Harmless or deadly? New study examines evolution of E. coli bacteria

 Genetic material from E. coli bacteria in farm animals could be contributing to the evolution of deadly pandemic strains of E. coli in humans, new research shows.

E. coli usually live as harmless bacteria in the gastrointestinal tracts of birds and mammals, including humans. They also reside, independent of a host, in environments such as water and soil, and in food products including chicken and turkey meat, raw milk, beef, pork and mixed salad.

These bacteria can cause disease if they possess or acquire factors that allow them survive in areas of the human body outside the gut.

E. coli is the primary source of urinary tract infections, a common reason for hospital admissions. It can also lead to sepsis, which kills 11 million people globally each year, and meningitis, an infection that affects the brain and spinal cord.

Dr Cameron Reid, from the University of Technology Sydney, said the aim of the study, recently published in Nature Communications, was to better understand the evolution and genomic characteristics of an emerging strain of E. coli known as ST58.

ST58 has been isolated from bloodstream infections in patients around the world, including France, where the number of infections with this strain was shown to have doubled over a 12 year period. ST58 is also more drug resistant than other strains.

"Our team analysed E. coli ST58 genomes from more than 700 human, animal and environmental sources around the world, to look for clues as to why it is an emerging cause of sepsis and urinary tract infections," said Dr Reid.

"We found that E. coli ST58 from pigs, cattle and chickens contain pieces of genetic material, called ColV plasmids, which are characteristic of this strain of disease causing E. coli," he said.

Plasmids are tiny double-stranded DNA molecules, separate from the bacterial chromosome, that can replicate independently and transfer across different E. coli strains, aiding the evolution of virulence.

Acquisition of ColV plasmids may prime E. coli strains to cause extra-intestinal infections in humans, and also increase the likelihood of antimicrobial resistance, the research suggests.

"Zoonosis, particularly in relation to E. coli, should not be viewed simply as the transfer of a pathogen from an animal to a human," said research co-author Professor Steven Djordjevic.

"Rather, it should be understood as a complex phenomenon arising from a vast network of interactions between groups of E. coli (and other bacteria), and the selective pressures they encounter in both humans and animals," he said.

The findings suggest all three major sectors of food animal production (cattle, chickens and pigs), have acted as backgrounds for the evolution and emergence of this pathogen.

"The contribution of non-human sources to infectious disease in humans is typically poorly understood and its potential importance under-appreciated, as the debate regarding the ecological origins of the SARS-CoV2 virus attest," said Dr Reid.

"In a globalised world, eminently susceptible to rapid dissemination of pathogens, the importance of pro-active management of microbial threats to public health cannot be understated."

The study has broad implications for public health policy that spans across food industry, veterinary and clinical settings.

"To date, infectious disease public health has been a reactive discipline, where action can only be taken after a pathogen has emerged and done some damage," said Dr Reid.

"Ideally, with the advent and widespread uptake of genome sequencing technology, future infectious disease public health can transition to a primarily pro-active discipline, where genomic surveillance systems are able to predict pathogen emergence and inform effective interventions."

Dr Reid said for such a system to work, it requires ongoing research and collaboration with government, public health bodies, food producers and clinicians, and it would involve surveillance of a variety of non-human sources of microbes.

"This would include domestic and wild animals -- particularly birds -- food products, sewerage and waterways, in what is referred to as a 'One Health' approach. Some microbes, like ST58 E. coli, know very few barriers between these increasingly interconnected hosts and environments.

"A One Health genomic pathogen surveillance system would be a revolution within public health and do much to break down historically human-centric approaches devoid of connection with the world around us."

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Story Source:

Materials provided by University of Technology Sydney. Note: Content may be edited for style and length.

