Asada M.,National Institute of Child Health and Development |
Asada M.,Otsuka Pharmaceutical Factory Inc. |
Rauch A.,Leibniz Institute for Age Research |
Shimizu H.,National Institute of Child Health and Development |
And 8 more authors.
Laboratory Investigation | Year: 2011
Glucocorticoids, such as dexamethasone, have been used as in vitro inducers of adipogenesis. However, the roles of the glucocorticoid receptor (GR) in adipogenesis have not been well characterized yet. Here, we show that inhibition of GR activity using the GR antagonist RU486 prevents human mesenchymal stem cell and mouse embryonic fibroblast (MEF) differentiation into adipocytes. Moreover, in MEFs isolated from GR knockout (GR null) and GR dim mice deficient in GR DNA-binding activity, adipogenesis was blocked. We identified glucocorticoid response element sites in the first intron of KLF15 by bioinformatical promoter analysis and confirmed their functional relevance by demonstrating GR interaction by chromatin immunoprecipitation. Moreover, transfection of MEFs with siRNA for KLF15 significantly attenuated the expressions of adipogenic-marker genes and the lipid accumulation. Our results provide a new mechanism for understanding glucocorticoids-dependent adipogenesis and that GR promotes adipogenesis via KLF15 gene expression as a transcriptional direct target. © 2011 USCAP, Inc All rights reserved.
News Article | August 31, 2016
Union rights A US national labour board has ruled that graduate students in the United States who work as teaching and research assistants at private universities must be recognized as employees, and therefore have a right to unionize. Graduate-student unions are already common at public institutions. The 23 August ruling relates to a case involving a group of students at Columbia University in New York City who have struggled to get their union recognized. There has been debate in recent years over the rights of graduate students, many of whom teach courses while completing their degrees. Obama creates largest marine park US President Barack Obama announced the creation of the world’s largest marine protected area on 26 August, with a huge expansion of the Papahānaumokuākea park in the northwest of the Hawaiian Islands. The move will take the park from its current size of around 360,000 square kilometres to 1.5 million square kilometres. The area is home to wildlife including whales, corals, millions of seabirds and the endangered Hawaiian monk seal (Neomonachus schauinslandi, pictured). Zika blood scans The US Food and Drug Administration (FDA) advised US blood banks on 26 August to test all blood donations for Zika virus, in light of the virus’s spread in the United States. Thousands of US travellers have been infected with Zika virus, but since July, 29 people in south Florida have contracted it locally through mosquitoes, and the virus is expected to spread to other states. Previously, the FDA recommended Zika blood screening only in states affected by the virus. Separately, Singapore has reported its first small cluster of locally transmitted cases. It joins Vietnam, Thailand and the Philippines as countries in southeast Asia that have also reported their first sporadic transmissions of the virus this year. Leprosy vaccine India is to begin testing the world’s first vaccine that exclusively targets leprosy. The disease, which is caused by the bacterium Mycobacterium leprae,newly affects 125,000 people in India each year — 60% of global new cases. The vaccine, developed in India, has been approved by the country’s drug-regulation agency as well as the US Food and Drug Administration. According to media reports, tests will begin in a few weeks in five districts in Bihar and Gujarat, treating people who live in close contact with infected individuals. Trials have shown that infections could be reduced by 60% in 3 years. China set for Mars The China National Space Administration is moving ahead with plans to send a rover to Mars in 2020. On 23 August, officials unveiled details of the lander, which will explore a low-latitude area in Mars’s northern hemisphere. The six-wheeled probe, to be named by a public contest, is designed to operate for at least 6 months; its 13 payloads will include a ground-penetrating radar to study rock layers. Other agencies aiming to send rovers to Mars during the 2020 launch opportunity include NASA and the European Space Agency. Robo-taxi trial Technology company nuTonomy said on 25 August that it will start trials of self-driving taxis in Singapore, in which customers will be able to request a ride using a smartphone app. Engineers from the company, which is based in Cambridge, Massachusetts, and Singapore, will ride in the car, ready to take the wheel as needed. The joint project with the Singapore Land Transport Authority aims to launch a fully autonomous taxi service by 2018. US ride-hailing company Uber and carmaker Volvo have said that they are starting similar trials in Pittsburgh, Pennsylvania. Italy earthquake A 6.2-magnitude earthquake struck central Italy in the early hours of 24 August, killing some 290 people and devastating towns in the Apennine mountains. The quake struck 40 kilometres from L’Aquila, where a similar event killed around 300 people in 2009. The region is tectonically complex, and seismologists had expected a rupture to occur there at any time. More than 900 aftershocks occurred, impeding recovery efforts. See page 15 for more. Airlander nosedive The world’s largest aircraft, which had a successful maiden flight in mid-August, has crash-landed on its second attempt. The 92-metre-long Airlander 10, which combines aeroplane and airship technology, nosedived on landing after the 100-minute test flight in Bedfordshire, UK, on 24 August (pictured). The cockpit of the craft was damaged, but nobody was injured, said the Airlander’s developer