Biology & Medicine News and Discussions

[Yuli Ban]

Every living cell contains its own bustling microcosm, with thousands of components responsible for energy production, protein building, gene transcription and more.

Scientists at the University of Illinois at Urbana-Champaign have built a 3D simulation that replicates these physical and chemical characteristics at a particle scale — creating a fully dynamic model that mimics the behavior of a living cell.

Published in the journal Cell, the project simulates a living minimal cell, which contains a pared-down set of genes essential for the cell’s survival, function and replication. The model uses NVIDIA GPUs to simulate 7,000 genetic information processes over a 20-minute span of the cell cycle – making it what the scientists believe is the longest, most complex cell simulation to date.

Minimal cells are simpler than naturally occurring ones, making them easier to recreate digitally.

“Even a minimal cell requires 2 billion atoms,” said Zaida Luthey-Schulten, chemistry professor and co-director of the university’s Center for the Physics of Living Cells. “You cannot do a 3D model like this in a realistic human time scale without GPUs.”

Once further tested and refined, whole-cell models can help scientists predict how changes to the conditions or genomes of real-world cells will affect their function. But even at this stage, minimal cell simulation can give scientists insight into the physical and chemical processes that form the foundation of living cells.

“What we found is that fundamental behaviors emerge from the simulated cell — not because we programmed them in, but because we had the kinetic parameters and lipid mechanisms correct in our model,” she said.

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Bone tissue engineering: Divalent metal cations stimulate new bone formation
https://medicalxpress.com/news/2022-02- ... tions.html
by Thamarasee Jeewandara , Medical Xpress

The concept of new bone formation via divalent cations is widely reported although the underlying mechanism of the process remains unclear. In a new report now published in Nature Communications, Wei Qiao and a team of scientists in orthopedics surgery, materials science, and biomaterials in China and the U.S. reported how cations can stimulate skeleton interoception to regulate bone formation by promoting prostaglandin E2 secretion (a potent inflammatory mediator) from macrophages. The immune response accompanied sprouting and arborization of nerve fibers to sense inflammatory cues and convey signals to the central nervous system. The process of activating skeleton interoception downregulated the sympathetic tone to facilitate new bone formation. The study revealed how divalent cations promote bone formation via the skeleton interoceptive circuit. This finding can prompt the development of new biomaterials during bone tissue engineering to promote the therapeutic power of divalent cations.

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A never-before-seen way bacteria infect cells
https://phys.org/news/2022-02-never-bef ... cells.html
by San Diego State University

Zombie bites and airborne transmission are some of the fictional and all-too-real methods that pathogens like bacteria and viruses use to infect new hosts. Biologists from San Diego State University have identified a new way that one type of bacteria invades multiple cells within a living organism.

The study, published this week in Nature Communications, describes how a new species of bacteria, Bordetella atropi, which the researchers named for the Greek fate Atropos responsible for cutting the threads of life, invades its roundworm host.

And it is aptly named because the bacteria changes its shape into a long thread, growing up to 100 times the usual size of one bacterium in the span of 30 hours without dividing.

By altering the genes of Bordetella atropi, the research team discovered that this invasive threading relies on the same genes and molecules that other bacteria use when they are in a nutrient-rich environment. However, these other bacteria only use this pathway to make subtly larger cells, whereas the B. atropi bacteria grows continuously.

Other bacteria often transform into threads, called filamentation, in response to dangerous environments or damage to their DNA. This lets them continue to grow in size, but delay dividing into new bacterial cells until they fix the damage caused by the stress.

[Yuli Ban]

Delivering what has been so challenging to produce, researchers present an engineered analog of tooth enamel – an ideal model for designing biomimetic materials – designed to closely mimic the composition and structure of biological teeth’s hard mineralized outer layer. It demonstrates exceptional mechanical properties, they say.

