Publisher Health

Hydrogen peroxide reacts with copper to produce hydroxyl radicals with strong antibacterial properties. However, this requires high copper concentrations because two copper atoms have to come close together, which occurs by chance. Now, scientists at Tokyo University of Science, Japan, engineered a long polymer with copper-containing side units that create regions with locally high copper density, boosting the antibacterial activity of hydrogen peroxide and paving the way to a new drug design concept.
The discovery of antibiotics was a huge breakthrough in medicine, which helped save countless lives. Unfortunately, their widespread use has led to the rapid evolution of highly resistant bacterial strains, which threaten to take humanity back to square one in the fight against infectious diseases. Even though researchers are seeking new design concepts for antibacterial drugs, the overall development of new agents is currently on the decline.
To tackle this serious problem, scientists at Tokyo University of Science, Japan, are exploring a novel approach to boost the in vivo antibacterial activity of hydrogen peroxide (H2O2), a commonly used disinfectant. In a recent study published in Macromolecular Rapid Communications, a team led by Assistant Professor Shigehito Osawa and Professor Hidenori Otsuka reported their success in enhancing H2O2 activity using carefully tailored copper-containing polymers.
To understand their approach, it helps to know how H2O2 acts against bacteria in the first place, and the role that copper plays. H2O2 can be decomposed into a hydroxyl radical (•OH) and a hydroxide anion (OH−), the former of which is highly toxic to bacteria as it readily destroys certain biomolecules. Copper in its first oxidation state, Cu(I), can catalyze the splitting of H2O2 into a hydroxyl radical and a hydroxide anion, turning into Cu(II) in the process through oxidation. Curiously, H2O2 can also catalyze the reduction of Cu(II) to Cu(I), but only if this reaction is somehow facilitated. One way to achieve this is to have Cu(II)-containing complexes get close enough together.
However, when using Cu(II)-containing complexes dissolved in a solution, the only way for them to come close together is by accidentally bumping into each other, which requires an excessively high concentration of copper. The team found a workaround to this issue by drawing inspiration from cellular chemistry, as Dr. Osawa explains: “In living organisms, copper forms complexes with proteins to efficiently catalyze redox reactions. For example, tyrosinase has two copper complex sites in close proximity to each other, which facilitates the formation of reaction intermediates between oxygen species and copper complexes. We thought we could leverage this type of mechanism in artificially produced polymers with copper complexes, even if dispersed in a solution.”
With this idea, the researchers developed a long polymer chain with dipicolylamine (DPA) as copper-containing complexes. These DPA-copper complexes were attached to the long polymer backbone as “pendant groups.” When these polymers are dispersed in a solution, the Cu(II) atoms in the pendant groups are kept in close proximity and locally high densities, vastly increasing the chances that two of them will be close enough to be reduced to Cu(I) by H2O2. Through various experiments, the scientists demonstrated that the use of these tailored polymers resulted in higher catalytic activity for the splitting of H2O2, resulting in more OH• even for lower concentrations of copper. Further tests using Escherichia coli cultures showed that these polymers greatly enhanced the antibacterial potential of H2O2.
While the results of this study open up a new design avenue for antimicrobial drugs, there may also be useful applications in the food industry as well. “Because copper is an essential nutrient for living organisms, the antibacterial agent developed in this study holds promise as an efficient food preservative, which could contribute to increasing the variety of foods that can be preserved over long shelf times,” highlights Dr. Osawa. Let us hope this new strategy makes it easier for us to keep microscopic menaces at bay!
Story Source:
Materials provided by Tokyo University of Science. Note: Content may be edited for style and length.

