Publisher Health

A new miniature 3D model of human bone marrow has been described today in the open-access eLife journal.
The model may help clinicians predict which patients will benefit from a new therapy for blood platelet disorders, such as Inherited Thrombocytopenias — a group of familial disorders that inhibit the production of platelets. It could also enable further study of these disorders and give scientists a new tool to test experimental treatments.
Platelets are cells that are necessary for the blood to clot and stop bleeding. Having too few platelets can lead to internal or serious bleeding after surgery or injuries, which is usually treated with therapies that cause clotting. Recent studies have shown that a drug called Eltrombopag increases the production of platelets, but not all patients appear to benefit from it. “Patients with the same apparent form of platelet disorder may respond differently to treatment with Eltrombopag,” says first author Christian Di Buduo, Research Assistant Professor at the Department of Molecular Medicine, University of Pavia, Italy.
To help determine which patients might benefit from the drug, Di Buduo and colleagues developed a mini 3D model of human bone marrow that combines a scaffolding of silk protein and culture of patient-derived cells to recreate the human bone marrow environment where platelets are produced. “This device is a significant improvement over previous models, requiring only a very small sample of blood to recreate platelet production,” Di Buduo explains.
The team then tested what happened when they added Eltrombopag to a blood sample from a patient with a platelet disorder that had previously been treated with the drug. Their results showed that the number of platelets produced in the model corresponded to how each patient had responded to treatment with Eltrombopag. The increase in the number of platelets collected from the model was comparable to the increase in the number of platelets in patients’ blood following treatment.
The authors say the model could eventually lead to personalised treatment for platelet disorders by helping clinicians match patients to the best treatment.
“This easy-to-reproduce system may also help scientists better understand what goes wrong in these disorders and how treatments work, as well as provide them with a new tool for testing new drugs that may lead to improved therapies in the future,” concludes senior author Alessandra Balduini, Principal Investigator and Professor at the University of Pavia.
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Research by scientists from University of Southampton (UK) and the Central University of Jharkhand (India) and has shown the first COVID-19 lockdown in India led to an improvement in air quality and a reduction in land surface temperature in major urban areas across the country.
The study found that travel and work restrictions imposed early in the pandemic resulted in a significant environmental improvement, due to an abrupt reduction in industrial activities and a major decrease in the use of land and air transport.
The international team used data from a range of Earth Observation sensors, including those from the European Space Agency’s Sentinel-5p and NASA’s MODIS sensors, to measure changes in surface temperature and atmospheric pollutants and aerosols. They concentrated on six major urban areas: Delhi, Mumbai, Kolkata, Chennai, Bangalore, and Hyderabad — comparing data from the 2020 March to May lockdown with pre-pandemic years.
Their findings, published in the journal Environmental Research, provide a strong evidence base for potential environmental benefits through larger scale policy implementation.
The researchers revealed a significant reduction in Nitrogen Dioxide (NO2), a greenhouse gas emitted from the combustion of fossil fuels, which equated to an average decrease of 12 percent throughout India and 31.5 percent over the six cities. There was a 40 percent reduction over the national capital, New Delhi. In India alone, about 16,000 premature deaths occur annually due to exposure to poor air quality.
The study also found Land Surface Temperature (LST) over major cities in India substantially declined in contrast with the previous five-year average (2015-2019) with day temperatures being up to 1°C cooler and those at night up to 2°C cooler.
Co- author Professor Jadu Dash, from University of Southampton, commented: “The lockdown provided a natural experiment to understand the coupling between urbanisation and local microclimate. We clearly observed that reduction in atmospheric pollutants (due to reduction in anthropogenic activity during lockdown) resulted in a decrease in local day and night-time temperature. This is an important finding to feed into the planning for sustainable urban development.”
Along with surface temperature, the atmospheric fluxes at the surface and top of the atmosphere also significantly declined over major parts of India. The reduction of greenhouse gas concentration, higher atmospheric water vapour content and meteorological conditions played a complex role in the land and near-surface temperature reduction.
