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Vampire Anatomy, According to The Vampire Diaries | CBR – CBR – Comic Book Resources

The vampires in The Vampire Diaries adhere to some elements from vampire lore, but with roots in dark magic, they are their own bloodthirsty fiends.

In literature, film and TV, the vampire has varied in appearance and abilities, although a few key traits remain the same. The vampire must consume human blood to survive, their power is at its peak during the night and a human must consume the blood of a vampire to become one themselves.The Vampire Diaries features some of the time-honored traditions of vampire lore but the show also introduces its own elements to the bloodthirsty fiends.

The rule that vampire blood is necessary to kick-start the transformation from human to bloodsucker has existed for generations of vampire stories, and The Vampire Diaries is no different. To become a vampire, a human must die with a vampire's blood in their system. The matter of the human's death itself is irrelevant -- although the body does have to be somewhat intact. However, humans hoping to become a creature of the night must either consume vampire blood orally or through injection, or have a vampire's blood poured on an open wound.

RELATED:The Vampire Diaries: How Damon and Stefan Became Vampires

The Vampire Diariesestablishes early on that in order to complete the transformation from human to vampire, a newly created vampire must consume human blood. Animal blood is not sufficient to sustain the transformation, so new vampires who want to adhere to a strict diet of animal blood are out of luck -- at least initially. A human need not die in the process, and vampires can utilizeunconventional methods to obtain the needed blood, likestealing blood donor bags or feeding from a recently deceased human. Regardless, a newly created vampire only has 24 hours to have their first taste of human blood or they will die permanently.

In theTheVampire Diariesuniverse,all vampires descend from the six Original vampires known as the Mikaelson Family -- Mikael, Finn, Elijah, Kol, Rebekah and Klaus. After the Originals were created in 1001 AD, they fed on human blood and thus created the first bloodlines, through which all vampires are connected. The magical properties of the Originals' blood is passed down through each vampire they sire and the ones their progeny sire, meaning that vampires are all one big family. Unfortunately, due to every vampire's link to the Mikaelsons, if one of the Originals die, their entire bloodline follows suit in less than a hour.

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Vampire Anatomy, According to The Vampire Diaries | CBR - CBR - Comic Book Resources

‘Grey’s Anatomy’ Fans Can’t Handle This Heartbreaking Callback to Lexie and Mark – Showbiz Cheat Sheet

Shonda Rhimes is known for creating many entertaining television shows. Private Practice, Scandal, and How to Get Away With Murder are just a few. More recently Rhimes has been in the headlines for her new upcoming Netflix show, Bridgerton, that is set to premiere later this year. Rhymes fans and followers are anxiously looking forward to the launch of the showrunners newest series. However, none of Rhimes shows quite compare to Greys Anatomy.

The ABC drama launched back in 2005, and became an instant television sensation. Currently, the series is preparing to air its 17th season. The premise of Greys Anatomy is centered around a group of surgical interns as they work together to navigate their professional and personal lives. Ellen Pompeo, Chandra Wilson, Kevin McKidd, and Jesse Williams are just a few of the talented and beloved actors and actresses who make up the cast of Greys Anatomy.

Over the years the audience and fans of the series have closely followed the drama and storylines of the characters that they love so dearly, and there is one in particular that still strikes a chord with many.

After airing for 16 seasons, it is safe to say fans and viewers of Greys Anatomy have seen their fair share of drama. Throughout the seasons some of the storylines probably stick out more than others. It was early on in the series during season three when Cristina Yang and Preston Burkes relationship and wedding came to a crashing halt.

A few seasons later and the fans tragically had to say goodbye to Dr. George OMalley after he pushed a pedestrian out of traffic only to get hit by the bus himself. The love story between Izzie Stevens and Denny Duquette, a sick heart patient, was another compelling storyline with a tragic ending.

The infamous plane crash and McDreamys death can be added to the list. When it comes to drama and heartbreak, the writers and producers of Greys Anatomy are actual professionals.