In communities with growing caseloads, vaccinated and unvaccinated people should return to masking in indoor public areas, health officials said.Revising a decision made just two months ago, the Centers for Disease Control and Prevention said on Tuesday that people vaccinated against the coronavirus should resume wearing masks in public indoor spaces in parts of the country where the virus is surging.C.D.C. officials also recommended universal masking for teachers, staff, students and visitors in schools, regardless of vaccination status and community transmission of the virus. With additional precautions, schools nonetheless should return to in-person learning in the fall, according to agency officials.The recommendations are another baleful twist in the course of America’s pandemic, a war-weary concession that the virus is outstripping vaccination efforts. The agency’s move follows rising case counts in states like Florida and Missouri, as well as growing reports of breakthrough infections of the more contagious Delta variant among people who are fully immunized.“The Delta variant is showing every day its willingness to outsmart us,” Dr. Rochelle Walensky, director of the C.D.C., said at a news briefing on Tuesday. Data from several states and other countries show that the variant behaves differently from previous versions of the coronavirus, she added: “This new science is worrisome and unfortunately warrants an update to our recommendation.”“This is not a decision we at CDC have made lightly,” Dr. Walensky added. “This weighs heavily on me.” Jen Psaki, the White House press secretary, said at a news conference on Tuesday that changing the guidance was crucial to “battling an ever-evolving virus” and that the Biden administration supported the effort.“Their job is to look at evolving information, evolving data, an evolving historic pandemic, and provide guidance to the American public,” Ms. Psaki said.“The virus is changing, we are dealing with a dynamic situation,” said Dr. Anthony S. Fauci, the Biden administration’s top pandemic adviser. The C.D.C. is correct to revisit its recommendations as the virus evolves, he said.“I don’t think you can say that this is just flip-flopping back and forth,” he added. “They’re dealing with new information that the science is providing.”The vaccines remain remarkably effective against the worst outcomes of infection with any form of the coronavirus, including hospitalization and death. But the new guidelines explicitly apply to both the unvaccinated and vaccinated, a sharp departure from the agency’s position since May that vaccinated people do not need to wear masks in most indoor spaces.Those recommendations, which seemed to signal a winding down of the pandemic, were based on earlier data suggesting that vaccinated people rarely become infected and almost never transmit the virus, making masking unnecessary.But that was before the arrival of the Delta variant, which now accounts for the bulk of infections in the United States. C.D.C. officials were persuaded by new scientific evidence showing that even vaccinated people may become infected and may carry the virus in great amounts, Dr. Walensky acknowledged at the news briefing.“The big concern is that the next variant that might emerge — just potentially a few mutations away — could evade our vaccine,” she said.Some public health experts welcomed the agency’s decision to revise its guidelines. Based on what scientists are learning about the Delta variant’s ability to cause breakthrough infections, “this is a move in the right direction,” said Dr. Celine Gounder, an infectious disease specialist at Bellevue Hospital Center in New York.The American Federation of Teachers and the National Education Association, the two leading teachers’ unions, strongly endorsed the C.D.C.’s move to universal masking in schools.“Masking inside schools, regardless of vaccine status, is required as an important way to deal with the changing realities of virus transmission,” said Randi Weingarten, president of the A.F.T. “It is a necessary precaution until children under 12 can receive a Covid vaccine and more Americans over 12 get vaccinated.”Dr. Rochelle Walensky, the C.D.C. director, during a Senate hearing earlier this month.Stefani Reynolds for The New York TimesWhether state and local health officials are willing to follow the agency’s guidance is far from certain. And there is sure to be resistance from pandemic-fatigued Americans, particularly in regions of the country where vaccination rates are low and concerns about the virus are muted.Some jurisdictions, like Los Angeles County and St. Louis County, Mo., have already reinstated mask mandates in response to rising cases. But Arkansas, one of the states with the highest numbers, has retained a ban on mask mandates even as vaccination rates lag.As recently as last week, a C.D.C. spokesman said that the agency had no plans to change its guidance, unless there were a significant change in the science. Researchers have begun to turn up disturbing new data.The Delta variant is thought to be about twice as contagious as the original version of the virus. Some research now suggests that people infected with the variant carry about a thousandfold more virus than those infected with other variants, and may stay infected for longer.C.D.C. officials were swayed by new research showing that even vaccinated people may carry great amounts of the variant virus in the nose and throat, hinting that they also may spread it to others.Large so-called viral loads may help explain reports of breakthrough infections in groups of vaccinated people. For example, an outbreak that began in Provincetown, Mass., after Fourth of July festivities there has grown to include at least 765 cases, according to Steve Katsurinis, chair of the Provincetown Board of Health.Of the 469 cases reported among Massachusetts residents alone, 74 percent were in people who were fully immunized, Mr. Katsurinis said.Smaller clusters of breakthrough infections have been reported after weddings, family reunions and dinner parties. Some of the infected had symptoms, but the vast majority were not seriously ill, suggesting that immunity produced by the vaccines quickly curbs the virus.Vaccines “are not a force field,” said Jennifer Nuzzo, an epidemiologist at Johns Hopkins University’s Bloomberg School of Public Health. Instead, vaccination trains the immune system to recognize cells that become infected with the virus..