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Anatomy

Why ‘Grey’s Anatomy’ Alum Katherine Heigl Described the Izzie-George Affair as ‘A Ratings Ploy’ – Showbiz Cheat Sheet

Katherine Heigl of Greys Anatomyportrayed Dr. Isobel (Izzie) Stevens for almost six seasons from 2005 to 2010.Frequently in storylines with co-star T.R. Knight, who played Izzies BFF George OMalley,Heigl was surprised when writers had the besties take a romantic turn.

While Heigl enjoyed working closely with Knightley, she felt conflicted over the storyline. With George married to Callie Torres (Sara Ramirez) at the time, Heigl felt Izzies actions were out of character.

In season 3, the friendship between George and Izzie turned physical after a night of too much alcohol. After confessing his actions to Callie, George embarked on a romantic relationship with Izzie. Heigl didnt think the plot twist was in line with her characters values.

That was kind of a big change for Izzie, wasnt it, after she was so up on her moral high ground, Heigl told Vanity Fair in 2007. They really hurt somebody, and they didnt seem to be taking a lot of responsibility for it.

Heigl wanted to remain true to her character and struggled with Izzies deviating from her wholesome persona.

RELATED:Why Greys Anatomy Alum Katherine Heigl Said This Comment Bothered Me The Most After Her Exit

I have a really hard time with that kind of thing, the Greys Anatomy alum revealed. Im maybe a little too black-and-white about it. I dont really know Izzie very well right now. Shes changed a lot. Im trying to figure her out and keep her real.

While she didnt fully agree with the shift between George and Izzie, Heigl realized that Greys Anatomy producers had to keep things interesting and hold their spot as a top-rated show.

It was a ratings ploy, the Suits actor remarked of the Izzie-George coupling. It was absolutely something that shocked people it wasnt predictable, and people didnt see it coming. Its our fourth season; theres not a lot of spontaneity left.

Heigl knew the series producers and writers needed to continually attract viewers, but she didnt want to compromise the integrity of the show.

Business is business, I understand that, she explained. But I want there to be some cooperation between the business end and the creative end, so theres some way of keeping it real.

Heigl revealed she was initially all for the romance between George and Izzie, mainly because it meant more time with Knight.

I was really excited about it in the beginning, she toldEntertainment Weeklyin 2010. I got to work more with my best friend and thats awesome.

When viewers werent buying in to the love story angle of the two pals, George and Izzie went back to platonic status. Clearly, Knight also held Heigl in high regard and enjoyed their time together on set.

RELATED:Greys Anatomy: Ellen Pompeo Singled Out Katherine Heigls Problem on the Show

A lot of us care way too much what people think, he told Vanity Fair. But its refreshing to have someone who speaks the kind of truth where your mouth just drops. To her, being up-front and straight with people is paramount. Theres a real freedom to that that Im still working on, but shes already got it. Its intrinsically who she is.

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Why 'Grey's Anatomy' Alum Katherine Heigl Described the Izzie-George Affair as 'A Ratings Ploy' - Showbiz Cheat Sheet

Anatomy

‘Kay’s Anatomy: A Complete (and Completely Disgusting) Guide to the Human Body’ – Newstalk

Author Adam Kay's best selling book This is Going to Hurt: Secret Diaries of a Junior Doctor gave readers a unique insight into the life of a medical professional and was the bestselling narrative non-fiction title of the decade.

Adam Kay joined Mark on Friday's edition of The Hard Shoulder to talk about his new book 'Kays Anatomy: A Complete (and Completely Disgusting) Guide to the Human Body'.

Can the human body be demystified for children and adults alike?

The rest is here:
'Kay's Anatomy: A Complete (and Completely Disgusting) Guide to the Human Body' - Newstalk

Cell Biology

Angelika Amon, cell biologist who pioneered research on chromosome imbalance, dies at 53 – MIT News

Angelika Amon, professor of biology and a member of the Koch Institute for Integrative Cancer Research, died on Oct. 29 at age 53, following a two-and-a-half-year battle with ovarian cancer.

"Known for her piercing scientific insight and infectious enthusiasm for the deepest questions of science, Professor Amon built an extraordinary career and in the process, a devoted community of colleagues, students and friends," MIT President L. Rafael Reif wrote in a letter to the MIT community.

Angelika was a force of nature and a highly valued member of our community, reflects Tyler Jacks, the David H. Koch Professor of Biology at MIT and director of the Koch Institute. Her intellect and wit were equally sharp, and she brought unmatched passion to everything she did. Through her groundbreaking research, her mentorship of so many, her teaching, and a host of other contributions, Angelika has made an incredible impact on the world one that will last long into the future.

A pioneer in cell biology

From the earliest stages of her career, Amon made profound contributions to our understanding of the fundamental biology of the cell, deciphering the regulatory networks that govern cell division and proliferation in yeast, mice, and mammalian organoids, and shedding light on the causes of chromosome mis-segregation and its consequences for human diseases.

Human cells have 23 pairs of chromosomes, but as they divide they can make errors that lead to too many or too few chromosomes, resulting in aneuploidy. Amons meticulous and rigorous experiments, first in yeast and then in mammalian cells, helped to uncover the biological consequences of having too many chromosomes. Her studies determined that extra chromosomes significantly impact the composition of the cell, causing stress in important processes such as protein folding and metabolism, and leading to additional mistakes that could drive cancer. Although stress resulting from aneuploidy affects cells ability to survive and proliferate, cancer cells which are nearly universally aneuploid can grow uncontrollably. Amon showed that aneuploidy disrupts cells usual error-repair systems, allowing genetic mutations to quickly accumulate.

Aneuploidy is usually fatal, but in some instances extra copies of specific chromosomes can lead to conditions such as Down syndrome and developmental disorders including those known as Patau and Edwards syndromes. This led Amon to work to understand how these negative effects result in some of the health problems associated specifically with Down syndrome, such as acute lymphoblastic leukemia. Her expertise in this area led her to be named co-director of the recently established Alana Down Syndrome Center at MIT.

Angelikas intellect and research were as astonishing as her bravery and her spirit. Her labs fundamental work on aneuploidy was integral to our establishment of the center, say Li-Huei Tsai, the Picower Professor of Neuroscience and co-director of the Alana Down Syndrome Center. Her exploration of the myriad consequences of aneuploidy for human health was vitally important and will continue to guide scientific and medical research.

Another major focus of research in the Amon lab has been on the relationship between how cells grow, divide, and age. Among other insights, this work has revealed that once cells reach a certain large size, they lose the ability to proliferate and are unable to reenter the cell cycle. Further, this growth contributes to senescence, an irreversible cell cycle arrest, and tissue aging. In related work, Amon has investigated the relationships between stem cell size, stem cell function, and tissue age. Her labs studies have found that in hematopoetic stem cells, small size is important to cells ability to function and proliferate in fact, she posted recent findings on bioRxiv earlier this week and have been examining the same questions in epithelial cells as well.

Amon lab experiments delved deep into the mechanics of the biology, trying to understand the mechanisms behind their observations. To support this work, she established research collaborations to leverage approaches and technologies developed by her colleagues at the Koch Institute, including sophisticated intestinal organoid and mouse models developed by the Yilmaz Laboratory, and a microfluidic device developed by the Manalis Laboratory for measuring physical characteristics of single cells.

The thrill of discovery

Born in 1967, Amon grew up in Vienna, Austria, in a family of six. Playing outside all day with her three younger siblings, she developed an early love of biology and animals. She could not remember a time when she was not interested in biology, initially wanting to become a zoologist. But in high school, she saw an old black-and-white film from the 1950s about chromosome segregation, and found the moment that the sister chromatids split apart breathtaking. She knew then that she wanted to study the inner workings of the cell and decided to focus on genetics at the University of Vienna in Austria.

After receiving her BS, Amon continued her doctoral work there under Professor Kim Nasmyth at the Research Institute of Molecular Pathology, earning her PhD in 1993. From the outset, she made important contributions to the field of cell cycle dynamics. Her work on yeast genetics in the Nasmyth laboratory led to major discoveries about how one stage of the cell cycle sets up for the next, revealing that cyclins, proteins that accumulate within cells as they enter mitosis, must be broken down before cells pass from mitosis to G1, a period of cell growth.

Towards the end of her doctorate, Amon became interested in fruitfly genetics and read the work of Ruth Lehmann, then a faculty member at MIT and a member of the Whitehead Institute. Impressed by the elegance of Lehmanns genetic approach, she applied and was accepted to her lab. In 1994, Amon arrived in the United States, not knowing that it would become her permanent home or that she would eventually become a professor.

While Amons love affair with fruitfly genetics would prove short, her promise was immediately apparent to Lehmann, now director of the Whitehead Institute. I will never forget picking Angelika up from the airport when she was flying in from Vienna to join my lab. Despite the long trip, she was just so full of energy, ready to talk science, says Lehmann. She had read all the papers in the new field and cut through the results to hit equally on the main points.

But as Amon frequently was fond of saying, yeast will spoil you. Lehmann explains that because they grow so fast and there are so many tools, your brain is the only limitation. I tried to convince her of the beauty and advantages of my slower-growing favorite organism. But in the end, yeast won and Angelika went on to establish a remarkable body of work, starting with her many contributions to how cells divide and more recently to discover a cellular aneuploidy program.

In 1996, after Lehmann had left for New York Universitys Skirball Institute, Amon was invited to become a Whitehead Fellow, a prestigious program that offers recent PhDs resources and mentorship to undertake their own investigations. Her work on the question of how yeast cells progress through the cell cycle and partition their chromosomes would be instrumental in establishing her as one of the worlds leading geneticists. While at Whitehead, her lab made key findings centered around the role of an enzyme called Cdc14 in prompting cells to exit mitosis, including that the enzyme is sequestered in a cellular compartment called the nucleolus and must be released before the cell can exit.

I was one of those blessed to share with her a eureka moment, as she would call it, says Rosella Visintin, a postdoc in Amons lab at the time of the discovery and now an assistant professor at the European School of Molecular Medicine in Milan. She had so many. Most of us are lucky to get just one, and I was one of the lucky ones. Ill never forget her smile and scream neither will the entire Whitehead Institute when she saw for the first time Cdc14 localization: You did it, you did it, you figured it out! Passion, excitement, joy everything was in that scream.

In 1999, Amons work as a Whitehead Fellow earned her a faculty position in the MIT Department of Biology and the MIT Center for Cancer Research, the predecessor to the Koch Institute. A full professor since 2007, she also became the Kathleen and Curtis Marble Professor in Cancer Research, associate director of the Paul F. Glenn Center for Biology of Aging Research at MIT, a member of the Ludwig Center for Molecular Oncology at MIT, and an investigator of the Howard Hughes Medical Institute.

Her pathbreaking research was recognized by several awards and honors, including the 2003 National Science Foundation Alan T. Waterman Award, the 2007 Paul Marks Prize for Cancer Research, the 2008 National Academy of Sciences (NAS) Award in Molecular Biology, and the 2013 Ernst Jung Prize for Medicine. In 2019, she won the Breakthrough Prize in Life Sciences and the Vilcek Prize in Biomedical Science, and was named to the Carnegie Corporation of New Yorks annual list of Great Immigrants, Great Americans. This year, she was given the Human Frontier Science Program Nakasone Award. She was also a member of the NAS and the American Academy of Arts and Sciences.

