Let it snow, says a happy Valley

first_imgA spell of heavy and widespread snowfall in the plains and upper reaches of the Kashmir Valley on Friday uplifted the mood here. In contrast to grim, violence-related pictures and posts, hundreds of local netizens, for a change, took to social media to live-stream snowfall or post selfies.The entire Kashmir valley, including capital Srinagar, received snowfall in the afternoon on Friday, as predicted by the Meteorological Department. As more snow fell, locals took to social media platforms to post videos of dancing kids, images of snowmen, and live-streamed driving through snow-clogged roads.Former chief minister and National Conference vice president Omar Abdullah also took to the Twitter to express his happiness. “Fresh snow is always gorgeous. It’s time to go back inside, leaving just footprints in the snow,” wrote Mr. Abdullah, as he uploaded his pictures with snow in the backdrop, and a video.Srinagar received the season’s second snowfall on Friday. Tourist hotspots of Gulmarg and Pahalgam recorded several feet of snowfall. “Weather will remain wet till January 6. Visibility will improve after the wet spell ends. Day temperature will also improve,” said Deputy Director, Met. Dept., Dr. Mukhtar Ahmad. Avalanche warning Snowfall did, however, play spoilsport for travellers as the Srinagar-Jammu and Srinagar-Poonch highways were closed “due to slippery road conditions and fears of landslides.” The Srinagar airport cancelled all flights scheduled in the afternoon,. An avalanche warning has been issued for all vulnerable areas of Anantnag, Kulgam, Budgam, Baramulla, Kupwara, Bandipora, Ganderbal, Kargil and Leh.last_img read more

Read More

Beau Belga not slowing down despite trade rumors

first_imgLATEST STORIES Garcia addresses trade rumors, says he’s good terms with his players Globe Business launches leading cloud-enabled and hardware-agnostic conferencing platform in PH AFP official booed out of forum Trending Articles PLAY LIST 00:50Trending Articles02:49Robredo: True leaders perform well despite having ‘uninspiring’ boss01:44Philippines marks anniversary of massacre with calls for justice01:29Police teams find crossbows, bows in HK university01:35Panelo suggests discounted SEA Games tickets for students02:42PH underwater hockey team aims to make waves in SEA Games01:19Fire erupts in Barangay Tatalon in Quezon City Read Next “If they want to trade me, I can’t do anything about it, but as of now, I’m with Rain or Shine and I need to play well for them.”Belga, along with Jericho Cruz and Raymond Almazan, are in the middle of trade rumors supposedly stemming from their disconnect over how coach Caloy Garcia is running the team.FEATURED STORIESSPORTSWATCH: Drones light up sky in final leg of SEA Games torch runSPORTSLillard, Anthony lead Blazers over ThunderSPORTSMalditas save PH from shutoutBut amid all talks, Belga was at his usual self, finishing with a double-double of 13 points, 13 rebounds, and three assists in the victory.It was the Sorsogon native’s way of staying professional knowing that as long as he’s wearing a Rain or Shine jersey, he has a responsibility to meet for the tea. “I’m with Rain or Shine as of now and I need to play because the bosses in Rain or Shine are the ones who are providing food for my family,” he said.Belga was the lone player involved in those trade talks who was willing to speak to the media. Jericho Cruz excused himself from the press, while Raymond Almazan quickly left the venue after the game. MOST READ View commentscenter_img Photo by Tristan Tamayo/ INQUIRER.netBeau Belga maintained that he has no say on whether Rain or Shine decides to trade him or any other player away.“Those things are already beyond our control,” he said in Filipino after the Elasto Painters’ 90-84 victory over Meralco on Friday.ADVERTISEMENT NEXT BLOCK ASIA 2.0 introduces GURUS AWARDS to recognize and reward industry influencers Typhoon Kammuri accelerates, gains strength en route to PH Brace for potentially devastating typhoon approaching PH – NDRRMC John Lloyd Cruz a dashing guest at Vhong Navarro’s wedding 2 ‘newbie’ drug pushers fall in Lucena sting Don’t miss out on the latest news and information. Slow and steady hope for near-extinct Bangladesh tortoiseslast_img read more

