Category Archives: Cell Biology

Cell Biology

Snake Venom Gland Organoids Produce Functional Toxins – The Scientist

Aminiaturized version of the snake venom gland that secretes functionally active toxins can be grown from stem cells, researchers describe January 23 in Cell.

Scientists have previously cultured these simplified tissues, called organoids, from mouse and human stem cells, including minibrains that model neuronal networks, but this study is the first to show that the same techniques work with snake tissue.

Hans Clevers, a principal investigator at the Hubrecht Institute for Developmental Biology and Stem Cell Research, and his team used human growth factors to culture the snake venom organoids, reports STAT, but there was one critical difference from mammalian organoids: temperature. The snake organoids needed to be kept a few degrees colder than cultures from mice and humans, Clevers tells STAT, because reptiles are cold-blooded.

The experiment started with three of Cleverss grad students who wondered whether they could grow organoids from other species, reports The Atlantic. They received the egg of a Cape coral cobra (Aspidelaps lubricus) from a breeder and used the labs protocols on mammalian organoids to generate miniature venom glands, which produced the same toxins as that of real snakes. The lab went on to grow organoids from eight other species.

Its a breakthrough, says snake venom toxicologist Jos Mara Gutirrez of the University of Costa Rica in San Jos who was not involved in the study, in remarks to Science. This work opens the possibilities for studying the cellular biology of venom-secreting cells at a very fine level, which has not been possible in the past.

Expanding scientists knowledge of snake venom has important implications for human health. According to the World Health Organization, an estimated 5.4 million people are bitten by snakes every year. Somewhere between 81,000 and 138,000 of those victims die as a result. This neglected public health issue is especially prevalent in Africa, Asia, and Latin America.

The current method of producing antivenom involves injecting a horse with snake venom and collecting the resulting antibodies, a centuries-old technique that requires milking a live snake. Venom gland organoids may be a safer and more economical alternative, reports The Atlantic.

The biotechnology they are describing is a potentially wonderful addition to the toolbox of toxins research generally, writes Leslie Boyer of the University of Arizonas VIPER Institute in an email to STAT. What will future studies reveal about the interaction of components of complex venoms? Can a practical harvest of toxins be generated for cost-effective use in future applications? How do cells full of deadly toxins avoid suicide?

Amy Schleunes is an intern atThe Scientist. Email her ataschleunes@the-scientist.com.

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Snake Venom Gland Organoids Produce Functional Toxins - The Scientist

Cell Biology

Meet the Culprits of Cell Culture Contamination – Technology Networks

The air is warm and humid, there is an abundance of food, and your friends come and go with their shiny toys. What sounds like a dreamy summer holiday is also the reality of in vitro cell culture experiments, and a golden opportunity for contaminants to intrude. Every person, reagent, and piece of equipment in the laboratory is a potential vehicle for invasive microbes, unwelcome cells and chemical impurities, which can create costly issues in both bench research and manufacturing. Cell culture contamination is a problem on many levels, creating immediate implications for experiments and wider issues for the scientific community.Consequences of cell culture contaminationContaminants can affect all cell characteristics (e.g. growth, metabolism, and morphology) and contribute to unreliable or erroneous experimental results. Cell culture contamination will likely create a need for experiments to be repeated, resulting in frustrating time delays and costly reagent wastage. Data derived from undetected contaminated cultures can end up published in scientific journals, allowing others to build hypotheses from dubious results. The pervasiveness of cross-contaminated and misidentified cell lines is a decades-long issue; in 1967, cell lines thought to be derived from various tissues were shown to be HeLa cells, a human cervical adenocarcinoma cell line.1 However, studies involving these misidentified cell lines continued to feature in hundreds of citations during the early 2000s.2This pattern is a well-acknowledged problem and threatens to undermine scientific integrity. The first published retraction in Nature Methods was due to cell line contamination3, and one conservative estimate of contaminated literature in 2017 found 32,755 articles reporting on research with misidentified cells.4 While many scientists may have been blissfully ignorant in the past, awareness of misidentified cell lines is growing.Deciding how best to deal with this knowledge is not straightforward and has been discussed extensively.4 In the interest of preventing further data contamination, a certificate of authentication of the origin and identity of human cells is now required by the International Journal of Cancer, and encouraged by funding agencies. Others have questioned whether mandatory testing really is the best way forward.3But what should be done about existing contaminated literature? Mass retraction of affected articles may disproportionately punish the careers of a few scientists, and could be a waste of resources containing potentially valuable data. One recently proposed system of self-retraction recommends replacing blame with praise in order to encourage self-correction.5 Post hoc labeling of published articles in the form of an expression of concern allows existing findings to remain accessible, while giving readers a chance to form their own judgement.

