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.

Thomas O'Loughlin, Antonina J. Kruppa, Andre L. R. Ribeiro, James R. Edgar, Abdulaziz Ghannam, Andrew M. Smith, and Folma Buss

Optineurin (OPTN) is a multifunctional protein involved in autophagy, secretion as well as NF-B and IRF3 signalling and OPTN mutations are associated with several human diseases. Here we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-B and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations linked to POAG cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. Using proximity labelling proteomics, we identify the LUBAC complex, CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-B and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment leading to altered pro-inflammatory cytokine secretion.

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.

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.

Stephen Kershaw, David J. Morgan, James Boyd, David G. Spiller, Gareth Kitchen, Egor Zindy, Mudassar Iqbal, Magnus Rattray, Chris M. Sanderson, Andrew Brass, Claus Jorgensen, Tracy Hussell, Laura C. Matthews, and David W. Ray

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. Upon ligand binding, activated GR mediates cellular effects by regulating gene expression, but some GR effects can occur rapidly without new transcription. We show GCs rapidly inhibit cell migration, in response to both GR agonist and antagonist ligand binding. The inhibitory effect on migration is prevented by GR knockdown with siRNA, confirming GR specificity, but not by actinomycin D treatment, suggesting a non-transcriptional mechanism. We identified a rapid onset increase in microtubule polymerisation following glucocorticoid treatment, identifying cytoskeletal stabilisation as the likely mechanism of action. HDAC6 overexpression, but not knockdown of αTAT1, rescued the GC effect, implicating HDAC6 as the GR effector. Consistent with this hypothesis, ligand-dependent cytoplasmic interaction between GR and HDAC6 was demonstrated by quantitative imaging. Taken together, we propose that activated GR inhibits HDAC6 function and thereby increases the stability of the microtubule network to reduce cell motility. We therefore report a novel, non-transcriptional mechanism whereby GCs impair cell motility through inhibition of HDAC6 and rapid reorganization of the cell architecture.

Dr. Mary Hagedorn, a marine biologist at the Smithsonian Institution, talks about her research to understand and conserve our oceans' corals. To meet more scientists, visit https://insider.si.edu.

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"I'm getting paid to do what I like doing," says entomologist David Roubik. He loved nature and being outdoors when he was a kid, and now he does fieldwork in the tropical forests of Panama. He loves to travel, and his research takes him around the world. Can his work, then, be called a job?

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In 2010 Dr. Rachel Collin visited her colleagues at the Universidad Austral de Chile in Valdivia to collect some very special snails for her research at the Smithsonian Tropical Research Institute, Panama.

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Digging up early human and animal remains from the field in Africa, performing examination and publishing research about her findings, then enticing and educating the public about the implications are all in a week's work for Briana Pobiner.

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Meet Smithsonian scientist Justin Touchon, a National Science Foundation (NSF) postdoctoral researcher at the Smithsonian Tropical Research Institute in Panama.

Justin's work focuses on developmental ecology and reproductive plasticity of the hourglass treefrog (Dendropsophus ebraccatus) and red-eyed treefrog (Agalychnis callidryas). Justin and his advisor, Karen Warkentin, were the first to have witnessed the frogs laying eggs in water, in addition to doing so on land -- something with major implications for the evolutionary biology of similar creatures.

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Meg studies intergroup competition in white‐faced capuchin monkeys by tracking them through radio telemetry collars and observing their behaviors.

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Follow botanist Candy Feller of the Smithsonian Environmental Research Center as she conducts field work on mangrove ecosystems at Carrie Bow Cay, a Smithsonian field research station in the Caribbean.

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“Our guide celebrates the beauty of some of the most attractive inhabitants of Panama’s undersea realm and provides an indispensable, easy-to-use tool for their identification,” say the Littlers.

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The move enhances coordination efforts for the 46-plot research network, which partners with more than 75 institutions in 21 countries.

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As the Rim Fire burns deeper into Yosemite, park managers are fighting fire with fire—and one of the Smithsonian’s ForestGEO plots was caught in the […]

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One way to avoid a cold or the flu, doctors say, is to stay away from crowded places. Viruses spread fast in places where people […]

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This year’s El Niño event is one of the strongest on record and is still ramping up. Large parts of the tropics are turning into […]

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The Smithsonian-Mason School of Conservation offers a range of compelling residential, hands-on, interdisciplinary programs in conservation biology for undergraduate and graduate students and professionals at […]

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A tiny invasive insect from Asia might have an effect on Chesapeake Bay waters. The emerald ash borer is killing millions of ash trees in […]

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Increased research is the key to developing more widely applicable detection systems to find pipe bombs before they explode and to help catch the perpetrators when a bomb has gone off, says a new report from a committee of the National Research Council.