Commenting on the research, Dr Bikash Parida, from Central University of Jharkhand said: “Aerosol optical depth (AOD) and absorption AOD showed a significant reduction which could be connected with the reduction in the emission sources across India during the lockdown. The aerosol type sources, such as organic carbon (OC), black carbon (BC), mineral dust, and sea salt also reduced significantly. Moreover, in central India, increases in AOD were attributed to the supply of dust aerosols transported from the western Thar desert region.”
Dr Gareth Roberts from the University of Southampton added: “Satellite instruments play a vital role in acquiring information on the Earth’s environment in a timely manner. This study has illustrated the importance of Earth Observation data for monitoring changes in the atmospheric pollutants, which are significant health risk, and in highlighting the impact that anthropogenic activities have on regional air quality.”
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A new discovery in Ewing sarcoma, an aggressive and often fatal childhood cancer, has uncovered the potential to prevent cancer cells from spreading beyond their primary tumour site.
The breakthrough provides new insight into what triggers the process that allows cancer cells to survive while traveling through the body in the bloodstream.
Researchers with the University of British Columbia and BC Cancer have learned that Ewing sarcoma cells — and likely other types of cancer cells — are able to develop a shield that protects them from the harsh environment of the bloodstream and other locations as they search for a new place to settle, or metastasize. The study has just been published in Cancer Discovery.
“You might think that a tumour cell could readily survive in the bloodstream, but it’s actually a very harsh environment,” said the study’s senior author Dr. Poul Sorensen, a distinguished scientist at BC Cancer, professor of pathology and laboratory medicine and director of the faculty of medicine’s newly-created Academy of Translational Medicine at the University of British Columbia.
“What we found was that Ewing sarcoma cells are able to develop an antioxidant response that shields them and allows them to survive as they circulate,” said Dr. Sorensen. “This is similar to a person in the Arctic having to put a thick coat on before they go outside. If they don’t shield themselves, they are exposed to dangerously harsh conditions under which they may not survive.”
Metastatic disease, which occurs when cancer has spread throughout the body, is the single most powerful predictor of poor outcome for cancer patients of all ages and has been a difficult process for researchers to study or for clinicians to target.

A research team led by scientists at Université de Montréal has developed a unique observational tool for assessing children up to 5 years of age who have had a concussion. The work is explained in a study published in the Journal of Head Trauma Rehabilitation.
Pediatric traumatic brain injury (TBI) is particularly prevalent in toddlers; they’re more likely to be injured because they have a lower sense of danger and are still developing physically. But parents and clinicians have trouble detecting symptoms of trauma, given the toddler’s limited verbal skills.
“A young child will not tell you that they have a headache or feel dizzy,” said Dominique Dupont, an UdeM postdoctoral student in neuropsychology and first author of the study.
“But assessing post-concussion symptoms is the cornerstone for patient management and follow-up,” she added. “Without documentation, it’s difficult to know whether they’re doing well or not.”
To address the lack of assessment tools for this age group, UdeM neuropsychology professor Miriam Beauchamp, who conducts research at the UdeM-affiliated CHU Sainte-Justine children’s hospital, designed a new observational tool that allows parents and clinicians to assess the child’s health status.
Can be damaging
Traditionally, it was suggested that TBI in early childhood did not have significant adverse effects, because the high plasticity of the brain at this time of life allowed for rapid recovery.

An odor-based test that sniffs out vapors emanating from blood samples was able to distinguish between benign and pancreatic and ovarian cancer cells with up to 95 percent accuracy, according to a new study from researchers at the University of Pennsylvania and Penn’s Perelman School of Medicine.
The findings suggest that the Penn-developed tool — which uses artificial intelligence and machine learning to decipher the mixture of volatile organic compounds (VOCs) emitting off cells in blood plasma samples — could serve as a non-invasive approach to screen for harder-to-detect cancers, such as pancreatic and ovarian.
The results will be presented at the annual American Society of Clinical Oncology meeting on June 4 by A. T. Charlie Johnson, PhD, the Rebecca W. Bushnell Professor of Physics and Astronomy in Penn’s School of Arts & Sciences (Abstract # 5544).
“It’s an early study but the results are very promising,” Johnson said. “The data shows we can identify these tumors at both advanced and the earliest stages, which is exciting. If developed appropriately for the clinical setting, this could potentially be a test that’s done on a standard blood draw that may be part of your annual physical.”
