Mechanical regulation of cancer cell apoptosis and autophagy: Roles of bone morphogenetic protein receptor, Smad1/5, and p38 MAPK

AbstractMechanical forces induced by interstitial fluid flow in and surrounding tissues and by blood/lymphatic flow in vessels may modulate cancer cell invasion and metastasis and anticancer drug delivery. Our previous study demonstrated that laminar flow-induced shear stress induces G2/M arrest in tumor cells. However, whether shear stress modulates final cell fate remains unclear. In this study, we investigated the role of flow-induced shear stress in modulating the survival of four human tumor cell lines, i.e., Hep3B hepatocarcinoma cells, MG63 osteosarcoma cells, SCC25 oral squamous carcinoma cells, and A549 carcinomic alveolar basal epithelial cells. Laminar shear stress (LSS) ranging from 0.5 to 12dyn/cm2 induced death of these four tumor cell lines. In contrast to LSS at 0.5dyn/cm2, oscillatory shear stress (OSS) at 0.5±4dyn/cm2 cannot induce cancer cell death. Both LSS and OSS had no effect on human normal hepatocyte, lung epithelial, and endothelial cells. Application of LSS to these four cell lines increased the percentage of cells stained positively for annexin V–FITC, with up-regulations of cleaved caspase-8, -9, and -3, and PARP. In addition, LSS also induced Hep3B cell autophagy, as detected by acidic vesicular organelle formation, LC3B transformation, and p62/SQSTM1 degradation. By transfecting with small interfering RNA, we found that the shear-induced apoptosis and autophagy are mediated by bone morphogenetic protein receptor type (BMPR)-IB, BMPR-specific Smad1 and Smad5, and p38 mitogen-activated protein kinase in Hep3B cells. Our findings provide insights into the molecular mechanisms by which shear stress induces apoptosis and autophagy in tumor cells

Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells

<p>Abstract</p> <p>Background</p> <p>Episodic cessation of airflow during sleep in patients with sleep apnea syndrome results in intermittent hypoxia (IH). Our aim was to investigate the effects of IH on cerebellar granule cells and to identify the mechanism of IH-induced cell death.</p> <p>Methods</p> <p>Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O₂concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio.</p> <p>Results</p> <p>According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus.</p> <p>Conclusions</p> <p>We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.</p

Mean structure and variability of the cold dome northeast of Taiwan

Author Posting. © The Oceanography Society, 2011. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 24 no. 4 (2011): 100–109, doi:10.5670/oceanog.2011.98.The "cold dome" off northeastern Taiwan is one of the distinctive oceanic features in the seas surrounding Taiwan. The cold dome is important because persistent upwelling makes the region highly biologically productive. This article uses historical data, recent observations, and satellite-observed sea surface temperatures (SST) to describe the mean structure and variability of the cold dome. The long-term mean position of the cold dome, using the temperature at 50 m depth as a reference, is centered at 25.625°N, 122.125°E. The cold dome has a diameter of approximately 100 km, and is maintained by cold ( 34.5) waters upwelled along the continental slope. The ocean currents around the cold dome, although weak, flow counterclockwise. The monsoon-driven winter intrusion of the Kuroshio current onto the East China Sea shelf intensifies the upwelling and carries more subsurface water up to the cold dome than during the summer monsoon season. On a shorter timescale, the cold dome's properties can be significantly modified by the passage of typhoons, which creates favorable physical conditions for short-term Kuroshio intrusions in summer. The surface expression of the cold dome viewed from satellite SST images is often not domelike but instead is an irregular shape with numerous filaments, and thus may contribute substantially to shelf/slope exchange. As a result of persistent upwelling, typhoon passage, and monsoon forcing, higher chlorophyll a concentrations, and thus higher primary productivity, are frequently observed in the vicinity of the cold dome.The National Science Council (NSC) of Taiwan sponsored this study under grant NSC98-2611-M-002-019-MY3. NSC supported C.-C. Chen under grant NSC98-2611-M-003-001-MY3

Observations of a freshwater pulse induced by Typhoon Morakot off the northern coast of Taiwan in August 2009