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{margin-bottom:15px;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}“The term breakthrough infection is probably a bit misleading,” she said. “It’s probably more realistic that we talk about breakthrough disease and how much of that is occurring.”Dr. Walensky on Tuesday again urged people to get vaccinated, noting that the rise of cases and hospitalizations is greatest in places with low vaccination rates and among unvaccinated people. She acknowledged that some vaccinated people can become infected with the Delta variant and may be contagious, but maintained that it was a rare event. But the C.D.C. is tracking only breakthrough infections that lead to hospitalization or death among vaccinated Americans. Officials have previously said that vaccinated people account for just 3 percent of hospitalizations.Dr. Gounder and other experts said that it is unclear how often vaccinated people transmit the virus to others, but it may be more common than scientists had predicted as the original virus spread.“We’ve seen increasing numbers of breakthrough infections, and it seems like most of those may be happening in places where people are exposed to a lot of Covid,” said Dr. Scott Dryden-Peterson, an infectious disease physician and epidemiologist at Brigham & Women’s Hospital in Boston, who has been reviewing breakthrough infections in Massachusetts.Masks can augment the effectiveness of the vaccine, said Dr. Scott Dryden-Peterson, an infectious disease physician. “Almost everywhere in the U.S. it’s a good idea,” he said.Brittainy Newman for The New York TimesVaccinated people — particularly people with weak immune systems or otherwise at high risk — should consider wearing masks even in areas of low transmission, he said: “Masks can effectively reduce the amount of virus that we breathe in and prevent us from getting sick, and so they augment the impact of our vaccine. Almost everywhere in the U.S., it’s a good idea.”Infections have been rising swiftly in the United States, to more than 56,000 daily cases on average, as of Tuesday, more than four times the number a month ago. Hospitalizations have also been ticking up in nearly all states, and deaths have risen to an average of 275 per day.“Given what we’re seeing, that’s absolutely needed right now to slow and curb transmission,” Dr. Robby Sikka, a physician who worked with the N.B.A.’s Minnesota Timberwolves, said of the new masking guidance.“Not everyone who has a breakthrough infection will be at risk for transmission, but it’s imperative to note that there is a risk of transmission,” he said.But Dr. Sikka noted that relying on states or localities to set masking rules will require more testing than is being done now to identify people with mild or asymptomatic infections. “That’s something that we’re probably not totally prepared to do,” he said.Given that the virus seems likely to become endemic, permanently embedded in American life, federal officials need to articulate an even clearer plan for long-term masking, Dr. Nuzzo said.“The question is, what are the off ramps for masking? It’s really important for us to define that,” she said. “If we want to continue to ask people to step up, we need to give them a vision of what we’re working toward.”The C.D.C. should have simply made a universal recommendation and told all Americans to wear masks indoors, said Ali Mokdad, an epidemiologist at University of Washington and former C.D.C. scientist.“The director said the guidance is for people in areas of high transmission, but if you look at the country, every state is seeing a rise in transmission,” Dr. Mokdad said. “So why not say, ‘Everybody in the U.S. should be wearing a mask indoors?’ The whole country is on fire.”

In communities with growing caseloads, vaccinated and unvaccinated people should return to masking in indoor public areas, health officials said.Revising a decision made just two months ago, the Centers for Disease Control and Prevention said on Tuesday that people vaccinated against the coronavirus should resume wearing masks in public indoor spaces in parts of the country where the virus is surging.C.D.C. officials also recommended universal masking for teachers, staff, students and visitors in schools, regardless of vaccination status and community transmission of the virus. With additional precautions, schools nonetheless should return to in-person learning in the fall, Dr. Rochelle Walensky, the agency’s director, said at a news briefing on Tuesday.The recommendations are another baleful twist in the course of America’s pandemic, a war-weary concession that the virus is outstripping vaccination efforts. The agency’s move follows rising case counts in states like Florida and Missouri, as well as growing reports of breakthrough infections of the more contagious Delta variant among people who are fully immunized.Jen Psaki, the White House press secretary, said at a news conference on Tuesday that changing the guidance was crucial to “battling an ever-evolving virus” and that the Biden administration supported the effort.“Their job is to look at evolving information, evolving data, an evolving historic pandemic, and provide guidance to the American public,” Ms. Psaki said.The vaccines remain remarkably effective against the worst outcomes of infection with any form of the coronavirus, including hospitalization and death. But the new guidelines explicitly apply to both the unvaccinated and vaccinated, a sharp departure from the agency’s position since May that vaccinated people do not need to wear masks in most indoor spaces.Those recommendations, which seemed to signal a winding down of the pandemic, were based on earlier data suggesting that vaccinated people rarely become infected and almost never transmit the virus, making masking unnecessary.But that was before the arrival of the Delta variant, which now accounts for the bulk of infections in the United States. C.D.C. officials were persuaded by new scientific evidence showing that even vaccinated people may become infected and may carry the virus in great amounts, according to three federal officials with knowledge of the discussions.Some public health experts welcomed the agency’s decision to revise its guidelines. Based on what scientists are learning about the Delta variant’s ability to cause breakthrough infections, “this is a move in the right direction,” said Dr. Celine Gounder, an infectious disease specialist at Bellevue Hospital Center in New York.The American Federation of Teachers and the National Education Association, the two leading teachers’ unions, strongly endorsed the C.D.C.’s move to universal masking in schools.