Natural tooth enamel – the thin outer layer of our teeth – is the hardest biological material in the human body. It is renowned for its high stiffness, hardness, viscoelasticity, strength, and toughness and exhibits exceptional damage resistance, despite being only several millimeters thick.

Tooth enamel’s unusual combination of properties is a product of its hierarchical architecture – a complex structure made up of mostly hydroxyapatite nanowires interconnected by an amorphous intergranular phase (AIP) consisting of magnesium-substituted amorphous calcium phosphate. However, accurately replicating this type of hierarchical organization in a scalable abiotic composite has remained a challenge.

Here, Hewei Zhao and colleagues present an engineered enamel that contains the essential hierarchical structure at multiple scales. The artificial tooth enamel (ATE) was produced using AIP-coated hydroxyapatite nanowires, which were aligned using dual-directional freezing in the presence of polyvinyl alcohol. According to the authors, this allowed the engineered structures to have an atomic, nanoscale, and microscale organization like natural enamel.

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Ebola vaccine being used in Congo produces lasting antibody response, study finds
https://medicalxpress.com/news/2022-02- ... ponse.html
by Brad Smith, University of California, Los Angeles

A new study by UCLA researchers and colleagues demonstrates that the Ebola vaccine known as rVSVΔG-ZEBOV-GP results in a robust and enduring antibody response among vaccinated individuals in areas of the Democratic Republic of Congo that are experiencing outbreaks of the disease. Among the more than 600 study participants, 95.6% demonstrated antibody persistence six months after they received the vaccine.

The study is the first published research examining post–Ebola-vaccination antibody response in the DRC, a nation of nearly 90 million. While long-term analyses of the study cohort continue, the findings will help inform health officials' approach to vaccine use for outbreak control, the researchers said.

Ebola, one of the world's deadliest viral diseases, was first identified in 1976 following an outbreak near the Ebola River in the DRC. Since then, outbreaks have occurred intermittently in sub-Saharan Africa, including 12 outbreaks in the DRC, where the disease remains endemic.

The single-dose rVSVΔG-ZEBOV-GP vaccine, officially licensed in 2019 by both the U.S. Food and Drug Administration and the European Medicines Agency, was administered to more than 300,000 individuals in the DRC during outbreaks between 2018 and 2020. Until now, however, studies examining the antibody response of vaccinated Congolese populations were lacking.

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Drug halts immune reactions to save damaged lungs
https://medicalxpress.com/news/2022-02- ... lungs.html
by Cold Spring Harbor LaboratoryJose M. Adrover/Egeblad lab/CSHL, 2022

A team of scientists led by Cold Spring Harbor Laboratory (CSHL) have discovered that disulfiram, an FDA-approved drug, prevents the immune system from producing toxic webs known as neutrophil extracellular traps (NETs). Many scientists suspect NETs help drive the development of acute respiratory distress syndrome (ARDS) in patients with severe COVID-19 and other life-threatening lung injuries.

Jose M. Adrover, a postdoctoral fellow in CSHL Professor Mikala Egeblad's lab, explains that NETs are usually released during infections when immune cells, called neutrophils, confront a threat that is too large for the tiny cells to battle directly. To extend their reach, neutrophils spew a sticky web of DNA and toxins, which indiscriminately poisons pathogens and the body's own cells. "They will damage everything, all around," Adrover says.

Because NETs can be so destructive, researchers in Egeblad's lab have been searching for ways to block their formation. Disulfiram, which has been used since the 1950s as a treatment for alcohol use disorders, was a promising candidate. "Disulfiram interferes with gasdermin D, a molecule needed to produce NETs", says Juliane Daßler-Plenker, a postdoctoral fellow in Egeblad's lab.

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Optogenetic control of parathyroid hormone secretion to prevent bone loss
https://medicalxpress.com/news/2022-02- ... -bone.html
by Chinese Academy of Sciences

Researchers led by Prof. Yang Fan from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences and their collaborators have proposed a new approach to control parathyroid hormone secretion in order to prevent secondary hyperparathyroidism (SHPT)-associated bone loss.