Co-authors include Erica L. Carpenter, PhD, director of the Circulating Tumor Material Laboratory and research assistant professor in the Perelman School of Medicine, Janos Tanyi, MD, PhD, an assistant professor of Obstetrics and Gynecology, and Cynthia Otto, DVM, PhD, director of the Working Dog Center and professor at Penn’s School of Veterinary Medicine (Penn Vet). The late George Preti, PhD, of the Monell Chemical Senses Center, is also co-author.
The Penn research team is currently working with VOC Health to commercialize the device, along with others, for research and clinical applications.
The electronic olfaction — “e-nose” — system is equipped with nanosensors calibrated to detect the composition of VOCs, which all cells emanate. Previous studies from the researchers demonstrated that VOCs released from tissue and plasma from ovarian cancer patients are distinct from those released from samples of patients with benign tumors.
Among 93 patients, including 20 patients with ovarian cancer, 20 with benign ovarian tumors and 20 age-matched controls with no cancer, as well as 13 patients with pancreatic cancer, 10 patients with benign pancreatic disease, and 10 controls, the vapor sensors discriminated the VOCs from ovarian cancer with 95 percent accuracy and pancreatic cancer with 90 percent accuracy. The tool also correctly identified all patients (a total of eight) with early-stage cancers.
The technology’s pattern recognition approach is similar to the way people’s own sense of smell works, where a distinct mixture of compounds tells the brain what it’s smelling. The tool was trained and tested to identify the VOC patterns more associated with cancer cells and those associated with cells from healthy blood samples in 20 minutes or less.
The team’s collaboration with Richard Postrel, CEO and chief innovation officer of VOC Health, has also led to an improvement in detection speed by 20 fold.
“Collaborating with researchers from the department of Physics and Astronomy, the Perelman School of Medicine, and Penn Vet has allowed us to perfect and integrate our own innovations — expediting the commercialization process,” Postrel said. “Initial prototypes of commercial devices able to detect cancer from liquids and vapors will be ready soon and be provided to these Penn researchers to further their work.”
In a related effort with VOC Health, Johnson, along with his co-investigator Benjamin Abella, MD, MPhil, a professor of Emergency Medicine, were awarded a two-year, $2 million grant by the National Institutes of Health National Center for Advancing Translational Sciences for the development of a handheld device that can detect the signature “odor” of people with COVID-19, which is based off the cancer-detection technology applied in this study.

ALS is a very severe neurodegenerative disease in which nerve cells in the spinal cord controlling muscles and movement slowly die. There is no effective treatment and the average life expectancy after being diagnosed with ALS is usually short. Because of this, new knowledge about the disease is urgently needed.
Now, researchers from the University of Copenhagen have gained new insights about ALS, by investigating the early development of the disease in a mouse model.
“We have found that networks of nerve cells in the spinal cord called inhibitory interneurons lose connection to motor neurons, the nerve cells that directly control muscle contraction. We do not yet know if these changes cause the disease. But the loss of the inhibitory signal could explain why the motor neurons end up dying in ALS,” says first and co-corresponding author to the new study Ilary Allodi, Assistant Professor at the Department of Neuroscience.
A lot of ALS research have focused on the motor neurons themselves, but the research group at the University of Copenhagen had a different approach.
“It is only natural that motor neurons have received major attention. They control our muscles, which is the challenge for ALS patients. Here, we wanted to investigate the circuit of interneurons in the spinal cord because they determine the activity of motor neurons. Since we found that there is a loss of connections between inhibitory interneurons and motor neurons that happens before the motor neuron death, we think that this loss could be a possible explanation for why the motor neurons ends up dying in ALS patients,” says Ole Kiehn, senior, co-corresponding author and Professor at the Department of Neuroscience.
Fast-twitch first
In ALS patients, the degeneration typically starts with what is called the fast-twitch motor neurons and then goes on to other motor neurons. This means that certain muscles and bodily functions are affected before others. Normally, patients lose coordination and speed in movement before more basic functions such as breathing. This is mirrored in the new findings, according to the researchers.

