New anatomical study of the human precuneus with geometric models

Emiliano Bruner, a paleoneurologist at the Centro Nacional de Investigación sobre la Evolución Humana (CENIEH), has just published a paper on the morphology of the precuneus in adult humans, which concludes that the variations in its length, height and thickness in the cerebral cortex are independent, suggesting that different cortical areas are involved in its growth, as well as in the differences between individuals that can be observed.

These differences are apparently related to the development of the cortical surface of the brain itself, and not to a deformation of the cranial cavity due to spatial constraints on the cranium. In the paper, this evidence is discussed within the framework of possible anatomical correspondences between human brain areas and the same areas described in other primates, whose functions and similarities still remain to be clarified.

To conduct this analysis, magnetic resonance scans of 50 individuals of both sexes and spatial models of cerebral geometry were used.

More developed in humans

The precuneus is the most medial region of the superior parietal lobules. It is particularly variable in its shape and size among adult individuals, and is much more highly developed in humans than in other primates. “The corresponding areas are also better developed in our species when we compare ourselves with other extinct hominids,” states Bruner.

At the cognitive level, the precuneus is principally involved in integrating the somatic information of the body with visual information, coordinating the body at the physical, chronological and social levels, and generating a virtual space involved in the imagination and the capacity for simulation.

Source: Read Full Article

‘Multi-omics’ adds new cell to immune family tree

WEHI researchers have used powerful ‘single cell multi-omics’ technologies to discover a previously unknown ancestor of T and B lymphocytes, which are critical components of our immune system.

Using an approach akin to breaking a sports team’s performance down to the individual player statistics, the researchers looked at multiple aspects of single developing immune cells to define which cells would only give rise to T and B lymphocytes. This revealed a new stage in lymphocyte development, information which could enrich future studies of the immune system. The discovery has also led to new research opportunities, with WEHI establishing of one of Australia’s first dedicated and integrated single cell research platforms in 2018, which is now being used to solve other research questions.

The research, which was published in Nature Immunology today, was led by Dr. Shalin Naik, Dr. Daniela Zalcenstein, Mr Luyi Tian, Mr Jaring Schreuder and Ms Sara Tomei.

Focussing on single cells

Our immune system comprises many different types of cells with different functions, but all immune cells are derived from a single type of cell, a blood stem cell. The development of different immune cell types occurs through a branching ‘family tree’ of immature cells. At earlier stages of immune cell development, individual cells can give rise to several different types of mature cell, but as development progresses, cells become more limited in which final mature cells they can produce.

T and B lymphocytes—which are critical for targeted, specific immune responses—are closely related immune cells, meaning they share many common steps in their development, said Dr. Naik. “Decades of research have defined how T and B lymphocytes develop, and the ‘branch points’ in their family tree when the developing cells lose the capacity to develop into other immune cell types,” he said.

Dr. Zalcenstein said that to gain new insights into questions such as how immune cells develop, the team established Australia’s first ‘single cell multi-omics’ platform, which is now available to all researchers within the Single Cell Open Research Endeavour (SCORE) established by Dr. Naik and Dr. Zalcenstein in collaboration with Dr. Stephen Wilcox of WEHI’s Genomics Hub and Associate Professor Matthew Ritchie.

“Multi-omics technologies combine different biological data sets—such as genomics, transcriptomics and proteomics—to compare different samples in more detail than is possible by looking at one data set. We have applied this approach to study individual cells, in this case developing immune cells, to understand in more detail which cells can give rise to lymphocytes. This approach is called single cell multi-omics,” she said.

“Rather than looking at data combined from many cells in a sample, we focus in on individual cells to understand the differences that exist within a larger population. It’s like looking at a football team—you can average out the number of goals, tackles and kicks per player in a game, but if you look at individual player statistics, you may discover that one player scored lots of goals, while another player was responsible for most of the tackles,” she said.

A new lymphocyte progenitor

SCORE’s study of immune cell precursors revealed a previously unrecognised cell type that could give rise to T and B lymphocytes, but not other immune cells.