Lastly, pathogens carried by cells (either intentionally or accidentally) or in components of the culture medium are potential health hazards, and laboratory-acquired viral infections have been reported.6-8 Indeed, the stakes are higher when cells are to be introduced into patients, highlighting the critical importance of quality control in cell therapies.

While pipetting is a key part of everyday laboratory work, it is also one of the stages most prone to contamination. As sample contamination can affect the reliability of results, it is important to know how it can be avoided, saving both time and money. Download this poster for ten tips to avoiding contamination in pipetting.

Avoid leaving your cultures out of the incubator for extended periods

Label all cultures clearly and unambiguously

Disinfect work surfaces before and after use

Check disinfectants are effective and appropriate choices for the job

Work with only one cell culture at a time

Use separate media and reagents for each individual cell line

Quarantine new cell lines until tested negative for mycoplasma

Avoid overusing and relying on antibiotics

Record how long a cell line has been kept in cultureThe design of the laboratory can also play a role; cabinets should be placed away from through-traffic, doors and air-conditioning inlets.6 Restricting area access to allow only essential laboratory personnel to enter reduces disturbances of airflow around the microbiological safety cabinet.

Water baths, CO2 incubators, shelves and water pans are common culprits and should be cleaned or autoclaved regularly, using a chemical disinfectant where appropriate. Other routes of infection include accidental spillages, contact with non-sterile surfaces, splash-back from pipetting or pouring, microscopic aerosol, and infestation by vertebrates, dust and mites.Research groups isolating stem cells use unique cell properties to filter out undesired cells, explains Dr Mei-Ju Hsu, postdoctoral researcher in stem cell therapy at Leipzig University. Dr Hsu notes that: one of the most important features of mesenchymal stem cells is the attachment and growth on the plastic surfaces without prior coating. This step serves as a good way to eliminate the non-adherent cells (e.g. blood cells) by the removal of supernatants.

Organoid researcher Hans Clevers, from the Hubrecht Institute for Developmental Biology and Stem Cell Research at Utrecht University, assesses genetic diversity in cells through the use of single nucleotide polymorphism (SNP) genotyping. The Clevers laboratory recently branched out from their work with mammalian cells to produce snake venom gland organoids. Dr Clevers notes that: We have come to realize that contamination of organoid cultures is a serious problem. We have observed that organoid cultures that are commonly used and are fast growers contaminate slower growing organoid cultures. Typical fast growers are the original mouse mini-guts that have popped up in various human organoid cultures in the lab. We SNP-type all human samples when they come in, which allows us to follow purity of human organoid cultures over time. Cheap, fast and crucial to avoid big mistakes.

Mycoplasma is one of the most common cell culture contaminants, with six species of mycoplasma accounting for 95% of all contamination. Therefore, it is important to improve our understanding of where mycoplasma contamination can stem from and how best to prevent it. Download this infographic to discover more about mycoplasma contamination in cell culture labs.

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Meet the Culprits of Cell Culture Contamination - Technology Networks

Cell Biology

America’s most widely consumed cooking oil causes genetic changes in the brain – University of California

New UC Riverside research shows soybean oil not only leads to obesity and diabetes, but could also affect neurological conditions like autism, Alzheimers disease, anxiety, and depression.

Used for fast food frying, added to packaged foods, and fed to livestock, soybean oil is by far the most widely produced and consumed edible oil in the U.S., according to the U.S. Department of Agriculture. In all likelihood, it is not healthy for humans.

It certainly is not good for mice. The new study, published this month in the journal Endocrinology, compared mice fed three different diets high in fat: soybean oil, soybean oil modified to be low in linoleic acid, and coconut oil.

