Places not to visit with parents

first_imgAs kids, we enjoyed travelling with parents and that was the beginning of our learning process. But certainly as adults it becomes more important to explore and experience on your own or with your friends for many reasons. We have listed few destinations for you where you should avoid taking your folks because it might give them a heart attack. Some places are best enjoyed alone.BangkokBangkok Thailand never fails to surprise as it has all on display for everyone. If you are a dirty soul and would like to explore Bangkok from every angle then chuck the idea to visit this place with your parents and get ready for ping pong shows, bizarre eateries and share a confab with fellow backpackers.BrazilBrazil A perfect destination for a young soul, a land of gorgeous people and gyrating dancers Brazil is the definition for exotic. This is certainly one place to be with your friends and go wild. So put on your most sultry outfit and groove on some Samba and Bachata. You really think that you can ever be with parents in Vegas? This is one place where gambling and getting married while you are dead drunk, is not a sin. The pouring drinks, casinos and a place where time has no value is certainly not a place for a family getaway.NepalNepal Known for its hippie trail in the 60’sm, Nepal is still a stoner’s hub and banned as it is. One should be very alert because you might draw preying eyes of the peddlers. But certainly you can enjoy the adventure sports in Nepal because it is rich in multitudes of terrain and landscape, facilitating some of the best extreme sports.advertisementlast_img read more

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China denies visa to Indian badminton team manager

first_imgThe China Open is already underway and India’s Saina Nehwal has bowed out as well. But India’s team manager Bamang Tago is stranded back home and is not allowed to travel to China. (Latest Sports stories)Tago has been denied visa by the Chinese Embassy and the reason is a perennial problem that the people from Arunachal Pradesh have been facing while visiting China.Tago was named manager of the Indian team for the China Open but the Chinese Embassy has said the decision is taken by the government official in Beijing and he will not be granted visa.”It is a clear case of discrimination since I come from Arunachal Pradesh,” thundered Tago, who is also the secretary general of the Arunachal Pradesh Badminton Association.The members of the Indian contingent had applied for visa on November 10 for the China Open, which is a prestigious Super Series tournament in the BWF calendar.”Unofficially, people in the embassy have told me that the only reason why I have been denied visa is because of where I hail from,” Tago told India Today.”But they can’t say this officially. That is the reason why they have informed me officially that the decision is taken by the officials sitting in Beijing,” he added.It is not the first time that people from Arunachal Pradesh have been denied visa by the Chinese government. In the past, China has often issued stapled visa to the Indian citizens. India have objected to issuance of stapled visa by China.advertisementTago was to lead a 14-member Indian team on the invitation of Fuzhou Municipal Sports Bureau to participate in the Thaihot China Open in Fuzhou, which started yesterday and will conclude on November 20.last_img read more

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10 months agoArsenal move for Juventus defender Medhi Benatia

first_imgTagsTransfersAbout the authorPaul VegasShare the loveHave your say Arsenal move for Juventus defender Medhi Benatiaby Paul Vegas10 months agoSend to a friendShare the loveArsenal have made a move for Juventus defender Medhi Benatia.Gazzetta dello Sport says the Gunners are keen to land the Juventus defender during the January transfer window.The 31-year-old has fallen down the pecking order with the Serie A champions.And with the Morocco international’s future uncertain in Turin, Arsenal have enquired about his availability.Unai Emery is open to bolstering his backline this month due to a spate of injuries.Benatia could potentially be used as part of the deal to take midfielder Aaron Ramsey to Turin. last_img read more

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21 days agoInter Milan striker Lautaro Martinez left frustrated by Barcelona defeat

first_imgAbout the authorCarlos VolcanoShare the loveHave your say Inter Milan striker Lautaro Martinez left frustrated by Barcelona defeatby Carlos Volcano21 days agoSend to a friendShare the loveInter Milan striker Lautaro Martinez left frustrated with their Champions League defeat at Barcelona.Inter lost 2-1 on Wednesday night, despite Martinez’s early opener.”My goal must be put to one side,” the forward told ESPN.“We had to win and we were doing very well, but the game ended with great bitterness.“We had to take more of the chances we made. Messi is the best player in the world and Barca are hard to beat when he’s is on the pitch.“You can’t leave him an inch of space because otherwise, the match gets out of hand.” last_img read more

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The Story of GORD FM

first_imgAdvertisement Login/Register With: As a radio programmer, I go through periods of confidence and insecurity. This week, I had lots of the former and a bit of the latter.We all knew it was coming but the news was still difficult to hear. I read my breaking news alert at 8:36 am Wednesday morning “Gord Downie has died”.Behind the scenes, we had been preparing for his passing for months and months. I work with a great team of passionate and caring and talented broadcasters who take their roles and responsibilities seriously and gosh, did I mention they are talented. They have balanced the morbid nature of planning for someone’s death with the audience expectations when it arrives. Where will our listeners turn at a time when they need comfort and to have their feelings validated with likemindedness? Advertisement READ MORE Twitter Advertisement Facebook LEAVE A REPLY Cancel replyLog in to leave a comment last_img read more

