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Three University of Oklahoma faculty receive National Institutes of Health funding to maximize their research

For the first time in one year, three faculty at the University of Oklahoma have received Maximizing Investigators’ Research Awards from the National…

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For the first time in one year, three faculty at the University of Oklahoma have received Maximizing Investigators’ Research Awards from the National Institutes of Health.

Credit: Provided by the University of Oklahoma

For the first time in one year, three faculty at the University of Oklahoma have received Maximizing Investigators’ Research Awards from the National Institutes of Health.

The recipients are Gallogly College of Engineering faculty Vivek Bajpai, Ph.D., John R. Clegg, Ph.D., and Stefan Wilhelm, Ph.D. The highly competitive five-year, $1,866,485 grants will support their ambitious research programs without the need to recompete for funding throughout the duration of their awards.

 

Bajpai, an assistant professor in the School of Sustainable Chemical, Biological and Materials Engineering, will lead the project, “Epigenetic and Transcriptional Mechanisms Driving Human Pigmentation Diversity.”

Using the gene-editing technology CRISPR, Bajpai led a recent discovery of 135 new melanin genes associated with human pigmentation.

“We discovered new factors (genes) which are present in our DNA that make us unique in terms of color and creates diversity among the human population,” Bajpai said. “But now the bigger questions are which of these genes are most important? How do changes in these genes cause pigmentation diseases, including melanoma, and can we exploit the power of these genes to engineer therapies against diseases? Our lab is utilizing cutting-edge technologies, diverse model systems and engineering principles to propel this project, which has both fundamental and applied directions.”

For this project, Bajpai’s research group will explore what controls the genes that make up pigment melanin in the skin – currently an open question in the field. He is trying to understand how these genes relate to one another and other genes in the body to determine if there are “critical nodes” that may be important for driving major shifts in the process of melanin synthesis that results in pigmentation.

“We found a class of genes called transcription factors,” he said. “These are the proteins which bind to the DNA, then they affect the production of many other proteins in the cells. In terms of gene functioning, some of the genes could be in a hierarchy and regulating a bunch of other genes, and we are further investigating this.”

Another aspect is the clinical and translational application of his project. Some market estimates cite the global market of pigmentation disorders treatments is $7 billion annually and is projected to reach $9.2 billion by 2028.

“Clearly, there is an unmet need,” Bajpai said. He envisions manipulating these genes’ actions in patients’ skin to obtain the desired pigmentation levels in patients who are suffering from hyper or hypopigmentation diseases.

This award will also allow his research group to investigate the link between lighter skin color and melanoma susceptibility. According to the Centers for Disease Control and Prevention, about 6 million people each year in the United States are treated for skin cancer of any kind, but of those, melanoma causes the most deaths among all types of skin cancer, and incidence rates have increased over time. Findings from a 2016 National Institutes of Health report showed overall melanoma mortality was higher in white non-Hispanics in Oklahoma than the national average.

Many of the 135 melanin genes Bajpai discovered are present at different levels in light- and dark-skinned humans. He believes their variable levels in skin cells contribute toward melanoma initiation. “By having a finer understanding of how these genes work in melanoma and manipulating their levels, we intend to engineer therapeutic strategies,” he said.

 

Clegg, an assistant professor of biomedical engineering, will lead the project, “Enabled by drug delivery: Studying the role of brain-resident and infiltrating myeloid cell phenotype in brain damage associated with inflammatory disease.”

Inflammation in the brain can have many causes, including traumatic injury, stroke, infection, some drug treatments or exposure to environmental toxins. When inflammation persists over weeks, months or even patients’ lifespans, persistent neurological disorders can result.

“Chronic inflammation underlies cognitive decline and neurodegenerative diseases,” Clegg said. “What’s wild is that there are no approved therapeutics to intervene in this inflammatory aspect of neurological diseases.”

While therapeutics are available to help patients manage symptoms or to help with functional issues such as memory, and physical therapy is available to help patients recover motor function, there are no approved therapeutics to address inflammation specifically.

“So far, clinical trials on anti-inflammatory therapy for brain injury have been unsuccessful,” he added. “This has motivated us to study the different immune cell populations that contribute to brain inflammation and to develop drug delivery systems that reduce brain inflammation in a targeted manner.”

Clegg’s research aims to fill the gap in scientists’ understanding of how to use drug delivery systems to intervene following various forms of brain injury.

Broadly, his research examines the efficacy of immunomodulatory therapeutics – a class of medical treatments that aim to modify the immune system – when delivered either locally to immune cells within the brain or globally to immune cells that are in other tissues or circulating in the body.

