Publisher Health

The United States has a dark history of court-sanctioned sterilization, but more recent rulings and legislation suggest it would violate a basic right.Among the stunning assertions that the pop star Britney Spears made to a Los Angeles probate judge this week, as she sought to end her protracted conservatorship, was one that shook experts in guardianship law and reproductive rights deeply. She said a team led by her father, who is her conservator, prevented her from having her IUD removed because the team did not want her to have more children.“Forcing someone to be on birth control against their will is a violation of basic human rights and bodily autonomy, just as forcing someone to become or stay pregnant against their will would be,” said Ruth Dawson, a principal policy associate at the Guttmacher Institute, a research group that supports reproductive rights.Court-condoned compelled contraception is rare in conservatorship. But the specter it raises — forced sterilization — does have a grim, extensive history in the United States, especially against poor women, women of color and inmates. In the early 20th century, the state-sanctioned practice was upheld by the United States Supreme Court.Although the court moved away from that position in the 1940s, and consensus arose through the growing canon on informed consent that forced sterilization was inhumane, the practice continued to be quietly tolerated.Finally, by the end of the 1970s, most states had repealed laws authorizing sterilization, although allegations of forced hysterectomies and tubal ligations on women in immigrant detention centers continue to be raised. It wasn’t until 2014 that California formally banned the sterilization of female inmates without consent.The scant law on the question in conservatorship indicates what an outlier the Spears case may be. In 1985, the California Supreme Court denied the petition of guardian parents of a 29-year-old woman with Down syndrome who wanted her to undergo a tubal libation.Typically, a conservator has temporary control over the finances and even medical care of an incapacitated person. Experts underscored that Ms. Spears’s assertion is unverified. But if it’s accurate, they said, the most likely rationale, however suspect, might be that Jamie Spears, her father, wants to protect her finances from a baby’s father, potentially her boyfriend, who is reportedly at odds with Mr. Spears.If a guardian fears that a ward will make financially unwise choices, “the remedy is not to say they can’t procreate,” said Sylvia Law, a health law scholar at New York University School of Law. “It’s unspeakable.”According to experts in trust and estate law, the handful of cases in which a guardian, usually a parent, has asked a court to order contraception involved severely disabled children.“Such a child would lack the capacity to understand that a penis and vagina could make a baby,” said Bridget J. Crawford, an expert on guardianship law at Pace University law school. “And that certainly is not the Britney Spears case.”Eugenics was a leading rationale for female sterilization. In the 1927 case Buck v. Bell, the Supreme Court upheld the right to sterilize a “feeble-minded” woman who had been committed to a state mental institution, with Justice Oliver Wendell Holmes infamously writing, “Three generations of imbeciles are enough.”Although the opinion was never formally overturned, in a 1942 case, Skinner v. Oklahoma, which challenged forced sterilization of certain convicted criminals, Justice William O. Douglas, writing for a unanimous court, said that the right to procreate was fundamental. “Any experiment the state conducts is to his irreparable injury,” he wrote. “He is forever deprived of a basic liberty.”While Ms. Spears has not been sterilized, Ms. Crawford said, if she is being prevented from getting her IUD removed, that would be a proxy for sterilization, in particular because she testified that she wanted to bear more children.Melissa Murray, who teaches reproductive rights and constitutional law at N.Y.U. law school, pointed to another unnerving element in the allegation by Ms. Spears, who, at 39, has been under her father’s guardianship for 13 years. Ms. Murray said that Ms. Spears, an adult, appeared to be living a legally constructed childhood.“It’s unusual that her father is making the kinds of decisions we’d expect a parent to make for a teenager,” she added.

Early in the COVID-19 pandemic, scientists identified how SARS-CoV-2, the virus that causes COVID-19, gets inside cells to cause infection. All current COVID-19 vaccines and antibody-based therapeutics were designed to disrupt this route into cells, which requires a receptor called ACE2.
Now, researchers at Washington University School of Medicine in St. Louis have found that a single mutation gives SARS-CoV-2 the ability to enter cells through another route — one that does not require ACE2. The ability to use an alternative entry pathway opens up the possibility of evading COVID-19 antibodies or vaccines, but the researchers did not find evidence of such evasion. However, the discovery does show that the virus can change in unexpected ways and find new ways to cause infection. The study is published June 23 in Cell Reports.