Read More

Layoff RoundUp Entrepreneur Forbes More …

first_imgIt’s a battlefield out there. Yesterday, b-to-b publisher Cygnus Business Media laid off 30 staffers, or about 6 percent of its workforce, and suspended publication of two photography titles.In terms of layoff/cutback stories, that was just the tip of the iceberg.Rumors surfaced late Tuesday about massive editorial layoffs at Irvine, California-based Entrepreneur Media. Two FOLIO: requests for comment have gone unanswered, but a knowledgeable source tells me that eight editorial staffers—including executive editor Charlotte Jensen and managing editor Mike Werling—have been cut. If that’s true, a quick count of editorial names on the masthead indicates that 15 print and online editorial employees remain—including a copy editor, a research editor, a listings assistant and two interns. There aren’t many people left to write the magazine. There also have been rumors that Forbes Media has started a second round of layoffs, this time letting go more than 50 people. My e-mail about the cuts was bounced from spokesperson to spokesperson and I never received an official response. Forbes announced a restructuring in November that resulted in 43 layoffs.The rumors hit b-to-b publishing, too. Sources told me today that Milo Media—which saw six staffers, including several publishers, walk out last week to form their own, competing publishing company—has closed down altogether. Phone calls and e-mails to president Mike Domke have not been returned.I also received a tip that Randolph, New Jersey-based Edgell Communications slashed employee salaries by 10 percent company-wide. That, it turns out, was true. “As consistent with Edgell’s operating philosophy, particularly over this recent downturn, the salary reduction was a proactive decision based on the high degree of uncertainty in the market,” a spokesperson wrote in an e-mail. “Our revenue forecasting—even over several months—has become increasingly unreliable.” Edgell, which reorganized late last year, said no layoffs were associated with the salary cuts.Even as I’m writing this, I’ve stumbled upon more rumors of layoffs and closings.It’s a tough time to be in magazine publishing. Sometimes it seems all you can do is put on your helmet and let the shrapnel fall.last_img read more