Lighting the way forward

Amons perseverance, deep curiosity, and enthusiasm for discovery served her well in her roles as teacher, mentor, and colleague. She has worked with many labs across the world and developed a deep network of scientific collaboration and friendships. She was a sought-after speaker for seminars and the many conferences she attended. In over 20 years as a professor at MIT, she has mentored more than 80 postdocs, graduate students, and undergraduates, and received the School of Sciences undergraduate teaching prize.

Angelika was an amazing, energetic, passionate, and creative scientist, an outstanding mentor to many, and an excellent teacher, says Alan Grossman, the Praecis Professor of Biology and head of MITs Department of Biology. Her impact and legacy will live on and be perpetuated by all those she touched.

Angelika existed in a league of her own, explains Kristin Knouse, one of Amons former graduate students and a current Whitehead Fellow. She had the energy and excitement of someone who picked up a pipette for the first time, but the brilliance and wisdom of someone who had been doing it for decades. Her infectious energy and brilliant mind were matched by a boundless heart and tenacious grit. She could glance at any data and immediately deliver a sharp insight that would never have crossed any other mind. Her positive attributes were infectious, and any interaction with her, no matter how transient, assuredly left you feeling better about yourself and your science.

Taking great delight in helping young scientists find their own eureka moments, Amon was a fearless advocate for science and the rights of women and minorities and inspired others to fight as well. She was not afraid to speak out in support of the research and causes she believed strongly in. She was a role model for young female scientists and spent countless hours mentoring and guiding them in a male-dominated field. While she graciously accepted awards for women in science, including the Vanderbilt Prize and the Women in Cell Biology Senior Award, she questioned the value of prizes focused on women as women, rather than on their scientific contributions.

Angelika Amon was an inspiring leader, notes Lehmann, not only by her trailblazing science but also by her fearlessness to call out sexism and other -isms in our community. Her captivating laugh and unwavering mentorship and guidance will be missed by students and faculty alike. MIT and the science community have lost an exemplary leader, mentor, friend, and mensch.

Amons wide-ranging curiosity led her to consider new ideas beyond her own field. In recent years, she has developed a love for dinosaurs and fossils, and often mentioned that she would like to study terraforming, which she considered essential for a human success to life on other planets.

It was always amazing to talk with Angelika about science, because her interests were so deep and so broad, her intellect so sharp, and her enthusiasm so infectious, remembers Vivian Siegel, a lecturer in the Department of Biology and friend since Amons postdoctoral days. Beyond her own work in the lab, she was fascinated by so many things, including dinosaurs dreaming of taking her daughters on a dig lichen, and even life on Mars.

Angelika was brilliant; she illuminated science and scientists, says Frank Solomon, professor of biology and member of the Koch Institute. And she was intense; she warmed the people around her, and expanded what it means to be a friend.

Amon is survived by her husband Johannes Weis, and her daughters Theresa and Clara Weis, and her three siblings and their families.

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Angelika Amon, cell biologist who pioneered research on chromosome imbalance, dies at 53 - MIT News

Cell Biology

Touch and taste? Its all in the suckers – ScienceBlog.com

We think because the molecules do not solubilize well, they could, for instance, be found on the surface of octopuses prey and [whatever the animals touch], saidNicholas Bellono, an assistant professor of molecular and cellular biology and the studys senior author. So, when the octopus touches a rock versus a crab, now its arm knows, OK, Im touching a crab [because] I know theres not only touch but theres also this sort of taste.

In addition, scientists found diversity in what the receptors responded to and the signals they then transmitted to the cell and nervous systems.

We think that this is important because it could facilitate complexity in what the octopus senses and also how it can process a range of signals using its semi-autonomous arm nervous system to produce complex behaviors, Bellono said.

The scientists believe this research can help uncover similar receptor systems in other cephalopods, the invertebrate family that also includes squids and cuttlefish. The hope is to determine how these systems work on a molecular level and answer some relatively unexplored questions about how these creatures capabilities evolved to suit their environment.

Not much is known about marine chemotactile behavior and with this receptor family as a model system, we can now study which signals are important for the animal and how they can be encoded, saidLena van Giesen, a postdoctoral fellow in theBellono Laband lead author of the paper. These insights into protein evolution and signal coding go far beyond just cephalopods.

Along with Giesen, other co-authors from the lab includePeter B. Kilian, an animal technician, andCorey A.H. Allard, a postdoctoral fellow.

The strategies they have evolved in order to solve problems in their environment are unique to them and that inspires a great deal of interest from both scientists and non-scientists alike, Kilian said. People are drawn to octopuses and other cephalopods because they are wildly different from most other animals.

The team set out to uncover how the receptors are able to sense chemicals and detect signals in what they touch, like an arm around a snail, to help them make choices.

Octopus arms are distinct and complex. About two-thirds of an octopuss neurons are located in their arms. Because the arms operate partially independently from the brain, if one is severed it can still reach for, identify, and grasp items.

People are drawn to octopuses and other cephalopods because they are wildly different from most other animals.

Peter B. Kilian

The team started by identifying which cells in the suckers actually do the detecting. After isolating and cloning the touch and chemical receptors, they inserted them in frog eggs and in human cell lines to study their function in isolation. Nothing like these receptors exists in frog or human cells, so the cells act essentially like closed vessels for the study of these receptors.

The researchers then exposed those cells to molecules such as extracts from octopus prey and others items to which these receptors are known to react. Some test subjects were water-soluble, like salts, sugars, amino acids; others do not dissolve well and are not typically considered of interest by aquatic animals. Surprisingly, only the poorly soluble molecules activated the receptors.

Researchers then went back to the octopuses in their lab to see whether they too responded to those molecules by putting those same extracts on the floors of their tanks. They found the only odorants the octopuses receptors responded to were a non-dissolving class of naturally occurring chemicals known as terpenoid molecules.

