bluuebunny/crossref_metadata_2025 huggingface dataset:
El Niño causes coral bleaching
Authors: Showstack Randy
Published: September 2022

El Niño's extremely warm waters in the Pacific Ocean have caused coral “bleaching” in the waters around the Galapagos Islands, Baja California, and Pacific coast of Panama, according to the National Oceanic and Atmospheric Administration (NOAA). The agency says the weather anomaly also has caused bleaching at sites in the Atlantic, including the Florida Keys.

Bleaching occurs as coral tissue expels zooxanthellae, a type of algae that resides in the coral, and is essential to the coral's survival. Corals normally recover, unless high ocean temperatures persist for too long a period or become too warm.
Looking for El Nino's silver lining
Authors: Showstack Randy
Published: September 2022

California, Florida, and other parts of the world that have been drenched by torrential rainfall from the current El Niño will have to take comfort in the silver lining inside the clouds for a few more months, according to U.S. Commerce Secretary William Daley. Meanwhile, regions that have been parched by El Niño will continue to look for those clouds. El Niño‐induced rains and droughts could continue through March, and taper off during the early part of the summer, Daley said at a February 12 news briefing.
Webby science awards
Authors: Showstack Randy
Published: September 2022

Two science sites on the Internet downloaded kudos at the 1998 Webby awards on March 6. Dubbed the Oscars of the Web, the awards presented by Web magazine this year honored Starchild, an astronomy‐oriented Web site for children ages 4–14 in the education category. The San Francisco Exploratorium, a hands‐on science center, won in the science category.

Other nominees included NASA's Pathfinder site and the Smithsonian Institute. They were among 6000 Web sites reviewed by the magazine.
National Ocean Sciences Bowl organized
Authors: Anonymous
Published: September 2022

The Consortium for Oceanographic Research and Education (CORE), with its member institutions, and in partnership with the National Marine Educators Association (NMEA), is organizing the first national competition for high school students on topics related to the study of the oceans. The competition, to be held annually, is called the National Ocean Sciences Bowl (NOSB).

The initiation of the program in 1998 coincides with the International Year of the Oceans. Sponsors include the Chief of Naval Research, Oceanographer of the Navy, NSF, NASA, and NOAA. Regional competitions were held in 16 states in late January and early February. Finals will be held in Washington, D.C., in late April 1998.
1998 Fellows Citations
Authors: Anonymous
Published: September 2022

AGU congratulates the 36 distinguished scientists who were selected by a committee of their peers to be AGU Fellows in 1998. This selection was based on the individuals' attainment of acknowledged eminence in a branch of geophysics.

The number of Fellows selected annually is limited to no more than 0.1% of the AGU membership. The new Fellows are listed below along with citations recognizing their specific achievements.
Backgrounder on ocean issues
Authors: Showstack Randy
Published: September 2022

A number of U.S. federal agencies with ocean‐related programs have collaborated to issue a hefty collection of “Year of the Ocean” discussion papers.

The background papers, released in March, serve as a primer for examining issues concerning marine science, environmental quality, global climate change, coastal hazards, fisheries, national security, and other issues related to oceans. Also included are surveys of U.S. domestic laws and international agreements concerning the oceans.
Ocean heroes
Authors: Showstack Randy
Published: September 2022

Ocean heroes Looking out over a lunchtime audience of about 500 scientists, business people, politicians, and environmental activists, actor Ted Danson commented that he was glad that shrimp had been served. “I like to say, if you can't eat them, why save them?” joked the former bartender on the long‐running television series, “ Cheers.”

Danson, well known for his comedic roles, was honored for his serious side as founder and president of American Oceans Campaign, during the National Oceans Conference last June in California.
Position statements
Authors: Anonymous
Published: September 2022

Historically, the government of the United States has called upon geophysical scientists to address some of the challenges that the country has faced, from historic expeditions to explore the frontier lands to modern attempts to map Earth's near‐space environment. As populations increase, as new technologies require a more detailed understanding of the environments in which they operate, as more demands are made upon non‐renewable sources, and as citizens demand better stewardship of the environment, the national and global demand for geophysical knowledge will continue to grow.

