Tiny Anolis lizards preserved since the Miocene in amber are giving scientists a true appreciation of the meaning of community stability. Dating back some 15 […]

The post Trapped in Amber: Ancient fossils reveal remarkable stability of Caribbean lizard communities appeared first on Smithsonian Insider.

Neanderthals (Homo neanderthalensis) were widespread across Europe and Western Asia for a long time, starting about 400,000 years ago. But things began to change when […]

The post Why did Neanderthals go extinct? appeared first on Smithsonian Insider.

Smithsonian scientists and colleagues have discovered a new genus and species of river dolphin that has long been extinct. They made the discovery after carefully […]

The post Fossil Specimen Reveals a New Species of Ancient River Dolphin appeared first on Smithsonian Insider.

If you were dumped into the middle of a desert, your first instinct would be to look for water—it is, after all, the stuff of […]

The post In Western China’s deserts an ancient competition for water resumes appeared first on Smithsonian Insider.

The Mojave Desert and Death Valley are among the hottest, driest places in North America. So how might climate change impact a resilient reptile that […]

The post Warming may shrink ancient range of heat loving desert lizard appeared first on Smithsonian Insider.

Contrary to popular imagery, massive volcanic eruptions or an asteroid impact may not have been the cause of the world’s first mass extinction. Rather, some […]

The post Did mystery worms cause world’s first mass extinction? appeared first on Smithsonian Insider.

New research by a team of archaeologists has revealed a curious connection between our traditional Thanksgiving dinner and the taste buds of prehistoric mammoths and […]

The post Study reveals ancient link between mammoth dung and pumpkin pie appeared first on Smithsonian Insider.

Tucked away on the lower levels of the Smithsonian’s National Museum of Natural History and National Museum of American History are some of science’s most […]

The post Smithsonian Libraries’ rare texts include early superstars of science appeared first on Smithsonian Insider.

The debate about the world’s oldest tattoos is over—they belong to Ötzi, the European Tyrolean Iceman who died and was buried beneath an Alpine glacier […]

The post Ancient Ink: Iceman Otzi Has World’s Oldest Tattoos appeared first on Smithsonian Insider.

Pulverized planet dust might lie around double stars » A planet like Star War’s Tatooine, which orbits twin suns, would have likely suffered from more […]

The post “Star Wars” Roundup: From Science Fiction to Science Fact appeared first on Smithsonian Insider.

Osteoarthritis in dogs is a serious and painful malady that effects many breeds. Recently Janine Brown, a biologist at the Smithsonian Conservation Biology Institute in […]

The post X-ray fluorescence shines new light on arthritis in dogs appeared first on Smithsonian Insider.

Scientists at the Smithsonian Institution and partners have published a paper that will help them save Panamanian frog species from extinction due to a deadly […]

The post New Study Helps Smithsonian Scientists Prioritize Frogs at Risk of Extinction appeared first on Smithsonian Insider.

The pink-headed duck was no lucky duck. In 1948 a single specimen of this waterfowl, Rhodonessa caryophyllacea, was donated to the Division of Birds of […]

The post Carotenoid pigments make extinct duck a rare bird indeed appeared first on Smithsonian Insider.

Smothered in tartar sauce and cheese it’s difficult to know just what species of fish lurks beneath the breaded surface of a fast-food fish sandwich. […]

The post Smithsonian scientist creating DNA database to track Caribbean conch and lobster appeared first on Smithsonian Insider.

It is rare but not entirely uncommon to see a manatee swimming in the Atlantic waters of Maryland and Virginia. This one was dead, however, […]

The post In face of mass extinctions, Smithsonian’s Global Genome Initiative quietly saves world’s DNA appeared first on Smithsonian Insider.

Remember the scene in Moonraker where Robert Kiel, as the steel-toothed character Jaws, bites through a tram cable that sends Roger Moore’s James Bond sprawling? […]

The post Smithsonian Discovery: 46-million-year-old beetle had zinc jaws appeared first on Smithsonian Insider.

Bald from snout to tail with baggy wrinkled skin and beady eyes, eastern African naked mole rats (Heterocephalus glaber) are subterranean mammals long credited with […]

The post Rare cancer cells discovered in naked mole rats appeared first on Smithsonian Insider.