“Masking inside schools, regardless of vaccine status, is required as an important way to deal with the changing realities of virus transmission,” said Randi Weingarten, president of the A.F.T. “It is a necessary precaution until children under 12 can receive a Covid vaccine and more Americans over 12 get vaccinated.”Dr. Rochelle Walensky, the C.D.C. director, during a Senate hearing earlier this month.Stefani Reynolds for The New York TimesWhether state and local health officials are willing to follow the agency’s guidance is far from certain. And there is sure to be resistance from pandemic-fatigued Americans, particularly in regions of the country where vaccination rates are low and concerns about the virus are muted.Some jurisdictions, like Los Angeles County and St. Louis County, Mo., have already reinstated mask mandates in response to rising cases. But Arkansas, one of the states with the highest numbers, has retained a ban on mask mandates even as vaccination rates lag.As recently as last week, a C.D.C. spokesman said that the agency had no plans to change its guidance, unless there were a significant change in the science. Researchers have begun to turn up disturbing new data.The Delta variant is thought to be about twice as contagious as the original version of the virus. Some research now suggests that people infected with the variant carry about a thousandfold more virus than those infected with other variants, and may stay infected for longer.C.D.C. officials were swayed by new research showing that even vaccinated people may carry great amounts of the variant virus in the nose and throat, hinting that they also may spread it to others, according to three federal officials familiar with the matter.Large so-called viral loads, particularly in the nose and throat, may help explain reports of breakthrough infections in groups of vaccinated people. For example, an outbreak that began in Provincetown, Mass., after Fourth of July festivities there has grown to include at least 765 cases, according to Steve Katsurinis, chair of the Provincetown Board of Health.Of the 469 cases reported among Massachusetts residents, 74 percent were in people who were fully immunized, Mr. Katsurinis said.Smaller clusters of breakthrough infections have been reported after weddings, family reunions and dinner parties. Some of the infected had symptoms, but the vast majority were not seriously ill, suggesting that immunity produced by the vaccines quickly curbs the virus.Vaccines “are not a force field,” said Jennifer Nuzzo, an epidemiologist at Johns Hopkins University’s Bloomberg School of Public Health. Instead, vaccination trains the immune system to recognize cells that become infected with the virus.“The term breakthrough infection is probably a bit misleading,” she said. “It’s probably more realistic that we talk about breakthrough disease and how much of that is occurring.”.css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{margin-bottom:15px;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}Dr. Walensky on Tuesday again urged people to get vaccinated, noting that the rise of cases and hospitalizations is greatest in places with low vaccination rates and among unvaccinated people. She acknowledged that some vaccinated people can become infected with the Delta variant and may be contagious, but maintained that it was a rare event. But the C.D.C. is tracking only breakthrough infections that lead to hospitalization or death among vaccinated Americans. Officials have previously said that vaccinated people account for just 3 percent of hospitalizations.Dr. Gounder and other experts said that it is unclear how often vaccinated people transmit the virus to others, but it may be more common than scientists had predicted as the original virus spread.“We’ve seen increasing numbers of breakthrough infections, and it seems like most of those may be happening in places where people are exposed to a lot of Covid,” said Dr. Scott Dryden-Peterson, an infectious disease physician and epidemiologist at Brigham & Women’s Hospital in Boston, who has been reviewing breakthrough infections in Massachusetts.Masks can augment the effectiveness of the vaccine, said Dr. Scott Dryden-Peterson, an infectious disease physician. “Almost everywhere in the U.S. it’s a good idea,” he said.Brittainy Newman for The New York TimesVaccinated people — particularly people with weak immune systems or otherwise at high risk — should consider wearing masks even in areas of low transmission, he said: “Masks can effectively reduce the amount of virus that we breathe in and prevent us from getting sick, and so they augment the impact of our vaccine. Almost everywhere in the U.S., it’s a good idea.”Infections have been rising swiftly in the United States, to more than 56,000 daily cases, on average, as of Tuesday, more than four times the number four weeks ago. Hospitalizations have also been ticking up in nearly all states, and deaths have risen to an average of 275 per day.“Given what we’re seeing, that’s absolutely needed right now to slow and curb transmission,” Dr. Robby Sikka, a physician who worked with the N.B.A.’s Minnesota Timberwolves, said of the new masking guidance.“Not everyone who has a breakthrough infection will be at risk for transmission, but it’s imperative to note that there is a risk of transmission,” he said.But Dr. Sikka noted that relying on states or localities to set masking rules will require more testing than is being done now to identify people with mild or asymptomatic infections. “That’s something that we’re probably not totally prepared to do,” he said.Given that the virus seems likely to become endemic, permanently embedded in American life, federal officials need to articulate an even clearer plan for long-term masking, Dr. Nuzzo said.“The question is, what are the off ramps for masking? It’s really important for us to define that,” she said. “If we want to continue to ask people to step up, we need to give them a vision of what we’re working toward.”

