Melatonin receptor expression in the zebra finch brain and peripheral tissues

The circadian endocrine hormone melatonin plays a significant role in many physiological processes such as modulating sleep/wake cycle and oxidative stress. Melatonin is synthesised and secreted during the night by the pineal gland and released into the circulatory system. It binds to numerous membrane, cytosolic and nuclear receptors in the brain and peripheral organs. Three G-protein linked membrane receptors (Mel-1A, Mel-1B and Mel-1C) have been identified in numerous species. Considering the importance of this hormone and its receptors, this study looks at the location and rhythmicity of three avian melatonin receptors Mel-1A, Mel-1B and Mel-1C using reserve transcription-polymerase chain reaction (RT-PCR) mRNA analysis techniques. This study shows successful partial cloning of the three receptors and gene expression analysis revealed significant rhythms of the Mel-1A receptor in the cerebellum, diencephalon, tectum opticum, telencephalon, and retina. Significant rhythms where found in the diencephalon, pineal gland, retina, tectum opticum and cerebellum of the Mel-1B receptor whereas Mel-1C appeared not to be rhythmically expressed in brain tissues studied. Mel-1A, Mel-1B and Mel-1C receptor mRNA where also present in peripheral tissues showing tissue-specific expression patterns

Molecular roles of Myo1c function in lipid raft exocytosis.

Lipid rafts are highly dynamic membrane subdomains enriched in specific protein and lipid components that create specialized 'organizing' platforms essential for an array of important cellular functions. The role of lipid rafts in membrane trafficking involves the constant remodelling of the plasma membrane through membrane uptake and balanced exocytosis of intracellular membranes. Our lab has identified the first motor protein, myosin 1c (Myo1c) involved in driving the recycling of lipid-raft enriched membranes from the perinuclear recycling compartment to the cell surface. This newly discovered role for Myo1c in lipid raft exocytosis is crucial for cell spreading, migration and pathogen entry; key cellular processes that require cell surface expansion and plasticity. Here we present a model suggesting Myo1c's possible molecular functions in lipid raft recycling and discuss its wider implications for important cellular functions

Neuroprotective effects of Cerebrolysin in triple repeat Tau transgenic model of Pick's disease and fronto-temporal tauopathies.

BackgroundTauopathies are a group of neurodegenerative disorders with accumulation of three-repeat (3R) or four-repeat (4R) Tau. While 3R tau is found in Pick's disease and Alzheimer's disease (AD), 4R tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and AD. We have previously shown that Cerebrolysin™ (CBL), a neuropeptide mixture with neurotrophic effects, ameliorates the pathology in amyloid precursor protein transgenic (tg) mouse model of AD and 4R tau, however it is unclear if CBL ameliorates the deficits and neuropathology in the mouse model of Pick's disease over expressing 3R tau.ResultsMice expressing 3R tau (L266V and G272V mutations) under the mThy-1 promoter were treated with CBL in two separate groups, the first was 3 months old (treated for 3 months, IP) and the second was 6 months old (treated for 3 months, IP) at the start of the treatment. We found that although the levels of total 3R tau were unchanged, CBL reduced the levels of hyper-phosphorylated tau in both groups of mice. This was accompanied by reduced neurodegenerative pathology in the neocortex and hippocampus in both groups and by improvements in the behavioral deficits in the nest-building test and water maze in the 3-6 month group.ConclusionTaken together these results support the notion that CBL may be beneficial in other taupathy models by reducing the levels of aberrantly phosphorylated tau

Insights into the Genetic History of French Cattle from Dense SNP Data on 47 Worldwide Breeds

BACKGROUND: Modern cattle originate from populations of the wild extinct aurochs through a few domestication events which occurred about 8,000 years ago. Newly domesticated populations subsequently spread worldwide following breeder migration routes. The resulting complex historical origins associated with both natural and artificial selection have led to the differentiation of numerous different cattle breeds displaying a broad phenotypic variety over a short period of time. METHODOLOGY/PRINCIPAL FINDINGS: This study gives a detailed assessment of cattle genetic diversity based on 1,121 individuals sampled in 47 populations from different parts of the world (with a special focus on French cattle) genotyped for 44,706 autosomal SNPs. The analyzed data set consisted of new genotypes for 296 individuals representing 14 French cattle breeds which were combined to those available from three previously published studies. After characterizing SNP polymorphism in the different populations, we performed a detailed analysis of genetic structure at both the individual and population levels. We further searched for spatial patterns of genetic diversity among 23 European populations, most of them being of French origin, under the recently developed spatial Principal Component analysis framework. CONCLUSIONS/SIGNIFICANCE: Overall, such high throughput genotyping data confirmed a clear partitioning of the cattle genetic diversity into distinct breeds. In addition, patterns of differentiation among the three main groups of populations--the African taurine, the European taurine and zebus--may provide some additional support for three distinct domestication centres. Finally, among the European cattle breeds investigated, spatial patterns of genetic diversity were found in good agreement with the two main migration routes towards France, initially postulated based on archeological evidence

Computational Study of Evolutionary Selection Pressure on Rainbow Trout Estrogen Receptors