“This cell occurred much earlier in lymphocyte development than we had suspected,” Dr. Naik said. “Previous techniques had grouped different immune progenitors together, but by studying individual cells we were able to identify one cell type that was committed to developing into T and B lymphocytes.”

The discovery adds a new layer to the family tree of T and B lymphocytes and could provide a boost to other areas of research.

“Understanding in more detail how T and B lymphocytes develop could lead to better approaches to regenerate these cells as a treatment for certain diseases,” Dr. Naik said. “We also know that many types of leukaemia arise from defects in early stages of immune cell development, so we are curious to know whether this progenitor cell has links to any forms of leukaemia.”

Source: Read Full Article

Coronavirus pushes classroom online leaving teachers to find new ways to connect with students

Virtual learning creates difficulties for ESL students

For non-native speaking English students, trying to get good grades while learning a new language can be challenging at the best of times, but as classes turn virtual some students are being left behind.

With the coronavirus mounting a resurgence in areas across the U.S., schools not already using a hybrid schedule to teach students may look to begin virtual learning in their districts. But by moving lessons online, teachers will lose the in-person connection they have with some students, which could make it difficult to pick up on cues regarding mental health.

“Teachers are translators of emotion,” Dr. Isaiah Pickens, a clinical psychologist who works with teachers and educators to identify and address racial inequality issues and mental health problems in students, told Fox News. “They are able to see students as an individual and in the context of the classroom.”

HEALTHY YOUNG PEOPLE MAY WAIT FOR CORONAVIRUS VACCINE UNTIL 2022, WHO OFFICIAL SAYS

Losing the physical classroom, however, doesn’t mean teachers have to lose the connection with their students. Pickens said teachers will still have plenty of information coming their way from students that could signal a larger issue is going on.

“If there’s a change in mood, there’s less engagement, hearing things as the student learns from home like arguments, etc., these allow educators to perk their ears up,” he said.

And while the safety of the physical classroom may be gone, there are many ways educators can provide support to their students virtually that might even be more helpful than before.

“The virtual world gives multiple modes for communicating, so there are multiple ways you can communicate something that you are experiencing,” Pickens said, adding that a chatroom, an email, or a video chat might actually make it easier for a student to approach a teacher with an issue rather than doing so in-person.

Others, however, may feel at a disadvantage to teaching their students remotely, especially those who never had the chance to meet their students in person to establish a baseline for their mood, demeanor or work habits. For those teachers, Pickens recommends looking for the universal signs that could mean emotional distress such as feelings of hopeless, incomplete assignments, low levels of engagement, or not participating in class activities online, or being a disruption like arguing with students in online chats.

“Teachers don’t need to be social workers, but what [recognizing these emotions] does is it normalizes that one, we’re all going through something right now and two, it’s OK to share parts of ourselves in virtual space to use that foundation to continue to connect and open up in many ways,” he said.  

Being direct when communicating with the student can help bolster their emotional being or let them know there is help available. Teachers should reach out directly to the student to let them know they notice a change in attitude, Pickens said.

“Being direct allows students to feel seen,” Pickens said. “Communicating that they are not a burden, whether virtual or in a private chat, saying ‘I’m wondering what it is that has you feeling whatever feeling they are feeling,’ it helps the kids have language to communicate. Think about who is the best ongoing support for the child, it might be a parent, or it might be a peer who can help make the kid feel less lonely – and sometimes it might be professional support.”

On the flip side, Pickens said virtual learning has helped teachers notice students who may have previously slipped through the cracks due to shyness or lack of confidence in the classroom, and those students are starting to blossom through online platforms. It’s also helping to identify students who might need more academic support.

CLICK HERE FOR COMPLETE CORONAVIRUS COVERAGE 

“One of the things teachers have been really praising is multiple ways to engage in class – students are engaging a lot more and it’s very easy to be a student by just participating in the chat,” he said.

Source: Read Full Article

New developments for the treatment of muscle spasticity after stroke and nervous system defects

Chronic muscle spasticity after nervous system defects like stroke, traumatic brain and spinal cord injury, multiple sclerosis and painful low back pain affect more than 10% of the population, with a socioeconomic cost of about 500 billion USD. Currently, there is no adequate remedy to help these suffering people, which generates an immense medical need for a new generation antispastic drugs.