Individuals, businesses, and governments all have a stake in the gathering of geophysical knowledge. But since individuals and businesses tend by necessity to be focused on specific concerns, the government's role is critical. Given the broad implications and impacts of many societal issues related to the Earth and its environment, the geophysical expertise and knowledge that are needed to manage them often extends across several government jurisdictions. For example, in order to manage its water supplies prudently, the public and its elected representatives must understand where water comes from and where it goes. Scientific research—on local and global scales, in the short and long term—is crucial to such understanding. Having the appropriate geophysical information can allow a society to synthesize the requisite data, set policies, write legislation, and make the necessary investments to accomplish societal objectives.
Outstanding student paper awards
Authors: Anonymous
Published: September 2022

The Volcanology, Geochemistry and Petrology (VGP) Section presented the following Outstanding Student Paper Awards at the AGU 1997 Fall Meeting in San Francisco, California, on last December.

Ken Koga presented a poster on “Kinetics of Garnet to Spinel Facies Transformation and Trace Element Re‐distribution.” Ken graduated from Rensselaer Polytechnic Institute in 1993 with a B.S. from the Department of Earth and Environmental Sciences. He currently is at the MIT/WHOI Joint Program working towards a Ph.D. with Nobumichi Shimizu of WHOI and Timothy Grove of MIT. Ken's general interests include petrology and geochemistry of minerals in various magma generation processes. His thesis projects involve experimental investigations of the kinetics of solid‐state chemical reactions among upper minerals and geochemical consequences of these reactions.
NASA office to track near‐Earth objects
Authors: Showstack Randy
Published: September 2022

NASA announced in mid‐July the creation of a new office to coordinate agency‐sponsored efforts to detect, track, and characterize potentially hazardous asteroids and comets that could approach the Earth.

The Near‐Earth Object Program Office, sited at the Jet Propulsion Laboratory (JPL) in Pasadena, Calif., will focus on locating at least 90% of the estimated 2,000 asteroids and comets that approach the Earth and are larger than about 1 km in diameter, by the year 2010.
Environmental justice regulations draw fire
Authors: Showstack Randy
Published: September 2022

Advocates of “environmental justice” say that proposed U.S. Environmental Protection Agency (EPA) regulations are necessary to ensure that an unfair share of industrial facilities and waste plants are not sited in poor and minority communities, as they claim has occurred in the past.

However, a number of state and local government agencies, business groups, and Democratic and Republican politicians argue that EPA guidelines—written to put some teeth into the Title VI clause of the Civil Rights Act that prohibits discrimination in all federally funded programs and activities—are unworkable and need to be overhauled.
Video about geoscience careers
Authors: Showstack Randy
Published: September 2022

A petroleum exploration geologist searches for gold. A physical oceanographer explores the Chesapeake Bay in Maryland and Virginia. A meteorologist with the National Weather Service tells of the fascination he has had with weather since he was a child.

Eleven of the nation's estimated 125,000 geoscientists in these and other areas provide glimpses into their profession in a straightforward, new, 40‐minute video,“Careers for Geoscientists.”
National assessment finds most U.S. water systems without violations
Authors: Showstack Randy
Published: September 2022

More than 90% of community water systems in the United States did not have any reported health violations according to the Environmental Protection Agency's (EPA) first annual national assessment of drinking water system compliance, which was released in August.

The report is one of the public right‐toknow provisions of Safe Drinking Water Act amendments of 1996; it is based on 1996 data provided by the states.
BP pledges to cut emissions
Authors: Showstack Randy
Published: September 2022

British Petroleum (BP), one of the world's biggest oil companies that could become even bigger if a merger with Amoco is approved, announced on September 18 that it will cut its emissions of greenhouse gases by 10% from a 1990 baseline of 40 million tons of carbon dioxide between now and the year 2010.

The target, which is double the amount of emissions reductions that industrialized nations agreed to under the Kyoto protocol on climate change, will now stand next to BP's financial targets, said John Browne, group chief executive of BP.
Women and minorities science bill becomes law
Authors: Showstack Randy
Published: September 2022

U.S. President Bill Clinton has signed into law a measure to establish a commission to identify and address problems associated with the recruitment, retention, and advancement of women, minorities, and persons with disabilities in science and engineering fields.

“Today, we have taken a positive step forward to strengthen and expand our high‐tech workforce by ensuring that women, minorities, and persons with disabilities have the skills necessary to compete in the Information Age,” said U.S. Rep. Connie Morella (R.‐Md.), who introduced the measure.
La Niña takes center stage
Authors: Showstack Randy
Published: September 2022

With La Niña cooling the central and eastern tropical Pacific, and potentially causing dramatic impacts on weather conditions, a number of organizations have produced excellent Web sites to track and forecast conditions and educate people about this counterpart to El Niño.
AAAS announces Grants Program for U.S.‐CEE‐NIS Collaboration
Authors: Anonymous
Published: September 2022

To increase the number of women scientists and engineers participating as PIs and co‐PIs in research collaborations in Central and Eastern Europe, The National Science Foundation has funded the Women's International Science Collaboration (WISC) Program. This new program, administered by the Program on Central and Eastern Europe of the American Association for the Advancement of Science (AAAS), provides grants to individual U.S. women scientists who plan to establish new research partnerships with their colleagues in Central and Eastern Europe (CEE) and the Newly Independent States of the former Soviet Union (NIS).
U.S. water infrastructure needs infusion, report notes
Authors: Showstack Randy
Published: September 2022

Aging water and wastewater infrastructure in the United States will threaten public health, as well as the health of rivers, lakes, and coastlines, unless the federal government provides cities, counties, and other local water agencies with a major influx of funding, according to a new report released by the Water Infrastructure Network (WIN).

The report, “Water Infrastructure Now: Recommendations for Clean and Safe Water in the 21st Century” calls for a federal investment of $57 billion over 5 years to maintain and upgrade drinking water, sewer, and stormwater infrastructure.
Simple model explains complex faulting
Authors: Ron Hagai , Beroza Greg , Nur Amos
Published: September 2022

The sequence of earthquakes in the Mojave Desert during the 20th century including the 1999 Hector Mine earthquake, has some puzzling features with respect to our usual view of earthquake faulting: (a) the Mojave sequence ruptured in four distinct directions of faulting that form two conjugate fault sets, one pair of which is not optimally oriented relative to the tectonic stress, (b) Parts of the ruptures and the earthquake alignments do not follow geologically well‐developed faults, (c) Some of the ruptures and the earthquake alignments cut across previously mapped faults.
Debate heats up over U.S. Energy Policy, as Senate Bill is introduced
Authors: Showstack Randy
Published: September 2022

Wrapping their proposal for a national energy policy in the cloak of national security and economic prosperity a group of mostly Republican U.S. senators introduced legislation on February 26 that was praised by numerous industry groups as far‐reaching, long overdue, and striking a balance between energy production and environmental protection.

The bill was panned by some other senators and conservation groups as short‐sighted because of what they said are its measures to continue relying on fossil fuels that could produce increased greenhouse gas emissions, its inadequate focus on energy‐use efficiency and alternative energies, and—perhaps most controversially—its call for opening parts of the Arctic National Wildlife Refuge (ANWR) for oil drilling.
Biocomplexity in the environment: Opportunities for biogeosciences research and education
Authors: Sundquist Eric T. , Barrera Enriqueta
Published: September 2022

The term “biocomplexity” has not been commonly encountered in the traditional Earth sciences. It is one of many concepts that are finding new significance in the growing efforts of Earth scientists to understand the role of organisms (including humans) in Earth processes.

Important opportunities for Earth science research are embodied in the recent National Science Foundation (NSF) program announcement, “Biocomplexity in the Environment: Integrated Research and Education in Environmental Systems.“ (See http://www.nsf.gov/pubs/2001/nsf0134/nsf0134.htm).

The announcement solicits proposals in four topical areas, all of which are subjects of active interest in biogeoscience research. Under the topic, “Dynamics of Coupled Natural and Human Systems” (CNH), emphasis is placed on support of interdisciplinary teams from the natural and social sciences to focus on subjects such as land use, vulnerability to environmental change, and “natural capital” (including fuel, water, and soil).
New network to monitor climate change
Authors: Heim Richard R.
Published: September 2022

Recent reports by the World Climate Research Programme and the National Research Council, including “Adequacy of Climate Observing Systems” (1999), have noted that current observational networks are inadequate for monitoring the Earth's climate system. The accuracy and fidelity of the data used to measure climate variability are crucial to both U.S. government monitoring efforts and U.S. industry. Even small biases can alter the interpretation of decadal climate variability and change. Although the United States is a leader in climate research, no national observing network is capable of ensuring long‐term climate records free of artificial biases—also known as inhomogeneitie—due to factors such as instrument changes, station relocations, and changes in the surrounding environment.
Deep drilling into a Hawaiian volcano
Authors: DePaolo Donald J. , Stolper Edward , Thomas Donald M.
Published: September 2022

Hawaiian volcanoes are the most comprehensively studied on Earth. Nevertheless, most of the eruptive history of each one is inaccessible because it is buried by younger lava flows or is exposed only below sea level. For those parts of Hawaiian volcanoes above sea level, erosion typically exposes only a few hundred meters of buried lavas (out of a total thickness of up to 10 km or more). Available samples of submarine lavas extend the time intervals of individual volcanoes that can be studied. However, the histories of individual Hawaiian volcanoes during most of their ˜1‐million‐year passages across the zone of melt production are largely unknown.
Citation for Scott Doney
Authors: Glover David M. , Doney Scott
Published: September 2022

“A man of genius makes no mistakes. His errors are volitional and are the portals of discovery. James Joyce, Ulysses (1922). ”After collaborating with Scott Doney for the past 14 years I know what Joyce meant. When working with someone as bright as Scott it inevitably happens that you just don't understand. And because we're trained skeptics the question immediately arises, ”has our friend and colleague made a mistake?“ But we're wrong; we just didn't see the portal through which people like Scott had already proceeded. Certainly this is what we reserve these awards of ‘outstandingness’ for; those whose insight lead through the portals of discovery”.
U.S. National Academy panel reviews climate change science
Authors: Showstack Randy
Published: September 2022

Could the administration of George W. Bush, which has rejected the Kyoto Protocol to reduce worldwide emissions of greenhouse gases—and which has reneged on a campaign pledge to regulate U.S. carbon dioxide emissions—sincerely be seeking the facts about climate change in time for the resumption of international negotiations on the issue in July?

That is the hope of an 11‐member committee of the U.S. National Academy of Sciences (NAS) that is working on an incredibly fast‐tracked report “The Science of Climate Change,” at the request of the administration. The project largely will review and synthesize findings from a number of earlier studies.
Olson and Pagano awarded Horton research grants
Authors: Anonymous
Published: September 2022

The Hydrology Section presented two Horton Research Grants at the 2001 Spring Meeting in Boston, Massachusetts, in May. The research grant, which is separate from the Horton Award, supports research projects in hydrology and water resources by doctoral candidates at institutions of higher learning. The objective of the Horton Research Grant is to foster graduate student research leading to the completion of doctoral dissertations.
The terrestrial reference frame and the dynamic Earth
Authors: Altamimi Zuheir , Angermann Detlef , Argus Don , Blewitt Geoff , Boucher Claude , Chao Ben , Drewes Hermann , Eanes Richards , Feissel Martine , Ferland Remi , Herring Tom , Holt Bill , Johannson Jan , Larson Kristine , Ma Chopo , Manning John , Meertens Chuck , Nothnagel Axel , Pavlis Erricos , Petit Gerard , Ray Jim , Ries John , Scherneck Hans‐Georg , Sillard Patrick , Watkins Mike
Published: September 2022

