Before iPhones and laptops there were human computers, some of whom worked at the Harvard College Observatory. Women like Henrietta Swan Leavitt, Williamina Fleming, and […]

The post Volunteers needed to preserve astronomical history and promote discovery appeared first on Smithsonian Insider.

The challenges of conceiving only get greater as we get older. But if you have some of the most prized genes within your entire species, […]

The post High hopes for 60 year-old crocodile to become mother again appeared first on Smithsonian Insider.

Bright orange with a distinctive call the Panamanian poison dart frog Andinobates geminisae lives in only a small area of the Caribbean Coast of Panama. […]

The post In modern amphibian “ark,” new species added with due diligence appeared first on Smithsonian Insider.

Zombies have been part of popular culture for decades. The living dead rising and taking over the world is a terrifying concept, worthy of Hollywood […]

The post It’s science: zombies already walk among us appeared first on Smithsonian Insider.

For the first time, astronomers have detected the presence of complex organic molecules, the building blocks of life, in a protoplanetary disk surrounding a young […]

The post Complex Organic Molecules Discovered in Infant Star System appeared first on Smithsonian Insider.

Size isn’t the only thing that’s small about the pygmy sloth―its population is too. But scientists at the Smithsonian say things may be looking up […]

The post Study reveals more Pygmy Sloths, But There Still Aren’t Many appeared first on Smithsonian Insider.

Warming temperatures may mean more generations of monarch butterflies in North America during summer months, say scientists who recently finished experiments with monarch caterpillars and […]

The post Warming temperatures may mean more monarch generations in some areas of North America appeared first on Smithsonian Insider.

Now here is something to ruminate on. About 85 percent of the methane produced by a cow comes out of its mouth as burps. The […]

The post Monitoring methane? Now there is a better way to measure 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.

A Smithsonian team of scientists re-examined a fossil sperm whale for the first time in 90 years and created an entirely new group in the […]

The post “Call Me Albicetus”: Fossil Sperm Whale Is Named in Honor of Moby-Dick appeared first on Smithsonian Insider.

She was a stunning brown queen; drowned some 46 million years ago in a shallow lake in Montana. Her remains, recently recovered along the Flathead […]

The post New Montana ant species emerge from 46-million-year-old rock appeared first on Smithsonian Insider.

If you were an average person in the 18th and early 19th centuries, chances are your wardrobe was 50 shades of beige, with maybe a […]

The post A Purple Accident and Its Vibrant Impact on the Modern World 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.

Seven fossil teeth exposed by the Panama Canal expansion project are the first evidence of a monkey on the North American continent before the Isthmus […]

The post First North American Monkey Fossils Found in Panama Canal Excavation appeared first on Smithsonian Insider.

As the Zika virus is rapidly taking hold around the world, health officials are racing to find its cause and prevent further spread of the […]

The post Smithsonian’s mosquito collection is weapon in battle against Zika appeared first on Smithsonian Insider.

 The distant planet GJ 1132b intrigued astronomers when it was discovered last year. Located just 39 light-years from Earth, it might have an atmosphere despite […]

The post Venus-like Exoplanet Might Have Oxygen Atmosphere, But Not Life appeared first on Smithsonian Insider.

In August astronomers announced that the nearby star Proxima Centauri hosts an Earth-sized planet (called Proxima b) in its habitable zone. At first glance, Proxima […]

The post Proxima Centauri Might Be More Sunlike Than We Thought appeared first on Smithsonian Insider.

In 1935, 101 cane toads from Hawaii were set loose in Australia to help control beetles that were decimating the Australian sugar crop. But instead […]

The post Discovery: Australia’s invasive cane toads modify their bodies to conquer new territory faster appeared first on Smithsonian Insider.

A one-cubic-foot approach to studying biodiversity as showcased in the new Biocube exhibit at the Smithsonian’s National Museum of Natural History has led to the […]

The post New parasitic crab species discovered during Smithsonian Biocube work in Solomon Islands appeared first on Smithsonian Insider.

Washington, D.C. is a city of symbols. The rites, rituals, and places that define Washington capture the aspirations of our nation and its citizens. Just […]

The post Trusted Sources: Why Museums and Libraries Are More Relevant Than Ever appeared first on Smithsonian Insider.