The same UC Riverside research team found in 2015 that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice. Then in a 2017 study, the same group learned that if soybean oil is engineered to be low in linoleic acid, it induces less obesity and insulin resistance.

However, in the study released this month, researchers did not find any difference between the modified and unmodified soybean oils effects on the brain. Specifically, the scientists found pronounced effects of the oil on the hypothalamus, where a number of critical processes take place.

The hypothalamus regulates body weight via your metabolism, maintains body temperature, is critical for reproduction and physical growth as well as your response to stress, said Margarita Curras-Collazo, a UC Riversideassociate professor of neuroscience and lead author on the study.

The team determined a number of genes in mice fed soybean oil were not functioning correctly. One such gene produces the love hormone, oxytocin. In soybean oil-fed mice, levels of oxytocin in the hypothalamus went down.

The research team discovered roughly 100 other genes also affected by the soybean oil diet. They believe this discovery could have ramifications not just for energy metabolism, but also for proper brain function and diseases such as autism or Parkinsons disease. However, it is important to note there is no proof the oil causes these diseases.

Additionally, the team notes the findings only apply to soybean oil not to other soy products or to other vegetable oils.

Do not throw out your tofu, soymilk, edamame, or soy sauce, said Frances Sladek, a UC Riverside toxicologist and professor of cell biology. Many soy products only contain small amounts of the oil, and large amounts of healthful compounds such as essential fatty acids and proteins.

A caveat for readers concerned about their most recent meal is that this study was conducted on mice, and mouse studies do not always translate to the same results in humans.

Also, this study utilized male mice. Because oxytocin is so important for maternal health and promotes mother-child bonding, similar studies need to be performed using female mice.

One additional note on this study the research team has not yet isolated which chemicals in the oil are responsible for the changes they found in the hypothalamus. But they have ruled out two candidates. It is not linoleic acid, since the modified oil also produced genetic disruptions; nor is it stigmasterol, a cholesterol-like chemical found naturally in soybean oil.

Identifying the compounds responsible for the negative effects is an important area for the teams future research.

This could help design healthier dietary oils in the future, said Poonamjot Deol, an assistant project scientist in Sladeks laboratory and first author on the study.

The dogma is that saturated fat is bad and unsaturated fat is good. Soybean oil is a polyunsaturated fat, but the idea that its good for you is just not proven, Sladek said.

Indeed, coconut oil, which contains saturated fats, produced very few changes in the hypothalamic genes.

If theres one message I want people to take away, its this: reduce consumption of soybean oil, Deol said about the most recent study.

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America's most widely consumed cooking oil causes genetic changes in the brain - University of California

Cell Biology

Postdoctoral Research Associate job with DURHAM UNIVERSITY | 193376 – Times Higher Education (THE)

Applications are invited for a Postdoctoral Research Associate to work on a project entitled

"Skin model engineering by harnessing the biomechanical forces exerted on skin cell nuclei".

As a collaboration between Drs Akis Karakesisoglou and Martin Goldberg, Department of Biosciences, Durham University and Steven Hyde, Oxford University we have designed new methodology to generate high quality in vitroskin models. The methodology works through using genetic engineering tools that re-program the biomechanical properties of skin cells.

We have gained funds from the Northern Accelerator (a research commercialisation collaboration between four North East Universities) to further develop the in vitro skin model and to commercialise the underlying technology.

The role of the post holder is to research and implement solutions in the fields of skin tissue engineering, skin tissue/cell biology and microscopy. The project will involve the creation and development of skin equivalent cell culture models using novel methods, then testing and analysing their structural and functional properties. The postholder will be helped by Drs Karakesisoglou, Goldberg and Hyde to find solutions and the candidate will need experience in the above fields to implement the solutions.

The post requires good skills in reporting research progress verbally, and in writing.

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Postdoctoral Research Associate job with DURHAM UNIVERSITY | 193376 - Times Higher Education (THE)

Cell Biology

Transcriptional scanning in the sperm may regulate rate of human evolution – News-Medical.net

Maturing sperm cells turn on most of their genes, not to follow their genetic instructions like normal, but instead to repair DNA before passing it to the next generation, a new study finds.