Hybrid Air Vehicles of Bedford. Airlander 10 is intended for use in surveillance, communication, aid delivery and even passenger travel. ‘No Planet B’ More than 150 Australian scientists sent an open letter on 24 August to the country’s prime minister, Malcolm Turnbull, urging action on global warming. The 2015 Paris climate agreement remains unbinding, and the world’s governments are “presiding over a large-scale demise of the planetary ecosystems”, the scientists wrote. Citing Turnbull’s 2010 statement that humanity has an obligation to the planet, the scientists called on the Australian government to do what is required to reduce carbon emissions and coal exports. “There is no Planet B,” the scientists wrote. Child-health chief Medical geneticist Diana Bianchi will be the new head of the US National Institute of Child Health and Development (NICHD), the National Institutes of Health (NIH) announced on 25 August. She replaces Alan Guttmacher, who retired in September 2015. As director, Bianchi will oversee the NICHD’s US$1.3-billion annual budget, which includes the Human Placenta Project and participation in a new NIH longitudinal study called Environmental Influences on Child Health Outcomes. Bianchi, who studies prenatal diagnostics, will take the helm on 31 October. Iranian physicist Omid Kokabee, a physicist who has been imprisoned in Iran for five years on an espionage conviction, has been granted freedom on parole, his lawyer said on 29 August. Kokabee, 34, was working on his PhD when he was jailed in Tehran in 2011. In April this year, he was moved to hospital to have kidney-cancer surgery. He was then granted temporary medical leave and released after his friends posted bail. Kokabee has maintained his innocence and said that he was persecuted for refusing to work on a military nuclear programme in Iran. See go.nature.com/2cb5ab0 for more. Physicist dies US particle physicist James Cronin died on 25 August, aged 84. In 1964, with colleague Val Fitch and their collaborators, Cronin discovered anomalies in the decay of kaon particles in an accelerator experiment at the Brookhaven National Laboratory in New York. The anomalies revealed a subtle asymmetry between matter and antimatter known as CP violation. Cronin and Fitch received a Nobel prize for their discovery in 1980. In the 1990s, Cronin became a driving force behind the Pierre Auger Observatory in Malargüe, Argentina, the largest cosmic-ray facility in the world, completed in 2004. Cronin was in the faculty of the University of Chicago in Illinois. By 2085, most cities will be too hot to host the summer Olympics, according to an analysis in The Lancet (K. R. Smith et al. Lancet 388, 642–644; 2016). Using climate modelling and a measure of heat stress, researchers judged the suitability of cities on the basis of whether conditions would be safe to run a marathon. Looking at the Northern Hemisphere, they found 25 cities in western Europe — and just 8 elsewhere — where temperatures were likely to be less than 26 °C in the shade, defined as low risk for marathon running. US$2 billion The latest estimate of the clean-up cost of a 2014 accident at a New Mexico underground nuclear-waste repository. The sum would make the nuclear accident, in which a drum containing radioactive waste blew up, the costliest in US history. Source: Los Angeles Times 4–7 September Researchers gather at the 10th Vaccine Congress in Amsterdam. www.vaccinecongress.com 6–9 September Enthusiasts head to the British Science Festival for activities and talks. britishsciencefestival.org
News Article | February 21, 2017
An analysis of 28 commercial physician-rating websites finds that search mechanisms are cumbersome, and reviews scarce, according to a study appearing in the February 21 issue of JAMA. Patients are increasingly seeking information about physicians online. Nearly 60 percent report that online reviews are important when choosing a physician. Because publicly reported quality data are not reported at the physician level, patients must consult physician-rating websites to find such reviews. Tara Lagu, M.D., M.P.H., of Baystate Medical Center, Springfield, Mass., and colleagues identified 28 physician-rating websites that met criteria for inclusion in the study. The researchers then used publicly available lists of registered and active physicians to identify a random sample of 600 physicians from three metropolitan areas (Boston, Portland, Ore.; and Dallas) and searched each website for reviews and calculated average and median number of reviews per physician per site. The authors found that few sites allowed the user to search by clinical condition, sex of physician, hospital affiliation, languages spoken, or insurance accepted. Across the 28 websites, there were 8,133 quantitative reviews for the 600 physicians. Among physicians with at least one review on any site, the median number was 7 reviews per physician across all sites. One-third of sampled physicians did not have a review on any site. The researchers write that despite certain study limitations, "these results demonstrate that it is difficult for a prospective patient to find (for any given physician on any commercial physician-rating website) a quantity of reviews that would accurately relay the experience of care with that physician." "Methods that use systematic data collection (e.g., surveys) may have a greater chance of amassing a sufficient quantity and quality of reviews to allow patients to make inferences about patient experience of care." Editor's Note: This work is supported by grants from the National Heart, Lung, and Blood Institute and from the National Institute of Child Health and Development of the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc. To place an electronic embedded link to this study in your story This link will be live at the embargo time: http://jamanetwork.