Their study was published in Nature Communications on Feb. 9.

Parathyroid hormone (PTH) is secreted by parathyroid chief cells. It plays an important role in maintaining calcium and phosphorus homeostasis and bone metabolism.

The regulation of PTH secretion in response to calcium fluctuations is mediated by calcium-sensing receptors (CaSRs) on parathyroid cells. However, in the progression of SHPT, the expression of CaSR in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. Excess PTH leads to a series of symptoms such as hypercalcemia, emotional abnormalities, and bone loss.

Traditional treatments including parathyroidectomy and calcium mimics cannot restore the rhythmic secretion of PTH. As a result, PTH cannot be physiologically regulated.

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Tiny, reusable sensing chip could lead to new point-of-care medical tests
https://phys.org/news/2022-02-tiny-reus ... dical.html
by Cory Nealon, University at Buffalo

The proliferation of point-of-care testing, from at-home blood glucose meters to COVID-19 rapid tests, is accelerating and improving medical care.

Continuing to upgrade the sensing technology that is fueling the growth of these products, however, is becoming increasingly challenging.

Some optical sensing chips, for example, contain nanostructures that are nearly as small as the biological and chemical molecules they're searching for. These nanostructures improve the sensor's ability to detect molecules. But their diminutive dimensions make it difficult to guide the molecules to the correct area of the sensor.

"It's kind of like building a new racing car that is more streamlined and therefore runs faster, but its door is made too small for the driver to enter the car," says Peter Q. Liu, Ph.D., assistant professor of electrical engineering at the University at Buffalo School of Engineering and Applied Sciences.

Liu—along with Xianglong Miao, a Ph.D. candidate in his lab, and Ting Shan Luk, Ph.D., at the Center for Integrated Nanotechnologies, Sandia National Laboratories—have created a new sensor that takes aim at this problem.

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Scopio Aims to Turn Hematology into Remote Work With $50 Million C Round
by Emma Betuel
February 9, 2022

https://techcrunch.com/2022/02/09/scopi ... m-c-round/

Introduction:

(TechCrunch) Today, if a hematologist wanted to dive into the exact organization and structure of your blood cells, they’d probably need a microscope in a lab. Scopio, an Israel-based startup that just closed a $50 million Series C round, argues that soon, a lot of that work could be done with nothing more than a laptop.

Founded in 2015, Scopio is an imaging company looking to re-imagine a common blood test called a peripheral blood smear. In essence, that’s a test where a doctor, usually looking to understand an anomaly in a blood cell count, literally takes a look at your blood cells. That process involves placing a smear of blood onto a slide, and examining the shape, size and structure of certain cells using a well-trained eye.

Scopio has developed a scanner, called Scopio100x, capable of imaging that whole blood sample, while maintaining the ability to achieve 100x magnification. The result is a zoomable, digital image that CEO and founder Itai Hayut argues will allow peripheral blood smears to be done remotely, and bring down the costs of these procedures in the first place. Once samples are scanned in the lab, they could be reviewed by hematologists working from anywhere.

You can zoom around in one of the images here.

“We’ve seen lines of people in hematology labs leaning over microscopes, in some cases, using a manual clicker to count cells,” Hayut told TechCrunch. “We thought this is just a perfect example of how computer vision tools can assist the experts, and get better results much quicker.”

Blood Cells
Scopio

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Enzyme treatment could make donor organs compatible with any patient
By Michael Irving
February 16, 2022
https://newatlas.com/medical/enzyme-tre ... or-organs/

Matching blood types from donor to recipient is one of the major problems in organ donation. Now, a team of researchers in Canada has developed an enzyme treatment to convert donated organs to the universal O blood type, allowing them to be safely transplanted into any patient.

A person’s blood type is determined by the antigens on the surface of their red blood cells. Those with type A blood have the A antigen, type B has the B antigen, AB has both and O has neither. For blood transfusions or organ transplants, these types need to be matched to prevent dangerous immune responses like organ rejection, but that’s a messy process that sees many patients missing out.

