'An underutilized tool:' UV-LED lights can kill coronaviruses and HIV with the flip of a switch, study finds

The same light bulbs used in offices and public spaces can destroy coronaviruses and HIV, according to a new study from U of T Scarborough.
Researchers killed both viruses using UV-LED lights, which can alternate between white light and decontaminating ultraviolet (UV) light. With a cheap retrofit, they could also be used in many standard lighting fixtures, giving them a “unique appeal” for public spaces, says Christina Guzzo, senior author of the study.
“We’re at a critical time where we need to use every single possible stop to get us out of this pandemic,” says Guzzo, an assistant professor in the department of biological sciences. “Every mitigation strategy that can be easily implemented should be used.”
UV lights kill viruses through radiation. Guzzo, alongside PhD students Arvin T. Persaud and Jonathan Burnie, first tested the lights on bacterial spores notorious for their resistance to this radiation (known as Bacillus pumilus spores).
“If you’re able to kill these spores, then you can reasonably say you should be able to kill most other viruses that you would commonly encounter in the environment,” says Guzzo, principal investigator at the Guzzo Lab.
Within 20 seconds of UV exposure, the spores’ growth dropped by 99 per cent.

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Researchers identify key complex for ribosome generation

UT Southwestern researchers have identified a four-protein complex that appears to play a key role in generating ribosomes — organelles that serve as protein factories for cells — as well as a surprising part in neurodevelopmental disorders. These findings, published in Cell Reports, could lead to new ways to manipulate ribosome production, which could impact a variety of conditions that affect human health.
“Ribosomes are fundamental for life, but we’ve had an incomplete understanding of how they’re put together and how the process of ribosome production is regulated,” said lead author Michael Buszczak, Ph.D., Professor of Molecular Biology and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “Our findings shed significant light on these questions.”
Dr. Buszczak explained that ribosomes are present in varying amounts in every cell of every organism on Earth. Because of their key role as protein producers, he added, variations from these natural set points can have deleterious consequences. For example, cancer cells tend to increase ribosome production to boost protein production necessary for unchecked cell division. In addition, a group of rare diseases known as ribosomopathies — characterized by abnormal ribosome production — manifests with a variety of symptoms including anemia, craniofacial defects, and intellectual disability.
Although every species has ribosomes, most of what’s known about ribosome biogenesis has come from the popular lab model, yeast. The basics of this process are the same for human ribosome biogenesis, Dr. Buszczak said, but the specifics are not. Consequently, the details that make human ribosome generation unique have been unknown.
To learn more about this process, Dr. Buszczak, Chunyang Ni, a graduate student in the Buszczak lab, and their colleagues, including Jun Wu, Ph.D., Assistant Professor of Molecular Biology at UTSW, started by developing a technique that prompted old ribosomes to glow red and newly generated ribosomes to glow green. The researchers used this tool on several different human cell types, confirming different rates of ribosome production in each.
Using the gene editing tool called CRISPR, the researchers inactivated individual genes to identify those that might be key players in ribosome biogenesis. Their search turned up four genes known as CINP, SPATA5L1, C1orf109, and SPATA5. Further research showed that these genes come together into a complex that strips a placeholder protein from ribosomes when assembly is almost complete, allowing a different protein to take its place for ribosome maturation.
Previously, SPATA5’s function in cells had been unknown; however, mutations in this gene have been associated with neurodevelopmental disorders including microcephaly, hearing loss, epilepsy, and intellectual disability. When the researchers inserted two of these mutations into cells, causing them to create a mutant SPATA5 protein, the cells couldn’t generate the normal level of functional ribosomes — suggesting that these neurodevelopmental disorders could stem from ribosome problems.
Dr. Buszczak said that he and his colleagues plan to study why the central nervous system appears to be more sensitive than other cell types to ribosomal disruptions. He added that these findings could eventually lead to new treatments for cancer, ribosomopathies, and other conditions affected by over- or under-production of proteins.
This work was supported by grants from the National Institute of General Medical Sciences (GM125812 and GM144043) and funding from the Simmons Cancer Center.
Other UTSW researchers who contributed to this study include Daniel A. Schmitz, Jeon Lee, and Krzysztof Paw?owski.
Dr. Buszczak is the E.E. and Greer Garson Fogelson Scholar in Medical Research. Dr. Wu is a Virginia Murchison Linthicum Scholar in Medical Research and a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar.
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Early life adversity, microglia dysfunction linked to aberrant adult stress responses, mental illness

