Japan's Warning For America

 by Michael Wilkerson via The Epoch Times,

Last week, Japan saw its currency, the yen, rapidly depreciate against the U.S. dollar and other world currencies to near record low levels. This drew the attention of financial markets and other observers, and—in some quarters—led to panic. There was concern that Japan, a formerly great nation now increasingly viewed as the “sick man of Asia,” was on the brink of a currency and financial markets crisis.

It wasn’t so long ago that Japan was the envy of the world. Japan’s postwar recovery and subsequent economic miracle produced by the 1980s the world’s second-largest economy after the United States. Numerous Japanese multinational corporations were admired by the business world as a result of their growth, efficiency, and managerial discipline. The state and big business were closely aligned in what appeared an unstoppable formula. Flush with cash and confidence, Japanese companies and investors were aggressively expansionist, acquiring market share, trophy properties, resources, and businesses in the United States and elsewhere. Much like concerns about China today, fears then abounded that Japan would overtake the United States as the global economic leader.

These fears were unfounded. “Japan Inc.” was a house built on a faulty foundation. Overly accommodative easy money, along with high leverage throughout the financial and corporate sectors, facilitated a massive stock market and real estate bubble, which eventually burst in 1990. The crash led to a depression from which Japan has never recovered, even after three decades. The question is, why not? Herein lies a lesson for the United States.

Repeated government bailouts of failing financial and industrial companies have perpetuated Japan’s crisis. Japan’s leaders and policies have repeatedly blocked the process of creative destruction, which—if allowed to run its course and cleanse the system—would have been a massive stimulus to entrepreneurship and economic vitality. However, rather than allow capitalism to work, the Japanese system doomed the country to a generation of stagnation.

As a result, Japan has endured three “lost decades” of weak economic growth, diminished purchasing power, lower and lower standards of living, loss of prestige and influence in the global community, and an aging population that the island nation’s resources are straining to support.

Japan now has the world’s highest government debt-to-GDP ratio, at 264 percent. Japan’s banks are walking zombies, unable to grow or lend because they have never restructured their balance sheets to clean up massive piles of debt left over from excesses of previous decades. The Bank of Japan (BOJ) holds government bonds and other assets equal to 127 percent of Japan’s GDP, the highest ratio of any central bank in the world. This portfolio resulted in over $70 billion in unrealized losses for the BOJ in six months of 2023 alone.

The Japanese yen has devalued against the U.S. dollar by more than 30 percent in just three years since 2021. Since the global financial crisis 2008–09, the yen has lost 75 percent of its value against gold. Because of Japan’s high reliance on imports, this loss of purchasing power has translated directly into a substantially lower standard of living for the Japanese people. In theory, Japan could support the yen by raising interest rates, but this is a political, monetary, and fiscal impossibility.

Decades of easy money policies are a central culprit and cause of this slow-moving trainwreck.

The Bank of Japan only began raising interest rates this March, some three years after the United States and the European Union brought their own easy money policies to an end. This was the first time the BOJ has raised rates since 2007, a move that pulled the official rate out of negative territory. Nonetheless, with inflation now approaching 2 percent, a short-term policy rate of zero to 0.1 percent means that real rates remain around negative 2 percent. This serves as an additional tax on Japanese households and an intended stimulus to spend today rather than save for tomorrow.

Money essentially is free in Japan, but no one can afford to borrow it, even if the banks can manage to lend it. The BOJ and the entire banking system stand in the penumbra of insolvency. Only Japan’s decade-long zero interest-rate policy has allowed Japan’s decrepit financial system to continue to stand following the 2008 financial crisis and the effects of COVID economic shutdowns. Japan cannot afford to raise interest rates to support its currency more than nominally above the zero bound without substantially raising debt service costs and exploding losses. This would bring the entire rickety system to the ground.

A growing economy might help ease the burden, but Japan’s economy is moribund. This is not surprising, as meaningful growth is impossible under mountains of debt. GDP shrank by 0.8 percent in the third quarter and eked out 0.1 percent growth in the fourth quarter. While the country thus barely escaped technical recession (two consecutive quarters of GDP decline), Japan hasn’t posted GDP growth above 2 percent in more than 20 years, save for two rebound quarters after the global shocks of the financial crisis and COVID.