Nocturnal, solitary and fiercely territorial the adult Egyptian pigmy shrew—one of the smallest mammals on earth—weighs just 7 grams. French zoologist Isidore Geoffroy Saint-Hilaire first […]

The post Sacred shrew mummies reveal species distribution in ancient Egypt appeared first on Smithsonian Insider.

The results are in, 2016 is going to be a good year for blue crabs in the Chesapeake Bay. An iconic figure embedded in the […]

The post Smithsonian Expert Urges Caution, Patience on Blue Crab Recovery appeared first on Smithsonian Insider.

Thirty years after the scimitar-horned oyrx were driven to extinction, the desert antelope will return to the last-known place it existed: Chad’s Sahelian grasslands. The […]

The post Extinct-in-the-Wild Antelope Return to the Grasslands of Chad appeared first on Smithsonian Insider.

A fossil that has been in the collection of the Smithsonian’s National Museum of Natural History since it was discovered in 1951 is today helping […]

The post New Species of Extinct River Dolphin Discovered in Smithsonian Collection appeared first on Smithsonian Insider.

In 2012, under a scientist’s watchful eye, a comb jelly ate some fish, digested it, and excreted the waste out its back end. In doing […]

The post By simply pooping, comb jellies expel long-held scientific misconception appeared first on Smithsonian Insider.

For centuries, cultures around the world have used masks in ritual dances and festivals to represent traditional characters. This copper mask, found in the Smithsonian’s […]

The post Mexican Masks: Tales Through Dance appeared first on Smithsonian Insider.

Sometimes there’s just no telling what will turn up at the local market. Fish biologist Jeff Williams of the Smithsonian’s National Museum of Natural History […]

The post Surprise: Distinctive new surgeonfish species makes an improbable debut appeared first on Smithsonian Insider.

Finding clean ways to store water is a challenge that humans have faced for millennia. In a new paper in Environmental Health, anthropologist Sabrina Sholts […]

The post Study shows ancient California Indians risked toxins from bitumen-coated bottles appeared first on Smithsonian Insider.

Covered in sharp spines, when harassed the porcupine fish inflates like a balloon. Think of a small soccer ball bristling all over with nails. Most predators […]

The post Indestructible jaws from ancient, extinct porcupine fish reveal new species appeared first on Smithsonian Insider.

Cats are notoriously fickle—purring in your lap one second, then swiping you with an indignant claw the next. One thing is certain however when it […]

The post Eons before viral kitten videos, ancient Egyptians adored cats appeared first on Smithsonian Insider.

Chances are, if you’ve been stung by a jellyfish along the Chesapeake Bay it was by a sea nettle jellyfish–one of the most common and […]

The post Scientists discover common sea nettle jellyfish is actually two distinct species appeared first on Smithsonian Insider.

A bat specimen collected in France at the end of World War I, since housed in the collections of the Smithsonian’s National Museum of Natural […]

The post DNA on 100-year-old bat from France may help fight deadly fungus in North America appeared first on Smithsonian Insider.

With a non-stop babble of hums, grunts and shrill squeals as they argue over fish and defend their territories, the Amazon’s giant otters are one […]

The post With voices joined in chorus, giant otter families create a distinct sound signature appeared first on Smithsonian Insider.

A new study from the Smithsonian Conservation Biology Institute (SCBI) is helping make headway in an area of animal management that has historically proven challenging: […]

The post Early indicator of cheetah pregnancy identified appeared first on Smithsonian Insider.

When “2001: A Space Odyssey” premiered April 2, 1968 at Washington, D.C.’s Uptown Theater—not far from the Smithsonian’s National Air and Space Museum—not everyone was […]

The post The real history behind science fiction’s ‘2001: A Space Odyssey’ appeared first on Smithsonian Insider.

 Extinct species don’t usually get a do-over… but don’t tell that to the scimitar-horned oryx. Erased from the wild for three decades, these desert […]

The post Podcast: Don’t call me extinct appeared first on Smithsonian Insider.

