The average residual tumor area after FGS (n = 16) was significan

The average residual tumor area after FGS (n = 16) was significantly smaller

than after BLS only (n = 24) (0.135 +/- 0.137 mm(2) and 3.338 +/- 2.929 mm(2), respectively; p = 0.007). The BLS treated mice had significantly reduced survival compared to FGS-and FGS-UVC-treated mice for both relapse-free survival (RFS) (p smaller than 0.001 and p smaller than 0.001, respectively) and overall survival (OS) (p smaller than 0.001 and p smaller than 0.001, respectively). FGS-UVC-treated mice had increased RFS and OS compared to FGS-only treated mice (p = 0.008 and p = 0.025, respectively); find more with RFS lasting at least 150 days indicating the animals were cured. The results of the present study suggest that UVC irradiation in combination with FGS has clinical potential to increase Selleckchem BMS-754807 survival.”
“Objectives To investigate the relationships between single-nucleotide polymorphisms (SNPs) in NOTCH4 and brain-derived neurotrophic factor (BDNF) with schizophrenia among Han Chinese in Southern China. Methods Two NOTCH4 SNPs (rs520688 and rs415929) and two BDNF SNPs (rs2030324 and rs12273539) were examined in 464 schizophrenics and 464 healthy controls

from Hunan province in South China, using the Sequenom MassARRAY((R)) iPLEX System. Results In the study population, rs520688 and rs2030324 were significantly associated with schizophrenia. A decreased risk of schizophrenia was associated with the rs520688 GA genotype (p = 0.035), whereas an increased risk of schizophrenia was associated with the rs2030324 CC/CT genotype (p = 0.044).

The genotype distributions of rs415929 in NOTCH4 and rs12273539 in BDNF did not differ significantly between the case and control groups. Although no allele-allele interactions were detected between rs520688 and rs2030324, recombination analysis revealed a combined effect of the two on the susceptibility to schizophrenia, with GA-TT decreasing and CT/CC-GG/GA increasing the risk of schizophrenia. Conclusion In conclusion, rs520688 in NOTCH4 and rs2030324 in BDNF are significantly associated with schizophrenia among Han Chinese in Southern China. The two had a combined effect on the susceptibility to schizophrenia among Han Chinese in Southern China, but this may not be caused by SIS3 mouse an allele-allele interaction.”
“Transplant recipients receive immunosuppressive drugs to prevent graft rejection and graft loss. Immunosuppressive drugs are dosed according to empiric treatment protocols, which consider the risk of under-or oversuppression, rejection, infection, cancer, and drug side effects. An individualized immunosuppressive protocol based on immune monitoring would be useful for avoiding undesired effects. In retrospective studies, numerous immune parameters were shown to be associated with clinical events. Their suitability for clinical application has to be proven in prospective studies.

This cross-sectional study investigated the prevalence and clinic

This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type 2 diabetic mellitus treated at hospitals in Korea. Methods Questionnaires and medical records were used to collect data on 4000 patients with Type 2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. Selleck PFTα Results The prevalence of neuropathy was 33.5% (n = 1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower

glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. Conclusion There was a high prevalence of peripheral neuropathy in patients with Type 2 diabetes in Korea and those patients were

far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention LY3023414 ic50 from clinicians to ensure better management of diabetes in Korea.”
“Improved fuel consumption and lower emissions are two of the key objectives for future transportation. Hybrid electric vehicles (HEVs), in which two IAP inhibitor or more power systems are combined, can meet these objectives through the capture and reuse of regenerated braking energy and through optimized use of the prime mover. However, more complicated power-management strategies are required for such vehicles. This paper explores the potential of applying to advanced power-management strategies for a diesel multiple-unit (DMU) train. These types

of vehicles have multiple diesel engines that are commonly operated in a homogenous manner. This paper analyzes the potential energy savings that may be obtained through the independent operation of the engines. Two widely investigated power-management strategies that have been developed for HEVs have been applied to a typical DMU railroad vehicle. Dynamic programming (DP) strategies have been applied to the results produced by a single-train motion simulator to identify the optimal instant power distribution between the engines. An adaptive rule-based online strategy based on the optimization results from the DP solution is then proposed and realized using a nonlinear programming optimization algorithm. Both strategies indicate acceptable agreement and show a fuel cost reduction of around 7%, in comparison with the evenly split engine operation.”
“Bronchopulmonary dysplasia (BPD) is a complex disorder secondary to gene-environment interactions, and is the commonest chronic lung disease in infancy.