Japan represents a slow-moving demographic disaster. Japan has the oldest median population of any major country in the world and the lowest fertility rate at 1.37. Japan’s fertility rate has been below the minimum population replacement rate (2.1) for 40 years, meaning that the country is both aging and losing economic productivity, and it is probably too late to reverse it.

This all represents a grave warning to the United States.

The U.S. government is chasing Japan for the ignoble title of most indebted nation. Overly indebted nations cannot grow. With federal government debt to GDP of 129 percent, a ratio which is increasing rapidly, the United States is now the fourth most indebted country in the world. Debt is growing more quickly now because the federal government refuses to wean itself off of deficit spending, including an additional $1.7 trillion in 2023, which must be funded by new debt, as must over $1 trillion in interest expense. This debt—and the cost to service it—acts as a drag on our economy. Deficit spending and the borrowing required to support it crowds out private market investment and financings.

Rather than let more insolvent banks and unprofitable firms fail, U.S. monetary policy since at least the 2008 financial crisis has propped up bad business models—and the asset values of otherwise worthless investments—by subsidizing the cost of capital well below the natural rate of interest. In a nation that has been the standard bearer and exporter of capitalism for more than two centuries, socialistic government policies are preventing capitalism from working at home. This will eventually catch up with our financial markets and economy, just as it did for Japan.

It is not just shortsighted monetary and financial policy that threatens U.S. competitiveness.

If Americans’ worsening attitudes toward the importance of marriage and children do not reverse course dramatically, the United States will face the same demographic fate as Japan. The fertility rate in the United States has been in decline since at least 2008, and reached a record low of 1.62 in 2023. This is well below the replacement rate, and thus unsustainable.

Progressives point to declining fertility rates and aging populations to justify mass illegal immigration, but this is a red herring. Bringing tens of millions of unskilled, uneducated, and culturally unassimilated migrants into the nation is not a benefit but rather an untenable burden on social infrastructure, an enervating drain on economic productivity, and an unbearable tax on legal citizens.

At least Japan got that part right.

https://www.zerohedge.com/markets/japans-warning-america

Uncovering the secret of long-lived stem cells

 Nothing lives forever, but compared to other cells in the body, hematopoietic stem cells (HSCs) are remarkably long-lived. HSCs are blood-forming cells -- they give rise to rapidly dividing progenitor cells, which in turn generate hundreds of billions of cells to fulfill the daily demand of oxygen-delivering red blood cells, disease-fighting white blood cells and clot-forming platelets.

HSCs typically remain dormant within the bone marrow, yet they possess the ability to activate and replenish blood cells continuously, maintaining a relatively youthful profile throughout the life of an organism. What is the secret of long-lived HSCs that wards off the effects of aging? A team led by researchers at Baylor College of Medicine revealed in Nature Cell Biology that the enzyme cyclophilin A, which is produced in large amounts in HSCs, is key for these cells to retain their regenerative potential and avert the effects of aging.

Long live the stem cells!

"A driving force of cellular aging is the accumulation of proteins that have reached the end of their useful life," said corresponding author Dr. André Catic, assistant professor and CPRIT Scholar in Cancer Research in the Huffington Center on Aging at Baylor. "With age, proteins tend to misfold, aggregate and accumulate inside the cell, which leads to toxic stress that can disrupt cell function."

Cells that frequently engage in cell division, like progenitor cells, can dispose of protein aggregates through dilution. On the other hand, long-lived HSCs, which do not divide often, face the problem of the accumulation of misfolded proteins and subsequent toxic stress. Nevertheless, HSCs remain impervious to aging. How do they do it?

"Understanding the molecular mechanisms that contribute to HSC aging not only contributes to the field of normal HSC biology, but also may have significant clinical relevance for cancer treatment," said co-first author of the work, Dr. Lauren Maneix, who was at the Catic lab while working on this project.

Molecular chaperones at work

Previous studies have shown that mammalian cells express several hundreds of molecular chaperones, proteins that preserve or change the three-dimensional conformation of existing proteins. Cyclophilins, one of the most abundant chaperones, have been implicated in the aging process. However, how they affect cellular proteins has not previously been studied.

Working with mice, the researchers first characterized the protein content of HSCs and discovered that cyclophilin A is a prevalent chaperone. Further experiments showed that the expression of cyclophilin A was significantly decreased in aged HSCs, and genetically eliminating cyclophilin A accelerated natural aging in the stem cell compartment. In contrast, reintroducing cyclophilin A into aged HSCs enhanced their function. Together, these findings support cyclophilin A as a key factor in the longevity of HSCs.

