+) myofibroblasts and α-SMA(-) stromal cells but not expressed on CD45(+) leukocytes. Thus, CD248 defines a subset of stromal cells, including but not limited to some myofibroblasts, linked to albuminuria and tubulointerstitial damage during tissue remodeling in CKD.


Subject(s)
Antigens, CD/analysis , Antigens, Neoplasm/analysis , Renal Insufficiency, Chronic/pathology , Stromal Cells/chemistry , Stromal Cells/pathology , Animals , Biomarkers , Case-Control Studies , Disease Progression , Gene Expression , Humans , Mice , Myofibroblasts/metabolism , Renal Insufficiency, Chronic/genetics , Tissue Distribution
14.
Nephrol Dial Transplant ; 23(9): 3030-2, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18586761

ABSTRACT

Wegener's granulomatosis (WG) is a chronic, relapsing, systemic autoimmune disease. Rituximab, a monoclonal antibody against human CD20, has shown promise as a novel treatment for WG. The monitoring of therapeutic B-cell 'depletion' by peripheral blood flow cytometry has been proposed to help monitor rituximab therapy. We report the case of a patient with known WG and granulomatous disease, successfully treated with rituximab, who relapsed whilst peripheral blood monitoring apparently indicated persistent B-cell depletion. Further investigations demonstrated CD20(+) B cells in tissue at sites of active disease. The implications for disease pathogenesis and clinical monitoring of disease are discussed.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/pathology , Immunologic Factors/therapeutic use , Aged , Antibodies, Monoclonal, Murine-Derived , Antigens, CD20/metabolism , B-Lymphocytes/metabolism , Granulomatosis with Polyangiitis/diagnostic imaging , Granulomatosis with Polyangiitis/immunology , Granulomatosis with Polyangiitis/metabolism , Humans , Immunohistochemistry , Lung/diagnostic imaging , Lung/metabolism , Lymphocyte Depletion , Male , Recurrence , Rituximab , Tomography, X-Ray Computed
15.
Can J Ophthalmol ; 42(5): 689-94, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17891197

ABSTRACT

BACKGROUND: We studied whether a new model of nurse-provision of conscious sedation for cataract surgery maintained patient satisfaction and safety. METHODS: We prospectively and non-randomly studied 106 patients who had outpatient cataract surgery on a day when an anaesthetist was present at the UBC, Vancouver Hospital Eye Care Centre, and 105 patients with no anaesthetist, but instead a surgical suite nurse trained to give conscious sedation was present. Questionnaires determined patient perception of well-being, pain, and anxiety before surgery, before discharge, at 48 hours and at 6 weeks postoperative. Hospital records and a surgeon questionnaire were used to determine complications. Ophthalmology records were used to determine visual acuity (preoperative and at 6 weeks). RESULTS: No anaesthetic complications were reported in either group and there were no significant differences in surgical complications. Patient responses to assessments of discomfort, well-being, and anxiety, preoperatively and postoperatively, were very similar on the nurse days and anaesthetist days. INTERPRETATION: Conscious sedation of cataract surgery patients can be safely and effectively provided by a trained nurse for selected patients. This nursing role is likely replicable in similar operating room settings.


Subject(s)
Cataract Extraction , Conscious Sedation/nursing , Intraoperative Care/standards , Nurse Anesthetists/standards , Professional Competence/standards , Quality Assurance, Health Care/methods , Adult , Aged , Aged, 80 and over , Conscious Sedation/standards , Female , Humans , Intraoperative Care/nursing , Male , Middle Aged , Outpatients , Patient Satisfaction , Prospective Studies , Surveys and Questionnaires
16.
Neurosci Lett ; 342(1-2): 13-6, 2003 May 15.
Article in English | MEDLINE | ID: mdl-12727306

ABSTRACT

We have previously speculated that elevated levels of nicotinamide N-methyltransferase (NNMT), the primary catabolic enzyme of nicotinamide, may result in reduced Complex I activity in idiopathic Parkinson's disease (IPD) in two ways: (1) reduction in the levels of nicotinamide available for nicotinamide adenine dinucleotide synthesis; and (2) increased methylation of compounds such as tetrahydroisoquinolines and beta-carbolines, which are potent Complex I inhibitors. Expression of NNMT was assessed in 91 cerebella (53 IPD, 38 control) using immunohistochemistry coupled with quantitative digital image analysis. Control cerebella showed a distribution of expression ascribed to low, intermediate and high expressors with ratios of 1:2:1 categories. Expression in the parkinsonian cerebella was significantly higher than in the control group (control group median expression 17%, mean expression 16.6%, range 0-51%, standard deviation 11.4%, standard error 1.9%; IPD group median expression 46%, mean expression 53.7%, range 21-100%, standard deviation 23.4%, standard error 3.2%; P<0.0001; unpaired t-test with Welch correction (parametric) and Mann-Whitney U-test (non-parametric)). These results confirm that NNMT expression is elevated in IPD, which may ultimately lead to neurodegeneration via a reduction in Complex I activity.


Subject(s)
Cerebellum/enzymology , Methyltransferases/metabolism , Parkinson Disease/enzymology , Case-Control Studies , Cerebellum/pathology , Gene Expression Regulation, Enzymologic , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Nicotinamide N-Methyltransferase , Parkinson Disease/pathology
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