András Málnási-Csizmadia, co-founder of Motorpharma Ltd. and professor at Eötvös Loránd University in Hungary leads the development of a first-in-class drug candidate co-sponsored by Printnet Ltd. MPH-220 directly targets and inhibits the effector protein of muscle contraction, potentially by taking one pill per day. By contrast, current treatments have low efficacy and cause a wide range of side effects because they act indirectly, through the nervous system.

“We receive desperate emails from stroke survivors, who suffer from the excruciating symptoms of spasticity, asking if they could participate in our research. We work hard to accelerate the development of MPH-220 to alleviate these people’s chronic spasticity,” said Prof. Málnási-Csizmadia.

The mechanism of action of MPH-220 and preclinical studies are recently published in Cell. Dr. Máté Gyimesi, CSO of Motorpharma Ltd. highlighted: “The scientific challenge was to develop a chemical compound which discriminates between skeletal and cardiac muscle myosins, the motor proteins of these contractile systems. This feature of MPH-220 makes it highly specific and safe.”

Prof. James Spudich, co-founder of Cytokinetics, MyoKardia and Kainomyx, all companies developing drugs targeting cytoskeletal components, is also very excited about MPH-220 as a possible next generation muscle relaxant. “Cytokinetics and MyoKardia have shown that cardiac myosin is highly druggable, and both companies have potential drugs acting on cardiac myosin in late phase clinical trials. Skeletal myosin effectors, however, have not been reported. Motorpharma Ltd. has now developed a specific inhibitor of skeletal myosin, MPH-220, a drug candidate that may reduce the everyday painful spasticity for about 10% of the population that suffers from low back pain and neurological injury related diseases,” said Professor Spudich, former chair of Stanford medical school’s Biochemistry department, a Lasker awardee.

Drug development specifically targeting myosins is becoming a distinguished area, as indicated by last week’s acquisition of MyoKardia by Bristol-Myers Squibb Co. for 13.1 billion dollars in an all-cash deal, in the hope of marketing their experimental heart drug targeting cardiac myosin. This business activity shows the demand for start-up biotech companies such as Myokardia or Motorpharma.

Source: Read Full Article

‘Sweet 16’ party becomes ‘superspreader’ event in New York

A 16th birthday party in New York state became a super-spreader event with dozens of attendees contracting coronavirus, according to officials.

The September 25 shindig at the plush Miller Place Inn on Long Island left 37 people infected with COVID-19 and forced more than 270 into quarantine.

Over 80 people attended the party, known as a “Sweet 16” in the United States, well above the state’s 50-person limit. The venue has been closed temporarily and fined $12,000, local officials said.

“We’ve never seen a super-spreader event like this before in Suffolk County,” tweeted the area’s county executive on Wednesday.

“People have to act responsibly so that we do not have another economic setback.”

New York state has largely kept coronavirus under control in recent months after 33,000 residents died from the virus, mainly in the spring.

But in recent weeks, infections have multiplied in some areas, especially in neighborhoods with large Orthodox Jewish populations.

Governor Andrew Cuomo closed non-essential businesses and capped places of worship at ten people in the so-called red zones.

New York City Mayor Bill de Blasio defended the measures on Thursday, citing tightened restrictions in Europe where cases are on the rise.

Source: Read Full Article

New study shows which medical procedures pose COVID-19 risk to health-care providers

Autopsy, airway suctioning and cardiopulmonary resuscitation are among the list of medical procedures that pose a risk of spreading COVID-19 from a patient to their health-care provider by creating aerosols, according to new research published in the journal BMJ Open Respiratory Research by an international team of experts including occupational health, preventive medicine and infectious disease specialists.

The team, led by University of Alberta medicine professor Sebastian Straube, carried out a systematic review of public health guidelines, research papers and policy documents from around the globe to determine which procedures are classified as aerosol-generating.

“What we sought to do was to understand which procedures generate aerosols and therefore require a higher grade of personal protective equipment,” said Straube, who also heads the preventive medicine division of the Faculty of Medicine & Dentistry.