Connecting cyclophilin A, intrinsically disordered proteins and HSC longevity

Next, the team investigated the proteins with which cyclophilin A interacts, preserving their stability. "We found that proteins enriched in intrinsically disordered regions are frequent targets of the chaperone," Catic said.

Intrinsically disordered proteins naturally change their 3-D conformation to interact with different proteins, nucleic acids or other molecules. Consequently, proteins rich in intrinsically disordered regions regulate many cellular processes by promoting specific activities between molecules. "Due to their flexible nature, intrinsically disordered proteins are inherently prone to aggregation. Cyclophilin A supports these proteins in fulfilling their functions and simultaneously prevents them from clumping," Catic said.

Furthermore, the findings suggest that cyclophilin A interacts with intrinsically disordered proteins from the moment of their synthesis. "As these proteins are being made, cyclophilin A makes sure they keep the appropriate conformations and are maintained at sufficient levels," Catic said. "Genetic depletion of cyclophilin A results in stem cells distinctively lacking intrinsically disordered proteins."

"For the first time, our study showed that producing disordered proteins and maintaining the structural diversity of the proteins in a cell plays a role in HSC aging," Maneix said.

Co-first author Polina Iakova, Charles G. Lee, Shannon E. Moree, Xuan Lu, Gandhar K. Datar, Cedric T. Hill, Eric Spooner, Jordon C. K. King, David B. Sykes, Borja Saez, Bruno Di Stefano, Xi Chen, Daniela S. Krause, Ergun Sahin, Francis T. F. Tsai, Margaret A. Goodell, Bradford C. Berk and David T. Scadden also contributed to this study.

Journal Reference:

1. Laure Maneix, Polina Iakova, Charles G. Lee, Shannon E. Moree, Xuan Lu, Gandhar K. Datar, Cedric T. Hill, Eric Spooner, Jordon C. K. King, David B. Sykes, Borja Saez, Bruno Di Stefano, Xi Chen, Daniela S. Krause, Ergun Sahin, Francis T. F. Tsai, Margaret A. Goodell, Bradford C. Berk, David T. Scadden, André Catic. Cyclophilin A supports translation of intrinsically disordered proteins and affects haematopoietic stem cell ageing. Nature Cell Biology, 2024; 26 (4): 593 DOI: 10.1038/s41556-024-01387-x

https://www.sciencedaily.com/releases/2024/04/240430180312.htm

Clogged arteries worsened by cells that behave like cancer cells

 Columbia University researchers have found cells inside clogged arteries share similarities with cancer and aggravate atherosclerosis, raising the possibility that anticancer drugs could be used to treat atherosclerosis and prevent heart attacks.

Their study found that smooth muscle cells that normally line the inside of our arteries migrate into atherosclerotic plaques, change their cell identity, activate cancer genes, and proliferate inside the plaques.

"Our study shows that these transformed muscle cells are driving atherosclerosis, opening the door to new ways to treat the disease, potentially with existing cancer drugs," says Muredach Reilly, MD, the Florence and Herbert Irving Endowed Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons and director of Columbia's Irving Institute for Clinical and Translational Research.

The study, published April 30 in Circulation, was led by Reilly and Huize Pan, now an assistant professor of medicine at Vanderbilt University Medical Center, who conducted the research when he was an associate research scientist at Columbia.

DNA damage, hyperproliferation

Atherosclerosis is the major cause of heart attacks and stroke around the world and occurs when fat deposits build up inside the arteries. Atherosclerosis can be reduced with a healthy diet or drugs called statins that slow or reverse the buildup of deposits.

Previous studies had found that smooth muscle cells metamorphose into different types of cells inside these atherosclerotic plaques and multiply to make up most cells within the plaques.

Yet until now, few studies had examined the cancer-like properties of the cells and if these changes contributed to atherosclerosis. To learn more, Reilly and Pan closely tracked the development of transformed smooth muscle cells in mice with atherosclerosis and sampled plaques of people with atherosclerosis.