The poor function of microglia, the brain’s immune cells in individuals exposed to early life adversity (ELA) promotes aberrant responses to stress in adulthood that may be linked to mental illness, according to a new study led by researchers at the University of California, Irvine. During brain development, microglia prune unnecessary synapses resulting in the formation of refined, functional circuits. Disruption of that process leaves too many synapses, changing the behavioral and hormonal responses to further stresses later in life.
The study, titled “Early-stress induced impairment of microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses,” was published online today in Cell Reports.
“Much of neuroscience and study of brain diseases has focused on the brain’s neurons. This study highlights that in addition to neurons, other brain cells, and especially immune cells, play crucial roles in brain health and disease,” said Tallie Z. Baram, distinguished professor in the Departments of Anatomy & Neurobiology, Pediatrics, Neurology, and Physiology & Biophysics at the UCI School of Medicine. “Neuroimmune interactions are a novel, important avenue to understanding and treating several brain disorders and mental illness and have been linked by other UCI researchers to Alzheimer’s disease.”
Brain development is governed by both genetics and early life experiences. Several mental illnesses, characterized by aberrant reactions to stress, often arise after ELA but its effect on stress-related brain circuit maturation was unclear. In the study, led by UCI Postdoctoral Fellow Jessica Bolton, who is now an Assistant Professor at Georgia State University, transgenic mice of both sexes were housed in temperature-controlled, quiet, uncrowded conditions on a schedule of 12 hours of light and 12 hours of dark, with free access to food and water. The control dams were place in cages with standard amounts of corn husk bedding and nesting material. The ELA dams received only one-half nestlet and reduced bedding materials.
Researchers found that ELA increased functional excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone-(CRH) expressing neurons, resulting from disrupted developmental synapse pruning by adjacent microglia in the mouse pups. These neuroimmune interactions during development thus made the CRH cells, and they mice, more vulnerability to stress.
“Our discoveries reveal that ELA leads to reduced microglial process dynamics during a sensitive period. We know this is a direct effect of ELA, because we artificially activated microglia in stressed neonatal mice, which prevented the synapse excess and the abnormal responses to stress during adulthood,” Baram said. “The next steps are to identify if the molecules that lead to microglial dysfunction can be used to prevent their malfunction and the resulting vulnerability to stress. This may be translatable to people.”
This work was supported by National Institutes of Health grants K99 MH120327, P50 MH096889, R01 MH73136, R01 NS14609, and R01 AI121945; the Brain & Behavior Research Foundation NARSAD Young Investigator Grant; and the Hewitt Foundation for Biomedical Research.
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Head-mounted microscope reaches deeper into mouse brains

Researchers have developed a miniature microscope that is designed for high-resolution 3D images inside the brains of living mice. By imaging deeper into the brain than previously possible with miniature widefield microscopes, the new lightweight microscope could help scientists better understand how brain cells and circuits operate.
“With further development, our microscope will be able to image neural activity over time while an animal is in a naturalistic environment or performing different tasks,” said lead author Omkar Supekar from the University of Colorado Boulder. “We show that it can be used to study cells that play an important role in neurological disorders such as multiple sclerosis.”
In the Optica Publishing Group journal Biomedical Optics Express, the researchers describe their new SIMscope3D, which images fluorescence emitted from tissue or fluorescent tags after the sample is exposed to certain wavelengths of light. The new device is the first miniature microscope to use structured illumination to remove out-of-focus and scattered light, which allowed imaging as deep as 260 microns on fixed brain tissue with an LED light source.
“Developing new treatments for neurological disorders requires understanding the brain at the cellular and circuit-level,” said research team lead Emily Gibson from the University of Colorado Anschutz Medical Campus. “New optical imaging tools — particularly those that can image deep into brain tissue like the microscope our team developed — are important for achieving this goal.”
Seeing deeper
Head mounted microscopes are used to image the brains of small rodents through transparent windows implanted into their skulls. Researchers have previously developed head-mounted widefield fluorescence microscopes, but light scattered by tissue prevents imaging deep into the brain. Miniature two-photon microscopes can overcome this drawback by eliminating out-of-focus light in each focal plane — a process known as optical sectioning — but typically require expensive pulsed lasers and complex mechanical scanning components.

