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Many of Ladysmith's long-term residents have fond memories of "Oyster Harbour" before it was transformed in 1967 by the opening of Transfer Beach Park. At one time, there were four major wharves at Ladysmith, and all of them have played an important part in the history of our city. The Coal or "Big" wharf, the Government (also known as the Fisherman's or "Dynamite' wharf) and further south, the Granby wharf each has its own history. However, this article will focus on the Transfer Wharf, which many historians believe was the most important wharf in Ladysmith while it existed.
At the end of the 19th century, it was clear to politicians and entrepreneurs that the success of British Columbia as a Canadian province required the development of a fast and efficient transportation system. For most of B.C. this meant a good railway system, as roads in most of the province consisted of little more than wagon trails. The truck and automobile era was just beginning, and overland travel was tedious and dangerous. In addition, although the 'linear' distance from the Alaskan panhandle to Victoria is less than 1000 kilometers, the actual B.C. coastline is nearly 26,000 km. long, and much of it can only be accessed by water. At the turn of the century, over 50 per cent of British Columbia's population of 36,000 lived on Vancouver Island, and if the Island was to prosper, both rail and water transportation were an economic and political necessity.
British Columbia's decision to become a Canadian province in 1871 was conditional on the federal government building a '"trans-continental railway". Many Islanders had argued that it made much more sense to join the United States than to be part of Canada. They were still angry that the Canadian Pacific Railway had its terminus at Vancouver rather than Esquimalt. The political compromise was the construction of the Esquimalt and Nanaimo Railway by Robert Dunsmuir, with Prime Minister John Macdonald driving in the last spike on August 13, 1886 at Shawinigan Lake.
Despite dismay at the high cost of construction (Historian Kit Willmott believed the E &N was built for $ 626,000 a mile!), mutterings about Robert Dunsmuir's conflict of interest (he was Premier of BC and President of the E &N at the same time), and an outrageous land grant equivalent to 20 per cent of Vancouver Island, the E & N was a great success. By 1888, passengers could board the train in Victoria at 8:00 A.M. and have lunch in Nanaimo. The return trip from Ladysmith to Victoria cost $1.25 and took just over two hours. The rail line quickly added special trains during the summer, including day outings to Shawnigan Lake and excursions for evening concerts at Goldstream for 25 cents.
For Ladysmith, the best was yet to come. Readers familiar with the town's early history will recall Dunsmuir's decision to relocate the families and workers at Extension Mine to the new community at Oyster Bay, and discontinue coal shipments from Departure Bay. Business was booming at the newly constructed Coal Wharf, and both passenger and freight service were provided through a fleet of vessels operated by the British Columbia Coast Steamship Service in conjunction with the E & N. The fishing and logging industries were also using the improved harbour facilities at Ladysmith to load their products for transshipment to both the mainland and overseas. The railway was also transporting ore mined at Mt. Sicker to a new smelter in Ladysmith. However, at the end of the 19th century, there was still a major problem transporting heavy equipment and machinery to Vancouver island. It had to be lightered off and on the Island or sent by scow to Victoria or Nanaimo, a costly and labour intensive enterprise. The solution was to construct a dedicated transfer slip so that boxcars could be shipped directly by railcar ferry to and from Vancouver Island without off loading the contents. The logical choice for the E & N was to build the facility at Oyster Bay! By early 1900 Transfer Wharf was ready for business. According to railway historian Don MacLachlan, the first shipment from the rail car ferry slip was a carload of lumber from John Coburn's mill at Shawnigan Lake. The first cars arriving on Vancouver Island at the new Transfer Wharf were CPR rail cars from Eastern Canada. Then, on December 2, 1900, the tug Czar arrived with Transfer No. 1, a railway car barge that could carry twelve boxcars on the forty mile crossing between Ladysmith and Vancouver. A new era had begun.
In 1905, the C.P.R. purchased the E & N. The rail line was quickly extended to Alberni (1911) Lake Cowichan (1912) and Courtenay (1914). Although a planned extension to Campbell River had to be abandoned with the outbreak of WW I, the major communities on the east coast of Vancouver Island were now connected by rail to the rest of the world. The CPR was already in the shipping business, and along with the railway came a small marine fleet consisting of the Joan, a wooden-hulled twin-screw steamer and the City of Nanaimo, which served communities on the east coast of Vancouver Island. Canadian Pacific now proceeded to fulfill its promise to provide a rail link from Halifax to Victoria.
On July 11th, 1908 a new steel-hulled tug – built for a cost of $75,000 by BC Marine Railways ship yard – arrived in Ladysmith harbour. The Nanoose was 120 feet in length, and powered by a single 600 hp engine capable of 12 knots. She was soon joined by the tugs Kyuquot and Qualicum. Between them they pulled five rail barges named "Transfer 1 though 5".
Although it was necessary to double the engines to haul the larger and heavier CPR rail cars over the Malahat, the system worked. The website Train web reports that traffic grew from 3471 cars outbound and 2891 inbound during 1907 to 17,282 out and 7459 in during 1942. The service was finally discontinued in 1955. Rail cars now use the new Wellcox loading facility in Nanaimo and the Transfer Wharf was torn down.
In a recent telephone conversation with noted CPR historian Robert Turner, he stated that "the Transfer Wharf era was an exciting time for Ladysmith. A home furnishing store in Victoria could receive a direct shipment of furniture from Ontario, and a load of newsprint from Port Alberni could arrive in Florida without ever leaving its rail car." For more than 50 years, Ladysmith remained a key link in connecting Vancouver Island to the railway transportation system of North America.
Ed Nicholson Ladysmith Historical Society.