Read More

IPL 2019 Mumbai Indians preview and SWOT analysis Rohit to turn hitman

first_img Mumbai Indians with their IPL trophyIANSMumbai has the world’s best death bowler in their ranks in Jasprit Bumrah and this time, he will have Malinga for company. The Sri Lankan has made a comeback to limited overs cricket for his nation and his looking fit. The master and apprentice can team up to completely choke out the opposition in the final overs.   WeaknessesThe team lacks a quality spinner. Mayank Markande started well last season but soon the batsmen figured him out and he was rendered ineffective. The franchise did not address this issue in the auctions which may worry them on pitches like the ones in Delhi and Chennai. The other spin bowling option is Anukul Roy but given the abundance of all-rounders already present, the 20-year-old will find it difficult to get a game. There are a few players seemingly past their prime in the squad. If they are not performing well, it will be difficult to include them in the team and asking seasoned campaigners like Malinga, Yuvraj or Pollard to sit on the bench might be a challenge. Read: Predicted playing XIsOpportunities A team of Mumbai Indians’ pedigree will always be gunning for the championship. This IPL affords them the opportunity to race ahead of CSK and become the most successful team in the history of the competition. The team certainly has the firepower to do so and if the players can play up to potential, they can go very deep in the tournament. Rohit Sharma has not been in great form of late and thus he can go back to opening the batting to get in scoring touch ahead of the World Cup. For Hardik Pandya, it is the time to get back into prime fitness and also score some runs with the bat apart from honing his death bowling skills.  Threats If the big guns like Yuvraj and Pollard do not fire, it will be extremely difficult to ask them to sit out given their reputation and achievements. This may affect the morale of the team which is not ideal for a tournament such as the IPL where games come thick and fast.  Mumbai Indians had a poor season in the 2018 edition of the Indian Premier League and will be extremely eager to return to their usual ways by securing a top-four finish. They, along with, Chennai Super Kings are the only teams to have won the IPL on three separate occasions. The franchise made some interesting buys in the auction as they bought back the services of Lasith Malinga and has also added Yuvraj Singh to their squad. They have also added to their wicketkeeping option by roping in Quinton de Kock. Here’s taking a look at Mumbai India’s strengths, weaknesses, opportunities and threats. Strengths Mumbai Indians has one of the strongest batting lineups in the tournament and it is packed from top to bottom. At the top, Suryakumar Yadav and Quinton de Kock will accompany Rohit Sharma while the middle order has Kieron Pollard, the Pandya brothers and Yuvraj Singh. They have a strong finisher in Ben Cutting. Close File photo of Mumbai Indians all-rounder Hardik Pandya.IANSThe travelling schedule in the IPL is pretty hectic and given the stakes of all the investors, the top players are expected to play every game. This is not ideal for someone like Hardik Pandya who has been facing problems with his back. Especially with the World Cup drawing near, he has to balance his workload, else India might face a problem with the team’s balance in the quadrennial event.  Mumbai Indians are favorites for IPL 2018 glory IBTimes VideoRelated VideosMore videos Play VideoPauseMute0:06/0:44Loaded: 0%0:06Progress: 0%Stream TypeLIVE-0:38?Playback Rate1xChaptersChaptersDescriptionsdescriptions off, selectedSubtitlessubtitles settings, opens subtitles settings dialogsubtitles off, selectedAudio Trackdefault, selectedFullscreenThis is a modal window.Beginning of dialog window. Escape will cancel and close the window.TextColorWhiteBlackRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentBackgroundColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentTransparentWindowColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyTransparentSemi-TransparentOpaqueFont Size50%75%100%125%150%175%200%300%400%Text Edge StyleNoneRaisedDepressedUniformDropshadowFont FamilyProportional Sans-SerifMonospace Sans-SerifProportional SerifMonospace SerifCasualScriptSmall CapsReset restore all settings to the default valuesDoneClose Modal DialogEnd of dialog window. COPY LINKAD Loading … Squad Rohit Sharma (C), Hardik Pandya, Jasprit Bumrah, Krunal Pandya, Ishan Kishan (WK), Suryakumar Yadav, Mayank Markande, Rahul Chahar, Anukul Roy, Siddhesh Lad, Aditya Tare, Kieron Pollard, Ben Cutting, Mitchell McClenaghan, Adam Milne, Jason Behrendorff, Evin Lewis, Quinton de Kock (WK), Lasith Malinga, Anmolpreet Singh, Barinder Sran, Pankaj Jaiswal, Rasikh Dar, Yuvraj Singhlast_img read more