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Manitoba considers calling in army to help northern First Nations

first_imgAPTN National NewsManitoba’s deputy premier says he’s prepared to ask the army to help resupply isolated and northern communities.That’s if warm weather on the prairies continues to delay building the winter road network.Construction is already weeks behind schedule because of unseasonable temperatures.That’s why numerous northern Manitoba First Nations have declared a state of emergency.In the Island Lake area, no ice raods means no supplies from Ottawa to address their water crisis.And other communities like Berens River have run out of fuel and may need to fly it in.Manto Sipi Cree Nation did run out of diesel last month, but are expecting their fuel supply to last if cold weather allows for the roads to open.last_img read more

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BET show Being Mary Jane Viacoms African and Afri

first_imgBET show Being Mary JaneViacom’s African and African-American culture and entertainment channel BET will launch on SVOD in France after inking a deal with fledgling streaming service Afrostream.The BET linear channel launches in France later this month. It is rolling out on the CanalSat, Numericable/SFR, Free and Bouygues Telecom pay TV platforms, giving it a reach of 17.6 million French homes.It will now have an additional SVOD presence on Afrostream. The France-based start-up grew out of a transactional video-on-demand stream on the MyTF1VOD service in France focused on African and African-American movies. It struck a movie deal with Sony Pictures Television soon after its launch announcement earlier this year.The service is backed by seed-funding enterprise Y Combinator.it was co-founded by theatre producer and entrepreneur Tonjé Bakang.The linear channel BET rolls out on November 17 and Afrostream subs will be able to access the service from launch. As well being able to view the live feed there will be a seven-day catch-up service.“I’m glad to be forging a strategic partnership with Afrostream and its founder, Tonjé Bakang.  Our collaboration will enable us to cater to the Black audience in France,” said Michael Armstrong, executive VP & GM, International Brand Development, VIMN. “While BET France will feature Black content from the US, this partnership will allow us to begin developing locally relevant content as well.”last_img read more

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Amazon Fire TV has rounded out its UK broadcaster

first_imgAmazon Fire TV has rounded out its UK broadcaster catch-up TV services offer by adding Channel 4’s on-demand platform, All 4.The Amazon service already offers BBC iPlayer, ITV Hub and Demand 5, as well as Netflix, UKTV Play, YouTube and other on-demand apps.Adding All 4 means Amazon Fire TV owners can now access programmes such as Catastrophe and Homeland on-demand, plus digital-only content, in the UK.Over theChristmas period All 4 also joined games console PS4’s offer. New foreign-language drama platform Walter Presents debuted on the console yesterday.last_img read more

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Another week another set of statistics heralding

first_imgAnother week, another set of statistics heralding doom for the US pay TV business. Stuart Thomson weighs up the evidence. This week saw the release of new statistics highlighting the dire trajectory of the US pay TV industry. While analysts’ respective counts of the extent of the losses may vary slightly, the direction of travel is clear. Cord-cutting is accelerating. Pay TV is going down.According to Kagan, traditional pay TV subscriptions dropped by 3.7% last year to 94 million. There is a slender silver lining: the rate of decline slowed down in the fourth quarter.Another analyst outfit, Leichtman Research Group, calculated that the top US pay TV providers accounting for 95% of the market lost close to one and a half million subscribers over the course of the year, double the loss experienced in 2016. The absolute number of losses would have been much greater – double in fact – had it not been for the growing bases of pay TV operators’ online offshoots such as DirecTV Now and Sling TV.Digital TV Research meanwhile predicted that US pay TV subscribers will decline by a further 10 million between now and the end of 2023, with penetration declining from a high of 87.6% in 2013 to just two thirds of TV homes five years from now.Digital TV Research also predicted that US pay TV revenues will decline to US$36.8 billion by 2023 from a peak of US$54.1 billion in 2013, with the lower take from online skinny bundles failing to offset losses from the big bundles US operators have traditionally.Figuring out the broad causes of this precipitous decline doesn’t require much head-scratching. This week also saw the publication of TiVo’s Online Video and Pay TV Trends report, which concluded squarely that the high price of pay TV packages provides the major incentive to cut the cord, with consumers expressing a strong desire only to pay for the channels they watch.The desire to pay less is reinforced by changes in consumption habits. In another report released this week, Parks Associates calculated that three fifths of video viewed in US broadband homes is now on-demand, non-linear content. Even linear viewing in fast migrating online, with 30% of heads of households under 35 now viewing live content primarily via an online service.From a European perspective, US pay TV seems hugely overpriced. The TiVo survey found that close to half of respondents pay between US$51-US$100 a month for pay TV, with 20% paying over US$126. And no single US pay TV operator has quite the same vice-like grip on premium live sports as the likes of a Sky. NFL rights, for example, are shared between the big four TV networks with cable offshoots such as NBC Sports and Fox Sports, cable network ESPN, owned by Disney, and the NFL Network. With Disney planning to launch direct-to-consumer ESPN+ and movie services next year, traditional pay TV’s appeal seems likely to diminish further.For pay TV providers, that would seem to leave broadband and multi-play as the last line of defence. Broadband is of course a strong line. Consumers may be abandoning subscription TV but they need a broadband connection in order to view Netflix and other OTT TV streaming services ­– including Disney’s. And in truth, US cable is still a huge cash-generating machine, with income receiving an additional boost this year thanks to President Donald Trump’s tax giveaway.Nevertheless, while pay TV operators are looking to broadband and multi-play to drive revenue growth and cash-flow, TV and media remain extremely important. The biggest player, Comcast, as owner of NBCUniversal, spans both infrastructure and premium content, and it is interesting to consider that Comcast and Disney are now rivals for control of Europe’s pay TV leader Sky.Comcast, with its huge infrastructure-based subscriber count, is by far the larger of the pair, with revenues of US$85 billion to Disney’s US$56 billion. However, it is instructive to note that Comcast’s Brian Roberts is adamant that the attraction of Sky is that it is “a media company”. Robert compared the pairing of the Comcast and Sky to what was achieved “when Comcast got together with NBCUniversal”. For Roberts at least, it seems that content is still King, and pay TV is still a business that makes sense.last_img read more