Author Posting. © Sears Foundation for Marine Research, 2013. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 71 (2013): 19-46, doi:10.1357/002224013807343452.In this paper we describe large-scale impacts from a typhoon on the circulation over the continental shelf and slope north of Taiwan. Typhoon Morakot was a category 2 tropical storm that landed in central Taiwan, but caused destruction primarily in southern Taiwan from Aug. 8–10, 2009. The typhoon brought record-breaking rainfall; approximately 3 m accumulated over four days in southern Taiwan. River discharge on the west coast of Taiwan increased rapidly from Aug. 6–7 and peaked on Aug. 8, yielding a total volume 27.2 km3 of freshwater discharged off the west coast of Taiwan over five days (Aug. 6–10). The freshwater mixed with ambient seawater, and was carried primarily by the northeastward-flowing Taiwan Strait current to the sea off the northern coast of Taiwan. Two joint surveys each measured the hydrography and current velocity in the Taiwan Strait and off the northeastern coast of Taiwan roughly one week and two and a half weeks after Morakot. The first survey observed an Ω-shaped freshwater pulse off the northern tip of Taiwan, in which the salinity was ∼1 lower than the climatological mean salinity. The freshwater pulse met the Kuroshio and formed a density front off the northeastern coast of Taiwan. The hydrographic data obtained in the second survey suggested that the major freshwater pulse left the sea off the northern and northeastern coasts of Taiwan, which may have been carried by the Kuroshio to the northeast. Biogeochemical sampling conducted after Morakot suggested that the concentrations of nutrients in the upper ocean off the northern coast of Taiwan increased remarkably compared with their normal values. A typhoon-induced biological bloom is attributed to the inputs both from the nutrient-rich river runoff and upwelling of the subsurface Kuroshio water.This study is supported by the National Science Council (NSC) of Taiwan under grant NSC98-2611-M-002-019-MY3. C.-C. Hung is supported by NSC under grant NSC100-2119-M- 110-003. LC was supported by ONR grant N00014-08-1-0557 and NOAA grant NA10OAR4320156

BOB-RED queue management for IEEE 802.15.4 wireless sensor networks

This study is aimed at exploring why many economists propose a transfer scheme and debt mutualisation for the Eurozone. This would equip the Eurozone with better tools to deal with an economic shock, like the 2010-2012 sovereign debt crisis, thus making it more financially stable. After the theoretical presentation, the study presents a unique institutional design with an EU Treasury that manages debt mutualisation and a transfer scheme as well as other competences that address other present economic challenges. Crucial to the study are the issues of moral hazard and adverse selection that arise when thinking of European economic integration.L’objectiu del treball és explorar la raó per la qual molts economistes proposen un sistema de transferències fiscals i la mutualització del deute a l’Eurozona. Així se la dotaria amb eines més efectives per pal·liar un xoc econòmic, com la crisi del deute sobirà del 2010-2012. A continuació, es presenta un disseny institucional únic d’un Tresor de l’Euro que gestionaria les competències esmentades (i d’altres) per combatre alguns dels reptes econòmics actuals. El risc moral i de selecció adversa, qüestions que sorgeixen en pensar la drecera que ha de prendre la integració econòmica Europea, són cabdals per aquest estudi

Roles of microRNAs in atherosclerosis and restenosis

Abstract Atherosclerosis is commonly appreciated to represent a chronic inflammatory response of the vascular wall, and its complications cause high mortality in patients. Angioplasty with stent replacement is commonly performed in patients with atherosclerotic disease. However, the restenosis usually has a high incidence rate in angioplasty patients. Although the pathophysiological mechanisms underlying atherosclerosis and restenosis have been well established, new signaling molecules that control the progress of these pathologies have continuously been discovered. MicroRNAs (miRs) have recently emerged as a novel class of gene regulators that work via transcriptional degradation and translational inhibition or activation. Over 30% of genes in the cell can be directly regulated by miRs. Thus, miRs are recognized as crucial regulators in normal development, physiology and pathogenesis. AIterations of miR expression profiles have been revealed in diverse vascular diseases. A variety of functions of vascular cells, such as cell differentiation, contraction, migration, proliferation and inflammation that are involved in angiogenesis, neointimal formation and lipid metabolism underlying various vascular diseases, have been found to be regulated by miRs. This review summarizes current research progress and knowledge on the roles of miRs in regulating vascular cell function in atherosclerosis and restenosis. These discoveries are expected to present opportunities for clinical diagnostic and therapeutic approaches in vascular diseases resulting from atherosclerosis and restenosis.</p

Comparing ozonation and biofiltration treatment of source water with high cyanobacteria-derived organic matter: the case of a water treatment plant followed by a small-scale water distribution system

