Mycotoxin contamination in organic and conventional cereal grain and products: A systematic literature review and meta-analysis.

There is still considerable controversy about the relative risk of mycotoxin exposure associated with the consumption of organic and conventional cereals. Using validated protocols, we carried out a systematic literature review and meta-analyses of data on the incidence and concentrations of mycotoxins produced by Fusarium, Claviceps, Penicillium, and Aspergillus species in organic and conventional cereal grains/products. The standard weighted meta-analysis of concentration data detected a significant effect of production system (organic vs. conventional) only for the Fusarium mycotoxins deoxynivalenol, with concentrations ∼50% higher in conventional than organic cereal grains/products (p < 0.0001). Weighted meta-analyses of incidence data and unweighted meta-analyses of concentration data also detected small, but significant effects of production system on the incidence and/or concentrations of T-2/HT-2 toxins, zearalenone, enniatin, beauvericin, ochratoxin A (OTA), and aflatoxins. Multilevel meta-analyses identified climatic conditions, cereal species, study type, and analytical methods used as important confounding factors for the effects of production system. Overall, results from this study suggest that (i) Fusarium mycotoxin contamination decreased between the 1990s and 2020, (ii) contamination levels are similar in organic and conventional cereals used for human consumption, and (iii) maintaining OTA concentrations below the maximum contamination levels (3.0 µg/kg) set by the EU remains a major challenge.

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson's disease.

Individuals with Parkinson's disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression.

Essential role for DNA-PK-mediated phosphorylation of NR4A nuclear orphan receptors in DNA double-strand break repair.

DNA-dependent protein kinase (DNA-PK) is a central regulator of DNA double-strand break (DSB) repair; however, the identity of relevant DNA-PK substrates has remained elusive. NR4A nuclear orphan receptors function as sequence-specific DNA-binding transcription factors that participate in adaptive and stress-related cell responses. We show here that NR4A proteins interact with the DNA-PK catalytic subunit and, upon exposure to DNA damage, translocate to DSB foci by a mechanism requiring the activity of poly(ADP-ribose) polymerase-1 (PARP-1). At DNA repair foci, NR4A is phosphorylated by DNA-PK and promotes DSB repair. Notably, NR4A transcriptional activity is entirely dispensable in this function, and core components of the DNA repair machinery are not transcriptionally regulated by NR4A. Instead, NR4A functions directly at DNA repair sites by a process that requires phosphorylation by DNA-PK. Furthermore, a severe combined immunodeficiency (SCID)-causing mutation in the human gene encoding the DNA-PK catalytic subunit impairs the interaction and phosphorylation of NR4A at DSBs. Thus, NR4As represent an entirely novel component of DNA damage response and are substrates of DNA-PK in the process of DSB repair.

Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.

α-synuclein, a protein enriched in Lewy bodies and highly implicated in neurotoxicity in Parkinson's disease, is distributed both at nerve terminals and in the cell nucleus. Here we show that a nuclear derivative of α-synuclein induces more pronounced changes at the gene expression level in mouse primary dopamine (DA) neurons compared to a derivative that is excluded from the nucleus. Moreover, by RNA sequencing we analyzed the extent of genome-wide effects on gene expression resulting from expression of human α-synuclein in primary mouse DA neurons. The results implicated the transcription factor Nurr1 as a key dysregulated target of α-synuclein toxicity. Forced Nurr1 expression restored the expression of hundreds of dysregulated genes in primary DA neurons expressing α-synuclein, and therefore prompted us to test the possibility that Nurr1 can be pharmacologically targeted by bexarotene, a ligand for the retinoid X receptor that forms heterodimers with Nurr1. Although our data demonstrated that bexarotene was ineffective in neuroprotection in rats in vivo, the results revealed that bexarotene has the capacity to coregulate subsets of Nurr1 target genes including the receptor tyrosine kinase subunit Ret. Moreover, bexarotene was able to restore dysfunctional Ret-dependent neurotrophic signaling in α-synuclein-overexpressing mouse DA neurons. These data highlight the role of the Nurr1-Ret signaling pathway as a target of α-synuclein toxicity and suggest that retinoid X receptor ligands with appropriate pharmacological properties could have therapeutic potential in Parkinson's disease. SIGNIFICANCE STATEMENT: How α-synuclein, a protein enriched in Lewy bodies in Parkinson's disease, is causing neuropathology in dopamine neurons remains unclear. This study elucidated how α-synuclein is influencing gene expression and how Nurr1, a transcription factor known to protect dopamine neurons against α-synuclein toxicity, can counteract these effects. Moreover, given the protective role of Nurr1, this study also investigated how Nurr1 could be pharmacologically targeted via bexarotene, a ligand of Nurr1's heterodimerization partner retinoid X receptor (RXR). The results showed that RXR ligands could increase neurotrophic signaling, but provided a mixed picture of its potential in a Parkinson's disease rat model in vivo. However, this study clearly emphasized Nurr1's neuroprotective role and indicated that other RXR ligands could have therapeutic potential in Parkinson's disease.

Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons.

Developmental transcription factors important in early neuron specification and differentiation often remain expressed in the adult brain. However, how these transcription factors function to mantain appropriate neuronal identities in adult neurons and how transcription factor dysregulation may contribute to disease remain largely unknown. The transcription factor Nurr1 has been associated with Parkinson's disease and is essential for the development of ventral midbrain dopamine (DA) neurons. We used conditional Nurr1 gene-targeted mice in which Nurr1 is ablated selectively in mature DA neurons by treatment with tamoxifen. We show that Nurr1 ablation results in a progressive pathology associated with reduced striatal DA, impaired motor behaviors, and dystrophic axons and dendrites. We used laser-microdissected DA neurons for RNA extraction and next-generation mRNA sequencing to identify Nurr1-regulated genes. This analysis revealed that Nurr1 functions mainly in transcriptional activation to regulate a battery of genes expressed in DA neurons. Importantly, nuclear-encoded mitochondrial genes were identified as the major functional category of Nurr1-regulated target genes. These studies indicate that Nurr1 has a key function in sustaining high respiratory function in these cells, and that Nurr1 ablation in mice recapitulates early features of Parkinson's disease.

Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses.

Demand for organic foods is partially driven by consumers' perceptions that they are more nutritious. However, scientific opinion is divided on whether there are significant nutritional differences between organic and non-organic foods, and two recent reviews have concluded that there are no differences. In the present study, we carried out meta-analyses based on 343 peer-reviewed publications that indicate statistically significant and meaningful differences in composition between organic and non-organic crops/crop-based foods. Most importantly, the concentrations of a range of antioxidants such as polyphenolics were found to be substantially higher in organic crops/crop-based foods, with those of phenolic acids, flavanones, stilbenes, flavones, flavonols and anthocyanins being an estimated 19 (95 % CI 5, 33) %, 69 (95 % CI 13, 125) %, 28 (95 % CI 12, 44) %, 26 (95 % CI 3, 48) %, 50 (95 % CI 28, 72) % and 51 (95 % CI 17, 86) % higher, respectively. Many of these compounds have previously been linked to a reduced risk of chronic diseases, including CVD and neurodegenerative diseases and certain cancers, in dietary intervention and epidemiological studies. Additionally, the frequency of occurrence of pesticide residues was found to be four times higher in conventional crops, which also contained significantly higher concentrations of the toxic metal Cd. Significant differences were also detected for some other (e.g. minerals and vitamins) compounds. There is evidence that higher antioxidant concentrations and lower Cd concentrations are linked to specific agronomic practices (e.g. non-use of mineral N and P fertilisers, respectively) prescribed in organic farming systems. In conclusion, organic crops, on average, have higher concentrations of antioxidants, lower concentrations of Cd and a lower incidence of pesticide residues than the non-organic comparators across regions and production seasons.

Optimal Volume Assessment for Serous Fluid Cytology.