[The octopus] was highly responsive to only the part of the floor that had the molecule infused, Bellono said. This led the researchers to believe that the receptors they identified pick up on these types of molecules and help the octopus distinguish what its touching. With the semi-autonomous nervous system, it can quickly make this decision: Do I contract and grab this crab or keep searching?

While the study provides a molecular explanation for this aquatic touch-taste sensation in octopuses through their chemotactile receptors, the researchers suggest further study is needed, given that a great number of unknown natural compounds could also stimulate these receptors to mediate complex behaviors.

Were now trying to look at other natural molecules that these animals might detect, Bellono said.

This research was supported by the New York Stem Cell Foundation, the Searle Scholars Program, the Sloan Foundation, the Klingenstein-Simons Fellowship, the National Institutes of Health, and the Swiss National Science Foundation.

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Touch and taste? Its all in the suckers - ScienceBlog.com

Cell Biology

Foundational research shows early gene therapy prevents Angelman syndrome – BioWorld Online

Scientists working at the University of North Carolina, Chapel Hill reported in the Oct. 21, 2020, issue of Nature on the successful development of a one-time specific sequence-directed gene therapy approach using the combination of AAV with CRISPR technology that successfully prevented the presentation of Angelman syndrome throughout the lifetime of a mouse model.

Lifelong gene therapy has held promise for decades now as one of the only approaches that could possibly address many neurodevelopmental genetic disorders. But even after decades of research, gene therapy still possesses significant risks due to untoward random genomic insertions of vectors that could ultimately cause other genetic disorders.

Meanwhile, it has been known for decades now that adeno-associated virus (AAV) is a particularly powerful potential gene therapy vector because AAV integrates into the genome so well. However, the integration of AAV has always been random and so it inherently comes with significant risk.

This is the first time that a treatment for Angelman syndrome has been shown to correct this neurodevelopmental disorder.

Principal investigator, Mark Zylka, professor of Cell Biology and Physiology in the Neuroscience Center, University of North Carolina, Chapel Hill, told BioWorld Science, "The key really from what we can tell is going early in treatment. So for the animals that have the disorder we can identify them with genotyping. If you catch it early, you can treat them one time and it lasts forever as far as we can tell.

That longevity, he said, "contrasts with treatments that are in development using antisense technologies that usually have to be injected every 4 months or so, which is not ideal for a pediatric disorder that will last a lifetime."

Angelman syndrome is caused by loss of function of the maternal Ube3a allele, while the paternal allele is normally silenced by a very long antisense noncoding RNA known as Ube3a-ATS. Previously in a 2011 Nature publication Zylka and collaborators demonstrated that a class of drugs called topoisomerase inhibitors could reactivate the paternal allele by interfering with Ube3a-ATS. So Zylka knew that if the paternal copy of Ube3a can be turned on, this will provide the possibility of treating the condition.

Topoisomerase inhibitors, which include chemotherapy agents such as irinotecan and doxorubicin, are not a therapeutic option for Angelman syndrome due to their broad-spectrum nature and toxicity. But with the development of CRISPR combined with AAV, the researchers have now developed a tool to precisely hone in on specific regions of the genome.

First, the team screened 250 different RNA guided CRISPR/Cas9 constructs in cell culture until they identified the best one (Spjw33) reactivating the Ube3a-ATS allele. These clones had the good fortune to target Snord115 genes within the large Ube3a-ATS locus. The Snord genes are functionally redundant, with over 100 of them present in both mice and humans.

Ultimately the CRISPR/Cas9 with the cloned RNA guide was used to a specific region of the DNA, where DNA was inserted into the Snord115 gene of the Ube3a-ATS locus. The inserted DNA possessed a polyadenylation signal that caused the premature termination of the Ube3a-ATS noncoding RNA such that it no longer silenced the paternal expression of Ube3a.

With the Ube3a now made in the mouse, it fully developed and no longer presented with any phenotypes resembling Angelman syndrome throughout the life of the animal.

In short, instead of deleting the gene, this approach disrupted the Ube3a-ATS gene by stopping its full production prematurely. Only a small nonfunctioning part of the noncoding RNA was still produced in treated animals.

Earlier is better

The broad implications are that the study proves that Angelman syndrome can be treated and possibly prevented, if it is done early enough.

Previous studies showed that if turning on the paternal copy later, even within just a few days after birth in a mouse, this approach does not prevent Angelman syndrome.

Zylka said, "It is like with a building. You want to make sure the foundation is done correctly. Tons of time is put into the foundation. If there is a problem with the foundation, then when building on top of it, it is very hard and next to impossible to go back and fix the foundation. When the brain is developing, it is the initial foundation upon which the brain is built that is critical and you cannot really go back and fix it. So this study now shows that you can fix the problem if you catch it early enough by administering just a single treatment."

One encouraging result was the lack of gene therapy occurring in the mother. The team injected the vector into the fetus, but no gene therapy was detectable in the mother's liver and brain. Instead, the gene therapy was restricted to only the fetus. This was remarkable and very important since AAV is well known to particularly target the liver.

The technology to identify fetuses with the mutation that causes Angelman syndrome is already available and currently used in hospitals around the world. Techniques like amniocentesis, chorionic villus sampling, and even newer noninvasive technologies involving taking extra blood from the mom can now detect fetal DNA and cells to find out if there are any Angelman syndrome mutations.

However, there has not been a strong incentive to look for Angelman syndrome given that there are no therapeutic options at this point.

Zylka hopes to ultimately test the approach in the clinic. But first-time gene therapy technologies are often only given one shot in clinical trials and safety is of primary concern. So, extensive further research will be necessary to not throw away his shot (Wolter, J.M. et al. Nature 2020, Advanced publication).