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Journal Reference:

1. Cameron J. Reid, Max L. Cummins, Stefan Börjesson, Michael S. M. Brouwer, Henrik Hasman, Anette M. Hammerum, Louise Roer, Stefanie Hess, Thomas Berendonk, Kristina Nešporová, Marisa Haenni, Jean-Yves Madec, Astrid Bethe, Geovana B. Michael, Anne-Kathrin Schink, Stefan Schwarz, Monika Dolejska, Steven P. Djordjevic. A role for ColV plasmids in the evolution of pathogenic Escherichia coli ST58. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-28342-4

https://www.sciencedaily.com/releases/2022/03/220301093707.htm

Why multiple myeloma returns

 Multiple myeloma is a cancer which affects 'plasma cells', a type of immune cell found in the bone marrow. This cancer can weaken the immune system, cause kidney damage, and weaken bones, which may lead to fractures. Average survival rates have improved considerably thanks to new treatment options. These include lenalidomide and pomalidomide, drugs which are often successful in forcing the cancer into remission. In nearly all cases, however, the cancer will become increasingly less susceptible to these drugs, meaning it develops drug resistance. When cancer growth eventually resumes despite treatment, the patient's prognosis is poor.

Using latest improvements for a method known as proteomics, an interdisciplinary team of researchers in Berlin was able to decode a previously unknown mechanism which can cause this type of relapse. "We were able to show that production of CDK6, a cell division-promoting cell cycle regulator, is particularly high once the cancer has become resistant to treatment," explains one of the study's two co-leads, Prof. Dr. Jan Krönke of the Department of Hematology, Oncology and Cancer Immunology on Campus Benjamin Franklin. "Based on our data, we believe that CDK6 inhibition could represent a new treatment approach in relapsed multiple myeloma."

Despite extensive DNA sequencing studies, treatment resistance in multiple myeloma has only rarely been linked to changes at the genetic level, such as gene mutations or gene deletions. "This suggests that the changes taking place within the cancer cell which would explain this relapse must take place at a different level," says the study's second co-lead, Dr. Philipp Mertins, an MDC researcher who heads the Proteomics Platform at both the MDC and the BIH. He continues: "The cancer cells' growth potential may also be subject to various means of control at the protein level. Here, we observed this type of effect in relation to the protein CDK6." The researchers employed cutting-edge mass spectrometry technology in order to establish whether changes at the protein level are responsible for the cancer becoming resistant to treatment. Using both pre- and post-relapse samples from patients with multiple myeloma, the researchers were able to quantify more than 6,000 different proteins.

Comparing cancer cells collected before and after relapse, the researchers found that a range of proteins were present at either higher or lower concentrations post-relapse. Using statistical and bioninformatics analyses, the researchers were able to trace the majority of these effects back to a single protein: cyclin-dependent kinase 6, or CDK6, an enzyme which controls the cell's entry into the cell division phase of the cell cycle.

As a first step, the researchers used cell cultures to demonstrate that CDK6 plays a key role in the development of treatment resistance in multiple myeloma. "When we artificially increased the amount of CDK6 present inside cultured myeloma cells, they lost their susceptibility to the drugs lenalidomide and pomalidomide," explains the study's first author, Dora Ng, a researcher at the Department of Hematology, Oncology and Cancer Immunology on Campus Benjamin Franklin. She adds: "However, when we also added a CDK6 inhibitor, the drugs became effective again and the cancer cells died. This shows that CDK6 inhibition enables at least a partial reversal of the myeloma cells' treatment resistance."

The researchers were then able to confirm this effect in an animal model, where the combination of pomalidomide with a CDK6 inhibitor significantly improved the odds of survival. "These data suggest that patients with treatment-resistant multiple myeloma may also benefit from the addition of CDK6 inhibitors," says Prof. Krönke, a researcher at the German Cancer Consortium's (DKTK) translational research center in Berlin, who is being funded via the DFG's Emmy Noether Program. "Further studies will be needed in order to test this hypothesis. One advantage is that some CDK6 inhibitors have already been authorized for use in the treatment of breast cancer."

The study's second first author, Dr. Evelyn Ramberger, was responsible for performing the project's protein analyses. A postdoc at Charité and the MDC/BIH Proteomics Platform, she is convinced that the technology holds enormous benefits for the field of cancer research: "We want to continue pursuing this new approach of using modern, comprehensive protein analyses to study cancer tissues -- both in multiple myeloma and other cancers. We hope this will unveil further treatment targets and biomarkers for use in personalized cancer medicine," she says.

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Story Source:

Materials provided by Charité - Universitätsmedizin Berlin. Note: Content may be edited for style and length.

