Maternal depletion of Piwi, a component of the RNAi system, impacts heterochromatin formation in Drosophila

A persistent question in epigenetics is how heterochromatin is targeted for assembly at specific domains, and how that chromatin state is faithfully transmitted. Stable heterochromatin is necessary to silence transposable elements (TEs) and maintain genome integrity. Both the RNAi system and heterochromatin components HP1 (Swi6) and H3K9me2/3 are required for initial establishment of heterochromatin structures in S. pombe. Here we utilize both loss of function alleles and the newly developed Drosophila melanogaster transgenic shRNA lines to deplete proteins of interest at specific development stages to dissect their roles in heterochromatin assembly in early zygotes and in maintenance of the silencing chromatin state during development. Using reporters subject to Position Effect Variegation (PEV), we find that depletion of key proteins in the early embryo can lead to loss of silencing assayed at adult stages. The piRNA component Piwi is required in the early embryo for reporter silencing in non-gonadal somatic cells, but knock-down during larval stages has no impact. This implies that Piwi is involved in targeting HP1a when heterochromatin is established at the late blastoderm stage and possibly also during embryogenesis, but that the silent chromatin state created is transmitted through cell division independent of the piRNA system. In contrast, heterochromatin structural protein HP1a is required for both initial heterochromatin assembly and the following mitotic inheritance. HP1a profiles in piwi mutant animals confirm that Piwi depletion leads to decreased HP1a levels in pericentric heterochromatin, particularly in TEs. The results suggest that the major role of the piRNA system in assembly of heterochromatin in non-gonadal somatic cells occurs in the early embryo during heterochromatin formation, and further demonstrate that failure of heterochromatin formation in the early embryo impacts the phenotype of the adult

Insulin signaling regulates neurite growth during ecdysone-dependent neuronal remodeling

The morphological rearrangement of neurons to accommodate new functions or activities is called "neuronal remodeling". Although neuronal remodeling is an important feature of nervous systems, the mechanisms governing the transition of neurons, from relatively stable states to more dynamic and differentiative remodeling states, are largely unknown. In holometabolous insects, there is a major transition from maintenance growth to organizational growth near the onset of metamorphosis, and these changes provide an unparalleled opportunity to explore the underlying mechanisms of neuronal remodeling. Many differentiated larval neurons are maintained throughout metamorphosis and undergo extensive remodeling, which involves the elimination of larval dendrites and axons (neurites) and the outgrowth and elaboration of adult-specific projections (Levine and Truman 1982; Brown, Cherbas et al. 2006). Here, I show that a metamorphosis-specific increase in insulin and insulin-like-growth factor signaling (IIS) promotes neuronal growth and axon branching after a long period of morphological stability during the larval stages. In a previous gain-of-function genetic screen, we found that overexpression of a negative effector in the IIS pathway, Forkhead box, sub-group O (FOXO), blocked the metamorphic growth of peptidergic neurons that secrete crustacean cardioactive peptide (CCAP) and bursicon. RNA interference (RNAi) and CCAP/bursicon cell-targeted expression of dominant negative constructs for other components of the IIS pathway [Insulin-like receptor (InR), Pi3K92E, Akt1, and S6K] also partially suppressed the growth of the CCAP/bursicon neuron somata and neurite arborization. In contrast, expression of wild-type or constitutively active forms of InR, Pi3K92E, Akt1, Rheb, and Target of rapamycin (TOR), as well as RNAi for negative regulators of the IIS pathway (PTEN and FOXO), stimulated overgrowth. Interestingly, InR displayed little effect on larval growth of the CCAP/bursicon neurons, but strong effects on the metamorphic outgrowth of these neurons. In addition, manipulations of IIS in a pan-peptidergic neuronal pattern revealed a general role in promoting organizational outgrowth of many neurons during metamorphosis. These results reveal that specific activation of IIS during metamorphosis facilitates renewed organizational growth in mature neurons. In order to further elucidate the molecular and cellular mechanisms governing IIS regulation of the metamorphic remodeling, I performed a genetic modifier screen to detect IIS-interacting genes. I screened 492 deficiency lines for modifiers of a foxo overexpression phenotype (wing expansion defects). A total of 14 deficiencies were confirmed as suppressors of foxo, and 19 were confirmed as enhancers. Two selected suppressors, Df(1)Exel6221 and Df(1)Exel6002, strongly reversed the effects of foxo on neuronal outgrowth. Df(1)Exel6221 also significantly rescued the phenotypes produced by expression of InRDN, suggesting that the gene(s) within Df(1)ExEL6221 might be involved in IIS-mediated growth during the neuronal remodeling process. The source of suppression in Df(1)Exel6002 was mapped to an individual locus, Su(z)2. Reduced expression of Su(z)2 by RNAi suppressed the effects of FOXO on neuronal outgrowth. Su(z)2 is a Zinc finger protein that belongs to the Drosophila Polycomb Group (PcG) protein family, the members of which function as negative regulators of transcription and chromatin modification (Brunk, Martin et al. 1991). This indicates that transcriptional regulation through chromatin modification by Su(z)2 may play an important role in reprogramming neuronal entry into the organizational growth phase, or in the execution of that growth program

A 100-m-Scale Modeling Study of a Gale Event on the Lee Side of a Long Narrow Mountain