They found striking parallels between changes in the smooth muscle cells and tumor cells, including hyperproliferation, resistance to cell death, and invasiveness

DNA damage, another hallmark of cancer, accumulated in the mouse and human smooth muscle cells and appears to accelerate atherosclerosis, the researchers found. The researchers could further accelerate atherosclerosis in mice by introducing a genetic mutation that increased DNA damage within the smooth muscle cells. Vascular tissue from healthy mice and people had no signs of smooth muscle cells with the DNA damage found in atherosclerotic plaques.

Reilly adds that they found no evidence of metastasis. "The cells stay inside existing plaques, which makes us think that they behave mostly like benign tumor cells, but more work needs to be done in humans and animal models to address this hypothesis," he says.

Treating atherosclerosis like cancer

If atherosclerosis is driven by cancer-like cells, anticancer therapies may be a potential new way to treat or prevent the disease.

The researchers explored that idea by treating atherosclerotic mice with a common cancer drug, niraparib, that targets cells with DNA damage. The drug significantly decreased the size of the atherosclerotic plaques and improved plaque stability (stable plaques reduce the odds of having a heart attack).

"This suggests that cancer drugs like niraparib could both prevent the buildup of plaques and treat atherosclerosis once its established," Reilly says. "But it's important to note that the experiment with niraparib was proof of a principle and does not directly translate to clinical use."

Other cancer drugs may also have benefits. "We need more work to select the best targets, safest targeted therapies, and vascular delivery strategies," Reilly says. "And we need to determine if different people have different types of DNA damage and mutations that drive the disease, and, if so, we can use that information to develop personalized therapies to treat atherosclerosis," Reilly says.

"Statins are very effective in many people at reducing atherosclerosis and preventing hearts attacks, but some people still have substantial cardiovascular risk. We think more research into the cancer-like properties of atherosclerosis will lead to new treatment options for these patients."

Journal Reference:

1. Huize Pan, Sebastian E. Ho, Chenyi Xue, Jian Cui, Quinian S. Johanson, Nadja Sachs, Leila S. Ross, Fang Li, Robert A. Solomon, E. Sander Connolly, Virendra I. Patel, Lars Maegdefessel, Hanrui Zhang, Muredach P. Reilly. Atherosclerosis Is a Smooth Muscle Cell–Driven Tumor-Like Disease. Circulation, 2024; DOI: 10.1161/CIRCULATIONAHA.123.067587

https://www.sciencedaily.com/releases/2024/05/240501101035.htm

Brain circuit IDd in mice that controls body's inflammatory reactions

 The brain can direct the immune system to an unexpected degree, capable of detecting, ramping up and tamping down inflammation, shows a new study in mice from researchers at Columbia's Zuckerman Institute.

"The brain is the center of our thoughts, emotions, memories and feelings," said Hao Jin, PhD, a co-first author of the study published online today in Nature. "Thanks to great advances in circuit tracking and single-cell technology, we now know the brain does far more than that. It is monitoring the function of every system in the body."

Future research could identify drugs that can target this newfound brain circuit to help treat a vast range of disorders and diseases in which the immune system goes haywire.

"This new discovery could provide an exciting therapeutic venue to control inflammation and immunity," said Charles S. Zuker, PhD, the study's senior author, a principal investigator at Columbia's Zuckerman Institute and a Howard Hughes Medical Institute investigator.

Recent work from the Zuker lab and other groups is revealing the importance of the body-brain axis, a vital pathway that conveys data between the organs and the brain. For example, Dr. Zuker and his colleagues discovered that sugar and fat entering the gut use the body-brain axis to drive the craving and strong appetite for sugary and fatty foods.

"We found all these ways in which the body is informing the brain about the body's current state," said co-first author Mengtong Li, PhD, a postdoctoral researcher in the Zuker lab. "We wanted to understand how much farther the brain's knowledge and control of the body's biology went."

The scientists looked for connections the brain might have with inflammation and innate immunity, the defense system shared by all animals and the most ancient component of the immune system. Whereas the adaptive immune system remembers previous encounters with intruders to help it resist them if they invade again, the innate immune system attacks anything with common traits of germs. The relative simplicity of innate immunity lets it respond to new insults more quickly than adaptive immunity.

Prior studies in humans revealed that electrically stimulating the vagus nerve -- a bundle of thousands of nerve fibers linking the brain and the body's internal organs -- could reduce the response linked to a specific inflammatory molecule. However, much remained unknown about the nature of this body-brain system: for instance, the generality of the brain's modulation of immunity and the inflammatory response, the selective lines of communication between the body and the brain, the logic of the underlying neural circuit, and the identity of the vagal and brain components that monitor and regulate inflammation.