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Journal Reference:

1. Yuen Lam Dora Ng, Evelyn Ramberger, Stephan R. Bohl, Anna Dolnik, Christian Steinebach, Theresia Conrad, Sina Müller, Oliver Popp, Miriam Kull, Mohamed Haji, Michael Gütschow, Hartmut Döhner, Wolfgang Walther, Ulrich Keller, Lars Bullinger, Philipp Mertins, Jan Krönke. Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-28515-1

https://www.sciencedaily.com/releases/2022/03/220301131117.htm

Role of lipids in the development of Alzheimer’s disease

 Neurons in the brain coexist with and rely on many other cell types to function properly. Astrocytes, which take their name from their star shape, ensure the survival of neurons by feeding and detoxifying them with the help of a multifunctional protein, APOE. One of three forms of this protein, APOE4, significantly increases the risk of developing Alzheimer's disease, but the mechanisms at play are unknown. A collaboration between the University of Geneva (UNIGE), the European Molecular Biology Laboratory (EMBL), the University of Zurich and the pharmaceutical company AbbVie has discovered a potential mechanism: far from ceasing to function, APOE4 is on the contrary more efficient. By triggering astrocytic lipid secretion, it causes the accumulation of potentially toxic lipids that are harmful to neurons, and thus might contribute to the development of Alzheimer's disease. These results published in the journal Cell Reports, shed new light on the neurodegenerative mechanisms of a disease that affects nearly 50 million people worldwide.

Astrocytes, present in very large numbers in the brain, have a major protective function. These cells secrete apolipoprotein E (or APOE), a small protein that forms particles containing lipids and vitamins to feed the neurons. It also detoxifies the neurons by getting them rid of "lipid waste" that could become harmful if not removed. As the neurons are unable to eliminate this waste on their own, APOE comes into play to collect it and bring it back to the astrocytes where it is destroyed.

The gene coding for APOE exists in three frequent variants in humans: APOE2, present in 8% of the population, APOE3, the most common, and APOE4, which is found in nearly 15% of people and increases the risk of developing Alzheimer's disease by a factor of ten. "The reasons why APOE4 increases the risk of Alzheimer's disease so significantly are not well understood," explains Anne-Claude Gavin, a professor in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine and holder of a Louis-Jeantet Foundation Chair, who directed this research together with Viktor Lakics, a Research fellow and Biology Area Leader in Neuroscience discovery at AbbVie. What are the mechanisms behind the dysfunction of APOE4? And above all, could they serve as a basis for prevention or therapy? To answer these questions, Anne-Claude Gavin and her team joined forces with scientists from the European Molecular Biology Laboratory (EMBL), the University of Zurich and AbbVie.

A protein that is too effective

Working on these questions, the research team identified novel molecular mechanisms that explain how APOE binds to astrocyte membranes to detect and extract the lipids it needs. Employing human cell lines with different APOE variants, in vitro experiments demonstrated that APOE is very efficient at transporting potentially harmful lipids produced in neurons. "And to our great surprise, the APOE4 variant proved to be even more efficient than the other forms," reveals Katharina Beckenbauer, a former post-doc in Anne-Claude Gavin's group, senior scientist at AbbVie, and one of the first authors of the work. "So, contrary to what we thought until now, the problem is not that APOE4 stops working, but, in fact, the opposite. And the mechanism goes haywire."

A hijacked function

As astrocytes age, they become less efficient and start to accumulate lipids rather than destroy them. "We modelled this process experimentally and observed the molecules secreted by the astrocytes," explains Karina Lindner, a PhD student in Anne-Claude Gavin's laboratory and one of the first authors of this work. "We observed that cellular ageing diverts APOE from its primary function -- transporting lipids to neurons and also recovering lipid waste from them -- towards the secretion of triglycerides, particular lipid species that could become harmful if not removed." And this phenomenon is exacerbated with APOE4: it stimulates the secretion of triglycerides, leading to their uncontrolled accumulation. This deleterious accumulation of potentially harmful lipids could very well be an important contributor to the neuronal death, a hallmark of Alzheimer's disease. "APOE4 would thus have the capacity to accelerate the pathological process in the disease through the mechanism we have discovered."

In order to better understand the details of the action of APOE and especially of the E4 variant, the scientists at UNIGE want now to determine how secretion of these potentially harmful lipids is regulated and whether this secretion can be detected in people suffering from Alzheimer's disease.

Story Source:

Materials provided by Université de Genève. Note: Content may be edited for style and length.

