Orbit Spaces of Gradient Vector Fields

We study orbit spaces of generalized gradient vector fields for Morse functions. Typically, these orbit spaces are non-Hausdorff. Nevertheless, they are quite structured topologically and are amenable to study. We show that these orbit spaces are locally contractible. We also show that the quotient map associated to each such orbit space is a weak homotopy equivalence and has the path lifting property.Comment: 16 pages, 4 figures; strengthened a main result (Corollary 3.5) and updated the introduction and the conclusio

Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia.

Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder. Patients have episodes that last 1 to 4 hours and are precipitated by alcohol, coffee, and stress. Previous research has shown that mutations in an uncharacterized gene on chromosome 2q33-q35 (which is termed PNKD) are responsible for PNKD. Here, we report the generation of antibodies specific for the PNKD protein and show that it is widely expressed in the mouse brain, exclusively in neurons. One PNKD isoform is a membrane-associated protein. Transgenic mice carrying mutations in the mouse Pnkd locus equivalent to those found in patients with PNKD recapitulated the human PNKD phenotype. Staining for c-fos demonstrated that administration of alcohol or caffeine induced neuronal activity in the basal ganglia in these mice. They also showed nigrostriatal neurotransmission deficits that were manifested by reduced extracellular dopamine levels in the striatum and a proportional increase of dopamine release in response to caffeine and ethanol treatment. These findings support the hypothesis that the PNKD protein functions to modulate striatal neuro-transmitter release in response to stress and other precipitating factors

Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development

The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex development. How Cdkn1c regulates corticogenesis is however not clear. To this end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous Cdkn1c function which at the mechanistic level mediates radial glial progenitor cell and nascent projection neuron survival. Strikingly, the growth-promoting function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting. Collectively, our results suggest that the Cdkn1c locus regulates cortical development through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally, our study highlights the importance to probe the relative contributions of cell intrinsic gene function and tissue-wide mechanisms to the overall phenotype

Knowledge and self-efficacy among healthcare providers towards novel tobacco products in Japan

Several new tobacco products, including e-cigarettes and heated tobacco products (HTPs), have become highly prevalent in Japan. As safety data continues to evolve, healthcare providers are considered important sources for product use, yet little is known about provider knowledge or self-efficacy to counsel patient about novel tobacco product use. This cross-sectional study used data from a Japanese Association of Smoking Control Science (JASCS) online survey of physicians, pharmacists, nurses, and public health practitioners (N = 277) to assess provider knowledge of novel tobacco products and self-efficacy to counsel patients about product use. Correlates of knowledge and self-efficacy were also assessed. More than half the sample had received previous training in treating tobacco use, but 62% of respondents had no knowledge of HTPs; 80% of respondents indicated that they occasionally or always provide smoking cessation support. Overall knowledge of HTPs was low (41.4% correct) with higher knowledge for HTPs containing nicotine (89% correct) vs. HTPs emitting no carbon monoxide (25%). Self-efficacy to counsel patients about novel tobacco products was low on a scale ranging from 10 to 70 (Mean = 31.2; Standard Deviation = 16.7). Greater knowledge of HTPs was associated with male gender, higher rates of training at JASCS and previous learning about HTPs at JASCS. (p < 0.05). The results suggested that healthcare providers' knowledge and self-efficacy regarding novel tobacco products remains low in Japan, but additional training may improve it

A single origin of the photosynthetic organelle in different Paulinella lineages

<p>Abstract</p> <p>Background</p> <p>Gaining the ability to photosynthesize was a key event in eukaryotic evolution because algae and plants form the base of the food chain on our planet. The eukaryotic machines of photosynthesis are plastids (e.g., chloroplast in plants) that evolved from cyanobacteria through primary endosymbiosis. Our knowledge of plastid evolution, however, remains limited because the primary endosymbiosis occurred more than a billion years ago. In this context, the thecate "green amoeba" <it>Paulinella chromatophora </it>is remarkable because it very recently (i.e., minimum age of ≈ 60 million years ago) acquired a photosynthetic organelle (termed a "chromatophore"; i.e., plastid) <it>via </it>an independent primary endosymbiosis involving a <it>Prochlorococcus </it>or <it>Synechococcus</it>-like cyanobacterium. All data regarding <it>P. chromatophora </it>stem from a single isolate from Germany (strain M0880/a). Here we brought into culture a novel photosynthetic <it>Paulinella </it>strain (FK01) and generated molecular sequence data from these cells and from four different cell samples, all isolated from freshwater habitats in Japan. Our study had two aims. The first was to compare and contrast cell ultrastructure of the M0880/a and FK01 strains using scanning electron microscopy. The second was to assess the phylogenetic diversity of photosynthetic <it>Paulinella </it>to test the hypothesis they share a vertically inherited plastid that originated in their common ancestor.</p> <p>Results</p> <p>Comparative morphological analyses show that <it>Paulinella </it>FK01 cells are smaller than M0880/a and differ with respect to the number of scales per column. There are more distinctive, multiple fine pores on the external surface of FK01 than in M0880/a. Molecular phylogenetic analyses using multiple gene markers demonstrate these strains are genetically distinct and likely comprise separate species. The well-supported monophyly of the <it>Paulinella chromatophora </it>strains analyzed here using plastid-encoded 16S rRNA suggests strongly that they all share a common photosynthetic ancestor. The strain M0880/a is most closely related to Japanese isolates (Kanazawa-1, -2, and Kaga), whereas FK01 groups closely with a Kawaguchi isolate.</p> <p>Conclusion</p> <p>Our results indicate that <it>Paulinella chromatophora </it>comprises at least two distinct evolutionary lineages and likely encompasses a broader taxonomic diversity than previously thought. The finding of a single plastid origin for both lineages shows these taxa to be valuable models for studying post-endosymbiotic cell and genome evolution.</p

