Nanobiomaterial Boosts Neuronal Growth in Mice With Spinal Cord Injuries (Material Science / Medicine)

Researchers from the Department of Orthopedics of Tongji Hospital at Tongji University in Shanghai have successfully used a nanobiomaterial called layered double hydroxide (LDH) to inhibit the inflammatory environment surrounding spinal cord injuries in mice, accelerating regeneration of neurons and reconstruction of the neural circuit in the spine. The researchers were also able to identify the underlying genetic mechanism by which LDH works. This understanding should allow further modification of the therapy which, in combination with other elements, could finally produce a comprehensive, clinically applicable system for spinal cord injury relief in humans.

The research appears in the American Chemical Society journal ACS Nano on February 2.

There is no effective treatment for spinal cord injuries, which are always accompanied by death of neurons, breakage of axons, or nerve fibers, and inflammation. Even though new neural stem cells continue to be generated by the body, this inflammatory microenvironment (the immediate, small-scale conditions at the injury site) severely hinders regeneration of neurons and axons. Worse still, the prolonged activation of immune cells in this area also results in secondary lesions of the nervous system, in turn preventing the stems cells from differentiating themselves into new cell types.

If this aggressive immune response at the injury site could be moderated, there is the possibility that neural stem cells could begin differentiation and neural regeneration could occur.

In recent years, a raft of novel nano-scale biomaterials — natural or synthetic materials that interact with biological systems — have been designed to assist activation of neural stem cells, along with their mobilization and differentiation. Some of these “nanocomposites” are capable of delivering drugs to the injury site and accelerate neuronal regeneration. These nanocomposites are especially attractive for spinal cord treatment due to their low toxicity. However, few have any ability to inhibit or moderate the immune reaction at the site, and so do not tackle the underlying problem. Moreover, the underlying mechanisms of how they work remains unclear.

Nanolayered double hydroxide (LDH) is a kind of clay with many interesting biological properties relevant to spinal cord injuries, including good biocompatibility (ability to avoid rejection by the body), safe biodegradation (breakdown and removal of the molecules after application), and excellent anti-inflammatory capability. LDH has already been widely explored in biomedical engineering with respect to immune response regulation, but mainly in the field of anti-tumor therapy.

“These properties made LDH a really promising candidate for the creation of a much more bene?cial microenvironment for spinal cord injury recovery,” says Rongrong Zhu of the Department of Orthopedics of Tongji Hospital, first author of the study.

Under the leadership of Liming Cheng, corresponding author of the study, the research team transplanted the LDH into the injury site of mice, and found that the nanobiomaterial had signi?cantly accelerated neural stem cells migration, neural di?erentiation, activation of channels for neuron excitation, and induction of action potential (nerve impulse) activation. The mice were also found to enjoy significantly improved locomotive behavior compared to the control group of mice. In addition, when the LDH was combined with Neurotrophin-3 (NT3), a protein that encourages the growth and differentiation of new neurons, the mice enjoyed even better recovery effects than the LDH on its own. In essence, the NT3 boosts neuronal development while the LDH creates an environment where that development is allowed to thrive.

Then, via transcriptional profiling, or analysis of gene expression of thousands of genes at once, the researchers were able to identify how the LDH performs its assistance. They found that once LDH is attached to cell membranes, it provokes greater activation of the “transforming growth factor-β receptor 2” (TGFBR2) gene, decreasing production of the white blood cells that enhance inflammation and increasing production of the white blood cells that inhibit inflammation. Upon application of a chemical that inhibits TGFBR2, they found the beneficial effects were reversed.

The understanding of how LDH performs these effects should now allow the researchers to tweak the therapy to enhance its performance and to finally create a comprehensive therapeutic system for spinal cord injuries–combining these biomaterials with neurotrophic factors like NT3-that can be used in clinical application on people.

