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Swiss Regenerative Medicine Biotech Closes €19M Series B

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The regenerative medicine startup Cutiss has raised €18.8M (CHF 20M) to commercialize its personalized skin graft treatment for burn patients in Switzerland and the European Union around 2022.

This is the final closing of a Series B round announced earlier this month. The lead investor in the oversubscribed round was the Swiss firm Gisev Family Office, with other contributions from new and existing investors including the US charity, the Wyss Foundation.

The University of Zurich life science spin-off targets large and deep burns that reach the lower layer of skin tissue called the dermis, which is needed for wound healing. These burns often result in painful, disfiguring scars. The current standard of treatment is a skin graft from elsewhere on the patient’s body. However, these aren’t available in large quantities, and can still result in scars because they contain little tissue from the dermis layer. 

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To address this problem, Cutiss harvests a tiny sample of healthy skin from the patient. Cells are expanded in vitro and then combined with a hydrogel to produce a personalized skin graft that contains both the epidermis and dermis layers.

Cutiss CEO Daniela Marino told me what makes her firm’s personalized skin grafts unique is they permanently cover deep skin defects. “We can produce large quantities of skin grafts starting from a ‘stamp-size biopsy,’ she said. “Because of the biological characteristics of our product, we expect minimal scarring after treatment.

The firm’s regenerative medicine candidate has completed a phase I clinical trial on pediatric patients and is currently in phase II testing in both adults and children. 

Cutiss will use the Series B funds to finance the development of its lead program for burns. This development includes completing ongoing phase II trials and scaling up the manufacture of the therapy. As the treatment has an orphan designation from the EMA, the company is still to decide with the EMA whether the treatment will require phase III trials. The aim is to file for market authorization in Switzerland and the EU in 2022.

We are working on the full automation of the manufacturing process, so that our product could be produced in different parts of the world, in a quick manner and also affordably,” Marino said. 

So we propose a personalized, permanent solution that can cover large areas, results in no scarring, and can be delivered to patients worldwide. There is no other product with those characteristics. 

Some current alternatives to patient skin grafts are used as temporary wound coverings but aren’t suitable for a permanent graft, such as from cadavers or animals. In contrast, Marino underlined that Cutiss’ candidate is more than temporary. 

What we do is an organ transplantation,” she said. “Skin is our largest organ, and our product remains on the body and regenerates after transplantation.

Cutiss has some big competition in the regenerative medicine field. One of the most advanced companies developing skin autograft alternatives is the UK pharma company Mallinckrodt. Its phase III-stage lab-grown skin is designed to be off-the-shelf rather than personalized, which could make it quicker to deliver to patients. Mallinckrodt aims to apply for FDA approval this year.


Images from Shutterstock

Source: https://www.labiotech.eu/medical/cutiss-regenerative-medicine/

Biotechnology

An IAP class in four-part harmony

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Just a few months shy of February graduation during the pandemic and the start of a fifth-year master’s program, senior Jeana Choi realized that she had never taught a class during the January Independent Activities Period (IAP). “I thought, wow, I can’t end my college experience like this,” she says. An electrical engineering and computer science major who minored in music, Choi, a violinist, became excited by the prospect of teaching about something she loved: classical music.

The result of this moment of inspiration?  “Classical Music in the Social Media Generation,” an IAP class featuring renowned performers Yo-Yo Ma, Hilary Hahn, Drew Forde, and Nahre Sol. Notable for their use of digital platforms to communicate directly with fans, they all make their music accessible to casual listeners and build new audiences. “They are literally world experts on the topic of connecting with people virtually,” says Choi.

She quickly identified collaborators for this venture: members of her string quartet, a group that had worked together nearly three years within MIT’s Chamber Music Society: violinist and computer science graduate student Jeff Chow ’20; violist Jiaxing Liu, a fourth-year majoring in biology and minoring in music and brain and cognitive sciences; and cellist and biological engineering postdoc Alex Wang PhD ’20.

“Instead of taking an IAP class, I thought it would be cool to be on the other side,” says Liu. “And this also seemed like a great way to give back to the entire MIT community.”

It had been difficult for the group during the previous spring, when the pandemic drove them off campus, and in the fall, when they were forced to play outside in MIT courtyards. Some members of the quartet would soon be completing their studies and departing MIT. “We wanted to end on a better note, and teaching this IAP class felt like a way to show appreciation to the arts departments of MIT, and to each other,” says Wang.