OBJECTIVE: This study aimed to investigate the optimal volume of serous fluid needed for accurate diagnosis using The International System for Reporting Serous Fluid Cytopathology (TIS), as well as to provide information on the distribution of serous effusion cases in the TIS categories (ND: non-diagnostic, NFM: negative for malignancy, AUS: atypia of undetermined significance, SFM: suspicious for malignancy, MAL: malignant) and relevant epidemiological data. METHODS: A retrospective analysis of 2340 serous effusion cases (pleural, peritoneal, and pericardial) from two hospitals between 2018 and 2020 was conducted. TIS categories were assigned to each case, and for 1181 cases, these were correlated with the volume of the analyzed fluid. RESULTS: Our study found statistically significant differences in volume distributions between certain TIS categories. Statistically lower volumes were observed in NFM compared to MAL, in UNCERTAIN (ND, AUS, SFM) compared to both MAL and NFM, and in NOT MAL (ND, NFM, AUS, SFM) compared to MAL. However, these differences were not substantial enough to hold any clinical relevance. CONCLUSIONS: This study suggests that while fluid volume may slightly influence the TIS category, it does not impact the diagnostic accuracy of serous effusion cytology. Therefore, the ideal serous effusion specimen volume can be defined solely by practical parameters.

NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection.

Induced expression of neuroprotective genes is essential for maintaining neuronal integrity after stressful insults to the brain. Here we show that NR4A nuclear orphan receptors are induced after excitotoxic and oxidative stress in neurons, up-regulate neuroprotective genes, and increase neuronal survival. Moreover, we show that NR4A proteins are induced by cAMP response element binding protein (CREB) in neurons exposed to stressful insults and that they function as mediators of CREB-induced neuronal survival. Animals with null mutations in three of six NR4A alleles show increased oxidative damage, blunted induction of neuroprotective genes, and increased vulnerability in the hippocampus after treatment with kainic acid. We also demonstrate that NR4A and the transcriptional coactivator PGC-1alpha independently regulate distinct CREB-dependent neuroprotective gene programs. These data identify NR4A nuclear orphan receptors as essential mediators of neuroprotection after exposure to neuropathological stress.

Effects of Agricultural Intensification on Mediterranean Diets: A Narrative Review.

INTRODUCTION: Mediterranean diets (MedDiets) are linked to substantial health benefits. However, there is also growing evidence that the intensification of food production over the last 60 years has resulted in nutritionally relevant changes in the composition of foods that may augment the health benefits of MedDiets. OBJECTIVE: To synthesize, summarize, and critically evaluate the currently available evidence for changes in food composition resulting from agricultural intensification practices and their potential impact on the health benefits of MedDiets. METHODS: We summarized/synthesized information from (i) systematic literature reviews/meta-analyses and more recently published articles on composition differences between conventional and organic foods, (ii) desk studies which compared food composition data from before and after agricultural intensification, (iii) recent retail and farm surveys and/or factorial field experiments that identified specific agronomic practices responsible for nutritionally relevant changes in food composition, and (iv) a recent systematic literature review and a small number of subsequently published observational and dietary intervention studies that investigated the potential health impacts of changes in food composition resulting from agricultural intensification. RESULTS AND DISCUSSION: There has been growing evidence that the intensification of food production has resulted in (i) lower concentrations of nutritionally desirable compounds (e.g., phenolics, certain vitamins, mineral micronutrients including Se, Zn, and omega-3 fatty acids, α-tocopherol) and/or (ii) higher concentrations of nutritionally undesirable or toxic compounds (pesticide residues, cadmium, omega-6 fatty acids) in many of the foods (including wholegrain cereals, fruit and vegetables, olive oil, dairy products and meat from small ruminants, and fish) that are thought to contribute to the health benefits associated with MedDiets. The evidence for negative health impacts of consuming foods from intensified conventional production systems has also increased but is still limited and based primarily on evidence from observational studies. Limitations and gaps in the current evidence base are discussed. Conclusions: There is now substantial evidence that the intensification of agricultural food production has resulted in a decline in the nutritional quality of many of the foods that are recognized to contribute to the positive health impacts associated with adhering to traditional MedDiets. Further research is needed to quantify to what extent this decline augments the positive health impacts of adhering to a traditional MedDiet.

Breeding Bread-Making Wheat Varieties for Organic Farming Systems: The Need to Target Productivity, Robustness, Resource Use Efficiency and Grain Quality Traits.