Read More

Khaleda goes to HC challenging EC

first_imgBNP chairperson Khaleda Zia. Prothom Alo File PhotoBNP chairperson Khaleda Zia filed a writ petition with the High Court challenging the legality of the election commission’s decision that rejected all her three nominations for contesting the 30 December election, reports UNB.Lawyer Nowshad Jamin, on behalf of Khaleda Zia, filed the petition with the concerned High Court bench on Saturday morning.The bench of justice Syed Refaat Ahmed and justice Md Iqbal Kabir is likely to hear the petition on Tuesday, said lawyer Kaiser Kamal, a counsel of Khaleda Zia.Earlier on Saturday, the election commission upheld returning officers’ decisions cancelling the candidature of jailed BNP chairperson Khaleda Zia for forthcoming national election.On the basis of majority opinions of the five election commissioners, the commission pronounced its judgment turning down Khaleda’s petitions filed to it to get back her candidacy in Feni-1, Bogura-6 and 7 constituencies.The lawyers of BNP chairperson Khaleda Zia on Wednesday filed appeals with the election commission against rejection of her nomination papers of three constituencies.On behalf of Khaleda Zia, lawyer Kaisar Kamal submitted the appeal for Feni-1 constituency while lawyer Nowshad Jamin for Bogura-6 and lawyer Masud Ahmed Talukder for Bogura-7 constituencies at Nirbachan Bhaban in the city.Earlier, the EC on Sunday (2 Dec) ditched Khaleda’s all the three nomination papers filed for contesting the polls from Feni-1, Bogura-6 and Bogura-7 seats for her conviction in two graft case.On 29 October, Khaleda was convicted and sentenced to seven years’ rigorous imprisonment by a special court in Dhaka in Zia Charitable Trust corruption case.Khaleda landed in jail after being sentenced to five years’ imprisonment in Zia Orphanage Trust case by the same court on 8 February. The High Court later on 30 October extended her jail terms in the case to 10 years.last_img read more

Read More

Soapy property improves electron mobility in organic semiconductors

first_img Citation: Soapy property improves electron mobility in organic semiconductors (2008, October 28) retrieved 18 August 2019 from https://phys.org/news/2008-10-soapy-property-electron-mobility-semiconductors.html Taking a step toward that goal, physicists have made an important advance in the development of organic semiconductors in terms of their electron mobility. Generally, organic semiconductors have low electron mobility, meaning that the overall motion of their electrons is too random and not directed enough to provide a good electric current and conductivity. The physicists demonstrated how to improve the electron mobility of liquid crystalline semiconductors to 0.27cm2/ V•s, which is 10 times higher than the current highest level for room-temperature columnar liquid crystalline materials. The physicists, from the University of Tokyo, Kyoto University, Osaka University, and the Japan Synchrotron Radiation Research Institute, published their study in a recent issue of the Journal of the American Chemical Society.The scientists modified a molecule known as a condensed porphyrin copper complex to make it self-assemble into a liquid crystalline state at room temperature (throughout a wide range from -17 to 99°C). They achieved the record mobility at a temperature of 16°C.The key modification was adding hydrophobic side chains to one side of the molecule and hydrophilic side chains to the other. By being both hydrophobic and hydrophilic, the molecule has now become “amphiphilic.” Other common amphiphilic substances include soaps and detergents, which have molecules that can both attach to grease and easily be washed away by water.The amphiphilic property is useful for improving electron mobility because amphiphilic molecules tend to gather together in an orderly manner. Specifically, the amphiphilic molecular design enhanced the ð-stacking interaction, and molecules with larger ð-conjugated cores tend to have higher electron mobility. The physicists explain that ð-stacking is improved due to a nanoscale phase separation caused by the incompatibility between the hydrophobic and hydrophilic side chains of the molecules.The scientists also noted that the new organic semiconductor is especially efficient at absorbing visible light, which could make them useful for organic thin-film solar cells.More information: Sakurai, Tsuneaki, et al. “Prominent Electron Transport Property Observed for Triply Fused Metalloporphyrin Dimer: Directed Columnar Liquid Crystalline Assembly by Amphiphilic Molecular Design.” J. Am. Chem. Soc., 130 (42), 13812-13813, 2008. 10.1021/ja8030714.via: Tech-On! Polarized optical micrograph of a condensed porphyrin copper complex molecule with hydrophobic and hydrophilic side chains. Image credit: Tsuneaki Sakurai, et al. Physicists use nanostructures to free photons for highly efficient white OLEDs (PhysOrg.com) — Organic semiconductors are a main component in a variety of future organic electronics, such as flexible flat-panel displays, inexpensive solar cells, and other unique devices. Because of their advantages – which include being energy-efficient, inexpensive, and lightweight – organic electronics are expected to compose a multi-billion industry. Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.last_img read more