The outer membrane of Gram-negative bacteria is highly impermeable to hydrophilic molecules of larger than 600 Da, protecting these bacteria from toxins present in the environment. In order to transport nutrients across this impermeable membrane, Gram-negative bacteria utilize a diverse family of outer-membrane proteins called TonB-dependent transporters. The majority of the members of this family transport iron-containing substrates. However, it is becoming increasingly clear that TonB-dependent transporters target chemically diverse substrates. In this work, the structure and phylogenetic distribution of the TonB-dependent transporter YncD are investigated. It is shown that while YncD is present in some enteropathogens, including Escherichia coli and Salmonella spp., it is also widespread in Gammaproteobacteria and Betaproteobacteria of environmental origin. The structure of YncD was determined, showing that despite a distant evolutionary relationship, it shares structural features with the ferric citrate transporter FecA, including a compact positively charged substrate-binding site. Despite these shared features, it is shown that YncD does not contribute to the growth of E. coli in pure culture under iron-limiting conditions or with ferric citrate as an iron source. Previous studies of transcriptional regulation in E. coli show that YncD is not induced under iron-limiting conditions and is unresponsive to the ferric uptake regulator (Fur). These observations, combined with the data presented here, suggest that YncD is not responsible for the transport of an iron-containing substrate.

Aldo-keto reductases (AKRs) are NADPH/NADP+-dependent oxidoreductase enzymes that metabolize an aldehyde/ketone to the corresponding alcohol. AKR4C14 from rice exhibits a much higher efficiency in metabolizing malondialdehyde (MDA) than do the Arabidopsis enzymes AKR4C8 and AKR4C9, despite sharing greater than 60% amino-acid sequence identity. This study confirms the role of rice AKR4C14 in the detoxification of methylglyoxal and MDA, and demonstrates that the endogenous contents of both aldehydes in transgenic Arabidopsis ectopically expressing AKR4C14 are significantly lower than their levels in the wild type. The apo structure of indica rice AKR4C14 was also determined in the absence of the cofactor, revealing the stabilized open conformation. This is the first crystal structure in AKR subfamily 4C from rice to be observed in the apo form (without bound NADP+). The refined AKR4C14 structure reveals a stabilized open conformation of loop B, suggesting the initial phase prior to cofactor binding. Based on the X-ray crystal structure, the substrate- and cofactor-binding pockets of AKR4C14 are formed by loops A, B, C and β1α1. Moreover, the residues Ser211 and Asn220 on loop B are proposed as the hinge residues that are responsible for conformational alteration while the cofactor binds. The open conformation of loop B is proposed to involve Phe216 pointing out from the cofactor-binding site and the opening of the safety belt. Structural comparison with other AKRs in subfamily 4C emphasizes the role of the substrate-channel wall, consisting of Trp24, Trp115, Tyr206, Phe216, Leu291 and Phe295, in substrate discrimination. In particular, Leu291 could contribute greatly to substrate selectivity, explaining the preference of AKR4C14 for its straight-chain aldehyde substrate.

The bond-valence method has been used for valence calculations of FeMo/V cofactors in FeMo/V proteins using 51 crystallographic data sets of FeMo/V proteins from the Protein Data Bank. The calculations show molybdenum(III) to be present in MoFe7S9C(Cys)(HHis)[R-(H)homocit] (where H4homocit is homocitric acid, HCys is cysteine and HHis is histidine) in FeMo cofactors, while vanadium(III) with a more reduced iron complement is obtained for FeV cofactors. Using an error analysis of the calculated valences, it was found that in FeMo cofactors Fe1, Fe6 and Fe7 can be unambiguously assigned as iron(III), while Fe2, Fe3, Fe4 and Fe5 show different degrees of mixed valences for the individual Fe atoms. For the FeV cofactors in PDB entry 5n6y, Fe4, Fe5 and Fe6 correspond to iron(II), iron(II) and iron(III), respectively, while Fe1, Fe2, Fe3 and Fe7 exhibit strongly mixed valences. Special situations such as CO-bound and selenium-substituted FeMo cofactors and O(N)H-bridged FeV cofactors are also discussed and suggest rearrangement of the electron configuration on the substitution of the bridging S atoms.

The new book Subsistence Economies of Indigenous North American Societies provides a comprehensive and in-depth documentation of how Native American societies met the challenges of […]

The post New book: “The Subsistence Economies of Indigenous North American Societies: A Handbook” appeared first on Smithsonian Insider.

As command module pilot for the Apollo 15 mission to the moon in 1971, Al Worden spent six days orbiting the moon, including three days completely alone, the most isolated human in existence. In Falling to Earth, Worden tells for the first time the full story around the dramatic events that shook NASA and ended his spaceflight career.

The post “Falling to Earth: An Apollo 15 Astronaut’s Journey to the Moon” by Al Worden with Francis French appeared first on Smithsonian Insider.

Yinlong Song, Yikan Zhang, Ying Pan, Jianfeng He, Yan Wang, Wei Chen, Jing Guo, Haiteng Deng, Yi Xue, Xianyang Fang, and Xin Liang

Microtubules dynamics is regulated by the plus end-tracking proteins (+TIPs) in cells. End binding protein 1 (EB1) acts as a master regulator in +TIPs networks by targeting microtubule growing ends and recruiting other factors. However, the molecular mechanism of how EB1 binds to microtubule ends with a high affinity remains to be an open question. Using single-molecule imaging, we show that the end-binding kinetics of EB1 changes along with the polymerizing and hydrolysis rate of tubulin dimers, confirming the binding of EB1 to GTP/GDP-Pi tubulin at microtubule growing ends. The affinity of wild-type EB1 to these sites is higher than monomeric EB1 mutants, suggesting that two CH domains in the dimer contribute to the end-binding. Introducing phosphomimicking mutations into the linker domain of EB1 weakens the end-binding affinity and confers a more curved conformation to EB1 dimer without compromising dimerization, suggesting that the overall architecture of EB1 is important for the end-binding affinity. Taken together, our results provide insights into understanding how the high-affinity end-binding of EB1 can be achieved and how this activity may be regulated in cells.

Laura O'Regan, Giancarlo Barone, Rozita Adib, Chang Gok Woo, Hui Jeong Jeong, Emily L. Richardson, Mark W. Richards, Patricia A.J. Muller, Spencer J. Collis, Dean A. Fennell, Jene Choi, Richard Bayliss, and Andrew M. Fry

EML4-ALK is an oncogenic fusion present in ~5% non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants with different patient outcomes. Here, we show in cell models that EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. It also recruits the NEK9 and NEK7 kinase to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4 as well as constitutive activation of NEK9 also perturb cell morphology and accelerate migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but not ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7 leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer.

Liza Botros MD., Manon C. A. Pronk PhD., Jenny Juschten MD., John Liddle, Sofia K. S. H. Morsing, Jaap D. van Buul PhD., Robert H. Bates, Pieter R. Tuinman MD. PhD., Jan S. M. van Bezu, Stephan Huveneers PhD., Harm Jan Bogaard MD. PhD., Victor W. M. van Hinsbergh PhD., Peter L. Hordijk PhD., and Jurjan Aman MD. PhD.

Aims: Endothelial barrier dysfunction leads to edema and vascular leak, carrying high morbidity and mortality. Previously, Abl kinase inhibition was shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for novel treatment strategies against vascular leakage syndromes.

Methods & Results: Bosutinib most potently protected against inflammation-induced endothelial barrier disruption. In vivo, bosutinib prevented LPS-induced alveolar protein extravasation in an acute lung injury mice model. Mechanistically, Mitogen-activated Protein 4 Kinase 4 (MAP4K4) was identified as important novel mediator of endothelial permeability, which signals via ezrin, radixin and moesin proteins to increase turnover of integrin-based focal adhesions. The combined inhibition of MAP4K4 and Arg by bosutinib preserved adherens junction integrity and reduced turnover of focal adhesions, which synergistically act to stabilize the endothelial barrier during inflammation.

Conclusion: MAP4K4 was identified as important regulator of endothelial barrier integrity, increasing focal adhesion turnover and disruption of cell-cell junctions during inflammation. Inhibiting both Arg and MAP4K4, the clinically available drug bosutinib may form a viable strategy against vascular leakage syndromes.

David Guerit, Pauline Marie, Anne Morel, Justine Maurin, Christel Verollet, Brigitte Raynaud-Messina, Serge Urbach, and Anne Blangy

Among hematopoietic cells, osteoclasts (Oc) and immature dendritic cells (Dc) are closely related myeloid cells with distinct functions; Oc participate skeleton maintenance while Dc sample the environment for foreign antigens. Such specificities rely on profound modifications of gene and protein expression during Oc and Dc differentiation. We provide global proteomic and transcriptomic analyses of primary mouse Oc and Dc, based on original SILAC and RNAseq data. We established specific signatures for Oc and Dc including genes and proteins of unknown functions. In particular, we showed that Oc and Dc have the same α and β tubulin isotypes repertoire but that Oc express much more β tubulin isotype Tubb6. In both mouse and human Oc, we demonstrate that elevated expression of Tubb6 in Oc is necessary for correct podosomes organization and thus for the structure of the sealing zone, which sustains the bone resorption apparatus. Hence, lowering Tubb6 expression hindered Oc resorption activity. Overall, we highlight here potential new regulators of Oc and Dc biology and illustrate the functional importance of the tubulin isotype repertoire in the biology of differentiated cells.