Led by NYU Grossman School of Medicine researchers and published online January 23 in Cell, the study focuses on a mystery of biology: human sperm cells activate by far the largest number of genes (90 percent), a pattern also seen in other species like mice, birds, and even fruit flies. Cells in most organs express about 60 percent of their genetic code, or just the subset of genes needed for a cell type to do its particular job.

It now seems obvious that sperm activate so many more genes as they develop because doing so runs them through a DNA repair process, and protects the integrity of messages about to be inherited.

We also found that such repair in sperm is less active in genes that are activated, or transcribed, less often. This supports the theory that evolution is using transcription frequency as a lever, dialing it up to preserve the DNA code in some genes, but turning it down to enable changes elsewhere when it contributes to survival."

Itai Yanai, PhD, senior author, director of the Institute for Computational Medicine, professor in Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine

An example of genes not activated, not repaired, and free to accumulate changes in sperm were those related to immunity, which must continually evolve if the body is to recognize and attack ever-changing bacterial and viral invaders.

To conduct the new study, the authors analyzed gene expression patterns during sperm maturation at single-cell resolution. They first collected samples of human testes tissue, biopsied from consented volunteers. Using microfluidics, they then passed all cells in the samples down a tube just large enough for them to flow through in single file.

Within the tube each cell was pushed into its own water droplet, which acted like a mini-test tube in which enzymes opened the cells and then attached cell-specific barcodes to each transcribed snippet of genetic material. The labeled transcripts were then used to create maps of which genes were turned on at each point during sperm maturation. The team then cross-referenced these findings with known DNA variations in human population databases to estimate how often repair occurred in a given gene.

Surprisingly, researchers found that genes activated even a few times during sperm cell development contained 15-20 percent fewer DNA code errors than unexpressed genes, with the difference attributed to transcription-coupled repair (TCR). This process replaces faulty DNA patches just before the instructions they contain are converted into a related genetic material, RNA, during transcription, the first step in gene expression. RNA transcripts are then read to build proteins that make up cell structures and signals.

Cellular processes, including transcription, along with toxins in the environment, continually introduce errors into DNA chains, with TCR weeding out some of the altered code. The difference, the researchers say, is that sperm cells appear to apply TCR to more genes than is normal, but then to halt gene expression by mechanisms unknown before proteins are made.

Moving forward, the research team will seek to confirm whether sperm-derived genetic changes occur more often in genes not expressed during the maturation of sperm.

This may reveal insights into the causes of many genetic diseases linked to changes in the sperm of aging fathers. Male reproductive cells are known to divide and multiply throughout a person's life, with errors introduced each time. The authors say this may provide a rationale for the existence of widespread scanning uniquely in sperm, because egg cells received by each female in the womb do not multiply for the rest of her life.

Furthermore, the team will determine whether cells in the brain, which also express a large percentage of their genes, employ "transcriptional scanning" like sperm cells, and whether the scanning fails with age to increase risk for neurodegenerative diseases. Embryonic stem cells also display the high-transcription, low-mutation signature that could indicate the presence of such scanning during development.

"Survival of the fittest is a foundation of evolutional theory, but what if other mechanisms bias which gene types are more susceptible to change before natural selection can act on them?" asks first author Bo Xia, a PhD candidate in Yanai's lab. "Such a bias in the testes would have a dramatic effect, but only over evolutionary time scales, say millions of years."

Source:

Journal reference:

Xia, B., et al. (2020) Widespread Transcriptional Scanning in the Testis Modulates Gene Evolution Rates. Cell. doi.org/10.1016/j.cell.2019.12.015.

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Cell Biology

Does coffee affect your biology? Yes, more than just waking you up – ThePrint

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Youre reading this with a cup of coffee in your hand, arent you? Coffee is the most popular drink in many parts of the world. Americans drink more coffee than soda, juice and tea combined.

How popular is coffee? When news first broke that Prince Harry and Meghan were considering Canada as their new home, Canadian coffee giant Tim Hortons offered free coffee for life as an extra enticement.

Given coffees popularity, its surprising how much confusion surrounds how this hot, dark, nectar of the gods affects our biology.

The main biologically active ingredients in coffee are caffeine (a stimulant) and a suite of antioxidants. What do we know about how caffeine and antioxidants affect our bodies? The fundamentals are pretty simple, but the devil is in the details and the speculation around how coffee could either help or harm us runs a bit wild.