RELATED: Greys Anatomy Fans Demand the Return of the Most Underrated Intern

Of all the past storylines and memories that have taken place on Greys Anatomy there is one in particular that many fans and viewers still struggle with.

A Reddit thread recently shared an image of Lexie Grey and Mark Sloane together cuddling in a hospital bed. After a sexual encounter gone wrong, Mark found himself with an excruciating penis injury.

Though a humorous instance, in the photo Lexie is seen playing with Marks hair, and the caption of the photo reads, Im going to stroke your hair, because thats what id like to have done to me when Im hurt. The sweet moment that took place between the two characters stirred up a lot of feelings for fans and viewers.

It is obvious that fans of Greys Anatomy still arent over the tragic ending that both Mark Sloan and Lexie Gray faced. During season 11 a horrendous plane crash caused both doctors to lose their lives.

The pair would never get the proper ending to their love story that so many of them were hoping for. When the photo of them together was posted in the thread, many people began sharing their unresolved feelings. One user commented, ok unnecessary roughness on this Tuesday afternoon ouch.

Many others joked about the unexpected feels and tears that the photo brought on. Though fans and viewers of Greys Anatomy should be used to tragic endings by now, it still doesnt seem to make it any easier, especially in the case of Mark and Lexie.

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'Grey's Anatomy' Fans Can't Handle This Heartbreaking Callback to Lexie and Mark - Showbiz Cheat Sheet

How genetics can help predict risks of cancer recurrence and improve treatment – Euronews

A biobank is a storage facility for biological samples including blood, human tissue and/or DNA. They can then be used at any time for future medical research or pioneering methods.

The Managing Director of Estonian Biobank, Andres Metspalu, gives us some insight:

"I started the Estonian Biobank about 20 years ago. Our biobank is pretty large for a small country. We have around 20% of the entire Estonian population over the age of 18 included in our biobank; which equates to more than 200,000 individuals.

"They have all been analysed genetically, which is really remarkable. That is why we can do this genetic medicine not only for cancer, but also for other diseases.

"More than 3,000 people have already received their genetic risk (result) from the biobank.

"This is what keeps me busy every day, doing research and also facilitating the use of this information in healthcare".

"We are mainly talking about (predicting the risks of developing diseases like) cancer, cardiovascular diseases and type-2 diabetes. We also study melanoma, prostate cancer and lung cancer.

"We are also doing pharmacogenomics, drug response (how our bodies respond to drug intake).

"Not all drugs work on everyone as (pharmaceutical) companies believe or expect. Some drugs (can be) pretty harmful. You (can) get reactions and you (can) get side effects. You may end up in hospital after taking prescription drugs.

"Genetics can predict some serious events. It (genetics) should be used. This is what we are trying to introduce into everyday medical practice in Estonia".

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How genetics can help predict risks of cancer recurrence and improve treatment - Euronews

Rare Disease Genetic Testing Market To Account To Grow At A CAGR Of 8.30% In The Forecast Period Of 2020 To 2027 | Leading Players- Quest Diagnostics,…

The universal Rare Disease Genetic Testing Market report conveys in-depth market study and future prospects of the Rare Disease Genetic Testing industry. Furthermore, the market report gives all the CAGR projections of the historic year 2018, base year 2019, and estimate time of 2020 2027. The market study and analysis of this report also lends a hand to figure out types of consumers, their views about the product, their buying intentions and their ideas for advancement of a product. This credible Rare Disease Genetic Testing Market report has been prepared with the thorough market analysis carried out by a team of industry experts, dynamic analysts, skilful forecasters and well-informed researchers.

Summary of the Report

Rare disease genetic testing market is expected to gain market growth in the forecast period of 2020 to 2027. Data Bridge Market Research analyses the market to account to grow at a CAGR of 8.30% in the above-mentioned forecast period. The increase in the facilities for patients affected by rare diseases has been directly impacting the growth of rare disease genetic testing market.