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Uber Is Building a Flying Taxi Technology Center in Paris

first_img Add to Queue Uber Is Building a Flying Taxi Technology Center in Paris Image credit: Uber It has had an adore/déteste relationship with the city of lights. –shares Learn how to successfully navigate family business dynamics and build businesses that excel. 3 min read May 24, 2018center_img Next Article Uber Free Webinar | July 31: Secrets to Running a Successful Family Business This story originally appeared on Engadget By Steve DentUber has wildly ambitious plans to send flying taxis soaring over cities, but building them will be orders of magnitude harder than anything it has ever done. As such, the company announced that it will open a Paris lab dedicated to its Elevate program called the Advanced Technologies Center in Paris (ATCP). Uber will spend €20 million ($23.4 million) over five years to develop the AI algorithms, air traffic control and other tech necessary for the service.Related: Uber Shows Off Its Flying Car Prototype! 3 Things to Know Today.Uber will recruit engineers, AI specialists and computer vision researchers when the center opens this fall. “Initial projects will include: machine learning-based transport demand modeling, high-density low-altitude air traffic management simulations, integration of innovative airspace transport solutions with European aviation regulators such as EASA and the development of smart grids to support future fleets of electric transport on the ground and in the air,” Uber said in a press release.Emmanuel Macron at Paris tech hub “Station F”France, under President Emmanuel Macron, is rapidly becoming a hub for machine learning research. Google recently said it that it’s building a deep learning team in the nation, and Facebook also plans to double its AI team there. The reason? France produces a lot of AI graduates at schools around the country, and plans to create a dedicate artificial intelligence program with the aim of doubling the number of students.With lots of demand for talent in France, though, Uber won’t necessarily find it easy to recruit grads or researchers. It has had a bumpy ride there, with executives still facing legal action over laws that forced it to shut down UberPop in 2015, following violent taxi strikes. As in the US, the company also has lingering reputation problems over sexual harassment and passenger safety that might figure into an AI researcher’s decision to work there.Related: Arizona Governor Suspends Uber’s Self-Driving Car TestsThe biggest problem, though, is that flying cars have never been done before, and for good reason: The technology, costs, logistics and regulations are all massively challenging. Experts are skeptical it will happen any time soon, and even Elon Musk, who likes flying things, said last year that “if somebody doesn’t maintain their flying car, it could drop a hubcap and guillotine you.” Register Now »last_img read more

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US Safety Agency Urges Galaxy Note 7 Owners to Stop Using Smartphone