The stimulant properties of caffeine mean that you can count on a cup of coffee to wake you up. In fact, coffee, or at least the caffeine it contains, is the most commonly used psychoactive drug in the world. It seems to work as a stimulant, at least in part, by blocking adenosine, which promotes sleep, from binding to its receptor.

Caffeine and adenosine have similar ring structures. Caffeine acts as a molecular mimic, filling and blocking the adenosine receptor, preventing the bodys natural ability to be able a rest when its tired.

This blocking is also the reason why too much coffee can leave you feeling jittery or sleepless. You can only postpone fatigue for so long before the bodys regulatory systems begin to fail, leading to simple things like the jitters, but also more serious effects like anxiety or insomnia. Complications may be common; a possible link between coffee drinking and insomnia was identified more than 100 years ago.

Also read:Coffee lovers have 50% less chance of developing most common type of liver cancer: Study

Different people respond to caffeine differently. At least some of this variation is from having different forms of that adenosine receptor, the molecule that caffeine binds to and blocks. There are likely other sites of genetic variation as well.

There are individuals who dont process caffeine and to whom drinks like coffee could pose medical danger. Even away from those extremes, however, there is variation in how we respond to that cup of coffee. And, like much of biology, that variation is a function of environment, our past coffee consumption, genetics and, honestly, just random chance.

We may be interested in coffee because of the oh-so-joyous caffeine buzz, but that doesnt mean that caffeine is the most biologically interesting aspect of a good cup of coffee.

In one study using rats, caffeine triggered smooth muscle contraction, so it is possible that caffeine directly promotes bowel activity. Other studies, though, have shown that decaffeinated coffee can have as strong an effect on bowel activity as regular coffee, suggesting a more complex mechanism involving some of the other molecules in coffee.

What about the antioxidants in coffee and the buzz that surrounds them? Things actually start out pretty straightforward. Metabolic processes produce the energy necessary for life, but they also create waste, often in the form of oxidized molecules that can be harmful in themselves or in damaging other molecules.

Antioxidants are a broad group of molecules that can scrub up dangerous waste; all organisms produce antioxidants as part of their metabolic balance. It is unclear if supplementing our diet with additional antioxidants can augment these natural defences, but that hasnt stopped speculation.

Antioxidants have been linked to almost everything, including premature ejaculation.

Are any of the claims of positive effects substantiated? Surprisingly, the answer is again a resounding maybe.

Coffee wont cure cancer, but it may help to prevent it and possibly other diseases as well. Part of answering the question of coffees connection to cancer lies in asking another: what is cancer? At its simplest, cancer is uncontrolled cell growth, which is fundamentally about regulating when genes are, or are not, actively expressed.

My research group studies gene regulation and I can tell you that even a good cup of coffee, or boost of caffeine, wont cause genes that are turned off or on at the wrong time to suddenly start playing by the rules.

The antioxidants in coffee may actually have a cancer-fighting effect. Remember that antioxidants fight cellular damage. One type of damage that they may help reduce is mutations to DNA, and cancer is caused by mutations that lead to the misregulation of genes.

Studies have shown that consuming coffee fights cancer in rats. Other studies in humans have shown that coffee consumption is associated with lower rates of some cancers.

Interestingly, coffee consumption has also been linked to reduced rates of other diseases as well. Higher coffee consumption is linked to lower rates of Parkinsons disease and some other forms of dementia. Strikingly, at least one experimental study in mice and cell culture shows that protection is a function of a combination of caffeine and antioxidants in coffee.

Higher coffee consumption has also been linked to lower rates of Type 2 diabetes. Complexity, combined effects and variation between individuals seems to be the theme across all the diseases.

At the end of the day, where does all this leave us on the biology of coffee? Well, as I tell my students, its complicated. But as most reading this already know, coffee will definitely wake you up in the morning.

Also read:Now, drink coffee without milk to cut your carbon footprint, Starbucks says

This is an updated version of a story originally published on Jan. 19, 2020. The original story called coffee the worlds most popular beverage. The term most popular can be defined differently. Retail sales of coffee outpace tea globally, but tea is the most consumed beverage after water.