Although there is evidence of harmful health and ecological effects associated with exposure to high doses of chemicals known as hormonally active agents – or endocrine disrupters – little is understood about the harm posed by exposure to the substances at low concentrations, such as those that typically exist in the environment, says a new report from a National Research Council committee.

Representatives from academies and research organizations around the world sent messages of condolence and support to members, officials and staff of the U.S. National Academies in the wake of terrorist attacks on the World Trade Center and the Pentagon. The following are excerpts from some of these messages.

The role of guns in U.S. society is a subject of intense policy debate and disagreement.

The National Academies today recommended guidelines for research involving human embryonic stem cells, and urged all institutions conducting such research to establish oversight committees to ensure that the new guidelines will be followed.

The high rate of premature births in the United States constitutes a public health concern that costs society at least $26 billion a year, according to a new report from the Institute of Medicine of the National Academies.

A new data network that integrates emerging research on the molecular makeup of diseases with clinical data on individual patients could drive the development of a more accurate classification of disease and ultimately enhance diagnosis and treatment, says a new report from the National Research Council.

Research to date on the effect of capital punishment on homicide rates is not useful in determining whether the death penalty increases, decreases, or has no effect on these rates, says a new report from the National Research Council.

A new report from the Institute of Medicine and National Research Council proposes priorities for a research agenda to improve understanding of the public health aspects of gun-related violence, including its causes, health burden, and possible interventions.

The Institute of Medicine today presented the Gustav O. Lienhard Award to Linda Aiken, Claire M. Fagin Leadership Professor of Nursing at the University of Pennsylvania School of Nursing, for her rigorous research demonstrating the importance of nursing care and work environments in achieving safe, effective, patient-centered, and affordable health care.

Efforts to convert civilian research reactors from weapon-grade highly enriched uranium (HEU) to low enriched uranium (LEU) fuels are taking significantly longer than anticipated, says a congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine.

Insufficient sleep can decrease a commercial motor vehicle (CMV) driver’s level of alertness, which may increase the risk of a crash, yet little is known about effective ways to minimize that risk, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Weather and environmental forecasts made several weeks to months in advance can someday be as widely used and essential as current predictions of tomorrow’s weather are, but first more research and sustained investment are needed, says a new report from the National Academies of Sciences, Engineering, and Medicine.

A new report from the National Academies of Sciences, Engineering, and Medicine that examines the regulations governing federally funded research recommends that Congress authorize and the president appoint an independent national commission to examine and update the ethical, legal, and institutional frameworks governing research involving human subjects.

Increasing energy demands and expanding industrial and agricultural activities worldwide are changing the composition of the atmosphere and contributing to major global challenges like climate change and air pollution. The study of atmospheric chemistry plays a key role in understanding and responding to these challenges, and research in this field has been successful in guiding policies to improve air quality in urban areas and reduce acid rain and stratospheric ozone depletion.

A new report from the National Academies of Sciences, Engineering, and Medicine highlights the complexity of communicating about science effectively, especially when dealing with contentious issues, and proposes a research agenda to help science communicators and researchers identify effective methods.

The U.S. Global Change Research Program (USGCRP) has made significant accomplishments to advance the science of global environmental change and improve the understanding of its impact on society through activities such as developing Earth-observing systems, improving Earth-system modeling capabilities, and advancing understanding of carbon-cycle processes, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The call for expanding undergraduates’ access to research experiences in science, technology, engineering, and mathematics (STEM) raises questions about their use and potential to increase students’ interest and persistence in these disciplines.

Good morning. Welcome to the release of the report Preparing for Future Products of Biotechnology, from the National Academies of Sciences, Engineering, and Medicine.

Federal agencies or other organizations responsible for sponsoring research or collecting data on technology and the workforce should establish a multidisciplinary research program that addresses unanswered questions related to the impact of changing technology on the nature of work and U.S. national economy, says a new report by the National Academies of Sciences, Engineering, and Medicine.

All stakeholders in the scientific research enterprise -- researchers, institutions, publishers, funders, scientific societies, and federal agencies – should improve their practices and policies to respond to threats to the integrity of research, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The social, behavioral, and economic (SBE) sciences make significant contributions to the National Science Foundation’s mission to advance health, prosperity and welfare, national defense, and progress in science, says a new report from the National Academies of Sciences, Engineering, and Medicine.

The academic biomedical research community should improve its ability to mitigate and recover from the impacts of disasters, says a new report from the National Academies of Sciences, Engineering, and Medicine.