Moderna on Tuesday became the next pharmaceutical company to apply to the U.S. Food and Drug Administration for full approval for its coronavirus vaccine for use in people 18 and older.Last month Pfizer and BioNTech applied to the agency for full approval of their vaccines for use in people 16 and older.“We look forward to working with the F.D.A. and will continue to submit data from our Phase 3 study and complete the rolling submission,” Stéphane Bancel, Moderna’s chief executive, said in a statement.Moderna’s vaccine was authorized for emergency use in December, and as of Sunday, more than 151 million doses had already been administered in the U.S., according to data from the Centers for Disease Control and Prevention.Moderna announced last week that its vaccine appeared to be highly effective in teenagers and that it planned to apply for emergency use authorization for adolescents in June. Pfizer’s vaccine was authorized for use in 12- to 15-year-olds last month.Both the Moderna and Pfizer vaccines require two shots spaced several weeks apart, and are built around messenger RNA, the genetic material that cells read to make proteins, to help generate antibodies to the virus.Full approval for each of the vaccines would allow the companies to market them directly to consumers and could make it easier for schools, employers and government agencies to require them. It could also encourage the U.S. military, which has had low uptake of vaccines, to mandate vaccinations for service members.Approval could also help raise public confidence in another vaccine, after the pace of vaccinations has dropped sharply since mid-April.A recent poll from the Kaiser Family Foundation showed signs that some hesitant people have been persuaded: About a third of people who had planned to “wait and see” whether they would get vaccinated said that they had made vaccine appointments or planned to do so.“I think there are many people who were on the fence, who were worried about things moving too rapidly and about possible side effects,” said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases and a vaccine expert. “But those concerns are being allayed as they see more of their friends and acquaintances celebrating getting vaccinated.”Jan Hoffman contributed reporting.

Women carrying human papillomavirus (HPV) run an elevated risk of preterm birth, a University of Gothenburg study shows. A connection can thus be seen between the virus itself and the risk for preterm birth that previously has been observed in pregnant women who have undergone treatment for abnormal cell changes due to HPV.
A Swedish study now published in the high-ranking journal PLOS Medicine comprises data on more than a million births. Accordingly, the researchers have compared very large groups. They emphasize that the findings do not support any assessment of risk levels in individual women of childbearing age.
Johanna Wiik, a PhD student in obstetrics and gynecology at Sahlgrenska Academy, University of Gothenburg, and also a gynecologist and obstetrician at the Department of obstetrics and gynecology at Sahlgrenska University Hospital, is the first author of the study.
“I would like to point out that the increase in risk for preterm birth is small for the individual woman carrying HPV. But our results support that young people should get into the vaccination program against HPV,” she says. Vaccination against HPV might not only prevent HPV related cancer but also be beneficial for pregnancy outcome.
Treatment for abnormal cervical cell changes due to HPV infection had previously been known to increase risk of preterm birth — defined as birth before 37 weeks’ gestation. The present study shows that HPV as such is linked to a raised risk of preterm birth, and of complications for the child.
The study is based on birth particulars registered in the Swedish Medical Birth Register, which have been merged with the country’s National Quality Registry for Cervical Cancer Prevention and the Swedish Cancer Register. Altogether, 1,044,023 births between 1999 and 2016 were included. Of the women concerned, 23,185 had previously received treatment, while 11,727 were untreated and had a positive HPV screening test immediately before or during their pregnancy.
Of the women previously treated for CIN, 9.1 percent gave birth prematurely. The corresponding proportion in the group with HPV infection in conjunction with their pregnancies was 5.9 percent. This was a statistically significant increase compared with a reference group of women whose cervical screening test had always been normal, of whom 4.6 percent gave birth prematurely.
Verena Sengpiel, Associate Professor of Obstetrics and Gynecology at Sahlgrenska Academy and obstetrician at Sahlgrenska University Hospital, is the study’s last author.
“Our study is register-based and, although we’ve adjusted for various factors in the analyses, we can’t reliably answer the question of whether it’s the virus itself that causes the pregnancy and childbirth complications. All we can do is show a statistical association,” she says.
“Soon we”ll be able to see how the incidence of preterm birth is affected after the vaccination program against HPV has been introduced. That will give us more information about whether there’s a causal connection between HPV infection itself and delivery outcome.”