News Article | March 25, 2016
Couples who wish to get pregnant may want to avoid caffeine because it's associated with an increased risk of miscarriage, a new study from the National Institutes of Health (NIH) suggests. For women, drinking more than two caffeinated drinks daily before getting pregnant was associated with a 74 percent higher risk of a miscarriage, according to the study published today (March 24) in the journal Fertility and Sterility. But women's caffeine consumption wasn't the only factor: Among couples in which the male partner drank more than two caffeinated beverages daily before conception, there was a 73 percent higher risk of a miscarriage, according to the study. [6 Myths About Miscarriage] "Our findings indicate that the male partner matters, too," Germaine Buck Louis, the director of Intramural Population Health Research at the National Institute of Child Health and Development and lead author on the study, said in a statement. "Male pre-conception consumption of caffeinated beverages was just as strongly associated with pregnancy loss as females'," Buck Louis said. The study included 501 couples in Michigan and Texas who had stopped using contraception and were trying to become pregnant. The couples were instructed to keep daily journals of their lifestyle behaviors, including smoking cigarettes and drinking alcohol and caffeinated beverages, according to the study. Couples who got pregnant within a year continued in the study until they gave birth or experienced a miscarriage, according to the study. Of the 344 couples who became pregnant, 98 experienced a miscarriage, according to the study. Women 35 and older were nearly twice as likely to miscarry as women younger than 35, according to the study. In addition to the caffeine findings, the researchers also found that women who took a daily multivitamin before and during pregnancy were less likely to have a miscarriage. Women who took a daily multivitamin before getting pregnant were 55 percent less likely to miscarry, according to the study. And women who continued to take the multivitamin during early pregnancy had a 79 percent lower miscarriage risk, according to the study. The protective effect from the multivitamin may come from the folate and vitamin B6 found in a multivitamin, both of which have been linked to decreased risk of miscarriage, according to the study. The study only showed an association between caffeine intake and miscarriage, and did not prove cause and effect. Previous studies have shown similar results, although the potential mechanism is still unknown, according to the study. The authors did note, however, that the findings of the study do not necessarily mean that drinking decaf instead of regular coffee is safer, as the study did not include information on decaffeinated drinks, they wrote. Couples may want to limit their caffeine intake to fewer than three daily beverages, and women should continue to to be advised to take daily multivitamins before and during pregnancy, the researchers wrote in their conclusion. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Kami D.,Kyoto Prefectural University of Medicine |
Kitani T.,Kyoto Prefectural University of Medicine |
Kishida T.,Kyoto Prefectural University of Medicine |
Mazda O.,Kyoto Prefectural University of Medicine |
And 8 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2014
Gene transfer technique has various applications, ranging from cellular biology to medical treatments for diseases. Although nonviral vectors, such as episomal vectors, have been developed, it is necessary to improve their gene transfer efficacy. Therefore, we attempted to develop a highly efficient gene delivery system combining an episomal vector with magnetic nanoparticles (MNPs). In comparison with the conventional method using transfection reagents, polyethylenimine-coated MNPs introduced episomal vectors more efficiently under a magnetic field and could express the gene in mammalian cells with higher efficiency and for longer periods. This novel in vitro separation method of gene-introduced cells utilizing the magnetic property of MNPs significantly facilitated the separation of cells of interest. Transplanted cells in vivo were detected using magnetic resonance. These results suggest that MNPs play multifunctional roles in ex vivo gene transfer, such as improvement of gene transfer efficacy, separation of cells, and detection of transplanted cells. From the Clinical Editor: This study convincingly demonstrates enhanced efficiency of gene transfer via magnetic nanoparticles. The method also enables magnetic sorting of cells positive for the transferred gene, and in vivo monitoring of the process with MRI. © 2014 Elsevier Inc.