In a fitting finale to their years at MIT, they designed “Classical Music in the Social Media Generation” around their shared musical passion and tailored to a youthful age cohort in the time of pandemic. Drawing 100 MIT students, alumni and faculty, the class proved a hit.

Music idols

Recruiting their distinguished guest lecturers took several frantic months. Members of the quartet were avid followers of these musicians on their varied digital platforms and understood what unique contributions they could make to the course. Sidelined from touring by the pandemic and more engaged than ever in reaching out remotely, the performers each agreed to anchor a one-hour class combining presentation and Q&A.

These classes offered a unique opportunity for MIT organizers, along with the IAP class members, to meet their musical idols. At the same time, the sessions revealed how professional musicians navigate a world where classical music is, as Choi says, “not as popular with the younger generation as it used to be.” Their guest lecturers demonstrated how they are reaching across this generational divide, “creating content that isn’t just playing, but engaging audiences through humor or interesting topics,” says Wang. 

Nahre Sol’s YouTube channel, for instance, features videos of what she calls “music as digested by a classical musician,” a series that includes low-fi hip-hop and pop. Through performances of familiar classics like “Happy Birthday” in the style of classical composers, which has drawn more than a million views in the past year, Sol has attracted more than 400,000 channel subscribers.

Drew Alexander Forde, known online as ThatViolaKid, approaches digital platforms from the perspective of an entrepreneur building a brand, with podcasts that touch on his interests outside of classical music. “He talked about being unique, having his own story, and how experiences shape who you are and what you want, which applies to anyone, in any career,” says Liu, who is thinking about his tips as she applies to medical school.

Hilary Hahn posts “Hahn Solos” as part of her blog, and aims to have “fun with creativity,” she told her IAP class. She incorporates visual and literary touches in her posts, and described her determination to remain upbeat with her fans and fellow musicians in spite of the pandemic. 

Above all, these musicians offered a sense of hope in hard times, a way of using music to bind together both an immediate and larger, virtual community. As the virus began its destructive course early last year, Yo-Yo Ma sought a way to help Covid-19 victims and essential workers. “I started Zooming into hospital rooms and to patients … and thanking people,” he said. But, he suggested, everyone can “make the effort … and connect to what you have not been connected to.” Ma concluded his class with a performance of one of his “Songs of Comfort,” a series of self-recorded videos he shared in the early days of the pandemic lockdown. 

Bittersweet finale

The remarks by Ma and the other performers resonated powerfully for the IAP organizers. With their time together at MIT rapidly approaching an end, they were reflective about the bonds music can forge. 

The quartet, says Liu, had been an oasis from big lecture halls, “the first class where I really got to know my classmates.” For Wang, chamber music wasn’t just about performing but making “important life connections,” he says. The quartet “evolved into something more,” a group that listened so intently to each other during practice that it became “almost a finishing-each-other’s-sentences kind of thing,” he says. Adds Chow, “We’re each other’s chamber music buddies … I don’t have the same relationship with any other friends.”

The intimacy of their relationship, says Choi, the result of watching and listening to each other carefully and respectfully, not only made the IAP class possible, but provided an unforgettable valedictory moment. “Though we might feel super alone in this pandemic, a community of 100 people came together, even virtually, which was comforting to see.”

This class was supported by MIT Music and Theater Arts and the Arts at MIT, with funding from The Council for the Arts at MIT, a group of alumni and friends with a strong commitment to the arts and serving the MIT community.

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Source: https://news.mit.edu/2021/iap-class-four-part-harmony-0305

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Gold River Productions Inc. (GRPS) appoints Sam Elias as Chief Revenue Officer and board member

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Palm Coast, FL, March 4, 2021 – OTC PR WIREGold River Productions, Inc. (OTC Pink: GRPS) announces the addition of Mr. Sam Elias to its team.  

With the recent announcement of distribution and availability of unique doctor crafted products to the marketplace, the Company is pleased to welcome Sam Elias to the GRPS fold. Mr. Elias has an amazing business background (see curriculum vitae – http://bit.ly/se457) and recognizes the ever-expanding potential of the company, especially with his active involvement in all matters from production to sale.