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When People Accept that Marriage is a Contract, Divorce Should Be Easier!
April 06, 2012
The family courts of most states, including Rhode Island's, grew out of the need to address the countless people who had become married and now wanted to go their separate ways. Yet the civil courts of most states already had large civil courts to address contract issues.
The general idea was whether to keep expanding the large civil courts a little bit more each time married people wanted to go their separate ways and each wanted a share of what they had built while they were married, or to create a new court or division of the court entirely to involve matters arising out of family situations, including for those people who wanted to leave their spouse and take part of what they had built together with them. Thus, the the family courts were born out of a need to address these issues and many others that grew out of "family situations."
A problem arises though from today's modern media and the romanticism that has grown out of marriage and made it a huge money-making industry.
Think about it. Many young women today dream of the day of their wedding from the time they own the Barbie Bride Doll(tm). They envision the elegant wedding dress and veil, the beautifully adorned bridesmaids accompanied by groomsmen wearing tuxedos with all variety of flowers displaying vibrant colors and filling the air with the sweet fragrance of love. Then there is the wonderful reception surrounded by friends and family and food fit for a king. It all culminates in the beginning of your life with your soulmate on a tropical island walking hand in hand along the beach as you kiss your perfect mate as the moonlight dances along the small soothing waves of the water.
Yet in all of this people have forgotten the origins of marriage that still remain today. Even today marriages throughout the United States require a wedding license application, witnesses are often needed for the exchange of vows (aka promises) to one another. At the end of the ceremony the parties to the marriage, the officiant and the witnesses sign the marriage certificate after the promises have been exchanged and they submit the document to the state to record the marriage.
Why is this all done? Take a look at it again. The husband and wife entered into a contract with one another. Their marriage is a contract.
The task of the family court in a divorce proceeding is to legally assist the parties when separating by dividing the contract that spouses entered into.
If you understand the concept of a contract, and accept that marriage is a legal contract being divided fairly by the court as if it were the division of a business partnership then you can more easily deal with it.
The main problem that arises in divorce proceedings is when husbands and wives are unable to extract their feelings about the relationship from the divorce itself. It's understandable why many people find that hard to do because it is the relationship and its promises that form the underlying basis for entering into the contract to begin with.
It is strongly suggested that if your emotions are strong and you are entering into divorce proceedings for any reason, that you should get some counseling to help you deal with your emotional reaction to the divorce.
It is not easy to deal with a divorce, especially when you are dealing with a long-term relationship. Yet the longer the divorce goes on, the more time, money and energy you usually spend on the legal proceeding itself rather than addressing your relationship issues and moving on with your life.
When you realize and accept that the emotional and legal aspects of a divorce can be separated from one another, then you are able to achieve a better result in both. Oversimplifying it, you then deal with your emotion about the breakdown of the relationship with your counselor and you deal with the practical aspects of the breakdown of the marriage and moving on (i.e. division of your assets and debts) in the family court.
By achieving this separation between these two aspects, divorce should be easier to some degree.
All my Best to All Who Go Before the Rhode Island Family Court,
I am Attorney Christopher A. Pearsall and I am "The Rhode Island Divorce Coach."

subset: commoncrawl


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This light up charging cable is built with perfect flexible and soft materials, this lightning cable can be folded and bent without cable quality damage. Light up iPhone charger cable has El technology. Once plugged in, light up iPhone charger cable allows you to see as the electricity flowing into the cell phone. When your device is fully charged, the light stays off. Time to say goodbye to your common charger cable and get this colorful light up charging cable which will meet all your needs in style and quality.


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There is currently no licensing regime for dog breeders in the Cayman Islands, despite the provision being part of the Animals Law for more than 15 years.
The Department of Agriculture confirmed it has not issued a single license for dog or cat breeders to operate in the territory. Brian Crichlow, deputy director of the Department of Agriculture, acknowledged the law requires anyone involved in the breeding or sale of pets to have a license.
But he said the necessary regulations to accompany the law had never been introduced and no licensing system has been set up. This oversight will be corrected in a coming review of the law, Mr. Crichlow claimed.
Animal welfare charities have warned that the failure to follow through with rules and regulations for breeders is fueling Cayman's feral dog problem and is linked to a whole host of other animal welfare issues.
Lesley Agostinelli, of the Cayman Animal Rescue Enthusiasts, said the charity frequently encounters issues related to unethical breeding practices.
She said CARE made a Freedom of Information request to the Department of Agriculture to obtain a list of all licensed breeders in an effort to identify illegal operators and educate them about their responsibilities under the law.
She said she was surprised to learn that there was no licensing regime at all.
"It is sad and demoralizing for us as an animal charity that is trying to support these laws and educate people on their obligations to find that we are not being supported in that sense," she added.
CARE funds a free community spay and neuter program, offers preventative vet care for pets in underprivileged communities, and has developed an education program on animal welfare for schools.
Ms. Agostinelli believes a proper licensing regime would help end unscrupulous "puppy mills" – breeders that churn out pups for profit without any concern for the welfare of the dogs in their care.
She said tighter regulation could also help ensure puppies were properly vaccinated, spayed and neutered, registered and linked to an owner to create a chain of accountability.
"We are not against breeding if it is done properly but the only way that will happen is if premises are licensed, and pets are required to be vaccinated and vets records maintained," she said.
Jason Jairam, of the Cayman Islands Humane Society, said he supported a proper licensing system for breeders.
"If you go on e-Cay or Facebook, any average Joe is selling dogs," he said. "Licensing would be a really good step for the government and for the community as well."
The Animals Law was amended in 2002 to require anyone breeding pets to be licensed and follow certain standards. But the regulations, which give the necessary detail to implement the law, were never created.
Mr. Crichlow indicated the law would be updated in the coming year and the regulations brought in.
"The Department and Ministry of Agriculture have recognized this and other shortcomings in the Animals Law and support a comprehensive update of the law to address these matters," he said.
Even without licensing, Mr. Crichlow said the Department of Agriculture could still investigate any abuses under broader animal protection legislation.
"Although no operators licenses have been issued in relation to the breeding of pet animals," he said, "any animal owner or person breeding a pet animal is required to adhere to accepted standards of animal welfare as set out in the Animals Law. Where the Department becomes aware of a situation where a person may be keeping an animal in conditions that do not meet acceptable animal welfare standards, such cases are actively investigated by the Department's Animal Welfare Officers."
If you value our service, if you have turned to us in the past few days or weeks for verified, factual updates, if you have watched our live streaming of press conferences or sent an article to a friend... please consider a donation. Quality local journalism was at risk before the coronavirus crisis. It is now deeply threatened. Even a small amount can go a long way to sustaining our mission of informing the public. We need our readers' financial support now more than ever.