The cost-effectiveness of drug synthesis depends on a number of factors, including the amount of waste produced. A team of researchers have now discovered a catalyst that achieves exceptionally high-precision addition of hydrogen to carbon-carbon bonds, improving targeted synthesis by avoiding convoluted multi-step processes, and reducing wasteful by-products. The authors herald the reaction as especially useful in the production of complex natural substances such as pheromones.

If approved by a judge next month, the plan would resolve thousands of lawsuits and set in motion the release of $4.5 billion to help cover costs from the opioid epidemic.A huge majority of more than 120,000 creditors of Purdue Pharma have voted to approve the company’s bankruptcy plan, a key step toward the eventual release of more than $4.5 billion dollars to help pay for the costs of the opioid epidemic and the resolution of thousands of lawsuits against the company and its owners, members of the billionaire Sackler family.Preliminary tabulation of voting by cities, states, tribes, insurers, families and caregivers of babies born with symptoms of withdrawal from being exposed to opioids in utero show that 95 percent favor the plan, the company said.Under the plan, the Sacklers would relinquish control of Purdue. The restructured company would re-emerge with a new name, and be run by an independently appointed board. Profits from sales of its signature prescription painkiller, OxyContin, and addiction-reversal drugs would flow into creditors’ trusts that would fund addiction prevention and treatment programs.The Sacklers, who have not filed for personal bankruptcy, would pay at least $4.5 billion of their personal funds over nine years (in addition to $225 million from a separate civil settlement with the Justice Department).Neither the company, nor the Sacklers, would admit to wrongdoing in connection with these lawsuits.Over the past two decades, more than 500,000 people in the United States have died from overdoses of prescription and illegal opioids, including a record annual number in 2020. Purdue, widely believed to have helped ignite the problem by downplaying the addictive potential of OxyContin and aggressively marketing the drug with misleading campaigns, pleaded guilty to two separate investigations by the Justice Department.For the complex plan to take effect, Judge Robert Drain of the U.S. Bankruptcy Court for the Southern District of New York, must sign off, a move long expected and now made even more likely by the full-throated results of the creditor vote. Purdue said it would release final voting tallies on Aug. 2, a week before a court hearing at which final objections will be aired, but the company does not anticipate that these results will change materially. The judge is expected to rule shortly after.Although a handful of states filed objections to the plan, as did the Department of Justice, those efforts seem unlikely to derail proceedings. Earlier this month, attorneys general for 15 states that had been among the most vociferous objectors, including Massachusetts and New York, said they had negotiated fresh terms that made the plan more palatable and now supported the plan.Among the new elements the states and Purdue reached during mediation was an agreement by the company to release more than 30 million documents to a public repository, including private communications with lawyers. Those documents are expected to unfurl the full story of the company’s and the Sacklers’ involvement in the selling of OxyContin.The Sacklers, long known for their philanthropy in the arts, would relinquish future naming rights to any institutions to which they donate until their contributions to the opioids settlement are paid in full.For nearly two years, the objecting states argued that they should be able to reach directly into the pockets of individual Sacklers, because they did not themselves file for bankruptcy protection. Under the terms of the Purdue plan, however, the Sacklers as well as their company have been released from all civil liability.Some members of Congress have introduced legislation to close a loophole in the bankruptcy code. It would permit states and possibly individuals to sue third-party owners of a company in bankruptcy who, like the Sacklers, have not themselves filed for bankruptcy. But if the legislation is passed, the Purdue plan and the status of the Sacklers will almost certainly have been long since resolved.

A new technology for cellular immunotherapy developed by Abramson Cancer Center researchers at Penn Medicine showed promising anti-tumor activity in the lab against hard-to-treat cancers driven by the once-considered “undruggable” KRAS mutation, including lung, colorectal, and pancreatic.
The study, published online in Nature Communications, successfully demonstrated using human cells that a T-cell receptor, or TCR, therapy could be designed to mobilize an immune system attack on mutated KRAS solid tumors and shrink them. The preclinical work has laid the groundwork for the first-in-human clinical trial now in the planning stages for the treatment of advanced pancreatic cancer in patients whose tumors harbor specific KRAS mutations and express a specific type of human leukocyte antigen, or HLA, the therapy is built to recognize.
“We’ve shown that targeting mutant KRAS immunologically is feasible and potentially generalizable for a group of patients with lung, colorectal and pancreatic tumors,” said senior author Beatriz M. Carreno, PhD, an associate professor of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania and a member of the Center for Cellular Immunotherapies, the Abramson Cancer Center, and Parker Institute for Cancer Immunotherapy at Penn. “We look forward to taking this research to the next level and closer to clinical study.”
