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Chinese Dinosaur Might Have Been as Iridescent as a Hummingbird

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Earlier this month, I wrote an article on a toy line of scientifically accurate Velociraptor action figures with plumage inspired by modern birds. I mused how impressive it would be if prehistoric raptors had been covered by feather patterns not unlike those in the toy line. Little did I know that two weeks later, researchers would reveal that some theropods had iridescent feathers that outshine David Silva’s velocifigures.

The Caihong juji, Mandarin for “rainbow with a big crest” (or just Caihong for short), was a “paravian theropod,” a clade commonly known for its winged forelimbs (even though many weren’t capable of flight) and enlarged sickle foot claws. In 2014, a farmer in the Qinlong County in the Hebei Province of Northeastern China gave a nearly complete Caihong fossil, feathers included, to The Paleontological Museum of Liaoning. Finding a complete skeleton is rare in paleontology and proved very helpful to the researchers. However, you might wonder just how scientists were able to determine the iridescent nature of the Caihong’s plumage. Two words: fossilized melanosomes.

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Melanosomes are organelles that create, store, and transport melanin, which determines the pigments/colors of animal hair, fur, skin, scales, and feathers. Upon examining the Caihong’s head, crest, and tail feathers with an electron microscope, scientists discovered platelet-shaped structures similar in shape to the melanosomes that give hummingbirds their iridescent coloring. The rest of the body feathers had melanosome structures similar to those in the grey and black feathers of penguins, which would have made for an odd sight: a duck-sized dinosaur with body feathers as drab as a raven’s and head and neck feathers more colorful than a peacock’s.

The inferred feather coloration of the Caihong is not its only unusual feature, though. The dinosaur had longer arm and leg feathers than its relatives, and its tail feathers created a “tail surface area” that was larger than the famous proto-bird the Archaeopteryx.  Furthermore, the Caihong had bony crests, which while common among most dinosaurs, are almost unheard of among paravian theropods. But, more importantly, it had proportionally long forearms, which is a feature of flight-capable theropods, even though scientists believe the Caihong didn’t fly. While this dinosaur apparently has the earliest examples of proportionally long forearms in the theropod fossil records, it still falls in line with the belief that the evolution of flight-capable feathers outpaced the evolution of flight-capable skeletons. The melanosomes, however, are the more intriguing discovery, since they are the earliest examples of “organized platlet-shaped nanostructures…in dinosaurian feathers.”

While paleontologists are confident the Caihong’s platelet structures are melanosomes, the researchers understand that their discovery is based partially on inference and could potentially be incorrect. If the structures aren’t melanosomes, well, that invalidates this entire article. But that’s what paleontology is all about: examining the evidence, creating inferences supported by that evidence, and changing those inferences when new information becomes available. Still, the concept of dinosaurs with iridescent feathers is pretty cool. If you want to learn more about the Caihong juji, you can read the original article on Nature.

All you have to do to get my attention is talk about video games, technology, anime, and/or Dungeons & Dragons - also people in spandex fighting rubber suited monsters.

Artificial Intelligence

Eric Lefkofsky, the billionaire founder of Groupon, has launched another initial public offering (IPO),tempus is an artificial intelligence (AI) health technology company

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Eric Lefkofsky is no stranger to the world of public listings, and he’s gearing up to embark on his fourth venture. With a net worth of nearly $4 billion, this serial entrepreneur has successfully taken three of his own businesses public.

Today, he is the founder of Tempus, a genomic testing and data analysis company that is preparing to go public. However, he gained significant recognition as one of the co-founders of Groupon, a daily deal pioneer. Groupon made headlines in 2011 when it went public with a valuation of nearly $13 billion, marking one of the most notable debuts of that year.

Groupon’s initial public offering (IPO) and the subsequent years were notoriously challenging. However, the public listings of Lefkofsky’s other two companies, InnerWorkings in 2006 and Echo Global Logistics in 2009, didn’t cause major concerns for investors and performed successfully. InnerWorkings, a supply chain startup that was founded in 2001, was recently sold to private equity for a significantly lower amount than its initial public offering market capitalization.

Throughout its 11-year tenure as a publicly traded company, the stock of Echo Global Logistics experienced a consistent increase in value. Eventually, a private equity firm bought it for a significant 50% premium over its closing trading price in 2021.

There were some controversies surrounding Groupon, including a situation where Lefkofsky allegedly took a significant amount of money from the company’s pre-IPO round. This left the company with limited working capital and resulted in a significant decrease in reported revenue after regulators examined the financials. This unconventional decision has also revealed another transaction based on his previous experiences. He successfully sold his dot-com-era business, Starbelly.com, in 2000, but regrettably, the company that bought it filed for bankruptcy a year later, according to some sources.

Lefkofsky has gained a reputation for having a knack for success, although it may not always translate to long-term gains for investors in his companies.

Tempus is Lefkofsky’s latest endeavor in building a company that will stand the test of time and provide significant value. His wife’s successful breast cancer treatment reportedly inspired him to establish Tempus in 2015.