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Roundworms’ egg cells have a backup plan

For reproduction to be successful, an egg cell must divide perfectly. Egg cell divisions are so error-prone, however, that they are the leading cause of miscarriages and birth defects in humans.
In a new study, Northwestern University researchers discovered a previously unknown mechanism in roundworms that protects their egg cells from division errors. Uncovering and understanding this hidden mechanism could ultimately lead to new strategies for combatting infertility in humans.
“Prior to our work, certain proteins were thought to be essential for cells to divide,” said Northwestern’s Sadie Wignall, who led the study. “However, when we removed these proteins, we were surprised to discover a previously hidden ‘backup’ mechanism that was able to kick in when the main proteins were missing. We uncovered something that other researchers missed because, if the major mechanism is in place, then you wouldn’t know that backup existed.”
The study was published today (March 29) in the journal eLife.
Wignall is an associate professor of molecular biosciences at Northwestern’s Weinberg College of Arts and Sciences. Gabriel Cavin-Meza, a graduate student in Wignall’s laboratory, is the paper’s first author.
When an egg is fertilized with sperm, the resulting embryo begins to rapidly divide, eventually developing into a healthy organism. If either the egg or the sperm have the wrong amount of genetic material, however, then the organism cannot properly develop.

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Prior COVID-19 infection linked to robust, accelerated immune response after first vaccine dose, researchers report

Since March 2020, the SARS-CoV-2 virus, the cause of coronavirus disease 2019 (COVID-19), has infected more than 460 million people worldwide. The vast majority of people who recover from infection demonstrate long-lasting immune memory of the virus. Little is known, however, about how this immune memory alters responses to SARS-CoV-2 mRNA vaccines, despite possible impacts on public health guidelines for vaccination.
Now, in recent research published in the journal JCI Insight, scientists at the Lewis Katz School of Medicine at Temple University show that responses to the Pfizer-BioNTech BNT162b2 mRNA vaccine differ significantly in individuals based on whether or not they were previously infected with SARS-CoV-2. Notably, those who had COVID before vaccination experienced rapid antibody production after the first vaccine dose, with little or no increase after the second dose. The opposite pattern was observed in infection-naive individuals.
“Our study shows that the presence of immune memory induced by prior infection alters the way in which individuals respond to SARS-CoV-2 mRNA vaccination,” explained Steven G. Kelsen, MD, Professor in the Department of Thoracic Medicine and Surgery at the Lewis Katz School of Medicine, and first author on the new report. “The lack of response after the second vaccine dose in previously infected individuals is especially relevant, because it could mean that some people may require only one dose or could potentially skip the booster shot.”
Dr. Kelsen and Temple colleagues carried out the study in health care workers, some having previously tested positive for SARS-CoV-2 infection and others never having been infected. In both groups, the researchers measured levels of neutralizing antibodies in blood samples taken at three different time points, including before vaccination and after each vaccine dose. They also performed qualitative assessment for local reactions and systemic symptoms, such as fever, headache, and fatigue, associated with vaccination.
While levels of neutralizing antibodies reached their maximum in some people with prior COVID illness after the first vaccine dose, individuals with no history of infection exhibited massive responses after the second dose. But those high levels also plummeted quickly, and for the COVID group, despite the lack of response to a second dose, individuals overall had longer-lasting immunity. Prior infection, however, was also linked to more frequent and longer-lasting adverse reactions to the vaccine.
“Previous studies had similarly reported long-lasting immunity and strong immune reactions in COVID patients,” Dr. Kelsen said. “We now provide new information on how prior infection interacts with vaccination in terms of measurable immune response and how individuals react to mRNA vaccines based on infection history.”
In future work, Dr. Kelsen and collaborators plan to modify their neutralizing antibody assay to detect Omicron and other SARS-CoV-2 variants. “We also are interested in understanding how long protection from a booster dose of the vaccine lasts,” he said.
Other researchers at the Lewis Katz School of Medicine who contributed to the study include Alan S. Braverman, Department of Thoracic Medicine and Surgery and Department of Anatomy; Mark O. Aksoy, Jacob A. Hayman, Puja S. Patel, and Charu Rajput, Department of Thoracic Medicine and Surgery; Huaqing Zhao and Susan G. Fisher, Department of Biomedical Education and Data Science; Michael R. Ruggieri Sr., Department of Anatomy; and Nina T. Gentile, Department of Emergency Medicine.
The study was supported by Temple University institutional funds.
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Study finds 10-second videos predict blood cancer relapse