Featured image: Nanobiomaterial boosts neuronal growth in mice: Researchers from the Department of Orthopedics of Tongji Hospital have successfully used a nanobiomaterial called layered double hydroxide (LDH) to inhibit the inflammatory environment surrounding spinal cord injuries in mice, accelerating regeneration of neurons and reconstruction of the neural circuit in the spine. Image credit: Liming Cheng, Rongrong Zhu, Department of Orthopedics, Tongji Hospital of Tongji University


Reference: Rongrong Zhu, Xingfei Zhu, Yanjing Zhu, Zhaojie Wang, Xiaolie He, Zhourui Wu, Lei Xue, Wenyong Fan, Ruiqi Huang, Zheng Xu, Xi Qi, Wei Xu, Yan Yu, Yilong Ren, Chen Li, Qian Cheng, Lan Ling, Shilong Wang, and Liming Cheng, “Immunomodulatory Layered Double Hydroxide Nanoparticles Enable Neurogenesis by Targeting Transforming Growth Factor-β Receptor 2”, ACS Nano 2021, 15, 2, 2812–2830. https://pubs.acs.org/doi/10.1021/acsnano.0c08727
https://doi.org/10.1021/acsnano.0c08727


Provided by Tongji University

Toronto Researchers Develop Rapid Low Cost Method to Measure COVID-19 Immunity (Medicine)

New test can accurately detect coronavirus antibodies in a drop of blood in less than an hour

Igor Stagljar made his career building molecular tools to combat cancer. But when the pandemic hit last March, he aimed his expertise at a new adversary, SARS-CoV-2.

Stagljar is a professor of biochemistry and molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at U of T’s Temerty Faculty of Medicine. Last spring, with support from U of T’s Toronto COVID-19 Action Fund, his team began developing a new method for measuring immunity to coronavirus in those who recovered from COVID-19.

They are now ready to reveal their creation — a pinprick test that accurately measures in under one hour concentration of coronavirus antibodies in blood. And it’s cheap, costing a toonie or about tenth of the cost of the market gold standard.

Their method has been published in a study out today in the journal Nature Communications.

“Our assay is as sensitive, if not better than any other currently available assay in detecting low levels of IgG antibodies, and its specificity, also known as false-positive rate, is as good as the best antibody test on the market,” said Stagljar who collaborated with public health agencies and blood banks from across Canada to have the test validated on blood samples taken from former COVID-19 patients.

Serological tests detect antibodies, protein molecules in blood that recognize and neutralize Sars-CoV-2 to prevent infection. Such tests are seen as a key tool for public health experts wanting to measure population immunity to be better able to manage the ongoing pandemic.

According to a January report by the national COVID Immunity Task Force, the majority of Canadians remain vulnerable to coronavirus infection with less than two percent testing positive for antibodies.

Population level studies can also help reveal duration of coronavirus immunity across patients who had different experiences of disease, from asymptomatic to severe. They also have the potential to reveal threshold antibody level required for protection after natural infection and vaccination.

“That level is still to be determined, but we do know that people who have been infected with SARS-CoV-2 have very diverse levels of antibodies, and it would not be surprising to find that below some baseline level they might not be protective,” said Zhong Yao, senior research associate in Stagljar’s lab and coinventor of the testing method.

Several serological tests have received regulatory approval with ELISA-based methods as the gold standard when it comes to measuring antibody concentration as a strength of individual immune response. But it comprises several laboratory steps that take six hours to complete, making it unsuitable for rapid diagnostics. Simpler methods using test strips, similar to pregnancy tests, provide fast results but are not quantitative and are less reliable.

The new method is called SATiN, for Serological Assay based on split Tripart Nanoluciferase. It is the first COVID-19 serology test that uses highly sensitive protein complementation chemistry in which a light-emitting luciferase protein is reconstituted from separate fragments as test readout.

Luciferase is initially supplied in fragments that cannot not glow on their own. One piece is attached on the viral spike protein, which antibodies bind to neutralise the virus, while another is hooked to a bacterial protein that antibodies also interact with. By binding simultaneously to the coronavirus spike protein and the bacterial protein, the antibody helps lock luciferase pieces together into a whole molecule. A flash of light ensues whose intensity is detected and converted into antibody concentration by a plate reader instrument. All reagents can be prepared from scratch and in bulk and this keeps the cost down.

Stagljar is now working with U of T’s intellectual property office and Toronto Innovation Acceleration Partners to find industry partners that would help make the method widely available. He is also collaborating with Dr. Prabhat Jha, Director of the Centre for Global Health Research at St. Michael’s Hospital and a professor at U of T’s Dalla Lana School of public Health, who is leading a long-term study to establish duration of immunity across 10,000 Canadians. In another project, Stagljar is working with Dr. Allison McGeer, Senior Clinician Scientist at Sinai Health System and also a professor at Dalla Lana, to assess antibody levels in people after vaccination.