In the longer term, basic research is necessary to identify highl

In the longer term, basic research is necessary to identify highly predictive biomarkers.”
“Blackberry yellow vein disease is the most important viral check details disease of blackberry in the United States. Experiments were conducted to

characterize a new virus identified in symptomatic plants. Molecular analysis revealed a genome organization resembling Grapevine leafroll-associated virus 3, the type species of the genus Ampelovirus in the family Closteroviridae. The genome of the virus, provisionally named blackberry vein banding associated virus (BVBaV), consists of 18,643 nucleotides and contains 10 open reading frames (ORFs). These ORFs encode closterovirid signature replication-associated and quintuple

gene block proteins, as well as four additional proteins of unknown S63845 solubility dmso function. Phylogenetic analyses of taxonomically relevant products consistently placed BVBaV in the same cluster with GLRaV-3 and other members of the subgroup I of the genus Ampelovirus. The virus population structure in the U.S. was studied using the replication associated polyprotein 1a, heat shock 70 homolog and minor coat proteins of 25 isolates. This study revealed significant intra-species variation without any clustering among isolates based on their geographic origin. Further analyses indicated that these proteins are under stringent purifying selections. High genetic variability and incongruent clustering of isolates suggested the possible involvement of recombination in the evolution of BVBaV. (C) 2013 Elsevier B.V. All rights reserved.”
“Previous

attempts at identifying an alternatively spliced dopamine (DA) D2 receptor in teleosts have proven unsuccessful. We provide evidence of a splicing event of a goldfish this website D2 (gfD2b1) receptor in the neuroendocrine brain of adult goldfish that produces a spliced short isoform (gfD2b1S). We also identify an additional novel D2b paralog (gfD2b2) that does not appear to be alternatively spliced in adult fish during the reproductive cycle. Relatively high mRNA levels of gfD2b1S were observed in the neuroendocrine brain and pituitary of sexually immature fish compared with sexually regressing fish. Real-time RT-PCR revealed that intraperitoneal injection of either SCH 23390 or sulpiride-D1- or D2-specific antagonists, respectively-decreased mRNA levels of gfD2b1S by 3.9-fold without affecting the unspliced isoforms. We suggest that the expression of the spliced D2 receptor modulates the inhibitory tone of DA throughout the reproductive cycle. The deduced amino acid sequence of gfD2b1S lacks 29 amino acids in the same region as the short isoform of mammalian D2. We propose that the gfD2b1S splice variant is the teleost ortholog of mammalian D2S. The hypothesis that D2 receptor splicing is a relatively recent innovation in higher tetrapods is not supported by our results.


“Recent developments have used light-activated channels or


“Recent developments have used light-activated channels or transporters to modulate neuronal activity. One such genetically-encoded modulator of activity, channelrhodopsin-2 (ChR2), depolarizes neurons in response to blue light. In this work, we first conducted electrophysiological studies of the photokinetics of hippocampal cells expressing ChR2, for various light stimulations. These and other experimental results were then NU7441 ic50 used

for systematic investigation of the previously proposed three-state and four-state models of the ChR2 photocycle. We show the limitations of the previously suggested three-state models and identify a four-state model that accurately follows the ChR2 photocurrents. We find that ChR2 currents decay biexponentially, a fact