Physical and Radiative Characteristics and Long Term Variability of the Okhotsk Sea Ice Cover

Much of what we know about the large scale characteristics of the Okhotsk Sea ice cover comes from ice concentration maps derived from passive microwave data. To understand what these satellite data represents in a highly divergent and rapidly changing environment like the Okhotsk Sea, we analyzed concurrent satellite, aircraft, and ship data and characterized the sea ice cover at different scales from meters to tens of kilometers. Through comparative analysis of surface features using co-registered data from visible, infrared and microwave channels we evaluated how the general radiative and physical characteristics of the ice cover changes as well as quantify the distribution of different ice types in the region. Ice concentration maps from AMSR-E using the standard sets of channels, and also only the 89 GHz channel for optimal resolution, are compared with aircraft and high resolution visible data and while the standard set provides consistent results, the 89 GHz provides the means to observe mesoscale patterns and some unique features of the ice cover. Analysis of MODIS data reveals that thick ice types represents about 37% of the ice cover indicating that young and new ice represent a large fraction of the lice cover that averages about 90% ice concentration, according to passive microwave data. A rapid decline of -9% and -12 % per decade is observed suggesting warming signals but further studies are required because of aforementioned characteristics and because the length of the ice season is decreasing by only 2 to 4 days per decade

Physical and Radiative Characteristic and Long-term Variability of the Okhotsk Sea Ice Cover

Much of what we know about the large scale characteristics of the Okhotsk Sea ice cover has been provided by ice concentration maps derived from passive microwave data. To understand what satellite data represent in a highly divergent and rapidly changing environment like the Okhotsk Sea, we take advantage of concurrent satellite, aircraft, and ship data acquired on 7 February and characterized the sea ice cover at different scales from meters to hundreds of kilometers. Through comparative analysis of surface features using co-registered data from visible, infrared and microwave channels we evaluated the general radiative and physical characteristics of the ice cover as well as quantify the distribution of different ice types in the region. Ice concentration maps from AMSR-E using the standard sets of channels, and also only the 89 GHz channel for optimal resolution, are compared with aircraft and high resolution visible data and while the standard set provides consistent results, the 89 GHz provides the means to observe mesoscale patterns and some unique features of the ice cover. Analysis of MODIS data reveals that thick ice types represents about 37% of the ice cover indicating that young and new ice types represent a large fraction of the ice cover that averages about 90% ice concentration according to passive microwave data. These results are used to interpret historical data that indicate that the Okhotsk Sea ice extent and area are declining at a rapid rate of about -9% and -12 % per decade, respectively

Embryonal subregion-derived stromal cell lines from novel temperature-sensitive SV40 T antigen transgenic mice support hematopoiesis

Throughout life, the hematopoietic system requires a supportive microenvironment that allows for the maintenance and differentiation of hematopoietic stem cells (HSC). To understand the cellular interactions and molecules that provide these functions, investigators have previously established stromal cell lines from the late gestational stage and adult murine hematopoietic microenvironments. However, the stromal cell microenvironment that supports the emergence, expansion and maintenance of HSCs during mid-gestational stages has been largely unexplored. Since several tissues within the mouse embryo are known to harbor HSCs (i.e. aortagonads-mesonephros, yolk sac, liver), we generated numerous stromal cell clones from these mid-gestational sites. Owing to the limited cell numbers, isolations were performed with tissues from transgenic embryos containing the ts SV40 Tag gene (tsA58) under the transcriptional control of constitutive and ubiquitously expressing promoters. We report here that the growth and cloning efficiency of embryonic cells (with the exception of the aorta) is increased in the presence of the tsA58 transgene. Furthermore, our results show that the large panel of stromal clones isolated from the different embryonal subregions exhibit heterogeneity in their ability to promote murine and human hematopoietic differentiation. Despite our findings of heterogeneity in hematopoietic growth factor gene expression profiles, high-level expression of some factors may influence hematopoietic differentiation. Interestingly, a few of these stromal clones express a recently described chordin-like protein, which is an inhibitor of bone morphogenic proteins and is preferentially expressed in cells of the mesenchymal lineage