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Journal Reference:

1. Karina Lindner, Katharina Beckenbauer, Larissa C. van Ek, Kevin Titeca, Sherida M. de Leeuw, Khader Awwad, Franziska Hanke, Alla V. Korepanova, Vladimir Rybin, Elizabeth Louise van der Kam, Eric G. Mohler, Christian Tackenberg, Viktor Lakics, Anne-Claude Gavin. Isoform- and cell-state-specific lipidation of ApoE in astrocytes. Cell Reports, 2022; 38 (9): 110435 DOI: 10.1016/j.celrep.2022.110435

https://www.sciencedaily.com/releases/2022/03/220301131037.htm

U.S. Supreme Court Mulls 'Pill Mill' Doctors' Opioid Convictions

 The U.S. Supreme Court on Tuesday wrestled with the circumstances under which doctors can be convicted of operating as drug dealers under the cover of their medical practices to illegally distribute opioid painkillers and other dangerous narcotics.

The justices heard arguments in an appeal by two doctors, Xiulu Ruan and Shakeel Kahn, of lower court rulings upholding their convictions on narcotics violations and related crimes stemming from what prosecutors called the misuse of medical licenses to engage in drug trafficking.

Lawyers for Ruan, who practiced in Alabama, and Kahn, who practiced in Arizona and then Wyoming, complained to the justices that jurors convicted the doctors of unlawfully dispensing massive amounts of opioids through "pill mill" clinics without having to weigh whether they had a "good faith" reason to believe their prescriptions were medically valid.

Some of the justices questioned why jurors should be instructed to consider the doctors' beliefs at all about the medical validity of their prescriptions when determining if they violated a federal law called the Controlled Substances Act.

Chief Justice John Roberts asked "how is that different" than if police pulled over a driver on a highway for going over a 50-mile-per-hour (80 km) speed limit who then argued that the speed limit should be higher. The driver would still get ticketed, Roberts said.

There has been an increase in U.S. criminal prosecutions of doctors who have prescribed addictive pain pills amid a law enforcement push to combat an opioid abuse epidemic that has caused hundreds of thousands of overdose deaths over the past two decades.

The Supreme Court took up the doctors' appeals amid divisions in lower courts about the standard under which doctors could be convicted of violating the Controlled Substances Act for writing prescriptions outside the bounds of professional practice.

Eric Feigin, a U.S. deputy solicitor general arguing for the government, said accepting the doctors' arguments would upend the purposes of licenses issued by the U.S. Drug Enforcement Administration for doctors to prescribe dangerous drugs.

"They want to be free of any obligation even to undertake any minimal effort to act like doctors when they prescribe dangerous, highly addictive and, in one case, lethal dosages of drugs to trusting and vulnerable patients," Feigin said.

Ruan was sentenced to 21 years in prison and Kahn to 25 years in separate criminal prosecutions.

Prosecutors said Ruan, through a clinic in Mobile, issued nearly 300,000 controlled-substance prescriptions from 2011 to 2015 and accepted kickbacks from drugmaker Insys Therapeutics Inc to prescribe a fentanyl spray to patients.

Prosecutors said Kahn regularly sold prescriptions for cash and unlawfully prescribed large amounts of opioid pills, resulting in at least one patient dying of an overdose.

Lawrence Robbins, Ruan's lawyer, said that while jurors are free to disbelieve that a doctor had a good faith belief in the medical validity of their drug prescriptions, they should be instructed by courts to consider that defense before reaching a verdict.

Justice Samuel Alito said the Controlled Substance Act by his reading had no mention of such a requirement.

"As for 'good faith,' I don't know where that word comes from at all," Alito said.

Justice Brett Kavanaugh said the statute's requirement of a "legitimate medical purpose" to prescribe controlled substances was vague and something "on which reasonable people can disagree."

Kavanaugh appeared open to instructing jurors to hear good faith defenses from doctors, saying jurors would almost certainly disbelieve them if they came in with "some outlandish theory."

https://www.usnews.com/news/top-news/articles/2022-03-01/u-s-supreme-court-mulls-pill-mill-doctors-opioid-convictions

Hong Kong leader calls for calm, after supermarkets emptied ahead of mass COVID testing

 Hong Kong's leader Carrie Lam called for calm on Tuesday after residents emptied supermarkets, stocking up on produce ahead of reports of compulsory mass COVID-19 testing and rumours of a city-wide lockdown.