“Where there is 80 percent agreement from a number of different source documents, we are reasonably confident that, yes, the classification of these procedures as aerosol-generating is accurate.”

Straube recommended that further research be done on the short list of procedures for which they found no consensus, such as taking throat swabs.

The team of 19 Canadian, British, American and other researchers includes renowned Oxford University primary care expert Trisha Greenhalgh and first author Tanya Jackson, Straube’s research associate. They came together to share their expertise at the outset of the COVID-19 pandemic and have published rapid reviews on the efficacy of respirator masks versus standard surgical masks, eye protection and shoe covers.

“We are providing a summary of the evidence to inform policy-making decisions and guideline development,” Straube said.

An aerosol is a suspension of fine solid or liquid particles in air, Straube said. “Larger particles settle in a reasonably short distance, and are referred to as ‘droplets’ in the infection control context,” the paper states. “Smaller particles can travel as aerosols on air currents, remaining in the air for longer and distributing over a wide area.”

Straube said the goal is to prevent health-care workers from becoming infected with COVID-19, both to protect them from severe disease as individuals and to maintain staffing levels in health-care systems during the pandemic.

Health-care workers who perform aerosol-generating procedures should wear filtering facepiece respirators, known as N-95 masks in North America, Straube said, along with other personal protective equipment (PPE) such as gloves, gowns and eye protection.

“PPE is typically displayed at the bottom rung of the hierarchy of hazard controls,” Straube said.

Source: Read Full Article

Scientists develop new precise therapeutic leukemia vaccine

Exploration of new leukemia antigens and construction of appropriate delivery systems using FDA-approved material are important strategies for developing leukemia vaccines for clinic use.

Researchers from the Institute of Process Engineering (IPE) of Chinese Academy of Sciences and Zhujiang Hospital of Southern Medical University have developed a new type of precise therapeutic vaccine against leukemia. It utilizes self-healing polylactic acid microcapsules for co-encapsulating a new epitope peptide and PD-1 antibody.

The study was published in Nature Biomedical Engineering on October 12.

Although the possibility of treating leukemia through vaccination has been established, therapeutic performance still falls short of expectations in clinic.

“Our clinical findings revealed the high expression of EPS8 and PD-1/PD-L1 in leukemia patients, which could be respectively used as a new type of leukemia antigen and a checkpoint target for a leukemia vaccine,” said Prof. Li Yuhua from Zhujiang Hospital.

In the novel vaccine, epitope peptides and PD-1 antibodies can be simply, mildly and efficiently loaded into polylactic acid microcapsules, facilitated by the unique self-healing feature of the microcapsule.

After a single vaccination, the deposition and degradation of microcapsules at the local injection site lead to recruitment of activated antigen-presenting cells and sustained release of both cargos.

“With the synergism of these two aspects, we observed a significant improvement in specific Cytotoxic T Lymphocyte (CTL) activation,” said Prof. Wei Wei from IPE.

The researchers also verified the availability of the novel vaccine using various epitope peptides in different models, such as murine leukemia, humanized cell line-derived leukemia xenograft (CDX) and patient-derived leukemia xenograft (PDX) models.

The microcapsule-based formulation demonstrated its superior performance over that of the ISA adjuvant (commercialized adjuvant) in all leukemia therapeutic models, showing the promise of the microcapsule-based vaccine for use against various leukemia antigens in clinic.

“With the advantages of FDA-approved polylactic acid material, convenience in preparing the vaccine formulation, diversity of vaccine components, and excellent therapeutic effect, the microcapsule-based vaccine exhibits great potential for clinical translation,” said Prof. Ma Guanghui from IPE.

Source: Read Full Article

New discovery could help improve cancer vaccines

Cancer vaccines have shown promise in treating certain tumors, such as melanoma. But such vaccines have limitations. They often target normal proteins that may be more abundant in the tumor but also are present in healthy tissue, which can lead to off-target effects that cause autoimmune disorders and also reduce the effectiveness of the vaccines.