Salubrinal chemical structure that can be explained by the four-state model. The model is composed of two closed (C1 and C2) and two open (O1 and O2) states, and our simulation results suggest that they might represent the dark-adapted (C1-O1) and light-adapted (C2-O2) branches. The crucial insight provided by the analysis of the new model is that it reveals an adaptation mechanism of the ChR2 molecule. Hence very simple organisms expressing ChR2 can use this form of light adaptation.”
“By employing a self-consistent approach, we reveal a number of unique properties of zigzag graphene nanoribbons under crossed electric and magnetic fields: (1) a very strong electrical polarization along the transverse direction of the ribbon, and (2) a strong nonlinear Hall current under a rather moderate electrical field. At the field strength of 5000 V/cm, the ratio of the nonlinear current to the linear current is around 1 under an applied magnetic field of 7.9 T. Our results suggest that graphene nanoribbons are an ideal system to achieve a large electrical polarizability. Our results also suggest that the nonlinear effect in graphene nanoribbons has been grossly underestimated without the self-consistent scheme proposed here. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3647783]“
“The study aimed at estimating the association between somatic GSK2879552 datasheet cell score (SCS) and two fertility traits:

non-returns to oestrus by 56 days (NR56), and number of days from calving to first insemination (CFI). The data were records of 298,016 test-day observations from 190,279 first and second lactation of Polish Holstein-Friesian (PHF) cows. The model used to evaluate the effect of preceding test-day SCS on NR56 included random herd effect and fixed effects of parity, year of calving, lactation stage at first insemination, month of first insemination, interval between preceding test-day and day of first insemination, and linear regression of NR56 on SCS. A similar model including fixed effects of parity, year of calving, month of first insemination, linear and quadratic regressions of CFI on SCS, and random herd effect was applied to analyse the relation between test-day SCS and CFI.

(C) 2012 Elsevier Inc All rights reserved “
“Background: Hy

(C) 2012 Elsevier Inc. All rights reserved.”
“Background: Hyperbranched polymers represent a new class of drug-delivery vehicle that can be used to prepare nanoparticles with uniform size distribution.\n\nMethods: BAY 73-4506 clinical trial In this study we prepared covalent conjugates between the photosensitizer chlorin(e6) and hyperbranched poly(ether-ester), HPEE. HPEE-ce6 nanoparticles were synthesized by carbodiimide-mediated reaction between HPEE and ce6, and characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), and transmission electron microscopy (TEM). The uptake and phototoxicity of HPEE-ce6 nanoparticles

towards human oral tongue cancer CAL-27 cells was detected by confocal laser scanning microscopy (CLSM) and MTT assay, respectively.\n\nResults: The absorption peak of HPEE-ce6 nanoparticles was red-shifted 12-nm compared with ce6, and TEM showed uniform nanoparticles with a diameter of 50-nm. HPEE-ce6 nanoparticles were taken up by CAL-27 cells

after 4 h incubation and localized in the cytoplasm. The MTT assay showed a significantly (P < 0.05) higher phototoxicity compared to free ce6 after 12 J/cm(2) of 660-nm laser illumination.\n\nConclusions: This is the first time to our knowledge that hyperbranched polymers have been used in PDT drug delivery. (c) 2011 Elsevier B.V. All rights reserved.”
“Background: buy Vorinostat Zonulin is a newly discovered protein that has an important role in the regulation of intestinal permeability. Our previous study showed that probiotics can decrease the rate of infectious complications in patients undergoing colectomy for colorectal cancer.\n\nObjective: The objective

was to determine the effects of the perioperative administration of probiotics on serum zonulin concentrations and the subsequent effect on postoperative infectious complications in patients undergoing colorectal surgery.\n\nDesign: A total of 150 patients with colorectal carcinoma were randomly assigned to the control group (n = 75), which received placebo, or the probiotics group (n = 75). Both the probiotics and placebo were given orally for 6 d preoperatively and 10 d postoperatively. Outcomes were measured by assessing bacterial translocation, postoperative intestinal https://www.selleckchem.com/HIF.html permeability, serum zonulin concentrations, duration of postoperative pyrexia, and cumulative duration of antibiotic therapy. The postoperative infection rate, the positive rate of blood microbial DNA, and the incidence of postoperative infectious complications-including septicemia, central line infection, pneumonia, urinary tract infection, and diarrhea-were also assessed.\n\nResults: The infection rate was lower in the probiotics group than in the control group (P < 0.05). Probiotics decreased the serum zonulin concentration (P < 0.001), duration of postoperative pyrexia, duration of antibiotic therapy, and rate of postoperative infectious complications (all P < 0.05).