Read More

Going places Microtubulemediated transport of inhibitory signals critical in stabilizing cell migration

first_imgA modified LEGI model and computer simulation that reproduces both persistent cell migration and oscillations. A diagram of the modified LEGI model that involves the production of both excitation and inhibitory signals in the frontal region, followed by the transport of inhibitory signals away from the front to maintain frontal protrusions and cell polarity in control cells. In nocodazole-treated cells, the impairment of the transport and the resulting accumulation of inhibitory signals at the front act against the excitation signals and cause the head to switch into a tail (A). Computer simulation of this mechanism for cells in 1D successfully reproduces both persistent migration (kymograph in B) and oscillations (kymograph in C). Diagrams of cell location and shape, colored to show the heat map of net signals, show the dynamics of net signals before and after the treatment of nocodazole (D). In addition, the period of oscillation increases upon the impairment of the generation of inhibitory signals (by increasing the delay), which mimics the effect of blebbistatin (kymograph in E). a.u. stands for an arbitrary unit used in computer simulation. See also Fig. S6 and Movies S4–S6. Credit: Zhang J et al. (2014) Microtubules stabilize cell polarity by localizing rear signals. Proc Natl Acad Sci USA 111(46):16383-16388. Explore further (Phys.org)—Microtubules – tubular polymers of tubulin (a globular protein) that are a component of the cytoskeleton found throughout cell cytoplasm – are involved in a range of cellular functions, including the movement of secretory vesicles, organelles, and intracellular substances; cell division (mitosis and meiosis), including the formation of mitotic spindles; and cell polarity, which refers to spatial differences in cellular shape, structure and function. However, the nature of the role of microtubules in cell polarity has yet to be clarified. At the same time, cell migration plays an essential role in many important physiological processes, such as embryogenesis, wound healing, and immune responses; in engineering applications such as tissue regeneration; and, when defective, in causing severe problems such as birth defects, vascular disease and tumor metastasis. A key area for investigation in the linkage between cell polarity and cell migration is that directional cell migration requires a defined polarity, generated by an integrated network of signals, adhesions (the protein-based binding of a cell to a surface or substrate) and cytoskeleton. Play A representative RPE-1 cell expressing RFP-zyxin and migrating on 1D strip, treated with nocodazole to induce oscillations. The movie shows the redistribution of zyxin upon nocodazole treatment. Related to Fig. 2. Credit: Zhang J et al. (2014) Microtubules stabilize cell polarity by localizing rear signals. Proc Natl Acad Sci USA 111(46):16383-16388. Moving forward, Wang tells Phys.org, the researchers would like to drill down the molecular mechanism and cellular structures for polarity control. “We found that a focal adhesion protein, zyxin, has some unique properties that parallel cell polarity, suggesting that it may be a key ‘readout’ of the LEGI mechanism as well as the control factor for cell polarity – and we’re now in the process of elucidating its functional role in cell polarity. In addition,” he continues, “while centrosomes have long been speculated to control cell polarity, we’re trying to establish a logical connection between centrosomes and the LEGI mechanism.” (The centrosome is an organelle that serves as the main microtubule organizing center, or MTOC, of the animal cell, where microtubules are nucleated.) Wang adds that they may also investigate fine regulation of cell migration based on the manipulation of microtubules or motor molecules without total depolymerization of microtubules, and a ‘biological clock’ based on oscillating polarity.Wang says that there are other areas of research that might benefit from their study. “Understanding the control mechanism of cell migration can greatly facilitate migration dependent processes such as tissue engineering and cancer treatment3,4. In addition, the elegant switch between positive and negative feedback may impact bio-inspired engineering, in which a man-made machine may use a biomimetic control mechanism to achieve innovative functions.”Specifically, Phys.org asked Wang if their findings might pertain to the observation that metastasis and neuroneogenic targeting have similar behavioral properties, and may share