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Tesla sued by Nevada over unpaid taxes automaker says its a clerical

Source: Charge Forward The state of Nevada, where Tesla has an important workforce, filed a lawsuit against the company for a supposed failure to pay $655,000 to the state’s Unemployment Compensation Fund.Tesla claims a ‘clerical error’. more…The post Tesla sued by Nevada over unpaid taxes, automaker says it’s a ‘clerical error’ appeared first on Electrek.

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September 2018 Bring New Sales Record For PlugIn Electric Cars In China

first_imgChina enters six-digits with a sales run in September.In September, some 104,900 plug-in electric cars were sold in China, which is 66% more than a year ago. It never was better (the previous record was 102,635 in December 2018), and as sales usually increase in the fall of each year, it’s just the foundation for more six-digit results in the following months.Because overall car sales decreased by 12%, plug-in share went through the roof to 5.2% (a new high).During the first nine months of 2018, some 649,356 plug-in electric cars were sold in China at an average 3.3% market share.See Also Quick Look At New Energy Vehicle Sales In China Through August 2018 Author Liberty Access TechnologiesPosted on October 22, 2018Categories Electric Vehicle News Source: Electric Vehicle News The biggest brand in the New Energy Car segment is BYD with 19%, while foreign brands all together take just 6% (including 2% Tesla and 2% BMW).The best-selling model in September was BYD Tang, which set its own new record (6,019) and was the top choice also in August. The Tang plug-in hybrid is available with 20 kWh or 24 kWh battery, which is quite decent for a PHEV.The next four places for the month were BEVs: Chery eQ (5,310), BYD Yuan (5,008), Hawtai EV160 (4,780) and JAC iEV S/E (4,621).YTD ranking leader BAIC EC-Series noted 3,943 sales – which means it keeps improving although still far from its best of times.Tesla apparently sold less than 200 Model X, while the NIO 1,766 ES8. BMW managed to sell 2,216 530e.Plug-in electric car sales in China – September 2018Source: EV Sales Blog BYD Sets 4th Straight Plug-In Car Sales Record Construction Already Underway At Tesla Gigafactory 3 In China: Videolast_img read more

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Whats It Like To Own A Honda Clarity PlugIn Hybrid For 8

first_img Honda Clarity PHEV Videos Claim Best In Class: Beats Volt, Fusion Energi Honda Releases Clarity Plug-In Hybrid Versus Chevy Volt Video Source: Electric Vehicle News Overall, reviews about the Clarity PHEV have been primarily positive. However, we’ve noted that many people are not so fond of the car’s facade. Still, it offers enough electric range to handle most people’s daily needs, it comes packed with standard active safety features, and it has a respectable amount of passenger and cargo volume.Now, we just need Honda to release a refreshed Clarity with sporty good looks. In a perfect world, we’d love to see Honda come forth with a truly competitive Clarity BEV that’s available for purchase nationwide. Sadly, the current offering is only leasing in select areas and provides a meager 89 miles of range, which is far from acceptable today.Check out the video to learn about Brad’s takeaways. Then, leave us your insight in the comment section below or on our Forum.Video Description via Brad on Cars on YouTube:DIY Car Review – 2018 Honda Clarity Hybrid 8 month reviewHey everyone!I noticed my other Clarity videos were gaining some views, so I thought I would share a bit of what ownership is like with one of these.As I state in the video, I am just shy of 15 000km on the car after about 8 months of ownership (I bought it new). I talk about the car itself, what I use the car for, and (most-importantly) how efficient it is! Have a look! What Honda Clarity Owners Want You To Know About Their Car As the Chevrolet Volt nears its departure, we’re getting an influx of Honda Clarity PHEV content.Honda has seemingly ramped up its Clarity Plug-In Hybrid marketing as of late. In addition, the car has sold well over the last eight months. In fact, the last two months have proven outstanding as far as deliveries are concerned. This is likely because the Clarity PHEV is the only real Chevrolet Volt rival with a solid all-electric range estimate. Not to mention the fact that Honda is a highly respected automaker. So, what does Brad on Cars think of his 2018 Clarity Plug-in Hybrid after eight months and ~15,000 km?Additional Honda Clarity Plug-In Hybrid Coverage: Author Liberty Access TechnologiesPosted on December 4, 2018Categories Electric Vehicle Newslast_img read more

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RollsRoyce hopes to shatter electric airplane speed record

first_imgSource: Rolls-Royce via New Atlas Source: Electric Vehicles Magazine A partnership led by Rolls-Royce is building an electric aircraft that it hopes will reach a top speed of over 300 mph and beat the previous speed record of 210 mph set in 2017 by Siemens.The project is part of a Rolls-Royce initiative called Accelerating the Electrification of Flight (ACCEL), which is partly funded by the UK government, and also involves corporate partners including electric motor and controller manufacturer YASA and aviation start-up Electroflight.Working out of Gloucestershire airport in central England, ACCEL is drawing on Formula E expertise in an effort to build an electric aircraft that tops out at over 300 mph to set a new e-plane record, and perhaps someday even exceed the 1931 Schneider Trophy record set by a Supermarine S.6B that used a Rolls-Royce “R” engine to reach 343 mph in 1931.The Rolls-Royce team is working on a battery pack with 6,000 cells that it claims is the most energy-dense ever to be installed in an aircraft. The powertrain will run at 750 V with a maximum power of 750 kW, and the pack will be cooled by an Active Thermal Management System Cooling radiator. The plane will have enough range to fly from London to Paris nonstop.Rolls-Royce has released a cool blueprint of the racing plane with a wealth of technical details. The battery pack feeds three 750R lightweight e-motors built by YASA. The three electrically-actuated blades of the single propeller operate at 2,400 rpm with an efficiency of up to 90 percent. Sensors will monitor 20,000 points in the powertrain to provide the engineers with plenty of data on performance.“This plane will be powered by a state-of-the-art electrical system and the most powerful battery ever built for flight,” says Matheu Parr, ACCEL Project Manager for Rolls-Royce. “In the year ahead, we’re going to demonstrate its abilities in demanding test environments before going for gold in 2020 from a landing strip on the Welsh coastline.”last_img read more

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MercedesBenz eSprinter Electric Van Completes Final Endurance Tests

first_imgSource: Electric Vehicle News Electric Van Face-Off – Mercedes eSprinter vs eVito More about winter tests:“Customers place the same demands on electric vans as they do on equivalent vehicles with combustion engines. One of the most important factors here: complete reliability – even in severe conditions. The winter endurance tests on the Mercedes-Benz eSprinter focussed precisely on this. For several weeks the development team subjected the fully-electric van to a true endurance test in Sweden’s Arjeplog. At temperatures as low as minus 30 degrees with icy roads and deep snow, the eSprinter proved its operability under extreme conditions. Thus the vehicle completed one of its last milestones on the way to its market launch in the second half of 2019.The vehicles were put through numerous complex tests on the difficult test site close to the Arctic Circle. Testing included driving on a frozen lake to examine the effects of extreme cold on handling, ergonomics and comfort using special measuring technology. The starting behaviour and low-temperature resistance of the drive components, software and interfaces were tested in cold cell facilities.How the vehicles respond to different weather conditions is critical to the electric vans functioning in tough daily operations, for example in the CEP sector (courier, express, package). With a range of around 1501 kilometres when configured with a battery capacity of 55 kWh, the eSprinter is perfectly designed for inner-city short-radius distribution. The tests in Sweden have shown: even in the unfavourable conditions described here, a range of around 1001 km is still available to the customer.Electromobility with Mercedes-Benz standards: high quality and safety demands are placed on the driver’s workplaceAnyone who drives a van daily, places high demands on the driver’s workplace. That is why quality and safety are equally important for electrically driven vans. Even at temperatures far below freezing, it must be possible to free the windows from ice as quickly as possible and heat the driver cabin reliably. To this end, the temperature of the test vehicles and their batteries was lowered to extremes in special cold cells in order to test the starting behaviour and thermal management during so-called cold starts. A further important element of the test: charging behaviour. The eSprinter is equipped with an integrated fast-charging function with which it can recharge around 80 % of its energy in 30 minutes – this is a great advantage in the daily routine of a van which must function reliably whatever the temperature.Also, reliable handling in ice and snow as well as resistance of the components to wintry conditions are vital to daily operations. This is exactly what the team of more than 30 engineers, electronics experts and mechanics from  Mercedes-Benz Vans have ensured in numerous tests in Sweden’s Arjeplog. The conclusion of the testers was that the eSprinter is fit for customer operations – even in Arctic conditions.“Yet again we asked a lot of our eSprinter during the final winter endurance tests,” says Benjamin Kaehler, Head of eDrive@VANs at Daimler AG. “Thanks to our comprehensive tests, we were able to squeeze out the last couple of percentage points from our second fully-electric van after the eVito on its way to complete market readiness. Particularly with regard to thermal management, so important to electric vans, we were able to gain insights which will make the eSprinter safer and more comfortable. We are very proud of the result and are looking forward to being able to offer our customers an extremely reliable product very soon that is more than suitable for everyday use, regardless of the conditions.”eSprinter on a par with the founder of the segmentIn Arjeplog, the eSprinter was subjected to its final winter endurance tests before it follows the eVito onto the market in the second half of 2019. Initially, the new eSprinter will be available as a panel van with a high roof and a permissible gross vehicle weight of 3500 kilogrammes. Its maximum load volume is 10.5 m³ just like a comparable Sprinter.Equipped with a battery capacity of 55 kWh, its range is an estimated 1501 kilometres with a maximum payload of 900 kilogrammes. With the second battery option, customers can prioritise other operational parameters. A capacity of 41 kWh allows the payload to be increased by around 140 kilogrammes to a total of 1040 kilogrammes with a range of about 1151 kilometres. The integrated fast-charging function provides for more flexibility; 80 % of battery charge can be recharged within 30 minutes.Similar to the entry-level diesel engine, the electric drive in the eSprinter has an output of 85 kW and a torque figure of up to 300 Newton metres. As for the eVito, the maximum speed can be configured to suit the task at hand: maximum speed can be set at 80 km/h, 100 km/h or even as much as 120 km/h.1Figures for the electric range are provisional. No EC type approval and certificate of conformity with official figures is available as yet. Differences between the stated figures and the official figures are possible” Mercedes-Benz Releases eSprinter Electric Van Specs Mercedes-Benz eSprinter survived in the Arctic CircleMercedes-Benz performs the final set of winter tests of the new all-electric eSprinter in Arjeplog, Sweden before market launch in the second half of 2019.According to the press release, the eSprinter with a 55 kWh battery even in unfavorable conditions at the Arctic Circle is still able to go 100 km (62 miles). The nominal range would be more like 150 km (93 miles).Besides range, the German manufacturer was testing charging and driving characteristics and low-temperature resistance in extreme conditions, as well as safety and ergonomics of the driver’s workplace and reliable handling on ice and snow.Mercedes-Benz eSprinter Author Liberty Access TechnologiesPosted on March 27, 2019Categories Electric Vehicle News The eSprinter will be the second electric van offered by Mercedes-Benz after the Mercedes-Benz eVito, which was introduced in 2018.Mercedes-Benz eSprinter:41.4 kWh batery or 55 kWh batteryexpected range of around 115 km (71 miles) with 41 kWh or around 150 km (93 miles) with 55 kWhpayload of 900 kg (55 kWh) or 1,040 kg (41 kWh) and maximum cargo volume is 10.5 m384 kW and 300 Nm of torquetop speed of 80 km/h conserves energy and increases the range (alternatively, it can be configured for a top speed of up to 120 km/h)80 % of battery charge can be recharged within 30 minutes 25 photos Daimler In Talks With Tesla For Electric Vanlast_img read more

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KL Gates Attorneys Sued for Conflict of Interest

first_img Password The legal malpractice case is claiming that the attorneys put one interest ahead of the other in a joint representation . . .You must be a subscriber to The Texas Lawbook to access this content. Remember me Usernamecenter_img Lost your password? Not a subscriber? Sign up for The Texas Lawbook.last_img

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Corporate Lawyer Arthur Howard Jumps to KL Gates

first_img Remember me Lost your password? Password Usernamecenter_img Not a subscriber? Sign up for The Texas Lawbook. K&L Gates has added its sixth lawyer in Houston since opening the office in February. Arthur A. Howard, previously at Haynes and Boone, will join the firm as a partner in its corporate/M&A practice. Howard focuses his practice on business transactions, advisory services, internal and governmental investigations, corporate governance, securities, finance, mergers and acquisitions. He has served as chief executive officer, president, chief operating officer, general counsel and a director in the manufacturing, construction, investment advisory, pension consulting and financial services industries . . .You must be a subscriber to The Texas Lawbook to access this content.last_img read more

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US Government Turns Off Federal Water Supply to Washington Pot FarmsMultiple Units

first_imgThe US Government has notified Chelan County that the use of Federally-contracted water to cultivate marijuana is Illegal. The US Department of the Interior has issued a letter to the County’s Department of Community Development that the US Bureau of Reclamation cannot allow the use of water and/or its facilities in the production of marijuana because the drug use is still illegal under Federal law. Chelan County Commissioners, Ron Walter, Keith Goehner and Doug England discussed the letter with News Radio 560 KPQ’s Steve Hair  . Audio Playerhttps://kpq.com/wp-content/uploads/2016/06/060716-PotWater.mp300:0000:0000:00Use Up/Down Arrow keys to increase or decrease volume.last_img read more

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New rat models could be useful in the fight against Alzheimers disease

first_img Source:https://munews.missouri.edu/news-releases/2018/0430-new-tools-could-uncover-important-answers-for-alzheimers-researchers/ Apr 30 2018Alzheimer’s disease currently affects more than 5.5 million Americans and is one of the costliest diseases to treat, according to the Alzheimer’s Association. Characterized by a buildup of plaque in the brain, few animal models exist that researchers could use to study this devastating disorder. Now, a team of researchers from the University of Missouri, publishing in PLOS ONE, developed a rat model that can be used to study the buildup of amyloid plaques and vascular abnormalities in the brain.”One of the defining traits of Alzheimer’s is the progressive accumulation of amyloid-β plaques in the brain,” said Yuksel Agca, associate professor of veterinary pathology and a researcher in the Comparative Medicine Program in the MU College of Veterinary Medicine. “Two proteins, APP and PS1 are linked to the development of Alzheimer’s disease in humans–and these two targets have become the basis for numerous studies. If we can identify how to manipulate amyloid-β build up, we can reduce the production of harmful plaques in the brain, leading to decreases in the onset of Alzheimer’s disease.”Related StoriesWearing a hearing aid may mitigate dementia riskResearchers discover new therapeutic target for treatment of Alzheimer’s diseaseMercy Medical Center adds O-arm imaging system to improve spinal surgery resultsThe MU researchers developed rats that had human APP and PS1 proteins. The rats then underwent behavioral assessments in the Barnes maze. The maze, which tracks rodent behavior is used to measure learning and spatial memory. In a series of experiments, the Alzheimer’s model rats that produced human APP and PS1 displayed poor memory and learning.After the maze experiments, the research team assessed amyloid-β levels through serum tests, as well as brain screenings, which showed vascular changes and amyloid-β plaques similar to the ones observed in humans suffering from Alzheimer’s disease.”We found that these rat models could be useful in the fight against Alzheimer’s in people,” Agca said. “Because of their shorter lifespans and their larger size, translational models such as rats are extremely helpful in ongoing studies of disease. The results can be translatable to humans in identifying targets for drugs as well as identifying everyday lifestyle changes we can make to help stave off disorders like Alzheimer’s. We hope this model will become beneficial as research continues to move forward.”Just like plaque on teeth or in arteries, plaque buildup in the brain can be decreased in people by maintaining a good diet and exercise, Agca said.last_img read more