As senior vice president of Seagull Software Systems, Mr. Elias was responsible for establishing integral relationships of IBM business development worldwide. Mr. Elias helped take Seagull Software Systems from $1,000,000 in revenue, grown to more than $20,000,000, with more than 1,500 clients and 500 ISV partners.  He helped to sell this company to Rocket Software in 2007 for a value exceeding $300,000,000, before becoming Senior Vice President and General Manager of Rocket Software, exceeding expectations and growing revenues from $41,000,000 to $85,000,000, while doubling its EBITDA to nearly $38,000,000.

Mr. Elias will be in charge of all things related to products from development to production to worldwide distribution and sales.

“I don’t want a salary.  I don’t need the money,” Mr. Elias explained to Chairman of the Board, Richard Goulding.  He explained further, “what I see is vast potential for this Company.  What you and Dr.’s Bond have assembled, is an untapped market.  Your products will compete with pharmaceuticals and be far less toxic.  While the initial distribution with All Star Brands is substantial, I think this could be much bigger.  I have the right connections for a worldwide market.  I will make this succeed.”

About Gold River Productions Inc., GRPS: 

Gold River will focus on market-targeted products including, but not limited to rare cannabinoids and effective products where a particular need is identified. Products for pain relief, sleep, etc. that will be distributed work in through convenience stores, independent pharmacies and more will have mass appeal to the market.

This document contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, which are subject to a number of risks and uncertainties, many of which are outside Gold River’s control. These include but are not limited to the impact of competitors’ products, services and pricing; product demand; market acceptance;  new product development; reliance on key strategic alliances; the regulatory environment;  fluctuations in operating results; and other risks which are detailed from time to time in the Company’s filings with the Securities and Exchange Commission and/or OTC Markets. Gold River disclaims any obligation to update or alter its forward-looking statements whether as a result of new information, subsequent events or otherwise.

Investor caution/added risk and uncertainties for investors in companies claiming involvement in COVID-19 initiatives –

On April 8, 2020, SEC Chairman Jay Clayton and William Hinman, the Director of the Division of Corporation Finance, issued a joint public statement on the importance of disclosure during the COVID-19 crisis.

The SEC and Self-Regulatory Organizations are targeting public companies that claim to have products, treatments or other strategies with regard to COVID-19.

The ultimate impact of the COVID-19 pandemic on the Company’s operations is unknown and will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration of the COVID-19 outbreak. Additionally, new information may emerge concerning the severity of the COVID-19 pandemic, and any additional preventative and protective actions that governments, or the Company, may direct, which may result in an extended period of continued business disruption, reduced customer traffic and reduced operations. Any resulting financial impact cannot be reasonably estimated at this time.

CONTACT: Gold River Productions, Inc.

support@grpsinc.com

www.GRPSInc.com
@grpsinc

goldriversocialmedia@gmail.com

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Source: https://otcprwire.com/gold-river-productions-inc-grps-appoints-sam-elias-as-chief-revenue-officer-and-board-member/

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Study reveals how egg cells get so big

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Egg cells are by far the largest cells produced by most organisms. In humans, they are several times larger than a typical body cell and about 10,000 times larger than sperm cells.

There’s a reason why egg cells, or oocytes, are so big: They need to accumulate enough nutrients to support a growing embryo after fertilization, plus mitochondria to power all of that growth. However, biologists don’t yet understand the full picture of how egg cells become so large.

A new study in fruit flies, by a team of MIT biologists and mathematicians, reveals that the process through which the oocyte grows significantly and rapidly before fertilization relies on physical phenomena analogous to the exchange of gases between balloons of different sizes. Specifically, the researchers showed that “nurse cells” surrounding the much larger oocyte dump their contents into the larger cell, just as air flows from a smaller balloon into a larger one when they are connected by small tubes in an experimental setup.

“The study shows how physics and biology come together, and how nature can use physical processes to create this robust mechanism,” says Jörn Dunkel, an MIT associate professor of physical applied mathematics. “If you want to develop as an embryo, one of the goals is to make things very reproducible, and physics provides a very robust way of achieving certain transport processes.”

Dunkel and Adam Martin, an MIT associate professor of biology, are the senior authors of the paper, which appears this week in the Proceedings of the National Academy of Sciences. The study’s lead authors are postdoc Jasmin Imran Alsous and graduate student Nicolas Romeo. Jonathan Jackson, a Harvard University graduate student, and Frank Mason, a research assistant professor at Vanderbilt University School of Medicine, are also authors of the paper.