Bipasha Dey and Richa Rikhy

Cell shape morphogenesis from spherical to polygonal occurs in epithelial cell formation in metazoan embryogenesis. In syncytial Drosophila embryos, the plasma membrane incompletely surrounds each nucleus and is organized as a polygonal epithelial-like array. Each cortical syncytial division cycle shows circular to polygonal plasma membrane transition along with furrow extension between adjacent nuclei from interphase to metaphase. In this study, we assess the relative contribution of DE-cadherin and Myosin II at the furrow for polygonal shape transition. We show that polygonality initiates during each cortical syncytial division cycle when the furrow extends from 4.75 to 5.75 µm. Polygon plasma membrane organization correlates with increased junctional tension, increased DE-cadherin and decreased Myosin II mobility. DE-cadherin regulates furrow length and polygonality. Decreased Myosin II activity allows for polygonality to occur at a lower length than controls. Increased Myosin II activity leads to loss of lateral furrow formation and complete disruption of polygonal shape transition. Our studies show that DE-cadherin-Myosin II balance regulates an optimal lateral membrane length during each syncytial cycle for polygonal shape transition.

Karolina Losenkova, Mariachiara Zuccarini, Marika Karikoski, Juha Laurila, Detlev Boison, Sirpa Jalkanen, and Gennady G. Yegutkin

Extracellular adenosine mediates diverse anti-inflammatory, angiogenic and vasoactive effects and becomes an important therapeutic target for cancer, which has been translated into clinical trials. This study was designed to comprehensively assess adenosine metabolism in prostate and breast cancer cells. We identified cellular adenosine turnover as a complex cascade, comprised of (a) the ectoenzymatic breakdown of ATP via sequential nucleotide pyrophosphatase/phosphodiesterase-1, ecto-5’-nucleotidase/CD73 and adenosine deaminase reactions, and ATP re-synthesis through counteracting adenylate kinase and nucleoside diphosphokinase; (b) the uptake of nucleotide-derived adenosine via equilibrative nucleoside transporters; and (c) the intracellular adenosine phosphorylation into ATP by adenosine kinase and other nucleotide kinases. The exposure of cancer cells to 1% O₂ for 24 hours triggered ~2-fold up-regulation of CD73, without affecting nucleoside transporters, adenosine kinase activity and cellular ATP content. The ability of adenosine to inhibit the tumor-initiating potential of breast cancer cells via receptor-independent mechanism was confirmed in vivo using a xenograft mouse model. The existence of redundant pathways controlling extracellular and intracellular adenosine provides a sufficient justification for reexamination of the current concepts of cellular purine homeostasis and signaling in cancer.

Aparna Sherlekar, Gayatri Mundhe, Prachi Richa, Bipasha Dey, Swati Sharma, and Richa Rikhy

Branched actin networks driven by Arp2/3 collaborate with actomyosin filaments in processes such as cell migration. The syncytial Drosophila blastoderm embryo also shows expansion of apical caps by Arp2/3 driven actin polymerization in interphase and buckling at contact edges by MyosinII to form furrows in metaphase. Here we study the role of Syndapin (Synd), an F-BAR domain containing protein in apical cap remodelling prior to furrow extension. synd depletion showed larger apical caps. STED super-resolution and TIRF microscopy showed long apical actin protrusions in caps in interphase and short protrusions in metaphase in control embryos. synd depletion led to sustained long protrusions even in metaphase. Loss of Arp2/3 function in synd mutants partly reverted defects in apical cap expansion and protrusion remodelling. MyosinII levels were decreased in synd mutants and MyosinII mutant embryos have been previously reported to have expanded caps. We propose that Syndapin function limits branching activity during cap expansion and affects MyosinII distribution in order to shift actin remodeling from apical cap expansion to favor lateral furrow extension.