The Zuker lab turned to a bacterial compound that sets off innate immune responses. The scientists found that giving this molecule to mice activated the caudal nucleus of the solitary tract, or cNST, which is tucked inside the brainstem. The cNST plays a major role in the body-brain axis and is the primary target of the vagus nerve.

The scientists showed that chemically suppressing the cNST resulted in an out-of-control inflammatory response to the immune insult: levels of pro-inflammatory molecules released by the immune system were more than three times higher than usual, and levels of anti-inflammatory immune compounds were roughly three times lower than normal. In contrast, artificially activating the cNST reduced pro-inflammatory molecule levels by nearly 70 percent and increased anti-inflammatory chemical levels almost tenfold.

"Similar to a thermostat, this newfound brain circuit helps increase or decrease inflammatory responses to keep the body responding in a healthy manner," said Dr. Jin, who started this study as a postdoctoral researcher in Dr. Zuker's lab. Dr. Jin is now a tenure track investigator at the National Institute of Allergy and Infectious Diseases. "In retrospect, it makes sense to have a master arbiter controlling this vital response."

Previous vagus nerve stimulation research in humans suggests the findings go beyond mice. The new research may also be in line with thousands of years of thought on the potential importance of the mind on the body.

"A lot of psychosomatic effects could actually be linked to brain circuits telling your body something," Dr. Jin noted.

The scientists identified the specific groups of neurons in the vagus nerve and in the cNST that help detect and control pro- and anti-inflammatory activity. "This opens up a new window into how the brain monitors and modulates body physiology," said Dr. Zuker, a professor of biochemistry, molecular biophysics and neuroscience at Columbia's Vagelos College of Physicians and Surgeons.

Discovering ways to control this newfound brain circuit may lead to novel therapies for common auto-immune diseases such as rheumatoid arthritis, type I diabetes, multiple sclerosis, neurodegenerative diseases, lupus, inflammatory bowel disease and Crohn's disease, as well as conditions such as long COVID syndrome, immune rejection of transplanted organs, and the potentially deadly outbursts known as cytokine storms that COVID infections can trigger.

Autoimmune diseases may affect roughly one in 10 individuals, a 2023 Lancet study suggested. In the United States alone, autoimmune diseases may cost the economy $100 billion annually, a figure that may be a gross underestimate, according to the Autoimmune Associatio

Harnessing the activity of this circuit may make a difference across a broad range of conditions affecting the immune system, and help treat dysregulated inflammatory states in people suffering from immune diseases and disorders, Drs. Jin and Li said.

Journal Reference:

1. Hao Jin, Mengtong Li, Eric Jeong, Felipe Castro-Martinez, Charles S. Zuker. A body–brain circuit that regulates body inflammatory responses. Nature, 2024; DOI: 10.1038/s41586-024-07469-y

https://sciencedaily.com/releases/2024/05/240501125818.htm

2nd Boeing-Linked Whistleblower Dies

 A whistleblower at Boeing supplier Spirit AeroSystems died Tuesday morning following a struggle with a 'sudden, fast-spreading infection,' the Seattle Times reports.

45-year-old Joshua Dean, a former mechanical engineer and quality auditor from Wichita, Kansas, alleged that Spirit leadership ignored manufacturing defects on the 737 MAX, including 'mechanics improperly drilling holes in the aft pressure bulkhead of the MAX.' When he brought this up with management, he said that nothing was done about it. So he filed a safety complaint with the FAA - and said that Spirit had used him as a scapegoat while they lied to the agency about the defects.

"After I was fired, Spirit AeroSystems [initially] did nothing to inform the FAA, and the public" regarding the bulkhead defects, said Dean in his complaint.

In November, the FAA suggested to Dean in a letter that his claims had merit, writing "The investigation determined that your allegations were appropriately addressed under an FAA-approved safety program," adding "However, due to the privacy provisions of those programs, specific details cannot be released."

Dean also gave a deposition in a Spirit shareholder lawsuit.

The shareholder lawsuit alleging that Spirit management withheld information on the quality flaws and harmed stockholders was filed in December. Supporting the suit, Dean provided a deposition detailing his allegations.