what has been termed an ancient genetic toolkit5 that plays a role in cancer. “Yes,” Wang affirmed. “Metastasis is driven by the migration of tumor cells. Our findings improve the understanding of the internal control circuit for cell migration, which will benefit the understanding and treatment of metastasis, – such that conditions that reduce the stability of tumor cell migration may be deployed for cancer treatment.” RPE-1 cells in 50 μM ciliobrevin D. Kymograph shows a representative RPE-1 cell treated with ciliobrevin D oscillating in a manner similar to those treated with nocodazole. (Scale bar, 50 μm, 60 min.) See also Figs. S1 and S7 and Movie S1.Credit: Zhang J et al. (2014) Microtubules stabilize cell polarity by localizing rear signals. See also Figs. S1 and S7 and Movie S1. Proc Natl Acad Sci USA 111(46):16383-16388. More information: Microtubules stabilize cell polarity by localizing rear signals, Proceedings of the National Academy of Sciences (2014) 111(46):16383-16388, doi:10.1073/pnas.1410533111Related:1Quantitative Studies of the Growth of Mouse Embryo Cells in Culture and their Development into Established Lines, Journal of Cell Biology (1963) 17(2):299–313, doi:10.1083/jcb.17.2.2992Periodic migration in a physical model of cells on micropatterns, Physical Review Letters (2013) 111(15):158102, doi:10.1103/PhysRevLett.111.1581023Race to the top: Decoding metastasis, Medical Xpress April 29, 20114Probing the invasiveness of prostate cancer cells in a 3D microfabricated landscape, Proceedings of the National Academy of Sciences (2011) 108(17):6853-6856, doi:10.1073/pnas.11028081085Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors, Physical Biology (2011) 8:015001, doi:10.1088/1478-3975/8/1/015001 Recently, scientists in the Department of Biomedical Engineering at Carnegie Mellon University, Pittsburgh obtained a series of analytical and experimental results showing that:Cells on micropatterned linear strips change from highly persistent migration into striking oscillations upon the disassembly of microtubulesPositive feedback in the local-excitation-global-inhibition, or LEGI, mechanism – which is responsible for migration persistence, and in which the response to a stimulus (such as chemotaxis, the movement of an organism in response to a chemical stimulus) is mediated through the balance between a fast, local excitation and a slower, global inhibition process – might be converted into negative feedback to drive oscillations upon the disassembly of microtubulesMicrotubules facilitate the transport of inhibitory signals and their global distributionFeedback in the integrated control circuit may be either positive or negative, depending on the relative position of excitation and inhibitory signalsThe scientists therefore concluded that these findings provide valuable insights into the role of microtubules in the control circuit of cell migration.Prof. Yu-Li Wang discussed the paper that he, Graduate Research Assistant Jian Zhang and Project Scientist Wei-Hui Guo published in Proceedings of the National Academy of Sciences, starting with the challenges involved in the team finding that depolymerization of microtubules caused cells to change from persistent to oscillatory migration. The issue, Wang tells Phys.org, is that without confining cell migration along a one-dimensional (1D) strip, depolymerization of microtubules simply causes cells to lose directional migration without showing recognizable oscillations – so confinement to 1D is required for the highly persistent migration before microtubule depolymerization as well as the oscillatory migration after depolymerization. “This is most likely due to limiting cell migration to two opposite directions,” he explains. “Oscillations become difficult to observe when the cell is able to switch among many different directions. Moreover,” he adds, “our observation was also facilitated by using the RPE-1 cell line, which has a relatively short oscillation period such that multiple cycles of oscillation may be observed before the cell enters division phase. RPE-1 cells therefore allowed unambiguous confirmation of the initial observation made with NIH/3T3 cells.” The retinal pigment epithelium, or RPE, is the pigmented cell layer just outside the neurosensory retina that nourishes retinal visual cells, and is firmly attached to the underlying choroid and overlying retinal visual cells. 