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Major Key Players of the Rare Disease Genetic Testing Market

Quest Diagnostics, Inc., Centogene N.V., Eurofins Scientific, Strand Life Sciences, Ambry Genetics, PerkinElmer, Inc., Macrogen, Inc., Baylor Genetics, Color, Health Network Laboratories, L.P., Preventiongenetics, Progenity, Inc., Invitae Corporation, 3billion, Inc., Arup Laboratories, Coopersurgical, Inc., Fulgent Genetics, Myriad Genetics, Inc., Laboratory Corporation Of America Holdings and Opko Health, Inc., among other domestic and global players.

GlobalRare Disease Genetic TestingMarket Scope and Market Size

Rare disease genetic testing market is segmented on the basis of disease type, technology, specialty and end use. The growth amongst these segments will help you analyze meager growth segments in the industries, and provide the users with valuable market overview and market insights to help them in making strategic decisions for identification of core market applications.

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Geographical Coverage of Rare Disease Genetic Testing Market

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Table of Contents

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Rare Disease Genetic Testing Market To Account To Grow At A CAGR Of 8.30% In The Forecast Period Of 2020 To 2027 | Leading Players- Quest Diagnostics,...

Increasing Government Investments and Favorable Policies to Aid the Growth of the Predictive Genetic Testing Market 2019 2029 – Eurowire

The global Predictive Genetic Testing market is forecasted to reach a market value of ~US$ XX Mn/Bn by the end of 2029 registering a CAGR growth of around XX% during the forecast period (2019-2029). The recent market report provides a detailed analysis of the current structure of the Predictive Genetic Testing market along with the estimated trajectory of the market over the course of the stipulated timeframe.

The report provides an in-depth assessment of the numerous factors that are anticipated to impact the market dynamics with utmost precision and accuracy. The SWOT and Porters Five Forces Analysis provides a clear picture about the current operations of the various market players operating in the global Predictive Genetic Testing market.

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Segmentation analysis

key players in the predictive genetic testing market. The significant competitive strength of the existing players in the evolving landscape of the global predictive genetic testing market is anticipated to offer new prospect in widening the application of the predictive genetic testing, substantially driving predictive genetic testing market growth. The key manufacturers of the predictive genetic testing are greatly concentrated on the technical edification of the end users to improve consumer outcomes. Furthermore, the adoptions of advanced predictive genetic testing services is expected to create lucrative growth opportunities for the service and third-party market competitors. Growing inclination toward trend in predict is prevention is estimated to offer growth opportunity for Predictive genetic testing market. Selection of treatment regimen with Predictive genetic testing is projected to aid capturing higher share in Predictive genetic testing market.

Geographically, global Predictive genetic testing market is segmented into seven key regions viz. North America, Latin America, Europe, South Asia, East Asia Oceania and Middle East & Africa. North America is prominent region in Predictive genetic testing Market. Advancement in genetic care facilities, higher adoption to lifestyle changes, increase awareness about genetic disease, increase in preventative care and favorable government policies have improved the regulatory scenario for predictive genetic testing devices in north America. Additionally in Asia pacific region considerably higher market growth rate is expected due to constantly rising population and higher incidence of genetic abnormality. Relatively affecting the Predictive genetic testing market.

Some of the major key players competing in the global Predictive genetic testing Market are Myriad Genetics, Inc., Abbott Laboratories, Illumina, Inc., Genesis GeneticsThermo Fisher Scientific, Inc., Bio-Rad Laboratories Inc., , Agilent Technologies, F. Hoffmann-La Roche Ltd., Counsyl, Inc., ARUP Laboratories. BGI among others.

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Increasing Government Investments and Favorable Policies to Aid the Growth of the Predictive Genetic Testing Market 2019 2029 - Eurowire

Researchers hope to harness the power of llama nanobodies to treat and prevent COVID-19 – FOX43.com

Llama nanobodies are surprisingly effective at neutralizing the virus, said researchers at the University of Pittsburgh School of Medicine.