“This mutation occurred at one of the spots that changes a lot as the virus circulates in the human population,” said co-senior author Sebla Kutluay, PhD, an assistant professor of molecular microbiology. “Most of the time, alternative receptors and attachment factors simply enhance ACE2-dependent entry. But in this case, we have discovered an alternative way to infect a key cell type — a human lung cell — and that the virus acquired this ability via a mutation that we know arises in the population. This is something we definitely need to know more about.”
The finding was serendipitous. Last year, Kutluay and co-senior author M. Ben Major, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Cell Biology & Physiology, planned to study the molecular changes that occur inside cells infected with SARS-CoV-2. Most researchers study SARS-CoV-2 in primate kidney cells because the virus grows well in them, but Kutluay and Major felt it was important to do the study in lung or other cells similar to the ones that are naturally infected. To find more relevant cells capable of growing SARS-CoV-2, Kutluay and Major screened a panel of 10 lung and head-and-neck cell lines.
“The only one that was able to be infected was the one I had included as a negative control,” Major said. “It was a human lung cancer cell line with no detectable ACE2. So that was a crazy surprise.”
Kutluay, Major and colleagues — including co-first authors and postdoctoral researchers Maritza Puray-Chavez, PhD, and Kyle LaPak, PhD, as well as co-authors Dennis Goldfarb, PhD, an assistant professor of cell biology & physiology and of medicine, and Steven L. Brody, MD, the Dorothy R. and Hubert C. Moog Professor of Pulmonary Diseases in Medicine, and a professor of radiology — discovered that the virus they were using for experiments had picked up a mutation. The virus had originally been obtained from a person in Washington state with COVID-19, but as it was grown over time in the laboratory, it had acquired a mutation that led to a change of a single amino acid at position 484 in the virus’s spike protein. SARS-CoV-2 uses spike to attach to ACE2, and position 484 is a hot spot for mutations. A variety of mutations at the same position have been found in viral variants from people and mice, and in virus grown in the lab. Some of the mutations found in virus samples taken from people are identical to the one Kutluay and Major found in their variant. The Alpha and Beta variants of concern have mutations at position 484, although those mutations are different.
“This position is evolving over time within the human population and in the lab,” Major said. “Given our data and those of others, it is possible that the virus is under selective pressure to get into cells without using ACE2. In so many ways, it is scary to think of the world’s population fighting a virus that is diversifying the mechanisms by which it can infect cells.”
To determine whether the ability to use an alternative entry pathway allowed the virus to escape COVID-19 antibodies or vaccines, the researchers screened panels of antibodies and blood serum with antibodies from people who have been vaccinated for COVID-19 or recovered from COVID-19 infection. There was some variation, but in general, the antibodies and blood sera were effective against the virus with the mutation.
It is not yet clear whether the alternative pathway comes into play under real-world conditions when people are infected with SARS-CoV-2. Before the researchers can begin to address that question, they must find the alternative receptor that the virus is using to get into cells.
“It is possible that the virus uses ACE2 until it runs out of cells with ACE2, and then it switches over to using this alternative pathway,” Kutluay said. “This might have relevance in the body, but without knowing the receptor, we cannot say what the relevance is going to be.”
Major added, “That’s where we’re going right now. What is the receptor? If it’s not ACE2, what is it?”

Muscular dystrophies are a group of genetic diseases that lead to the progressive loss of muscle mass and function in patients, with the incurable Duchenne Muscular Dystrophy (DMD), which affects all the body’s muscles primarily in boys, being particularly severe. DMD can be caused by more than 7,000 unique mutations in the largest gene of the human genome, which encodes a central protein in muscle fibers. While this astounding number of mutations all variably block muscle function, the affected muscles share another common feature — chronic inflammation.
As chronic inflammation significantly contributes to the speed and severity of muscle degeneration, researchers are pursuing different anti-inflammatory approaches that could be applied to the weakening muscles of DMD patients. Thus far, it has become clear that broad, systemically applied anti-inflammatory therapies cannot reach sufficient efficacies in individual muscles and that, in addition, they can be toxic to patients and increase their risk of infections. To overcome these barriers, locally acting therapies that could be applied on-site at affected muscles would have significant advantages.