The mutated DNA of cancer cells often produces abnormal proteins, whose fragments can help distinguish the tumor from healthy tissue. Such protein fragments could be harnessed to train the immune system to attack the tumors with, in theory, few side effects. Now, a broad collaboration of scientists in academia and industry have identified the most important features of the protein fragments to help researchers design better immunotherapies against cancer.

The study, co-led by researchers at Washington University School of Medicine in St. Louis, appears Oct. 9 in the journal Cell.

These abnormal protein fragments are called neoantigens. The new study identifies five features of neoantigens that optimize the ability to trigger the body’s T cells to attack the cancer and leave healthy tissue untouched. Using the new criteria, the researchers used computer modeling to accurately predict 75% of effective neoantigens and eliminate 98% of ineffective mutant proteins in melanoma and a common type of lung cancer.

The research team, called the Tumor Neoantigen Selection Alliance (TESLA), has made the computer model and dataset freely available to the research community to speed the development of cancer vaccines and other immunotherapies.

“For scientists working to create personalized cancer vaccines that target the unique neoantigens of an individual patient’s tumor, this is a resource that is desperately needed,” said co-senior author Robert D. Schreiber, PhD, the Andrew M. Bursky & Jane M. Bursky Distinguished Professor of Pathology and Immunology. “There has been an explosion of approaches to try and figure out which are the best mutant proteins to target in a tumor. This broad approach is more accurate and will help to design anticancer vaccines that potentially are more effective for patients.”

The features that the researchers identified as most important in selecting effective neoantigens include the abundance of a specific neoantigen in the tumor; the strength with which the neoantigen binds to vital immune proteins so the T cells can see it; the stability of the neoantigen on the immune protein complex; how much more often the immune proteins preferentially bind to the neoantigen versus the normal protein; and how foreign or distinct the neoantigen is from the normal protein.

Schreiber said that all these factors make sense in selecting the best neoantigens, but he was surprised by some of the findings on criteria that were not important for neoantigen effectiveness.

“We were able to eliminate some of the assumptions that we scientists sometimes make about what makes a good neoantigen,” said Schreiber, who also directs the Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs at Washington University School of Medicine. “For example, there has been a general sense that the mutant proteins that make the best neoantigens are the most hydrophobic — meaning they repel water. It turns out, that characteristic didn’t show any relationship to neoantigen effectiveness.”

Schreiber also pointed out that this study is focused on neoantigens that activate what are called CD8 T cells, which he describes as the immune system’s foot soldiers, those responsible for killing the tumor cell. He said future work should focus on neoantigens that also activate a different type of cell, CD4 T cells. Schreiber calls these the generals, cells that stay behind the front lines but direct the foot soldiers in their anti-cancer mission.

“In order to get a good immune response against a tumor, you need to activate both CD4 and CD8 T cells,” Schreiber said. “In future work, we would like to conduct a similar analysis to identify the best neoantigens for triggering the CD4 T cells as well. In designing an effective vaccine, we think we need at least one good CD8 neoantigen and one good CD4 neoantigen to trigger immune rejection of a tumor.”

The TESLA initiative, led by the Parker Institute for Cancer Immunotherapy and the Cancer Research Institute, includes 33 research teams from universities, biotech companies, pharmaceutical companies and nonprofit research institutes.

Source: Read Full Article

Study identifies brain cells most affected by epilepsy and new targets for their treatment

Epilepsy is one of the most common neurological diseases. It is caused by a malfunction in brain cells and is usually treated with medicines that control or counteract the seizures.

Scientists from the Faculty of Health and Medical Sciences, University of Copenhagen and Rigshospitalet have now identified the exact neurons that are most affected by epilepsy. Some of which have never been linked to epilepsy before. The newfound neurons might contribute to epileptogenesis—the process by which a normal brain develops epilepsy—and could therefore be ideal treatment targets.

“Our findings potentially allows for the development of entirely new therapeutic approaches tailored towards specific neurons, which are malfunctioning in cases of epilepsy. This could be a breakthrough in personalized medicine-based treatment of patients suffering from epileptic seizures,” says Associate Professor Konstantin Khodosevich from Biotech Research & Innovation Center (BRIC), Faculty of Health and Medical Sciences.