In a new study from Vanderbilt University Medical Center, 10-second videos of white blood cell motion in the skin’s microvasculature greatly improved the prediction of which stem cell and bone marrow transplant patients would have a relapse of their blood cancer.
In the typical immune response, white blood cells are seen to interact with the inner walls of veins, rolling along them like bowling balls before adhering to them, then exiting through them to go to sites of inflammation.
Transplant patients whose white blood cells were caught on video with greater adherence levels and greater rolling along vessel walls were more than three times as likely to have cancer relapse or die, compared to those with normal adherence and rolling levels.
The stark finding, much more predictive than established models of blood cancer relapse and death, was reported March 26 in JAMA Dermatology and presented the same day in Boston at the annual meeting of the American Academy of Dermatology.
In a previous study involving noninvasive microscopy and graft-versus-host disease, the researchers stumbled on what appeared to be an association between higher white blood cell activity and cancer relapse.
“When we were able to turn our focus to this activity and measure it carefully in this new study, we found the association to be indeed striking,” said Inga Saknite, PhD, adjoint assistant professor of Dermatology, who gave the presentation in Boston. Saknite led the study with Eric Tkaczyk, MD, PhD, assistant professor of Dermatology and Biomedical Engineering, director of the Vanderbilt Dermatology Translational Research Clinic and staff dermatologist at Nashville VA Medical Center.

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Long Covid May Become a Crisis for Black Americans, Experts Say

It has long been clear that Black Americans have experienced high rates of coronavirus infection, hospitalization and death throughout the pandemic.But those factors are now leading experts to sound the alarm about what will may come next: a prevalence of long Covid in the Black community and a lack of access to treatment.Long Covid — with chronic symptoms like fatigue, cognitive problems and others that linger for months after an acute Covid-19 infection has cleared up — has perplexed researchers, and many are working hard to find a treatment for people experiencing it. But health experts warn that crucial data is missing: Black Americans have not been sufficiently included in long-Covid trials, treatment programs and registries, according to the authors of a new report released on Tuesday.“We expect there are going to be greater barriers to access the resources and services available for long Covid,” said one of the authors, Dr. Marcella Nunez-Smith, who is the director of Yale University’s health equity office and a former chair of President Biden’s health equity task force.“The pandemic isn’t over, it isn’t over for anyone,” Dr. Nunez-Smith said. “But the reality is, it’s certainly not over in Black America.”The report, called the State of Black America and Covid-19, outlines how disinvestment in health care in Black communities contributed to Black people contracting Covid at higher rates than white people. Black people were then more likely to face serious illness or death as a result.The Black Coalition Against Covid, the Yale School of Medicine and the Morehouse School of Medicine were authors of the report, which also offers recommendations to policy leaders.In the first three months of the pandemic, the average weekly case rate per 100,000 Black Americans was 36.2, compared with 12.5 for white Americans, the authors write. The Black hospitalization rate was 12.6 per 100,000 people, compared with 4 per 100,000 for white people, and the death rate was also higher: 3.6 per 100,000 compared with 1.8 per 100,000.“The severity of Covid-19 among Black Americans was the predictable result of structural and societal realities, not differences in genetic predisposition,” the report says.Black Americans were overrepresented in essential-worker positions, which increased the risk of exposure to the virus, the authors write. And they were also more likely than white Americans to live in multigenerational homes or crowded spaces, be incarcerated, or live in densely populated areas.Many Black Americans who contracted the coronavirus experienced serious illness because of pre-existing conditions like obesity, hypertension and chronic kidney disease, which themselves were often the result of “differential access to high-quality care and health promoting resources,” the report says.The authorization of the first coronavirus vaccines was seen by many experts as a light at the end of the tunnel, but new disparities emerged, driven by both vaccine hesitancy and limited access to the shots.Though the gap in vaccinations has since narrowed — 80 percent of Black Americans were fully vaccinated as of January, compared with 83 percent of white Americans, the report says — disparities persist.“We understand that there remains unfinished work yet to do to save and protect our communities from the Covid-19 pandemic,” wrote Dr. Reed Tuckson, who in April 2020 co-founded the Black Coalition Against Covid.And when it comes to unfinished work, long Covid is top of mind.“So much of even getting a long Covid diagnosis is tied to having had a positive test right at the beginning,” said Dr. Nunez-Smith, adding that early on in the pandemic, many Black Americans “weren’t able to secure a test and in some cases, were denied testing.”She emphasized the importance of investing adequate resources into studying long Covid. “Like everything else, without intentionality, we’re not going to get to equity there,” she said.