Thomas Merritt, Professor and Canada Research Chair, Chemistry and Biochemistry, Laurentian University

This article is republished from The Conversation under a Creative Commons license.

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Does coffee affect your biology? Yes, more than just waking you up - ThePrint

Cell Biology

Huntington’s Protein Has Unexpected Roles in Body Movement and Aging – Technology Networks

A Duke University research team has identified a new function of a gene called huntingtin, a mutation of which underlies the progressive neurodegenerative disorder known as Huntingtons Disease.Using genetic mouse models, they have discovered that neurons in the striatum, a brain area involved in controlling movement, require the huntingtin gene for regulating the bodys movements, maintaining cell health during aging, and developing functioning connections between cells.

Addressing the genes role in maintaining those neural connections may provide a new avenue against Huntingtons, the researchers said.

Huntingtons Disease is an inherited neurodegenerative disorder that usually emerges in mid-life and leads to impaired motor control, dementia, and psychiatric symptoms. While the genetic basis of this lethal disease was identified more than two decades ago, there are no approved treatments yet to slow its progression or cure it.

The disease is caused by a mutation in one of a persons two copies of the huntingtin gene. The mutation results in the production of an aberrant version of the huntingtin protein, which is toxic to neurons. Although the mutant protein is expressed throughout the body, neurons of the striatum are specifically vulnerable to its effects and degenerate as the disease progresses.

While the mutant huntingtin protein is damaging to neurons, it may also interfere with the remaining, non-mutated huntingtins ability to perform its normal functions.

Drugs currently being tested in clinical trials are designed to block the defective huntingtin protein, but they also end up decreasing the amount of normal huntingtin in neurons. Huntingtin is known to play several important functions in cells, but its specific role in striatal neuron health and function was not known.

We hypothesized that the normal huntingtin gene plays a critical role in neuronal health and connectivity, and we wanted to determine what happens to striatal neurons that have had huntingtin eliminated, said lead author Cagla Eroglu, an associate professor of cell biology and neurobiology and the co-director of Regeneration Next Initiative at Duke.

In the study, the team found that deleting the huntingtin gene specifically from the striatal neurons of very young mice caused these neurons to die as the mice aged, similar to the pattern of neuron death seen in Huntingtons Disease. They also found that mice lacking huntingtin in their striatal neurons were impaired in their ability to control their movement. Importantly, this loss of movement regulation happened even before the neurons themselves started to die.

These findings suggest that cell death itself might not be the only trigger of Huntingtons Disease symptoms, Eroglu said.

In a healthy brain, striatal neurons control movement by communicating with other neurons through connections called synapses. The researchers found that striatal neurons lacking huntingtin formed abnormal synaptic connections, which could potentially explain the problematic motor function of the mice.

We believe changes at the neuronal and synapse level happening before cell death are contributing to the progression of the disease, said Caley Burrus, a PhD candidate in Eroglus lab and first author of the study.

Its possible, the authors said, that therapies to address the faults at the level of the synapse may be beneficial for patients. The team is continuing the research by investigating the precise role huntingtin plays in synapse development, which might lead to specific drugs designed to target these deficits.

Understanding the critical roles huntingtin plays in neurons is essential to designing therapies that will help individuals with Huntingtons Disease in the safest and most effective way possible, Eroglu said.ReferenceBurrus et al. (2020) Striatal Projection Neurons Require Huntingtin for Synaptic Connectivity and Survival. Cell Reports. DOI: https://doi.org/10.1016/j.celrep.2019.12.069

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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Huntington's Protein Has Unexpected Roles in Body Movement and Aging - Technology Networks

Cell Biology

Study Uncovers Unexpected Connection Between Gliomas, Neurodegenerative Diseases – Newswise

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Newswise A protein typically associated with neurodegenerative diseases like Alzheimers might help scientists explore how gliomas, a type of cancerous brain tumor, become so aggressive.

The new study, in mouse models and human brain tumor tissues, was published inScience Translational Medicineand found a significant expression of the protein TAU in glioma cells, especially in those patients with better prognoses.