first_img Autoplay: On | Off 2 Delicious Summer Entertaining Ideas North Carolina superintendent says new app can help reduce violence in schools 2 Musts for Tackling Allergy Season –shares Rock and Roll Hall of Fame Guitarist Don ‘Fingers’ Felder Releases New Album Economy adds 75K jobs in May Owners of Samsung Electronics Co. Ltd. Galaxy Note 7 smartphones should stop using the devices and turn them off because of the threat of a battery fire, the U.S. Consumer Product Safety Commission said on Friday.The CPSC said in a statement it was working with Samsung to announce an official recall of the devices as soon as possible. The agency said it is working quickly to determine whether a replacement Galaxy Note 7 is an acceptable remedy for Samsung or their phone carriers to provide to consumers.(Reporting by Eric Beech; Editing by Mohammad Zargham) Saint Laurent dazzles with men’s collection on Malibu beach Samsung Galaxy Figure Out Your Family Tree Just in Time For Father’s Day A Petition Is Coming ? for a ‘Game of Thrones’ Final Season Do-Over Cannes: ticketless festival-goers seek seats for films Southern Charm’ Star Talks New Season Figure Out Your Family Tree Just in Time For Father’s Day Father’s Day is such a special moment for the whole family to come together and spend quality time with one another – and those are moments dad will cherish. What better way for dad to connect with his loved ones than learning about his family’s stor Lifeminute tv Summer Beauty Survival Must-Haves 1 min read How Human Behavior is Hurting Animals and What We Can Do to Protect Them U.S. Safety Agency Urges Galaxy Note 7 Owners to Stop Using Smartphone Airbnb Wants to Take You on an All-Inclusive Adventure Albany Steps Closer to Releasing Trump’s State Tax Returns After Assembly Vote DiCaprio, Pitt want to team up again after Tarantino hit Congress Is Back as President Trump Heads to the UK A LifeMinute with Ryan Seacrest Photo of solider placing flag at Tomb of Unknown Solider goes viral Former world paragliding champion Rémy soars over Pyrenees Learn from renowned serial entrepreneur David Meltzer how to find your frequency in order to stand out from your competitors and build a brand that is authentic, lasting and impactful. HBO’s ‘Chernobyl’ Phenomenon Summer is here and there are some great looks this season for women of all shapes and sizes. Check out the hottest styles for hourglass, rectangle and pear shaped women. IHOP Sees Explosive Growth in To-Go Sales A Safe Way to Get Rid Of Bugs in Your Home Swimwear Styles for All Shapes and Sizes Delicious Summer Entertaining Ideas New York takes aim at skyscrapers’ sky-high energy usage Justin Bieber Launches Plant-Based Deodorant Heat Snapshot Sophie Turner Talks Dark Phoenix, Co-Star Jessica Chastain and GoT Summer Beauty Survival Must-Haves Memorial Day Weekend Heat Wave Could Smash May Records Cannes: ticketless festival-goers seek seats for films Airbnb Wants to Take You on an All-Inclusive Adventure Turning Up the Heat in the Southeast for Holiday Weekend US Navy: Russian destroyer almost collided with cruiser in the Philippine Sea 2020 Toyota Camry 2020 Ballots May Have a New Box to Check ? Vice President A LifeMinute with John Lithgow: The Actor Discusses His Latest Projects Beyond Meat Earnings Are Beyond Analyst Expectations 2 Musts for Tackling Allergy Season A Petition Is Coming ? for a ‘Game of Thrones’ Final Season Do-Over September 12, 2016 Memorial Day Weekend Heat Wave Could Smash May Records Next Article Add to Queue The requested video is no longer available Figure Out Your Family Tree Just in Time For Father’s Day Figure Out Your Family Tree Just in Time For Father’s Day Consumer Product Safety Commission is working with Samsung to announce an official recall of the device. This story originally appeared on Reuters Sophie Turner Talks Dark Phoenix, Co-Star Jessica Chastain and GoT Economy adds 75K jobs in May Embed Up Next: Figure Out Your Family Tree Just in Time For Father’s Day Reuters Privacy Policy   |   Terms of Use Sunlight Shines on Grand Canyon BACK A Safe Way to Get Rid Of Bugs in Your Home Fireside Chat | July 25: Three Surprising Ways to Build Your Brand IndyCar Beefing Up Business as Indy 500 Approaches Enroll Now for $5last_img read more

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At This Restaurant Human Interaction Is Discouraged