Agronomic protocols (rotation, tillage, fertilization and crop protection) commonly used in organic and conventional crop production differ significantly and there is evidence that modern varieties developed for conventional high-input farming systems do not have the combination of traits required for optimum performance in organic farming systems. Specifically, there is evidence that prohibition on the use of water-soluble, mineral N, P and K fertilizers and synthetic pesticide inputs in organic farming results in a need to revise both breeding and selection protocols. For organic production systems, the focus needs to be on the following: (i) traits prioritized by organic farmers such as high nutrient use efficiency from organic fertilizer inputs, competitiveness against weeds, and pest and disease resistance, (ii) processing quality parameters defined by millers and bakers and (iii) nutritional quality parameters demanded by organic consumers. In this article, we review evidence from variety trials and factorial field experiments that (i) studied to what extent there is a need for organic farming focused breeding programs, (ii) investigated which traits/trait combinations should be targeted in these breeding programs and/or (iii) compared the performance of modern varieties developed for the conventional sector with traditional/older varieties favored by organic farmers and/or new varieties developed in organic farming focused breeding programs. Our review focuses on wheat because there have been organic and/or low-input farming focused wheat breeding programs for more than 20 years in Europe, which has allowed the performance of varieties/genotypes from organic/low-input and conventional farming focused breeding programs to be compared.

Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells.

Signaling factors involved in CNS development have been used to control the differentiation of embryonic stem cells (ESCs) into mesencephalic dopamine (mesDA) neurons, but tend to generate a limited yield of desired cell type. Here we show that forced expression of Lmx1a, a transcription factor functioning as a determinant of mesDA neurons during embryogenesis, effectively can promote the generation of mesDA neurons from mouse and human ESCs. Under permissive culture conditions, 75%-95% of mouse ESC-derived neurons express molecular and physiological properties characteristic of bona fide mesDA neurons. Similar to primary mesDA neurons, these cells integrate and innervate the striatum of 6-hydroxy dopamine lesioned neonatal rats. Thus, the enriched generation of functional mesDA neurons by forced expression of Lmx1a may be of future importance in cell replacement therapy of Parkinson disease.

Diet and food type affect urinary pesticide residue excretion profiles in healthy individuals: results of a randomized controlled dietary intervention trial.

BACKGROUND: Observational studies have linked pesticide exposure to various diseases, whereas organic food consumption has been associated with positive health outcomes. Organic farming standards prohibit the use of most pesticides, and organic food consumption may therefore reduce pesticide exposure. OBJECTIVES: To determine the effects of diet (Western compared with Mediterranean) and food type (conventional compared with organic) and sex on urinary pesticide residue excretion (UPRE), as well as associations between specific diet components and UPRE. METHODS: In this 2-wk, randomized dietary intervention trial, healthy adults were randomly allocated to an intervention (n = 13) or conventional (n = 14) group. Whereas participants in the intervention group consumed a Mediterranean diet (MedDiet) made entirely from organic foods, the conventional group consumed a MedDiet made entirely from conventional foods. Both groups consumed habitual Western diets made from conventional foods before and after the 2-wk intervention period. The primary outcome was UPRE. In addition, we assessed diet composition and pesticide residue profiles in foods eaten. Participants were aware of group assignment, but the study assessors were not. RESULTS: During the intervention period, total UPRE was 91% lower with organic (mean 17 µg/d; 95% CI: 15, 19) than with conventional (mean 180 µg/d; 95% CI: 153, 208) food consumption (P < 0.0001). In the conventional group, switching from the habitual Western diet to the MedDiet increased insecticide excretion from 7 to 25 µg/d (P < 0.0001), organophosphate excretion from 5 to 19 µg/d (P < 0.0001), and pyrethroid residue excretion from 2.0 to 4.5 µg/d (P < 0.0001). Small but significant effects of sex were detected for chlormequat, herbicide, and total pesticide residue excretion. CONCLUSIONS: Changing from a habitual Western diet to a MedDiet was associated with increased insecticide, organophosphate, and pyrethroid exposure, whereas organic food consumption reduced exposure to all groups of synthetic chemical pesticides. This may explain the positive health outcomes linked to organic food consumption in observational studies. This trial was registered at www.clinicaltrials.gov as NCT03254537.