“It’s really useful to have that quantitative ability to know what someone’s antibody status is, whether it’s from a past infection or a vaccination. This will be of crucial importance for the next stage of the pandemic, especially now when governments of all countries started with mass vaccinations with recently approved anti-COVID-19 vaccines”, Stagljar said.

Featured image: Co-inventors Igor Stagljar, investigator at the Donnelly Centre and U of T professor, and Zhong Yao, senior research associate at the Donnelly Centre. © Farzaneh Aboualizadeh


Reference: Yao, Z., Drecun, L., Aboualizadeh, F. et al. A homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies. Nat Commun 12, 1806 (2021). https://www.nature.com/articles/s41467-021-22102-6 https://doi.org/10.1038/s41467-021-22102-6


Provided by University of Toronto

Hormone Drugs May Disarm COVID-19 Spike Protein and Stop Disease Progression (Medicine)

A new Penn Medicine study shows how anti-androgen drugs disrupt key receptors required for viral invasion of cells

Hormone drugs that reduce androgen levels may help disarm the coronavirus spike protein used to infect cells and stop the progression of severe COVID-19 disease, suggests a new preclinical study from researchers in the Abramson Cancer Center at the University of Pennsylvania and published online in Cell Press’s iScience.

Researchers show how two receptors–known as ACE2 and TMPRSS2–are regulated by the androgen hormone and used by SARS-CoV-2 to gain entry into host cells. Blocking the receptors with the clinically proven inhibitor Camostat and other anti-androgen therapies prevented viral entry and replication, they also showed in lab studies.

The findings provide more insight into the molecular mechanisms of the virus but also support the use of anti-androgen therapies to treat COVID-19 infections, which are currently being investigated in clinical trials and have produced promising results. They also support data showing increased mortality and severity of disease among men compared to women, who have much lower levels of androgen.

“We provide the first evidence that not only TMPRSS2, which is known to be regulated by androgen, but ACE2 can also be directly regulated by this hormone,” said senior author Irfan A. Asangani, PhD, an assistant professor of Cancer Biology in the Perelman School of Medicine at the University of Pennsylvania. “We also show that the SARS-CoV-2 spike relies on these two receptors to impale and enter cells, and that they can be blocked with existing drugs. That’s important because if you stop viral entry, you reduce the viral load and disease progression.”

Camostat is a drug approved for use in Japan to treat pancreatitis that inhibits TMPRSS2. Other anti-androgen therapies, including androgen deprivation therapy used to treat prostate cancer, serve similar functions.

Driven by the disparity in COVID-19 rates between men and women, the cancer researchers sought to better understand the role androgen and its receptors played in infections, which has long been known to be a driver of prostate cancer.

The researchers performed experiments with a pseudotype SARS-CoV-2, which carries the spike proteins of the virus but not its genome.

In mice with significantly reduced androgen levels and cells treated with anti-androgen treatments, the researchers found little to no expression of TMPRSS2 and ACE2, suggesting both are regulated by the hormone. They also observed how inhibiting TMPRSS2 with Camostat blocked priming of the spike for entry into cells. That drug, as well as enzalutamide, an anti-androgen therapy used to treat prostate cancer, also blocked the virus’ entry into lung and prostate cells. Combining these therapies, they found, significantly reduced virus entry into cells.

“Together, our data provide a strong rationale for clinical evaluations of TMPRSS2 inhibitors, androgen-deprivation therapy / androgen receptor antagonists alone or in combination with antiviral drugs as early as clinically possible to prevent COVID-19 progression,” the authors wrote.

In March, researchers from Brazil reported preliminary results of 600 hospitalized patients in a clinical trial investigating proxalutamide, a new anti-androgen therapy, for the treatment of COVID-19. The drug reduced mortality risk by 92 percent and shortened the median hospital stay by nine days versus the standard of care, the researchers reported.

Next, Asangani and his colleagues will partner with Susan R. Weiss, PhD, a professor of Microbiology and co-director of the Penn Center for Research on Coronaviruses and Other Emerging Pathogens, to investigate the findings further using live SARS-CoV-2, as well as anti-androgen therapies’ ability to block different variants of the virus, which continue to emerge and are often differentiated by their spike proteins.

