Broad spectrum late blight resistance in potato differential set plants MaR8 and MaR9 is conferred by multiple stacked R genes

Phytophthora infestans is the causal agent of late blight in potato. The Mexican species Solanum demissum is well known as a good resistance source. Among the 11 R gene differentials, which were introgressed from S. demissum, especially R8 and R9 differentials showed broad spectrum resistance both under laboratory and under field conditions. In order to gather more information about the resistance of the R8 and R9 differentials, F1 and BC1 populations were made by crossing Mastenbroek (Ma) R8 and R9 clones to susceptible plants. Parents and offspring plants were examined for their pathogen recognition specificities using agroinfiltration with known Avr genes, detached leaf assays (DLA) with selected isolates, and gene-specific markers. An important observation was the discrepancy between DLA and field trial results for Pi isolate IPO-C in all F1 and BC1 populations, so therefore also field trial results were included in our characterization. It was shown that in MaR8 and MaR9, respectively, at least four (R3a, R3b, R4, and R8) and seven (R1, Rpi-abpt1, R3a, R3b, R4, R8, R9) R genes were present. Analysis of MaR8 and MaR9 offspring plants, that contained different combinations of multiple resistance genes, showed that R gene stacking contributed to the Pi recognition spectrum. Also, using a Pi virulence monitoring system in the field, it was shown that stacking of multiple R genes strongly delayed the onset of late blight symptoms. The contribution of R8 to this delay was remarkable since a plant that contained only the R8 resistance gene still conferred a delay similar to plants with multiple resistance genes, like, e.g., cv Sarpo Mira. Using this “de-stacking” approach, many R gene combinations can be made and tested in order to select broad spectrum R gene stacks that potentially provide enhanced durability for future application in new late blight resistant varieties

Association between brain-derived neurotrophic factor gene polymorphisms and fibromyalgia in a Korean population: a multicenter study

Abstract Background Several lines of evidence imply that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of fibromyalgia (FM); in this regard, patients with FM have altered blood and cerebrospinal fluid levels of BDNF. In this study, we explored the association between BDNF gene polymorphisms and FM susceptibility and the severity of symptoms. Methods In total, 409 patients with FM and 423 healthy controls in 10 medical centers were enrolled from the Korean nationwide FM survey. The alleles and genotypes at 10 positions in the BDNF gene were genotyped. Results The allele and genotype frequencies of BDNF rs11030104 differed significantly between the patients with FM and the controls (P = 0.031). The GG genotype of rs11030104 had a protective effect against FM (P = 0.016), and the G allele of rs11030104 was negatively associated with the presence of FM compared with the A allele (P = 0.013). In comparison, although the allele and genotype frequencies of BDNF rs12273539 did not differ between the two groups, the TT genotype of BDNF rs12273539 was associated with susceptibility to FM (P = 0.038). Haplotype analyses implied that some BDNF haplotypes have a protective effect against FM. Finally, several genotypes and haplotypes of the BDNF gene contributed to specific symptoms of FM. Conclusions This study is the first to evaluate the associations between BDNF gene polymorphisms and FM. Our results imply that some BDNF single-nucleotide polymorphisms and haplotypes are associated with susceptibility to, and contribute to the symptoms of, FM

Neuritin Attenuates Cognitive Function Impairments in Tg2576 Mouse Model of Alzheimer's Disease

<div><p>Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s) and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD) patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.</p></div

Neuritin increases synaptophysin expression in rat primary neuron cultures.

<p>Primary cultured cortical neurons were transfected at DIV 10 with EGFP or neuritin subcloned in a flag-IRES-EGFP vector by employing a calcium phosphate method. 3 days after transfection, the cells were lysed and Western blotting analysis was performed with an anti-synaptophysin antibody. β-actin was used as a loading control. Densitometric analysis was also performed. Neuritin transfection significantly increased synaptophysin expression levels by approximately 3.6-fold (*<i>p</i><0.05, Student's <i>t</i>-test). The data are presented as the mean ±SEM (n = 5 dishes from 5 independent cultures for each group).</p

Neuritin up-regulates neurogenesis in the dentate gyrus of 7-week-old SD rats.