Specifically, we demonstrate the biological counteraction of Lfci

Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term HIF inhibitor (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and

pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative

and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability click here of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. J. Cell. Physiol. 228: 18841896, 2013. (c) 2013 Wiley Periodicals, Inc.”
“Cotinine is the most common biomarker used to assess nicotine exposure and abstinence. It can be measured in various matrices including saliva, plasma, and urine. Previous research with adults has shown high correlations between saliva and plasma cotinine concentrations. However, the research has not examined this relationship

in adolescents. Additionally, variability in saliva flow and metabolism across gender, ethnicity, and age may impact the relationship between saliva and plasma cotinine concentration. Our aim was to examine the relationship between saliva and plasma cotinine concentration in a group of nicotine-dependent adolescent smokers. Additionally, we examined these correlations RepSox cell line across gender, ethnicity and age. The sample consisted of 66 adolescent smokers (age 15.1 +/- 1.3, 63.6% girls, 66.7% European American, CPD 18.3 +/- 8.5, FTND 7.1 +/- 13). Saliva and plasma specimens were collected before the treatment phase of a nicotine replacement therapy trial and analyzed. The relationship between saliva and plasma cotinine concentration was analyzed using Pearson’s correlation coefficients. We performed a secondary analysis using multiple regressions to compare correlations across race, gender and age. Results indicated a positive correlation between saliva cotinine and plasma cotinine concentration (r=0.84, p<0.001). Differences in correlations across age were significant (t=3.03, p<0.01). Differences across ethnicity approached significance (t=-1.93, p=0.058).

Although sodium lauryl sulfate (SLS) is a common dentifrice ingre

Although sodium lauryl sulfate (SLS) is a common dentifrice ingredient, the influence of this ion on plaque fluid and salivary fluid fluoride has not been examined. The purpose of this study was to investigate the effect of SLS on these parameters and to examine the effect of this ion on total (or whole) plaque fluoride, an important source of plaque fluid fluoride after a sufficient interval following Go 6983 supplier fluoride administration, and on total salivary fluoride, a parameter often used as a surrogate measure of salivary fluid fluoride. Ten subjects accumulated plaque

for 48 h before rinsing with a 12 mmol/lNaF (228 mu g/g F) rinse containing or not containing 0.5% (w/w) SLS. SLS had no statistically significant effect on total plaque and total saliva fluoride but significantly increased salivary fluid and plaque fluid fluoride (by 147 and 205%, respectively). These results suggest that the nonfluoride components of topical agents can be manipulated to improve the fluoride release characteristics from oral Pevonedistat chemical structure fluoride reservoirs and that statistically

significant change may be observed in plaque fluid and salivary fluid fluoride concentrations that may not be observed in total plaque and total saliva fluoride concentrations. (C) 2015 S. Karger AG, Basel”
“Background Patients with chronic obstructive pulmonary disease (COPD) who are not severely hypoxaemic at rest may experience significant breathlessness on exertion, and ambulatory oxygen is often prescribed Givinostat chemical structure in this circumstance despite a lack of conclusive evidence for benefit. This study aimed to determine whether such patients benefit from domiciliary ambulatory oxygen and, if so, which factors may be associated with benefit.\n\nMethods This was a 12 week, parallel, double-blinded, randomised, placebo-controlled trial of cylinder air versus cylinder oxygen, provided