A major step towards more effective drugs

It is the first time a study investigates how every single neuron in the epileptic zone of the human brain is affected by epilepsy. The researchers have analyzed more than 117,000 neurons, which makes it the largest single cell dataset for a brain disorder published so far.

Neurons have been isolated from tissue resected from patients being operated as part of the Danish Epilepsy Surgery Programme at Rigshospitalet in Copenhagen.

“These patients continue to have seizures despite the best possible combination of anti-seizure drugs. Unfortunately, this is the case for 30-40% of epilepsy patients. Active epilepsy imposes serious physical, cognitive, psychiatric and social consequences on patients and families. A more precise understanding of the cellular mechanism behind epilepsy could be a major step forward for developing drugs specifically directed against the epileptogenic process compared to the current mode of action reducing neuronal excitability in general throughout the brain’ says associate professor Lars Pinborg, head of the Danish Epilepsy Surgery Program at Rigshospitalet.

From ‘neuronal soup’ to single cell analysis

The study from the Khodosevich Group differs from previous work by using single cell analysis. Earlier studies on neuronal behavior in regards to epilepsy have taken a piece of the human brain and investigated all the neurons together as a group or a ‘neuronal soup.” When using this approach, diseased cells and healthy cells are mixed together, which makes it impossible to identify potential treatment targets.

“By splitting the neurons into many thousands of single cells, we can analyze each of them separately. From this huge number of single cells, we can pinpoint exactly what neurons are affected by epilepsy. We can even make a scale from least to most affected, which means that we can identify the molecules with the most promising potential to be effective therapeutic targets,” says Khodosevich.

Next step is to study the identified neurons and how their functional changes contribute to epileptic seizures. The hope is to then find molecules that can restore epilepsy related neuronal function back to normal and inhibit seizure generation.

Expanding knowledge on underlying mechanisms of epilepsy

The study confirms expression from key genes known from a number of previous studies, but is also a dramatic expansion of knowledge on the subject. Previously, gene expression studies have identified a couple of hundred genes that changes in epilepsy.

Source: Read Full Article

New book considers the ‘bullshit asymmetry principle’

The “bullshit asymmetry principle” tells us that it takes far more energy to disprove bullshit than it takes to generate bullshit. In a world full of misleading statistics, gaslighting politicians and press-release-driven science, unmanaged bullshit abounds. In their book, “Calling Bullshit: The Art of Skepticism in a Data-Driven World,” (Random House, 2020) former SFI External Professor Carl T. Bergstrom (University of Washington) and Jevin D. West (University of Washington) unpack the ease with which misinformation has leached into every corner of society and call for a healthy dose of skepticism in science, media and everyday life.

These days, going online, turning on the television, or even using your cell phone means being inundated with content competing for clicks in a social media landscape where bullshit thrives. “We don’t understand how humans make collective decisions once you give them social media,” Bergstrom says. “And we don’t really have any adequate theory of what happens once you take all the computers in the world and you link them together and then people start sending [bullshit] to each other and resending it.”

Like many scientists who study complex systems, Bergstrom is fascinated by network phenomena. His current obsession with bullshit actually builds on his earlier career in epidemiology, when he studied how diseases spread over networks. “Then we saw social media come along and all of a sudden it was the same networks again, and things were spreading on networks, but what was spreading on networks was bullshit.”

To combat the pervasiveness of bullshit, Bergstrom and West call for a generation to be educated on ways to identify, interrogate and reject misinformation. “We need to improve media literacy,” West says. “We need to spend more time on education. We need to spend more time on research.” While it would be impossible to undo the impact of every piece of bullshit individually, the general population can be trained to understand when they’re reading, watching, or listening to something that is misleading, manipulated, or false.

Engagement from scientists at this juncture is also crucial. Places like the Santa Fe Institute are perfectly positioned to ask big questions, uncover deep and nuanced data, and share these findings with the greater community—all without compromising truth in the service of clicks.

“I think especially younger generations of scientists understand the power of media and of social media,” Bergstrom says. “And they have the desire to do more than advanced science in isolation, but to actually have an influence on society in various positive ways.”

Source: Read Full Article