He expressed his surprise at the lack of data involved in her care during an interview with Forbes last year. “I became obsessed with the notion that there existed a wealth of technology designed for various industries that could be utilized in cancer care to empower physicians to make informed decisions based on data.”

He resigned as Groupon’s CEO in 2015, at a time when the company’s value had dropped to $2.6 billion. Groupon currently has a market capitalization of approximately $600 million. During that period, Lefkofsky directed his attention towards Lightbank, an early-stage venture firm.

It is worth noting that, according to the Tempus S-1 filing, he has not received any salary in the past two years. Unfortunately, the S-1 did not disclose more than two years’ worth of executive compensation for any named officer. Additionally, the filing states that he is entitled to receive a payment of $800,000 and a $800,000 bonus commencing in 2025. Furthermore, despite not receiving a salary, he received a substantial $5.3 million dividend from company stock this year, as indicated in the prospectus. In addition, the filing revealed that Tempus has taken care of the expenses related to $7.5 million worth of preferred shares and has also covered his private plane costs, amounting to $200,000.

Tempus saw a significant increase in revenues, with a growth of 66% from $321 million in 2022 to $531 million in 2023. However, the company continues to experience significant financial losses, with net losses of $290 million in 2023 and $214 million in 2022. Despite the challenging financials, there is a positive development in the operating loss margin, which has decreased from 83% in 2022 to 37% in 2023, as stated in the S-1 filing.

Additionally, Lefkofsky-founded Pathos AI and Tempus have a partnership. Pathos AI is a drug discovery platform that was established in 2020. Pathos compensates Tempus for the privilege of licensing its data. Meanwhile, Ryan Fukushima, the COO of Tempus, also takes on the role of CEO at Pathos and divides his time between the two companies.

There are additional signs that suggest Lefkofsky has a greater level of influence at Tempus than is typically seen.

Tempus has not yet disclosed its principal stockholder’s chart, but it is evident that Lefkofsky, a billionaire, is among them and owns a minimum of 5% of the company. It is clear that he is determined to maintain complete control of the company once it becomes publicly traded. Tempus has given his shares an impressive 30 votes per share. It is not uncommon to have super voting shares, but typically 10 votes per share is more common, while 20 votes is considered to be on the higher side. It is noteworthy that the CEO of a healthcare company has a significantly high level of shareholder influence. It remains to be seen if this influence will be diminished in future S-1s, which would indicate potential investor concerns.

However, Tempus’ S-1 filing makes it abundantly clear that Lefkofsky plays a crucial role in the company’s future. According to a healthcare VC interviewed, Tempus owes much of its growth and success in raising capital to Lefkofsky’s impressive marketing and fundraising abilities.

Tempus secured an impressive $1.42 billion in funding from a range of investors, including Lightbank, NEA, Revolution Growth, T. Rowe Price, Novo Holdings, Franklin Templeton, and Baillie Gifford. The company’s most recent valuation was $8.1 billion in October 2022. Tempus’ S-1 filing disclosed a recent $200 million investment from SoftBank.

No matter the amount of capital raised in its IPO, Tempus’ prospectus clearly states that the company is still a long way from reaching breakeven and will require additional capital in the future. Typically, unprofitable companies make sure to include this information in their prospectuses. However, it is important to note that investors may anticipate Tempus to have a follow-on public offering in the future, which could potentially impact their share price negatively.

Despite generating only $5.5 million in revenue from AI, which represents approximately 1% of its total revenue in 2023, Tempus is actively positioning itself as an AI company.

“Tempus is taking a risk by betting on their growth and the opportune moment for AI in the life sciences industry. However, the company’s current offering has yet to demonstrate its effectiveness,” commented the healthcare investor.

The company stated in its S-1 filing that its AI product line is still in its early stages, but it intends to incorporate AI, including generative AI, into all of its diagnostic tools. Tempus has chosen not to provide any additional comments beyond the information stated in the S-1.

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Biology

Weight Loss Launchpad: Space Technology Enhances the Effectiveness of Obesity mRNA Treatment

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Researchers at Penn Engineering have devised an innovative approach for the synthesis of a vital component of lipid nanoparticles (LNPs), drawing inspiration from space shuttle technology. LNPs play a crucial role in the administration of mRNA therapeutics, as exemplified by the Pfizer-BioNTech and Moderna COVID-19 vaccines. They enhance the ease of LNP manufacturing and enhance their efficacy in facilitating the transportation of mRNA into cells for medical interventions.

In an article published in Nature Communications, Michael J. Mitchell, an Associate Professor in the Department of Bioengineering, presents a novel approach for the synthesis of ionizable lipidoids. These lipidoids are crucial chemical constituents of lipid nanoparticles (LNPs) that play a crucial role in safeguarding and delivering therapeutic payloads. In this study, Mitchell et al. conducted an investigation of the efficacy of mRNA drug delivery for the treatment of obesity as well as the potential of gene-editing techniques for the management of hereditary disorders.

Optimizing the Production Process
Prior research has demonstrated that lipidoids possessing branching tails exhibit superior efficacy in delivering mRNA to cells. However, the processes involved in synthesizing these molecules are both time-consuming and expensive. According to Xuexiang Han, a postdoctoral student in the Mitchell Lab and co-first author of the research, we present an innovative approach for the effective and economical production of these lipidoids.