Patients with glioma are given a better prognosis when their tumor expresses a mutation in a gene called isocitrate dehydrogenase 1 (IDH1). In this international collaborative study led by the Instituto de Salud Carlos III-UFIEC in Madrid, Spain, those IDHI mutations stimulated the expression of TAU. Then, the presence of TAU acted as a brake for the formation of new blood vessels, which are necessary for the aggressive behavior of the tumors.

We report that the levels of microtubule-associated protein TAU, which have been associated with neurodegenerative diseases, are epigenetically controlled by the balance between normal and mutant IDH1/2 in mouse and human gliomas, says co-authorMaria G. Castro, Ph.D., a professor of neurosurgery and cell and developmental biology at Michigan Medicine. In IDH1/2 mutant tumors, we found that expression levels of TAU decreased with tumor progression.

That means levels of TAU could be used as a biomarker for tumor progression in mutant IDH1/2 gliomas, Castro says.

Her team, funded by the National Institutes of Health, collaborated with lead and senior study authors at the Centro de Biologa Molecular Severo Ochoa and the Instituto de Salud Carlos III-UFIEC, both in Madrid. Those researchers are funded by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Spanish Association Against Cancer (AECC).

"The IDH-TAUEGFR triad defines the neovascular landscape of diffuse gliomas,Sci. Transl. Med.DOI:10.1126/scitranslmed.aax1501

Adapted from a press release from theGlioma Lab(group leader Pilar Snchez-Gmez) at the Instituto de Salud Carlos III-UFIEC in Madrid, Spain.

Versin en espaol.

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Study Uncovers Unexpected Connection Between Gliomas, Neurodegenerative Diseases - Newswise

Cell Biology

MIT spin-out partners with Cambridge Consultants to co-develop the first Flowfect system – News-Medical.net

Jan 22 2020

MIT spin-out company Kytopen has engaged Cambridge Consultants to co-develop the first Flowfect system. Flowfect is a scalable, gentle process that yields billions of high-quality engineered cells in minutes. The system will streamline the engineering of a wide array of human and human-derived cells for use in next-generation cell therapies, with the goal of expanding access to powerful new living medicines.

Kytopens non-viral Flowfect technology uses continuous fluid flow combined with electric fields for high efficiency delivery of payloads such as mRNA, DNA, and CRISPR. The technology is compatible with a variety of cells, including iPSCs, primary T cells, and other human hematopoietic cells, being developed for immuno-oncology and gene editing applications. This first system, considered an alpha device, will represent a leap forward in the emerging cell therapy space, enabling therapeutic partners to realize improved transfection throughput and scalability, while maintaining cell health and function.

Cell therapies are a new category of living medicines with curative potential. Cells are collected from a patient, genetically modified to create highly personalized therapies, and then reinfused into the patient. A small number of these therapies have moved from clinical trials to market approval, but the industry must address challenges in manufacturability, scalability and cost if the full potential for patients is to be realized. The Kytopen team recognized this opportunity and has developed an elegant solution that both fits within the manufacturing process and has the potential to improve current approaches. The core technology was developed in the laboratory of Professor Cullen Buie at MIT. Subsequently, Buie and Kytopen CEO and Co-Founder Paulo Garcia joined MITs The Engine, an ecosystem of tough tech companies, to fully realize the technologys potential.

Having demonstrated rapid and high-performance cell transfection in continuous flow, Kytopen recognized the benefit of engaging with a proven development partner to take this technology off the bench and into a fully designed, closed system. This system will be a pre-production prototype, used by pharma partners to demonstrate Kytopens new approach in the development and manufacture of cell therapies. Cambridge Consultants was chosen due to its deep expertise in emerging cell therapy manufacturing and its ability to provide rapid turnkey development of the instrument, building on a decades-long history in regulated medical device development. Kytopen also valued Cambridge Consultants local proximity, in Boston MA, enabling close collaboration with their in-house engineering and biology teams during this co-development effort.

Cambridge Consultants has become the partner of choice for ambitious businesses seeking to develop the radical new devices behind the commercialization and scale-up of new therapies. This strength is underpinned by multidisciplinary teams, with expertise in biology and device development, as well as deep market knowledge. As a result, Cambridge Consultants is able to generate radical and new solutions that enable its clients to deliver faster access to emerging therapies.