Penn co-authors of the study include Qu Deng, Reyaz ur Rasool, Ronnie M. Russell, and Ramakrishnan Natesan.

Featured image credit: gettyimages


Reference: Qu Deng et al., “Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19”, 24(3), 2021. 2021. DOI: https://doi.org/10.1016/j.isci.2021.102254


Provided by University of Pennsylvania School of Medicine

Prostate Cancer Uses Metabolic Switch to Thrive After Hormone Therapy (Medicine)

Finding points toward a new approach that directly targets the cancer’s fuel source

Studying the cellular metabolism of prostate cancer, a team of Duke Health-led researchers identified a key reason hormone therapies eventually fail, while also laying out a way to bypass the problem using an entirely new therapeutic approach.

The findings, published during the week of March 22 in the Proceedings of the National Academy of Sciences, describe how hormone therapies target the androgen receptor to essentially starve tumor cells of a crucial fuel source. This initially works well to halt tumor growth, but then the cancer cells compensate, switching to a different enzyme to exploit the fuel and proliferating as they become resistant to hormone therapies. 

The team of Duke Cancer Institute researchers used that finding to propose a treatment strategy that eliminates the need to inhibit the androgen receptor completely. Their goal is to directly target the tumor’s preferred source of fuel – an amino acid called glutamine. 

In studies using prostate cancer cell lines, human prostate cancer tissue and animal models, the novel therapeutic strategy successfully inhibited tumor growth. Clinical trials are in being planned using a currently available drug that inhibits glutamine use by tumor cells.

“Instead of inhibiting androgen receptor using hormonal therapy, a better therapeutic strategy is to inhibit glutamine utilization directly,” said senior author Jiaoti Huang, M.D., Ph.D., chair of Duke’s Department of Pathology.

“Since glutamine is not essential for normal tissue, there will be fewer side effects, which is one of the biggest downsides to hormonal therapies,” Huang said. “Direct inhibition of the enzyme that controls glutamine utilization would also make it more difficult for tumor cells to develop resistance.”

Huang and co-authors — including Daniel George, M.D., professor in the departments of Medicine and Surgery at Duke who leads the clinical trial design — initiated the study to better understand prostate cancer cell metabolism, which still has many unknowns. 

They found that hormone therapy initially inhibits a certain form of glutamine-converting enzyme called kidney-type glutaminase (KGA). This KGA enzyme depends on the androgen receptor and makes it possible for cancer cells to use glutamine. By suppressing it, hormonal therapies successfully slow cancer growth for a time.

But the tumor cells eventually find a workaround, switching to a different enzyme — glutaminase C (GAC) — which doesn’t rely on androgen receptor. When tumors make this switch to GAC, they proliferate aggressively, becoming castration-resistant prostate cancer.

“Our work demonstrates this metabolic switch to be one of the key mechanisms in therapeutic resistance and disease progression,” George said.

By targeting glutamine metabolism, the researchers pioneered a way to bypass the complex androgen receptor signaling processes, instead directly suppressing the production of energy and building blocks required by prostate cancer cells, essentially starving tumor cells to death. 

 “Since metabolic activity directly controls cellular proliferation, it may be more difficult for the tumor cells to overcome a metabolic inhibition to develop resistance,” Huang said. “Our study shows that pharmacological inhibition of GAC can significantly suppress castration-resistant prostate cancer.”

In addition to Huang and George, study authors include Lingfan Xu, Yu Yin, Yanjing Li, Xufeng Chen, Yan Chang, Hong Zhang, Juan Liu, James Beasley, Patricia McCaw, Haoyue Zhang, Sarah Young, Jeff Groth, Qianben Wang, Jason W. Locasale, Xia Gao, Dean G. Tang, Xuesen Dong, Yiping He and Hailiang Hu.

The work received support from the Department of Defense (DOD-W81XWH-19-1-0411), the Prostate Cancer Foundation Movember Valor Challenge Award (2018), and the National Institutes of Health (K99- K99CA237618).