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- This event has passed.
DateJuly 13 9:00 am – 1:00 pm
About the Event
Clearwater Marine Aquarium partners with Ocean Aid 360 and Tampa Bay Watch for the 2019 Summer Closure Ghost Trap Rodeo. This event will occur during the closure of the fishery when any and all traps are legal to be removed per our permitted efforts.
What is a Ghost Trap? A derelict trap which is no longer actively being fished. If left untouched, this trap may have many adverse effects such as entrapment and death for smaller fish species or line entanglement around larger marine animals.
The 2019 Summer Closure Ghost Trap Rodeo will be held on Saturday, July 13 from 9:00am-1:00pm in six locations around Tampa Bay:
- Bellaire
- Ft. Desoto
- Warner's Bayou (Bradenton)
- EG Simmons (Ruskin)
- Courtney Campbell
- Demen's Landing (St. Pete)
For more information, visit here: https://myfwc.com/fishing/saltwater/trap-debris/
Volunteer Signup
*If you are planning to participate, all costs including gas for the boat will be the responsibility of the boat owner and/or team.


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It's 30 for 30 time, baby!
I think you probably all know the drill for this 30 for 30 thing, so let's skip the part where I question my decision to participate and the clothes I chose to include, and get this show on the road.
The line-up:
And that equals 30.
So here we go...
Yours truly,
30 for 30


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Payton Carvalho has been dancing since the age of four and is trained in Ballet, Pointe, Jazz, Tap, Contemporary and Hip-Hop. She has completed her CDTA Tap and Jazz Examinations along with RAD Ballet Examinations up to Grade 8.
After high school, Payton moved to New York City to study dance at the American Musical and Dramatic Academy, on scholarship. Living in New York allowed Payton to train with top professionals in the industry at Broadway Dance Center, Steps on Broadway, and various master classes.
Payton's love for teaching started at a young age and she feels very fortunate to share her passion with the students at GRAD.


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Iranian Army Commander Major General Ataollah Salehi underscored the necessity for building all defensive equipment and weapons inside the country.
Salehi made the remarks while visiting an exhibition of research and applied sciences at Shahid Sattari University of Aeronautical Engineering in Tehran on Monday.
"The efforts of professors and students of Sattari University should be based on faith, thinking, creativity and indigenization of the needed equipment similar to the past in line with the guidelines of the Supreme Leader (of the Islamic Revolution Ayatollah Seyed Ali Khamenei) and Commander in Chief and at the service of the Islamic Republic," he said.
Salehi called on commanders and officials of Shahid Sattari University of Aeronautical Engineering to improve relations with other military universities and science, research and industrial-defense centers.
In recent years, Iran has made great achievements in the defense sector and gained self-sufficiency in manufacturing essential military hardware and defense systems.
Yet, Iranian officials have always stressed that the country's military and arms programs serve defensive purposes and should not be perceived as a threat to any other country.
In relevant remarks in August, Iranian Air Force Commander Brigadier General Hassan Shah Safi underlined the need for long-term planning in the field of parts manufacturing and indigenizing production of the parts and components needed for his force's fighter jets and aircraft.
"We should pay heed to (airplane) parts manufacturing more than before by adopting long-term planning in the field and looking at the far-away horizons," Brigadier General Shah Safi said.
"We have fully supplied all the parts needed by the air force through expediting a parts manufacturing movement, cooperation with defense ministry's aviation industries organization in manufacturing testers and utilizing veterans' experiences," he added.


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What Kendall & Kris Jenner's Rosie The Riveter Election Day Photo Means
Back in September, the Kardashians courted controversy when it was rumored that Kim Kardashian wasn't sure who she was voting for. But Kim shut down those rumors firmly and gracefully, and in recent days, many of the Kardashians and Jenners have been posting regular social media support for Hillary Clinton, with Kris Jenner assuring fans on Instagram that "all of us are voting for Hillary Clinton." The matriarch's Election Day Instagram post is just as enthusiastically pro-Clinton, and this time she's highlighting family ties as well as historical significance. Both Jenner and her daughter Kendall don matching red bandannas and blue jumpsuits in the new photo, bringing to light the significance of this particular election cycle.
The Instagram post features a split image, with a close-up of Kendall on the left side dressed in a flawless Rosie the Riveter costume and the word "vote" in large letters overhead where Rosie's traditional "we can do it" slogan would be. On the left side is mom Kris in the same costume, with the welding sparks of industrialization blurry in the background. The two are both flexing their muscles, just like in the Rosie original image. The caption is a simple "#WeAreWithHer" and it comes with an American flag emoji.
The Jenners and Kardashians know how to make a statement and they plan everything about their public image down to the smallest detail, so you know that the symbolism and timing of the photo was 100 percent intentional. It's also hugely effective, bringing attention to the ways that this election has historical significance for women. The image of Rosie the Riveter, drawn by J. Howard Miller, comes from World War II, when most of the country's men were enlisted to fight overseas and women were left to take on active roles in the workforce and society as a whole. Rosie, with her strong arms, determined stare, impressively on-point makeup, and encouraging "we can do it" slogan, represented the power and ability of American women. She was a reminder that women were a critical part of not only the war effort, but of the structure of America as a whole: politically, socially, industrially, and intellectually. Rosie showed that America was a land of strong women who could make a difference.
By choosing to honor Rosie the Riveter in 2016 on Election Day, the Jenners are making the statement that women are as strong and influential as ever — especially when they vote. In a sense, they are saying that, just as America's women stepped up and took control during the crisis of World War II, so they are taking control and making changes in this new, critically important historical moment: the 2016 presidential election between Donald Trump and Hillary Clinton. As the country is on the precipice of either historically electing America's first woman president or electing the man who ran one of the most racist and sexist campaigns in history, the Jenners are letting fans know that they're thinking of and embodying strong women from America's past.
Image: Wikimedia Commons