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Mariupol Residents Describe How Russian Forces Deprived Them of Food and Water

Residents of Mariupol, Ukraine described how Russian forces use hunger as a weapon of war in a monthlong siege of the southern port. “No roof, no food and no water,” survivors texted relatives who escaped.LVIV, Ukraine — After Russian forces surrounded the city of Mariupol in southern Ukraine, cutting off its water and fuel and preventing aid convoys from entering, Yulia Beley sheltered in a neighbor’s basement with her three daughters and struggled to survive.Her husband was off defending the city, so she ventured out as bombs rained down to fetch water from a distant well and tried to comfort her children while the shelling shook the walls and ceiling. In time, the family’s food dwindled and Ms. Beley, a baker, said she fed her hungry children one bowl of porridge a day to share between them. Her 6-year-old daughter, Ivanka, dreamed of the poppy seed sweet rolls her mother had made before the war.“It tears you apart,” said Ms. Beley, 33, still traumatized after her escape from the city a week ago. “I just sobbed, just cried, screaming into the pillow when no one could see.”Shortly after Russia invaded Ukraine, it laid siege to Mariupol, using the ancient warfare tactic to try to starve the once-bustling city of 430,000 people into surrender.Women pushing mostly empty shopping carts near a damaged block of apartments in Mariupol on March 17. Residents have struggled to find food and water since Russian troops laid siege to the city.Alexander Ermochenko/ReutersFrom the days when armies surrounded medieval castles in Europe to the battle of Stalingrad in World War II and the squeeze put on rebel communities in Syria during the 11-year civil war, militaries have used sieges throughout history regardless of the catastrophic effects on civilians caught in the middle.This month, Secretary of State Anthony J. Blinken accused Russia of “starving” cities in Ukraine. He invoked the memory of the brother of President Vladimir V. Putin of Russia, Viktor, who died in infancy during the German siege of Leningrad during World War II.“It is shameful,” Mr. Blinken said. “The world is saying to Russia: ‘Stop these attacks immediately. Let the food and medicine in. Let the people out safely, and end this war of choice against Ukraine.’”Scholars of siege warfare say the tactic serves different purposes: to weaken enemies while avoiding clashes that can kill the besieging force’s own soldiers, or to freeze active fronts while attacking forces reposition. But the grueling nature of sieges — and how they use hunger to turn people’s own bodies against them — give them a psychological power unique among war tactics, according to scholars and siege survivors.“Siege is a way to break the will and humiliate — and finally to control,” said Mouna Khaity, a health and gender researcher who lived through the Syrian government’s five-year siege of Eastern Ghouta, an area near Damascus.Syrians displaced from Eastern Ghouta, near Damascus, waiting to receive food at a shelter in Horjelli, Syria, in 2018.Hassan Ammar/Associated PressDepriving a residential area of food while bombarding it serves not only to flush out combatants, she said, but to communicate to everyone trapped inside: “You are not an equal human to me. You don’t deserve to eat, drink, have medicine or even breathe!”After they surrounded Mariupol last month, Russian forces cut off the city from everything it needed to live, the mayor, Vadym Boychenko, said on Ukrainian national television. They also destroyed the city’s power plants, cutting off electricity for residents as temperatures froze, Mr. Boychenko said, and then the water and gas, essential for cooking and heating.Some civilians managed to flee, making harrowing journeys through destroyed streets and Russian checkpoints. But about 160,000 people are believed to still be trapped inside the city, Mr. Boychenko said, and more than two dozen buses sent days ago to evacuate them had not been able to enter the city because of Russian shelling.On Monday, the International Committee of the Red Cross said it was ceasing relief operations in Mariupol because the warring parties could not guarantee the safety of aid workers.Residents lined up for hot food in an improvised bomb shelter in Mariupol on March 7.Evgeniy Maloletka/Associated PressAlmost 5,000 people, including about 210 children, have been killed there, the mayor estimated, but the figures could not be confirmed because of the difficulty of getting information.Russian forces are in control of parts of Mariupol, President Volodymyr Zelensky of Ukraine told a group of independent Russian journalists on Sunday. But the center of the city continues to hold, according to Ukrainian and British military assessments.An aide to the mayor, Pyotr Andryuschenko, told The New York Times that an estimated 3,000 Ukrainian fighters from the Azov Battalion were defending the city against about 14,000 Moscow-backed soldiers.When the siege began, one Mariupol resident, Kristina, said she, her husband and two children camped out in the entryway of their building, hoping it would provide better shelter and protection than their apartment.Her husband, a business analyst, ventured out to find water and she cooked on an open fire. They also collected rainwater and snow, boiling the water to sterilize it.An armored convoy of pro-Russian troops filled a road leading to Mariupol on Monday.Alexander Ermochenko/ReutersShe read fairy tales to try to distract the children, but once they got hungry, “the fire was gone from their eyes,” said Kristina, who did not want to use her full name for fear of retribution. “They had no interest in anything.”“We ate once a day,” she said. “It was mostly in the morning or in the evening that the children cried out, saying, ‘I want to eat.’”Her family finally fled the city, but left behind her father and grandparents. She has struggled to keep tabs on them because the city’s phone networks are mostly out.Last week, she said, they sent a text that read: “No roof, no food and no water.”Doctors who study hunger and starvation describe a grim process of the body mining itself to stay alive. First, it burns glucose stored in the liver, then fat, then muscle.Residents passed by a fallen electricity pylon and a destroyed apartment building in Mariupol on March 25.Alexander Ermochenko/ReutersWhile dehydration can call kill in less than a week, a well-nourished adult can survive for more than 70 days on water alone. Children, the elderly and the ill succumb more quickly.Other research has shown that starvation not only weakens the body but disturbs the mind.Nancy Zuker, a professor of psychiatry and behavioral sciences at Duke University, said research done during World War II on 36 male conscientious objectors who ate a low calorie diet modeled on that given to prisoners of war showed they had suffered “significant psychological consequences.”Russia-Ukraine War: Key DevelopmentsCard 1 of 3Ongoing peace talks.