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First genomic survey of gonorrhea maps antibiotic resistance across Europe

first_img Source:https://www.sanger.ac.uk/news/view/gonorrhoea-surveillance-study-maps-antibiotic-resistance-across-europe May 16 2018The first European-wide genomic survey of gonorrhea has mapped antibiotic resistance in this sexually transmitted disease throughout the continent. Researchers at The Centre for Genomic Pathogen Surveillance (CGPS), the Wellcome Sanger Institute, European Centre for Disease Control, and their collaborators also showed that using DNA sequencing data they could accurately determine antibiotic resistance and identify incorrect laboratory test results. This genomic approach could one day help doctors prescribe the most effective antibiotics for each region.Reported in The Lancet Infectious Diseases, the study has also established an open genomic database of gonorrhea. The new resource will support real-time ongoing surveillance of gonorrhea worldwide, which public health officials could use to monitor which strains of gonorrhea are present globally and where new antibiotic resistance is emerging.Gonorrhea is the second most prevalent bacterial sexually transmitted infection (STI) globally and is caused by the bacterium Neisseria gonorrhoeae. The WHO estimates that gonorrhoea infects 88 million people globally each year. Amongst other complications, it can cause pelvic inflammatory disease and infertility if left untreated, and in some cases leads to life-threatening complications such as meningitis. Transmitted during unprotected sex, many strains of gonorrhea are now difficult to treat due to the rise in antibiotic resistance.To understand the extent of multidrug resistant strains and determine the best method for surveillance, the researchers studied 1054 samples of N. gonorrheae collected from 20 countries across Europe in 2013. Each sample was tested locally for type and antibiotic sensitivity, and was sent to a central laboratory for DNA extraction. The DNA was then sequenced and the data analyzed at the Centre for Genomic Pathogen Surveillance and made accessible via their online platform, creating the first European-wide database of gonorrhea.The scientists discovered that using genomic data allowed them to identify clinically important, antibiotic resistant strains much more accurately than existing typing techniques, and to identify incorrect laboratory antibiotic resistance results.Related StoriesResearchers investigate how antibiotic produced by the microbiome kills bacteriaInterdisciplinary approach reduces the use of broad spectrum antibioticsNatural antibiotic made by Tübingen researchers interacts with human defense mechanismsProf David Aanensen, a corresponding author on the paper and Director of The Centre for Genomic Pathogen Surveillance, Wellcome Sanger Institute, said: “Ours is the most comprehensive, structured genomic study of gonorrhea to date, and data are available to healthcare workers worldwide to compare and view emerging strains of gonorrhea. This combination of a new method with an accessible database and interpretation tools provides a genomic baseline of gonorrhea strains and antibiotic resistance across Europe, which will strengthen real-time, surveillance of gonorrhea.Dr Simon Harris, first author on the paper from the Wellcome Sanger Institute, said: “Our study shows that current methods for typing strains of gonorrhea are not very effective for surveillance. We show that whole genome sequencing gives a true picture of where sensitive and resistant strains are circulating, which will allow doctors to quickly spot the emergence of new, antibiotic resistant gonorrhea strains. A follow up study starting this year will show how the picture changes with time.”The web application is openly available online, and healthcare officials from around the world can use it and add their own genomic data. This will enable them to monitor the strains and antibiotic resistance emerging in each geographic area. Ongoing surveillance would allow clinics to offer the most appropriate antibiotics and help to delay the onset of further antibiotic resistance.Dr Gianfranco Spiteri, an author on the paper from the European Centre for Disease Prevention and Control which co-ordinates the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), said: “Drug-resistant bacteria are becoming a huge public health threat. To control them, we badly need new tools to identify and track new infections and antibiotic resistant strains. This new approach will allow European-wide genomic surveillance of gonorrhea which directly influences infection control on a national level and helps to prevent gonorrhea. This approach can also be expanded to other infections.”last_img read more

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Researchers report new signaling exchange that mediates normal mammary gland development

first_imgMay 18 2018The human body develops most tissue types during fetal development, in a mother’s uterus. Yet one only tissue develops after birth: the mammary gland. This milk-producing organ, a defining characteristic of mammals, is also the site of one of the most common cancers, breast cancer, which affects roughly one in eight women in the United States over the course of their lifetime.Cancer cells can commandeer molecular pathways used in normal physiological functions to wreak havoc in the body. That is why Rumela Chakrabarti, an assistant professor of biomedical sciences in Penn’s School of Veterinary Medicine, pays close attention to the molecular mechanisms at work in the mammary gland.”Cancer cells are smart,” she says. “They can actually hijack the normal cellular machinery to use for their benefit. I’m interested in the cellular signaling that is having an impact in normal development as well as in the initiation and development of breast cancer.”In a paper out this week in the journal Science, Chakrabarti and colleagues report a crucial new signaling exchange that mediates normal mammary gland development by regulating the mammary stem cell niche, which was not previously understood.The discovery, the result of years of work that began when Chakrabarti was a postdoctoral researcher at Princeton University in the lab of her co-corresponding author, Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology, indicates that mammary gland stem cells communicate with macrophages, a type of immune cell, using a protein called Delta-like-ligand 1 (Dll1), which is part of the Notch signaling pathway. They find that this molecular chatter is essential for the survival of the mammary stem cells, which leads to mammary gland development. And because the Notch pathway and other molecular components of the communications between mammary stem cells and macrophages have been implicated in breast cancer genesis and spread, future studies of the pathway in the context of cancer may bear crucial information for diagnosis and treatment.Going into this work, scientists knew that mammary stem cells existed, helping to remodel the breast tissue through the changes associated with puberty, pregnancy, and lactation. But no one had a good way of identifying them, or a solid understanding of their interactions with surrounding cells.As a first step, Chakrabarti and colleagues compared the gene expression profiles of mammary stem cells versus non-stem cells, and found Dll1 to be among the genes most differentially expressed between the two cell types. Honing in, they developed a mouse model that lacked Dll1 predominantly in the mammary gland. Through every life stage, these mice had problems with mammary gland development, and females did not produce milk after giving birth. They also had significantly fewer mammary stem cells and macrophages compared with normal mice.Related StoriesNew study reveals ‘clutch’ proteins responsible for putting T cell activation ‘into gear’Living with advanced breast cancerNew protein target for deadly ovarian cancer”People have identified other genes that affect mammary gland development,” Chakrabarti says, “but usually the defect is temporary and the mammary gland can somehow bypass it over time. With this gene, we found it cannot be compensated, it affects every stage of development, including pregnancy.”Using additional reporter mouse models, developed by collaborators Hans Clevers of the Netherlands’ Hubrecht Institute and Ioannis Aifantis of New York University, the researchers tracked mammary stem cells based on associated florescent color, confirming that Dll1 was indeed a marker of stem cells that were able to give rise to every cell type in the mammary gland.Because Dll1 was known to be a ligand of Notch signaling, or a molecule that binds to another molecule, the next step was to find its “receiving” molecule. Screening a variety of cell types that exist in the environment of the mammary gland, they narrowed in on macrophages. Working with Ming Li of Memorial Sloan Kettering Cancer Center, who provided mouse models where Notch signaling in macrophages is deleted, they found that mammary stem cells depended on macrophages to function normally.Further gene expression studies elucidated the relationship, showing that the stem cells used Dll1 to communicate with macrophages, and the macrophages released the signaling proteins, such as Wnt3, 10, and 16 to support the environment around mammary stem cells, allowing them to thrive.The fact that both Wnt and Notch signaling are involved in supporting the mammary stem cell niche provides a strong clue that the relationship and signaling pathways that link stem cells and macrophages may play a role in breast cancer, as aberrant functioning of both of these pathways have previously been shown to present in breast cancer.”That is where the lab is now looking,” says Chakrabarti. “How are these pathways functioning in breast cancer?”If changes in Dll1 expression are found to play a role in the early stages of cancer, Chakrabarti says the molecule offers a promising biomarker and a target for cancer therapy. As a ligand, it could be zeroed in on without the toxicity of some other types of drugs that operate in the same pathway, which function by inhibiting receptors and sometimes have problematic side effects.”The lab is very interested in detecting early changes in cancer,” Chakrabarti says. “That’s why we are looking very closely at normal development and physiology.” Catching the changeover from normal to malignant at an early stage, she notes, is the best way to save lives. Source:https://penntoday.upenn.edu/news/cellular-signaling-drives-mammary-gland-development-and-maybe-breast-cancerlast_img read more

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How rival opioid makers sought to cash in on alarm over oxycontins

first_imgAug 2 2018As Purdue Pharma faced mounting criticism over deaths linked to OxyContin, rival drugmakers saw a chance to boost sales by stepping up marketing of similarly dangerous painkillers, such as fentanyl, morphine and methadone, Purdue internal documents reveal.Purdue’s 1996-2002 marketing plans for OxyContin, which Kaiser Health News made public this year for the first time, offer an unprecedented look at how that company spent millions of dollars to push opioids for growing legions of pain sufferers. A wave of lawsuits demanding reimbursement and accountability for the opioid crisis now ravaging communities has heightened awareness about how and when drug makers realized the potential dangers of their products.The Purdue documents lay out how the company and its biggest competitors were jockeying for market share. Some of those drugmakers’ sales promotions downplayed or ignored the risks of taking opioids, or made false claims about their safety, federal regulators have asserted in warning letters to the companies.Purdue first offered OxyContin as a remedy for moderate to severe cancer pain in 1996. Within three years, the company viewed the cancer market as too limited, with $261 million in potential annual sales versus $1.3 billion for a broader range of chronic pain care, the company’s marketing reports said.”That was a pretty good recipe for a blockbuster,” said Andrew Kolodny, who directs Physicians for Responsible Opioid Prescribing, an advocacy group critical of drug industry marketing.Purdue has become the most high-profile drugmaker linked to the surging opioid crisis. But other opioid manufacturers didn’t sit by idly as sales of OxyContin skyrocketed, topping $1 billion in 2000, despite reports of overdose deaths and addiction.Purdue’s marketing reports indicate the company was worried about losing business to fentanyl-laced patches called Duragesic, as well as morphine pills and, to a lesser degree, methadone — which some managed-care groups and Medicaid health plans preferred because it cost much less than OxyContin. Methadone and morphine are made by a variety of drug companies.In its 1999 marketing report, Purdue noted that Janssen Pharmaceuticals, an arm of drug giant Johnson & Johnson, was making “slow but steady” progress in promoting its Duragesic patches. The patches, which users attach to their skin, deliver a dose of fentanyl, an opioid drug about 50 to 100 times more powerful than morphine, according to the Drug Enforcement Administration.Purdue estimated that Janssen would spend about $4 million in 1999 on medical journal advertising to persuade doctors to prescribe the patches for “early treatment of non-cancer pain and pain in the more frail elderly.” That is more than triple what Janssen spent the year before, according to the 2000 Purdue marketing report. In a statement to KHN, a Janssen spokesman said the company quit “actively marketing” Duragesic in 2008.Purdue also spent millions on medical journal ads — and like Janssen, it drew criticism from the Food and Drug Administration for minimizing the dangers of opioids, government records show.In 2000, the Food and Drug Administration criticized Purdue for exaggerating the benefits of using OxyContin to treat arthritis, while in 2003 the agency found that some other ads had “grossly overstated” OxyContin’s safety.Janssen also drew the ire of the FDA. In March 2000, the agency called some claims made for Duragesic “false or misleading,” including the suggestion that the drug “has less potential for abuse than other currently available opioids.”In September 2004, the FDA told Janssen to “immediately cease” making “false or misleading” claims, including saying that Duragesic was “less abused than other opioid drugs.” In its statement to KHN, Janssen said its marketing actions were “appropriate and responsible,” adding that it “acted quickly to investigate and successfully resolve FDA’s inquiries.”The Purdue marketing reports are part of a cache of documents the company provided to the Florida attorney general’s office in 2002. The Florida attorney general released them to two Florida newspapers in 2003 after Purdue lost a court battle to keep them under wraps.Related StoriesPatients taking opioids for chronic pain could face health care access problemsLiving with advanced breast cancerStudy: Nearly a quarter of low-risk thyroid cancer patients receive more treatment than necessaryMore than 1,500 groups, mostly cities, counties and states, are suing Purdue Pharma, Janssen and several competitors and drug distributers in federal court in Cleveland demanding reimbursement for treatment costs and other compensation. In a statement to KHN, Purdue said: “We vigorously deny these allegations and look forward to the opportunity to present our defense.”The growing cluster of lawsuits argue that drugmakers set out to deceive doctors and the public by claiming their products presented little risk.For its part, Purdue accused Janssen of trying to exploit public alarm over OxyContin-linked deaths to spark new sales of Duragesic.”It has been reported that Janssen sales representatives are using improper techniques to capitalize on the negative press surrounding OxyContin Tablets and the issue of abuse and diversion,” reads the 2002 Purdue marketing plan.In fact, opioids made by Purdue’s rivals also contributed to overdose deaths in those years and have continued to do so. In 2016, more than 42,000 people died nationwide from opioid-related causes, according to the Department of Health and Human Services.Florida was one of the early states to see a rise in overdose deaths tied to prescription drugs. Florida medical examiner’s toxicology reports in 2002 detected oxycodone, the active ingredient in OxyContin, in hundreds of overdose fatalities. Abusers realized they could crush the pills and inject or snort the powder to get high. Many others died after mixing the pills with sedatives also prescribed by their doctors.Florida medical examiner files also showed that abuse of fentanyl pain patches, methadone and morphine took many lives. Some abusers had figured out how to drain the Duragesic patch of its liquid fentanyl and inject it like heroin, or otherwise ingest it.In July 2005, the FDA warned health care professionals about abuse of fentanyl patches. In December 2007, FDA cited reports of deaths and “life-threatening adverse events” when the fentanyl patch “was used to treat pain in opioid-naïve patients and when opioid-tolerant patients have applied more patches than prescribed, changed the patch too frequently and exposed the patch to a heat source.”Purdue also kept an eye on methadone, noting in a 1999 marketing plan that “market research as well as reports from the sales force indicates that methadone use is increasing in both the management of cancer pain and non-malignant pain due to its low cost.” But as methadone won acceptance for treating pain, it also began to kill with alarming frequency.The FDA in November 2006 warned of deaths and dangerous side effects among patients “newly starting methadone for pain control and in patients who have switched to methadone after being treated for pain with other strong narcotic pain relievers.”KHN’s coverage of prescription drug development, costs and pricing is supported in part by the Laura and John Arnold Foundation. This article was reprinted from khn.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente. Fred Schulte: fschulte@kff.org, @fredschultelast_img read more

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Routine oral care to treat gum disease may improve cognitive function in

first_img Source:http://www.the-aps.org/ Reviewed by James Ives, M.Psych. (Editor)Aug 29 2018Routine oral care to treat gum disease (periodontitis) may play a role in reducing inflammation and toxins in the blood (endotoxemia) and improving cognitive function in people with liver cirrhosis. The study is published ahead of print in the American Journal of Physiology–Gastrointestinal and Liver Physiology.Cirrhosis, which is a growing epidemic in the U.S., is the presence of scar tissue on the liver. When severe, it can lead to liver failure. Complications of cirrhosis can include infections throughout the body and hepatic encephalopathy, a buildup of toxins in the brain caused by advanced liver disease. Symptoms of hepatic encephalopathy include confusion, mood changes and impaired cognitive function.Related StoriesNew findings could facilitate the development of hepatitis C mouse modelResearchers describe the impact of chronic hepatitis D on parts of the immune systemStudy: People with type 2 diabetes are at particular risk of deadly liver diseasePrevious research shows that people with cirrhosis have changes in gut and salivary microbiota– bacteria that populate the gastrointestinal tract and mouth–which can lead to gum disease and a higher risk of cirrhosis-related complications. In addition, studies have found that people with cirrhosis have increased levels of inflammation throughout the body, which is associated with hepatic encephalopathy.Researchers studied two groups of volunteers that had cirrhosis and mild-to-moderate periodontitis. One group received periodontal care (“treated”), including teeth cleaning and removal of bacteria toxins from the teeth and gums. The other group was not treated for gum disease (“untreated”). The research team collected blood, saliva and stool samples before and 30 days after treatment. Each volunteer took standardized tests to measure cognitive function before and after treatment.The treated group, especially those with hepatic encephalopathy, had increased levels of beneficial gut bacteria that could reduce inflammation, as well as lower levels of endotoxin-producing bacteria in the saliva when compared to the untreated group. The untreated group, on the other hand, demonstrated an increase in endotoxin levels in the blood over the same time period. The improvement in the treated group “could be related to a reduction in oral inflammation leading to lower systemic inflammation, or due to [less harmful bacteria] being swallowed and affecting the gut microbiota,” the research team wrote.Cognitive function also improved in the treated group, suggesting that the reduced inflammation levels in the body may minimize some of the symptoms of hepatic encephalopathy in people who are already receiving standard-of-care therapies for the condition. This finding is relevant because there are no further therapies approved by the U.S. Food and Drug Administration to alleviate cognition problems in this population, the researchers said. “The oral cavity could represent a treatment target to reduce inflammation and endotoxemia in patients with cirrhosis to improve clinical outcomes.”last_img read more

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Study uncovers four neuron types in the peripheral auditory system

first_imgReviewed by James Ives, M.Psych. (Editor)Sep 12 2018Researchers at Karolinska Institutet have identified four types of neurons in the peripheral auditory system, three of which are new to science. The analysis of these cells can lead to new therapies for various kinds of hearing disorders, such as tinnitus and age-related hearing loss. The study is published in Nature Communications.When sound reaches the inner ear, it is converted into electrical signals that are relayed to the brain via the ear’s nerve cells in cochlea. Previously, most of these cells were considered to be of two types: type 1 and type 2 neurons, type 1 transmitting most of the auditory information. A new study by scientists at Karolinska Institutet shows that the type 1 cells actually comprise three very different cell types, which tallies with earlier research showing variations in the electrical properties and sonic response of type 1 cells.Three different routesRelated StoriesNew gene-editing protocol allows perfect mutation-effect matchingDysfunctional neurons repaired in dementia mouse modelHow an orchestra of neurons control hunger pangs”We now know that there are three different routes into the central auditory system, instead of just one,” says François Lallemend, research group leader at the Department of Neuroscience, Karolinska Institutet, who led the study. “This makes us better placed to understand the part played by the different neurons in hearing. We’ve also mapped out which genes are active in the individual cell types.”The team conducted their study on mice using the relatively new technique of single-cell RNA sequencing. The result is a catalogue of the genes expressed in the nerve cells, which can give scientists a solid foundation for better understanding the auditory system as well as for devising new therapies and drugs.”Our study can open the way for the development of genetic tools that can be used for new treatments for different kinds of hearing disorders, such as tinnitus,” says Dr Lallemend. “Our mapping can also give rise to different ways of influencing the function of individual nerve cells in the body.”Crucial functionThe study shows that these three neuron types probably play a part in the decoding of sonic intensity (i.e. volume), a function that is crucial during conversations in a loud environment, which rely on the ability to filter out the background noise. This property is also important in different forms of hearing disorders, such as tinnitus or hyperacusis (oversensitivity to sound).”Once we know which neurons cause hyperacusis we’ll be able to start investigating new therapies to protect or repair them,” explains Dr Lallemend. “The next step is to show what effect these individual nerve cells have on the auditory system, which can lead to the development of better auditory aids such as cochlear implants.”The researchers have also shown through comparative studies on adult mice that these different types of neurons are already present at birth. Source:https://ki.se/en/news/discovery-of-new-neurons-in-the-inner-ear-can-lead-to-new-therapies-for-hearing-disorderslast_img read more

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UNC Health Care extends free access to virtual care service in the

first_imgReviewed by James Ives, M.Psych. (Editor)Sep 18 2018In the aftermath of Hurricane Florence and continued challenging conditions across much of the state, UNC Health Care has extended its offer of free access to its virtual care service, UNC Urgent Care 24/7.Free access will be available for persons physically located in the State of North Carolina through Sunday, September 23rd at 11:59 pm.This service from UNC Health Care provides patients with real-time access to physicians via phone, tablet or computer.To register and create a UNC Urgent Care 24/7 account, patients must visit www.UNCurgentcare247.com or visit the Apple App and Google Play stores to download the app to a smartphone or tablet. Patients should use the offer code UNCFLORENCE2018 from the website or app.Related StoriesSupplements claiming to boost brain health are ‘too good to be true’, warn expertsGender inequality bad for everyone’s health finds researchFirst smartphone app to detect childhood ear infectionVirtual visit fees were initially waived for hurricane victims Friday – Sunday (September 14-16). Free access has been extended to assist hurricane victims across the state as conditions still limit many residents from traveling, as well as those who are displaced or are located at emergency shelters.The service offers convenient and around-the-clock care from anywhere in North Carolina for non-emergency medical issues.Appropriate conditions for the service include: allergies, coughs, fever, headaches, nausea, insect bites, pink eye, sore throat, rash, vomiting and more.”Last week, we said this was a way for UNC Health Care to serve North Carolinians during Hurricane Florence,” explained Dr. Bill Roper, CEO of UNC Health Care. “Post-storm, we recognize a continuing need for this delivery of health care service for non-acute conditions. We hope this will provide some degree of relief to folks who may not be able to leave their homes or access their usual providers.”How does it work?During virtual visits, a physician connects with patients by phone or Internet through a private and secure connection. The physician can diagnose problems, recommend treatment and prescribe medications when appropriate (excluding opioids and other controlled substances). Patients with true emergencies, including chest pain, should still go to a hospital emergency department. Please note that patients should use the offer code UNCFLORENCE2018 from the website or app to receive a consultation free of charge during the extended period.The program is offered through MDLIVE, the nation’s leading provider of virtual medicine services and software. Source:http://news.unchealthcare.org/news/2018/september/unc-health-care-extends-free-access-period-to-virtual-care-service-for-hurricane-victimslast_img read more

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Polar Bear Evolution Was Fast and Furious

For polar bears, being tubby is a way of life. Fat can make up 50% of their body weight; the blubber-laden seals they eat make bacon look downright healthy. Now, a new, extensive comparison of the genomes of polar bears and their closest relative, the brown bear, has revealed how polar bears survive such unhealthy diets.The work also suggests that the bears evolved these changes relatively quickly, likely because they had to adapt to extreme conditions that forced them to switch to a diet that would be toxic to other mammals. “It’s a schoolbook example of evolution,” says Eske Willerslev, an evolutionary geneticist at the University of Copenhagen who helped the lead the research.Brown bears—some of which are called grizzlies—and polar bears are closely related and are even able to interbreed. In the past few years, researchers have used genetic information to sort out this relationship and to understand how polar bears thrive in the frigid Arctic, feeding primarily on seals and other marine life captured from holes in the ice. This work has included sequencing the animals’ genomes, which has indicated that polar bears are truly a distinct species that at times lived apart from brown bears and at times intermingled and interbred with them. But researchers disagree about when the polar bear began to split off from brown bears, with estimates ranging from about 600,000 years to as much as 5 million years ago. 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Country Click to view the privacy policy. Required fields are indicated by an asterisk (*) In the latest sequencing effort, Willerslev and researchers from Denmark, China, and the United States analyzed the genomes of 80 polar bears from Greenland and 10 brown bears from North America and Europe. “[It’s] the most comprehensive genomic data set to date, as far as bears are concerned,” says Frank Hailer, an evolutionary biologist from Goethe University Frankfurt in Germany.Drawing on that data, Willerslev and his colleagues conclude that polar bears split off from brown bears between 343,000 and 479,000 years ago. Although little more than a blink in time from an evolutionary perspective, that was long enough for key genetic differences to evolve, they note in a report today in Cell.The most distinctive polar bear genes include many related to fat processing and to the development of the heart and circulatory system. Indeed, nine of the 16 most distinctive genes are ones that in humans are associated with heart disease, Willerslev says. One that stood out was a gene called APOB, which helps transfer fat from blood into cells.In brown bears, the sequence of this gene varies from one bear to another, but all the polar bears surveyed have an identical version, with the exact same genetic code at nine variable spots in the gene, about half of which should change the function of the APOB protein.That all polar bears have the same version indicates that it is very beneficial, perhaps enabling the animals to eat lots of fat without developing artery-clogging plaques that can plague humans who eat high-fat diets, says study co-author Eline Lorenzen, a molecular ecologist at the University of California (UC), Berkeley. An independent chemical analysis of a 120,000-year-old fossil polar bear jawbone showed that the species was already dependent on marine prey by then—a big switch from the brown bear’s chiefly vegetarian fare—indicating that these genetic changes occurred in just a few hundred thousand years. “That’s very surprising for such a large mammal,” she says.Given the number of genomes studied and the sophisticated analysis used, the date for when the species diverges is “the best estimate of what we’ve gotten so far, and it makes sense,” says Beth Shapiro, an evolutionary biologist at UC Santa Cruz, whose earlier work also suggested these bears split less than a million years ago. But Charlotte Lindqvist, an evolutionary biologist from the University at Buffalo in New York who has proposed a much earlier date for the origin of the polar bear, is not completely convinced. “The evolutionary history of these animals has probably been very complex,” with the two species separating and interbreeding multiple times, she points out. “I don’t really see that [new study] resolves anything.”Both she and Hailer contend that researchers need to get genomes from a wider distribution of bears, particularly brown bears. “It might be that some conclusions will be altered when the genetic diversity within these bears can be characterized more thoroughly,” Hailer says. read more

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Injecting live malaria parasites into people safely immunizes them from the disease

first_imgThe biotech company Sanaria harvests sporozoites (yellow) that cause malaria from mosquito salivary glands (red), which it then injects into people to immunize them.  Sign up for our daily newsletter Get more great content like this delivered right to you! Country Email A malaria vaccine approach that might strike some as radical has had stunning success in a small human trial. Its developers contend the unusual strategy could serve as a backbone of campaigns that attempt to eliminate the devastating disease.“It’s an extremely exciting piece of work,” says Pedro Alonso, who heads the Global Malaria Programme at the World Health Organization (WHO) in Geneva, Switzerland. “It’s not the most conventional approach of immunization, but given the magnitude of the malaria problem, it’s well worth pursuing.”Vaccines typically train the immune system with a harmless version of the disease-causing organism. But traditional malaria vaccines that contain a weakened version, or just pieces of, the Plasmodium parasite that causes the disease have had lackluster success. Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Click to view the privacy policy. Required fields are indicated by an asterisk (*)center_img So researchers from Sanaria, a biotech company that makes various malaria vaccines in Rockville, Maryland, and their collaborators at the University of Tübingen in Germany upped the ante: They injected live Plasmodium sporozoites—the form of the parasite that establishes the infection—into the veins of nine people. The volunteers got three injections at 4-week intervals. They also took antimalaria chloroquine pills shortly before, during, and shortly after receiving the sporozoites, which crippled the parasite in the liver before it could return to the bloodstream in a disease-causing form.When the researchers “challenged” the nine vaccinated participants with the sporozoites 10 weeks later and did not give them chloroquine, no one became infected and no serious side effects occurred, they report today in Nature. In contrast, 13 people who were challenged and did not receive the vaccine all had the parasites in their blood (at which point they received treatment).The success with live sporozoites is not a first: In 2009, researchers reported 100% protection in 10 volunteers taking chloroquine who were “vaccinated” by having mosquitoes infected with P. falciparum intentionally bite them. But the team admitted that using mosquitoes as the delivery vehicle does “not represent a widely implementable vaccine strategy.” (To make the chemoprophylaxis vaccine—or CVac, as Sanaria calls it—the company harvests and purifies sporozoites from the salivary glands of mosquitoes.)The researchers don’t know how long protection from CVac will last. Adults who have built up natural immunity to malaria after surviving infections lose that protection within a few years if they move to an area without malaria transmission.However, modeling shows that if 90% of a population received injections of these sporozoites at the proper dose, coupled with mass “chemoprophylaxis” with drugs like chloroquine for only 6 months, it would “halt malaria and eliminate the parasite,” says Sanaria’s founder and CEO Stephen Hoffman. “We think that would be revolutionary,” he says, noting that “mass drug administration” to prevent malaria already takes place in some locales.That may not be a realistic strategy, cautions epidemiologist Marcel Tanner, who heads the Swiss Tropical and Public Health Institute in Basel and has worked in Africa for 38 years. “If you don’t have enough dirt on your shoes to know how this goes, you can overlook simple operational problems.” For example, failure to properly follow the sporozoite injections with antimalarial treatment could lead to serious illness and even death. “I could imagine many ethical boards and governments would have hesitations,” Tanner says.Still, he says, CVac could work well for travelers or military troops temporarily visiting malarial areas—and maybe on an island or in other well-defined areas where you can “vaccinate and treat like a military action.” Injecting live malaria parasites into people safely immunizes them from the disease London School of Hygiene & Tropical Medicine/Science Source By Jon CohenFeb. 15, 2017 , 1:00 PMlast_img read more

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What made Triceratops so horny

first_imgimageBROKER/Alamy Stock Photo What made Triceratops so horny? By Gretchen VogelMar. 20, 2018 , 8:01 PMcenter_img Horn-faced dinosaurs like Triceratops had elaborate frills and spurs that adorned their skulls and grew more elaborate—and diverse—through the eons. Later species, such as Chasmosaurus belli (above), sported frills that were up to a meter long. Paleontologists have floated several ideas about what spurred the evolution of such elaborate headgear. Recently, some have suggested it might have been a way to communicate with other dinosaurs, helping them recognize members of their own species.To test whether species recognition was the driving force behind the adornments, scientists examined whether horn-faced species that shared territory also had more distinct ornaments. They compared 350 different characteristics in 1035 different species pairs. Thirty-eight of the pairs existed at the same time in the same region, and 63 more lived at the same time on the same continent, though their fossils have not ever been found together in the same area. The researchers found no evidence that any of the pairs were more distinct from each other than pairs that came from different eras or completely different regions.That means it’s unlikely that the horns evolved to help animals recognize their own species, the researchers conclude in a paper published today in the Proceedings of the Royal Society B. It’s more plausible, they say, that the horny bling was driven by socio-sexual signaling: Frills and horns were advertisements of health and strength, and bigger, fancier ones helped their owner attract a mate.last_img read more

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How an ancient cataclysm may have jumpstarted life on Earth

first_img P A head start Multiple lines of evidence from chemistry, biology, and geology help explain how RNA could have emerged, leading to the first life, surprisingly soon after Earth formed. 4.5 4.2 N Microbial mats called stromatolites emerged early in life’s history—and still persist at Shark Bay in Australia. 4.53 bya The long-standing explanation has been that after Earth cooled enough to form a crust, additional metals arrived in a hail of meteors. On the basis of ages of moon rocks brought back by Apollo astronauts, geologists suspected this assault was particularly intense from 3.8 billion to 4.1 billion years ago, a period they refer to as the Late Heavy Bombardment (LHB).But that scenario has problems, Benner says. For starters, fossil evidence of complex microbial mats called stromatolites shows up in rocks just a few hundred million years younger than the hypothetical bombardment. That’s a narrow window in which to move from zero organic molecules to full-blown cellular life.Zircons—those tiny, durable crystals—also pose a challenge, says Elizabeth Bell, a geologist at UC Los Angeles. Zircons are hardy enough to have remained intact even as the rocks that originally housed them melted while cycling into and out of the planet’s interior.In 2015, Bell and her colleagues reported in the Proceedings of the National Academy of Sciences that zircons dated to 4.1 billion years ago contain flecks of graphitic carbon with a lifelike combination of carbon isotopes—biased toward carbon’s lighter isotope over its heavier one. Bell concedes that an as-yet-unknown nonbiological process might account for that isotope mix, but she says it suggests life was already widespread 4.1 billion years ago, before the end of the LHB. Other recent zircon data, including samples from as long ago as 4.32 billion years, hint that very early Earth had both liquid water and dry land, suggesting it was more hospitable to life than originally thought. “We’re pushing back further and further the time when life could have been formed on Earth,” Bell says.Collision courseMojzsis argues that a moon-size cataclysm 4.47 billion years ago could explain both Earth’s veneer of precious metals and an early start for life. In December 2017, he and two colleagues published a set of extensive computer simulations in Earth and Planetary Science Letters showing how the current distribution of metals could have originated in the rain of debris from such an impact. Simone Marchi, a planetary scientist at the Southwest Research Institute in Boulder, and colleagues reached much the same conclusion in a paper the same month in Nature Geoscience. Marchi’s team, however, simulated not one moon-size impactor, but several smaller bodies, each about 1000 kilometers across.Whether one impact or a few, those collisions would have melted Earth’s silicate crust, an event that appears to be recorded in data on isotopes of uranium and lead, according to Mojzsis. The collisions also would have profoundly affected Earth’s early atmosphere. Before the impact, the cooling magma and rocks on the surface would have spurted out gases, such as carbon dioxide, nitrogen, and sulfur dioxide. None of those gases is reactive enough to produce the organic compounds needed to make RNA. But Benner notes the blanket of hydrogen generated by the impact’s metallic hail would have formed exactly the kind of chemically reducing atmosphere needed to produce the early organics. Robert Hazen, a geologist at the Carnegie Institution’s Geophysical Laboratory in Washington, D.C., agrees that hydrogen could help. With that reducing atmosphere, the wide array of minerals on the planet’s surface could have acted as catalysts to propel the chemical reactions needed to make simple organics, Hazen says.Just before the impact, Mojzsis says, “there was no persistent niche for the origin of life.” But after the impact and a brief period of cooling, he adds, “at 4.4 billion years ago, there are settled niches for the propagation of life.””I’m delighted,” Benner says. “Steve [Mojzsis] is giving us everything we need” to seed the world with prebiotic chemicals. And by eliminating the need for the LHB, the impact scenario implies organic molecules, and possibly RNA and life, could have originated several hundred million years earlier than thought. That would allow plenty of time for complex cellular life to evolve by the time it shows up in the fossil record at 3.43 billion years ago.Enduring enigmasNot everybody accepts that tidy picture. Even if geologists’ new view of early Earth is correct, the RNA world hypothesis remains flawed, says Loren Williams, a physical chemist at the Georgia Institute of Technology here and an RNA world critic who attended the workshop. “I like talking to Steve Benner,” Williams says. “But I don’t agree with him.”One major problem with the RNA world, he says, is that it requires a disappearing act. An RNA molecule capable of faithfully copying other RNAs must have arisen early, yet it has vanished. “There’s no evidence for such a thing in modern biology,” Williams says, whereas other vestiges of ancient RNA machines abound. The ribosome’s RNA core, for example, is virtually unchanged in every life form on the planet. “When biology makes something, it gets taken and used over and over,” Williams notes. Instead of an RNA molecule that can copy its brethren, he says, it’s more likely that early RNAs and protein fragments called peptides coevolved, helping each other multiply more efficiently.Advocates of the RNA world hypothesis concede they can’t explain how early RNA might have copied itself. “An important ingredient is still missing,” Carell says. Researchers around the globe have designed RNA-based RNA copiers in the lab. But those are long, complex molecules, made from 90 or more RNA bases. And the copiers tend to copy some RNA letters better than others.Still, enough steps of an RNA-first scenario have come into focus to convince advocates that others will follow. “We are running a thought experiment,” says Matthew Powner, a chemist at University College London. “All we can do is decide what we think is the simplest trajectory.”That thought experiment was on full display in the workshop’s final session. Ramon Brasser of the Tokyo Institute of Technology, one of Mojzsis’s collaborators, stood at the front of a small conference room and drew a timeline of Earth’s earliest days. A red slash at 4.53 billion years ago on the left side of Brasser’s flip chart marked Earth’s initial accretion. Another slash at 4.51 billion years ago indicated the moon’s formation. A line at 4.47 billion years ago marked the hypothetical impact of the planetesimal that gave rise to an atmosphere favorable to organic molecules.Benner asked Brasser how long Earth’s surface would have taken to cool below 100°C after the impact, allowing liquid water to host the first organic chemical reactions. Probably 50 million years, Brasser said. Excited, Benner rushed up to the timeline and pointed to a spot at 4.35 billion years ago, adding a cushion of extra time. “That’s it, then!” Benner exclaimed. “Now we know exactly when RNA emerged. It’s there—give or take a few million years.” Some of Earth’s oldest mineral fragments, called zircons, were recently extracted from rock in Australia’s Jack Hills. They harbor chemical inclusions that suggest early Earth was cool enough to have liquid water. P P P H 2 N NH 2 H 2 N ATLANTA—A cataclysm may have jump-started life on Earth. A new scenario suggests that some 4.47 billion years ago—a mere 60 million years after Earth took shape and 40 million years after the moon formed—a moon-size object sideswiped Earth and exploded into an orbiting cloud of molten iron and other debris.The metallic hailstorm that ensued likely lasted years, if not centuries, ripping oxygen atoms from water molecules and leaving hydrogen behind. The oxygens were then free to link with iron, creating vast rust-colored deposits of iron oxide across our planet’s surface. The hydrogen formed a dense atmosphere that likely lasted 200 million years as it ever so slowly dissipated into space.After things cooled down, simple organic molecules began to form under the blanket of hydrogen. Those molecules, some scientists think, eventually linked up to form RNA, a molecular player long credited as essential for life’s dawn. In short, the stage for life’s emergence was set almost as soon as our planet was born. O 4.3 4.5 3.7 3.8 Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe FRANS LANTING/NATIONAL GEOGRAPHIC IMAGE COLLECTION How an ancient cataclysm may have jump-started life on Earth 3.9 O OH OH OH OH OH O O N N N N N N NH NH N N N Today, Benner says, “The amount of yelling has gone down.” A steady stream of new data has bolstered scenarios for how RNA could have arisen. For example, although Benner and his colleagues had previously shown how ribose may have formed, they could not explain how some of its ingredients—namely, the highly reactive small molecules formaldehyde, glycolaldehyde, and glyceraldehyde—could have survived. Geochemists have long thought that reactions sparked by lightning and ultraviolet (UV) light could have produced such compounds. However, Benner says, “There’s no way to build up a reservoir” of those compounds. They can react with one another, devolving into a tarlike glop.Benner now has a possible solution, which builds on recent work suggesting early Earth had a wet-dry cycle. On the basis of evidence from tiny, almost indestructable mineral crystals called zircons, researchers think a modest amount of dry land was occasionally doused with rain. In a not-yet-published study, he and colleagues in the United States and Japan have found that sulfur dioxide, which would have belched from volcanoes on early Earth, reacts with formaldehyde to produce a compound called hydroxymethanesulfonate (HMS). During dry times, HMS would have accumulated on land “by the metric ton,” Benner says. The reverse reaction would have happened more slowly, regenerating formaldehyde. Then, when rains came, it could have washed in a steady trickle into puddles and lakes, where it could react to form other small organic molecules essential for building RNA. Similar processes, Benner says, could have provided a steady supply of glycolaldehyde and glyceraldehyde as well.The sugar ribose is only one piece of RNA. The molecule also strings together four ring-shaped bases, which comprise the letters of the genetic code: cytosine (C), uracil (U), adenine (A), and guanine (G). Making them requires a supply of electron-rich nitrogen compounds, and identifying a plausible source for those has long challenged origin of life researchers. But other recent advances in prebiotic chemistry, which assume a supply of those compounds, have identified a set of reactions that could have produced all four of RNA’s genetic letters at the same time and place. In 2009, for example, Sutherland and his colleagues reported a plausible prebiotic reaction for