at 6 l/min intranasally, for use during any activity provoking breathlessness. Patients underwent baseline measurements of arterial blood gases and lung function. Outcome measures assessed dyspnoea, health-related quality of life, mood disturbance, functional status and cylinder utilisation. Data were analysed on an intention-to-treat basis, p <= 0.05.\n\nResults 143 subjects (44 female), mean +/- SD age 71.8 +/- 9.8 years, forced expiratory volume in 1 s (FEV(1)) 1.16 +/- 0.51 lites, Pao(2) 9.5 +/- 1.1 kPa (71.4 +/- 8.5 mm Hg) were randomised, including 50 patients with exertional desaturation to <= 88%. No significant differences in any outcome were found between groups receiving air or oxygen. Statistically significant but clinically small improvements in dyspnoea and depression were observed in the whole study group over the 12 weeks of the study.\n\nConclusion In breathless patients with COPD who do not have severe resting hypoxaemia, domiciliary ambulatory oxygen confers no benefits in terms of dyspnoea, quality of life or function.

It was shown that the use of a failure criterion to calculate the

It was shown that the use of a failure criterion to calculate the registration accuracy and reliability is not required, since all the information about a registration method can be determined from the estimated distribution of registration errors.\n\nConclusions: The proposed simulated image data set with quite realistic synthetic 2D images, depicting this website soft tissues and outliers, is especially suitable for preliminary testing of 3D/2D registration algorithms. Since the aim of this article is to provide

objective comparison and unbiased evaluation of 3D/2D registration methods, the standardized evaluation methodology is available upon request from the authors. (c) 2010 American Association of Physicists Acalabrutinib inhibitor in Medicine. [DOI: 10.1118/1.3476414]“
“Background:

Participatory health education interventions and/or community-based primary health care in remote regions can improve child survival. The most recent data from Guinea Bissau shows that the country ranks 5(th) from bottom globally with an under-five mortality rate of 198 per 1000 live births in 2007. EPICS ( Enabling Parents to Increase Child Survival) is a cluster randomised trial, which is currently running in rural areas of southern Guinea Bissau. It aims to evaluate whether an intervention package can generate a rapid and cost-effective reduction in under-five child mortality. The purpose of the study described here was to understand levels of knowledge on child health and treatment-seeking and preventative behaviours in southern Guinea Bissau in order to develop an effective health education component for the EPICS trial. The study also aimed to assess the effect of gender and ethnicity on knowledge and behaviour.\n\nMethods: Women and men were interviewed in their households using a structured questionnaire. Characteristics of the households and of the interviewed women and men were tabulated. The number of correct answers given to the health knowledge and practice questions and their percentage distribution

were tabulated by items and by gender. An overall health knowledge score was derived.\n\nResults: There are low levels of appropriate knowledge on child health, some inappropriate practices and generally low vaccination coverage. Health knowledge ABT-263 chemical structure scores improve significantly amongst those who have accessed higher education. Differences in health knowledge between women and men become insignificant once age and education are accounted for.\n\nConclusions: Health education activities should be an integral part of a package to improve child survival in rural Guinea Bissau. These activities should focus on diarrhoea, malaria, pneumonia, pregnancy, delivery, neonatal care and vaccination coverage, as these are areas where knowledge and practices were found to be inadequate in this study.

We identified an epidermal enhancer in the 5′ flanking region of

We identified an epidermal enhancer in the 5′ flanking region of an ortholog of Hox1 (Ci-Hox1) in the ascidian Ciona intestinalis. This enhancer element drives the transcription of a lacZ reporter gene in the epidermis in the posterior trunk and the anterior tail region of tailbud-stage embryos. Inhibition of retinoic acid synthesis resulted in inactivation of the expression of the reporter gene. The enhancer contains a putative retinoic acid response element. When this element was mutagenized, the expression of the reporter gene disappeared from the epidermis. This

sequence was also required for the selleck compound response to exogenously administered retinoic acid. A heterodimeric nuclear receptor, consisting of the retinoic acid receptor and retinoid X receptor, bound to this sequence. These results indicate that retinoic acid directly activates the epidermal enhancer of Ci-Hox1. This is the first demonstration that retinoic acid is necessary for endogenous gene expression in ascidian embryos. (C) 2009 Elsevier Inc. All rights reserved.”
“Fecal samples and behavioral data were collected at a fortnightly basis during 11 months period from see more free-living male American kestrels living in southeast Brazil (22 degrees S latitude). The aim was to investigate

the seasonal changes in testicular and adrenal steroidogenic activity and their correlation to reproductive behaviors and environmental factors. The results revealed that monthly mean of fecal glucocorticoid metabolites GSK621 molecular weight in May and June were higher than those estimated in November. in parallel, monthly mean of androgen metabolites in September was higher than those from January to