KRAS mutations are among the most prevalent mutations observed in cancers and have been shown to drive tumor development and growth. Only recently have targeted therapies been shown to successfully treat a specific KRAS mutation found most commonly in lung cancer; however, no treatments currently exist for the majority of other KRAS mutations more prevalent in other tumor types. Immunological targeting of mutant KRAS represents an alternative treatment approach but has been less studied and understood.
Using a multiomics approach, the Penn team identified specific neoantigens associated with mutations at the G12 site on the KRAS gene. Neoantigens are protein fragments that form on the cancer cell surface when certain mutations occur in tumor DNA. More than 75 percent of the alterations in the KRAS protein occur at G12, making it an ideal site to target with therapies.
Armed with this knowledge, the researchers tested a TCR therapy directed toward specific KRAS G12 mutations present in conjunction with particular HLA types highly prevalent among patients. They showed in a mouse tumor model that it was effective at attacking and eliminating tumor cells. HLAs are an important part of the immune system because they encode cell surface molecules that present specific neoantigens to the T-cell receptors on T cells.
In other words, HLAs are key genetic codes needed for these engineered T cells to find and attack tumors.
The research further supports the use of neoantigens for targeting tumor cells, for both cellular therapy and cancer vaccines, which have been underway at Penn Medicine and elsewhere.
Importantly, the neoantigen and HLA information from this latest study is being used to develop TCR therapies to treat solid tumors, as well as new cancer vaccines. Based off these latest findings, the team initiated a vaccine clinical trial led by Mark O’Hara, MD, an assistant professor of Hematology-Oncology at Penn and co-author on the study, in pancreatic cancer targeting mutated KRAS.
The first clinical trial for the TCR therapy is projected to launch as soon as 2022, depending on regulatory approval, at Penn’s Abramson Cancer Center for patients with advanced pancreatic cancer who have both the KRAS mutation and specific HLA types identified in this latest study — which could represent up to 10 percent of patients with pancreatic cancer. The study opens the door, however, to expand the patient population as researchers continue to discover more about the neoantigens derived from regions of the KRAS gene and other mutated oncogenes implicated in driving cancer.
“We provide evidence that this oncogenic protein is a very promising clinical target of immune-based therapies,” said lead author Adham Bear, MD, PhD, an instructor in the division of Hematology-Oncology at Penn and member of the Parker Institute for Cancer Immunotherapy at Penn. “The goal, now that we have identified these neoantigens and T cell receptors, is to translate these findings and apply them to develop new therapies at Penn.”
The study was supported by the National Institutes of Health (R01 CA204261, P30 CA016520, CA196539 and CA232568), The Stand Up to Cancer/Lustgarten Foundation Pancreatic Cancer Collective, the Penn Institute for Immunology, and the Parker Institute for Cancer Immunotherapy.

Many times we eat, not because we are hungry, but because of social pressures or because the food is so appetizing, that, even though we are full, we just want another bite.
Overeating, whether it is guided by hunger or pleasure, typically leads to obesity, which affects about 42% of the adults in the U.S., according to the Centers for Disease Control and Prevention. Looking to contribute to the development of effective treatments for obesity, an international team led by researchers at Baylor College of Medicine investigated in an animal model how the brain regulates feeding triggered by hunger or other factors.
Led by Dr. Yong Xu, professor of pediatrics — nutrition and molecular and cellular biology at Baylor, the team discovered that although the brain regulates both types of feeding behavior through serotonin-producing neurons in the midbrain, each type of feeding is wired by its own independent circuit that does not influence the other type of feeding. The researchers also identified two serotonin receptors and two ion channels that can affect the feeding behaviors, opening the possibility that modulating their activities might help regulate overeating. The study appears in the journal Molecular Psychiatry.
Mapping the roads that control feeding behavior in the brain
Xu and his colleagues identified two distinct brain circuits formed by serotonin-producing neurons in the midbrain. One of the circuits extends to the hypothalamus, while the other projects into another region of the midbrain. These circuits play very distinct roles in regulating feeding.
“We discovered that the circuit that projects to the hypothalamus primarily regulates hunger-driven feeding, but does not influence the non-hunger driven feeding behavior,” Xu said. “The other circuit that projects into the midbrain regulates primarily the non-hunger driven feeding, but not the feeding behavior triggered by hunger. This indicates that, at the circuit level, the brain wires the two types of feeding behavior differently.”
The other significant contribution of this work refers to the identification of potential molecular targets associated with the circuits that could be used to treat overeating.
“One potential target is serotonin receptors, which are molecules that mediate the functions of the neurotransmitter serotonin produced by the neurons,” Xu explained. “We found that two receptors, serotonin 2C receptor and serotonin 1B receptor, are involved in both types of feeding behavior. Our data suggests that combining compounds directed at both receptors might produce a synergistic benefit by suppressing feeding.”