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Amyloid precursor protein
Amyloid precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. Its primary function is not known, though it has been implicated as a regulator of synapse formation,[5] neural plasticity[6], antimicrobial activity [7], and iron export.[8] APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.
APP is an ancient and highly conserved protein.[9] In humans, the gene for APP is located on chromosome 21 and contains 18 exons spanning 290 kilobases.[10][11] Several alternative splicing isoforms of APP have been observed in humans, ranging in length from 639 to 770 amino acids, with certain isoforms preferentially expressed in neurons; changes in the neuronal ratio of these isoforms have been associated with Alzheimer's disease.[12] Homologous proteins have been identified in other organisms such as Drosophila (fruit flies), C. elegans (roundworms)[13], and all mammals.[14] The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's native-state biological functions.[14]
Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimer's disease.[15][16][17] For example, several mutations outside the Aβ region associated with familial Alzheimer's have been found to dramatically increase production of Aβ.[18]
A mutation (A673T) in the APP gene protects against Alzheimer's disease. This substitution is adjacent to the beta secretase cleavage site and results in a 40% reduction in the formation of amyloid beta in vitro.[19]
A number of distinct, largely independently-folding structural domains have been identified in the APP sequence. The extracellular region, much larger than the intracellular region, is divided into the E1 and E2 domains, linked by an acidic domain (AcD); E1 contains two subdomains including a growth factor-like domain (GFLD) and a copper-binding domain (CuBD) interacting tightly together.[21] A serine protease inhibitor domain, absent from the isoform differentially expressed in the brain, is found between acidic region and E2 domain.[22] The complete crystal structure of APP has not yet been solved; however, individual domains have been successfully crystallized, the growth factor-like domain,[23] the copper-binding domain,[24] the complete E1 domain[21] and the E2 domain.[20]
Post-translational processingEdit
APP undergoes extensive post-translational modification including glycosylation, phosphorylation, sialylation, and tyrosine sulfation, as well as many types of proteolytic processing to generate peptide fragments.[25] It is commonly cleaved by proteases in the secretase family; alpha secretase and beta secretase both remove nearly the entire extracellular domain to release membrane-anchored carboxy-terminal fragments that may be associated with apoptosis.[14] Cleavage by gamma secretase within the membrane-spanning domain after beta-secretase cleavage generates the amyloid-beta fragment; gamma secretase is a large multi-subunit complex whose components have not yet been fully characterized, but include presenilin, whose gene has been identified as a major genetic risk factor for Alzheimer's.[26]
The amyloidogenic processing of APP has been linked to its presence in lipid rafts. When APP molecules occupy a lipid raft region of membrane, they are more accessible to and differentially cleaved by beta secretase, whereas APP molecules outside a raft are differentially cleaved by the non-amyloidogenic alpha secretase.[27] Gamma secretase activity has also been associated with lipid rafts.[28] The role of cholesterol in lipid raft maintenance has been cited as a likely explanation for observations that high cholesterol and apolipoprotein E genotype are major risk factors for Alzheimer's disease.[29]
Biological functionEdit
Although the native biological role of APP is of obvious interest to Alzheimer's research, thorough understanding has remained elusive.
Synaptic formation and repairEdit
The most-substantiated role for APP is in synaptic formation and repair;[5] its expression is upregulated during neuronal differentiation and after neural injury. Roles in cell signaling, long-term potentiation, and cell adhesion have been proposed and supported by as-yet limited research.[14] In particular, similarities in post-translational processing have invited comparisons to the signaling role of the surface receptor protein Notch.[30]
APP knockout mice are viable and have relatively minor phenotypic effects including impaired long-term potentiation and memory loss without general neuron loss.[31] On the other hand, transgenic mice with upregulated APP expression have also been reported to show impaired long-term potentiation.[32]
The logical inference is that because Aβ accumulates excessively in Alzheimer's disease its precursor, APP, would be elevated as well. However, neuronal cell bodies contain less APP as a function of their proximity to amyloid plaques.[33] The data indicate that this deficit in APP results from a decline in production rather than an increase in catalysis. Loss of a neuron's APP may affect physiological deficits that contribute to dementia.
Somatic recombinationEdit
In neurons of the human brain, somatic recombination occurs frequently in the gene that encodes APP.[34] Neurons from individuals with sporadic Alzheimer's disease show greater APP gene diversity due to somatic recombination than neurons from healthy individuals.[34]
Anterograde neuronal transportEdit
Molecules synthesized in the cell bodies of neurons must be conveyed outward to the distal synapses. This is accomplished via fast anterograde transport. It has been found that APP can mediate interaction between cargo and kinesin and thus facilitate this transport. Specifically, a short peptide 15-amino-acid sequence from the cytoplasmic carboxy-terminus is necessary for interaction with the motor protein.[35]
Additionally, it has been shown that the interaction between APP and kinesin is specific to the peptide sequence of APP.[36] In a recent experiment involving transport of peptide-conjugated colored beads, controls were conjugated to a single amino acid, glycine, such that they display the same terminal carboxylic acid group as APP without the intervening 15-amino-acid sequence mentioned above. The control beads were not motile, which demonstrated that the terminal COOH moiety of peptides is not sufficient to mediate transport.
Iron exportEdit
A different perspective on Alzheimer's is revealed by a mouse study that has found that APP possesses ferroxidase activity similar to ceruloplasmin, facilitating iron export through interaction with ferroportin; it seems that this activity is blocked by zinc trapped by accumulated Aβ in Alzheimer's.[8] It has been shown that a single nucleotide polymorphism in the 5'UTR of APP mRNA can disrupt its translation.[37]
The hypothesis that APP has ferroxidase activity in its E2 domain and facilitates export of Fe(II) is possibly incorrect since the proposed ferroxidase site of APP located in the E2 domain does not have ferroxidase activity.[38][39]
As APP does not possess ferroxidase activity within its E2 domain, the mechanism of APP-modulated iron efflux from ferroportin has come under scrutiny. One model suggests that APP acts to stabilize the iron efflux protein ferroportin in the plasma membrane of cells thereby increasing the total number of ferroportin molecules at the membrane. These iron-transporters can then be activated by known mammalian ferroxidases (i.e. ceruloplasmin or hephaestin).[40]
Hormonal regulationEdit
The amyloid-β precursor protein (AβPP), and all associated secretases, are expressed early in development and play a key role in the endocrinology of reproduction – with the differential processing of AβPP by secretases regulating human embryonic stem cell (hESC) proliferation as well as their differentiation into neural precursor cells (NPC). The pregnancy hormone human chorionic gonadotropin (hCG) increases AβPP expression[41] and hESC proliferation while progesterone directs AβPP processing towards the non-amyloidogenic pathway, which promotes hESC differentiation into NPC.[42][43][44]