first_imgFood Businesses Stephen J. Bronner With its ‘low-interaction dining,’ food is the focus at Ichiran, a popular chain in Asia that recently expanded to Brooklyn, N.Y. 72shares Next Article When was the last time you truly focused on eating? By that I mean, you placed the food in your mouth, chewed and concentrated on the flavors as they hit your taste buds, without any distractions.I can’t recall the last time I ate without doing something else, such as talking to another person or reading something on my phone.Related: 15 Crazy Fast Food Items From Around the WorldWe all know about the dangers of multitasking, but very rarely do we make an effort to avoid it while we’re eating. Perhaps we should. There are many benefits to meditation, and tuning out our surroundings to focus on food seems like an ideal time to reflect. (Wait, would that be multitasking?)And now there’s a place in New York that aims to help its customers do just that.Image credit: Ichiran NY | FacebookIchiran, which has around 60 locations in Asia, opened a location a few weeks ago in the Bushwick neighborhood of Brooklyn. The chain is known for “low-interaction dining,” according to The New York Times, which, by the way, serves as its differentiating factor in a city filled with plenty of ramen spots. Patrons at the restaurant sit individually at “flavor concentration booths,” with dividers between them. Customers don’t even see the server’s face as they place their orders. (To be sure, the restaurant also features a traditional dining room.)Related: This French Foodie Sensation Is Coming to the StatesPart of me loves this no-bullshit approach to a meal. I am an animal. I need sustenance. Do not get between me and my next meal. Let me eat — and not get distracted by anything else.Image credit: Ichiran NY | FacebookAlas, Ichiran only serves pork-bone based soup with its ramen, and I try to avoid eating mammals, so I won’t get to try this isolationist eatery.Then again, maybe I can just lock myself in a closet with my salad during my next lunch break. Image credit: Ichiran At This Restaurant, Human Interaction Is Discouraged News Directorcenter_img Learn from renowned serial entrepreneur David Meltzer how to find your frequency in order to stand out from your competitors and build a brand that is authentic, lasting and impactful. Enroll Now for $5 2 min read November 4, 2016 Fireside Chat | July 25: Three Surprising Ways to Build Your Brand Entrepreneur Staff Add to Queuelast_img read more

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Bizzabo Study 84 of B2B Tech Leaders Say Event Marketing is Critical

first_img B2B tech organizationsBizzaboEvent Marketing Trends reportEvent Success Platform Previous ArticleBelgian Telecom Provider Speeds Delivery of Customer Services with OracleNext ArticleHCL Technologies Announces Close of Acquisition of Select IBM Products Bizzabo Study: 84% of B2B Tech Leaders Say Event Marketing is Critical to Success MTS Staff WriterJuly 2, 2019, 4:23 pmJuly 2, 2019 Bizzabo’s Study Also Finds 69 Percent of B2B Tech Organizations Plan on Investing More in Events Than They Did in 2018Bizzabo, the world’s leading end-to-end Event Success Platform, released its 2019 B2B Tech Event Marketing Trends report. The company analyzed responses from +1,000 senior-level marketers on how they think about events, discovering everything from how to use events to accelerate sales and lead generation, to how marketers believe in-person events compared to traditional marketing channels and more.More than any other group, B2B tech marketers see real value in events. According to Bizzabo’s study, B2B tech marketers are 18 percent more likely to allocate over 21 percent of their marketing budgets to in-person events, when compared to the cross-sector average.In addition, the study found that in 2019, 69 percent of B2B tech organizations plan on investing more in events than they did in 2018.Marketing Technology News: Broadvoice Welcomes Kim McLachlan as Senior Vice President of Sales and Marketing“B2B tech marketers believe that in-person events comprise the most valuable channel for achieving their business goals,” said Eran Ben-Shushan, Co-Founder and CEO of Bizzabo. “We’ve discovered that, on average, these organizations invest more in events than companies from other sectors.”Bizzabo’s study also saw that in comparison to organizations in other sectors, B2B tech organizations are 3.3x more likely to spend nearly one-quarter of their total events budget on hosting or sponsoring events rather than attending them.Marketing Technology News: Connected TV is Transforming the Digital Advertising Ecosystem: ExtremLatest Video Benchmarks Report Shows 49% of Video Ad Impressions Going to CTV84% of leadership (VPs & C-Suite) believe in-person events are critical. It was also discovered via Bizzabo’s analysis that the majority (84%) of leadership (VPs and C-Suite) believe in-person events are a critical component of their company’s success. In fact, B2B leadership in tech, specifically, spend 2x as much on events than B2B marketers overall.In addition, it was established that organizers who use event software to demonstrate ROI are 10x more likely to receive leadership support for their events.“We’ve seen leadership in the B2B tech sector backing in-person events when the events team is able to prove event ROI,” said Ben-Shushan. “In fact, tech leadership spends twice as much on events then B2B marketers overall.”Marketing Technology News: New Competitive Report by BIA Advisory Services Shows Similarities and Differences Among Leading Call Tracking Platformslast_img read more

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Paternal exercise has significant impact on childs lifelong metabolic health

