A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals.

Synapses are often far from the soma and independently cope with proteopathic stress induced by intense neuronal activity. However, how presynaptic compartments turn over proteins is poorly understood. We show that the synapse-enriched protein EndophilinA, thus far studied for its role in endocytosis, induces macroautophagy at presynaptic terminals. We find that EndophilinA executes this unexpected function at least partly independent of its role in synaptic vesicle endocytosis. EndophilinA-induced macroautophagy is activated when the kinase LRRK2 phosphorylates the EndophilinA-BAR domain and is blocked in animals where EndophilinA cannot be phosphorylated. EndophilinA-phosphorylation promotes the formation of highly curved membranes, and reconstitution experiments show these curved membranes serve as docking stations for autophagic factors, including Atg3. Functionally, deregulation of the EndophilinA phosphorylation state accelerates activity-induced neurodegeneration. Given that EndophilinA is connected to at least three Parkinson's disease genes (LRRK2, Parkin and Synaptojanin), dysfunction of EndophilinA-dependent synaptic macroautophagy may be common in this disorder

Triplet Exciton Generation in Bulk-Heterojunction Solar Cells based on Endohedral Fullerenes

Organic bulk-heterojunctions (BHJ) and solar cells containing the trimetallic nitride endohedral fullerene 1-[3-(2-ethyl)hexoxy carbonyl]propyl-1-phenyl-Lu3N@C80 (Lu3N@C80-PCBEH) show an open circuit voltage (VOC) 0.3 V higher than similar devices with [6,6]-phenyl-C[61]-butyric acid methyl ester (PC61BM). To fully exploit the potential of this acceptor molecule with respect to the power conversion efficiency (PCE) of solar cells, the short circuit current (JSC) should be improved to become competitive with the state of the art solar cells. Here, we address factors influencing the JSC in blends containing the high voltage absorber Lu3N@C80-PCBEH in view of both photogeneration but also transport and extraction of charge carriers. We apply optical, charge carrier extraction, morphology, and spin-sensitive techniques. In blends containing Lu3N@C80-PCBEH, we found 2 times weaker photoluminescence quenching, remainders of interchain excitons, and, most remarkably, triplet excitons formed on the polymer chain, which were absent in the reference P3HT:PC61BM blends. We show that electron back transfer to the triplet state along with the lower exciton dissociation yield due to intramolecular charge transfer in Lu3N@C80-PCBEH are responsible for the reduced photocurrent

Bisphenol A Effects on Gonadotroph Function:Disruption of Pituitary Cell-Cell Communication?

International audienc

Non-Breeding Song Rate Reflects Nutritional Condition Rather than Body Condition

Numerous studies have focused on song in songbirds as a signal involved in mate choice and intrasexual competition. It is expected that song traits such as song rate reflect individual quality by being dependent on energetic state or condition. While seasonal variation in bird song (i.e., breeding versus non-breeding song) and its neural substrate have received a fair amount of attention, the function and information content of song outside the breeding season is generally much less understood. Furthermore, typically only measures of condition involving body mass are examined with respect to song rate. Studies investigating a potential relationship between song rate and other indicators of condition, such as physiological measures of nutritional condition, are scant. In this study, we examined whether non-breeding song rate in male European starlings (Sturnus vulgaris) reflects plasma metabolite levels (high-density lipoproteins (HDL), albumin, triglycerides and cholesterol) and/or body mass. Song rate was significantly positively related to a principal component representing primarily HDL, albumin and cholesterol (and to a lesser degree plasma triglyceride levels). There was only a trend toward a significant positive correlation between song rate and body mass, and no significant correlation between body mass and the abovementioned principal component. Therefore, our results indicate that nutritional condition and body mass represent different aspects of condition, and that song rate reflects nutritional rather than body condition. Additionally, we also found that intra-individual song rate consistency (though not song rate itself) was significantly positively related to lutein levels, but not to body mass or nutritional condition. Together our results suggest that the relation between physiological measures of nutritional condition and song rate, as well as other signals, may present an interesting line of future research, both inside and outside the breeding season

Use of a nested PCR-enzyme immunoassay with an internal control to detect Chlamydophila psittaci in turkeys

BACKGROUND: Laboratory diagnosis of Chlamydophila psittaci, an important turkey respiratory pathogen, is difficult. To facilitate the diagnosis, a nested PCR-enzyme immunoassay (PCR-EIA) was developed to detect the Cp. psittaci outer membrane protein A (ompA) gene in pharyngeal swabs. METHODS: The fluorescein-biotin labelled PCR products were immobilized on streptavidin-coated microtiter plates and detected with anti-fluorescein peroxidase conjugate and a colorimetric substrate. An internal inhibition control was included to rule out the presence of inhibitors of DNA amplification. The diagnostic value of the ompA nested PCR-EIA in comparison to cell culture and a 16S-rRNA based nested PCR was assessed in pharyngeal turkey swabs from 10 different farms experiencing respiratory disease. RESULTS: The sensitivity of the nested PCR-EIA was established at 0.1 infection forming units (IFU). Specificity was 100%. The ompA nested PCR-EIA was more sensitive than the 16S-rRNA based nested PCR and isolation, revealing 105 out of 200 (52.5%) positives against 13 and 74 for the latter two tests, respectively. Twenty-nine (23.8%) out of 122 ompA PCR-EIA negatives showed the presence of inhibitors of DNA amplification, although 27 of them became positive after diluting (1/10) the specimens in PCR buffer or after phenol-chloroform extraction and subsequent ethanol precipitation. CONCLUSION: The present study stresses the need for an internal control to confirm PCR true-negatives and demonstrates the high prevalence of chlamydiosis in Belgian turkeys and its potential zoonotic risk. The ompA nested PCR-EIA described here is a rapid, highly sensitive and specific diagnostic assay and will help to facilitate the diagnosis of Cp. psittaci infections in both poultry and man

Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n=144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(β)=1.20, p=0.060] and decreased levels of reduced glutathione (GSH) [exp(β)=0.55, p=0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(β)=0.83, exp(β)=0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(β)=1.73, p-value=0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.This research was supported in part by research grants from the European Union Commission (H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), from the Institute of Health Carlos III, supported by European Regional Development Fund/FEDER (FIS-PI13/02406, FISPI14/ 00067, FIS-PI16/01820, FIS-PI16/01812, FIS-PI16/01858 and FIS-PI17/01743), and from the Consejería de Salud, Junta de Andalucía (PS-0506-2016). Funding for the equipment used was provided by Velux Fonden, Augustinus Fonden and Svend Andersen Fonden. The authors thank Kirsten og Freddy Johansens Fond and the International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC, Rigshospitalet, Copenhagen University) for economic support. Dr. Juan Pedro Arrebola is under contract within Ramón y Cajal Program (Ministerio de Economía, Industria y Competitividad de España, RYC-2016-20155)

Parthenogenic Blastocysts Derived from Cumulus-Free In Vitro Matured Human Oocytes

Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis..Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer