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What did Megalodon eat? Anything it wanted — including other predators.

New Princeton research shows that prehistoric megatooth sharks — the biggest sharks that ever lived — were apex predators at the highest level…

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New Princeton research shows that prehistoric megatooth sharks — the biggest sharks that ever lived — were apex predators at the highest level ever measured.

Credit: Photo by Harry Maisch

New Princeton research shows that prehistoric megatooth sharks — the biggest sharks that ever lived — were apex predators at the highest level ever measured.

Megatooth sharks get their name from their massive teeth, which can each be bigger than a human hand. The group includes Megalodon, the largest shark that ever lived, as well as several related species.

While sharks of one kind or another have existed since long before the dinosaurs — for more than 400 million years — these megatooth sharks evolved after the dinosaurs went extinct and ruled the seas until just 3 million years ago.

“We’re used to thinking of the largest species — blue whales, whale sharks, even elephants and diplodocuses — as filter feeders or herbivores, not predators,” said Emma Kast, a 2019 Ph.D. graduate in geosciences who is the first author on a new study in the current issue of Science Advances. “But Megalodon and the other megatooth sharks were genuinely enormous carnivores that ate other predators, and Meg went extinct only a few million years ago.”

Her adviser Danny Sigman, Princeton’s Dusenbury Professor of Geological and Geophysical Sciences, added, “If Megalodon existed in the modern ocean, it would thoroughly change humans’ interaction with the marine environment.”

A team of Princeton researchers has now discovered clear evidence that Megalodon and some of its ancestors were at the very highest rung of the prehistoric food chain – what scientists call the highest “trophic level.” Indeed, their trophic signature is so high that they must have eaten other predators and predators-of-predators in a complicated food web, say the researchers.

“Ocean food webs do tend to be longer than the grass-deer-wolf food chain of land animals, because you start with such small organisms,” said Kast, now at the University of Cambridge, who wrote the first iteration of this research as a chapter in her dissertation. “To reach the trophic levels we’re measuring in these megatooth sharks, we don’t just need to add one trophic level — one apex predator on top of the marine food chain — we need to add several onto the top the modern marine food web.”

Megalodon has been conservatively estimated at 15 meters long — 50 feet — while modern great white sharks typically top out around five meters (15 feet).

To reach their conclusions about the prehistoric marine food web, Kast, Sigman and their colleagues used a novel technique to measure the nitrogen isotopes in the sharks’ teeth. Ecologists have long known that the more nitrogen-15 an organism has, the higher its trophic level, but scientists have never before been able to measure the tiny amounts of nitrogen preserved in the enamel layer of these extinct predators’ teeth.

“We have a series of shark teeth from different time periods, and we were able to trace their trophic level versus their size,” said Zixuan (Crystal) Rao, a graduate student in Sigman’s research group and a co-author on the current paper.  

One way to tuck in an extra trophic level or two is cannibalism, and several lines of evidence point to that in both megatooth sharks and other prehistoric marine predators.

The nitrogen time machine

Without a time machine, there’s no easy way to recreate the food webs of extinct creatures; very few bones have survived with teeth marks that say, “I was chewed on by a massive shark.”

Fortunately, Sigman and his team have spent decades developing other methods, based on the knowledge that the nitrogen isotope levels in a creature’s cells reveal whether it is at the top, middle or bottom of a food chain.

“The whole direction of my research team is to look for chemically fresh, but physically protected, organic matter — including nitrogen — in organisms from the distant geologic past,” said Sigman.

A few plants, algae and other species at the bottom of the food web have mastered the knack of turning nitrogen from the air or water into nitrogen in their tissues. Organisms that eat them then incorporate that nitrogen into their own bodies, and critically, they preferentially excrete (sometimes via urine) more of nitrogen’s lighter isotope, N-14, than its heavier cousin, N-15.

In other words, N-15 builds up, relative to N-14, as you climb up the food chain.

Other researchers have used this approach on creatures from the recent past — the most recent 10-15 thousand years — but there hasn’t been enough nitrogen left in older animals to measure, until now.

Why? Soft tissue like muscles and skin are hardly ever preserved. To complicate matters, sharks don’t have bones — their skeletons are made of cartilage.

But sharks do have one golden ticket into the fossil record: teeth. Teeth are more easily preserved than bones because they are encased in enamel, a rock-hard material that is virtually immune to most decomposing bacteria.

“Teeth are designed to be chemically and physically resistant so they can survive in the very chemically reactive environment of the mouth and break apart food that can have hard parts,” Sigman explained. And in addition, sharks aren’t limited to the 30 or so pearly whites that humans have. They are constantly growing and losing teeth — modern sand sharks lose a tooth every day of their decades-long lives, on average — which means that every shark produces thousands of teeth over its lifetime.

“When you look in the geologic record, one of the most abundant fossil types are shark teeth,” said Sigman. “And within the teeth, there is a tiny amount of organic matter that was used to build the enamel of the teeth — and is now trapped within that enamel.”

Since shark teeth are so abundant and are preserved so well, the nitrogen signatures in enamel provide a way to measure status in the food web, whether the tooth fell from a shark’s mouth millions of years ago or yesterday.

Even the largest tooth has only a thin casing of enamel, of which the nitrogen component is only a tiny trace. But Sigman’s team has been developing more and more refined techniques for extracting and measuring these nitrogen isotope ratios, and with a little help from dentist drills, cleaning chemicals and microbes that ultimately convert the nitrogen from within the enamel into nitrous oxide, they’re now able to precisely measure the N15-N14 ratio in these ancient teeth.

“We’re a little bit like a brewery,” he said. “We grow microbes and feed our samples to them. They produce nitrous oxide for us, and then we analyze the nitrous oxide they produced.”

The analysis requires a custom-built, automated nitrous oxide preparation system that extracts, purifies, concentrates and delivers the gas to a specialized stable isotope ratio mass spectrometer.

“This has been a multiple-decades-long quest that I’ve been on, to develop a core method to measure these trace amounts of nitrogen,” Sigman said. From microfossils in sediments, they moved on to other types of fossils, like corals, fish ear bones and shark teeth. “Next, we and our collaborators are applying this to mammalian teeth and dinosaur teeth.”

A deep dive into the literature during lockdown

Early in the pandemic, while her friends were making sourdough starters and bingeing Netflix, Kast pored through the ecologic literature to look for nitrogen isotope measurements of modern marine animals.

“One of the cool things that Emma did was really dig into the literature — all the data that’s been published over decades — and relate that to the fossil record,” said Michael (Mick) Griffiths, a paleoclimatologist and geochemist at William Patterson University and a co-author on the paper.

As Kast quarantined at home, she painstakingly built up a record with more than 20,000 marine mammal individuals and more than 5,000 sharks. She wants to take things much further. “Our tool has the potential to decode ancient food webs; what we need now is samples,” said Kast. “I’d love to find a museum or other archive with a snapshot of an ecosystem — a collection of different kinds of fossils from one time and place, from forams near the very base of the food web, to otoliths — inner ear bones — from different kinds of fish, to teeth from marine mammals, plus shark teeth. We could do the same nitrogen isotope analysis and put together the whole story of an ancient ecosystem.”

In addition to the literature search, their database includes their own samples of shark teeth. Co-author Kenshu Shimada of DePaul University connected with aquariums and museums, while co-authors Martin Becker of William Patterson University and Harry Maisch of Florida Gulf Coast University gathered megatooth specimens on the sea floor.

“It’s really dangerous; Harry’s a dive master, and you really need to be an expert to get these,” said Griffiths. “You can find little shark teeth on the beach, but to get the best-preserved samples, you need to go down to the bottom of the ocean. Marty and Harry have collected teeth from all over the place.”

He added: “It’s been a really collaborative effort to obtain the samples to pull this together. In general, collaborating with Princeton and other regional universities is really exciting because the students are amazing and my colleagues there have been really great to work with.”

Alliya Akhtar, a 2021 Ph.D. graduate from Princeton, is now a postdoctoral researcher in Griffiths’ lab. 

“The work I did for my dissertation (looking at isotopic composition of seawater) posed as many questions as it answered, and I was incredibly grateful to have the opportunity to continue working on some of these with a collaborator/mentor I respect,” Akhtar wrote in an email. “I’m most excited about all the work that is still to be done, all the mysteries yet to be solved!”

“Cenozoic megatooth sharks occupied extremely high trophic positions,” by Emma R. Kast, Michael L. Griffiths, Sora L. Kim, Zixuan C. Rao, Kenshu Shimada, Martin A. Becker, Harry M. Maisch, Robert A. Eagle, Chelesia A. Clarke, Allison N. Neumann, Molly E. Karnes, Tina Lüdecke, Jennifer N. Leichliter, Alfredo Martínez-García, Alliya A. Akhtar, Xingchen T. Wang, Gerald H. Haug and Daniel M. Sigman appears in the June 22 issue of Science Advances (DOI: 10.1126/sciadv.abl6529). This study was supported by the Scott Fund of the Department of Geosciences, Princeton University, by grants from the National Science Foundation Sedimentary Geology and Paleobiology (1830581 to M.L.G. and M.A.B.; 1830638 to R.A.E.; 1830480 to S.L.K.; and 1830858 to K.S.), the European Research Council Consolidator Grant Agreement 681450 (to J.N.L., awarded to T. Tütken), the Max Planck Society (to A.M-G. and G.H.H.), and the American Chemical Society Award, Petroleum Research Fund Undergraduate New Investigator Grant, PRF #54852-UNI2 (to M.L.G.).


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Aging-US | Time makes histone H3 modifications drift in mouse liver

BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone…

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BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.”

Credit: Hillje et al.

BUFFALO, NY- June 30, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.”

Aging is known to involve epigenetic histone modifications, which are associated with transcriptional changes, occurring throughout the entire lifespan of an individual.

“So far, no study discloses any drift of histone marks in mammals which is time-dependent or influenced by pro-longevity caloric restriction treatment.”

To detect the epigenetic drift of time passing, researchers—from Istituto di Ricovero e Cura a Carattere Scientifico, University of Urbino ‘Carlo Bo’, University of Milan, and University of Padua—determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. 

“In this study, we used chromatin immunoprecipitation sequencing technology to acquire 108 high-resolution profiles of H3K4me3, H3K4me1, H3K27me3 and H3K27ac from the livers of mice aged between 3 months and 12 months and fed 30% caloric restriction diet (CR) or standard diet (SD).”

The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, reduced the extent of changes occurring during the first year of life in these genomic regions.

“In conclusion, while our data do not establish that the observed changes in H3 modification are causally involved in aging, they indicate age, buffered by caloric restriction, releases the histone H3 marking process of transcriptional suppression in gene desert regions of mouse liver genome most of which remain to be functionally understood.”

DOI: https://doi.org/10.18632/aging.204107 

Corresponding Author: Marco Giorgio – marco.giorgio@unipd.it 

Keywords: epigenetics, aging, histones, ChIP-seq, diet

Sign up for free Altmetric alerts about this article:  https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204107

About Aging-US:

Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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FDA asks for COVID boosters to fight Omicron’s BA.4, BA.5 subvariants

The U.S. Food and Drug Administration on Thursday recommended booster doses of COVID-19 vaccines be modified beginning this fall to include components…

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FDA asks for COVID boosters to fight Omicron’s BA.4, BA.5 subvariants

By Michael Erman

June 30 (Reuters) – The U.S. Food and Drug Administration on Thursday recommended booster doses of COVID-19 vaccines be modified beginning this fall to include components tailored to combat the currently dominant Omicron BA.4 and BA.5 subvariants of the coronavirus.

The FDA said manufacturers would not need to change the vaccine for the primary vaccination series, saying the coming year will be “a transitional period when this modified booster vaccine may be introduced.”

FILE PHOTO: Signage is seen outside of the Food and Drug Administration (FDA) headquarters in White Oak, Maryland, U.S., August 29, 2020. REUTERS/Andrew Kelly/File Photo

The new booster shots would be bivalent vaccines, meaning doses would target both the original virus as well as the Omicron subvariants.

The decision follows a recommendation by the agency’s outside advisers to change the design of the shots this fall in order to combat more prevalent versions of the coronavirus. read more

BA.4 and BA.5 are now estimated to account for more than 50% of U.S. infections, according the U.S. Centers for Disease Control and Prevention, and have also become dominant elsewhere.

The FDA said in a statement on Thursday that it hoped the modified vaccines could be used in early to mid-fall.

Pfizer Inc (PFE.N) with partner BioNTech SE (22UAy.DE) and Moderna Inc (MRNA.O) have been testing versions of their vaccines modified to combat the BA.1 Omicron variant that caused the massive surge in cases last winter.

Although they have said those vaccines worked against BA.1 and the more recently circulating variants, they did see a lower immune response against BA.4 and BA.5.

The companies had already been manufacturing their BA.1 vaccines, and said on Tuesday that swapping to a BA.4/BA.5 version could slow the rollout.

Pfizer/BioNTech, which on Wednesday announced a $3.2 billion contract to supply more COVID vaccine doses to the United States, said they would have a substantial amount of BA.4/BA.5 vaccine ready for distribution by the first week of October. read more

Moderna said it would be late October or early November before it would have the newly modified vaccine ready.

Reporting by Michael Erman in New Jersey and Leroy Leo in Bengaluru; Editing by Jonathan Oatis and Bill Berkrot

Our Standards: The Thomson Reuters Trust Principles.

Source: Reuters

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Marketing automation startup Retail Rocket nabs $24M for expansion

Retail Rocket, a retention management platform for brands, today announced that it raised $24 million in a Series A round led by Cyprus-based private equity…

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Retail Rocket, a retention management platform for brands, today announced that it raised $24 million in a Series A round led by Cyprus-based private equity fund Flintera. In addition to the fundraising, Retail Rocket revealed that it acquired SailPlay, a startup developing software to help retailers build loyalty programs and send mass message campaigns.

New York-based SailPlay had raised $3.3 million prior to the acquisition. Founded in 2013 by Leonid Shangin and Yakov Filippenko, the company offered services to collect customer data and leverage it to create games, texts, and tasks designed to encourage repeat business.

As for Retail Rocket, it launched in 2012 headed by Moscow Business School of Management classmates, Nick Khlebinsky and Andrey Chizh, who’d attempted but failed to gain traction with several startups. The learnings from their previous efforts were the springboard for Retail Rocket, which after multiple pivots eventually grew its customer base to over 1,000 companies including Nintendo, Puma, and Decathlon.

“The digital marketing world is growing very fast and the demand for highly-skilled professionals is constantly increasing,” CEO Khlebinsky said. “The complexity of digital marketing tools is booming too — just several years ago we couldn’t imagine the technologies we use today.”

According to Khlebinsky, Retail Rocket uses a mathematical model to segment first-time buyers of a company’s product. By analyzing their actions — for example, the links they click on — the platform attempts to figure out their wants and preferences.

Image Credits: Retail Rocket

Retail Rocket also offers tools for campaign management like email marketing and web-based push notifications, as well as an engine that attempts to identify the best timing and communication channel (e.g., SMS) to make personalized offers. The goal is to create a “system of loyalty and retention management” for both online and offline customers, Khlebinsky said, that ultimately boosts business.

“We work with ecommerce on a performance-based pricing model,” Khlebinsky explained. “In most countries, the pandemic lockdowns spiked online sales, thus we experienced a temporary revenue increase. After the lockdown ended, there was a decrease, but to levels exceeding the pre-lockdown months, because a lot of people were forced to change their buying habits towards online shoppings.”

Absent independent reviews of Retail Rocket’s platform, it’s unclear whether its approach might beat out rivals like SalesForce, SAP, Bloomreach, and Dynamic Yield. But the promise of software that predictably drives repeat business is alluring. According to HubSpot, a mere 5% increase in customer retention can boost profits by 25% to 95%.

Retail Rocket has around 150 employees spread across offices in the Netherlands, Germany, Spain, Italy, and Chile, and it plans to double down on mergers and purchases in the coming months. Sources close to the company tell TechCrunch that Retail Rocket has $50 million set aside for acquisitions alone.

“Retail Rocket popped on our radars thanks to their international expansion and ability to set up sales teams in Europe and Latin America,” Flintera partner Sergey Vasin said in a statement. “We were impressed with the company’s results given the limited amount of investment they raised. The company was bootstrapping its growth after the seed round. Despite that, the efficiency of Retail Rocket products surpasses those of international competitors. We expect that the global e-commerce market will continue its growth at more than 10% per annum, with Latin America leading the race.”

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