News Article | September 27, 2016
Expecting mothers experiencing nausea and vomiting during pregnancy may find some comfort in the results of a recent study that backs up the notion that morning sickness is a sign of a healthy pregnancy. Researchers at the National Institute of Child Health and Development examined data from women already enrolled in a larger study that analyzed the effects of taking aspirin on pregnancy loss and live birth. Out of the 1,200 women enrolled in the “Effects of Aspirin in Gestation and Reproduction Trial” from June 2007 to July 2011, 797 became pregnant. The study, published in the journal JAMA Internal Medicine, also focused on women who already lost at least one pregnancy. The participants kept a diary daily during their first trimester, which rated their morning sickness symptoms. In the second and third trimesters, the women completed monthly questionnaires about their symptoms. Overall, the results showed that women who experienced morning sickness were 50 to 75 percent less likely to experiencing a loss. To break it down further, about 18 percent of the women reported experiencing nausea at week two, and three percent had nausea with vomiting. By week eight, that number jumped to 57 percent and 27 percent, respectively. Those who experienced just nausea by week eight were 50 percent less likely to lose the pregnancy, and participants who endured vomiting were 75 percent less likely. Nearly 24 percent, or 188 of the 797 women, lost their pregnancy. “It’s a common thought that nausea indicates a healthy pregnancy, but there wasn’t a lot of high-quality evidence to support this belief,” said the study’s first author, Stefanie N. Hinkle, Ph.D, a staff scientist in NICHD’s Epidemiology Branch. “Our study evaluates symptoms from the earliest weeks of pregnancy, immediately after conception, and confirms that there is a protective association between nausea and vomiting and a lower risk of pregnancy loss.” The NICHD researchers overcame limitations seen in previous research by enrolling women as they were trying to conceive to track the pregnancy from the very beginning. They were also able to rule out other contributing factors such as alcohol or smoking, as well as fetal characteristics that may play a role in development. "These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss," the researchers explain in their paper. The researchers theorize that sickness during pregnancy may indicate viable placental tissue, because the tissue has released a sufficient amount of hormones—but the rapid change also produces a nauseous side effect. On the other hand, the researchers explain, if a woman is not experiencing any nausea, it could mean that not enough hormones were released and the placental tissue is less viable. But the team cautions women from making any generalizations from the study results, noting that every individual is different and not all pregnancies are the same.
Kayama T.,Tokyo Medical and Dental University |
Kayama T.,Jikei University School of Medicine |
Mori M.,Tokyo Medical and Dental University |
Mori M.,National Institute of Child Health and Development |
And 10 more authors.
Molecular and Cellular Biology | Year: 2016
Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro. Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx-/- mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx. In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration. © 2016, American Society for Microbiology. All Rights Reserved.
PubMed | National Institute of Child Health and Development
Type: Journal Article | Journal: Laboratory investigation; a journal of technical methods and pathology | Year: 2011
Glucocorticoids, such as dexamethasone, have been used as in vitro inducers of adipogenesis. However, the roles of the glucocorticoid receptor (GR) in adipogenesis have not been well characterized yet. Here, we show that inhibition of GR activity using the GR antagonist RU486 prevents human mesenchymal stem cell and mouse embryonic fibroblast (MEF) differentiation into adipocytes. Moreover, in MEFs isolated from GR knockout (GR(null)) and GR(dim) mice deficient in GR DNA-binding activity, adipogenesis was blocked. We identified glucocorticoid response element sites in the first intron of KLF15 by bioinformatical promoter analysis and confirmed their functional relevance by demonstrating GR interaction by chromatin immunoprecipitation. Moreover, transfection of MEFs with siRNA for KLF15 significantly attenuated the expressions of adipogenic-marker genes and the lipid accumulation. Our results provide a new mechanism for understanding glucocorticoids-dependent adipogenesis and that GR promotes adipogenesis via KLF15 gene expression as a transcriptional direct target.