AβPP and its cleavage products do not promote the proliferation and differentiation of post-mitotic neurons; rather, the overexpression of either wild-type or mutant AβPP in post-mitotic neurons induces apoptotic death following their re-entry into the cell cycle.[45] It is postulated that the loss of sex steroids (including progesterone) but the elevation in luteinizing hormone, the adult equivalent of hCG, post-menopause and during andropause drives amyloid-β production[46] and re-entry of post-mitotic neurons into the cell cycle.
Amyloid precursor protein has been shown to interact with:
APP interacts with reelin, a protein implicated in a number of brain disorders, including Alzheimer's disease.[67]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000142192 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022892 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J (Jul 2006). "Synapse formation and function is modulated by the amyloid precursor protein". The Journal of Neuroscience. 26 (27): 7212–21. doi:10.1523/JNEUROSCI.1450-06.2006. PMC 6673945. PMID 16822978.
- ^ Turner PR, O'Connor K, Tate WP, Abraham WC (May 2003). "Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory". Progress in Neurobiology. 70 (1): 1–32. doi:10.1016/S0301-0082(03)00089-3. PMID 12927332.
- ^ Moir RD, Lathe R, Tanzi RE (2018). "The antimicrobial protection hypothesis of Alzheimer's disease". Alzheimer's & Dementia. 14 (12): 1602–1614. doi:10.1016/j.jalz.2018.06.3040. PMID 30314800.
- ^ a b Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (Sep 2010). "Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease". Cell. 142 (6): 857–67. doi:10.1016/j.cell.2010.08.014. PMC 2943017. PMID 20817278.
- ^ Tharp WG, Sarkar IN (April 2013). "Origins of amyloid-β". BMC Genomics. 14 (1): 290. doi:10.1186/1471-2164-14-290. PMC 3660159. PMID 23627794.
- ^ Yoshikai S, Sasaki H, Doh-ura K, Furuya H, Sakaki Y (Mar 1990). "Genomic organization of the human amyloid beta-protein precursor gene". Gene. 87 (2): 257–63. doi:10.1016/0378-1119(90)90310-N. PMID 2110105.
- ^ Lamb BT, Sisodia SS, Lawler AM, Slunt HH, Kitt CA, Kearns WG, Pearson PL, Price DL, Gearhart JD (Sep 1993). "Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice [corrected]". Nature Genetics. 5 (1): 22–30. doi:10.1038/ng0993-22. PMID 8220418.
- ^ Matsui T, Ingelsson M, Fukumoto H, Ramasamy K, Kowa H, Frosch MP, Irizarry MC, Hyman BT (Aug 2007). "Expression of APP pathway mRNAs and proteins in Alzheimer's disease". Brain Research. 1161: 116–23. doi:10.1016/j.brainres.2007.05.050. PMID 17586478.
- ^ Ewald, Collin Y.; Li, Chris (2012-04-01). "Caenorhabditis elegans as a model organism to study APP function". Experimental Brain Research. 217 (3–4): 397–411. doi:10.1007/s00221-011-2905-7. ISSN 0014-4819. PMC 3746071. PMID 22038715.
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Further readingEdit
- Beyreuther K, Pollwein P, Multhaup G, Mönning U, König G, Dyrks T, Schubert W, Masters CL (Sep 1993). "Regulation and expression of the Alzheimer's beta/A4 amyloid protein precursor in health, disease, and Down's syndrome". Annals of the New York Academy of Sciences. 695 (1 Transduction): 91–102. doi:10.1111/j.1749-6632.1993.tb23035.x. PMID 8239320.
- Straub JE, Guevara J, Huo S, Lee JP (Jun 2002). "Long time dynamic simulations: exploring the folding pathways of an Alzheimer's amyloid Abeta-peptide". Accounts of Chemical Research. 35 (6): 473–81. doi:10.1021/ar010031e. PMID 12069633.
- Annaert W, De Strooper B (2003). "A cell biological perspective on Alzheimer's disease". Annual Review of Cell and Developmental Biology. 18 (1): 25–51. doi:10.1146/annurev.cellbio.18.020402.142302. PMID 12142279.
- Koo EH (Nov 2002). "The beta-amyloid precursor protein (APP) and Alzheimer's disease: does the tail wag the dog?". Traffic. 3 (11): 763–70. doi:10.1034/j.1600-0854.2002.31101.x. PMID 12383342.
- Van Nostrand WE, Melchor JP, Romanov G, Zeigler K, Davis J (Nov 2002). "Pathogenic effects of cerebral amyloid angiopathy mutations in the amyloid beta-protein precursor". Annals of the New York Academy of Sciences. 977 (1): 258–65. Bibcode:2002NYASA.977..258N. doi:10.1111/j.1749-6632.2002.tb04824.x. PMID 12480759.
- Ling Y, Morgan K, Kalsheker N (Nov 2003). "Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer's disease". The International Journal of Biochemistry & Cell Biology. 35 (11): 1505–35. doi:10.1016/S1357-2725(03)00133-X. PMID 12824062.
- Kerr ML, Small DH (Apr 2005). "Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: function, regulation of proteolysis, and implications for drug development". Journal of Neuroscience Research. 80 (2): 151–9. doi:10.1002/jnr.20408. PMID 15672415.
- Maynard CJ, Bush AI, Masters CL, Cappai R, Li QX (Jun 2005). "Metals and amyloid-beta in Alzheimer's disease". International Journal of Experimental Pathology. 86 (3): 147–59. doi:10.1111/j.0959-9673.2005.00434.x. PMC 2517409. PMID 15910549.
- Tickler AK, Wade JD, Separovic F (Aug 2005). "The role of Abeta peptides in Alzheimer's disease". Protein and Peptide Letters. 12 (6): 513–9. doi:10.2174/0929866054395905. PMID 16101387.
- Reinhard C, Hébert SS, De Strooper B (Dec 2005). "The amyloid-beta precursor protein: integrating structure with biological function". The EMBO Journal. 24 (23): 3996–4006. doi:10.1038/sj.emboj.7600860. PMC 1356301. PMID 16252002.
- Watson D, Castaño E, Kokjohn TA, Kuo YM, Lyubchenko Y, Pinsky D, Connolly ES, Esh C, Luehrs DC, Stine WB, Rowse LM, Emmerling MR, Roher AE (Dec 2005). "Physicochemical characteristics of soluble oligomeric Abeta and their pathologic role in Alzheimer's disease". Neurological Research. 27 (8): 869–81. doi:10.1179/016164105X49436. PMID 16354549.
- Calinisan V, Gravem D, Chen RP, Brittin S, Mohandas N, Lecomte MC, Gascard P (2006). "New insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium". Frontiers in Bioscience. 11 (1): 1646–66. doi:10.2741/1911. PMID 16368544.
- Vetrivel KS, Thinakaran G (Jan 2006). "Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments". Neurology. 66 (2 Suppl 1): S69–73. doi:10.1212/01.wnl.0000192107.17175.39. PMID 16432149.
- Gallo C, Orlassino R, Vineis C (Feb 2006). "[Recurrent intraparenchimal haemorrhages in a patient with cerebral amyloidotic angiopathy: description of one autopsy case]". Pathologica. 98 (1): 44–7. PMID 16789686.
- Coulson EJ (Aug 2006). "Does the p75 neurotrophin receptor mediate Abeta-induced toxicity in Alzheimer's disease?". Journal of Neurochemistry. 98 (3): 654–60. doi:10.1111/j.1471-4159.2006.03905.x. PMID 16893414.
- Menéndez-González M, Pérez-Pinera P, Martínez-Rivera M, Calatayud MT, Blázquez Menes B (2006). "APP processing and the APP-KPI domain involvement in the amyloid cascade". Neuro-Degenerative Diseases. 2 (6): 277–83. doi:10.1159/000092315. PMID 16909010.
- Neve RL, McPhie DL (Apr 2007). "Dysfunction of amyloid precursor protein signaling in neurons leads to DNA synthesis and apoptosis". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1772 (4): 430–7. doi:10.1016/j.bbadis.2006.10.008. PMC 1862818. PMID 17113271.
- Chen X, Stern D, Yan SD (Dec 2006). "Mitochondrial dysfunction and Alzheimer's disease". Current Alzheimer Research. 3 (5): 515–20. doi:10.2174/156720506779025215. PMID 17168650.
- Caltagarone J, Jing Z, Bowser R (Apr 2007). "Focal adhesions regulate Abeta signaling and cell death in Alzheimer's disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1772 (4): 438–45. doi:10.1016/j.bbadis.2006.11.007. PMC 1876750. PMID 17215111.
- Wolfe MS (Feb 2007). "When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease". EMBO Reports. 8 (2): 136–40. doi:10.1038/sj.embor.7400896. PMC 1796780. PMID 17268504.
External linksEdit
|Wikimedia Commons has media related to Amyloid precursor protein.
- GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease
- Amyloid+Protein+Precursor at the US National Library of Medicine Medical Subject Headings (MeSH)
- Entrez Gene: APP amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease)
- Human APP genome location and APP gene details page in the UCSC Genome Browser.