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Foundational research shows early gene therapy prevents Angelman syndrome - BioWorld Online

Cell Biology

Touch and Taste? It’s All in The Octopus Tentacles – Technology Networks

Octopuses have captured the human imagination for centuries, inspiring sagas of sea monsters from Scandinavian kraken legends to TV's "Voyage to the Bottom of the Sea" and, most recently, Netflix's less-threatening "My Octopus Teacher." With their eight suction-cup covered tentacles, their very appearance is unique, and their ability to use those appendages to touch and taste while foraging further sets them apart.

In fact, scientists have wondered for decades how those arms, or more specifically the suction cups on them, do their work, prompting a number of experiments into the biomechanics. But very few have studied what is happening on a molecular level. In a new report, Harvard researchers got a glimpse into how the nervous system in the octopus' arms (which operate largely independently from its centralized brain) manage this feat.

The work published Thursday in Cell.

The scientists identified a novel family of sensors in the first layer of cells inside the suction cups that have adapted to react and detect molecules that don't dissolve well in water. The research suggests these sensors, called chemotactile receptors, use these molecules to help the animal figure out what it's touching and whether that object is prey.

"We think because the molecules do not solubilize well, they could, for instance, be found on the surface of octopuses' prey and [whatever the animals touch]," said Nicholas Bellono, an assistant professor of molecular and cellular biology and the study's senior author. "So, when the octopus touches a rock versus a crab, now its arm knows, 'OK, I'm touching a crab [because] I know there's not only touch but there's also this sort of taste.'"

In addition, scientists found diversity in what the receptors responded to and the signals they then transmitted to the cell and nervous systems.

"We think that this is important because it could facilitate complexity in what the octopus senses and also how it can process a range of signals using its semi-autonomous arm nervous system to produce complex behaviors," Bellono said.

The scientists believe this research can help uncover similar receptor systems in other cephalopods, the invertebrate family that also includes squids and cuttlefish. The hope is to determine how these systems work on a molecular level and answer some relatively unexplored questions about how these creatures' capabilities evolved to suit their environment.

"Not much is known about marine chemotactile behavior and with this receptor family as a model system, we can now study which signals are important for the animal and how they can be encoded," said Lena van Giesen, a postdoctoral fellow in the Bellono Lab and lead author of the paper. "These insights into protein evolution and signal coding go far beyond just cephalopods."

Along with Giesen, other co-authors from the lab include Peter B. Kilian, an animal technician, and Corey A.H. Allard, a postdoctoral fellow.

"The strategies they have evolved in order to solve problems in their environment are unique to them and that inspires a great deal of interest from both scientists and non-scientists alike," Kilian said. "People are drawn to octopuses and other cephalopods because they are wildly different from most other animals."

The team set out to uncover how the receptors are able to sense chemicals and detect signals in what they touch, like a tentacle around a snail, to help them make choices.

Octopus arms are distinct and complex. About two-thirds of an octopus's neurons are located in their arms. Because the arms operate partially independently from the brain, if one is severed it can still reach for, identify, and grasp items.

The team started by identifying which cells in the suckers actually do the detecting. After isolating and cloning the touch and chemical receptors, they inserted them in frog eggs and in human cell lines to study their function in isolation. Nothing like these receptors exists in frog or human cells, so the cells act essentially like closed vessels for the study of these receptors.

The researchers then exposed those cells to molecules such as extracts from octopus prey and others items to which these receptors are known to react. Some test subjects were water-soluble, like salts, sugars, amino acids; others do not dissolve well and are not typically considered of interest by aquatic animals. Surprisingly, only the poorly soluble molecules activated the receptors.

Researchers then went back to the octopuses in their lab to see whether they too responded to those molecules by putting those same extracts on the floors of their tanks. They found the only odorants the octopuses receptors responded to were a non-dissolving class of naturally occurring chemicals known as terpenoid molecules.

"[The octopus] was highly responsive to only the part of the floor that had the molecule infused," Bellono said. This led the researchers to believe that the receptors they identified pick up on these types of molecules and help the octopus distinguish what it's touching. "With the semi-autonomous nervous system, it can quickly make this decision: 'Do I contract and grab this crab or keep searching?'"

While the study provides a molecular explanation for this aquatic touch-taste sensation in octopuses through their chemotactile receptors, the researchers suggest further study is needed, given that a great number of unknown natural compounds could also stimulate these receptors to mediate complex behaviors.

"We're now trying to look at other natural molecules that these animals might detect," Bellono said.

This research was supported by the New York Stem Cell Foundation, the Searle Scholars Program, the Sloan Foundation, the Klingenstein-Simons Fellowship, the National Institutes of Health, and the Swiss National Science Foundation.

Reference:

Lena van Giesen. Corey A.H. Allard Nicholas W. et al. Molecular basis of chemotactile sensation in octopus. Cell, 2020 DOI: 10.1016/j.cell.2020.09.008

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Touch and Taste? It's All in The Octopus Tentacles - Technology Networks

Immunology

OSE Immunotherapeutics Presents OSE-230 as a Novel Agonist Monoclonal Antibody Therapy Triggering Resolution of Chronic Inflammation – BioSpace

The first presentation of new data characterizing the anti-ChemR23 antibody was at the FOCIS Virtual Annual Meeting held October 28-31, 2020

NANTES, France, Oct. 30, 2020 (GLOBE NEWSWIRE) -- OSE Immunotherapeutics (ISIN: FR0012127173; Mnemo: OSE) presented preclinical efficacy data for novel agonist monoclonal antibody therapy, OSE-230, at the 2020 Federation of Clinical Immunology Societies (FOCIS) Annual Meeting being held virtually on October 28-31, 2020. OSE-230 is an agonist antibody against ChemR23, also known as chemerin chemokine-like receptor 1 (CMKLR1), a G-protein coupled receptor (GPCR) expressed on myeloid immune cells known to modulate inflammation.

