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    Research Article
    A 48 kDa integral membrane phosphoprotein orchestrates the cytoskeletal dynamics that generate amoeboid cell motility in sperm
    Lawrence L. LeClaire III , Murray Stewart , Thomas M. Roberts
    Journal of Cell Science 2003 116: 2655-2663; doi:10.1242/jcs.00469
    Lawrence L. LeClaire
    Murray Stewart
    Thomas M. Roberts
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    Protrusion of the lamellipod in the crawling sperm of Ascaris is tightly coupled to the localized vectorial assembly and bundling of the major sperm protein cytoskeleton. In cell-free extracts of sperm, vesicles derived from the leading edge membrane reconstitute protrusion by directing the assembly of columnar meshworks of major sperm protein filaments that push the vesicle forward as they elongate. Treatment with proteases or a tyrosine phosphatase abolished vesicle activity, suggesting the involvement of a membrane phosphoprotein. Fractionation of vesicle proteins by sequential detergent lysis, size exclusion chromatography and immunoprecipitation with antiphosphotyrosine antibody identified a 48 kDa integral membrane phosphoprotein as the only sperm membrane component required to nucleate major sperm protein polymerization under physiological conditions. Immunolabeling assays showed that this protein is distributed uniformly in the sperm plasma membrane, but that its active phosphorylated form is located only at sites of major sperm protein polymerization at the leading edge. Because this protein specifies sites of cytoskeletal assembly, we have named it major sperm protein polymerization organizing protein (MPOP). The phosphorylation of MPOP is pH sensitive and appears to require a soluble tyrosine kinase. Comparison of the activity of MPOP to that of analogous membrane proteins in actin-based systems emphasizes the importance of precise transmission of information from the membrane to the cytoskeleton in amoeboid cell motility.

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    The spatially controlled polymerization of cytoskeletal proteins plays a key role in many forms of cell motility. For example, lamellipodial protrusion ( Black New Era Edition Perforated Logo Cap Boris Bidian Saberi Z6pob00
    ), endocytic vesicle translocation ( Jeng and Welch, 2001 ; Merrifield et al., 1999 ), and the intracellular or extracellular movement of selected pathogenic bacteria and viruses ( FOOTWEAR Espadrilles Farewell 0Ro8m9u8o
    ; Sanger et al., 1996 ) all depend on the local activation of regulatory proteins to target actin polymerization to membrane surfaces. In these crawling cells, the localized filament assembly that drives lamellipodial protrusion is initiated by proteins of the Wiskott-Aldrich syndrome protein (WASp)/Scar family, cortactin and a series of proteins that contain unique pleckstrin homology (PH) domains that interact with the membrane at the leading edge and activate the actin nucleating Arp2/3 complex ( Higgs and Pollard, 1999 ). Actin severing proteins, such as severin and gelsolin, are also activated at the leading edge and contribute to cytoskeletal assembly by generating new barbed ends for filament elongation ( Flanagan et al., 2001 ). However, the exact mechanisms for controlling cytoskeletal construction and harnessing this process to drive leading edge extension are not yet fully understood.

    Full Instructions: How to Drag Drop Photos on Your iPhone in iOS 11

    Just like with all of the apps and features listed above, the Notes app also has some great drag-and-drop features available. You can select text, images, sketches, and pretty much anything else you can throw in a note, then drag and drop it to somewhere else on the document. It works great for reorganizing the current note you're in, but when in landscape mode, you can even drag and drop items into another note.

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    For groups of words, highlight all of them and then long-press on the group until you see the text pop out, then drag and drop to wherever you want. For just one word, you don't need to highlight anything; Just long-press on the word, then drag and drop. It works the same for images — just be careful not to use 3D Touch, or you'll "peek and pop" into the expanded image preview instead.

    Reminders is a relatively simple app, so there's not much you can drag and drop except for words, phrases, numbers, etc. However, you can also reorder items in your list by dragging and dropping.

    Just like in notes, long-press on the word or selection of text until it pops out slightly, then drag and drop to wherever necessary on your list. Or, just long-press on the whole items in the list to reorder it right away. If in landscape mode, you can also drag and drop text and to-dos as new to-dos in a different list of reminders.

    Just like most of the above options, dragging and dropping text and images in an email draft is super easy in Mail. Just long-press on the word, highlighted text, image, etc., wait for it to pop out slightly, then drag and drop into place.

    In the new Files app, a file manager that includes iCloud Drive, Dropbox, Box, Google Drive, and other third-party cloud storage services, you can drag and drop files and folders — but there are some restrictions.

    You can't drag and drop files or folders from third-party services such as Dropbox or Google Drive to anywhere else — you can only drag and drop files inside the iCloud Drive location. And you can only drag and drop files and folders into folders that are within the folder you are already in.

    When in landscape mode, you can also drag and drop files or folders over the Tags section in the Browse sidebar to give them the appropriately colored tag, which is faster than using the selection menu. However, the bad thing with reordering files within a folder or dragging them over to the Tags section is that if the file is in iCloud, it's very easy to download it onto your iPhone in the process.