Two separate teams of scientists have identified major challenges for the development of life in what has recently become one of the most famous exoplanet […]

The post There’s more to extraterrestrial life than planets in “habitable zone” orbits 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.

One of Earth’s most evolutionarily unique species is also the world’s most trafficked mammal: pangolins, or “scaly anteaters.” A new study from the Smithsonian Conservation […]

The post Using genetics to help save world’s most trafficked mammal: the pangolin appeared first on Smithsonian Insider.

Flitting swiftly through the darkness above the tropical forest canopy in Central and South America, a group of cute little bats with dog-like faces have […]

The post More sky puppies! Scientists discover two new species of dog-faced bat appeared first on Smithsonian Insider.

Marine mammologist Matthew Leslie aims his crossbow from the bow of a moving boat at the dolphins riding the breaking waves below. A dolphin will […]

The post Some dolphins cross the Pacific more easily than others. Why that matters for protecting them appeared first on Smithsonian Insider.

Very early on, cockroach moms found out maternal care gave their offspring a better chance at survival. The cockroach parenting method—which includes feeding, guarding and […]

The post Helicopter cockroach moms have protected their young for millions of years appeared first on Smithsonian Insider.

Every queen deserves a castle, and the ruler of the Smithsonian’s National Zoo’s naked mole-rat colony is no different. After 27 years in a maze […]

The post Building a naked mole-rat dream home at the Smithsonian’s National Zoo appeared first on Smithsonian Insider.

l-Hydroxyproline (l-Hyp) is a nonstandard amino acid that is present in certain proteins, in some antibiotics and in the cell-wall components of plants. l-Hyp is the product of the post-translational modification of protein prolines by prolyl hydroxylase enzymes, and the isomers trans-3-hydroxy-l-proline (T3LHyp) and trans-4-hydroxy-l-proline (T4LHyp) are major components of mammalian collagen. T4LHyp follows two distinct degradation pathways in bacteria and mammals, while T3LHyp is metabolized by a two-step metabolic pathway that is conserved in bacteria and mammals, which involves a T3LHyp dehydratase and a Δ1-pyrroline-2-carboxylate (Pyr2C) reductase. In order to shed light on the structure and catalysis of the enzyme involved in the second step of the T3LHyp degradation pathway, the crystal structure of Pyr2C reductase from the archaeon Thermococcus litoralis DSM 5473 complexed with NADH and l-proline is presented. The model allows the mapping of the residues involved in cofactor and product binding and represents a valid model for rationalizing the catalysis of Pyr2C reductases.

Death-associated protein kinase 1 (DAPK1) is a serine/threonine protein kinase that regulates apoptosis and autophagy. DAPK1 is considered to be a therapeutic target for amyloid-β deposition, endometrial adenocarcinomas and acute ischemic stroke. Here, the potent inhibitory activity of the natural anthraquinone purpurin against DAPK1 phosphorylation is shown. Thermodynamic analysis revealed that while the binding affinity of purpurin is similar to that of CPR005231, which is a DAPK1 inhibitor with an imidazopyridazine moiety, the binding of purpurin was more enthalpically favorable. In addition, the inhibition potencies were correlated with the enthalpic changes but not with the binding affinities. Crystallographic analysis of the DAPK1–purpurin complex revealed that the formation of a hydrogen-bond network is likely to contribute to the favorable enthalpic changes and that stabilization of the glycine-rich loop may cause less favorable entropic changes. The present findings indicate that purpurin may be a good lead compound for the discovery of inhibitors of DAPK1, and the observation of enthalpic changes could provide important clues for drug development.

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.

Mycoplasma hyopneumoniae is a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins from M. hyopneumoniae may be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, from M. hyopneumoniae is presented and shows N- and C-terminal α/β domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agreement with this structural information, sequence analyses show similarities to substrate-binding members of the ABC transporter superfamily, with P46 facing the extracellular side as a functional subunit. In the structure with xylose, P46 was also bound to a high-affinity (Kd = 29 nM) Fab fragment from a monoclonal antibody, allowing the characterization of a structural epitope in P46 that exclusively involves residues from the C-terminal domain. The Fab structure in the complex with P46 shows only small conformational rearrangements in the six complementarity-determining regions (CDRs) with respect to the unbound Fab (the structure of which is also determined in this work at 1.95 Å resolution). The structural information that is now available should contribute to a better understanding of sugar nutrient intake by M. hyopneumoniae. This information will also allow the design of protocols and strategies for the generation of new vaccines against this important swine pathogen.

Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LARFN1–4) showed a characteristic L shape. SAXS data suggested limited flexibility within LARFN1–4, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LARIg1–3) and the four C-terminal FNIII domains (LARFN5–8) both bound heparin, while LARFN1–4 did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LARIg1–3 and LARFN5–8, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR.

The number of new X-ray crystallography-based submissions to the Protein Data Bank appears to be at the beginning of a decline, perhaps signalling an end to the era of the dominance of X-ray crystallography within structural biology. This letter, from the viewpoint of a young structural biologist, applies the Copernican method to the life expectancy of crystallography and asks whether the technique is still the mainstay of structural biology. A study of the rate of Protein Data Bank depositions allows a more nuanced analysis of the fortunes of macromolecular X-ray crystallography and shows that cryo-electron microscopy might now be outcompeting crystallography for new labour and talent, perhaps heralding a change in the landscape of the field.

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.

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.

Olivia R. Grafinger, Genya Gorshtein, Tyler Stirling, Megan I. Brasher, and Marc G. Coppolino

Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr⁵⁶⁷. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion.

Benjamin Ziman, Peter Karabinis, Paul Barghouth, and Nestor J. Oviedo

Nutrient availability upon feeding leads to an increase in body size in the planarian Schmidtea mediterranea. However, it remains unclear how food consumption integrates with cell division at the organismal level. Here we show that Sirtuins is evolutionarily conserved in planarians and specifically demonstrate that Sirtuin-1 (Smed-Sirt-1) regulates organismal growth by impairing both feeding behavior and intestinal morphology. Disruption of Smed-Sirt-1 with either RNAi or pharmacological treatment leads to reduced animal growth. Conversely, enhancement of Smed-Sirt-1 with resveratrol accelerates growth. Differences in growth rates were associated with changes in the amount of time to locate food and overall consumption. Furthermore, Smed-Sirt-1(RNAi) animals displayed reduced cell death and increased stem cell proliferation accompanied by impaired expression of intestinal lineage progenitors and reduced branching of the gut. Altogether, our findings indicate Sirtuin-1 is a crucial metabolic hub capable of controlling animal behavior, tissue renewal and morphogenesis of the adult intestine.

Victor J. F. Kitano, Yoko Ohyama, Chiyomi Hayashida, Junta Ito, Mari Okayasu, Takuya Sato, Toru Ogasawara, Maki Tsujita, Akemi Kakino, Jun Shimada, Tatsuya Sawamura, and Yoshiyuki Hakeda

Osteoporosis is associated with vessel diseases attributed to hyperlipidemia, and bone resorption by multinucleated osteoclasts is related to lipid metabolism. In this study, we generated low-density lipoprotein receptor (LDLR)/lectin-like oxidized LDL receptor-1 (LOX-1) double knockout (dKO) mice. We found that, like LDLR single KO (sKO), LDLR/LOX-1 dKO impaired cell-cell fusion of osteoclast-like cells (OCLs). LDLR/LOX-1 dKO and LDLR sKO preosteoclasts exhibited decreased uptake of LDL. The cell surface cholesterol levels of both LDLR/LOX-1 dKO and LDLR sKO osteoclasts were lower than the levels of wild-type OCLs. Additionally, the amount of phosphatidylethanolamine (PE) on the cell surface was attenuated in LDLR/LOX-1 dKO and LDLR sKO pre-OCLs, while the PE distribution in wild-type OCLs was concentrated on the filopodia in contact with neighboring cells. Abrogation of the ATP binding cassette G1 (ABCG1) transporter, which transfers PE to the cell surface, caused decreased PE translocation to the cell surface and subsequent cell-cell fusion. The findings of this study indicate the involvement of a novel cascade (LDLR~ABCG1~PE translocation to cell surface~cell-cell fusion) in multinucleation of OCLs.