Persistent inflammation is a characteristic feature of all chronic inflammatory or autoimmune diseases and if not controlled or resolved, it can lead to further tissue damage and give rise to tissue fibrosis with eventual loss of organ function. Most anti-inflammatory agents act using a mechanism that blocks pro-inflammation pathways. In contrast, OSE Immunotherapeutics is developing OSE-230 as a first-in-class therapeutic agent with the potential to resolve chronic inflammation by driving affected tissues to complete the inflammation program and restore tissue integrity.

Nicolas Poirier, Chief Scientific Officer of OSE Immunotherapeutics, said: OSE-230 represents a disruptive concept in the resolution of inflammation, a failed process in potentially all chronic inflammatory diseases. The data presented show that OSE-230 is the first monoclonal antibody triggering the activation of specialized receptors of resolution to restore tissue homeostasis, integrity and functions. Chronic inflammatory diseases are the most significant cause of death worldwide* and their incidence is growing, highlighting the patientsneed for disruptive innovations to manage such complex diseases.Our findings provide strong evidence for the therapeutic potential of OSE-230 tobe developed in various chronic inflammation and autoimmune pathologies and reinforce OSEs position in the immunotherapy field targeting myeloid cellsin autoimmune and chronic inflammatory diseases andin immuno-oncology.

The oral presentation entitled Agonist anti-ChemR23 mAb blunts tissue neutrophil accumulation and triggers chronic colitis inflammation resolution shows efficacy results for OSE-230 in chronic inflammatory preclinical models and ex vivo human models. The main results from the presentation are as follows:

These results were based on OSEs key findings:

*Chronic Inflammation; Roma Pahwa , Amandeep Goyal, Pankaj Bansal, Ishwarlal Jialal; In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan.; 2020 Aug 10.

ABOUT OSE ImmunotherapeuticsOSE Immunotherapeutics is an integrated biotechnology company focused on developing and partnering therapies to control the immune system for immuno-oncology and autoimmune diseases. The companys immunology research and development platform is focused on three areas: T-cell-based vaccination, Immuno-Oncology (focus on myeloid targets), Auto-immunity & Inflammation. Its balanced first-in-class clinical and preclinical portfolio has a diversified risk profile:

Vaccine platform

Immuno-oncology platform

Auto-immunity and inflammation platform

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Forward-looking statementsThis press release contains express or implied information and statements that might be deemed forward-looking information and statements in respect of OSE Immunotherapeutics. They do not constitute historical facts. These information and statements include financial projections that are based upon certain assumptions and assessments made by OSE Immunotherapeutics management in light of its experience and its perception of historical trends, current economic and industry conditions, expected future developments and other factors they believe to be appropriate.

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OSE Immunotherapeutics Presents OSE-230 as a Novel Agonist Monoclonal Antibody Therapy Triggering Resolution of Chronic Inflammation - BioSpace

Immunology

Analysis: What do waning COVID-19 antibodies tell us about immunity and vaccines? – Reuters

LONDON (Reuters) - Growing evidence that COVID-19 antibody levels can wane swiftly after someone is infected is not necessarily bad news for immunity, experts said on Thursday, and does not mean protection offered by coronavirus vaccines will be weak or short-lived.

FILE PHOTO: Convalescent plasma samples in vials are seen before being tested for COVID-19 antibodies at the Bloodworks Northwest Laboratory during the coronavirus disease (COVID-19) outbreak in Renton, Washington, U.S. September 9, 2020. Picture taken September 9, 2020. REUTERS/Lindsey Wasson/File Photo

Specialists in immunology and viruses warned against reading too much into studies of antibody levels in the blood of people previously infected with COVID-19, cautioning that antibody readings do not translate directly into levels of protective immunity.

The concentration of antibodies in your blood does not equal immunity, said Eleanor Riley, a professor of immunology and infectious disease at Britains University of Edinburgh.

She and other experts said reports earlier this week which suggested immunity to COVID-19 might decline in line with falling blood antibody levels failed to account for the many complexities in how the body builds immunity to infections.

Immunity is not something we can just wrap up in measuring an antibody or T-cell response, she told Reuters. Immunity is about the system working together so that next time you come across the infection, you either wont get it at all or wont get seriously ill from it. Thats protective immunity.

While antibodies induced by natural COVID-19 infection may start to decline in few months, as a study by researchers at Imperial College found on Tuesday, the many potential COVID-19 vaccines in development are designed to induce more durable immunity by invoking strong so-called immune memory.

Antibody responses are usually short-lived because once they have done their job you dont need them, said Jonathan Stoye, head of virology at Britains Francis Crick Institute.

But that doesnt mean that immunity, either induced by infection or by vaccination, is necessarily short-lived: Memory cells can respond to and combat a new infection.

Since SARS-CoV-2, the virus that causes COVID-19, is a new human virus, scientists dont yet know what levels of immunity will turn out to be protective. But many of the vaccine makers are touting both the antibody and T-cell responses, which are increasingly seen as important to lasting immunity.

The immune system is very complicated. We know antibodies are important, but theyre not the whole story, said Lawrence Young, a professor of molecular oncology at Britains Warwick University. The important thing here is immune memory.

Key to the process of immunity are memory cells known as T- and B-lymphocytes. Having made antibodies to a certain virus in an initial infection, the body uses these cells to remember that pathogen, so when you are next exposed to the virus, the antibody response kicks in much sooner, Young said.

With vaccines, a key feature is that scientists developing them can select as targets the most important bits of the pathogen - in COVID-19s case these include the so-called spike protein on the surface of SARS-CoV-2 virus - to get the strongest and most lasting memory responses from T and B lymphocytes.