    Aside from the apps listed above, you can also drag and drop text and images in other stock Apple apps such as Message (when composing a text). Found more Apple apps that let you use drag and drop? Share them with us!

    Carey’s Cleveland upbringing was not particularly joy-filled. His father died when Carey was just 8, succumbing to a brain tumor. His mother worked two jobs to support her three sons and couldn’t afford to take Carey to see a psychiatrist to help deal with the trauma. Feeling isolated and depressed for much of his adolescence, things didn’t improve when he attended Kent State University: He was expelled twice for poor grades.

    At rock bottom, Carey started reading self-help titles like University of Success and Your Erroneous Zones . The books changed Carey’s way of thinking, getting him out of his frustrated mindset. He later moved to California, joined the Marine Reserves, and began eyeing a career in stand-up comedy.

    Kevin Winter, Getty Images

    While writing jokes for a friend who worked in radio—Carey again turned to books, taking out a joke-writing title from a local library—he began Gold Fiji Mini Hoop Earrings Monica Vinader vAPCo
    a stand-up act. Attending an open-mic night at the Sahara in Las Vegas didn’t go well (he bombed), but after putting in years of practice, Carey got two breaks. The first was Star Search , a talent competition hosted by Tonight Show sidekick Ed McMahon, and the second was the Tonight Show itself. In 1991, Carey was invited to perform and appeared to win over Johnny Carson, a move that caught the attention of television executives eager to find another stand-up to build a sitcom around. The Drew Carey Show debuted in 1995 and ran for nine seasons.

    Wearing black horn-rimmed glasses for the first half of his career helped make Carey an identifiable presence on television. In 2001, when he got LASIK to correct his vision, he no longer needed them to see. But because his persona was so closely intertwined with spectacles, Carey continued wearing the frames—this time with clear lenses—for work. When he opts to go without them, he finds that fans can be oblivious to the fact they’re talking to him. Conversing with a small group in a Cleveland night club one year, Carey told them he was on television and host of The Price is Right . “I thought Drew Carey hosted The Price is Right ,” one replied.


    After signing a deal in 1998 to endorse the AW burger chain, Carey found himself in trouble over his sitcom character’s preference for McDonald’s. In November of that year, an episode of The Drew Carey Show featured Carey lost in China and TROUSERS Casual trousers Fly3 S2yA3Dy8ax
    into a Golden Arches location for a meal. AW took offense and refused to pay the remainder of the comic’s endorsement fee. They also insisted he return the $450,000 already remitted to him. “I didn't eat at the McDonald's on the show,” Carey told Esquire in 2007. “I grabbed a fry off a kid's plate, but I didn't get any of the food. When I was in China, I ate at AW almost every day. There was one around the corner from where we were staying. I like the company. I thought we had a good relationship.”

    These and other forward-looking statements are based on each party's respective management's current views and assumptions and involve risks and uncertainties that could significantly affect expected results. Results may be materially affected by factors such as: risks associated with transactions generally, such as the inability to obtain, or delays in obtaining, required approvals under applicable anti-trust legislation and other regulatory and third party consents and approvals; the occurrence of any event, change or other circumstances that could give rise to the termination of the merger agreement; the outcome of any legal proceedings that may be instituted following announcement of the transaction; potential volatility in the capital markets and the impact on the ability to complete the proposed debt and equity financing necessary to consummate the acquisition of Blue Buffalo; failure to retain key management and employees of Blue Buffalo; General Mills' level of indebtedness as a result of the transactions and its ability to achieve its objective of reducing indebtedness; issues or delays in the successful integration of Blue Buffalo's operations with those of General Mills, including incurring or experiencing unanticipated costs and/or delays or difficulties; difficulties or delays in the successful transition from the information technology systems of Blue Buffalo to those of General Mills as well as risks associated with other integration or transition of the operations, systems and personnel of Blue Buffalo; failure or inability to implement growth strategies in a timely manner; unfavorable reaction to the transaction by customers, competitors, suppliers and employees; future levels of revenues being lower than expected and costs being higher than expected; conditions affecting the industry generally; local and global political and economic conditions; conditions in the securities market that are less favorable than expected; and changes in the level of capital investment, and other risks described in General Mills' filings with the Securities and Exchange Commission, including General Mills' Annual Report on Form 10-K for the fiscal year ended May 28, 2017 and in Blue Buffalo's filings with the Securities and Exchange Commission, including Blue Buffalo's Annual Report on Form 10-K for the fiscal year ended December 31, 2016 .

    Actual results could differ materially from those projected in the forward-looking statements. Neither General Mills, nor Blue Buffalo undertakes any obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

    Additional Information and Where to Find It

    Blue Buffalo will prepare an information statement on Schedule 14C for its stockholders with respect to the approval of the transaction described herein. When completed, the information statement will be mailed to Blue Buffalo's stockholders. You may obtain copies of all documents filed by Blue Buffalo with the SEC regarding this transaction, free of charge, at the SEC's website, www.sec.gov or from Blue Buffalo's website at ir.bluebuffalo.com .

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