Now, a research team at Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) led by Wyss Institute Founding Core Faculty member David Mooney, Ph.D., has developed a new approach in which specifically designed anti-inflammatory nanoparticles (NPs) that could be applied locally and selectively to chronically inflamed muscles severely affected or at more immediate risk of deterioration, and maybe difficult to reach with oral therapeutics. In an advanced mouse model of DMD, this strategy increased the volume of muscles covered by myofibers and improved muscle functions by boosting the numbers of infiltrating anti-inflammatory regulatory T cells (Tregs). The findings are published in Science Advances.
A biomaterial-based solution: design and validation
“Using NP-based cytokine delivery, we can create a therapeutic immune status in muscles affected by DMD that targets inflammation as a universal driver of the disease,” said Mooney, who leads the Wyss Institute’s Immuno-Materials Platform and is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS. “Given the localized delivery of the highly effective cytokine interleukin-4 (IL-4), this approach could be developed as a stand-alone therapy, or in the future be used in combination with genetic approaches designed to repair specific DMD mutations in patients.”
Pro-inflammatory and anti-inflammatory immune cells recruited to wasting muscles and further differentiating in them are thought to play an active game of tug-of-war. Both can temporarily get the upper hand with muscles going through continuous cycles of myofiber injury and regeneration while, in the longer-term, injury always wins. Importantly, the identities and activities of immune cells are controlled by pro- and anti-inflammatory cytokines, immune-modulating molecules that are released by immune or other cells in muscle tissue.

Parents of children with the most complex medical conditions are more likely to report poor or fair mental health and struggle to find community help, according to a study completed by researchers at University of Rochester Medical Center (URMC) and Golisano Children’s Hospital. The study was published in Pediatrics, the journal of the American Academy of Pediatrics (AAP).
The study, “A National Mental Health Profile of Parents of Children with Medical Complexity,” examined parent-reported data from the National Survey of Children’s Health, and compared three groups: households of children with medical complexity (CMC), households of noncomplex children with special health care needs, and households of children without special health care needs.
CMC are defined as the 1 percent of children with the most complex medical conditions. They tend to have multiple chronic health conditions and disabilities, and frequently utilize health care services. Examples of CMC include those with cerebral palsy, serious congenital heart defects, or genetic disorders. Given these children’s significant needs, their caregivers are challenged to balance treating their child with completing other family responsibilities.
The study found the following:
-About 20 percent of parents of CMC reported poor or fair mental health, more than 5 times the proportion of parents of children who did not have medical problems.
-In addition, 36 percent of parents of CMC reported not knowing where to go for help in their community when they encounter difficulties, which was more than 2 times the proportion of parents of children who did not have medical problems.

A new study could lead to improved decision making in assigning treatments for children with the aggressive cancer rhabdomyosarcoma after revealing key genetic changes underlying development of the disease.
In the largest and most comprehensive study of rhabdomyosarcoma to date, scientists found that specific genetic changes in tumours are linked to aggressiveness, early age of onset and location in the body.
All these factors affect the chances that children will survive their disease — and understanding how they are driven by a cancer’s genetics could lead to new ways of tailoring treatment for each patient.
Rhabdomyosarcoma is a rare type of cancer that resembles muscle tissue and mostly affects children. Less than 30 per cent of children with rhabdomyosarcoma who have relapsed or whose cancer has spread will survive.
The new international study, led by researchers at The Institute of Cancer Research, London, could help pick out children with particularly aggressive cancers in need of intense treatment and close monitoring. It could also identify other children who could benefit from less aggressive therapy and could be spared some of the most severe side effects of treatment.
The researchers are already planning to incorporate the new insights into the design of upcoming clinical trials aiming to improve the management of the disease.

New research from the University of California, Santa Cruz shows how regional shelter-in-place orders during the coronavirus pandemic emboldened local pumas to use habitats they would normally avoid out of fear of humans. This study, published in the journal Current Biology, is part of a growing wave of research working to formally document the types of unusual changes to wildlife movements and behaviors that people around the world reported during pandemic lockdowns.