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#BLMVP Matchday 1 candidate: Thomas Müller
He may not have got on the scoresheet, but Thomas Müller pulled all the strings as he orchestrated FC Bayern München to a 6-0 opening day victory over SV Werder Bremen.
Top facts - Müller
Is Müller in your Official Fantasy Bundesliga side? If not, sign him up now!
Three Bayern players had just one man to thank that they got on the scoresheet in Bayern's Matchday 1 rout. The champions' very own 'space invader' set up Robert Lewandowski, Philipp Lahm and Franck Ribery. But did he do enough to earn your vote as Matchday 1 MVP?
Vote for Müller for #BLMVP on our twitter channel now!
- ...Aubameyang has found the net on three of his four opening day appearances in the Bundesliga...and has taken his Matchday 1 tally to an impressive six in total....the reigning African Footballer of the Year only needed four shots on goal to complete his brace....his performance would have earned 17 Official Fantasy Bundesliga points!
Click here for the Bayern v Bremen Match Centre
Watch: All 20 of Thomas Müller's goals in 2015/16


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Read the comments under Cate Blanchett's Oscar acceptance speech video and you'll find a bunch of angry fans of Amy Adams.
This year at the Oscars Amy Adams got a Best actress nomination for "American hustle" and lost out to Cate Blanchett for her performance in "Blue Jasmine". Previously, she had had 4 nominations for Best supporting actress: in "Junebug" (lost to Rachel Weisz in "The constant gardener"), in "Doubt" (lost to Penelope Cruz in "Vicky Cristina Barcelona"), in "The fighter" (lost to Melissa Leo in the same film) and in "The master" (lost to Anne Hathaway in "Les misérables").
The fans complain about her having been nominated 5 times and never won, and fear that she'll be the female Leonardo DiCaprio.
Before continuing, I should note that I do like Amy Adams, and find her the best thing in "American hustle", better than Christian Bale, who in this film has a pale, unremarkable performance, better than the overrated Jennifer Lawrence and the always-the-same Bradley Cooper and better than the film itself. Her Sydney has all that is required: sauciness, confidence, manipulation, emotional depth and a drive for survival. She lets us see the tragedy behind the character, the vulnerability underneath that mask of confidence and total control, though sometimes makes us wonder whether she's sincere or using people for some plan. Jennifer Lawrence's character should be the more interesting part, the driving force, but Amy Adams becomes the emotional centre of the film.
However, the idea that she could defeat Cate Blanchett or that she deserved the Oscar more, is absurd. I say this not because I'm a fan of Cate. Daniel Day-Lewis was great in "Gangs of New York" and Adrien Brody's career has gone downhill since his win, but Adrien Brody's performance in "The pianist" has greater emotional depth and therefore deserves the award. Last year Daniel won for "Lincoln" and I'm glad he did, but if the Oscar had gone to Joaquin Phoenix instead, I would have accepted it calmly, without spite, since Joaquin Phoenix's phenomenal in "The master". I think Meryl Streep's performance in "Doubt" is excellent, though not more remarkable than her previous ones for she's always excellent, is much greater than Kate Winslet's performance in "The reader"- a lovely actress who was miscast and unable to go beyond the miscasting, but if I find it sad that Meryl didn't win for the heartbreaking film "A cry in the dark", I can't disagree with the Academy's decision to award Jodie Foster, who was unforgettable in "The accused". Which is to say, my admiration for Cate has nothing to do with my judgment. Cate Blanchett's portrayal of Jasmine is 1 of those flawless, outstanding, jaw-dropping, phenomenal portrayals of very complex, multifaceted and deep characters, performances which can't be topped and which definitely win. Such performances are not common- 1st it depends on the writer to create such a character, then the rest is done by the actor. Jennifer Lawrence in "Silver linings playbook" isn't. Sandra Bullock in "The blind side" isn't. Reese Witherspoon in "Walk the line" isn't. Gwyneth Paltrow in "Shakespeare in love" isn't. Frances McDormand in "Fargo" isn't. Jodie Foster in "The silence of the lambs" isn't. I don't mean that they don't deserve their Oscars- what I mean is that there are some performances that must win, because the idea that they don't is unthinkable, unimaginable, incomprehensible, and the ones mentioned aren't like that- in another year they might not have won. The performances I consider phenomenal can be such as Marion Cotillard in "La vie en rose", Hilary Swank in "Million dollars baby", Meryl Streep in "Sophie's choice", Vivien Leigh in "A streetcar named Desire" and "Gone with the wind"... and now Cate Blanchett in "Blue Jasmine".
To go back to Amy Adams, I have no comment on the 1st nomination, as I haven't watched "Junebug" and "The constant gardener". In "Doubt", her character doesn't give her (or anybody) a chance to shine and she's overshadowed by Viola Davis (nominated in the same category), Meryl Streep and Philip Seymour Hoffman. In "The fighter", Christian Bale and Melissa Leo take turns to steal the show, pushing everyone else to the background. In "The master", next to the wonderful Joaquin Phoenix and Philip Seymour Hoffman, she manages to create a strong and deep impression on me, with her sweet, calm voice and piercing, lunatic eyes, which another person might not have done, but Anne Hathaway's heartbreaking in "Les misérables".
I don't know what her fans have to complain about.
As someone who does like Amy Adams, I hope she gets truly fascinating roles (unlike that one in "Doubt") and some luck (unlike the way Hugh Jackman and Joaquin Phoenix, whom I both like, got a role of a lifetime and were nominated the same year with Daniel Day-Lewis). But angry because she got 5 nominations and never won? That's absurd.