PITTSBURGH An unlikely hero has emerged as a potential ally in the fight against COVID-19. Researchers at UPMC are seeing hope for a coronavirus treatment in tiny llama antibodies.

These llama antibodies are called nanobodies and they are much smaller than human antibodies. Their tiny stature gives them the unique ability to latch onto the coronavirus spike protein, blocking the virus from infecting cells.

Dr. Yi Shi, assistant professor of cell biology at the University of Pittsburgh School of Medicine, turned to a llama named Wally to generate these nanobodies. He said they are surprisingly effective at neutralizing the virus.

What we did was we immunized llama Wally with the virus spike protein. Then, it took about 50 to 55 days for Wally to develop nanobodies that can bind very tightly to this virus spike protein, explained Dr. Shi.

Using a mass spectrometry-based technique that Dr. Shi has been perfecting for the past three years, he and his lab team identified the nanobodies in Wallys blood that bind to SARS-CoV-2 most strongly, preventing its spread to cells.

Nanobodies are very stable and potentially could be stored for a long time after production. They can also be delivered by an inhaler directly to the lungs, which makes them particularly promising for respiratory infections such as COVID-19, according to the National Institutes of Health.

Traditional SARS-CoV-2 antibodies require an IV, which dilutes the product throughout the body, necessitating a much larger dose and costing patients and insurers around $100,000 per treatment course, said Dr. Shi.

Dr. Shi said his nanobodies taken from Wally can sit at room temperature for six weeks and can be administered to people via an inhaler or nasal spray to treat or prevent COVID-19. Since SARS-CoV-2 is a respiratory virus, the nanobodies could find and latch onto it in the respiratory system, before it even has a chance to do damage.

I think it is mostly effective for early stage treatment, Dr. Shi added. Basically, preventing the disease from a mild stage to the severe disease.

Dr. Shi said Wally was not harmed during the pre-clinical study. Owners on his farm in Minnesota said Wally is doing great with his llama friends, always coming to greet people when they enter his pen.

Researchers have a long way to go before any treatments are ready for public use. Dr. Shi is hoping to garner enough support to finalize their pre-clinical studies and begin clinical trials for testing.

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Researchers hope to harness the power of llama nanobodies to treat and prevent COVID-19 - FOX43.com

Cell-Free Technology Comes Of Age: BioBits Is Changing The Way We Teach Biology – Forbes

BioBits kits are designed to be used by students and teachers with no biological training. They use ... [+] simple, hands-on experiments, to teach concepts of synthetic and molecular biology. Credit: Wyss Institute at Harvard University (https://wyss.harvard.edu/news/biobits-new-biology-kits-for-a-new-generation-of-kids/)

Hundreds of AP (Advanced Placement) Biology students across eight Boston public schools could be finding a silver lining in online high school. Thanks to a grant from the Massachusetts Life Sciences Center, their curriculum now includes cutting-edge, hands-on biotechnology kits that are being delivered to their doorstep.

Born from a collaboration between MIT and Northwestern University, BioBits is the latest product by miniPCR bio, which specializes in making low-cost biotech equipment for students and scientists alike. Realizing the drastic need for online methods of instruction, they partnered with Mass Insight to develop a BioBits take-home lab activity that teaches AP biology students the central dogma of biology: transcription and translation.

As schools continue to be closed, one thing is increasingly clear: online instruction is hard, not just for students, but also for educators. They are away from their usual workplace. They only interact with the kids through screens. They have very limited opportunities for meaningful engagement and all of a sudden, you open up this little box full of biology, says Sebastian Kraves, Co-Founder of miniPCR.

The safety and accessibility of BioBits is hard to beat. Biology is an expensive field to dabble in, but $100 is enough to provide a classrooms worth of BioBits kits. Since there are no live organisms like bacteria, expensive equipment necessary for the most basic biology lab freezers, incubators, and sterile tools are no longer a limiting factor.