first_img Source:https://www.joslin.org/ Reviewed by Alina Shrourou, B.Sc. (Editor)Oct 22 2018Recent studies have linked development of type 2 diabetes and impaired metabolic health individuals to their parents’ poor diet, and there is increasing evidence that fathers play an important role in obesity and metabolic programming of their offspring.In a new study published today in the journal Diabetes, researchers at Joslin Diabetes Center have shown that paternal exercise has a significant impact on the metabolic health of their offspring well into adulthood.The study was led by Laurie Goodyear, PhD, senior investigator and head of the Section on Integrative Physiology and Metabolism at Joslin and professor of medicine at Harvard Medical School. The study was co-led by Kristin Stanford, PhD, a physiology and cell biology researcher who is now with The Ohio State University College of Medicine at the Wexner Medical Center.Related StoriesSupervised fun, exercise both improve psychosocial health of children with obesityRegular physical activity can be effective in reducing pain from arthritisResearchers identify molecular pathway underpinning exercise and improved motor learningGoodyear and Stanford investigated how a father’s exercise regimen would affect his offspring’s metabolic health. Using a mouse model, they fed male mice either a normal diet or a high-fat diet for three weeks. Some mice from each diet group were sedentary and some exercised freely. After three weeks, the mice bred and their offspring ate a normal diet under sedentary conditions for a year.The researchers report that adult offspring from sires who exercised had improved glucose metabolism, decreased body weight and a decreased fat mass.”It really shows how important it is for men to exercise prior to conceiving because it will have lifelong effects on the health of their offspring. When we put the males on a high-fat diet, it had a terrible effect on the offspring; but what was surprising was that situation was completely reversed when the male added in exercise. So translated to humans, even if dad isn’t eating really well, he can still affect his offspring positively by exercising,” said Goodyear. “This also will dramatically decrease the risk of developing type 2 diabetes for the offspring,” added Goodyear.The team also found that exercise caused changes in the genetic expression of the father’s sperm that suppress poor dietary effects and transfer to the offspring.”We saw a strong change in their small-RNA profile. Now we want to see exactly which small-RNAs are responsible for these metabolic improvements, where it’s happening in the offspring and why,” Stanford said.The researchers believe the results support the hypothesis that small RNAs in sperm could help transmit paternal environmental information to the next generation.last_img read more

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Triple negative breast cancer develop resistance to chemotherapy by turning on molecular

first_imgReviewed by James Ives, M.Psych. (Editor)Apr 19 2019Researchers at The University of Texas MD Anderson Cancer Center have discovered that triple negative breast cancer (TNBC) cells can develop resistance to frontline, or neoadjuvant, chemotherapy not by acquiring permanent adaptations, but rather transiently turning on molecular pathways that protect the cells.The study, published today in Science Translational Medicine, also identifies a vulnerability that may provide a new treatment option for resistant TNBC. Among those pathways activated is a metabolic process, known as oxidative phosphorylation, which can be targeted by a small-molecule drug developed by MD Anderson’s Therapeutics Discovery division.”Modern chemotherapy is highly effective for nearly half of patients with triple negative breast cancers,” said corresponding author Helen Piwnica-Worms, Ph.D., professor of Experimental Radiation Oncology. “However, the remaining half of women will not fully respond to neoadjuvant chemotherapy, and there currently are no approved treatments to improve outcomes for them. Understanding how tumor cells become resistant will allow us to identify new targets to better treat resistant disease.”According to the American Cancer Society, an estimated 268,000 women will be diagnosed with breast cancer this year, of which 15 to 20 percent will have TNBC. Standard treatment for patients with TNBC is neoadjuvant chemotherapy followed by surgery to remove the tumor. For women with tumors that don’t fully respond to chemotherapy, there is a much higher risk of recurrence and death from the disease, said Piwnica-Worms.In order to study how TNBC cells become resistant to treatment, the researchers created mouse models, known as patient-derived xenografts (PDXs), of TNBC using tumor samples from patients enrolled in the ARTEMIS clinical trial, led by MD Anderson’s Breast Cancer Moon Shot™.Patients enrolling in ARTEMIS have tumor biopsies taken before and after neoadjuvant chemotherapy treatment, which enable researchers to study why some tumors are resistant and discover more effective strategies to bring cures to more patients. The work is part of MD Anderson’s Moon Shots Program™, a collaborative effort designed to accelerate the development of scientific discoveries into clinical advances that save patients’ lives.Related StoriesAI-enabled device detects if targeted chemotherapy is workingRutgers researchers create new device to see if targeted cancer therapy is workingScientists discover how resistance to the chemotherapy drug 5-fluorouracil arisesPiwnica-Worms’ team identified several PDX models that responded to chemotherapy at first, but eventually developed resistance and resumed tumor growth. If treatment was paused, however, the residual tumors once again became sensitive to chemotherapy, indicating the resistance was temporary.Under the microscope, tumors showed distinct changes during treatment, but regrown tumors appeared similar to those before treatment. Further, an analysis of individual tumor cells showed that the heterogeneity of cells in a given tumor was maintained after treatment, suggesting that chemotherapy did not select for a small subset of resistant cells.Characterization of gene expression changes revealed a set of pathways activated as part of the resistant state, which were turned off when chemotherapy was discontinued. The researchers confirmed many of these molecular changes were mirrored in biopsies taken from ARTEMIS patients.Hoping to find new treatment targets for resistant TNBC, the researchers discovered that these cells had become dependent on oxidative phosphorylation for energy production. This pathway is the target of IACS-10759, the first-small molecular discovered and developed by MD Anderson’s Therapeutics Discovery division.When treating the PDX mice with IACS-10759 following chemotherapy treatment, the researchers observed a synergistic effect, suggesting sequential treatment of chemotherapy and IACS-10759 could prolong the duration of treatment response. IACS-10579 is now in clinical trials for a variety of hematological and solid cancer types.”Our study provides a compelling rationale for defining additional properties that enable triple negative breast cancers to survive chemotherapy treatment, so that combination therapies can be developed to eradicate this disease,” says Piwnica-Worms. “A long-term goal is to avoid the use of chemotherapy in patients with resistant disease and instead employ targeted therapies to avoid unnecessary treatments and harsh side effects.”Source: https://www.mdanderson.org/last_img read more