Golden jackals, for example, were spotted foraging in broad daylight in urban Tel Aviv, Israel, and mountain lions were seen strolling through downtown Santiago, Chile. Urban environments had suddenly become quiet and empty as shelter-in-place orders brought human movement to a grinding halt — an effect some researchers have called the “anthropause.” Wildlife seemed to be taking advantage. The new study shows this was certainly true for pumas in the Santa Cruz Mountains. Researchers were able to clearly connect changes in the cats’ habitat use with reduced human mobility during shelter-in-place orders.
Chris Wilmers, an environmental studies professor at UC Santa Cruz, led this research. Wilmers is the principal investigator for the Santa Cruz Puma Project, and he has been studying local mountain lion populations for over a decade. In particular, his research uses data from GPS tracking collars placed on wild pumas to show how fear of humans affects mountain lion behavior and ecology. When the pandemic hit, his team was already tracking data from several collared cats, and he recognized a unique research opportunity.
“When the shelter-in-place orders started, it was immediately clear that things were very different,” Wilmers said. “You’d go outside and there were very few cars. Entire neighborhoods were completely quiet. So we wondered how this might affect the mountain lion population. Would they respond this quickly to reduced human presence?”
To answer that question, the team analyzed about two years worth of mountain lion tracking data for a set of six collared cats to see where the pumas roamed and what types of habitats they used. Researchers compared these tracks with the distribution of housing density and the geographic boundaries of the “urban edge,” which indicates where vehicle and pedestrian traffic is heightened. During regional shelter-in-place orders, they found that cats were significantly more likely to move into or closer to the urban edge. And these changes happened rapidly: within days or weeks of the beginning of COVID-19 lockdowns.
In an effort to hone in on the cause of this change, the team ruled out any influence of natural factors — like topography, vegetation cover, or distance to the nearest water source — that might affect the cats’ choice of habitats. They also compared year-over-year tracking data to show that seasonal variability wasn’t affecting the results. Pumas do have a strong preference for habitats with lower housing density, but this factor did not change significantly during the study period. The key difference that appeared to be driving the trend of mountain lions moving into urban areas was reduced human mobility during the pandemic.
After regional shelter-in-place orders went into effect on March 17, 2020, local human mobility declined more than 50 percent, according to Apple mobility data, which show the number of navigation requests for driving and walking trips received through Apple Maps. During this time period, when people confined themselves in their homes, the data showed a strong relationship between declining levels of human mobility and pumas’ increased willingness to venture closer to or into urban areas.
“We found that they totally relaxed their fear of the urban edge,” Wilmers said. “It’s not that they weren’t scared of cities; they were still scared, but only of high housing density, not the extra impact of human mobility. If you take all the car trips and pedestrian trips and human mobility out of it, then, all of a sudden, mountain lions don’t fear the city as much.”
Wilmers says this finding helps to build understanding of the unique impacts of human mobility on wildlife. Conservation efforts often focus on the ways that humans are destroying habitats — through development and pollution, for example — but the mere presence of people moving across a landscape also takes a toll on animals that fear humans. And this too is a conservation challenge.
“It’s important because our mobility just keeps increasing,” Wilmers explained. “In the early part of the 20th century, we got cars, and that really increased our mobility. Now we have things like ride-sharing apps, mountain bikes, and electric bikes, and these are all ways that we’re becoming more and more mobile across more types of landscapes. It’s an important thing to think about as we try to conserve and manage ecosystems.”
Another key point this research illustrates is that fear, or the removal of a source of fear, can bring about rapid changes in animal behavior that ripple out through ecosystems. Ecologists call this concept the “landscape of fear.” And the pandemic showed just how integrated into this landscape humans really are. People are usually the ones exerting the influence of fear upon other animals, but there are some things that even we fear.
“Humans have always been the top dog in landscapes of fear, but this study shows that those influences of humans can be reversed relatively quickly by a pathogen, particularly a pandemic-causing pathogen,” Wilmers said. “It’s interesting from a theoretical perspective, and it’s also important in a practical sense because it shows that, not only are pandemics going to have major health consequences for people, but there are also going to be important ecological impacts.”

The body’s immune cells naturally fight off viral and bacterial microbes and other invaders, but they can also be reprogrammed or “trained” to respond even more aggressively and potently to such threats, report UCLA scientists who have discovered the fundamental rule underlying this process in a particular class of cells.