Clegg’s research group is developing new and creative ways to deliver immune-modulating compounds using nanomaterials and hydrogels. These delivery systems can be designed to target immune cells that cause or exacerbate brain inflammation.

“My lab’s projects generally fall into one of three areas, and this award focuses on two of those overarching topics,” Clegg said. “We are making new nanomaterials that target myeloid cells, with emphasis on bone marrow-derived immune cells. Second, we’re developing injectable gels that form anti-inflammatory niches for local drug delivery in the brain.”

The third area, outside of the scope of this award, is fabricating new model systems to test drug delivery materials.

 

Wilhelm, an associate professor of biomedical engineering, leads the project, “A novel framework for nanomedicine development.”

Building on the research that contributed to the development of mRNA vaccines for COVID-19, Wilhelm is using this award to develop a new generation of lipid nanoparticles to potentially treat a wide range of diseases.

“We are proposing various types of surface modifications for lipid nanoparticles that involve different types of synthetic polymers and biomolecules,” Wilhelm said. “Our hope is that we can tailor the targeting specificity of these nanoparticles to various cell types, opening up new possibilities where these types of nanomaterials can be used for diseases other than infectious diseases.”

However, Wilhelm cautions that a challenge with lipid nanoparticle technology is that the safety and efficacy depend on controlling where those nanoparticles end up in the body.

Wilhelm’s lab has applied a 3D super-resolution imaging technique, known as expansion microscopy, combined with a technique for imaging metallic nanoparticles within cells to realize a significantly improved ability to see nanoparticles within cells.

“We have shown in the literature now that we can do super-resolution imaging of cells containing metallic nanoparticles. Now, we are switching gears, and we are essentially translating what we have developed so far with metallic nanoparticles to also include lipid nanoparticles,” he said. “With our experience in imaging technologies and our expertise in nanomaterial synthesis and characterization, we are now putting these together to create a new generation of safer, more effective, and more efficient lipid nanoparticles that can be used to deliver payloads to target cells in the body against different types of diseases.”

This proof-of-concept research aims to show that by understanding the transport and characteristics like the biodistribution of these nanoparticles inside cells, customized therapeutics can be developed that are safe and effective.

 

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About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university located in Norman, Oklahoma. OU serves the educational, cultural, economic and health care needs of the state, region and nation. For more information visit www.ou.edu.


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International

As yen weakens and interest peaks, Bank of Japan balances on a policy precipice

Quick Take The Bank of Japan (BOJ) stands at a critical juncture, striving to maintain a delicate balance amid a changing economic landscape. Recent data…

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Quick Take

The Bank of Japan (BOJ) stands at a critical juncture, striving to maintain a delicate balance amid a changing economic landscape. Recent data shows that the 10-year yield, which the BOJ has endeavored to keep below 1%, has touched 0.8, a peak unseen since 2013. Simultaneously, the BOJ has labored not to let the Yen weaken, yet it continues to be pressured as it drops further against the US dollar, crossing the 150 mark for the first time in over a year.

There is burgeoning speculation about possible BOJ interventions in these market movements. As the central bank continues to uphold negative interest rates, a shift towards positive rates might become inevitable in the foreseeable future. It’s a precarious fulcrum of financial strategies that the BOJ is balancing on, with market tempests stirring on one side and the stability of the national currency on the other.

This scenario highlights the intricate dynamics of monetary policies and the profound impact they can have on both national and global economies. A closer look at the situation illuminates the complexities in the BOJ’s policy decisions and the broader implications on the financial landscape.

JPY: (Source: Trading View)

The post As yen weakens and interest peaks, Bank of Japan balances on a policy precipice appeared first on CryptoSlate.

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Poland, Austria, & Czechia Introduce Temporary Border-Checks With Slovakia To Curb Illegal Migration

Poland, Austria, & Czechia Introduce Temporary Border-Checks With Slovakia To Curb Illegal Migration

Authored by Thomas Brooke via Remix…

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Poland, Austria, & Czechia Introduce Temporary Border-Checks With Slovakia To Curb Illegal Migration

Authored by Thomas Brooke via Remix News,

Poland, Austria and Czechia will all introduce random checks at the countries’ borders with Slovakia from midnight on Wednesday following an influx of illegal immigration.

Temporary checks will be conducted along the length of the border for an initial 10-day period until Oct. 13.

They will focus specifically on road and railway border crossings, although, pedestrians and cyclists may also be asked for documentation. Anyone within the vicinity of the border may be requested to identify themselves.

“The numbers of illegal migrants to the EU are starting to grow again,” said Czech Prime Minister Petr Fiala following the announcement. “We don’t take the situation lightly.”

“Citizens need a valid passport or identity card to cross the border,” the Czech Interior Ministry added.