Molecular dynamics simulations were used to determine the binding affinities between the hormone 17-estradiol (E2) and different estrogen receptor (ER) isoforms in the rainbow trout, Oncorhynchus mykiss. Previous phylogenetic analysis indicates that a whole genome duplication prior to the divergence of ray-finned fish led to two distinct ER isoforms, ER and ER, and the recent whole genome duplication in the ancestral salmonid created two ER isoforms, ER and ER. The objective of our computational studies is to provide insight into the underlying evolutionary pressures on these isoforms. For the ER subtype our results show that E2 binds preferentially to ER over ER. Tests of lineage specific N/S ratios indicate that the ligand binding domain of the ER gene is evolving under relaxed selection relative to all other ER genes. Comparison with the highly conserved DNA binding domain suggests that ER may be undergoing neofunctionalization possibly by binding to another ligand. By contrast, both ER and ER bind similarly to E2 and the best fitting model of selection indicates that the ligand binding domain of all ER genes are evolving under the same level of purifying selection, comparable to ER

The Asco meteorite (1805): New petrographic description, chemical data, and classification

Abstract— We present magnetic measurements, chemical analyses, and petrographic observations of the poorly studied Asco historical meteorite fall (1805). These new data indicate that this meteorite has been previously misclassified as an L6 ordinary chondrite. Asco is reclassified as an H6 ordinary chondrite with shock stage S3. An interesting feature of this meteorite is the presence of chromite‐plagioclase assemblages with variable textures

Circadian phenotype composition is a major predictor of diurnal physical performance in teams

Team performance is a complex phenomenon involving numerous influencing factors including physiology, psychology, and management. Biological rhythms and the impact of circadian phenotype have not been studied for their contribution to this array of factors so far despite our knowledge of the circadian regulation of key physiological processes involved in physical and mental performance. This study involved 216 individuals from 12 different teams who were categorized into circadian phenotypes using the novel RBUB chronometric test. The composition of circadian phenotypes within each team was used to model predicted daily team performance profiles based on physical performance tests. Our results show that the composition of circadian phenotypes within teams is variable and unpredictable. Predicted physical peak performance ranged from 1.52pm to 8.59pm with performance levels fluctuating by up to 14.88% over the course of the day. The major predictor for peak performance time of day in a team is the occurrence of late circadian phenotypes. We conclude that circadian phenotype is a performance indicator in teams that allows new insight and a better understanding of team performance variation in the course of a day as often observed in different groupings of individuals

Wasta- Triadic Governance and Trust in Jordanian Business

Purpose This research analyses the trust building and collective-action functions of Wasta in Jordanian business. Design/methodology/approach This research analyses the collective-action function of Wasta in Jordanian business. By demonstrating the role of informal institutions and personal trust in economic cooperation, Wasta will be approached as a mechanism contributing to personal trust and reducing transaction costs. Wasta as a concept is introduced, and the historical development, its various functions and ethical ambiguity are discussed. Based on the review of Wasta-literature, a three-dimensional model of Wasta is presented. By connecting Wasta to the insights of new institutional economics and transaction cost economics a new perspective on Wasta as a potentially beneficial institution is provided. The trust-building function of Wasta is explored in detail by empirical analysis. The empirical section of this research is based on 28 interviews mostly conducted in Jordan. The sample consisted of two groups of respondentsone with 17 and the other with 11 interviewees. It analyses the role of personal trust in Jordanian business relations and identifies patterns of trust-building based on Wasta in business situations in which personal trust is required. Considering the important role of triadic governance as emerging in the interviews and the ethically ambiguous perception of Wasta in the current literature, a model based on game theory is developed to distinguish between harmful and beneficial categories of Wasta. Findings The interviews revealed that personal trust between business partners is considered vital for the success of a business-relationship, anticipating a perceived ineffectiveness of formal institutions. The cornerstone of personal trust-building is structural embeddedness set up through middlepersons and the availability of traditional mediation mechanisms. Two phases of a trust creation process have been identified. In the first stage individual trustworthiness is explored through third parties prior to entering into cooperation and joint ventures. Trust emergence in the second stage is based on the availability of an intervening middleperson (Waseet), providing normative pressure and mediation in case of a dispute. Both stages are connected as middlepersons establishing new business relations face some moral obligation in the event of opportunistic behaviour or defection of the trustee, to whom references have been given. Intercession and mediation as dimensions of Wasta are interrelated and embedded in a cultural narrative of indigenous Arab traditions serving as antecedents of trust. Besides the structural function of network closure and an intervening third party, the processes of mediation and intercession as a culturally embedded habitus serve as social capital in situations in which personal trust is required. Based on the interviews a conceptualisation of Wasta and a typology of trust in Jordanian business relations are provided. Considering the ethically ambiguous connotations of Wasta in public and scientific discourse, it will be argued that it is not Wasta as such that leads to harmful results but structural conditions depriving actors of the options of voice and exit. These findings provide new knowledge and put this analysis at the forefront of academic research in this field

Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion.

MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.This work was financially supported by the Wellcome Trust (F.B., D.A.T. and H.B.), the Deutsche Forschungsgemeinschaft Grant MA 1081/19–1 (D.J.M) and the Medical Research Council (F.B and C. K.-I.). The CIMR is in receipt of a strategic award from the Wellcome Trust (100140).This is the final published version. It first appeared at http://www.tandfonline.com/doi/abs/10.4161/15548627.2014.984272#.VNo0Gy6Qne4