Paulo Garcia, CEO and Co-Founder of Kytopen, commented:

We are excited to partner with Cambridge Consultants to help us accelerate the engineering of our standalone FlowfectTM System. The standalone system will be made available to select biotech and pharma partners to evaluate using their proprietary cell-payload combinations and existing workflows. We selected Cambridge Consultants for their expertise in product development following medical device guidelines, with deep understanding of the non-viral cell therapy industry that we wish to impact. We anticipate that this will be a step towards securing long-term clinical manufacturing partnerships with therapeutic companies developing the next-generation of cell therapies.

Mike Dunkley, Senior Vice President at Cambridge Consultants, commented:

Kytopens Flowfect technology has been developed from the ground up to deliver high-performance transfection of cells in both R&D and clinical manufacturing scenarios using identical core technology. The combined benefit of improved performance and faster scale-up that this approach delivers will help cell therapy pioneers tackling the challenges of high cost and manufacturing quality associated with currently available technology. Were delighted to be partnering with Kytopen, using our expertise in device engineering and regulated development to accelerate its progress to alpha, and widening access to these revolutionary new therapies.

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MIT spin-out partners with Cambridge Consultants to co-develop the first Flowfect system - News-Medical.net

Cell Biology

Even Tardigrades Will Feel the Heat of Climate Change – Eos

The microscopic water bears that can survive desiccation, extreme cold, and even trips to the Moon have a key weakness: heat. A recent study tested the survivability of a tardigrade species at elevated temperatures over an extended period. The team found that the lethal temperature for active tardigrades is only 1.2C hotter than the maximum recorded temperature where the samples were taken.

We can conclude that active tardigrades are vulnerable to high temperatures, though it seems that these critters would be able to acclimatize to increasing temperatures in their natural habitat, lead author Ricardo Neves said in a statement. Neves is a postdoctoral researcher in cell biology and physiology at the University of Copenhagen in Denmark.

When given time to adjust, the active tardigrades could withstand slightly higher temperatures for the experimental time frame. Desiccated tardigradesinactive from being dehydratedcould withstand significantly higher temperatures for a longer time.

This is not the first study to test the upper limits of tardigrades heat tolerance, but it is the first to test the animals resilience for an hour or longer, the team said. The researchers gathered samples of Ramazzottius varieornatus, a tardigrade species typically found in temporary freshwater habitats, from a roof gutter in Niv, Denmark.

The researchers exposed tardigrades to different levels of heat for 1 and 24 hours to find the lethal temperature, which they defined as the temperature at which 50% of the population died. They tested active tardigrades, desiccated tardigrades, and active tardigrades given a period of acclimation.

Active tardigrades were the most vulnerable to heat: lethal temperatures at 1 hour were 37.1C without acclimation and 37.6C with a short acclimation period. Desiccated tardigrades were more heat resistant than active ones, just like they are more tolerant of the cold. Half the desiccated population survived an hour at 82.7C. For the 24-hour exposure time, however, the lethal temperature dropped significantly to just 63.1C.

Its probability to withstand climate change is limited. The results indicate that hydrated or desiccated specimens of Ramazzottius varieornatus are able to tolerate high temperatures, but only for a short time, said Lorena Rebecchi, an associate professor of zoology at the University of Modena and Reggio Emilia in Italy. This indicates that its probability to withstand climate change is limited.

Rebecchi, who was not involved with this research, said that the results might be applicable to other tardigrade speciesthere are more than 1,000. Some species inhabiting mosses and lichens of temperate regions or Antarctica have a similar tolerance, she said.

The hottest temperature ever recorded in Denmark was 36.4C, only 1.2C higher than the active, acclimated tardigrades 1-hour heat tolerance. On average, the maximum temperature for Denmark is around 22C, but this value is likely to climb in the next decade.

Tardigrades are renowned for their ability to tolerate extreme conditions, the researchers wrote, but their endurance towards high temperatures clearly has an upper limithigh temperatures thus seem to be their Achilles heel.

Neves and colleagues published these results in January in Scientific Reports.

Kimberly M. S. Cartier (@AstroKimCartier), Staff Writer

Link:
Even Tardigrades Will Feel the Heat of Climate Change - Eos