The Czech policy would also be adopted by neighboring Austria, the country’s Interior Minister Gerhard Karner confirmed.

Poland had already announced its intention to reintroduce checks on the Slovak border with the number of migrants along the Balkans migration route continuing to surge. Prime Minister Mateusz Morawiecki said last week he was “instructing Minister of Interior Mariusz Kamiński to check on buses, coaches, and cars crossing the border when it is suspected there could be illegal migrants on board.”

“In recent weeks, we detected and detained 551 illegal migrants at the border with Slovakia. This situation causes us to take decisive action,” Kaminski added.

Slovak caretaker Prime Minister Ludovit Odor acknowledged the growing issue of illegal migration in his country but insisted that the problem needs a European solution rather than individual nations restricting border access.

He claimed that the decision by the three neighboring countries had been fueled by the Polish government, which is involved in a tightly contested election campaign, with Poles heading to voting booths on Oct. 15.

“The whole thing has been triggered by Poland, where an election will soon take place, and the Czech Republic has joined in,” Odor said.

Slovakia revealed last month that the number of illegal migrants detained by its authorities this year had soared nine-fold to over 27,000. The majority of detainees comprise young men from the Middle East using the Balkan migratory route through Serbia as they seek to migrate to northwestern Europe.

The winner of Sunday’s general election in Slovakia, former Prime Minister Robert Fico, has vowed to tackle the issue more robustly by promising to reintroduce border checks with neighboring Hungary.

“It will not be a pretty picture,” Fico told journalists as he threatened to use force to dispel illegal migrants detected on Slovak territory.

Tyler Durden Wed, 10/04/2023 - 02:00

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EU Wants To Pay Off Hungary To The Tune Of €13BN So Orban Doesn’t Veto Ukraine Aid

EU Wants To Pay Off Hungary To The Tune Of €13BN So Orban Doesn’t Veto Ukraine Aid

Hungary’s Viktor Orbán has long been an opponent of…

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EU Wants To Pay Off Hungary To The Tune Of €13BN So Orban Doesn't Veto Ukraine Aid

Hungary's Viktor Orbán has long been an opponent of the mainstay of EU policy on Ukraine, having also persistently criticized Kiev for discrimination against Hungarian minorities, and demanding that a 2017 law restricting the use of minority languages be changed. He's also refused to ratify Sweden's entry into NATO.

Orbán has further throughout the conflict stood against policies which escalate against Moscow, and has constantly warned against stumbling into a WW3 scenario involving direct NATO-Russia clash. He told Tucker Carlson in a recent interview that "the Third World War сould be knocking on our door so we have to be very careful." With Budapest having been a consistent thorn in the side of the EU, Brussels now wants to pay the Hungarians off.

AFP/Getty Images

"The European Commission is preparing to unfreeze around €13 billion in funds for Hungary to try to avoid Prime Minister Viktor Orbán vetoing EU aid for Ukraine, in a move likely to draw criticism from the European Parliament," Politico reports Tuesday.

"The Commission needs the unanimous backing of the bloc's 27 countries for an update to the EU’s long-term budget, which includes a €50 billion funding pot for Ukraine," the report adds.

Akin to what's currently going down in Washington with a group of Republicans holding up Ukraine funding, Brussels may soon have its own Ukraine aid blockage problem. EU aid for Kiev which was previously approved runs out in December, hence the urgency for EU leadership in wanting to push through a new package.

A week ago, Orbán gave a speech declaring Hungary will no longer support Ukraine in any way unless certain significant policies are changed both in Kiev and in the European Union.

He stressed in the words given before parliament that "Hungary is doing everything for peace" but that "unfortunately the Russian-Ukrainian war continues, tens of thousands of people are victims." Thus, he continued, "Diplomats must take control back from the hands of the soldiers, otherwise it will be in vain for women to wait for their sons and fathers and husbands to come home."

The Hungarian leader has stood against ratcheting Western sanctions on Moscow, instead choosing to maintain a generally positive diplomatic relationship with the Kremlin.

He also a week ago charged that Kiev and its backers have cheated Budapest by "Ukrainian grain dumping" into his country. He had also laid out, per The Hill:

... that he was protesting a 2017 law in Ukraine that limits ethnic Hungarians from speaking their own language, particularly in schools and said Hungary would not support Ukraine on international issues "until the previous laws are restored."

Needless to say EU officials are panicking, and are readying a lucrative quid pro quo with Hungary (based on freeing frozen funds related to the prior years' so-called "rule of law" punitive measures"), so that EU aid to Ukraine doesn't get blocked at a crucial moment that Washington funding is drying up.

Tyler Durden Wed, 10/04/2023 - 02:45

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