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Jewish Medical Student Association
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The Jewish Medical Student Association is an organization affiliated with the Wayne State University School of Medicine. Run by first- and second-year medical students, JMSA offers a variety of opportunities to connect with and volunteer for the Jewish community of Detroit and its surrounding suburbs. Come join us in having a great 2013-2014 academic year!
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Lil Mo Opens Up Saying "I Never Thought I Could Get Off Opioids"
Lil Mo shared a revealing message about overcoming her opioid addiction on the gram. The brutally honest post is of a photograph of a black background with white writing that reads, "I never thought I could get off opioids." The opioid crisis is serious and seems to have infiltrated Lil Mo's life but thankfully the artist has kicked the habit and has a positive message to send.
Charley Gallay/Getty Images
The caption on the black and white picture says, "BUT I DID!!!!!!! the OPPS is real mad that I can speak about not having to wake up and pop a 30 PLUS, addi, tramadol and/or whatever else was brought into the house by the devil." The Superwoman singer continued her caption stating, "was just the MONEY. Not gonna even CAP. Spent sooooo much (money) paying other people bills just to be high and a functioning addict. Glad I let the TOXIC GO!!!!"
The post continues with the talented entertainer stating that she still has more work to do and "more people to cut off" but she is celebrating her sobriety publicly on the gram. After such a hard battle with incredibly addictive substances, this is definitely something to be proud of.
Lil Mo promises that 2020 will be a big year for her and her children, and says thank you to her supporters who helped her get to this good place.


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The second 'Candidate of the Term' winner was Caroline Brown, one of our Tutors at Academic Appointments. Progress Lead Lisa , nominated her based on the feedback she has received from both the carers and pupils that she works with, as one describes her as "amazing and both myself and the school have seen progress and confidence in the children. She is an asset to Academic Appointments".
Today at our Tuition Open Day Lisa presented Caroline with her certificate and prize.
Academic Appointments would like to thank our Progress Lead, carers and pupils Caroline works with for taking part in 'Candidate of the Term'. Thank you to Caroline for all her hard work, dedication and resilience that she has shown. She is truly an Ambassador for Academic Appointments!


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TheminiSD Cardis a restricted form factor detachable and portable reminiscence gadget supposed to be used in fallacy telephones/cellphones, digital cameras, MP3 players and lots of different devices.