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Once the Children Got Hungry, ‘the Fire Was Gone From Their Eyes’

Residents of Mariupol, Ukraine described how Russian forces use hunger as a weapon of war in a monthlong siege of the southern port. “No roof, no food and no water,” survivors texted relatives who escaped.LVIV, Ukraine — After Russian forces surrounded the city of Mariupol in southern Ukraine, cutting off its water and fuel and preventing aid convoys from entering, Yulia Beley sheltered in a neighbor’s basement with her three daughters and struggled to survive.Her husband was off defending the city, so she ventured out as bombs rained down to fetch water from a distant well and tried to comfort her children while the shelling shook the walls and ceiling. In time, the family’s food dwindled and Ms. Beley, a baker, said she fed her hungry children one bowl of porridge a day to share between them. Her 6-year-old daughter, Ivanka, dreamed of the poppy seed sweet rolls her mother had made before the war.“It tears you apart,” said Ms. Beley, 33, still traumatized after her escape from the city a week ago. “I just sobbed, just cried, screaming into the pillow when no one could see.”Shortly after Russia invaded Ukraine, it laid siege to Mariupol, using the ancient warfare tactic to try to starve the once-bustling city of 430,000 people into surrender.Women pushing mostly empty shopping carts near a damaged block of apartments in Mariupol on March 17. Residents have struggled to find food and water since Russian troops laid siege to the city.Alexander Ermochenko/ReutersFrom the days when armies surrounded medieval castles in Europe to the battle of Stalingrad in World War II and the squeeze put on rebel communities in Syria during the 11-year civil war, militaries have used sieges throughout history regardless of the catastrophic effects on civilians caught in the middle.This month, Secretary of State Anthony J. Blinken accused Russia of “starving” cities in Ukraine. He invoked the memory of the brother of President Vladimir V. Putin of Russia, Viktor, who died in infancy during the German siege of Leningrad during World War II.“It is shameful,” Mr. Blinken said. “The world is saying to Russia: ‘Stop these attacks immediately. Let the food and medicine in. Let the people out safely, and end this war of choice against Ukraine.’”Scholars of siege warfare say the tactic serves different purposes: to weaken enemies while avoiding clashes that can kill the besieging force’s own soldiers, or to freeze active fronts while attacking forces reposition. But the grueling nature of sieges — and how they use hunger to turn people’s own bodies against them — give them a psychological power unique among war tactics, according to scholars and siege survivors.“Siege is a way to break the will and humiliate — and finally to control,” said Mouna Khaity, a health and gender researcher who lived through the Syrian government’s five-year siege of Eastern Ghouta, an area near Damascus.Syrians displaced from Eastern Ghouta, near Damascus, waiting to receive food at a shelter in Horjelli, Syria, in 2018.Hassan Ammar/Associated PressDepriving a residential area of food while bombarding it serves not only to flush out combatants, she said, but to communicate to everyone trapped inside: “You are not an equal human to me. You don’t deserve to eat, drink, have medicine or even breathe!”After they surrounded Mariupol last month, Russian forces cut off the city from everything it needed to live, the mayor, Vadym Boychenko, said on