Shimanto geosyncline and Kuroshio paleoland

The late Mesozoic to early Neogene geosyncline in the Outer zone of Southwest Japan has been studied in detail in the Kii Peninsula by the Research Group for the Shimanto Geosyncline. The existence of the Kuroshio Paleoland to the south of the geosyncline was inferred by various sedimentologic evidences. The Shimanto belt in the Kii Peninsula is divided from north to south into three zones of Cretaceous, Eocene and Oligocene to lower Miocene. In these belts thick geosynclinal sediments were accumulated showing coarsening upward. The southward migration of the basin occurred in Cretaceous/Eocene, Eocene/Oligocene, and in early Miocene. In the present paper the reconstruction of paleogeography of the Shimanto geosyncline was attempted and the Kuroshio Paleoland was discussed in relation to the geohistory of the Philippine Sea. In spite of the detailed geologic survey in the Kii Peninsula there is no evidence of large exotic blocks nor tectonic mélanges, and this does not support the plate tectonic model ofthe Pacific-type orogeny for the Shimanto belt.ArticleJournal of Physics of the Earth. 26(suppl):357-366 (1978)journal articl

Identification of candidate anti-cancer molecular mechanisms of compound kushen injection using functional genomics

Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 human breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1 and 2 mg/mL total alkaloids), and the effect of CKI on cell proliferation and apoptosis were measured using XTT and Annexin V/Propidium Iodide staining assays respectively. Transcriptome data of cells treated with CKI or 5-Fluorouracil (5-FU) for 24 and 48 hours were subsequently acquired using high-throughput Illumina RNA-seq technology. In this report we show that CKI inhibited MCF-7 cell proliferation and induced apoptosis in a dose-dependent fashion. We integrated and applied a series of transcriptome analysis methods, including gene differential expression analysis, pathway over-representation analysis, de novo identification of long non-coding RNAs (lncRNA) as well as co-expression network reconstruction, to identify candidate anti-cancer molecular mechanisms of CKI. Multiple pathways were perturbed and the cell cycle was identified as the potential primary target pathway of CKI in MCF-7 cells. CKI may also induce apoptosis in MCF-7 cells via a p53 independent mechanism. In addition, we identified novel lncRNAs and showed that many of them might be expressed as a response to CKI treatment.Zhipeng Qu, Jian Cui, Yuka Harata-Lee, Thazin Nwe Aung, Qianjin Feng, Joy M. Raison, Robert Daniel Kortschak, David L. Adelso

SHIMANTO GEOSYNCLINE AND KUROSHIO PALEOLAND

The late Mesozoic to early Neogene geosyncline in the Outer zone of Southwest Japan has been studied in detail in the Kii Peninsula by the Research Group for the Shimanto Geosyncline. The existence of the Kuroshio Paleoland to the south of the geosyncline was inferred by various sedimentologic evidences. The Shimanto belt in the Kii Peninsula is divided from north to south into three zones of Cretaceous, Eocene and Oligocene to lower Miocene. In these belts thick geosynclinal sediments were accumulated showing coarsening upward. The southward migration of the basin occurred in Cretaceous/Eocene, Eocene/Oligocene, and in early Miocene. In the present paper the reconstruction of paleogeography of the Shimanto geosyncline was attempted and the Kuroshio Paleoland was discussed in relation to the geohistory of the Philippine Sea. In spite of the detailed geologic survey in the Kii Peninsula there is no evidence of large exotic blocks nor tectonic mélanges, and this does not support the plate tectonic model ofthe Pacific-type orogeny for the Shimanto belt.ArticleJournal of Physics of the Earth. 26(suppl):357-366 (1978)journal articl

Neutrino oscillation experiments and limits on lepton-number and lepton-flavor violating processes

Using a three neutrino framework we investigate bounds for the effective Majorana neutrino mass matrix. The mass measured in neutrinoless double beta decay is its (11) element. Lepton-number and -flavor violating processes sensitive to each element are considered and limits on branching ratios or cross sections are given. Those processes include $\mu^- e^+$ conversion, $K^+ \to \pi^- \mu^+ \mu^+$ or recently proposed high-energy scattering processes at HERA. Including all possible mass schemes, the three solar solutions and other allowed possibilities, there is a total of 80 mass matrices. The obtained indirect limits are up to 14 orders of magnitude more stringent than direct ones. It is investigated how neutrinoless double beta decay may judge between different mass and mixing schemes as well as solar solutions. Prospects for detecting processes depending on elements of the mass matrix are also discussed.Comment: 16 pages, 2 figure

Ultrastructural and functional fate of recycled vesicles in hippocampal synapses

Efficient recycling of synaptic vesicles is thought to be critical for sustained information transfer at central terminals. However, the specific contribution that retrieved vesicles make to future transmission events remains unclear. Here we exploit fluorescence and time-stamped electron microscopy to track the functional and positional fate of vesicles endocytosed after readily releasable pool (RRP) stimulation in rat hippocampal synapses. We show that most vesicles are recovered near the active zone but subsequently take up random positions in the cluster, without preferential bias for future use. These vesicles non-selectively queue, advancing towards the release site with further stimulation in an actin-dependent manner. Nonetheless, the small subset of vesicles retrieved recently in the stimulus train persist nearer the active zone and exhibit more privileged use in the next RRP. Our findings reveal heterogeneity in vesicle fate based on nanoscale position and timing rules, providing new insights into the origins of future pool constitution

A preferentially segregated recycling vesicle pool of limited size supports neurotransmission in native central synapses

At small central synapses, efficient turnover of vesicles is crucial for stimulus-driven transmission, but how the structure of this recycling pool relates to its functional role remains unclear. Here we characterize the organizational principles of functional vesicles at native hippocampal synapses with nanoscale resolution using fluorescent dye labeling and electron microscopy. We show that the recycling pool broadly scales with the magnitude of the total vesicle pool, but its average size is small (∼45 vesicles), highly variable, and regulated by CDK5/calcineurin activity. Spatial analysis demonstrates that recycling vesicles are preferentially arranged near the active zone and this segregation is abolished by actin stabilization, slowing the rate of activity-driven exocytosis. Our approach reveals a similarly biased recycling pool distribution at synapses in visual cortex activated by sensory stimulation in vivo. We suggest that in small native central synapses, efficient release of a limited pool of vesicles relies on their favored spatial positioning within the termina

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation

Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in Xenopus results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development

Fractional deletion of Compound Kushen Injection indicates cytokine signaling pathways are critical for its perturbation of the cell cycle

Published online: 02 October 2019We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.T. N . Aung, S. Nourmohammadi, Z. Qu, Y. Harata-Lee, J. Cui, H. Y. Shen, A. J. Yool, T. Pukala, Hong Du, R. D. Kortschak, W. Wei, D. L. Adelso

Actin: its cumbersome pilgrimage through cellular compartments

In this article, we follow the history of one of the most abundant, most intensely studied proteins of the eukaryotic cells: actin. We report on hallmarks of its discovery, its structural and functional characterization and localization over time, and point to present days’ knowledge on its position as a member of a large family. We focus on the rather puzzling number of diverse functions as proposed for actin as a dual compartment protein. Finally, we venture on some speculations as to its origin