Diet, but not food type, significantly affects micronutrient and toxic metal profiles in urine and/or plasma; a randomized, controlled intervention trial.

BACKGROUND: Observational studies have linked Mediterranean Diets (MedDiets) and organic food consumption with positive health outcomes, which may be explained by higher mineral micronutrient and phenolic intake and lower dietary exposure to toxic compounds. OBJECTIVES: We aimed to determine the effects of diet and food type (organic compared with conventional) on urinary excretion (UE) and/or plasma concentrations of mineral micronutrients, phenolics, and toxic metals. METHODS: Healthy adult participants were randomly allocated to a conventional (n = 14) or an intervention (n = 13) group. During a 2-wk period, the intervention group consumed a MedDiet made entirely from organic foods, whereas the conventional group consumed a MedDiet made from conventional foods. Before and after the intervention period, both groups consumed their habitual Western diets made from conventional foods. The primary outcome was UE and/or plasma concentrations of selected mineral micronutrients, toxic metals, and phenolic markers. In addition, we monitored diets using food diaries. The participants were aware of study group assignment, but the study assessors were not. RESULTS: Changing from a Western Diet to a MedDiet for 2 wk resulted in significant increases in UE of total phenolics and salicylic acid (by 46% and 45%, respectively), the mineral micronutrients Co, I, and Mn (by 211%, 70%, and 102%, respectively), and the toxic metal Ni (by 42%), and plasma Se concentrations (by 14%). However, no significant effects of food type (organic compared with conventional) were detected. Redundancy analysis identified vegetables, coffee, wine, and fruit as positive drivers for UE of phenolic markers and mineral micronutrients, and fish consumption as a positive driver for UE of Cd and Pb. CONCLUSIONS: Although small effects of food type cannot be ruled out, our study suggests that only changing to a MedDiet with higher fruit and vegetable, and lower meat, consumption results in a large increase in phenolic and mineral micronutrient intakes. This trial was registered at clinicaltrials.gov as NCT03254537.

Disease Duration Influences Gene Expression in Neuromelanin-Positive Cells From Parkinson's Disease Patients.

Analyses of gene expression in cells affected by neurodegenerative disease can provide important insights into disease mechanisms and relevant stress response pathways. Major symptoms in Parkinson's disease (PD) are caused by the degeneration of midbrain dopamine (mDA) neurons within the substantia nigra. Here we isolated neuromelanin-positive dopamine neurons by laser capture microdissection from post-mortem human substantia nigra samples recovered at both early and advanced stages of PD. Neuromelanin-positive cells were also isolated from individuals with incidental Lewy body disease (ILBD) and from aged-matched controls. Isolated mDA neurons were subjected to genome-wide gene expression analysis by mRNA sequencing. The analysis identified hundreds of dysregulated genes in PD. Results showed that mostly non-overlapping genes were differentially expressed in ILBD, subjects who were early after diagnosis (less than five years) and those autopsied at more advanced stages of disease (over five years since diagnosis). The identity of differentially expressed genes suggested that more resilient, stably surviving DA neurons were enriched in samples from advanced stages of disease, either as a consequence of positive selection of a less vulnerable long-term surviving mDA neuron subtype or due to up-regulation of neuroprotective gene products.

Effect of irrigation, fertiliser type and variety on grain yield and nutritional quality of spelt wheat (Triticum spelta) grown under semi-arid conditions.

Previous studies reported higher antioxidant and mineral micronutrient concentrations in organic compared to conventional wheat flour, but the reasons are poorly understood. Here we report results from a long-term, factorial field experiment designed to assess effects of variety choice, supplementary irrigation and contrasting fertilization regimes used in organic and conventional production on the nutritional quality and yield of spelt wheat grown in a semi-arid environment. Long-straw (Oberkulmer, Rubiota, ZOR) varieties had 10-40% higher grain Cu, Fe, Mn and Zn concentrations, while the modern, short straw variety Filderstolz had 15-38% higher grain antioxidant activity. Supplementary irrigation and the use of manure instead of mineral NPK as fertilizer had no substantial effect on the nutritional composition of spelt grain, but increased grain yields by ~ 150 and ~ 18% respectively. Overall, this suggests that breeding/variety selection is the most promising approach to improve the nutritional quality of spelt grain in semi-arid production environments.