After a panel blew off a Boeing 737 MAX plane in January, bringing new attention to the quality lapses at Spirit, one of Dean’s former Spirit colleagues confirmed some of Dean’s allegations. -Seattle Times

He had been in good health, and 'was noted for having a healthy lifestyle,' according to the report.

He had been in critical condition for two weeks, according to his aunt Carol Parsons, who said he became ill and went to the hospital due to breathing difficulties. He was intubated, after which he developed pneumonia and then MRSA, a serious bacterial infection.

His condition deteriorated rapidly, and he was airlifted from Wichita to a hospital in Oklahoma City, Parsons said. There he was put on an ECMO machine, which circulates and oxygenates a patient’s blood outside the body, taking over heart and lung function when a patient’s organs don’t work on their own. -Seattle Times

Doctors had considered amputating both hands and both feet.

"It was brutal what he went through," said Parsons. "Heartbreaking."

Dean was fired in April 2023, after which he filed a complaint with the Department of Labor, alleging he had been terminated in retaliation for blowing the whistle.

He was represented by the South Carolina law firm that represented Boeing whistleblower John "Mitch" Barnett, who was found dead in an 'apparent suicide' in March in Charleston.

Barnett was in the middle of giving depositions suggesting that Boeing retaliated against him over complaints related to quality issues when he was found dead from a gunshot wound.

The Charleston County Coroner’s Office reported Barnett’s death appeared to be “from a self-inflicted gunshot wound.” Almost two months later, the police investigation into his death is still ongoing. -Seattle Times

"Whistleblowers are needed. They bring to light wrongdoing and corruption in the interests of society. It takes a lot of courage to stand up," said Brian Knowles, one of Dean's lawyers. "It’s a difficult set of circumstances. Our thoughts now are with John’s family and Josh’s family."

In March, Boeing was rumored to be in talks to buy Spirit, as both companies have come under increasing pressure from airline customers and federal regulators to shore up quality issues following a January 5th incident in which a door plug blew out mid-flight on a 737 MAX 9.

Four days later, United Airlines found "loose bolts" on 737 MAX doors following an emergency inspection.

https://www.zerohedge.com/political/it-was-brutal-2nd-boeing-linked-whistleblower-dies

Trump campaign calls commission’s refusal to move up debates ‘unacceptable’

 Former President Trump’s campaign called the Commission on Presidential Debate’s refusal to move up its debate schedule “unacceptable” Tuesday and suggested the 45th president could go around the body that’s sponsored all general election presidential debates for decades. 

“The Presidential Debate Commission’s schedule does not begin until after millions of Americans will have already cast their ballots. This is unacceptable, and by refusing to move up the debates, they are doing a grave disservice to the American public who deserve to hear from both candidates before voting begins,” Trump campaign spokespeople Chris LaCivita and Susie Wiles said in a statement. 

The Trump campaign had asked the commission earlier this month for debates “much earlier” than the planned kickoff of a first debate in mid-September, as the former president pressures President Biden to go head-to-head.

“We are committed to making this happen with or without the Presidential Debate Commission. We extend an invitation to every television network in America that wishes to host a debate, and we once again call on Joe Biden’s team to work with us to set one up as soon as possible,” LaCivita and Wiles said.

The CPD on Wednesday hit back at the Trump campaign’s claims, stressing that the first debate, scheduled for Sept. 16, will be “the earliest televised general election debate ever held.” 

“Yesterday, it was claimed that the CPD’s schedule does not begin until after ‘millions of Americans will have already cast their ballots.’ The CPD purposefully chose September 16 after a comprehensive study of early voting rules in every state,” the nonprofit said in a release, referencing the Trump campaign’s comments. 

“The CPD has only one mission: to sponsor and produce general election debates that inform and educate the public. Our schedule is designed with that single mission in mind. The colleges and universities preparing to host these debates look forward to being part of an historic 2024 series of forums.”

Biden said last week that he’s “happy” to debate Trump, now that both 2024 hopefuls have secured the delegates they need to become their respective party’s presumptive nominees. Biden and his campaign have largely sidestepped directly addressing debates with Trump, while the Republican has gotten more vocal with his calls for the incumbent to take the stage and face off with him.

“Crooked Joe Biden just announced that he’s willing to debate! Everyone knows he doesn’t really mean it, but in case he does, I say, ANYWHERE, ANYTIME, ANYPLACE, an old expression used by Fighters,” Trump said in a response post on Truth Social.