In addition, the team identified ion channels associated with the circuits that also might offer an opportunity to regulate the feeding behaviors. “One is the GABA A receptor, a chloride channel, found to be important in regulating serotonin circuits during hunger-driven feeding, but not during non-hunger driven feeding,” Xu said.
The other is a potassium channel that influences feeding triggered by hunger-independent cues, but not hunger-driven feeding. “There is a clear segregation of these two ion channels,” Xu said. “They have distinct functions in feeding behavior, which suggests they also could be target candidates to regulate overeating.”
The findings have encouraged the researchers to conduct future studies to identify more molecules that could modulate the activity of the ion channels to produce anti-overeating effects in animal models. “We also want to explore how external factors related to nutrition might affect ion channel functions at the molecular level,” Xu said.
Story Source:
Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

The highly infectious nature of the new coronavirus (SARS-COV-2) has changed social habits throughout the world. Even with vaccinations on the rise, many countries hesitate to allow their residents to return to pre-pandemic activity. Moreover, they continue to demand that infected people isolate themselves for a minimum number of days after the onset of symptoms in a one-size-fits-all manner.
In a new study, a multi-national effort that included researchers at the Institute for Advanced Study of Biology (ASHBi), Kyoto University, Japan, uses a mathematical simulator of the SARS-COV-2 dynamics to demonstrate that the number of days can be reduced for many patients if PCR tests are used.
Patient isolation is one of the most effective if not most effective means of preventing the spread of SARS-COV-2. Beginning last year, people had to quickly adapt to weeks-long isolation after testing positive or showing symptoms, but these policies are exhausting societies. To maintain public cooperation, policymakers are seeking guidelines that shorten the isolation period while minimizing the risk of releasing infectious patients.
Dr. Shingo Iwami, an Associate Investigator at ASHBi and author of the study, explains that countries would be wise to consider more personalized decisions to shorten the isolation period.
“Longer isolation periods surely prevent transmission, but also impose substantial burden on isolated patients,” he said. “We found that PCR tests can shorten the isolation period without increasing the risk of further infection.”
PCR tests provide a measure of the viral load in the patient, which is an indicator of infection risk.
To demonstrate the benefits of PCR tests for deciding isolation periods, Iwami and his colleagues, including Keisuke Ejima from Indiana University (United States) and Yong Dam Jeong from Pusan University (South Korea), assessed isolation periods with and without PCR tests using the new simulator. On average, they found that using PCR tests reduced the isolation period by 2 days compared with the one-size-fits-all approach.
“This is not a big surprise,” said Iwami. “The one-size-fits-all approach considers only the symptom onset, but PCR tests provide information on viral load.”
However, he admits that PCR tests may not be feasible everywhere. Because the tests require health professionals, they are costly and must be conducted at designated locations. Thus, a system dependent on PCR tests is more likely to succeed if patients are isolated in dedicated facilities and will be much harder to implement if patients are isolated at home.
With these points in mind, Iwami said that the current guidelines adopted, which depend on clinical and epidemiological data, are overall fairly good.
“Considering the resources available when they were made, current guidelines can reasonably control infection risk. Close collaboration between clinicians, epidemiologists and mathematicians is essential to designing guidelines that are both effective and executable.”
Story Source:
Materials provided by Kyoto University. Note: Content may be edited for style and length.

Cell-free DNA (cfDNA) shed into the blood was discovered in the late 1940s but with rapid advances in genomics and computational analytics in just the past few years, researchers at Georgetown Lombardi Comprehensive Cancer Center now believe that studying tags, or modifications to this type of DNA, may lead to a better understanding of how to assess, and possibly modulate, treatment approaches for cancer and other diseases. Their perspective, drawn from a review of studies to date, appears July 27 in Frontiers in Genetics.
During cell death, which is a normal part of tissue regeneration, cfDNA is shed from tissue. The shed cfDNA can be isolated from a blood sample, thus providing a reading of cell death across the body in both normal and cancer cells without the need for taking invasive biopsy samples.
“Taking tumor tissue biopsies is a hit or miss process and is usually not a good representation of the whole tumor or its spread,” says Anton Wellstein, MD, PhD, professor of oncology and pharmacology at Georgetown Lombardi and corresponding author for this article. “Using blood, or liquid biopsies, on the other hand, provides a homogeneous representation of cfDNA that is being shed from all types of cells.”
The scientists note that short fragments of DNA and chemical modifications to those fragments, known as methyl groups, help tell researchers what cell type the respective snippet of DNA came from because these methylation patterns are unique to specific cell types. By using cfDNA to compare damage to cells from various forms of treatment with undamaged normal cells from the same tissue, the researchers can analyze a treasure-trove of data about how the cells in a tissue are affected by treatments and other external forces. This knowledge could be key in assessing if a therapy is effective and what adverse effects it may cause.
