Cod1p/Spf1p is a P-type ATPase involved in ER function and Ca2+ homeostasis

The internal environment of the ER is regulated to accommodate essential cellular processes, yet our understanding of this regulation remains incomplete. Cod1p/Spf1p belongs to the widely conserved, uncharacterized type V branch of P-type ATPases, a large family of ion pumps. Our previous work suggested Cod1p may function in the ER. Consistent with this hypothesis, we localized Cod1p to the ER membrane. The cod1Δ mutant disrupted cellular calcium homeostasis, causing increased transcription of calcium-regulated genes and a synergistic increase in cellular calcium when paired with disruption of the Golgi apparatus–localized Ca2+ pump Pmr1p. Deletion of COD1 also impaired ER function, causing constitutive activation of the unfolded protein response, hypersensitivity to the glycosylation inhibitor tunicamycin, and synthetic lethality with deletion of the unfolded protein response regulator HAC1. Expression of the Drosophila melanogaster homologue of Cod1p complemented the cod1Δ mutant. Finally, we demonstrated the ATPase activity of the purified protein. This study provides the first biochemical characterization of a type V P-type ATPase, implicates Cod1p in ER function and ion homeostasis, and indicates that these functions are conserved among Cod1p's metazoan homologues

Modeling Concept Combinations in a Quantum-theoretic Framework

We present modeling for conceptual combinations which uses the mathematical formalism of quantum theory. Our model faithfully describes a large amount of experimental data collected by different scholars on concept conjunctions and disjunctions. Furthermore, our approach sheds a new light on long standing drawbacks connected with vagueness, or fuzziness, of concepts, and puts forward a completely novel possible solution to the 'combination problem' in concept theory. Additionally, we introduce an explanation for the occurrence of quantum structures in the mechanisms and dynamics of concepts and, more generally, in cognitive and decision processes, according to which human thought is a well structured superposition of a 'logical thought' and a 'conceptual thought', and the latter usually prevails over the former, at variance with some widespread beliefsComment: 5 pages. arXiv admin note: substantial text overlap with arXiv:1311.605

Symmetry, bifurcation and stacking of the central configurations of the planar 1+4 body problem

In this work we are interested in the central configurations of the planar 1+4 body problem where the satellites have different infinitesimal masses and two of them are diametrically opposite in a circle. We can think this problem as a stacked central configuration too. We show that the configuration are necessarily symmetric and the other sattelites has the same mass. Moreover we proved that the number of central configuration in this case is in general one, two or three and in the special case where the satellites diametrically opposite have the same mass we proved that the number of central configuration is one or two saying the exact value of the ratio of the masses that provides this bifurcation.Comment: 9 pages, 2 figures. arXiv admin note: text overlap with arXiv:1103.627

Southward propagating auroral structure in meso-micro scale obtained from ground-based multiple observations at Poker Flat Research Range

第3回極域科学シンポジウム/第36回極域宙空圏シンポジウム 11月26日（月）、27日（火） 国立極地研究所 2階ラウン

Euler configurations and quasi-polynomial systems

In the Newtonian 3-body problem, for any choice of the three masses, there are exactly three Euler configurations (also known as the three Euler points). In Helmholtz' problem of 3 point vortices in the plane, there are at most three collinear relative equilibria. The "at most three" part is common to both statements, but the respective arguments for it are usually so different that one could think of a casual coincidence. By proving a statement on a quasi-polynomial system, we show that the "at most three" holds in a general context which includes both cases. We indicate some hard conjectures about the configurations of relative equilibrium and suggest they could be attacked within the quasi-polynomial framework.Comment: 21 pages, 6 figure

Gene response profiles for Daphnia pulex exposed to the environmental stressor cadmium reveals novel crustacean metallothioneins

<p>Abstract</p> <p>Background</p> <p>Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species <it>Daphnia pulex</it>, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene transcription that suggest their biological roles and their potentially toxicological features in responding to this important environmental contaminant.</p> <p>Results</p> <p>Our microarray identified genes reported in the literature to be regulated in response to cadmium exposure, suggested functional attributes for genes that share no sequence similarity to proteins in the public databases, and pointed to genes that are likely members of expanded gene families in the <it>Daphnia </it>genome. Genes identified on the microarray also were associated with cadmium induced phenotypes and population-level outcomes that we experimentally determined. A subset of genes regulated in response to cadmium exposure was independently validated using quantitative-realtime (Q-RT)-PCR. These microarray studies led to the discovery of three genes coding for the metal detoxication protein metallothionein (MT). The gene structures and predicted translated sequences of <it>D. pulex </it>MTs clearly place them in this gene family. Yet, they share little homology with previously characterized MTs.</p> <p>Conclusion</p> <p>The genomic information obtained from this study represents an important first step in characterizing microarray patterns that may be diagnostic to specific environmental contaminants and give insights into their toxicological mechanisms, while also providing a practical tool for evolutionary, ecological, and toxicological functional gene discovery studies. Advances in <it>Daphnia </it>genomics will enable the further development of this species as a model organism for the environmental sciences.</p

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS