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Multiple Sclerosis Provoked by DNA Traps That Promote Immune Cell Specialization

Increase in the levels of NETs—neutrophil extracellular traps, web like structures made of DNA and histones that trap pathogens—have been linked to autoimmune diseases. In a new study, scientists show NETs, through their histones, activate T cells…

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Scientists have discovered a new mechanism by which web-like DNA structures called neutrophil extracellular traps (NETs)—a bacteria-fighting weapon in the immune system’s arsenal—provoke the onset of autoimmune diseases such as multiple sclerosis (MS).

In a study published in the journal Nature Communications on January 26, titled “Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2,” researchers from The Australian National University (ANU) demonstrate NETs activate T cells and enhance the differentiation of a subset of proinflammatory T cells called Th17 that are a key player in autoimmune diseases and are crucial for immunity against fungal and bacterial infections. The innate stimulation of an adaptive immune cell-type generates a feedback loop that amplifies autoimmunity.

“This discovery is significant as it provides a novel therapeutic target to disrupt these harmful inflammatory responses,” said Alicia Wilson, PhD, from the Johannes Gutenberg-University Mainz in Germany, who is first-author of the paper. “It opens the doors to the development of new therapies targeting this harmful NET-Th17 interaction, hopefully improving treatments for MS and other autoimmune conditions in the future.”

“My group mainly works with a multiple sclerosis laboratory model,” said Anne Bruestle, senior author of the paper and associate professor at the department of immunology and infectious disease at ANU. “We realized that neutrophil extracellular traps (NETs) are up in the blood before symptoms are seen. So, we wondered if these NETs might have an enhancing effect on inflammatory Th17 cells.”

NETs, that resemble spider webs in structure and function, are extruded from activated neutrophils, a type of white blood cell. NETs trap and kill bacteria, protecting the body from infection. This new study shows NETs also function to abnormally increase the strength of Th17 cells.

Scanning electron microscope image of NETs engulfing fungal cells in an infected mouse lung (WikiCommons/Urban CF, et al, PloS Pathog, 2009).

Beneficial under normal conditions, Th17 cells can cause undesirable inflammation when over-activated, promoting autoimmune diseases. “We found that the NETs cause Th17 cells to become more powerful, which enhances their detrimental effects,” said Bruestle.

“We describe a new way how NETs can directly activate Th17 cells and even more important, how to block this unwanted activation,” said Bruestle. “This has implications for a variety of Th17 cell associated autoimmune conditions such as multiple sclerosis or psoriasis where we believe inhibiting NET-induced activation of Th17 cells might be a novel treatment concept.”

Understanding the mechanism that enables NETs to turn friendly Th17 cells into foes can help develop targeted therapies for autoimmunity. Bruestle and a team of international researchers believe a drug called mCBS, originally designed to treat sepsis, could be used to target Th17 cells and treat MS. The drug was developed by Christopher Parish, PhD, and his team at ANU.

“Because we see in both mice and humans that a group of proteins in NETs called histones can activate Th17 cells and cause them to become harmful, it makes sense that our histone-neutralising drug, mCBS, which was developed to treat sepsis, may also be able to inhibit the undesirable effects of NETs which are linked to driving MS,” said Parish.

Bruestle said, “We used the recently described histone/NET inhibitor, mCBS. This inhibitor is currently under phase 1b/2 clinical trial in sepsis and acute respiratory distress syndrome (ARDS)—a known complication in severe COVID-19 cases.”

Bruestle added, “While we cannot prevent autoimmune diseases such as MS, thanks to these types of therapies we hope to treat the condition and make it more manageable for people living with MS.”

Bruestle and her team are currently using inhibitors of NET-Th17 interactions in models of Th17-mediated autoimmunity to develop and optimize treatment options for autoimmune conditions such as MS.

The post Multiple Sclerosis Provoked by DNA Traps That Promote Immune Cell Specialization appeared first on GEN - Genetic Engineering and Biotechnology News.

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Six Commodities Investments to Buy as Putin Wages War on Ukraine

Six commodities investments to buy amid the sustained attack of Ukraine by Russia’s President Vladimir Putin and rising inflation provide potential to…

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Six commodities investments to buy amid the sustained attack of Ukraine by Russia’s President Vladimir Putin and rising inflation provide potential to profit even as the market has been pulling back so far in 2022.

The six commodities investments to buy include those involved in oil, gold and grain due to current supply shortages that are showing no signs of abating anytime soon. Putin’s order for Russian troops to invade Ukraine on Feb. 24 has disrupted the neighboring nation’s agricultural production, led to the theft of grain and imposed an ongoing blockade in the Black Sea to stop farmers from exporting their crops.

Crude oil inventories are down to a “dangerously low point” across Europe, North America and Organisation for Economic Co-operation and Development (OECD) Asia, just as spare production capacity from OPEC+ nations slid to the lowest levels since April 2020, according to BofA Global Research. Inventories of petroleum products also have fallen to “precarious levels” for middle distillates and even gasoline as the market heads into the peak of the U.S. summer driving season, the investment firm added.

As a result, refined petroleum cracks — the differences between crude oil and the prices of the wholesale petroleum products such as gasoline — recently have “spiked to record levels,” contributing to volatility, BofA wrote. In addition, strategic oil barrels held by OECD governments already are low and likely to decline steeply going forward, leaving consumers exposed to future negative supply shocks, BofA predicted.

Pension Fund Chairman Recommends Broad Commodity Funds

Bob Carlson, a pension fund chairman who also leads the Retirement Watch investment newsletter, recommended Cohen & Steers MLP & Energy Opportunity Fund (MLOAX) to all the portfolios in his June 2022 issue. 

Oil and natural gas should be good investments as Europe looks to reduce dependence on Russian exports, Carlson told me. Plus, energy producers in the United States are focused on increasing cash flow and earnings, not maximizing drilling expenses in the short run to increase output, he added.

Bob Carlson, who leads Retirement Watch, meets with Paul Dykewicz.

Good investment opportunities can be found with companies that provide the pipelines, storage facilities and other infrastructure needed to supply the world with oil, natural gas and other energy sources, Carlson continued. 

“One of the attractive qualities of these investments is that their revenues are independent of the prices of the commodities,” Carlson counseled. “The firms charge fees for their services, and the fees often are adjusted for inflation. Their revenues and earnings depend on the volume of commodities passing through their facilities, not the price of the commodity.”

Key energy service companies provide total returns, aided by current income and price appreciation, through investments in energy-related master limited partnerships (MLPs) and securities of industry companies, Carlson pointed out. Those businesses are expected to derive at least 50% of their revenues or operating income from exploration, production, gathering, transportation, processing, storage, refining, distribution or marketing of natural gas, crude oil and other energy resources.

Chart courtesy of www.stockcharts.com

Cohen & Steers Fund Leads List of Six Commodities Investments to Buy

Cohen & Steers MLP & Energy Opportunity Fund recently held 53 positions and had 50% of its portfolio in the 10 largest positions. Top holdings of the fund included Enbridge (NYSE: ENB), Cheniere Energy (NYSEAMERICAN: LNG), Williams Companies (NYSE: WMB), TC Energy (NYSE: TRP) and Energy Transfer (NYSE: ET).

The fund has achieved strong returns since April 2020. Indeed, it has been on an upward trajectory since the second half of December 2021.

“Crucially, oil prices have held up well even in the face of a slowing Chinese economy and widespread lockdowns,” according to BofA. “Given that most China indicators point to a major decline in mobility across the country, any improvement in the COVID-19 situation in large Chinese cities could send oil prices much higher.”

Carlson’s Chooses DBA to Join Six Commodities Investments to Buy

Despite the evils of war, investors still can profit from the rise in grain prices and other commodities through the futures markets, even as many other equities slip. Instead of buying futures directly, investors can purchase diversified agriculture commodities through Invesco DB Agriculture Fund (DBA), Carlson said.

That ETF seeks to track changes in the DBIQ Diversified Agriculture Index Excess Return. The ETF also earns interest income from cash it invests primarily in treasury securities, while holding them as collateral for the futures contracts.

The major holdings in the index are soybeans, wheat, corn, coffee and live cattle. The index is reconstituted each November.

Chart courtesy of www.stockcharts.com

Gold Funds Featured Among Six Commodities Investments to Buy

Carlson also is recommending gold through iShares Gold Trust (IAU). He described it as the “cheapest, most liquid way” to invest in the shiny yellow metal.

Gold has had its ups and downs in the face of rising global inflation, Russia’s invasion of Ukraine, China’s increasing military flyovers of nearby Asian nations and other geopolitical conflicts. At the same time, the U.S. dollar has been appreciating amid high inflation after the Fed recently raised interest rates by 0.5% and promised additional increases later in 2022.

However, there are many risks for the U.S. dollar, so continuing to hold gold remains a good hedge, Carlson counseled.

IAU has retreated since early March, so investors seeking to buy it now that it is rebounding still may do so. Those who believe inflation may stay through 2022 can try to capture gains before the trend no longer is a friend.

Chart courtesy of www.stockcharts.com

Skousen Calls GLD One of the Six Commodities Investments to Buy

“Gold has done far better than stocks, which are down 15-25% this year,” said Mark Skousen, who is recommending SPDR Gold Shares (NYSE Arca: GLD) in his Forecasts & Strategies investment newsletter. 

Mark Skousen, head of Forecasts & Strategies, meets with Paul Dykewicz.

GLD has risen nearly 16% since Skousen recommended it about two years ago. Gold climbed 2021 in anticipation of rising inflation, but its performance has been flat so far this year. If gold truly is an indicator of inflation, the previous yellow metal’s stagnant price may be signaling that price inflation will wane heading into 2023.

The investment objective is for the GLD shares to reflect the performance of the price of gold bullion, after subtracting the trust’s expenses. The trust, formed on November 12, 2004, physically holds gold bars.

The trust’s shares are designed for investors who want a cost-effective and convenient way to invest in gold, according to the company’s prospectus. Skousen, who also leads the Five Star Trader, Home Run Trader, TNT Trader and Fast Money Alert services, recently was a featured speaker at the Vancouver Resource Investment Conference and advised attendees that he recommended gold as a minor holding in every portfolio.

Chart courtesy of www.stockcharts.com

EPD Is Another of the Six Commodities Investments to Buy

Oil has done much better as an inflation hedge than gold, Skousen said. One example is his recommendation of Enterprise Products Partners (EPD, $27, 7% yield), up 27% year to date.

EPD has been the “best performer” in the Forecasts & Strategies investment newsletter so far this year, Skousen said. Enterprise Products Partners is one of the largest publicly traded partnerships and a key North American provider of midstream energy services to producers and consumers of natural gas, natural gas liquids (NGLs), crude oil, refined products and petrochemicals. 

The company’s services include natural gas gathering, treating, processing, transportation and storage. In addition, Enterprise Products Partners provides NGL transportation, fractionation, storage and import and export terminals. It further offers crude oil gathering, transportation, storage and terminals, along with petrochemical and refined products transportation, storage and terminals, as well as a marine transportation business.

I personally have owned Enterprise Products Partners since shortly after the 2020 stock market crash when I bought the stock as it started to recover. The stock has been trending upward since the end of 2021.

Chart courtesy of www.stockcharts.com

Money Manager Picks One of Six Commodities Investments to Buy

A seasoned investment professional told me that she likes farm machinery company Deere (NYSE: DE) to profit from agriculture. Michelle Connell, a former portfolio manager who now serves as president of Dallas-based Portia Capital Management, said she still likes Deere despite its 14% drop after it reported results last week.

Michelle Connell, CEO, Portia Capital Management

Deere’s key issues are supply-related, since demand for agricultural equipment remains strong, especially for the company’s machinery that is more environmentally friendly than its rivals, Connell continued.

Deere is also focused on providing the farming industry with autonomous equipment, Connell counseled. Wall Street analysts expect Deere to have a better story and performance in the second half of 2022 and in full-year 2023.

Connell cited the following to support her recommendation of Deere: 

-More than half its revenues come from large agriculture.

-If the war in Ukraine continues, U.S. farmers will benefit from higher prices for their crops.

-Increased agricultural profits mean that that farmers and farming corporations will be more likely to buy large, expensive farm equipment.  

Deere has fallen back since its recent high on April 20, so investors should be able to purchase shares at reduced prices, Connell continued.

Chart courtesy of www.stockcharts.com

Supply Chains May Improve as China Starts to Lower COVID Curbs

China is easing its COVID-19 restrictions and it could allow goods produced there to start flowing normally again in the coming weeks. China’s lockdowns have affected an estimated 373 million people, including roughly 40% of its gross domestic product (GDP). Disrupted supply chains have affected products such as rice, oil and natural gas.

Shanghai, home to the world’s largest port and 25 million residents, has strained to unload cargo due to strict regulations that have caused shipping containers to stack up. Some Shanghai residents posted videos online to complain about needing food, even though government officials sought to block such public expressions of frustration.

Chinese authorities also drew public criticism for forcibly separating young children with COVID-19 from their parents to prioritize stopping the spread of a new, contagious subvariant of Omicron, BA.2. The variant also has been causing new infections in European nations such as Germany, the Netherlands and Switzerland.

U.S. COVID Deaths Climb Past 1-Million Mark

U.S. COVID-19 deaths crossed the 1-million mark last week and have climbed further to 1,002,726 as of May 24, according to Johns Hopkins University. Cases in the United States, as of that date, hit 83,501,455. America retains the dubious distinction as the country with the highest numbers of COVID-19 deaths and cases.

COVID-19 deaths worldwide totaled 6,280,342 on May 24, according to Johns Hopkins. Cases across the globe have climbed to 526,664,642.

Roughly 77.8% of the U.S. population, or 258,562,059, have obtained at least one dose of a COVID-19 vaccine, as of May 24, the CDC reported. Fully vaccinated people total 221,001,614, or 66.6%, of America’s population, according to the CDC. The United States also has given at least one COVID-19 booster vaccine to 102.9 million people, up about 500,000 in the past week.

New data on so-called “long-haul” COVID patients released on May 24 reported that even though some symptoms improve others may persist, according to the Northwestern Medicine Neuro COVID-19 Clinic. Most of the 52 patients monitored in the Northwestern study reported “brain fog,” numbness or tingling, headache, dizziness, blurred vision and fatigue, even 15 months after initial diagnoses of COVID-19.

The six commodities investments to buy are intended to profit from rising energy, gold and grain prices. Despite the market’s volatility, the highest inflation in 40 years, the Fed’s plan for further interest rate hikes to curb price hikes and increasing federal deficits, investors are finding profitable opportunities in energy, gold and grains.

Paul Dykewicz, www.pauldykewicz.com, is an accomplished, award-winning journalist who has written for Dow Jones, the Wall Street Journal, Investor’s Business Daily, USA Today, the Journal of Commerce, Seeking Alpha, Guru Focus and other publications and websites. Paul, who can be followed on Twitter @PaulDykewicz, is the editor of StockInvestor.com and DividendInvestor.com, a writer for both websites and a columnist. He further is editorial director of Eagle Financial Publications in Washington, D.C., where he edits monthly investment newsletters, time-sensitive trading alerts, free e-letters and other investment reports. Paul previously served as business editor of Baltimore’s Daily Record newspaper. Paul also is the author of an inspirational book, “Holy Smokes! Golden Guidance from Notre Dame’s Championship Chaplain,” with a foreword by former national championship-winning football coach Lou Holtz. The book is great as a gift and is endorsed by Joe Montana, Joe Theismann, Ara Parseghian, “Rocket” Ismail, Reggie Brooks, Dick Vitale and many others. Call 202-677-4457 for multiple-book pricing.

 

The post Six Commodities Investments to Buy as Putin Wages War on Ukraine appeared first on Stock Investor.

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Moderna CEO Laments ‘Throwing 30 Million Doses In The Garbage Because Nobody Wants Them’

Moderna CEO Laments ‘Throwing 30 Million Doses In The Garbage Because Nobody Wants Them’

Moderna CEO Stéphane Bancel is complaining about…

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Moderna CEO Laments 'Throwing 30 Million Doses In The Garbage Because Nobody Wants Them'

Moderna CEO Stéphane Bancel is complaining about having to 'throw away' 30 million doses of Covid-19 vaccine because 'nobody wants them.'

"It's sad to say, I'm in the process of throwing 30 million doses in the garbage because nobody wants them. We have a big demand problem," Bancel told an audience at the World Economic Forum, adding that attempts to contact various governments to see if anyone wants to pick up the slack was a total fail.

"We right now have governments - we tried to contact ... through the embassies in Washington. Every country, and nobody wants to take them."

"The issue in many countries is that people don't want vaccines."

Watch:

Bancel's comments come days after Bloomberg reported that EU health officials want to amend contracts with Pfizer and other vaccine makers in order to reduce supplies

During a virtual meeting organized by Polish Health Minister Adam Niedzielski, governments shared a joint letter to the EU Commission which reads: "We hope that the discussion with the commission and among member states will allow flexibility in the vaccine agreements," adding "We are also counting on vaccine producers to show understanding to the exceptional challenges that Poland is facing supporting Ukraine and giving shelter to millions of Ukrainian citizens fleeing the war."

Some countries are seeking to amend so-called advanced purchase agreements signed with producers, as demand for shots wanes and budgets come under strain from the fallout of the war in Ukraine and the costs of accommodating refugees.

Adjusting deals with suppliers could grant member states the right to “re-phase, suspend or cancel altogether vaccine deliveries with short shelf life,” Estonia, Latvia and Lithuania’s prime ministers wrote in a joint letter to Commission President Ursula Von Der Leyen late last month.

Meanwhile, in a separate letter the health ministry of Bulgaria called for an "open dialog" with the commission and pharmaceutical companies, arguing that the current arrangement forces member states to "purchase quantities of vaccines they don’t need."

Tyler Durden Tue, 05/24/2022 - 21:45

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Nearly 108,000 overdose deaths in 2021: Pitt team forecast devastating toll five years ago

PITTSBURGH, May 24, 2022 – A grim prediction made half a decade ago by University of Pittsburgh School of Public Health epidemiologists and modelers…

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PITTSBURGH, May 24, 2022 – A grim prediction made half a decade ago by University of Pittsburgh School of Public Health epidemiologists and modelers has come true: More than 100,000 people are now dying from drug overdoses annually in the U.S. The milestone comes as the International Journal of Drug Policy publishes a special section of the June issue reflecting on the exponential growth in drug-related deaths the Pitt team uncovered in 2017.

Credit: Courtesy of University of Pittsburgh

PITTSBURGH, May 24, 2022 – A grim prediction made half a decade ago by University of Pittsburgh School of Public Health epidemiologists and modelers has come true: More than 100,000 people are now dying from drug overdoses annually in the U.S. The milestone comes as the International Journal of Drug Policy publishes a special section of the June issue reflecting on the exponential growth in drug-related deaths the Pitt team uncovered in 2017.

The special section – based around the Pitt team’s landmark research article in Science that analyzed nearly four decades of U.S. drug overdose data – contains commentary by four teams of epidemiologists, addiction specialists, modelers and drug policy experts, as well as an update from the original authors and an editorial by one of the journal’s senior editors.

“Since 1979, drug overdose deaths in the U.S. have inexorably climbed along a near-perfect exponential curve, despite changes in the popularity of different drugs, new drug control policies, changing demographics, economic upswings and downturns, wars – and now a global pandemic,” said Donald S. Burke, M.D., Distinguished University Professor of Health Science and Policy in Pitt Public Health’s Department of Epidemiology and senior author of the Science publication. “The fact that we’re still seeing this exponential growth in another five years of data – 413,000 more young Americans dead – shows that we really don’t understand the deep drivers of the epidemic.”

Following their Science publication, Burke and his colleagues published several more articles involving U.S. drug overdose death data. Notably, the team reported in Nature Medicine that the generation a person was born into – Silent Generation, Baby Boomer, Generation X or Millennial – strongly predicts how likely they are to die from a drug overdose, and at what age.

And, when drug overdose deaths diverged from their predictions, taking a celebrated downturn in 2018, the team showed in the journal Addiction that it was a result of a decrease in supply of the potent synthetic opioid carfentanil, and not a sign of the drug overdose epidemic abating. Sure enough, overdose deaths snapped right back onto the exponential curve in the following year.

“There are theories, but nobody has an explanation for why drug overdose deaths so consistently stick to this exponential growth pattern, marching ever upward at an annual pace of 7.4%,” said Hawre Jalal, M.D., Ph.D., who was lead author of the Science paper while at Pitt and is now at the University of Ottawa. “Five years ago, leaders in the drug addiction and policy fields called our findings a coincidence. We need to stop denying that this exponential growth will continue if we don’t get at the root causes and fix them.”

In his editorial introducing the International Journal of Drug Policy special edition, Peter Reuter, Ph.D., distinguished professor in the University of Maryland School of Public Policy, noted that although the Science manuscript had been cited by scientists hundreds of times since its original publication to support that drug overdose rates are rising, no one had investigated the underlying cause of the relentless increase.

“It’s hard to imagine that this growth rate can continue much longer,” Reuter writes. “The notion that we might see 200,000 fatal overdoses annually in 2030 is simply too frightening, though we would have made the same statement in 2010 when the figure was a mere 38,000.”

In their article for the special section, Burke and Jalal suggest that a “systems” analysis including, but not limited to, surveillance data from electronic health records, urine screening, wastewater testing, law enforcement drug seizures, surveys to measure societal well-being and despair, and the economics of the drug trade will be necessary to understand the exponential growth. Computational models and simulations will then need to be designed to guide and test interventions, they said.

“Improved understanding of the deep causal drivers of the epidemic may be necessary to bend the curve,” they conclude. “Unless something different is done, the death toll will probably continue to increase exponentially.”

#  #  #

About the University of Pittsburgh School of Public Health

Founded in 1948, the University of Pittsburgh School of Public Health is a top-ranked institution of seven academic departments partnering with stakeholders locally and globally to create, implement and disseminate innovative public health research and practice. With hands-on and high-tech instruction, Pitt Public Health trains a diverse community of students to become public health leaders who counter persistent population health problems and inequities. 

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