Local media reported compulsory COVID testing would start after March 17, sparking concerns many people will be forced to isolate and families with members testing positive would be separated.

Lam appealed to the public "not to fall prey to rumours to avoid unnecessary fears being stirred," with the supply of food and goods remaining normal, according to a statement on Tuesday.

"There is no need for members of the public to worry, they should stay vigilant and pay attention to the information disseminated by the government so as to avoid being misled by rumours."

Officials are planning to test the city's 7.4 million people three times over nine days, with the government recommending that people stay home during the period, Sing Tao newspaper reported, citing unidentified sources.

Exemptions would be made for those who buy food, seek medical treatment and maintain societal operations. Hong Kong's stock market would continue to operate, the paper said.

Lam had previously said she was not considering a city-wide lockdown.

The Chinese ruled city has seen coronavirus infections surge some 34 times to over 34,000 on Monday from just over 100 at the start of February. Deaths are also climbing, with facilities for storing dead bodies at hospitals and public mortuaries at maximum capacity. read more

Hong Kong continues to stick to a COVID policy of "dynamic zero", the same as mainland China, which seeks to curb all outbreaks at any cost. The Chinese ruled territory has implemented its most draconian measures since the start of the pandemic in 2020.

The rules have exacerbated separation fears among many families, with many fleeing ahead of the mass testing scheme and the build out of tens of thousands of isolation centres. read more

Lam, who inspected a mainland Chinese built isolation centre on Monday, said the team had raced against the clock to "create a miracle" in the city's construction industry.

The Tsing Yi facility, located in the northwest of the city, would provide around 3,900 rooms for infected people with mild or no symptoms and others who need to isolate, she said.

https://www.reuters.com/world/asia-pacific/hong-kong-leader-calls-calm-after-supermarkets-emptied-ahead-mass-covid-testing-2022-03-01/

Biden to blame social media for ‘mental health crisis’ at State of the Union

 President Biden plans to castigate social media companies for contributing to “a national mental health crisis” Tuesday night in his first State of the Union speech — while noting other factors such as the COVID-19 pandemic, which has been blamed for fueling record-high numbers of drug overdose deaths over the past two years.

Biden will host former Facebook worker Frances Haugen, who accused the company of failing to censor misinformation and content harmful to teens, as one of his guests to underscore his attack on tech giants.

“The president believes tech companies should be held accountable for the harms they cause,” a White House official told reporters on a call previewing the portion of his speech.

A White House release said Biden “will announce a strategy to address our national mental health crisis,” including funds for federal programs that promote mental health at colleges and other communities.

Facebook whistleblower Frances Haugen will be a guest of President Biden at his State of the Union.

Drew Angerer

The White House is accusing social media companies of gender bias that discourages women from pursuing jobs in fields like engineering.

stnazkul

Biden also wants “to ban excessive data collection on and targeted advertising online for children and young people,” the release said.

The president’s forthcoming annual budget will request $5 million for “research on social media’s harms, as well as the clinical and societal interventions we might deploy to address them,” according to a fact sheet that also accuses companies of gender bias by delivering pornographic results when people search for “girls” of various races.

Biden wants to “stop discriminatory algorithmic decision-making that limits opportunities for young Americans,” the White House said.

President Joe Biden will propose $5 million in funding toward researching the harms social media inflicts on society and ways to combat them.

J. Scott Applewhite

“When a girl searches for jobs online, platforms will too often push her away from fields like engineering that historically have excluded women,” the fact sheet contended. “Searches for ‘Black girls,’ ‘Asian girls,’ or ‘Latina girls’ too often return harmful content, including pornography, rather than role models, toys, or activities.”

The White House statement acknowledged other causes of mental health issues but didn’t specifically mention drug overdose deaths, which surpassed 100,000 in a 12-month period ending in April 2021. The 28.5 percent spike was driven by illicit fentanyl coming largely from China. The potent compound is increasingly cut into non-opioid drugs and pressed into counterfeit prescription pills while also wiping out a generation of addicts unwittingly hooked on painkillers by Purdue Pharma’s OxyContin.

“Our country faces an unprecedented mental health crisis among people of all ages,” the White House statement said.