Much research has gone into preventing organ rejection in recent years. Scientists have been experimenting with special coatings for blood vessels, drugs that increase protective T cells in organs, nanoparticles that “hide” the organ from the immune system, and protein baths that strip out all the donor’s cells so they can be replaced with the recipient’s.

For the new study, researchers from a range of institutions across Canada tested an experimental enzyme treatment to remove antigens from donated organs, essentially converting them into the universal type O. Two enzymes from the human gut, known as FpGalNAc deacetylase and FpGalactosaminidase, have previously been shown to convert type A blood cells to type O, so the team tested if they would also work for organs.

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Researchers identify protein complex critical in helping control cell death
https://phys.org/news/2022-02-protein-c ... death.html
by University of South Florida

Cell death plays an important role in normal human development and health but requires tightly orchestrated balance to avert disease. Too much can trigger a massive inflammatory immune response that damages tissues and organs. Not enough can interfere with the body's ability to fight infection or lead to cancer.

Zhigao Wang, Ph.D., associate professor of cardiovascular sciences at the University of South Florida Health (USF Health) Morsani College of Medicine, studies the complex molecular processes underlying necroptosis, which combines characteristics of apoptosis (regulated or programmed cell death) and necrosis (unregulated cell death).

During necroptosis dying cells rupture and release their contents. This sends out alarm signals to the immune system, triggering immune cells to fight infection or limit injury. Excessive necroptosis can be a problem in some diseases like stroke or heart attack, when cells die from inadequate blood supply, or in severe COVID-19, when an extreme response to infection causes organ damage or even death.

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Scientists obtain first high-resolution 3D image of muscle protein nebulin
https://phys.org/news/2022-02-scientist ... uscle.html
by Max Planck Society

Scientists have obtained the first high-resolution 3D image of nebulin, a giant actin-binding protein that is an essential component of skeletal muscle. This discovery has brought to light the chance to better understand the role of nebulin, as its functions have remained largely nebulous due to its large size and the difficulty in extracting nebulin in a native state from muscle. The team of Max Planck researchers, led by Stefan Raunser, Director at the Max Planck Institute of Molecular Physiology in Dortmund, in collaboration with Mathias Gautel at King's College London, used electron cryo-tomography to decipher the structure of nebulin in impressive detail. Their findings could lead to novel therapeutic approaches to treat muscular diseases, as genetic mutations in nebulin are accompanied by a dramatic loss in muscle force known as nemaline myopathy.

Skeletal and heart muscles contract and relax upon sliding of parallel filaments of the proteins myosin and actin. Nebulin, another long slender protein, which is present only in skeletal muscle, pairs up with actin, stabilizing and regulating it. Mutations in the gene encoding nebulin can produce an abnormal nebulin that causes nemaline myopathy, an incurable neuromuscular disorder with various degrees of severity, from muscle weakness to speech impediments and respiratory problems.

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Newly developed radio-labeled molecule enables real-time imaging of innate immune activity

by University of Texas M. D. Anderson Cancer Center
https://phys.org/news/2022-02-newly-rad ... -time.html

Researchers at The University of Texas MD Anderson Cancer Center have developed a new radio-labeled molecule capable of selectively reacting with certain high-energy radicals that are characteristic of innate immune activity, which may allow a non-invasive approach to monitor inflammation in real time by positron emission tomography (PET) imaging.

The preclinical study, published today in Nature Biotechnology, takes advantage of new chemistry techniques to synthesize 4-[18F]Fluoro-1-Naphthol ([18F]4FN) as a novel reporter of myeloperoxidase (MPO) activity—a key enzyme active in the innate immune response. The molecule may be able to pinpoint areas of inflammation in a variety of clinical settings, such as inflammatory diseases, infections and immunotherapy-related side effects.