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New protein target for deadly ovarian cancer

first_imgThe good news about the newly discovered protein is that it can be inhibited, thus inactivating cell processes within ovarian cancer cells to switch them from a constitutively proliferative cell cycle to one which results in senescence, or going to sleep. The key role of the protein was identified on cell culture experiments by researchers at Penn State College of Medicine.The current study focused on teasing out the differences in the metabolism of ovarian cancer cells by comparing them with cells from a normal fallopian tube.The route used to achieve this was quantitative spectrometry, which helped analyze the metabolites produced by various cellular pathways in the two type of tissue. Among the differences, it was revealed that cancer cells utilized glucose, a form of sugar, via the key energy cycle called the citric acid cycle, far more often, as against the more common use of an oxygen-requiring pathway called aerobic glycolysis. This accounts for the presence of a high level of citric acid activity in all high-grade serous ovarian cancer cells.  Related StoriesLiving with advanced breast cancerUsing machine learning algorithm to accurately diagnose breast cancerMother calls for protein shake regulation after daughter diesThis means that many therapies which inhibit the breakdown of glucose (glycolysis) to destroy cancer cells may be quite ineffective. Dahl commented that this could often result, in fact, in the production of toxins that harm normal healthy tissue.Instead, the team in the current study looked at the effects of inhibiting the wildtype or normal form of an enzyme, isocitrate dehydrogenase 1 (IDH 1), which plays a vital part in the citric acid cycle. They selected this protein because it was the only one in this pathway that is expressed at higher levels in both adherent and spheroid tumor cells. Increased activity of this enzyme severely impacts progression-free survival, which is an important outcome measured in assessing the effectiveness of any cancer therapy.Mutants of this protein are common in other tumors, but the wildtype form is typically present in cells within HGSC. The researchers hypothesize that the presence of this enzyme is an important advantage to these cells, and its inhibition is a key step to inducing senescence.The researchers found that suppressing the work of this protein stopped cell division completely by suppressing the activity of multiple other genes, inhibiting vital metabolic pathways. Both adherent cells of the primary tumor, and spheroid cells of secondary HGSC, become senescent when the wildtype IDH 1 enzyme is inhibited. Thus, this could be an excellent way to treat HGSC at all stages. This is an important consideration, as ovarian cancers are rarely diagnosed at early stages.While there are already FDA (US Food and Drug Administration)-approved drugs against one of the mutant forms of this enzyme, the team wondered whether they would work against the wildtype form as well. They found that one did, and this is now a part of their continued research agenda.Aird says, “One of our long-term goals is to try and repurpose this already-approved drug as a treatment for this form of ovarian cancer.” Besides adapting existing drugs against the enzyme to fight this type of cancer, the researchers want to examine the differences in the metabolic functioning of normal and HGSC cells more closely. Another goal is to examine the effectiveness of combining IDH 1 inhibitors with other treatments. Journal reference:Targeting IDH1 as a Prosenescent Therapy in High-grade Serous Ovarian Cancer, Erika S. Dahl, Raquel Buj, Kelly E. Leon, Jordan M. Newell, Yuka Imamura, Benjamin G. Bitler, Nathaniel W. Snyder and Katherine M. Aird, Mol Cancer Res June 17 2019 DOI: 10.1158/1541-7786.MCR-18-1233, http://mcr.aacrjournals.org/content/early/2019/06/17/1541-7786.MCR-18-1233 By Dr. Liji Thomas, MDJul 14 2019A new study shows that targeting a specific protein found within quickly spreading high-grade serous carcinomas (HGSC) of the ovary could help contain these cancers. HGSC is the most common and deadly form of epithelial ovarian cancer, which is itself the deadliest cancer of the female reproductive tract. When HGSC spreads outside the ovaries, within the peritoneal cavity, it forms detached balls called spheroids, which may look and act differently from the adherent cells of the primary tumor.The study is published in the current issue of the journal Molecular Cancer Research. However, as researcher Erika Dahl explains, “A hallmark of cancer cells is that their metabolic processes are often different from normal, healthy cells.”  This is called metabolic reprogramming. As one of the outcomes, study author Katherine Aird says, “Cancer cells can grow forever without stimulus.” 70% of HGSC relapse despite treatment, becoming resistant to chemotherapy, which makes the new discovery a true potential breakthrough in the treatment of this tumor.All life at cellular and organism level depends upon thousands of life processes that provide and degrade a range of chemicals required for proper function of the cells and tissues. These intricately interdependent processes together they make up the body’s metabolism. Cancer cell Illustration. Image Credit: Jovan Vitanovski / Shutterstocklast_img read more