Some vaccines also contain stimulators or boosters, known as adjuvants, which can supercharge the response, and others are designed to be given in multiple doses to ensure higher concentrations of antibodies will create stronger memories.

The idea is that while the natural infection may give you poor memory that may not last, the vaccine will give you strong memory that does last, said Danny Altmann, a professor of immunology at Imperial College London.

Reporting by Kate Kelland, editing by Kirsten Donovan

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Analysis: What do waning COVID-19 antibodies tell us about immunity and vaccines? - Reuters

Immunology

Transforming coronavirus protein into a nanoparticle could be key to effective COVID-19 vaccine – UB Now: News and views for UB faculty and staff -…

A UB-led research team has discovered a technique that could help increase the effectiveness of vaccines against the novel coronavirus, the virus that causes COVID-19.

Jonathan F. Lovell, associate professor in the Department of Biomedical Engineering, is the primary investigator on the research, titled SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination, which was published online today in Advanced Materials.

COVID-19 has caused a disruptive global pandemic, infecting at least 40 million worldwide and causing more than 220,000 deaths in the United States alone. Since it began spreading in early 2020, biomedical researchers have been in active pursuit of an effective vaccine.

According to Lovell, one answer might lie in designing vaccines that partially mimic the structure of the virus. One of the proteins on the virus located on the characteristic COVID spike has a component called the receptor-binding domain, or RBD, which is its Achilles heel. That is,he says, antibodies against this part of the virus have the potential to neutralize the virus.

It would be appealing if a vaccine could induce high levels of antibodies against the RBD, Lovell says. One way to achieve this goal is to use the RBD protein itself as an antigen; that is, the component of the vaccine that the immune response will be directed against.

The team hypothesized that by converting the RBD into a nanoparticle (similar in size to the virus itself) instead of letting it remain in its natural form as a small protein, it would generate higher levels of neutralizing antibodies and its ability to generate an immune response would increase.

Lovells team had previously developed a technology that makes it easy to convert small, purified proteins into particles through the use of liposomes, or small nanoparticles formed from naturally occurring fatty components. In the new study, the researchers included within the liposomes a special lipid called cobalt-porphyrin-phospholipid, or CoPoP. That special lipid enables the RBD protein to rapidly bind to the liposomes,forming more nanoparticles that generate an immune response, Lovell explains.The team observed that when the RBD was converted into nanoparticles, it maintained its correct, three-dimensional shape and the particles were stable in incubation conditions similar to those in the human body. When laboratory mice and rabbits were immunized with the RBD particles, high antibody levels were induced. Compared to other materials that are combined with the RBD to enhance the immune response, only the approach with particles containing CoPoP gave strong responses.

Other vaccine adjuvant technology does not have the capacity to convert the RBD into particle-form, Lovell notes.

We think these results provide evidence to the vaccine-development community that the RBD antigen benefits a lot from being inparticle format, he says. This could help inform future vaccine design that targets this specific antigen.

Lovells co-authors on the study include Wei-Chiao Huang, Shiqi Zhou, Xuedan He and Moustafa T. Mabrouk, all from the UB Department of Biomedical Engineering; Kevin Chiem and Luis Martinez-Sobrido, both from Texas Biomedical Research Institute; Ruth H. Nissly, Ian M. Bird and Suresh V. Kuchipudi, all from the Animal Diagnostic Laboratory, Department of Veterinary and Biomedical Sciences at Pennsylvania State University; Mike Strauss and Joaquin Ortega from the Department of Anatomy and Cell Biology at McGill University; Suryaprakash Sambhara from the Immunology and Pathogenesis Branch of the U.S. Centers for Disease Control and Prevention; Elizabeth A. Wohlfert from the UB Department of Microbiology and Immunology; and Bruce A. Davidson from the Department of Anesthesiology and the Department of Pathology and Anatomical Sciences at UB.

Lovell founded the Lovell Lab at UB in 2012. It is focused on developing novel nanomedicine approaches to meet unmet needs in treating and preventing disease. He is also a co-founder of POP Biotechnologies Inc., a preclinical stage biotechnology company developing next-generation drug and vaccines products.

The study was supported by the U.S. National Institutes of Health and the Facility for Electron Microscopy Research (FEMR) at McGill University. FEMR is supported by the Canadian Foundation for Innovation, Quebec Government and McGill.

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Transforming coronavirus protein into a nanoparticle could be key to effective COVID-19 vaccine - UB Now: News and views for UB faculty and staff -...

Immunology

How a misconception about coronavirus immunity is causing thousand of needless deaths – Salon

The popular conceptionof a "vaccine" is that it is aninoculationthat makes you immune to a pathogen if not for life, at least for a very long time. On that principal, much of the world's hope for a return to a pre-pandemic normalcy has rested on avaccine for the novel coronavirus, the cause of COVID-19.

Yet that common conception of how vaccines work, it turns out, isn't entirely accurate. The reason relates to two concepts "transient immunity" and"durable immunity." Understanding these are the key to understanding how the pandemic will finally end.

First, a brief primer on the most common misconception about immunity: the idea that once you've contracted a virus, or once you've been vaccinated against it, you can no longer get said virus. Neither of those are necessarily true: there are viruses which people can contract multiple times, because the body's immune system essentially "forgets" how to create immunity to it after a period of time. Likewise, there are vaccines which only confer short-term immunity, and for which we have to get re-vaccinated for periodically.

Currently, we don't know for certain which category the novel coronavirus falls into although mounting evidence suggests that immunity against it won't last. Indeed, there are multiple cases of patients who have contracted the virus multiple times within a few months. While they could be outliers with poor immune systems, the more cases of re-infection that emerge suggest not.

But there's one more catch: Vaccines can actually confer different types of immunity than infections can say, long-term as opposed to short-term.