making C and U, chemically related letters known as pyrimidines. Then, in 2016, a team led by chemist Thomas Carell from Ludwig Maximilian University in Munich, Germany, reported coming up with a plausible way to make A and G, known as purines. The trouble was that Sutherland’s and Carell’s routes to pyrimidines and purines required different reaction conditions, making it difficult to imagine how they could have taken place side by side.At the workshop, Carell reported a possible solution. He and his colleagues found that simple compounds likely present on early Earth could react in several steps to produce pyrimidines. Nickel and other common metals trigger the last step in the sequence by swiping electrons from intermediate compounds, causing them to react with one another. It turns out that gaining electrons enables the metals to then carry out a final step in synthesizing purines. What’s more, those steps can produce all four nucleosides in one pot, thereby offering the first plausible explanation for how all four RNA letters could have arisen together.Benner calls Carell’s solution very clever. But not everyone is on board. Sutherland notes that those reactions are inefficient; any nucleosides they produced might fall apart faster than they could accumulate. To address that concern, others argue that more stable RNA-like compounds, rather than RNA itself, might have emerged first and helped form the first chemical system that could reproduce itself. Later, those RNA mimics might have given way to more efficient modern biomolecules such as RNA. Email O O O O O O O – O O O – O – O – O O O O 3.43 bya Ada Yonath, Weizmann Institute of Science 4.4 4.6 Crystal Shi 4.1 bya 3.8 bya 4.51 byaRNA 4.47 bya GuanineAdenineCytosineUracilRibosePhosphate N. DESAI/SCIENCE 4.4 O 4.35 bya O Sign up for our daily newsletter Get more great content like this delivered right to you! Country The impact scenario joins new findings from laboratory experiments suggesting how the chemicals spawned on early Earth might have taken key steps along the road to life—steps that had long baffled researchers. Many in the field see a consistent narrative describing how and when life was born starting to take shape. “Fifteen years ago, we only had a few hazy ideas” about how life may have come about, says Andrej Lupták, a chemist at the University of California (UC), Irvine, who attended the meeting. “Now, we’re seeing more and more pieces come together.”The case isn’t settled, Lupták and others say. Researchers still disagree, for example, over which chemical path most likely gave rise to RNA and how that RNA combined with proteins and fats to form the earliest cells. Nevertheless, Benner says, “The field is in a new place. There is no question.”The RNA worldLife as we know it likely emerged from an “RNA world,” many researchers agree. In modern cells, DNA, RNA, and proteins play vital roles. DNA stores heritable information, RNA ferries it inside cells, and proteins serve as chemical workhorses. The production of each of those biomolecules requires the other two. Yet, the idea that all three complex molecules arose simultaneously seems implausible.Since the 1960s, a leading school of thought has held that RNA arose first, with DNA and proteins evolving later. That’s because RNA can both serve as a genetic code and catalyze chemical reactions. In modern cells, RNA strands still work alongside proteins at the heart of many crucial cellular machines.In recent years, chemists have sketched out reactions that could have produced essential building blocks for RNA and other compounds. In 2011, for example, Benner and his colleagues showed how boron-containing minerals could have catalyzed reactions of chemicals such as formaldehyde and glycolaldehyde, which were probably present on early Earth, to produce the sugar ribose, an essential component of RNA. Other researchers have laid out how ribose may have reacted with other compounds to give rise to individual RNA letters, or nucleosides.But critics such as Robert Shapiro, a biochemist at New York University in New York City who died in 2011, often pointed out that when researchers produced one pre-RNA chemical component or another, they did so under controlled conditions, adding purified reagents in just the right sequence. How all those steps could have occurred in the chaotic environment of early Earth is unclear at best. “The analogy that comes to mind is that of a golfer, who having played a golf ball through an 18-hole course, then assumed that the ball could also play itself around the course in his absence,” Shapiro wrote in 2007 in Scientific American. He favored a “metabolism first” view of life’s origin, in which energetic small molecules trapped inside lipidlike membranes or other compartments established chemical cycles resembling metabolism, which transformed into more complex networks. Other researchers, meanwhile, have argued that simple proteins were a more likely driver of early life because their amino acid building blocks are far simpler than the nucleotides in RNA.Arguments have sometimes been heated. At a 2008 meeting on the origin of life in Ventura, California, Shapiro and John Sutherland, a chemist at the University of Cambridge in the United Kingdom, wound up shouting at each other. “Bob was very critical about published routes to prebiotic molecules,” Sutherland says. If the chemistry wasn’t ironclad, “he felt it failed.” That scenario captivated participants at an October 2018 conference here, where geologists, planetary scientists, chemists, and biologists compared notes on the latest thinking on how life got its start. No rocks or other direct evidence remain from the supposed cataclysm. Its starring role is inferred because it would solve a bevy of mysteries, says Steven Benner, an origin of life researcher at the Foundation for Applied Molecular Evolution in Alachua, Florida, who organized the Origins of Life Workshop.The metal-laden rain accounts for the distribution of metals across our planet’s surface today. The hydrogen atmosphere would have favored the emergence of the simple organic molecules that later formed more complex molecules such as RNA. And the planetary crash pushes back the likely birthdate for RNA, and possibly life’s emergence, by hundreds of millions of years, which better aligns with recent geological evidence suggesting an early emergence of life. 4.1 Click to view the privacy policy. Required fields are indicated by an asterisk (*) NASA/MCT/MCT VIA GETTY IMAGES 4.6 bya 4.568 billion years ago (bya) By Robert F. ServiceJan. 10, 2019 , 11:00 AM Whichever route RNA’s letters took, other researchers have recently worked out how minerals likely present on early Earth could have added phosphate groups to RNA nucleosides, an essential step toward linking them into long strings of RNA that could then have acted as catalysts and a rudimentary genetic code. And many experiments have confirmed that once RNA chains begin to grow, they can swap RNA letters and even whole sections with other strands, building complexity, variation, and new chemical functions. At the meeting, for example, Niles Lehman, a chemist at Portland State University in Oregon, described experiments in which pairs of 16-letter-long RNA chains, known as 16-mers, rearranged to form 28-mers and 4-mers. “This is how we can go from short things that can be made prebiotically to more complex molecules,” Lehman said. Later, he quipped, “If you give me 8-mers, I’ll give you life.”That process may help explain how more complex RNA molecules arose, including those that can propel the synthesis of simple proteins. At the meeting in Atlanta, chemist Ada Yonath presented one such prototypical proteinmaking RNA. Yonath, of the Weizmann Institute of Science in Rehovot, Israel, shared the 2009 Nobel Prize in Chemistry for working out the atomic structure of the ribosome, the complex molecular machine inside today’s cells that translates the genetic code into proteins. Yonath’s original structure was of a bacterium’s ribosome. Since then, she and her colleagues, along with other groups, have mapped the ribosomes of many other species. Modern ribosomes are behemoths, made up of dozens of protein and RNA components. But at their core, all ribosomes have a sinuous string of RNA with a narrow slit through which budding proteins emerge. The structure is virtually identical across species, unchanged after billions of years of evolution.Her group has now synthesized that ribosomal core, which she refers to as the protoribosome. At the meeting, she reported that her team’s protoribosome can stitch together pairs of amino acids, the building blocks of proteins. “I think we’re seeing back to how life began billions of years ago,” Yonath says.All that is still a long way from demonstrating the emergence of life in a test tube. Nevertheless, Clemens Richert, a chemist at the Institute of Organic Chemistry at the University of Stuttgart in Germany, says the recent progress has been heartening. “We’re finding reactions that work,” he says. “But there are still gaps to get from the elements to functional biomolecules.”Earth’s mysteriesOne major gap is identifying a source for the energetic nitrogen-containing molecules needed to make the RNA bases. Lightning and UV light acting on compounds in the atmosphere may have made enough of them, says Jack Szostak, an origin of life expert at Harvard University. At the meeting, Stephen Mojzsis, a geologist at the University of Colorado in Boulder, argued that the moon-size impact is a more plausible spark.Mojzsis didn’t set out to grapple with the origin of life. Rather, he and his colleagues were looking for ways to make sense of a decades-old geological conundrum: the surprising abundance of platinum and related metals in Earth’s crust. In the standard picture of Earth’s formation, they simply shouldn’t be there. The violent assembly of the planet from smaller bodies 4.53 billion years ago would have left it as a boiling sea of magma for millions of years. Dense elements, such as iron, gold, platinum, and palladium, should have sunk to the planet’s core, whereas silicon and other light elements floated nearer the surface. Yet as the wares in any jewelry store testify, those metals remain plentiful near the planet’s surface. “Precious metals in the crust are thousands of times more abundant than they should be,” Mojzsis says. I think we’re seeing back to how life began billions of years ago. 3.4 Solar system forms.Earth forms.Moon forms.Proposed impact of planetesimal forms “reducing” atmosphere. Earth cools enough to have both land and water.Approximate timing of formation of RNA.Zircon materials show hints of life in ratio of carbon isotopes. Proposed end of Late Heavy Bombardment.Fossils attributed to micro-organisms. 3.6 O O 4.0 This 4.1-billion-year-old zircon mineral (x-ray image) contains carbon isotopes suggestive of life. 4.46 bya 3.5last_img read more

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