Kelly L. Dunlevy, Valentina Medvedeva, Jade E. Wilson, Mohammed Hoque, Trinity Pellegrin, Adam Maynard, Madison M. Kremp, Jason S. Wasserman, Andrey Poleshko, and Richard A. Katz

A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via "tethering proteins" that function to bridge heterochromatin and the nuclear membrane or nuclear lamina. We identified previously a human tethering protein, PRR14, that binds heterochromatin through an N-terminal domain, but the mechanism and regulation of nuclear lamina association remained to be investigated. Here we identify an evolutionarily conserved PRR14 nuclear lamina binding domain (LBD) that is both necessary and sufficient for positioning of PRR14 at the nuclear lamina. We also show that PRR14 associates dynamically with the nuclear lamina, and provide evidence that such dynamics are regulated through phosphorylation-dephosphorylation of the LBD. Furthermore, we identified a PP2A phosphatase recognition motif within the evolutionarily conserved PRR14 C-terminal Tantalus domain. Disruption of this motif affected PRR14 localization to the nuclear lamina. The overall findings demonstrate a heterochromatin anchoring mechanism whereby the PRR14 tether simultaneously binds heterochromatin and the nuclear lamina through two separable, modular domains. The findings also describe an optimal PRR14 LBD fragment that could be used for efficient targeting of fusion proteins to the nuclear lamina.

Ganlu Deng, Yihong Chen, Cao Guo, Ling Yin, Ying Han, Yiyi Li, Yaojie Fu, Changjing Cai, Hong Shen, and Shan Zeng

Epithelial-mesenchymal transition (EMT) is a crucial process for cancer cells to acquire metastatic potential, which primarily causes death in gastric cancer (GC) patients. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β family that plays an indispensable role in human cancers. However, little is known about its roles in GC metastasis. In this study, BMP4 was found to be frequently overexpressed in GC tissues and was correlated with patient's poor prognosis. BMP4 was upregulated in GC cell lines and promoted EMT and metastasis of GC cells both in vitro and in vivo, while knockdown of BMP4 significantly inhibited EMT and metastasis of GC cells. Meanwhile, the inhibitor of DNA binding 1 (Id1) was identified as a downstream target of BMP4 by PCR arrays and upregulated via Smad1/5/8 phosphorylation. Id1 knockdown attenuated BMP4-induced EMT and invasion in GC cells. Moreover, Id1 overexpression in BMP4 knockdown cells restored the promotion of EMT and cell invasion. In summary, BMP4 induced EMT to promote GC metastasis by upregulating Id1 expression. Antagonizing BMP4 may be a potential therapeutic strategy in GC metastasis.

Isabella Guardamagna, Elisabetta Bassi, Monica Savio, Paola Perucca, Ornella Cazzalini, Ennio Prosperi, and Lucia A. Stivala

Assessing DNA repair is an important endpoint to study the DNA damage response for investigating the biochemical mechanisms of this process and the efficacy of chemotherapy, which often uses DNA damaging compounds. Numerous in vitro methods to biochemically characterize DNA repair mechanisms have been developed so far. However, they show some limitations mainly due to the lack of chromatin organization. Here we describe a functional cell-free system to study DNA repair synthesis in vitro, using G1-phase nuclei isolated from human cells treated with different genotoxic agents. Upon incubation in the correspondent damage-activated cytosolic extracts, containing biotin-16-dUTP, nuclei are able to initiate DNA repair synthesis. The use of specific DNA synthesis inhibitors markedly decreased biotinylated dUTP incorporation, indicating the specificity of the repair response. Exogenously added human recombinant PCNA protein, but not the sensors of UV-DNA damage DDB2 or DDB1, stimulated UVC induced dUTP incorporation. In contrast, a DDB2^PCNA- mutant protein, unable to associate with PCNA, interfered with DNA repair synthesis. Given its responsiveness to different type of DNA lesions, this system offers an additional tool to study DNA repair mechanisms.

Formed some 250,000 years ago when the Nile River pushed through a low channel near Wadi Tushka, it flooded the eastern Sahara, creating a lake that at its highest level covered more than 42,000 square miles.

The post Ancient megalake discovered beneath Sahara Desert appeared first on Smithsonian Insider.