From a global public health standpoint, you can see how returning to any sense of normalcy depends on our understanding of coronavirus immunity. In other words, does coronavirus immunity last a lifetime, a year, or as short as a few months? Do those who have been infected already need a vaccine, or are they already immune?

It doesn't help that the science is constantly shifting on this, and month-to-month, scientific studies have slightly different conclusions.As Salon has previously reported, the data and research currently suggests that immunity isn't lifelong like the measles. However, it's hard to know how long immunity lasts because it's such a new virus, but here is everything that scientists currently know.

First, let's talk about immunity

There aremyriadways the human body can fight off a viral infection.Dr. Charles Chiu, a professor of infectious diseases at the University of CaliforniaSan Francisco, pointed Salon to three specific ones: passive immunity, neutralizing antibody immunity, and active immunity.

"The idea is that with any viral infection, including an infection from the novel SARS-CoV-2, is that patients who have intact or healthy immune systems will mount an immune response," Dr. Charles Chiu, a professor of infectious diseases at the University of CaliforniaSan Francisco, told Salon. This, he said, isknown as "passive immunity."

"That's really antibody-centered," Chiu said. "The idea is that the B cells, which are white blood cells in your blood, will react to the virus, and will produce antibodies."

These antibodies, Chiu said, can be used one of two different ways. One way is that the antibodies will be "neutralizing" and bind to the virus. Hence, the name, these antibodies will "neutralize," or inactivate, the coronavirus. This is called "neutralizing antibody immunity."

"The idea is that if you're immune, if there's a next time and you are reinfected, then those antibodies are already circulating and present in your blood and they will neutralize the virus immediately," Chiu explained. "So you will, you'll be less likely or you will not be reinfected."

However, not all antibodies are neutralizing. Chiu pointed to HIV (human immunodeficiency virus) as an example of a virus that creates antibodies that aren't neutralizing.

"You will make antibodies in response to a viral infection, but you may not necessarily make neutralizing antibodies that will prevent you from getting reinfected," Chiu noted.

Then, there's "active immunity," which is another type of immune response that's mediated by another type of white blood cells, T cells.

"T cells will actively react to [the virus], they're memory T cells that sort of remember when you've been infected before," Chiu said. "If you get exposed again, those T cells will then kick in and help to prevent you from getting reinfected."

Understanding "durable" and "transient" immunity

Immunologists are trying to figure out whether novel coronavirus infection confersdurable immunity or transient immunity. These termsreferto the strength and period of the type of immunity. For example, if the antibodies made due to a viral infectionare durable, that means immunity is long-lasting. If they're transient, that means they only last a short while.

As mentioned above, mounting evidence suggests that immunity to the novel coronavirusis transient. But just how transient? We don't know, but there is more evidence every week. In September, researchers published a study in the scientific journal Nature Medicine suggesting that people who contract the novel coronavirus and then become immune may stay that way for up to twelve months, based on studying four different seasonal coronaviruses.

However, as Chiu noted there are a couple of differences between the novel coronavirus (SARS-CoV-2)and the seasonal ones. One is that they've been around longer, meaning they're more diverse because they've had more time to mutate.

"It hasn't had the time to mutate widely and to become very divergent," Chiu said. "And what that means is that it's possible that vaccines that are directed specifically against SARS-CoV-2 are more likely to be durable; they're more likely to last longer and be effective longer, perhaps because there's less divergence within this particular strain versus the other seasonal coronaviruses."

What does this mean for COVID-19?

There have been several studies on antibodies and SARS-CoV-2. In one study, researchers tracked COVID-19 patients over time and found that the amount of their antibodies peaked following the onset of symptoms and then began to decline. For some study participants, the antibodies were almost all undetectable within three months. A more recent study of patients in Britain showed a similar trend. But as Nature explained in an article, it could just take minute numbers of antibodies to prevent a reinfection and fight off the coronavirus again.

Most importantly, however, vaccines can confer different types of immunity than actually contracting the virus. Indeed, immunologists note that a vaccine could have durable immunity even if the natural response is transient.

"The vaccine doesn't have to mimic or mirror the natural infection," Shane Crotty, a virologist at the La Jolla Institute for Immunology, told the New York Times.

Immunologists have been pointing to the human papillomavirus (HPV) as an example of a virus that has a poor immune response and weak antibodies, but a durable vaccine immune response that lasts for at least a decade.

Considering that the coronavirus likely has transient immunity, this would make it harder for countries and cities to achieve herd immunitythrough letting the virus spread.

"It really depends on how transient it is, and how rapidly we can really ramp up to be able to vaccinate a sufficient proportion of the population to develop herd immunity," Chiu said, adding that vaccine hesitancy is another barrier if the coronavirus vaccine requires multiple doses to be effective. "We already have issues right now with adherence to the flu vaccine, and there's no reason to think that it's going to be different."

That means that humanity's best bet forachieving durable immunity is still through a vaccine. Relying on a strategy of waiting for herd immunity to be achieved is "flawed," according to a paper by a group of researcherspublished in The Lancet.

"There is no evidence for lasting protective immunity to SARS-CoV-2 following natural infection, and the endemic transmission that would be the consequence of waning immunity would present a risk to vulnerable populations for the indefinite future," the researchers wrote. "Such a strategy would not end the COVID-19 pandemic but result in recurrent epidemics, as was the case with numerous infectious diseases before the advent of vaccination."

In other words, political leaders who have pinned hopes of defeating the virus on achieving herd immunity will not only fail, but will needlessly kill their citizens in the process. President Donald Trump as well as UK Prime Minister Boris Johnson have both touted a strategy of achieving herd immunity through deliberate public health inaction in order to let the virus run its course through citizens.

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How a misconception about coronavirus immunity is causing thousand of needless deaths - Salon