Reference: Lingfan Xu, Yu Yin, Yanjing Li, Xufeng Chen, Yan Chang, Hong Zhang, Juan Liu, James Beasley, Patricia McCaw, Haoyue Zhang, Sarah Young, Jeff Groth, Qianben Wang, Jason W. Locasale, Xia Gao, Dean G. Tang, Xuesen Dong, Yiping He, Daniel George, Hailiang Hu, Jiaoti Huang, “A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer”, Proceedings of the National Academy of Sciences Mar 2021, 118 (13) e2012748118; DOI: 10.1073/pnas.2012748118


Provided by Duke Health

Beyond the Mouse Model: Yale Project Advances Treatments for Lung Disease (Medicine)

In 2020, a Yale-led team created a high-resolution atlas of all the cells in the human lung, an ambitious project that yielded insights into how cells are affected by the disease Idiopathic Pulmonary Fibrosis (IPF), which induces progressive scarring of lung tissue.

The researchers, led by Dr. Naftali Kaminski, are now taking that project one step further, expanding the atlas to identify signatures specific to different stages of the disease and then, with the help of artificial intelligence, exploring compounds that might reverse those signatures.

They hope the new advancements might inspire new therapies for treating pulmonary fibrosis in a way that is much faster and relevant to humans than relying on animal studies.

They are calling the new project the Pulmonary Fibrosis (PF) Connectome.

“Drug companies have libraries of thousands of compounds that could be used for therapeutics,” said Kaminski, the Boehringer Ingelheim Pharmaceuticals Inc. Professor of Medicine (pulmonary) and section chief of pulmonary, critical care, and sleep medicine at Yale School of Medicine. “By identifying compounds that reverse the cell and disease stage fibrosis signatures, we could prioritize those that are likely to stop or even reverse pulmonary fibrosis, not only slow it down.”

Once they’ve identified around 100 high priority compounds, he said, researchers will test these on lung slices, cultured in the lab from human lungs.

In patients with pulmonary fibrosis, increased scarring of the lung makes breathing progressively more difficult and prevents oxygen from reaching the bloodstream. The disease is often fatal. Across the country, an estimated 200,000 people suffer from IPF, and 40,000 die annually from the disease.

Current FDA-approved therapies work by slowing disease progression. Kaminski, who has been at the forefront of pulmonary fibrosis research for years, said that the scientific understanding has increased dramatically in recent years. But these insights have had limited impact on new therapies because “much of drug development uses models that have little semblance to the human lung.”

“Using human tissue from stages of progressing disease to determine the potential antifibrotic efficacy of compounds could overcome this limitation,” he said.

Three Lakes Foundation, a nonprofit organization dedicated to better understanding IPF, is providing significant funding for the two-year PF Connectome project, as part of the multimillion budget for the Three Lakes Consortium for Pulmonary Fibrosis (TLC4PF).

Kaminski said that the research team hopes to emerge with three to six promising drug candidates for a clinical study. He was recently part of a team that discovered that a cancer and Alzheimer’s drug, saracatinib, could be a potential therapy for IPF using methods similar to the ones that will be employed in the PF Connectome.

“We would never have considered this drug,” he said, “but because of computational analysis, we could build a rationale. If it were not for COVID-19, this trial would have started a year ago, but I’m glad to say that now we are recruiting.” (Clinical trial information is available here.)

Using human tissue in the search for effective drugs offers a marked contrast to relying on mouse models. That approach can take decades to reach human patients due to the slow testing and approval process. Between the acceleration of single-cell RNA sequencing — which allows scientists to profile in detail thousands of individual cells — the discovery of genetic biomarkers for fibrosis, and new insights into treatment pathways revealed by the IPF cell atlas, researchers are at a tipping-point moment, Kaminski said.

This research could also advance understanding of the long-term consequences of COVID-19, Kaminski added, noting that a small percentage of COVID-19 patients develop fibrotic complications in their lungs. While the connection between the two diseases is not yet fully understood, he said there are important parallels that his research might help uncover.

Other members of the research team include Ziv Bar-Joseph, a professor of computational biology and machine learning at Carnegie Mellon University; Geremy Clair, a scientist at the Pacific Northwest National Laboratory; Jun Ding, an assistant professor at McGill University; Dr. Oliver Eickelberg, a professor at the University of Pittsburgh’s Department of Medicine; and Xiting Yan, assistant professor of pulmonary and biostatistics in Yale School of Medicine’s Center for Precision Pulmonary Medicine (P2MED).