“Fine-tuning these applications of cfDNA analysis is challenging and requires in-depth approaches, both at the genome sequencing level and computationally,” explains Megan Barefoot, a MD/PhD student in the Wellstein lab at the Cancer Center and lead author of the article. “Methylated cfDNA has opened a new and minimally invasive way to detect damage to cells in the body as there are often hundreds of methyl markers per cell that can mark, very specifically, where the cells came from, much like a barcode scanner at a grocery checkout tells the store the identity of a particular product. Combined biological and computational analyses make deciphering these methylation patterns/molecular barcodes possible so that researchers can trace the origins of cfDNA.”
The end-result of these analyses aids investigators in determining the tissue of origin of a cancer, for example, and also allows researchers, when comparing damaged cells to healthy cells, to see where the damage originated, especially if it was due to a certain type of treatment.
“This approach can be applied to any therapy that will impact tissue equilibrium by causing cells in tissues to become damaged and die, including chemotherapy, radiation, and immunotherapy. This review really helps set the stage for our future research efforts,” concludes Wellstein. “My lab is very actively pursuing methods and technologies that further refine analyses of methylated cfDNA. We believe these efforts are affordable and will soon become standard in labs and they should make a difference in advancing the understanding and treatment of many cancers.”
Georgetown University has a patent application, with Wellstein and Barefoot as named inventors, on some of the aspects mentioned in the article.
This work was supported in part by funding from the National Institutes of Health (T32 CA009686, F30 CA250307, R01 CA23129, and P30 CA51008).
Story Source:
Materials provided by Georgetown University Medical Center. Note: Content may be edited for style and length.

New research conducted in monkeys reveals that T cells are not critical for the recovery of primates from acute COVID-19 infections. T cell depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Furthermore, strongly T cell-depleted macaques still develop potent memory responses to a second infection.
The findings, published in the mBio, an open-access journal of the American Society for Microbiology, have implications for the development of second-generation vaccines and therapeutics.
“We started this study early in the pandemic, trying to figure out how to make a good model to study the disease in humans using animals. The monkeys turned out to be more resistant to the disease than we expected, so we wanted to try to figure out why that was and try to gain some insights into the disease in humans as well,” said lead study author Kim Hasenkrug, PhD, senior investigator in the Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, in Hamilton, Montana. “We now know that the antibody response is the most critical response for protection by vaccination, not the T cell response.”
In the new study, the researchers used classic reagents known to deplete CD4+ and CD8+ T cells in rhesus macaques. While CD8+ T cells directly attack infected cells and kill them, CD4+ T cells are helper T cells that trigger the immune response by recognizing pathogens and secreting cytokines, small proteins, that signal other immune cells to act, including CD8+ T cells and antibody-producing B cells.
One week after depleting the macaques of CD4+ T cells, CD8+ T cells, or both at the same time, the researchers infected the animals with SARS-CoV-2. “We depleted, we infected them and then we continued the depletions during the first week of infection to make sure the animals were well depleted. Then we studied their blood to see how they were responding in terms of their T cells and B cells,” said Hasenkrug. For six weeks, the researchers studied nasal swabs and bronchoalveolar lavages to measure virus in the nose, mouth and lungs, and rectal swabs to see if the gut was shedding virus. After six weeks, the researchers re-challenged the monkeys with SARS-CoV-2 and they repeated their collection of virus and blood samples, which allowed the researchers to evaluate immune memory responses. “If there is a memory response, you get a much quicker immune response and control of the virus. That is how vaccinations work. Once your body has seen a viral pathogen, the next time it sees it, you can get a much faster and stronger immune response,” said Dr. Hasenkrug.
The researchers found that the monkeys were able to mount a good memory response against the virus regardless of T cell depletion. “We found we got really good memory responses regardless of whether we depleted T cells or not. Basically, we found very strong virus neutralizing antibodies, and they are the most important antibodies in controlling the infection. That was unexpected by most immunologists, virologists and vaccinologists,” said Hasenkrug.
“The other thing that happens during a memory response is that antibodies mature, becoming, stronger and more potent at binding the viral pathogen. We saw indications of this through what’s called “class switching,,” said Hasenkrug.
“Class switching” was also unexpected in these monkeys with depleted T cells. “We don’t have a firm explanation as to why that happened, but we think it involves some sort of compensatory response, which you can see in our study. For example, when we depleted CD8+ T cells, we saw stronger CD4+ T cell or B cells responses in some animals. When the animals are missing something, they will try to make up for it by making more of something else.”
Hasenkrug doesn’t know why the T cells didn’t turn out to be more important, but it is probably a good thing that they are not required, because then, people who fail to mount sufficient T cell responses still have opportunities to recover.
“This implies that the innate immune response is critical for initial control of the virus, rather than the adaptive immune responses we studied,” said Hasenkrug.