In a study published June 18 in the journal Science, the researchers identified a key molecular mechanism within macrophages, infection-fighting cells of the innate immune system, that determines whether — and how well — the cells can be trained. Their findings could help pave the way for future targeted strategies to enhance the function of the immune system.
“Like a soldier or an athlete, innate immune cells can be trained by past experiences to become better at fighting infections,” said lead author Quen Cheng, an assistant clinical professor of infectious diseases at UCLA’s David Geffen School of Medicine. However, he noted, the researchers had previously observed that some experiences seemed to be better than others for immune training. “This surprising finding motivated us to better understand the rules that govern this process.”
Whether immune training occurs depends on how the DNA of the cell is wrapped. In human cells, for instance, more than 6 feet of DNA must fit into the cell’s nucleus, which is so small that it is not visible to the naked eye. To achieve this feat, the DNA is tightly wrapped into chromosomes.
Only selected regions of the DNA are exposed and accessible, and only the genes in those accessible regions are able to respond and fight infection, said senior author Alexander Hoffmann, UCLA’s Thomas M. Asher Professor of Microbiology and director of the Institute for Quantitative and Computational Biosciences.
However, by introducing a stimulus to a macrophage — for example, a substance derived from a microbe or pathogen, as in the case of a vaccine — previously compacted DNA regions can be unwrapped. This unwrapping exposes new genes that will enable the cell to respond more aggressively, in essence training it to fight the next infection, Hoffmann said.

When most Americans think of seaweed, they probably conjure images of a slimy plant they encounter at the beach. But seaweed can be a nutritious food too. A pair of UConn researchers recently discovered Connecticut-grown sugar kelp may help prevent weight gain and the onset of conditions associated with obesity.
In a paper published in the Journal of Nutritional Biochemistry by College of Agriculture, Health, and Natural Resources faculty Young-Ki Park, assistant research professor in the Department of Nutritional Sciences, and Ji-Young Lee, professor and head of the Department of Nutritional Sciences, the researchers reported significant findings supporting the nutritional benefits of Connecticut-grown sugar kelp. They found brown sugar kelp (Saccharina latissima) inhibits hepatic inflammation and fibrosis in a mouse model of diet-induced non-alcoholic steatohepatitis, a fatty liver disease.
They studied the differences between three groups of mouse models. They placed two on high-fat diets but incorporated sugar kelp, a kind of seaweed, into the diet of one. The third group was on a low-fat diet as a healthy control. The group that ate sugar kelp had lower body weight and less adipose tissue inflammation — a key factor in a host of obesity-related diseases — than the other high-fat group.
Consuming sugar kelp also helped prevent the development of steatosis, the accumulation of fat in the liver. Nonalcoholic steatohepatitis (NASH) is a condition often associated with obesity that can cause inflammation and reduced functionality in the liver.
The mice on the sugar kelp diet also had healthier gut microbiomes. The microbiome is a collection of bacteria and other microorganisms in and on our bodies. The diversity and composition of the microbiome are key to maintaining a host of health functions.
“I wasn’t surprised to see the data, as we know seaweeds are healthy,” Lee says. “But it’s still pretty amazing data as this is the first scientific evidence for health benefits of the Connecticut-grown sugar kelp.”
This study is the first time researchers have looked at the link between the US-grown sugar kelp and obesity.

Scientists from Helmholtz Zentrum München revise the current textbook knowledge about gastrulation, the formation of the basic body plan during embryonic development. Their study in mice has implications for cell replacement strategies and cancer research.
Gastrulation is the formation of the three principal germ layers — endoderm, mesoderm and ectoderm. Understanding the formation of the basic body plan is not only important to reveal how the fertilized egg gives rise to an adult organism, but also how congenital diseases arise. In addition, gastrulation serves as the basis to understand processes during embryonic development called epithelial-to-mesenchymal transition which is known to lead to cancer metastasis in adulthood when dysregulated.
“The famous biologist Lewis Wolpert once said that it is not birth, marriage or death, but gastrulation which is truly the most important time of our life. However, there are many things we still don’t know about this phenomenon,” says study leader Heiko Lickert.