Featured image: Illustration of human lungs with drug compound symbols superimposed © stock.adobe.com


Provided by Yale University

COVID-19 Drives a More Severe Form of Acute Kidney Injury, Yale Study Finds (Medicine)

Patients who develop acute kidney injury (AKI) while being treated for COVID-19 have significantly worse kidney function in the months after their hospital discharge than non-COVID patients with AKI, new Yale research finds.

In a study of patients who experienced AKI at five hospitals, researchers found that individuals who were also diagnosed with COVID-19 had a 12-fold greater loss of kidney function six months after hospitalization than those who did not have COVID. The findings were published in JAMA Network Open.

“COVID-AKI looks like a different form of AKI in terms of long-term effects,” said lead author Dr. F. Perry Wilson, associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator.

Acute kidney injury is an abrupt decline in the kidney’s filtration function that is typically found in 15% of hospitalized patients and increases a patient’s likelihood of death ten-fold.

For reasons that are still not clear, the condition is more common in patients with COVID-19. Earlier research has shown that 24% to 57% of patients hospitalized with COVID-19 developed AKI. In fact, this latest research suggests that the disease may cause a more serious form of AKI to develop.

To measure kidney function, researchers looked at the estimated glomerular filtration rate (eGFR), which measures how much blood passes through the glomeruli, small filters in the kidney, each minute. Specifically, they look at how much creatinine — a chemical waste produced by the muscles — is in the blood. A healthy person has an eGFR of 90 or more milliliters per minute. A person with AKI will see a decline of 1 to 2 milliliters per minute, representing a mild loss of kidney function. But in the COVID-AKI patients, Perry said, the decline is about 12 milliliters per minute.

The observed drop in eGFR among patients with COVID-AKI was independent of patient demographics, comorbidities, or the severity of the AKI, suggesting it was the result of the hyperinflammatory state associated with COVID-19 or the residual effects of the virus, researchers said. These patients continued to have faster decline in eGFR after discharge, increasing the likelihood of long-term kidney disease, dialysis, and death.

The study involved 182 patients with COVID-19-associated AKI and 1,430 patients who had AKI but not COVID-19 at five hospitals in Connecticut and Rhode Island.

While researchers do not know what is driving this more aggressive form of AKI in COVID patients, they speculate in the study that COVID-AKI may induce tubulointerstitial fibrosis, or scarring driven by inflammation within the kidney.

It may be possible, in part, to mitigate this progression by optimizing blood pressure control and making sure any diabetes is well controlled, Wilson said. His team will continue to follow these COVID-AKI patients to further understand the long-term effects of the condition, he said.

Featured image: Illustration kidney being attacked by virus © stock.adobe.com


Reference: James Nugent, Abinet Aklilu, Yu Yamamoto, Michael Simonov, Aditya Biswas, Lama Ghazi, Jason Greenberg, Sherry Mansour, Dennis Moledina, F. Perry Wilson, “Assessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19”, JAMA Netw Open. 2021;4(3):e211095. doi: 10.1001/jamanetworkopen.2021.1095


Provided by Yale University

Yale Researchers Create Map of Undiscovered Life (Biology)

Less than a decade after unveiling the “Map of Life,” a global database that marks the distribution of known species across the planet, Yale researchers have launched an even more ambitious and perhaps important project — creating a map of where life has yet to be discovered.

For Walter Jetz, a professor of ecology and evolutionary biology at Yale who spearheaded the Map of Life project, the new effort is a moral imperative that can help support biodiversity discovery and preservation around the world.

“At the current pace of global environmental change, there is no doubt that many species will go extinct before we have ever learned about their existence and had the chance to consider their fate,” Jetz said. “I feel such ignorance is inexcusable, and we owe it to future generations to rapidly close these knowledge gaps.”

The new map of undiscovered species was published March 22 in the journal Nature Ecology & Evolution. A browsable version is available at mol.org/patterns/discovery.

Lead author Mario Moura, a former Yale postdoctoral associate in Jetz’s lab and now professor at Federal University of Paraiba, said the new study shifts the focus from questions like “How many undiscovered species exist?” to more applied ones such as “Where and what?”