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NissanRenault on smoother road but speed bumps loom analysts

first_imgThe new team in Renault’s driving seat face some politically sensitve decisions, with the company ingrained in the French psyche Gaetan Toulemonde, a French auto analyst at Deutsche Bank, told AFP that French interference is a problem and urged Renault to reduce its stake in Nissan.”Don’t forget Volvo more than 20 years ago. The marriage broke up because of the French state,” said the expert, referring to a failed merger between Renault and the Swedish manufacturer.’National property’Despite ongoing strains, analysts generally agree the two firms are now so closely interconnected that a split would be catastrophic.They need each other to develop the technology for electric vehicles, automated driving and connected cars—as well as to compete with the likes of Toyota and Volkswagen, said Lewis.”Given their platform development for the next decade is already intertwined, divorcing now would be difficult” she added.Nakanishi agreed, saying it would now be “impossible” now to end the alliance. “It took 20 years to get to this level. It would take 20 years to unwind,” he said.But Renault is also deeply ingrained in the economy and psyche of France, making any reduced presence politically sensitive.”I want the French people to know: not a day goes by where we are not following as closely as possible the situation of Renault and the alliance,” said Economy Minister Bruno Le Maire.And the bond between France and Renault was summed up in an editorial in the regional French press after the appointments were made public.”Which family has not one day driven in a Renault… it embodies the car of the people.”Referring to French rock star Johnny Hallyday, the editorial concludes: “Renault is to the car what Johnny was to French music. National property.” Explore further Citation: Nissan-Renault on smoother road but speed bumps loom: analysts (2019, January 25) retrieved 17 July 2019 from https://phys.org/news/2019-01-nissan-renault-smoother-road-loom-analysts.html “They need to reduce their stake. That is the only solution to regain trust and make the alliance workable,” added Nakanishi, as reports in the Japanese media said Paris was pushing for a full-on merger. Renault’s appointment of a new leadership duo to replace the detained Carlos Ghosn should ease tensions with Japanese partner Nissan, analysts say, although the French state’s close involvement remains a brake on ties. Carlos Ghosn took Nissan from the verge of bankruptcy and built it into the key partner of a fractious alliance France pushes Japan to accept Renault-Nissan merger: reports Ghosn was the linchpin of the three-way alliance that also includes Mitsubishi Motors, credited with driving together a sometimes fractious threesome with headquarters 10,000 kilometres apart to become the world’s top-selling auto group.But his shock arrest in Tokyo on charges of financial misconduct immediately drove a wedge between Nissan and Renault, with dark mutterings in Paris of a “coup” orchestrated by CEO Hiroto Saikawa to depose his former mentor and seize more power within the group.Saikawa himself confessed Thursday that communications had been “a bit difficult” since the arrest, noting that while Nissan had immediately jettisoned Ghosn as chairman, Renault kept him on as they awaited evidence against him.However, the appointment of old Asia hand Thierry Bollore as permanent CEO and Jean-Dominique Senard from tyre manufacturer Michelin as chairman, should open a “new chapter” in ties, Saikawa told reporters in Tokyo.Janet Lewis, head of transportation research at Macquarie Capital Securities, told AFP the alliance was “in many respects an unprecedented success story” and said it was “positive that Renault is moving forward” with Thursday’s appointments.But she added: “I believe it is less helpful that the French government seems to be so involved in the alliance.”‘Passion to be independent’ Much of the tension between the partners stems from a complex ownership structure that gives Renault 43 percent of Nissan and the French state just over 15 percent in Renault—making Paris the pivotal player.Nissan now outsells its French counterpart and its broad global footprint means it deserves to be seen as more than a junior partner, said Lewis.”Renault should be prepared to alter the working relationship to reflect what Nissan brings to the table—among other things a very strong position in both North America and China, markets where Renault has limited to no presence,” the analyst told AFP.Seen from Nissan’s perspective, the “strong interference” of the French state is “not fair”, according to Takaki Nakanishi, an auto analyst based in Tokyo.Ghosn rescued Nissan from the verge of bankruptcy by tying it to the alliance but now the Japanese firm “has a passion to be independent. They do not want to be part of the French state”, said Nakanishi. © 2019 AFP 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

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