[[abstract]]High cyanobacteria-derived dissolved organic carbon (DOC) in source water can cause drinking water quality to deteriorate, producing bad taste, odor, toxins, and possibly elevated levels of disinfection byproduct (DBP) precursors. Conventional water treatment processes do not effectively remove algal organic substances. In this study, rapid-sand-filtration effluent from a water treatment plant on Kinmen Island, where serious cyanobacterial blooms occurred, was used to evaluate the DOC- and DBP-removal efficiency of ozonation and/or biofiltration. To simulate a small-scale water distribution system following water treatment, 24 h simulated distribution system (SDS) tests were conducted. The following DBPs were analyzed: trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), and trichloronitromethane (TCNM). Applying biological activated-carbon filtration (BAC) on its own achieved the greatest reduction in SDS-DBPs. Ozonation alone caused adverse effects by promoting THM, HAA, and TCNM formation. Ozonation and BAC filtration yielded better DOC removal (51%) than BAC filtration alone (41%). Considering the cost of ozonation, we suggest that when treating high cyanobacterial organic matter in water destined for a small-scale water distribution system, BAC biofiltration alone could be an efficient, economical option for reducing DBP precursors. If DOC removal needs to be improved, preceding ozonation could be incorporated.[[notice]]補正完

BOB-RED queue management for IEEE 802.15.4 wireless sensor networks

<p>Abstract</p> <p>Multimedia services over resource constrained wireless sensor networks (WSNs) face a performance bottleneck issue from the gateway node to the sink node. Therefore, the queue management at the gateway node is crucial for diversified messages conveyed from the front nodes to the sink node. In this article, beacon order-based random early detection (BOB-RED) queue management is proposed. BOB-RED is a dynamic adaptation scheme based on adjusting beacon interval and superframe duration in the IEEE 802.15.4 MAC superframe accompanied with RED queue management scheme to increase the transmission efficiency of multimedia over WSNs. We focus on the performance improvement upon different traffic loads over WSNs. Evaluation metrics include end-to-end delay, packet delivery ratio, and energy consumption in IEEE 802.15.4 beacon enabled mode. Simulation results show that BOB-RED can effectively decrease end-to-end delay and energy consumption compared to the DropTail scheme.</p

Characteristics analysis for the flash flood-induced debris flow

Typhoon Haitang caused landfall on Taiwan during 15–21 July, 2005 and brought 2,279 mm of maximum cumulative rain with a maximum intensity of 176 mm/h. The torrential rain was mainly distributed from the central mountain range to southern Taiwan and triggered 222 slopeland-related hazards. Among the hazard events, there were 17 debris flows, 157 cases of traffic cut-off, three large-magnitude deep-seated landslides, and 10 villages isolated in the off-track mountainous areas. The debris flows initiated in southern Taiwan were associated with torrential rain, short channel length (<2 km), and small basin area (<3 km2), and were speculated to be induced by flash flood. These flash flood-induced debris flows have a higher rainfall intensity-duration threshold for initiation than in other areas. The deep-seated landslides, isolated villages due to traffic cut-off in off-track mountain areas, and recurrent hazards in areas affected by the ML 7.6 Chi-Chi earthquake in 1999 are characteristics of slopeland hazards in Taiwan in recent years. One of the most urgently needed mitigation strategies in response to slopeland hazards is the plan for enhancing self-rescue disaster resistance in off-track mountainous villages in Taiwan.17 page(s

Effects of Swimming Pool Conditions and Floor Types on White Roman Geese’s Physical Condition Scores and Behaviors in an Indoor Rearing System

Biosecurity problems, including the continual risk of avian influenza spread by wild birds, have severely affected traditional free-range waterfowl production systems. Regulations and techniques for indoor goose production require more considerations for animal welfare. This study investigated the effects of swimming pool conditions and different floor types on the physical condition scores and behaviors of indoor-reared White Roman geese. A total of 48 male and 48 female White Roman geese reared from the age of 15 to 84 days were randomly allocated to pens with or without a swimming pool and with either mud or perforated plastic floors. Providing a swimming pool improved geese’s eye and feather cleanliness and breast blister scores at the age of 84 days. Compared with geese reared on a mud floor, those reared on a perforated plastic floor had better feather cleanliness and higher breast blister scores at the age of 56 and 84 days. Providing a swimming pool to indoor-reared geese may reduce the proportion of abnormal behaviors, such as injurious feather pecking, by increasing water-related behaviors. This study suggests a more appropriate environment design for better balancing commercial goose production with animal welfare in an indoor rearing system