Freeze-dried cell extracts are shelf-stable and can ship worldwide. In the past few months, BioBits kits have been delivered to places outside the United States such as Denmark, Indonesia, and Chile - just to name a few.

Starting next year, they will even make their way to the International Space Station. MiniPCR and Boeing manage the annual Genes in Space challenge, where students will soon be able to submit BioBits experiment ideas, one of which will be selected for an astronaut to conduct on board the ISS.

While the science lesson in these kits is simple: cells make proteins from genes, it begs another question: how is this possible without the living cell itself?

Teachers will stop me and say, wait, wait, I get transcription and translation. But tell me more about that cell-free technology. I didn't realize you could do that, Ally Huang recalls. She and Jessica Stark made the concept of the synthetic biology educational kit a reality during their graduate studies at MIT and Northwestern, respectively.

The core breakthrough is cell-free technology. While it has been used for applications ranging from diagnostics to manufacturing, the way it is making its way into the classroom is a subtle but important shift.

If cell-free technology is robust, safe, and cheap enough for students to tinker with, it could be coming out of lag phase into its exponential growth of potential applications, suggests Dr. Mike Jewett, Professor of Chemical and Biological Engineering at Northwestern.

While the field is still young, substantial effort is being made to increase diversity and equity. This could be one place where synthetic biology could truly embody the values of the twenty-first century.

There's really great research that shows that engagement with science early in a student's career and in meaningful hands-on ways is a great way to get students interested in science. And so I would hope that BioBits and other hands-on activities can be implemented in schools to encourage people from all different backgrounds to pursue careers in STEM, Jessica emphasizes.

The personal backgrounds of the eclectic team behind BioBits shows just how much of an impact access could make.

BioBits kits are designed so that students and teachers with no previous biological training can ... [+] perform their own genetic experiments without the need for expensive and bulky lab equipment, at a fraction of the cost. Credit: Megan Beltran (https://phys.org/news/2018-08-biobits-synthetic-biology-k-students.html)

My favorite gift as a kid was a chemistry kit that I got from my grandmother in the very early 70s, Dr. Jim Collins reminisces. Hes now a Professor of Bioengineering at MIT.

And as a parent of two college-age kids, both interested in science. I introduced them to the chemistry kits, I got the electronic kits, I got the robotic kits, and was really disappointed that there was nothing biological that could be acquired.

Professor Jewett was drawn into biology through the chemistry behind living systems. Ally was fascinated by a fetal pig dissection in high school. Jessica, by the idea that tiny proteins operate every function inside a cell.

Sebastian got a copy of The Voyage of the Beagle from his grandmother at age 12. I did not have any hands on labs. I barely had any science classes. My high school back in Argentina was very resource limited, and also very social sciences oriented. And I went on to study economics. With BioBits, Sebastian is determined to change that narrative.

In sharp contrast to the breakneck increase in our ability to engineer biology, biology education has not changed for generations until, perhaps, now.

Im the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference andweekly digest. Thank you toDesiree Hofor additional research and reporting in this article.

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Cell-Free Technology Comes Of Age: BioBits Is Changing The Way We Teach Biology - Forbes

Brain Development and Disorder Research Receives $1.5 Million NSF Boost – USC Viterbi School of Engineering

A 15-day-old brain organoid: Department of Biomedical Engineering researchers are partnering with Keck School of Medicine of USC to improve the creation of these materials, which can help us better understand brain development and disorders.Image/ Giorgia Quadrato

The human brain is an incredibly complex organ to study in its living tissue form. Researchers cannot experiment on human tissue directly, and animal models are often too different to human physiology to be effective.

For this reason, in the last decade, neurological research has been increasingly turning to brain-on-a-chip organoid models to give researchers living examples to demonstrate brain development, and how to effectively treat brain diseases and disorders. Organoids are grown out of stem cells into new cell clusters that mimic the structure of and features of a whole organ, such as the brain.