"There has been a long-standing interest in imaging inflammation and redox in general, but most current approaches generate high levels of background noise from biological processes that generate lower-energy radicals," said corresponding author David Piwnica-Worms, M.D., Ph.D., chair of Cancer Systems Imaging. "Our molecule is tuned toward inflammation mediated by high-energy radicals, offering the potential to selectively monitor activation of innate immunity."

The innate immune response is the body's first line of defense against invading pathogens. In contrast to the adaptive immune response, innate immunity is nonspecific and acts broadly against infections or foreign agents. Innate immunity is largely driven by myeloid cells, including neutrophils, macrophages and natural killer (NK) cells.

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Aiming to end the refrigeration of vaccines
https://medicalxpress.com/news/2022-02- ... cines.html
by CSIRO

Researchers at Australia's national science agency, CSIRO, have developed a technique that addresses the challenge of transporting temperature-dependent vaccines, which researchers hope may increase access in rural and remote communities in Australia and developing countries.

The World Health Organisation estimates that at least 50 percent of vaccines are wasted globally each year, with a lack of facilities and temperature control the major cause.

Recently published in Acta Biomaterialia, CSIRO researchers encapsulated live virus vaccines with a dissolvable crystalline material called MOFs (metal organic frameworks), which protected the integrity of the vaccines for up to 12 weeks and at temperatures as high as 37 degrees Celsius. Without refrigeration the vaccines would otherwise last only a few days.

CSIRO scientist and immunologist, Dr. Daniel Layton, said the breakthrough science would now focus on proving the approach for other animal and human vaccines, including mRNA COVID-19 vaccines.

"Vaccination is undoubtedly one of the most effective medical interventions, saving millions of lives each year, however delivering vaccines, particularly to developing countries, is challenging because they often lack the cold storage supply chains required to keep the vaccine viable," Dr. Layton said.

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Discovery of central signaling pathway in immune cells
https://medicalxpress.com/news/2022-02- ... cells.html
by Medical University of Vienna

Autoimmune diseases are triggered when the immune system malfunctions and attacks the body's own structures. Although there is not, as yet, any cure for such diseases, their progression can be slowed down by therapeutic measures. Researchers at MedUni Vienna's Center for Physiology and Pharmacology have now discovered a central signaling pathway in immune cells that may help in the development of a new therapeutic approach. Their study was recently published in the journal Cell Reports.

The immune system protects the body from infections of all kinds and is designed to distinguish between foreign threats and the body's own tissues. T cells, which are deployed at the command of other immune cells, the dendritic cells, are an important component of the immune system. The dendritic cells are not only responsible for activating the T cells but also for deactivating them—primarily to prevent them from attacking the body's own tissues. This mechanism, known as immunotolerance, is the key to the current treatments for autoimmune diseases, whereby certain pharmaceutical agents (JAK inhibitors) are used. The aim is to inhibit T-cell activity against endogenous structures, so as to slow down the progression of the autoimmune disease.

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Extreme heat linked to increase in mental health emergency care
https://medicalxpress.com/news/2022-02- ... gency.html
by Boston University School of Medicine

During periods of extreme heat, clinicians should expect to see an increase in patients requiring mental health services, according to a new study led by Boston University School of Public Health researchers.

Published in the journal JAMA Psychiatry, the study found that days with higher-than-normal temperatures during the summer season in the United States were associated with increased rates of emergency department (ED) visits for any mental health-related condition, particularly substance use, anxiety and stress disorders, and mood disorders.

The impact of heat on physical health is well documented, but few studies have examined the effects of extreme heat on mental health. This nationwide study is the largest and most comprehensive analysis of daily ambient temperature and mental health-related ED visits among US adults of all ages. As days of extreme heat are expected to increase due to worsening climate change, the findings fill a critical gap in research and provide evidence-based support for proactive interventions and policy solutions that can reduce heat-related crises.