In a new study, researchers could show that the formation of the endoderm germ layer is driven by a different mechanism than it has been assumed for a long time. In contrast to the mesoderm, which undergoes an epithelial-to-mesenchymal transition, the endoderm forms independent of this process. The researchers revealed that its formation is regulated by mechanisms of epithelial cell plasticity that allows cells to leave an epithelium and migrate away. During this process, a gene regulatory protein shields the endoderm from undergoing a mesenchymal transition.
A better understanding of endoderm formation has the potential to advance cell replacement therapy (by improving stem cell differentiation into endoderm in vitro). Moreover, epithelial cell plasticity might be an alternative mechanism of cancer cell metastasis and further studies could identify novel targets for therapeutic intervention.
“Our study has not only revealed further details of germ layer formation, but also has broader implications for stem cell differentiation and cancer metastasis of the most common and deadliest cancers worldwide,” explains first author Katharina Scheibner.
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Materials provided by Helmholtz Zentrum München – German Research Center for Environmental Health. Note: Content may be edited for style and length.

The brain’s neurons tend to get most of the scientific attention, but a set of cells around them called astrocytes — literally, star-shaped cells — are increasingly being viewed as crucial players in guiding a brain to become properly organized.
Specifically, astrocytes, which form about half the mass of a human brain, seem to guide the formation of synapses, the connections between neurons that are formed and remodeled as we learn and remember.
A new study from Duke and UNC scientists has discovered a crucial protein involved in the communication and coordination between astrocytes as they build synapses. Lacking this molecule, called hepaCAM, astrocytes aren’t as sticky as they should be, and tend to stick to themselves rather than forming connections with their fellow astrocytes.
This finding, in studies on mice with the gene for hepaCAM knocked out of their astrocytes, is an important clue in efforts to understand several brain disorders, including cognitive decline, epilepsy and autism spectrum disorders. The work appears June 24 in the journal Neuron.
A rare disorder called megalencephalic leukoencephalopathy (MLC) is also known to be caused by a mutation in the hepaCAM gene, and this work might provide answers about what exactly has gone wrong. MLC is a developmental disorder that grows progressively worse, causing macrocephaly (a large head), swelling of the brain’s white matter, intellectual disability and epilepsy.
By removing hepaCAM selectively from astrocytes to see what it does, “we sort of made the cells into introverts,” said senior author Cagla Eroglu, an associate professor of cell biology at the Duke University School of Medicine. “They’re normally wanting to reach out, but without hepaCAM, they started to hug themselves instead.”
“If the astrocyte makes junctions to its neighbors, then you start to have a network,” Eroglu said. “To make a functional brain, you need a functional astrocytic network.”
The researchers zeroed in on hepaCAM by looking for genes that are highly active in astrocytes and which have been implicated in brain dysfunction. They partnered with another group working on hepaCAM at the University of Barcelona, but that group has been looking at the molecule for its role in regulating chloride signaling channels in astrocytes.
The Duke group found that removing hepaCAM from astrocytes led to a synaptic network that was too easily excited and not as well dampened. “The effect on the inhibitory synapses was the strongest,” said first author Katie Baldwin, who recently became an assistant professor of cell biology and physiology at the University of North Carolina at Chapel Hill. “You’re putting the inhibition down and the excitation up, so that really could point to a mechanism for epilepsy.”
Baldwin, who did this work as a postdoctoral researcher in Eroglu’s lab, is planning to further pursue these questions in her new lab at UNC, testing whether hepaCAM-deficient mice behave differently or have changes in learning and memory, or whether they exhibit the stress and social anxiety that are markers of autism spectrum disorders. She said they might also reintroduce the disease-mutation versions of the protein to mice that were born without it to see what effects it has.
“We know hepaCAM is interacting with itself between two astrocytes, but we don’t know what it’s interacting with at the synapse,” Baldwin said. “We don’t know if it could be interacting with hepaCAM which is also found in the neurons, or if it could be some other protein that we don’t know about yet.”
This research was supported by the U.S. National Institutes of Health (R01DA047258, R01NS102237, F32 NS100392), Foerster-Bernstein Family, The Hartwell Foundation, and the European Research Council (725780 LinPro).
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Materials provided by Duke University. Original written by Karl Leif Bates. Note: Content may be edited for style and length.