3T3 cells – from a cell line originally established in 1962, and published1 in 1963, by George J. Todaro and Howard Green at New York University School of Medicine – has become the standard fibroblast cell line. (Fibroblasts are the most common connective tissue cell in animals.) PausePlay% buffered00:0000:00UnmuteMuteDisable captionsEnable captionsSettingsCaptionsDisabledQuality0SpeedNormalCaptionsGo back to previous menuQualityGo back to previous menuSpeedGo back to previous menu0.5×0.75×Normal1.25×1.5×1.75×2×Exit fullscreenEnter fullscreen Play Persistent migration and oscillation of RPE-1 cells. The movie shows representative RPE-1 cells migrating persistently as a control or showing oscillations when treated with nocodazole or ciliobrevin D on 1D strips. Related to Figs. 1, 2, and 6. Credit: Zhang J et al. (2014) Microtubules stabilize cell polarity by localizing rear signals. Proc Natl Acad Sci USA 111(46):16383-16388. The second analytic conclusion was based on a primary difference between cells and man-made machines – the former involve dynamic localization of structures and signals, while the latter usually consist of components with a fixed location and geometrical relationship – so depending on the relative position of excitation and inhibitory signals in cells, the resulting feedback in the integrated control circuit may be either positive or negative. In contrast, the lack of dynamic localization in most man-made machines keeps them from exhibiting this conversion. “Although rarely realized in man-made machines, transport-dependent conversion between positive and negative feedback in the cell makes intuitive sense for regulating dynamically localized activities.” Wang points out. “When negative signals are transported away from positive signals, it creates a positive feedback by suppressing the activities elsewhere that may compete with the existing frontal end. Conversely, when negative signals are allowed to accumulate in the vicinity of positive signals, they cause negative feedback by overpowering positive signals.”The scientists suggest that microtubules are required not for the generation, but rather for the maintenance, of cell polarity by mediating the global distribution of inhibitory signals. “We found that after the depolymerization of microtubules, cells are still able to move directionally for more than an hour before reversing the direction,” Wang says. “Therefore, cells without microtubules are able to establish a direction of migration but are not able to maintain the polarity for an extended period of time as control cells do. The defect may be explained by the inability to remove the accumulating inhibitory signals at the leading edge, which eventually overpower the excitation signals required for maintaining frontal protrusion activities.”A key finding discussed in the paper is that disassembly of microtubules induces cell oscillation by allowing inhibitory signals to accumulate at the front, which stops frontal protrusion and allows the polarity to reverse. “According to the LEGI model, frontal protrusion activities are determined by the balance between excitation and inhibitory signals,” Wang explains. “Upon the loss of microtubules and the associated transport mechanism, the cell is no longer able to move inhibitory signals away from the leading edge where they are generated, and therefore cannot achieve their global distribution.” Specifically, the accumulating inhibitory signals eventually overcome the excitation signal to stop frontal protrusion activities – and at the same time, the suppression of protrusion activities elsewhere also becomes compromised due to the defective global transport. “Spontaneously-generated excitation signals are then allowed to accumulate and cause the formation of a new front,” Wang adds, “which in the case of cells confined to 1D translates into the reversal of polarity.” The researchers also found that in addition to oscillation, their modified LEGI mechanism can create a range of possible cell behaviors as a result of different relative dynamics of excitation and inhibitory signals – and thereby, the variable interplay between shape, mechanics, and polarity. “The magnitude of inhibitory signals is determined by the relative rate between the generation and transport-mediated depletion.” Wang adds. “Our model accounts for the key elements between signal generation and transport – and while previous models, such as that created by Brian Camley and his colleagues2, incorporate some of the relevant parameters such as cell adhesion and shape to generate oscillation, they are unable to generate as wide a range of activities.”Wang notes that their mathematical model is capable of generating testable, verifiable predictions. One of the primary predictions was that longer cells should oscillate with a longer period; another prediction was that inhibition of