Tara L. Mastro, Vishnu P. Tripathi, and Susan L. Forsburg

Translesion synthesis polymerases (TLSPs) are non-essential error-prone enzymes that ensure cell survival by facilitating DNA replication in the presence of DNA damage. In addition to their role in bypassing lesions, TLSPs have been implicated in meiotic double strand break repair in several systems. Here we examine the joint contribution of four TLS polymerases to meiotic progression in the fission yeast S. pombe. We observed the dramatic loss of spore viability in fission yeast lacking all four TLSPs which is accompanied by disruptions in chromosome segregation during meiosis I and II. Rec8 cohesin dynamics are altered in the absence of the TLSPs. These data suggest that the TLSPs contribute to multiple aspects of meiotic chromosome dynamics.

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.

Laurence Haren, Dorian Farache, Laurent Emorine, and Andreas Merdes

-tubulin is a major protein involved in the nucleation of microtubules in all eukaryotes. It forms two different complexes with proteins of the GCP family (gamma-tubulin complex proteins): -tubulin small complexes (TuSCs), containing -tubulin and GCPs 2 and 3, and -tubulin ring complexes (TuRCs), containing multiple TuSCs, in addition to GCPs 4, 5, and 6. Whereas the structure and assembly properties of TuSCs have been intensively studied, little is known about the assembly of TuRCs, and about the specific roles of GCPs 4, 5, and 6. Here, we demonstrate that two copies of GCP4 and one copy each of GCP5 and GCP6 form a salt-resistant sub-complex within the TuRC that assembles independently of the presence of TuSCs. Incubation of this sub-complex with cytoplasmic extracts containing TuSCs leads to the reconstitution of TuRCs that are competent to nucleate microtubules. In addition, we investigate sequence extensions and insertions that are specifically found at the amino-terminus of GCP6, and between the GCP6 grip1 and grip2 motifs, and we demonstrate that these are involved in the assembly or stabilization of the TuRC.

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.

Sanjeev Chavan Nayak and Vegesna Radha

C3G (RapGEF1) plays a role in cell differentiation and is essential for early embryonic development in mice. In this study, we identify C3G as a centrosomal protein colocalizing with cenexin at the mother centriole in interphase cells. C3G interacts through its catalytic domain with cenexin, and they show interdependence for localization to the centrosome. C3G depletion caused a decrease in cellular cenexin levels. Centrosomal localization is lost as myocytes differentiate to form myotubes. Stable clone of cells depleted of C3G by CRISPR/Cas9 showed the presence of supernumerary centrioles. Overexpression of C3G, or a catalytically active deletion construct inhibited centrosome duplication. Cilia length is longer in C3G knockout cells, and the phenotype could be reverted upon reintroduction of C3G or its catalytic domain. Association of C3G with the basal body is dynamic, decreasing upon serum starvation, and increasing upon reentry into the cell cycle. C3G inhibits cilia formation and length dependent on its catalytic activity. We conclude that C3G inhibits centrosome duplication and maintains ciliary homeostasis, properties that may be important for its role in embryonic development.

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.

Mei Wang, Luping Yu, Shu Wang, Fan Yang, Min Wang, Lufan Li, and Xin Wu

RNA-binding protein LIN28A is required for maintaining tissue homeostasis, including the reproductive system, but the underlying mechanisms on how LIN28A regulates germline progenitors remain unclear. Here, we dissected LIN28A-binding targets using high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) in the mouse testes. LIN28A preferentially binds to CDS or 3'UTR regions through these sites with GGAG(A) sequences enriched within mRNAs. Further investigation of Lin28a null mouse testes indicated that meiosis-associated mRNAs mediated by LIN28A were differentially expressed. Next, ribosome profiling revealed that the mRNA levels of these targets were significantly reduced in polysome fractions, and their protein expression levels decreased in the Lin28a null mouse testes, even when meiotic arrest in null mouse testes was not apparent. Collectively, these findings provide a set of binding targets that are regulated by LIN28A, which may potentially be the mechanism for the prominent role of LIN28A in regulating mammalian undifferentiated spermatogonia fates and male fertility.

The geologic faults responsible for the rise of the eastern Andes mountains in Colombia became active 25 million years ago—18 million years before the previously accepted start date for the Andes’ rise.

The post Andes Mountains Are Older Than Previously Believed appeared first on Smithsonian Insider.