For now, the first presidential debate on the commission’s calendar is set for Sept. 16 at Texas State University in San Marcos, followed by a vice presidential debate Sept. 25 at Lafayette College in Easton, Pa. Two more presidential debates are slated for October in Virginia and Utah.

Trump notably skipped all the GOP primary debates held this cycle, citing his polling advantage over his Republican rivals. He’s currently on trial in New York, facing criminal charges in connection with a hush money payment made during the 2016 cycle.

https://thehill.com/homenews/campaign/4634227-trump-campaign-calls-commissions-refusal-to-move-up-debates-unacceptable/

Therapy to kill hypervirulent bacteria developed

 University of Central Florida College of Medicine researcher Renee Fleeman is on a mission to kill drug-resistant bacteria, and her latest study has identified a therapy that can penetrate the slime that such infections use to protect themselves from antibiotics.

In a study published recently in Cell Reports Physical Science, Fleeman showed that an antimicrobial peptide from cows has potential for treating incurable infections from the bacterium Klebsiella pneumoniae. The bacteria, commonly found in the intestines, is usually harmless. It becomes a health hazard when it enters other parts of the body and can cause pneumonia, urinary tract and wound infections. Those at highest risk include seniors and patients with other health problems such as diabetes, cancer, kidney failure and liver disease. However, younger adults and people without additional health problems can acquire urinary tract and wound infections from the bacteria that cannot be treated by antibiotics available today.

The CDC reports that antibiotic resistant bacteria are a growing global health threat. A 2019 study found that nearly 5 million people died worldwide that year from drug-resistant infections. A large portion of those deaths are attributable to K. pneumoniae because it has a 50% death rate without antibiotic therapy.

These bacteria are more resistant to drugs when they live in a biofilm -- microorganisms that stick together and are embedded in a protective slime. Recent studies have shown that 60-80% of infections are associated with bacteria biofilms, which increase their drug resistance.

"It's Iike a coat that bacteria put around itself," Fleeman says.

Her research is examining ways to remove the protective coat and expose the bacteria so it can be killed by the body's immune system or antibiotics that currently cannot pass through the biofilm. Through that research, Fleeman discovered how the peptides made by cows can quickly kill K. pneumoniae.

She determined that the peptides interact with sugar connections that keep the slime intact. She likened the process to cutting into a chain-linked fence. Once multiple chains are cut, the integrity of the slime structure is damaged, and the peptide can enter and destroy the bacteria that are no longer protected.

"Our research has shown polyproline peptide can penetrate and begin to break the slime barrier down in as little as an hour after treatment," says Fleeman.

The peptide has another advantage -- once it breaks through the protective slime barrier, tests showed it killed the bacteria better than antibiotics used as a last resort to treat incurable infections. Peptides kill the bacteria by punching holes in their cell membrane, causing death quickly compared to other antibiotics that inhibit growth from inside the cell.

The peptide could also be used as a topical treatment for a wide range of uses, especially for the military, to treat open wounds in the field. "Bacteria divide every 30 minutes, so you have to act fast," Fleeman says.

The next phase of her research will seek to understand the biology behind the peptide's efficacy and if combinations of other drugs would aid in its application.

Her research is funded through a three-year National Institutes of Health funding Pathway to Independence R00 grant and is in its second year. Her study initially started as a K99 award at University of Texas at Austin, where she worked before joining UCF in September of 2022.

Fleeman says research into resistant infections must continue because they pose such a threat to health.

"It is estimated that by 2050, antibiotic resistant bacterial infections will be the number one cause of human deaths," she says. "Our work is focused on preparing for this post-antibiotic era battle, where common antibiotics that we take for granted will no longer be effective, jeopardizing cancer therapy, organ transplants, and any modern medical advancement that relies on effective antibiotic therapies."

Journal Reference:

1. Laura De los Santos, Robert L. Beckman, Christina DeBarro, James E. Keener, Marcelo D.T. Torres, Cesar de la Fuente-Nunez, Jennifer S. Brodbelt, Renee M. Fleeman. Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms. Cell Reports Physical Science, 2024; 5 (3): 101869 DOI: 10.1016/j.xcrp.2024.101869

https://www.sciencedaily.com/releases/2024/05/240501193701.htm