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text: Micron Technology, Inc. is an American global corporation based in Boise, Idaho which produces many forms of semiconductor devices, including dynamic random-access memory, flash memory, and solid-state drives. Its consumer products are marketed under the brands Crucial Technology and Lexar. Micron and Intel together created IM Flash Technologies, which produces NAND flash memory.


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China Culture Center
Come and join CCC's Chinese painting class. You don't have necessarily learnt Chinese painting before, just have to be enthusiastic and be willing to hold a brush. Traditional Chinese painting is done with a brush dipped in black or colored ink; oils are not used. As with calligraphy, the most popular materials on which paintings are made of are paper and silk. The finished work can be mounted on scrolls, such as hanging scrolls or handscrolls.
The class will be conducted in English. The supplies or the Four Treasures of the Study - the ink brush, ink, paper(made of rice & bamboo), and inkstone - are provided by them.
· You don't necessarily have learnt Chinese painting before, just be enthusiastic and be willing to hold a brush.
· Both beginners and higher level can enjoy and grasp the skills in the class.
· You can choose to join just one single class or attend the whole course.
· The class is in small group and conducted in English.
Price: RMB 200/ class/ person. Both visitors and expatriates are welcome to join. Registration is essential. No walk-ins.
China Culture Center
They are an cultural education organization that has tasked ourselves to share (in English) with others the wonder and diversity of Chinese history and culture.
They are a privately owned and self-sustained organization. They use our innovative travel (CCC Travel) and corporate products to fund our not-for-profit research and cultural education programs.
Most of all, They are a group of English-speaking cultural enthusiasts who want to introduce you to everything about this country, from Confucius to calligraphy, Genghis Khan to green tea, martial arts to feng shui. They are an organization for anyone looking for a way to explore China's past, present and future.
Since culture is the embodiment of the history and customs of a nation, CCC strives to provide a window into Chinese society.
They were the first cultural organization to specifically cater for foreigners living in Beijing, and since 2000, CCC has become the most trusted travel and learning center, through which expatriates, as well as their visiting families and friends, experience the original China. In addition to a core group of expatriates who frequent our tours, lectures and classes to enrich their knowledge about China, more and more independent travelers and returning visitors are choosing the CCC to help them get under the surface of China.


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(SL) – YES that is a REAL image. Hurricane Matthew is scarier than ever and most people believe the image that appeared on weather maps is a bad omen. Even though Matthew lost some wind speed overnight reducing it to a Category 3 storm at 115 mph but is expected to regain Category 4 strength by the time is reaches Florida.
Matthew's high winds and rainfall caused landslides, flooding, and the destruction of homes and businesses across Haiti, the Dominican Republic and Cuba who were starting rebuilding efforts today. 17 People are reportedly dead. The storm is now headed towards the Bahamas.
In the US, Florida Governor Rick Scott has issued a state of emergency and fears Matthew could do as much damage as Andrew did in 1992; while South Carolina Governor Nikki Haley says she's prepared to evacuate at least a million people. North Carolina and Georgia will also be effected by Matthew.
At it's height, the hurricane was a Category 5 with wind speeds of more than 157 mph. Those speeds have dropped but forecasters predict it will strengthen to a Category 4 hurricane by the time it pummels Florida, Georgia, South Carolina and North Carolina.
The National Hurricane Center in Miami has just extended its hurricane watch in Florida top cover a 350-mile stretch from Deerfield Beach near Fort Lauderdale, to Fernandina Beach, meaning hurricane force winds of 74 mph or higher could occur within two days.
The worrying forecast was made all the more unsettling by the appearance of the strange skull formation in the weather map of Hurricane Matthew yesterday. It is REAL and not photo-shopped.


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More than 13 years since her last big screen appearance, video game heroine Lara Croft is getting the reboot treatment – and now we have our first hints of what her next story will be about.
2001's 'Lara Croft: Tomb Raider' and its 2003 sequel 'Lara Croft Tomb Raider: The Cradle of Life' saw Angelina Jolie memorably portray the role (alas, she was the only really memorable thing about either film), but the upcoming 'Tomb Raider' will see recent Oscar-winner Alicia Vikander (Best Supporting Actress for 'The Danish Girl') don the iconic vest and shorts.
Early rumours had suggested this new take on 'Tomb Raider,' the best-selling video game series launched by Core Design and Eidos Interactive back in 1996, would be an origin story of sorts for the iconic British aristocrat and treasure hunter – and the film's producer Graham King has now more or less confirmed this.
King tells Hey U Guys, "This is kind of what we call a 'back to the roots story'.
"This is a young Lara Croft in search to see if her father is dead or alive, so it has a very emotional part to it, and I think that's what Alicia found so interesting about it.
The producer continued, "I think the storytelling is really good and I think we've got the right crew and a great director, and I think it's going to be a lot of fun making a film like this."
Directorial duties on 'Tomb Raider' have been handed to Roar Uthaug, Norwegian director of disaster movie 'The Wave' and Viking adventure 'Escape.'
'Tomb Raider' is due in US cinemas 16 March 2018 – no UK release date has been confirmed at present.
Read More:
Director in talks for Mortal Kombat reboot
Paul Feig won't do another remake after Ghostbusters
Gal Gadot on wearing the Wonder Woman suit


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Recently I have re-discovered google maps. One amazing function I wasn't aware of was to plot various points and create your own map in "My Maps".
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Male Breast Reduction Richmond
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Most 15 Wire Shelving, Rv Closet Ideas
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Wire Shelving, Rv Closet - Our rv came with manufacturing unit hooked up wall netting within the bunkroom. I was skeptical before everything however it has grew to become out to be a extraordinary solution for some larger greater awkward gadgets that gained't fit within the closets just like the boys' hydration packs and rock band guitars. I'm hoping to procure an idea or two. I recognise i did whilst i was scripting this put up! Now i need to recognize approximately you! How do you store area for your rv? Any organizational suggestions to percentage?.
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