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The procedure entails the amalgamation of three chemical compounds, namely an amine “head,” two alkyl epoxide “tails,” and two acyl chloride “branched tails.” The observed similarity between the fully developed lipidoid and a space shuttle affixed to two booster rockets is not a mere coincidence. Han, a college student, recounts that a documentary on the space shuttle left a lasting impression on him due to the remarkable design of the solid rocket boosters that facilitated the shuttle’s entry into orbit. According to Han, it was determined that the addition of two branch tails as “boosters” to the lipidoid might enhance the transportation of mRNA.

The addition of branching tails greatly improved the ability of LNPs containing the new lipidoid to deliver mRNA to specific cells, similar to how boosters help a rocket get into the atmosphere. “We saw a big increase in the production of a hormone that controls metabolism in certain cells after these lipidoids were used to deliver mRNA.” This development is highly promising, particularly in the context of obesity treatment,” states Mitchell.

The article titled “In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors,” authored by Xuexiang Han, Junchao Xu, Ying Xu, Mohamad-Gabriel Alameh, Lulu Xue, Ningqiang Gong, Rakan El-Mayta, Rohan Palanki, Claude C. Warzecha, Gan Zhao, Andrew E. Vaughan, James M. Wilson, Drew Weissman, and Michael J. Mitchell, was published in Nature Communications on February 26, 2024.
The provided DOI, 10.1038/s41467-024-45537-z,

The research was carried out at the University of Pennsylvania School of Engineering and Applied Science and received funding from the National Institutes of Health (Award DP2 TR002776), the Burroughs Wellcome Fund Career Award at the Scientific Interface, the National Science Foundation CAREER Award (CBET-2145491), and the American Cancer Society (Grant RSG-22-122-01-ET).

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Biology

Skin cell DNA could potentially be utilized to create eggs for in vitro fertilization in the future

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Researchers are exploring a new process that has the potential to transform fertility treatment by transferring DNA from skin cells into a donor egg. In the future, this technology could allow women without viable eggs and men in same-sex relationships to have children who are genetically linked to them, although it is not yet ready for clinical usage.

Egg cells that are damaged or deteriorated due to disease, medical procedures, or aging frequently lead to infertility. This treatment involves exchanging the nucleus of a donor egg with the nucleus of a skin cell from the parent to address the issue. After the process, you get an operational egg that only contains genetic material from the intended parent and not from the donor.

The process is known as somatic cell nuclear transfer, and despite its name, it is complex and intricate.

There is a precedent from almost 20 years ago, when the first-ever cloning of an animal, Dolly the sheep, generated interest in adapting this method to people.

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Dolly was produced using genetic material from a lone adult sheep. The experts from Oregon Health & Science University (OHSU) explained the novel procedure, which enables the creation of embryos with DNA from both parents.

We are specifically excluding the topic of human cloning.

In January 2022, the researchers initially confirmed the feasibility of their experimental approach. The recent study has advanced this by showing how to attain an accurate chromosome count in the egg cell from the start.

Human sex cells, known as gametes, are haploid, containing half the number of chromosomes compared to other cells in the body. When a haploid egg cell and a haploid sperm cell fertilize one another, the resulting embryo becomes diploid and has a full complement of chromosomes.

OHSU’s team extracted egg cells from mice and removed their nuclei, then substituted them with nuclei from mouse skin cells. “But wait!” you exclaimed. Are skin cells diploid? They are indeed, but the team has a clever answer. They can prompt the implanted nucleus to release half of its chromosomes, creating a haploid cell that closely resembles a normal egg cell.

The eggs can undergo in vitro fertilization (IVF) with sperm, a common process utilized in fertility clinics worldwide. When successful, it leads to the creation of an embryo with chromosomes from both parents.

The approach has an advantage in the rapid production of eggs. Alternative approaches now being studied involve converting skin cells into induced pluripotent stem cells and then guiding these cells to develop into eggs or sperm.

Dr. Paula Amato, the study author, clarified that they are bypassing the process of cell reprogramming. Our technique’s advantage lies in its ability to circumvent the lengthy culture time required for cell reprogramming. Over the course of several months, numerous detrimental genetic and epigenetic alterations might occur.

The ultimate goal, as outlined by senior author Dr. Shoukhrat Mitalipov, is to create eggs for those who do not possess their own, but achieving this objective is still some years in the future. Aleksei Mikhalchenko, the primary author, emphasized the importance of doing a comprehensive assessment of safety, efficacy, and ethical considerations before considering the technique for clinical application.

The Supreme Court of Alabama’s declaration that embryos should be considered as children has brought IVF back into the public spotlight, with many predicting it would be a significant topic in the upcoming US presidential election. The implications of advancements in assisted reproduction will have a global impact, as approximately 1 in 6 people globally are impacted by infertility.

Using a donor egg without integrating DNA from the donor would be a significant and innovative development in reproductive treatment. This work has advanced science’s comprehension of how this concept could perhaps be realized in the future.

The research is featured in Science Advances.

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