"Emergency department visits represent some of the costliest interactions within the healthcare system," says study lead author Dr. Amruta Nori-Sarma, assistant professor of environmental health at BUSPH. "Addressing the needs of the most vulnerable to preempt some of these visits can have a positive impact on individual health and costs, as well as preserve healthcare resources for other emergencies."

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Meat-eating extends human life expectancy worldwide
https://medicalxpress.com/news/2022-02- ... dwide.html
by Michele Ann Nardelli, University of Adelaide

Has eating meat become unfairly demonized as bad for your health? That's the question a global, multidisciplinary team of researchers has been studying and the results are in—eating meat still offers important benefits for overall human health and life expectancy.

Study author, University of Adelaide researcher in biomedicine Dr. Wenpeng You, says humans have evolved and thrived over millions of years because of their significant consumption of meat.

"We wanted to look more closely at research that has thrown a negative spotlight on meat consumption in the human diet," Dr. You says.

"Looking only at correlations of meat consumption with people's health or life expectancy within a particular group, and or, a particular region or country, can lead to complex and misleading conclusions.

"Our team broadly analyzed the correlations between meat eating and life expectancy, and child mortality, at global and regional levels, minimizing the study bias, and making our conclusion more representative of the general health effects of meat eating."

Published in the International Journal of General Medicine today, the study examined the overall health effects of total meat consumption in 170+ countries around the world.

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3D micromesh-based hybrid printing for microtissue engineering
https://phys.org/news/2022-02-d-microme ... issue.html
by Thamarasee Jeewandara , Phys.org

Bioprinting is widely applicable to develop tissue engineering scaffolds and form tissue models in the lab. Materials scientists use this method to construct complex 3D structures based on different polymers and hydrogels; however, relatively low resolution and long fabrication times can result in limited procedures for cell-based applications.

In a new report now available in Nature Asia Materials, Byungjun Lee and a team of scientists in mechanical engineering at Seoul National University, Seoul, Korea, presented a 3D hybrid-micromesh assisted bioprinting method (Hy-MAP) to combine digital light projection, 3D printed micromesh scaffold sutures, together with sequential hydrogel patterning. The new method of bioprinting offered rapid cell co-culture via several methods including injection, dipping and draining. The work can promote the construction of mesoscale complex 3D hydrogel structures across 2D microfluidic channels to 3D channel networks.

Lee et al. established the design rules for Hy-MAP printing via analytical and experimental investigations. The new method can provide an alternative technique to develop mesoscale implantable tissue engineering constructs for organ-on-a-chip applications.

[Yuli Ban]

Jimi Olaghere thought he would have to wait decades to be freed from his sickle cell disease - but now scientists have engineered his blood to overcome the disease which left him in constant pain.

"It's like being born again," says Jimi, one of the first seven sickle cell patients to have benefited from a revolutionary new gene-editing treatment being trialled in the US. He says it has changed his life.

"When I look back, it's like, 'Wow, I can't believe I lived with that.'"

Jimi, 36, has lived with sickle cell since childhood. "You always have to be in a war mindset, knowing that your days are going to be filled with challenges."

The disease runs in families. It is caused by a genetic mutation that leads to the body making abnormal haemoglobin. This is the protein that is packed into red blood cells and carries oxygen around the body. Red blood cells are normally round and squishy, but mutated haemoglobin can make them rigid and take on their characteristic sickle shape.

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Developing ultrathin films for stretchable and sturdy bioelectronic membranes
https://phys.org/news/2022-03-ultrathin ... ranes.html
by University of California, Los Angeles

UCLA researchers have developed a unique design of ultrathin films for highly flexible yet mechanically robust bioelectronic membranes that could pave the way for diagnostic on-skin sensors that fit precisely over the body's contours and conform to its movements.

Science recently published a paper describing the research co-led by Xiangfeng Duan, professor of chemistry and biochemistry; and Yu Huang, professor and chair of the Materials Science and Engineering Department at the UCLA Samueli School of Engineering.