“Known species are the ‘working units’ in many conservation approaches, thus unknown species are usually left out of conservation planning, management, and decision-making,” Moura said. “Finding the missing pieces of the Earth’s biodiversity puzzle is therefore crucial to improve biodiversity conservation worldwide.”

According to conservative scientific estimates, only some 10 to 20 percent of species on earth have been formally described. In an effort to help find some of these missing species, Moura and Jetz compiled exhaustive data that included the location, geographical range, historical discovery dates, and other environmental and biological characteristics of about 32,000 known terrestrial vertebrates. Their analysis allowed them to extrapolate where and what kinds of unknown species of the four main vertebrate groups are most likely to yet be identified.

They looked at 11 key factors which allowed the team to better predict locations where undiscovered species might be located. For instance, large animals with wide geographical ranges in populated areas are more likely to have already been discovered. New discoveries of such species are likely to be rare in the future. However, smaller animals with limited ranges who live in more inaccessible regions are more likely to have avoided detection so far.

“The chances of being discovered and described early are not equal among species,” Moura said. For instance, the emu, a large bird in Australia, was discovered in 1790 soon after taxonomic descriptions of species began. However, the small, elusive frog species Brachycephalus guarani wasn’t discovered in Brazil until 2012, suggesting more such amphibians remain to be found.

Moura and Jetz show that the chances of new species discovery varies widely across the globe. Their analysis suggests Brazil, Indonesia, Madagascar, and Colombia hold the greatest opportunities for identifying new species overall, with a quarter of all potential discoveries. Unidentified species of amphibians and reptiles are most likely to turn up in neotropical regions and Indo-Malayan forests.

Moura and Jetz also focused on another key variable in uncovering missing species — the number of taxonomists who are looking for them.

“We tend to discover the ‘obvious’ first and the ‘obscure’ later,” Moura said. “We need more funding for taxonomists to find the remaining undiscovered species.”

But the global distribution of taxonomists is greatly uneven and a map of undiscovered life can help focus new efforts, Jetz noted. That work will become increasingly important as nations worldwide gather to negotiate a new Global Biodiversity Framework under the Convention of Biological Diversity later this year and make commitments to halting biodiversity loss.

“A more even distribution of taxonomic resources can accelerate species discoveries and limit the number of ‘forever unknown’ extinctions,” Jetz said.

With partners worldwide, Jetz and colleagues plan to expand their map of undiscovered life to plant, marine, and invertebrate species in the coming years. Such information will be help governments and science institutions grapple with where to concentrate efforts on documenting and preserving biodiversity, Jetz said.

Featured image: Map of Undiscovered life © Yale


Reference: Moura, M.R., Jetz, W. Shortfalls and opportunities in terrestrial vertebrate species discovery. Nat Ecol Evol (2021). https://www.nature.com/articles/s41559-021-01411-5 https://doi.org/10.1038/s41559-021-01411-5


Provided by Yale University

How Cellular Fingertips May Help Cells “Speak” to Each Other? (Biology)

Researchers from Nara Institute of Science and Technology have broadened the known functions of an under-appreciated cell structure, with possible applications in wound closure and cancer therapy

What if you found out that you could heal using only a finger? It sounds like science fiction, reminiscent of the 1982 movie E.T. Well, it turns out that your body’s own cells can do something similarly unexpected. Researchers at Nara Institute of Science and Technology (NAIST) report in a new study seen in Developmental Cell a means by which cells may use “fingers” to communicate instructions for wound closure.

NAIST project leader Shiro Suetsugu has devoted his career to studying how cells shape themselves, initiate and accept communication among one other. An under-appreciated means of doing so is through filopodia, small finger-like cellular projections that are more commonly known to help certain cells crawl in the body.

“Filopodia are well-recognized as cellular locomotion machinery. Less understood is how filopodia help cells communicate, and the molecular details of how this is done,” says Suetsugu.

A focus of this line of research should be the proteins known by the acronym I-BAR. I-BAR proteins are well-known to help bend the plasma membrane, the “skin” of many cells, for filopodia formation and thus facilitate movement.

“We identified an I-BAR protein that severs filopodia,” says Suetsugu. An important element of this scission may be mechanical force, a stimulus that your body commonly applies to cells.