Co-principal investigator Megan McCain from the USC Viterbi Department of Biomedical Engineering will partner with fellow co-principal investigators Giorgia Quadrato and Leonardo Morsut in the Department of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine of USC on a four year, $1.5m NSF-funded project to vastly improve the process of developing brain organoids. The project aims to make the end products more consistent and reliable as tools for brain researchers.

McCain is the Chonette Early Career Chair and assistant professor of biomedical engineering at USC Viterbi. She said that one of the biggest hurdles in the current process of organoid creation was their lack of uniformity.

Researchers start with a small group of human stem cells, and then give them some chemical cues to direct their development into brain tissue, but ultimately, the cells are mostly left to their own devices, so they often grow very randomly, McCain said. They divide and differentiate into other cell types in a somewhat haphazard process. So if you make ten organoids, all ten of them will look slightly different.

A brain organoid in a fluidic device from the labs of Megan McCain and Giorgia Quadrato.

McCain said it was this issue that could be detrimental to the accuracy of using organoids in certain types of research, such as the testing of therapeutics and how the brain responds to these drugs, and that organoids needed to be more uniform and reproducible in order to be more effective tools.

Drug testing with organoids today is very challenging because it is hard to separate the effect of the drug from the inherent variability of the organoids themselves, McCain said.

Morsut said that his part of the project involves developing synthetic molecular tools to simplify the analysis of what happens during the formation of brain organoids in a laboratory setting.

The normal molecules that are used by the cells to self-organize, as well as to make decisions, are linked in very complex networks, and we need artificial tools to tease apart the contributions of these different components, Morsut said. The challengeand the exciting partis to use these tools to explain the remarkable phenomenon of self-organization.

McCain said her lab will focus on the device sidethe organ-on-chipand make microfluidic components for growing and studying organoids under more defined conditions.

This will likely improve reproducibility and possibly organoid maturity, which is another major bottleneck, McCain said.

In order to do this, McCains lab will be repurposing a microfluidic device that they previously used to help explanted zebrafish hearts to remain alive longer and regenerate, while also live-imaging the process.

The device, when applied to brain organoids, will constrain the cells in chambers where the team can run experiments through them in a more controlled way, to see if this improves the consistency of the end product.

And we will also be able to image and monitor their reproducibility by putting them in this little device where theyre all growing in the same configuration, McCain said.

Quadrato, an expert in brain organoids, said she was excited about the collaboration, because a multidisciplinary approach was needed to improve the relevance of current organoids.

One way to improve brain organoid-to-organoid reproducibility is to expose them to small molecules to direct differentiation of the stem cells, Quadrato said.

She said that these small molecules unfortunately sometimes have problematic side effects, such as impairing the survival of other non-neural cell types, or skewing tests of potential treatments for brain diseases and disorders.

In our proposal, we suggest an alternative strategy to increase brain organoid reproducibility that does not cause these side effects, and therefore can be used to create organoids to accurately model disease, Quadrato said.

Further information about the project is available from the National Science Foundation.

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Brain Development and Disorder Research Receives $1.5 Million NSF Boost - USC Viterbi School of Engineering

Zavala Named One of the Most Inspiring Hispanic/Latinx Scientists in America – CSUN Today

Our aim in assembling these names is to put an end to the harmful myth that there are not enough diverse scientists to give seminars, serve as panelists or fill scientific positions, the authors wrote. We hope it will help to change the perception of what a scientist looks like and makes our collective image more representative of society at large.

Zavala, who has taught at CSUN since 1988, was the first Mexican American woman in the country to earn a Ph.D. in botany. Since coming to CSUN, she has played an integral part in building the national reputation of CSUNsDepartment of Biologyas a place where students, particularly those from underserved communities, thrive and successfully pursue advanced degrees at top-tier research institutions.

She has served as director of CSUNs Maximizing Access to Research Careers Undergraduate Student Training in Academic Research (MARC U-STAR) program since 1990 and Research Initiatives for Scientific Enhancement (RISE) since 1993. Her work as a mentor and advocate for countless students who have gone through these programs earned her recognition from the White House. In 2000, Zavala received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring from former President Bill Clinton. And in 2017,Zavala was named the first Latina Fellow of the American Society of Cell Biologyin its 57-year history.