“Two out of five adults report symptoms of anxiety or depression. And, Black and Brown communities are disproportionately under-treated — even as their burden of mental illness has continued to rise. Even before the pandemic, rates of depression and anxiety were inching higher. But the grief, trauma, and physical isolation of the last two years have driven Americans to a breaking point.”

Although criticism of Big Tech platforms often is bipartisan — with both Biden and former President Donald Trump supporting changes to Section 230 immunity for third-party content — Republicans are more likely to blame US mental health woes on issues such as the mandatory masking of students and remote learning due to COVID-19.

The White House failed to specifically mention overdoses as part of the mental health crisis.

BackyardProduction

“If you’re a parent of a child with asthma, as one parent shared with me, wearing a mask for now close to two years has been just a very difficult experience,” Virginia GOP Attorney General Jason Miyares said in a recent interview.

“I had another parent who shared with me [that] their daughter, they used to be an all-A student, is now a mostly ‘C’ student because they wear glasses and the school has gone from a joy to complete misery,” Miyares added. “And another parent of a school–age child said how excited their child was, their daughter was, that for the very first time, they could see what their best friend from school actually looks like. I mean, think about the mental health crisis as well [and the effect] that we’re having on our kids.”

https://nypost.com/2022/03/01/biden-to-blame-social-media-for-mental-health-crisis-at-state-of-the-union/

Gemini Axes 80% of Workforce, Names Interim CEO, in Restructuring

 Gemini Therapeutics, a clinical-stage biopharma company dedicated to developing treatments for genetically defined age-related macular degeneration (AMD), announced a series of corporate updates Monday. Among these is a corporate restructuring that will see a drastic 80% of the company's workforce laid off. 

The Cambridge, Massachusetts-based company has seemingly been struggling for a while. When Gemini announced its Q2 financial updates in August 2021, it showed a net loss of $16.4 million, compared to a net loss of $6.8 million during Q2 2020. 

The company chalked up the losses to an increase in operating expenses, which were $5.5 million for the quarter (compared to only $1.1 million for the same quarter in 2020). Gemini said the increased expenses were due to becoming a public company and from increasing headcount. 

After such dismal updates, it wasn't a surprise when Gemini announced it was cutting 20% of its staff in October 2021. In the press release, the company said it was reducing its research and non-clinical programs to better focus on GEM103, a precision medicine for geographic atrophy secondary to dry AMD. Gemini called the pivotal clinical trial of GEM103 "resource-intensive." 

And resource-intensive it must have been because a week later, Gemini began offering inducement grants to purchase more than 217,000 shares of the company's common stock under NASDAQ Listing Rule 5635(c)(4).

By the time 2021's Q3 financial report came around in November, Gemini's net losses were $18.6 million, and operating expenses were $5.0 million. 

Still, the company had a few rays of hope. Its ongoing Phase IIa, multi-center study of GEM103 was going well. At the AAO meeting in November 2021, Gemini presented GEM103 study data which showed the drug was well-tolerated across 510 intravitreal injections with no ocular serious adverse events. The company also still had $150.1 million in cash assets. 

But the losses kept coming, and now Gemini is cutting 24 of its employees—around 80% of its remaining workforce. The company said these layoffs are designed to keep it focused on developing GEM307, a new antibody for human complement factor H protein, a protein essential for retinal health. Gemini plans to continue working on clinical development for GEM307. 

The corporate update included other announcements related to restructuring. Jason Meyenburg, the CEO, president and director of Gemini, is stepping down, although he will remain an advisor to the company. Meyenberg will be succeeded by Georges Gemayel, Ph.D., as interim president and CEO. Gemayel was appointed as Gemini's chair of the board of directors in May 2021. 

Gemayel, who has more than 30 years of experience in the pharmaceutical industry, had expressed excitement in joining the company.

"Gemini has a very exciting approach to treat dry AMD that could bring to the market a best-in-class product," he had said when he was appointed as chair. 

Now that Gemayel will be serving as interim CEO and president, he said he is evaluating "strategic alternatives." Gemini has not set a timeline for these alternatives, and the company says it will not offer further comments until the board of directors has decided which route they will pursue. 

"We have decided to reduce the Company's operations to preserve financial resources until the strategic evaluation process concludes," Gemayel said. 

https://www.biospace.com/article/gemini-therapeutics-corporate-updates-include-layoffs-new-leadership/