The researchers emphasize the importance of heeding calls for gynecological cell sampling, in order to detect any cervical cell changes due to HPV infection. Johanna Wiik again:
“The earlier these abnormal cell changes are detected, the better we can follow and treat them. And when you’re admitted to maternity care, it’s a good idea to tell your midwife if you’ve had cervical cell changes, and whether you’ve been treated for them. Then the maternity health staff can take that information into account when planning the monitoring of your pregnancy.”
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The genetic material of most organisms is carried by DNA, a complex organic molecule. DNA is very long — for humans, the molecule is estimated to be about 2 m in length. In cells, DNA occurs in a densely packed form, with strands of the molecule coiled up in a complicated but efficient space-filling way. A key role in DNA’s compactification is played by histones, structural-support proteins around which a part of a DNA molecule can wrap. The DNA-histone wrapping process is reversible — the two molecules can unwrap and rewrap — but little is known about the mechanisms at play. Now, by applying high-speed atomic-force microscopy (HS-AFM), Richard Wong and colleagues from Kanazawa University (NanoLSI WPI) provide valuable insights into the spatiotemporal dynamics of DNA-histone interactions.
The researchers looked at the interaction between DNA and a histone called H2A, one of the five main histones. To check the applicability of HS-AFM as a viable tool for imaging the DNA-histone interaction, they first focused on H2A in its native state. Wong and colleagues were able to image the topology of the molecule, and how it changes over time. Importantly, they showed that the HS-AFM process, during which a tapping force is constantly exerted on the molecule, does not lead to conformational changes or actual damage.
For real-time observation of the DNA-H2A interaction with HS-AFM, the scientists prepared DNA samples with different lengths and forms: plasmid (long and circular), long-linearized and short-linearized DNA, with the latter having the highest motility. The experiments showed that the choice of substrate on which to put the DNA for AFM imaging is crucial; a particular type of lipid layer was found to be good as it does not strongly absorb DNA strands.
The observations of the interaction of H2A with short-linearized DNA, which the researchers nicknamed ‘inchworm DNA’, led to the most notable results. Specifically, four different interaction situations could be distinguished: touching, sliding, sandwiching and wrapping, with the associated motions indeed resembling the movements of inchworms.
Wong and colleagues also investigated the effect of ionic strength on the DNA-histone binding affinity, by changing the salt concentration of the liquid containing the DNA-histone aggregate. When increasing the liquid’s salinity, the aggregate was found to dissolve. When diluting the liquid again — and so reducing the salt content — the aggregate reformed. This result shows that varying the ionic strength (i.e., the salt concentration) of the environment of the DNA-H2A complex provides a way to mimic the variations in the strength of DNA-histone interactions as they happen in living organisms.
The report of Wong and colleagues represents the first real-time observation of DNA-histone interactions, and convincingly shows the applicability of HS-AFM for studying this kind of biological process, also in the context of diseases. Quoting the researchers: “[Our work] demonstrates … the potential to study protein aggregation and protein-nucleic acid aggregate formation in various human diseases.”
Finally, it is worth highlighting the contribution of the paper’s first author, Goro Nishide, who is a pre-doctoral student at the Division of Nano Life Science in the Graduate School of Frontier Science Initiative at Kanazawa University. Mr Nishide played a key role in the reported research, supervised by Professor Wong and Dr. Lim, by performing the experiments, co-designing the study and co-writing the paper. Mr Nishide is also enrolled in Kanazawa University’s WISE program for Nano-Precision Medicine, Science and Technology, an initiative aimed at innovations in disease prevention, diagnosis, and treatment methods based on exploiting our increased understanding of biological and other processes at the nanoscale.
Background
Atomic force microscopy Atomic force microscopy (AFM) is an imaging technique in which the image is formed by scanning a surface with a very small tip. Horizontal scanning motion of the tip is controlled by piezoelectric elements, while vertical motion is converted into a height profile, resulting in a height distribution of the sample’s surface. As the technique does not involve lenses, its resolution is not restricted by the so-called diffraction limit as in X-ray diffraction, for example. In a high-speed setup (HS-AFM), the method can be used to produce movies of a sample’s structural evolution in real time, as a typical biomolecule can be scanned in 100 ms or less. Now, Richard Wong and colleagues from Kanazawa University have successfully applied the HS-AFM technique to study the wrapping of DNA around structural proteins.
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