In this study, a gale event that occurred on the lee side of a long narrow mountain was investigated, together with the associated mountain flows, using a realistic-case large-eddy simulation (LES) that is based on the Weather Research and Forecasting Model. The mountain is located on the southeastern Tibetan Plateau, where approximately 58 gales occur annually, mostly in the afternoons during the winter season. Benefitting from realistic topography and high horizontal resolution as fine as 111 m, the LES can replicate features similar to the wind fields observed during the gale period. Investigation of the early morning wind structure over the mountain revealed that weak inflows were blocked, reversed, and divided in the upstream area and that some weak lee waves, rotors, and two clear lee vortices were evident downstream. As the upstream wind accelerated and the boundary layer developed during the daytime, the lee waves became amplified with severe downslope wind and rotors. The interaction and coherent structure of the downslope wind, rotor, and vortices were investigated to show the severe wind distribution. The mountain drags associated with blocking and amplified lee waves are displayed to show the potential impact on the large-scale model. The linear lee-wave theory was adopted to explain the wave evolution during this event together with a discussion of the uncertainty around low-level nonlinear processes

GPU Accelerated High Intensity Ultrasound Acoustical Power Computation

International audienceThe simulation of the hepatocellular carcinoma therapy effects is often used for the intervention planning. As the physical-based model of the simulation is very time-consuming, the speed of this method becomes an obstacle during the clinical application simulation. In order to accelerate the simulation, a GPU-based (Graphic Processing Unit) acceleration method of the pressure field estimation is proposed in this paper. The results demonstrate that the proposed acceleration method can solve the time-consuming problem

Re-Expression of AKAP12 Inhibits Progression and Metastasis Potential of Colorectal Carcinoma In Vivo and In Vitro

Background: AKAP12/Gravin (A kinase anchor protein 12) is one of the A-kinase scaffold proteins and a potential tumor suppressor gene in human primary cancers. Our recent study demonstrated the highly recurrent loss of AKAP12 in colorectal cancer and AKAP12 reexpression inhibited proliferation and anchorage-independent growth in colorectal cancer cells, implicating AKAP12 in colorectal cancer pathogenesis. Methods: To evaluate the effect of this gene on the progression and metastasis of colorectal cancer, we examined the impact of overexpressing AKAP12 in the AKAP12-negative human colorectal cancer cell line LoVo, the single clone (LoVo-AKAP12) compared to mock-transfected cells (LoVo-CON). Results: pCMV6-AKAP12-mediated AKAP12 re-expression induced apoptosis (3 % to 12.7%, p,0.01), migration (89.667.5 cells to 31.064.1 cells, p,0.01) and invasion (82.765.2 cells to 24.763.3 cells, p,0.01) of LoVo cells in vitro compared to control cells. Nude mice injected with LoVo-AKAP12 cells had both significantly reduced tumor volume (p,0.01) and increased apoptosis compared to mice given AKAP12-CON. The quantitative human-specific Alu PCR analysis showed overexpression of AKAP12 suppressed the number of intravasated cells in vivo (p,0.01). Conclusion: These results demonstrate that AKAP12 may play an important role in tumor growth suppression and the survival of human colorectal cancer

Pathological Evidence Exploration in Deep Retinal Image Diagnosis

Though deep learning has shown successful performance in classifying the label and severity stage of certain disease, most of them give few evidence on how to make prediction. Here, we propose to exploit the interpretability of deep learning application in medical diagnosis. Inspired by Koch's Postulates, a well-known strategy in medical research to identify the property of pathogen, we define a pathological descriptor that can be extracted from the activated neurons of a diabetic retinopathy detector. To visualize the symptom and feature encoded in this descriptor, we propose a GAN based method to synthesize pathological retinal image given the descriptor and a binary vessel segmentation. Besides, with this descriptor, we can arbitrarily manipulate the position and quantity of lesions. As verified by a panel of 5 licensed ophthalmologists, our synthesized images carry the symptoms that are directly related to diabetic retinopathy diagnosis. The panel survey also shows that our generated images is both qualitatively and quantitatively superior to existing methods.Comment: to appear in AAAI (2019). The first two authors contributed equally to the paper. Corresponding Author: Feng L

Effect of herbaceous biomass and food waste addition in anaerobic digestion of sewage sludge

13301甲第4482号博士（学術）金沢大学博士論文要旨Abstract 要約Outlin

Effect of herbaceous biomass and food waste addition in anaerobic digestion of sewage sludge

13301甲第4482号博士（学術）金沢大学博士論文本文Ful

Gamifying Impromptu Speech for ESL/EFL Students

[EN] This paper outlines an impromptu speech activity entitled “Dented Helmet vs. Spambot” intended as part of any introductory public speaking course. The activity is designed to overcome specific affective and cognitive challenges of ESL/EFL students, in particular Chinese learners, and is inspired by the principles of gamification (Kapp, 2012) with core gaming elements such as “freedom to fail”, “rapid feedback”, and “storytelling”, The activity requires “Rory’s Story Cubes” (a set of nine six-sided dice designed to spark creativity) and a special set of slides. An exploratory assessment of the effectiveness of our proposed activity was conducted on a sample of Chinese EFL sophomores enrolled in an international branch campus of a U.S. university in China, with 81 students completing our questionnaire. Overall, our findings provided some initial support to the effectiveness of our activity in terms of strenghtening students’ ability to communicate orally “off the cuff”, promoting students’ understanding of the role of storytelling in effective presentations, fostering students’ understanding of the major organizational formats used in organizing speeches, and increasing students’ awareness of their nonverbal communication during oral presentations.Girardelli, D.; Barroero, P.; Gu, T. (2016). Gamifying Impromptu Speech for ESL/EFL Students. En 2nd. International conference on higher education advances (HEAD'16). Editorial Universitat Politècnica de València. 18-25. https://doi.org/10.4995/HEAD16.2015.2431OCS182