Effect of Organic and Conventional Production Methods on Fruit Yield and Nutritional Quality Parameters in Three Traditional Cretan Grape Varieties: Results from a Farm Survey.

The antioxidants found in grapes and wine have been linked to health benefits in humans, but may be affected by agronomic parameters, grape type/variety, and processing. Here, we report results of a farm survey which investigated the effects of production system (organic vs. conventional) and grape variety on fruit yield, total antioxidant activity/capacity (TAA, assessed by the Trolox Equivalent Antioxidant Capacity (TEAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays), and total concentrations of total phenolics (TPC) and anthocyanins (TAC) in grapes of one red (Kotsifali) and two white (Villana and/or Vidiano) traditional Cretan grape varieties. Analysis of variance (ANOVA) results showed that grape variety choice had a more substantial effect on TPC, TAA, and TAC than primary production protocols, and significant interactions were identified between production system and grape variety choice for TAATEAC. Specifically, TAATEAC was significantly (57%) higher in organic than conventional Vidiano grapes, while there was no significant effect of production system on TAATEAC in Kotsifali and Villana grapes. As expected from previous studies, the TAC was substantially higher in red Kotsifali grapes. Redundancy analysis (RDA) identified grape variety as the only strong explanatory variable/driver for yield, TPC, TAA, and TAC of table grapes, and positive associations were detected between the variety Vidiano and both TPC and TAATEAC. All other explanatory variables included in the RDA (including supplementary irrigation, orchard orientation, production system, soil type, vineyard age, plant density, and fertiliser inputs) explained only a small proportion of the additional variation.

Basic life support skill retention by medical students: a comparison of two teaching curricula.

AIM: In December 2005 the new guidelines for resuscitation were released and a new curriculum for the teaching of basic life support (BLS) was adopted. The aim of the present study was to investigate the effectiveness of the new guidelines and teaching curriculum on the BLS skill retention of medical students 1 year following their initial training. METHODS: The study was conducted in two consecutive academic years and compared BLS skill retention of two groups of medical students in their fourth year of medicine. The first group (group A) was taught the old guidelines with the old curriculum in the year 2005 and was re-assessed in 2006, and the second group (group B) was taught the new guidelines with the new curriculum in the year 2006 and was re-assessed in 2007. RESULTS: Significantly more students in group B assessed signs of life, located the compression area correctly and performed good quality chest compressions compared with the group taught the old guidelines with the old curriculum. CONCLUSIONS: The most important BLS skill, good quality chest compressions, was retained by significantly more students who were taught the new resuscitation guidelines according to the new curriculum.

Effects of Production Region, Production Systems and Grape Type/Variety on Nutritional Quality Parameters of Table Grapes; Results from a UK Retail Survey.

Grapes contain high concentrations of secondary metabolites and antioxidants that have been linked to a reduction of several chronic diseases. Here, we report results of a UK retail survey, which investigated the effect of the production region (Mediterranean vs. South Africa), grape type (white vs. red vs. black) and variety, and production system (organic vs. conventional) on antioxidant activity and concentrations of phenolic compounds in table grapes. Black grapes had ~180% total antioxidant activity (TAA), ~60% higher total phenolic content (TPC) and ~40 times higher anthocyanin concentrations (TAC) than white grapes, while red grapes had intermediate levels of TAA, TPC and TAC. The effects of season and production system and differences between varieties of the same grape type were substantially smaller. Grapes imported from Mediterranean countries in summer had a 14% higher TPC and ~20% higher TAA than grapes imported from South Africa in winter, and organic grapes had a 16% higher TPC and 22% higher TAA, but ~30% lower TAC than conventional grapes. Significant differences in TPC, TAA and/or TAC between organic and conventional grapes could only be detected for specific grape types, varieties and/or sampling years.

Author Correction: Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson's disease.

Cell replacement is a long-standing and realistic goal for the treatment of Parkinson's disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.