A physical process

In female fruit flies, eggs develop within cell clusters known as cysts. An immature oocyte undergoes four cycles of cell division to produce one egg cell and 15 nurse cells. However, the cell separation is incomplete, and each cell remains connected to the others by narrow channels that act as valves that allow material to pass between cells.

Members of Martin’s lab began studying this process because of their longstanding interest in myosin, a class of proteins that can act as motors and help muscle cells contract. Imran Alsous performed high-resolution, live imaging of egg formation in fruit flies and found that myosin does indeed play a role, but only in the second phase of the transport process. During the earliest phase, the researchers were puzzled to see that the cells did not appear to be increasing their contractility at all, suggesting that a mechanism other than “squeezing” was initiating the transport.

“The two phases are strikingly obvious,” Martin says. “After we saw this, we were mystified, because there’s really not a change in myosin associated with the onset of this process, which is what we were expecting to see.”

cluster of cells
Clustered fruit fly nurse cells squeeze their contents into a large egg cell.

Martin and his lab then joined forces with Dunkel, who studies the physics of soft surfaces and flowing matter. Dunkel and Romeo wondered if the cells might be behaving the same way that balloons of different sizes behave when they are connected. While one might expect that the larger balloon would leak air to the smaller until they are the same size, what actually happens is that air flows from the smaller to the larger.

This happens because the smaller balloon, which has greater curvature, experiences more surface tension, and therefore higher pressure, than the larger balloon. Air is therefore forced out of the smaller balloon and into the larger one. “It’s counterintuitive, but it’s a very robust process,” Dunkel says.

Adapting mathematical equations that had already been derived to explain this “two-balloon effect,” the researchers came up with a model that describes how cell contents are transferred from the 15 small nurse cells to the large oocyte, based on their sizes and their connections to each other. The nurse cells in the layer closest to the oocyte transfer their contents first, followed by the cells in more distant layers.

“After I spent some time building a more complicated model to explain the 16-cell problem, we realized that the simulation of the simpler 16-balloon system looked very much like the 16-cell network. It is surprising to see that such counterintuitive but mathematically simple ideas describe the process so well,” Romeo says.

The first phase of nurse cell dumping appears to coincide with when the channels connecting the cells become large enough for cytoplasm to move through them. Once the nurse cells shrink to about 25 percent of their original size, leaving them only slightly larger than their nuclei, the second phase of the process is triggered and myosin contractions force the remaining contents of the nurse cells into the egg cell.

“In the first part of the process, there’s very little squeezing going on, and the cells just shrink uniformly. Then this second process kicks in toward the end where you start to get more active squeezing, or peristalsis-like deformations of the cell, that complete the dumping process,” Martin says.

Cell cooperation

The findings demonstrate how cells can coordinate their behavior, using both biological and physical mechanisms, to bring about tissue-level behavior, Imran Alsous says.

“Here, you have several nurse cells whose job it is to nurse the future egg cell, and to do so, these cells appear to transport their contents in a coordinated and directional manner to the oocyte,” she says.

Oocyte and early embryonic development in fruit flies and other invertebrates bears some similarities to those of mammals, but it’s unknown if the same mechanism of egg cell growth might be seen in humans or other mammals, the researchers say.

“There’s evidence in mice that the oocyte develops as a cyst with other interconnected cells, and that there is some transport between them, but we don’t know if the mechanisms that we’re seeing here operate in mammals,” Martin says.

The researchers are now studying what triggers the second, myosin-powered phase of the dumping process to start. They are also investigating how changes to the original sizes of the nurse cells might affect egg formation.

The research was funded by the National Institute of General Medical Sciences, a Complex Systems Scholar Award from the James S. McDonnell Foundation, and the Robert E. Collins Distinguished Scholarship Fund.

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Source: https://news.mit.edu/2021/study-reveals-how-egg-cells-get-so-big-0304

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Eyeless roundworms sense color

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Roundworms don’t have eyes or the light-absorbing molecules required to see. Yet, new research shows they can somehow sense color. The study, published on March 5 in the journal Science, suggests worms use this ability to assess the risk of feasting on potentially dangerous bacteria that secrete blue toxins. The researchers pinpointed two genes that contribute to this spectral sensitivity and are conserved across many organisms, including humans.