“Laser experiments showed that the force required for scission is approximately 8-20 kilopascals. These forces are similar to the 4-13 kilopascals, experienced by cells in blood capillaries,” Suetsugu says.

Severed filopodia go on to form structures called extracellular vesicles, a popular research topic in biology. Extracellular vesicles were used to basically be considered the trash bags of cells, used for disposing cellular waste. However, the vesicles are now considered to be communication packets rather than waste bags. “The pertinence of these vesicles to cancer metastasis has piqued researchers’ and clinicians’ interest,” notes Suetsugu.

What does this have to do with cell-cell communication? A simulated cell-scale wound healed faster when it was treated with filopodia-derived extracellular vesicles than if untreated. In other words, an I-BAR protein first induced filopodia scission and vesicle production. These vesicles then sent cellular signals that promoted cell migration toward one another, in a way that may promote wound closure.

By understanding how cells fully use their molecular machinery to send instructions to other cells, Suetsugu is optimistic that medical practitioners will develop new means to safely treat cancer and other diseases.

“Certain BAR proteins are pertinent to cancer cell biology. BAR proteins are also pertinent to cell locomotion. By learning more about how these proteins aid cell-cell communication, we may find better ways to stop cancer cells from spreading,” he says.

Featured image: The lattice light sheet microscopic images of the filopodia by expressing the I-BAR domain protein MIM. The vesicles that were released by the scission of MIM-induced filopodia are highlighted by yellow. The microscope locates at Mimori-Kiyosue lab (RIKEN). © Yuko Mimori-Kiyosue and Shiro Suetsugu


Reference: Tamako Nishimura*, Takuya Oyama*, Hooi Ting Hu*, Toshifumi Fujioka*, Kyoko Hanawa-Suetsugu, Kazutaka Ikeda, Sohei Yamada, Hiroki Kawana, Daisuke Saigusa, Hiroki Ikeda, Rie Kurata, Kayoko Oono-Yakura, Manabu Kitamata, Kazuki Kida, Tomoya Hikita, Kiyohito Mizutani, Kazuma Yasuhara, Yuko Mimori-Kiyosue, Chitose Oneyama, Kazuki Kurimoto, Yoichiroh Hosokawa, Junken Aoki, Yoshimi Takai, Makoto Arita & Shiro Suetsugu, “Filopodium-derived vesicles produced by MIM enhance the migration of recipient cells”, Developmental Cell, 2021, 56(6). DOI: 10.1016/j.devcel.2021.02.029 .


Provided by NAIST

Negative Mood Linked to Prolonged Amygdala Activity (Neuroscience)

Similar brain activity patterns to negative and subsequent neutral stimuli connected to increase in negative mood

How the amygdala responds to viewing negative and subsequent neutral stimuli may impact our daily mood, according to new research published in JNeurosci.

The amygdala evaluates the environment to find potential threats. If a threat does appear, the amygdala can stay active and respond to new stimuli like they are threatening too. This is helpful when you are in a dangerous situation, but less so when spilling your coffee in the morning keeps you on edge for the rest of the day.

In a recent study, Puccetti et al. examined data collected from the “Midlife in the US” longitudinal study. Participants completed a psychological wellbeing assessment and eight daily telephone interviews to assess their mood. They also came into the lab for an fMRI task: they viewed negative, positive, and neutral images with a picture of a neutral facial expression in between each image.

When the amygdala activated in a similar pattern as the participants viewed negative images and the neutral faces that followed, this persistent activity predicted increases in negative daily mood and decreases in positive daily mood. In turn, participants who experienced increased positive mood displayed greater psychological wellbeing. These results suggest amygdala activity influences how a person feels day-to-day, which can impact overall psychological wellbeing.

Featured image: Left amygdala persistence following negative images predicts psychological well-being via daily positive affect. © Puccetti et al., JNeurosci 2021


Paper title: Nikki A. Puccetti, Stacey M. Schaefer, Carien M. van Reekum, Anthony D. Ong, David M. Almeida, Carol D. Ryff, Richard J. Davidson and Aaron S. Heller, “Linking Amygdala Persistence To Real-World Emotional Experience and Psychological Well-Being”, Journal of Neuroscience 22 March 2021, JN-RM-1637-20; DOI: https://doi.org/10.1523/JNEUROSCI.1637-20.2021


Provided by Society for Neuroscience