Ukrainian national television. They also destroyed the city’s power plants, cutting off electricity for residents as temperatures froze, Mr. Boychenko said, and then the water and gas, essential for cooking and heating.Some civilians managed to flee, making harrowing journeys through destroyed streets and Russian checkpoints. But about 160,000 people are believed to still be trapped inside the city, Mr. Boychenko said, and more than two dozen buses sent days ago to evacuate them had not been able to enter the city because of Russian shelling.On Monday, the International Committee of the Red Cross said it was ceasing relief operations in Mariupol because the warring parties could not guarantee the safety of aid workers.Residents lined up for hot food in an improvised bomb shelter in Mariupol on March 7.Evgeniy Maloletka/Associated PressAlmost 5,000 people, including about 210 children, have been killed there, the mayor estimated, but the figures could not be confirmed because of the difficulty of getting information.Russian forces are in control of parts of Mariupol, President Volodymyr Zelensky of Ukraine told a group of independent Russian journalists on Sunday. But the center of the city continues to hold, according to Ukrainian and British military assessments.An aide to the mayor, Pyotr Andryuschenko, told The New York Times that an estimated 3,000 Ukrainian fighters from the Azov Battalion were defending the city against about 14,000 Moscow-backed soldiers.When the siege began, one Mariupol resident, Kristina, said she, her husband and two children camped out in the entryway of their building, hoping it would provide better shelter and protection than their apartment.Her husband, a business analyst, ventured out to find water and she cooked on an open fire. They also collected rainwater and snow, boiling the water to sterilize it.An armored convoy of pro-Russian troops filled a road leading to Mariupol on Monday.Alexander Ermochenko/ReutersShe read fairy tales to try to distract the children, but once they got hungry, “the fire was gone from their eyes,” said Kristina, who did not want to use her full name for fear of retribution. “They had no interest in anything.”“We ate once a day,” she said. “It was mostly in the morning or in the evening that the children cried out, saying, ‘I want to eat.’”Her family finally fled the city, but left behind her father and grandparents. She has struggled to keep tabs on them because the city’s phone networks are mostly out.Last week, she said, they sent a text that read: “No roof, no food and no water.”Doctors who study hunger and starvation describe a grim process of the body mining itself to stay alive. First, it burns glucose stored in the liver, then fat, then muscle.Residents passed by a fallen electricity pylon and a destroyed apartment building in Mariupol on March 25.Alexander Ermochenko/ReutersWhile dehydration can call kill in less than a week, a well-nourished adult can survive for more than 70 days on water alone. Children, the elderly and the ill succumb more quickly.Other research has shown that starvation not only weakens the body but disturbs the mind.Nancy Zuker, a professor of psychiatry and behavioral sciences at Duke University, said research done during World War II on 36 male conscientious objectors who ate a low calorie diet modeled on that given to prisoners of war showed they had suffered “significant psychological consequences.”Russia-Ukraine War: Key DevelopmentsCard 1 of 3Ongoing peace talks.

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