<p>(A) A experimental scheme is shown. 7-week-old male SD rats were injected with EGFP- or neuritin-lentiviral particles in the dentate gyrus of the hippocampus using a stereotaxic apparatus (n = 6 for each group). BrdU was intraperitoneally administered for 6 days. (B) After 2 weeks, GFP expression was confirmed by confocal laser scanning microscopy. The scale bars indicate 200 µm (low-scaled panel) and 50 µm (magnified panel). (C) Brain sections were stained with anti-GFP (green), anti-BrdU (red), and anti-NeuN (purple) antibodies. Orthogonal analysis of the staining was conducted by confocal microscopy. (D) Cells stained with BrdU antibody were counted. (E) Staining with anti-GFP and anti-BrdU antibodies was performed and counted. (F) Staining with anti-BrdU, anti-NeuN and anti-GFP antibodies was performed and counted. The results were normalized as percentage ratios to the staining in EGFP expressing rats. Rats with neuritin expression showed an increase in BrdU/GFP expressing cells by 330.77±130.78% compared to the rats with EGFP expression. Quantitative analysis of triple staining with BrdU/NeuN/GFP antibodies showed that neuritin expression induced a significant increase of newly generated neuronal cells in the dentate gyrus by 338.46±123.08% compared to EGFP-injection (*<i>p</i><0.05, Student's <i>t</i>-test).</p

Neuritin restores the reduction in the dendritic spine density and the maturity of individual spines in Tg2576 neurons.

<p>(A) Representative images of dendrites and spines of rabies virus encoding EGFP-infected neurons are shown in the designated conditions. Scale bar represents 10 µm. (B) A summary histogram shows mean numbers of spines. Neuritin peptide (150 ng/ml) was added as a treatment for 3 days, and the dendritic spine density was then analyzed. The reduction in dendritic spine density in Tg2576 neurons (32.57±2.80/100 µm) was significantly increased to match the normal control levels in wt neurons (56.75±1.95/100 µm). (C) Proportion of spines (type I, II, III and IV) were analyzed by their morphology. Tg2576 neurons revealed a significant decrease particularly in type II spines (mushroom type; mature spines with a large head, >0.6 µm, and a short neck), but yielded a slightly higher density of type I spines (stubby type; less mature spines, relatively small spine head, <0.6 µm, and short neck, <0.3 µm) compared to the other groups. (D) A summary histogram showing mean numbers of each type of spine in the designated conditions (*<i>p</i><0.05, ***<i>p</i><0.001, one-way ANOVA followed by <i>post hoc</i> Bonferroni test).</p

Neuritin is down-regulated in human AD brains.

<p>(A) Neuritin mRNA levels in the cortex (medial frontal gyrus) and hippocampus of age-matched control subjects (69, 79 and 80 years old) and AD patients (67, 75, 81 and 87 years old) were evaluated by qRT-PCR. Neuritin mRNA levels in the cortex and hippocampus of the AD brains were significantly lower than those of the age-matched control subjects. The relative ratio of neuritin to GAPDH mRNA in the AD patients was 15.10±6.28% compared to control subjects in cortical regions and 69.16±5.95% compared to the control subjects in the hippocampus (***<i>p</i><0.001 and *<i>p</i><0.05, respectively, Student's <i>t</i>-test). Data are presented as the mean ± SEM. (B) Human brain tissues embedded in paraffin were cut into 4 µm-thick coronal sections and were used to perform immunohistochemistry with an anti-neuritin antibody (red) and DAPI (blue) staining. The fluorescent images were collected from the dentate gyrus, the CA1 and CA3 regions of the hippocampus on an LSM 510 confocal microscope (Zeiss). The black and white images merged with DAPI staining are also shown. The results are representative of 3 human AD brains and 3 age-matched control brains. Scale bars represent 100 µm.</p

Determinants of quality of life in patients with fibromyalgia: A structural equation modeling approach

<div><p>Objective</p><p>Health-related quality of life (HRQOL) in patients with fibromyalgia (FM) is lower than in patients with other chronic diseases and the general population. Although various factors affect HRQOL, no study has examined a structural equation model of HRQOL as an outcome variable in FM patients. The present study assessed relationships among physical function, social factors, psychological factors, and HRQOL, and the effects of these variables on HRQOL in a hypothesized model using structural equation modeling (SEM).</p><p>Methods</p><p>HRQOL was measured using SF-36, and the Fibromyalgia Impact Questionnaire (FIQ) was used to assess physical dysfunction. Social and psychological statuses were assessed using the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Arthritis Self-Efficacy Scale (ASES), and the Social Support Scale. SEM analysis was used to test the structural relationships of the model using the AMOS software.</p><p>Results</p><p>Of the 336 patients, 301 (89.6%) were women with an average age of 47.9±10.9 years. The SEM results supported the hypothesized structural model (χ² = 2.336, df = 3, p = 0.506). The final model showed that Physical Component Summary (PCS) was directly related to self-efficacy and inversely related to FIQ, and that Mental Component Summary (MCS) was inversely related to FIQ, BDI, and STAI.</p><p>Conclusions</p><p>In our model of FM patients, HRQOL was affected by physical, social, and psychological variables. In these patients, higher levels of physical function and self-efficacy can improve the PCS of HRQOL, while physical function, depression, and anxiety negatively affect the MCS of HRQOL.</p></div

Significant pathways of the final model.

<p>FIQ: Fibromyalgia Impact Questionnaire, BDI: Beck Depression Inventory, STAI: State-Trait Anxiety Inventory, PCS: physical component summary, MCS: mental component summary.</p