dynein (one of many proteins that bind to microtubules, in this case a motor protein responsible for the transports of cargos away from the cell front) should cause similar oscillations as those caused by microtubule disassembly. Wang emphasizes that both of these predictions were verified with experiments. , Physical Review Letters The scientists also faced a hurdle when applying computer modeling to understand how positive LEGI feedback might be converted into negative feedback to drive oscillations upon microtubule disassembly. “The main challenge was to model not only excitation and inhibitory signals at different locations, but also a transport process responsible for delivering the inhibitory signals away from the frontal region for global distribution,” Wang explains, “because the oscillation phenomenon can be produced only when the model includes all the essential elements.”center_img © 2014 Phys.org , Physical Biology PausePlay% buffered00:0000:00UnmuteMuteDisable captionsEnable captionsSettingsCaptionsDisabledQuality0SpeedNormalCaptionsGo back to previous menuQualityGo back to previous menuSpeedGo back to previous menu0.5×0.75×Normal1.25×1.5×1.75×2×Exit fullscreenEnter fullscreen Citation: Going places: Microtubule-mediated transport of inhibitory signals critical in stabilizing cell migration polarity (2014, December 9) retrieved 18 August 2019 from https://phys.org/news/2014-12-microtubule-mediated-inhibitory-critical-stabilizing-cell.html Journal information: Proceedings of the National Academy of Sciences Persistent migration of cells on 1D strips and the corresponding localization of focal adhesion proteins. Related to Fig. 1. Immunofluorescence staining of tensin in a representative RPE-1 cell (A; scale bar, 25 μm) shows no apparent polarization. Kymograph (B; scale bar, 50 μm, 60 min) and time series (C; 90-min interval; scale bar, 100 μm; arrow indicates the direction of migration) of representative NIH 3T3 fibroblasts exhibiting persistent migration on 1D strips. RFP-zyxin in NIH 3T3 cells migrating on 1D strips localizes to the tail region (D). (Scale bar, 50 μm.) Credit: Zhang J et al. (2014) Microtubules stabilize cell polarity by localizing rear signals. Proc Natl Acad Sci USA 111(46):16383-16388. , Journal of Cell Biology A new mechanism affecting cell migration found Despite the complexity of their investigation, the researchers addressed these challenges in a number of ways. They showed that microtubules play a key role in maintaining the positive feedback in the LEGI mechanism, and as described above that positive feedback of the LEGI mechanism for persistent migration may be readily converted into a negative feedback for oscillations. “We found that, in order to generate oscillation, the production of inhibitory signals must lag behind the production of excitation signals,” Wang tells Phys.org. “This is consistent with the general understanding that delay differential equations have the capability to generate oscillations.” In addition, he continues, they used a highly reliable micropatterning method, developed in their lab, which grafts linear polyacrylamide on glass surfaces to block cell migration for confining cell migration to a 1D strip. “We also used a computer model – also implemented in our lab – that simulates not only the control circuit, but also its effect on cell migration.”The paper presents two analytic conclusions, the first being that microtubules facilitate the transport of inhibitory signals and their global distribution. “Our reasoning was guided by the conversion from persistent migration – known to depend on LEGI-based positive feedback – to oscillation, which in general requires negative feedback,” Wang says. “The simplest way for this conversion to occur involves the inhibition of global distribution of negative signals, which fits perfectly with the well-documented function of microtubules in intracellular transport.” Wang points out that this type of reverse reasoning – where an intuitive hypothesis to provide a simple explanation of a biological phenomenon is made before seeking experimental evidence or computational verification – is widely practiced for understanding complex biological phenomenon that are too difficult to address through forward dissection. “Our results further imply that a cell is able to measure its own length based on the time required for end-to-end microtubule-mediated transport,” Wang continues. “Other cellular processes may be similarly affected by the time for the transport of molecular signals along the cell length.” This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.last_img read more

Read More