“It’s amazing to me that a tiny worm — with neither eyes nor the molecular machinery used by eyes to detect colors — can identify and avoid a toxic bacterium based, in part, on its blue color,” says H. Robert Horvitz, the David H. Koch Professor of Biology at MIT, a member of the McGovern Institute for Brain Research and the Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute Investigator, and the co-senior author of the study. “One of the joys of being a biologist is the opportunity to discover things about nature that no one has ever imagined before.”

The roundworm in question, Caenorhabditis elegans, is only about a millimeter long. Despite their minute stature and simple nervous system, these nematodes display a complex repertoire of behaviors. They can smell, taste, sense touch, react to temperature, and even escape or change their feeding patterns in response to bright, blue light. Although researchers once thought that these worms bury themselves deep in soil, it’s becoming increasingly clear that C. elegans prefers compost heaps above ground that offer some sun exposure. As a result, roundworms may have a need for light- and color-sensing capabilities after all.

The decomposing organic matter where C. elegans resides offers an array of scrumptious microbes, including bacteria like Pseudomonas aeruginosa, which secretes a distinctive blue toxin. Previous studies showed that worms in the lab feed on a lawn of P. aeruginosa for a few hours and then begin avoiding their food — perhaps because the bacteria continue to divide and excrete more of the colorful poison. Dipon Ghosh, Horvitz lab postdoc and the study’s first author, wondered whether the worms were using the distinctive color to determine if their meal was too toxic to consume.

Over the course of his experiments, Ghosh noticed that his worms were more likely to flee the colorful bacterial lawn if it was bathed in white light from a nearby LED bulb. This finding was curious on its own, but Ghosh wanted know if the blue toxin played a role as well.

To test this theory, he first exchanged the blue toxin for a harmless dye of the same color, and then for a clear, colorless toxin. On its own, neither substitute was sufficient to spur avoidance. Only together did they prompt a response — suggesting the worms were assessing both the toxic nature and the color of the P. aeruginosa secretions simultaneously. Once again, this behavioral pattern only emerged in the presence of the LED’s white light.

Intrigued, Ghosh wanted to examine what it was about the blue color that triggered avoidance. This time, he used two colored LED lights, one blue and one amber, to tint the ambient light. In doing so, he could control the ratio of wavelengths without changing the total energy delivered to the worms. The beam had previously contained the entire visible spectrum, but mixing the amber and blue bulbs allowed Ghosh to tweak the relative amounts of short-wavelength blue light and long-wavelength amber light. Surprisingly, the worms only fled the bacterial lawn when their environment was bathed in light with specific blue:amber ratios.

“We were able to definitively show that worms aren’t sensing the world in grayscale and simply evaluating the levels of brightness and darkness,” Ghosh says. “They’re actually comparing ratios of wavelengths and using that information to make decisions — which was thoroughly unexpected.”

It wasn’t until Ghosh ran his experiments again, this time using various types of wild C. elegans, that he realized the popular laboratory strain he’d been using was actually less color-sensitive compared to its close relatives. After analyzing the genomes of these worms, he was able to identify two genes in particular (called jkk-1 and lec-3) that contributed to these variations in color-dependent foraging.

Although the two genes play many important functions in a variety of organisms, including humans, they are both involved in molecular pathways that help cells respond to stress caused by damaging ultraviolet light.

“We’ve discovered that the color of light in the worm’s environment can influence how the worm navigates the world,” Ghosh says. “But our work suggests that many genes, in addition to the two we’ve already identified, can affect color sensitivity, and we’re now exploring how.”

The notion that worms can sense color is “astounding” and showcases nature’s innovation, according to Leslie Vosshall, Robin Chemers Neustein Professor and Howard Hughes Medical Institute Investigator at The Rockefeller University, who was not involved in the study. “These worms are sliding around in a dim muck with colorful, toxic bacteria. It would be helpful to see and avoid them, so the worms somehow evolved a completely new way to see.”

Vosshall is curious about which cells in C. elegans help discriminate light, as well as the specific roles that the jkk-1 and lec-3 genes play in mediating light perception. “This paper, like all important papers, raises many additional questions,” she says.

Ghosh suspects the lab’s findings could generalize to other critters besides roundworms. If nothing else, it’s clear that light-sensitivity does not always require vision — or eyes. C. elegans are seeing the light, and now so are the biologists.

This research was funded by the Howard Hughes Medical Institute and National Institute of General Medical Sciences.

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Source: https://news.mit.edu/2021/eyeless-roundworms-sense-color-0304

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