April and from October to November. Molt took place from January to March, whereas copulation was observed from June to October but peaked in September. Nest activity and food transfer to females occurred predominantly in October, and parental behavior was noticed only in November. Territorial aggressions were rare and scattered throughout the year. Multiple regression analysis revealed that fecal androgen levels are predicted by photoperiod and copulation, while fecal glucocorticoid levels are only predicted by photoperiod. Bivariate correlations showed that fecal androgen metabolites were positively correlated with fecal glucocorticoid metabolites and copulation, but negatively correlated with molt. Additionally, copulation was positively correlated with food transfer to females and nest activity, but negatively correlated with molt. These findings suggest that male American kestrels living in southeast Brazil exhibit significant seasonal changes in fecal androgen and glucocorticoid concentrations, which seem to be stimulated by decreasing daylength but not by rainfall or temperature. (C) 2009 Elsevier Inc. All rights reserved.”
“Human T-cell leukemia virus type 1 (HTLV-1) has a reputation for being extremely difficult to study in cell culture.

0 mm and 29 metastases were evaluated by tissue microarray The s

0 mm and 29 metastases were evaluated by tissue microarray. The sections were stained for the following proteins: p16INK4 (p16), cyclin D1, cyclin-dependent kinase 4 (Cdk4), retinoblastoma protein, tumor suppressor protein

p53, and p21 cell cycle regulator (p21) using a streptavidine-biotin-peroxidase technique for immunohistochemistry. Thick selleck chemicals llc melanomas (> 1.0 mm) and metastases lost p16 expression in 100% of the cases and in-situ and thin melanomas (9 1.0 mm) had low rate of p16 expression (7.9%). When comparing thin versus thick melanomas, thin melanomas showed higher expression of cyclin D1 and cytoplasmatic Cdk4, and thick melanomas had increased expression of nuclear Cdk4, tumor suppressor protein p53, and p21. Primary tumors, when compared with metastases, had higher cytoplasmatic Cdk4 expression. None of the studied proteins influenced overall or disease-free survival. Our results suggest that loss of p16 expression was a constant feature in primary and metastatic melanomas. Cyclin D1 expression seems to be related to initial phases of melanoma development. see more An increase in p21 expression could represent a cell cycle

control in proliferating cells with reduced p16 and/or increased nuclear Cdk4 expression. Melanoma Res 19:135-141 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.”
“P>Alpha-synuclein is a natively unfolded protein that aggregates and forms inclusions

that are associated with a range of diseases that include Parkinson’s Disease and Dementia with Lewy Bodies. The mechanism behind the formation of these inclusions and their possible role in disease remains unclear. Alpha-synuclein has also been shown to bind metals including copper and iron. We used a cell culture model of alpha-synuclein aggregation to examine the relationship between metals and formation of aggregates of the protein. While the levels of iron appear to have no role in aggregate formation or localisation of the protein in cells, copper appears to be important for both aggregation and cellular localisation of alpha-synuclein. Reduction in cellular copper resulted in a great decrease in aggregate formation both in terms Selleckchem GDC0068 of large aggregates visible in cells and oligomers observed in western blot analysis of cell extracts. Reduction in copper also resulted in a change in localisation of the protein which became more intensely localised to the plasma membrane in medium with low copper. These changes were reversed when copper was restored to the cells. Mutants of the copper binding domains altered the response to copper. Deletion of either the N- or C-termini resulted in a loss of aggregation while deletion of the C-termini also resulted in a loss of membrane association. Increased expression of alpha-synuclein also increased cell sensitivity to the toxicity of copper.