She also oversees CSUNs work as one of three institutions sharing a first-of-its-kind $3 million, five-year grant from the National Science Foundation to create aHispanic-Serving Institutions(HSI) Resource Hub. The hub is charged with reaching out to colleges and universities across the country to build partnerships that will support STEM education, increase STEM research and education capacity at HSIs, and encourage the implementation of cutting-edge training.

Zavalas research focuses on the manipulation of genes as a way to improve plant productivity by enhancing root growth. She also is studying ways to make beans more nutritious.

In addition to being a Fellow of the American Society of Cell Biology, she is also a Fellow of the American Association for the Advancement of Science and, in 2016, became the first Latina Fellow of the American Society of Plant Biologists.

To be named a Fellow is a recognition of your research and the contributions you have made to a particular field of study, Zavala said in 2017. Its nice recognition from your peers. But I am looking forward to the time when Im not the first, but one of several Latina Fellows.

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Zavala Named One of the Most Inspiring Hispanic/Latinx Scientists in America - CSUN Today

Singapore scientists discover immune pathway that causes immunodeficiency – BSA bureau

The novel pathway can be a target for liver disease and cancer drugs that failed trials due to inflammatory side effects

Scientists from Singapores A*STARs Institute of Molecular and Cell Biology (IMCB), in collaboration with doctors from KK Womens and Childrens Hospital (KKH), have discovered a new immune pathway based on an investigation of severe immunodeficiency caused by a novel mutation in the NFKBIA gene. The findings were published inThe Journal of Clinical Investigation.

A recent investigation with a rare primary immunodeficiency disease involving a two-week old infant with recurrent infections alongside lung, skin and liver damage instigated the discovery. Scientists at A*STAR identified a new genetic variant in NFKBIA that changed the levels of soluble proteins called cytokines, produced by white blood cells to drive inflammation. Abnormally high production of one cytokine, IL-1, was identified as the key derangement. Crucially, the clinical team was able suppress the patients disease by rational administration of the IL-1-blocking drug, Anakinra, based on these scientific results.

The research team, along with Singapore Immunology Network (SIgN) discovered a previously unknown pathway, which controls IL-1 production. By replicating the mutation in pre-clinical and cellular models, experimental results conclusively showed that the patients genetic variant was the cause of IL-1 hyper-production, and hence the disease. These findings have implications for the development of treatments against liver disease and cancer that target this novel pathway.

While other mutations in NFKBIA have been reported before to cause disease, this mutation has never before been identified. It is the only mutation in which hyper-production of IL-1, severe liver cholestasis and systemic inflammation were documented. The research team believes the mutation limits immune responses via the suppression of many pro-inflammatory cytokines. Yet at the same time, it causes over-production of IL-1, leading to liver damage and inflammation. Using this bedside-to-bench approach of identifying the underlying genetic causes of immunodeficiency diseases, previously unknown pathways which control immune responses can be revealed. These then serve as targets for personalised treatment strategies," said Dr John Connolly, a Research Director at IMCB and co-corresponding author of the study.

The research team will further examine which new mediators are responsible for controlling IL-1 production by this genetic variant, given that this regulatory association between the protein encoded in NFKBIA and IL-1 was not observed previously. As this novel pathway has also been a popular target for cancer drugs that failed trials due to inflammatory side effects, the team will investigate whether these new mediators are responsible for the failure of these drugs, and determine if the side effects can be circumvented.

Image Caption:Staining for the signalling protein NFB (green) in skin cells from a healthy individual (left) and the patient (right) after immune stimulation. The patients novel NFKBIA variant impairs entry of NFB into nucleus (blue). This defect led to changes in cytokine production, resulting in both immunodeficiency and multi-organ damage.

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Singapore scientists discover immune pathway that causes immunodeficiency - BSA bureau