As early as the 15th century Swedes noticed that rocks in their harbors were slowly rising out of the sea [Ekman, 1991]. These local observations were not sufficient to distinguish whether the rocks were rising or the sea level falling. Later, it was realized that Fennoscandia was still rebounding from the last Ice Age. This historical observation is still relevant today. How can you know whether a point on the Earth's surface is slowly moving up, down, or horizontally? One must relate local measurements to a stable and accurate reference frame, one whose scale is much larger than the problem at hand. We remain concerned with sea‐level variations, but present‐day studies recognize that change must be measured from a global point of view and with respect to a globally well‐defined reference frame. Thus, the regional and national geodetic datums developed over the past 200 years are inappropriate for studying global‐level problems.
Bush outlines climate stance in wake of National Academy Report
Authors: Showstack Randy
Published: September 2022

Whether or not one agrees with U.S. President George W. Bush's positions on climate change and his rejection of the Kyoto Protocol to the United Nations Framework Convention on Climate Change, the early handling of these matters—which foreign policy advisor Condoleezza Rice recently acknowledged could have been better finessed and communicated to other countries—seems to have prompted the Bush administration to take a more thorough and engaged look at the entire issue of climate change.

Two widely anticipated products of this review were unveiled in early June: a report by the National Academy of Sciences (NAS) on the science of climate change, and an address by the president in which he outlined the administration's evolving stance on the issue and proposed a series of initiatives to deal with it.
The Dating Game: One Man's Search for the Age of the Earth
Authors: Frankel Henry
Published: September 2022

Arthur Holmes, who lived from 1890 to 1965, was one of the greatest geologists of the first half of the 20th century. He was particularly successful at applying developments in physics to geological problems. Holmes worked on fundamental problems—the origins of igneous rocks and mountains, mantle convection, the age of the Earth, and continental drift—and he played central roles in major controversies about the latter two of these topics. His Principles of Physical Geology was a wonderful introduction to geology. Although historians have discussed Holmes' work on continental drift, they have paid little attention to his dating of the Earth. Discovery of the Earth's age was a major scientific accomplishment. Holmes also devoted much more attention to dating questions than to continental drift. Over 50 of his papers were about dating, while fewer than 10 dealt with continental drift.
Broader management principles for U.S. fisheries urged
Authors: Showstack Randy
Published: September 2022

Structural engineers can teach a thing or two to fisheries managers and others who believe in the concept of “maximum sustained yields,” or MSYs, of fish, according to Larry Crowder, professor of marine biology at Duke University. MSYs are among the management principles that some people blame for the decline of U.S. fisheries.

“We continue to make decisions that put severe pressure on these [fisheries] resources and that fail to buffer the fish—and the fishing industry—from variability wrought by both natural forces and human hands,” Crowder told the U.S. House of Representatives Subcommittee on Fisheries, Conservation, Wildlife, and Oceans, on June 14.
Nielsen Receives 2001 Horton medal
Authors: Nielsen Donald R. , Puente Carlos E.
Published: September 2022

Donald R. Nielsen was awarded the Robert E. Horton Medal at the AGU Spring Meeting Honors Ceremony, which was held May 31, 2001, in Boston, Massachusetts. The medal recognizes outstanding contributions to the geophysical aspects of hydrology.
Finding the right rocks on Mars
Authors: Hargraves R. B. , Knudsen J. M. , Madsen M. B. , Bertelsen P.
Published: September 2022

Locating a rock on the surface of Mars that bears unambiguous evidence of the existence—prior or present—of life on that planet is, understandably, the “Holy Grail” of NASAs sample return missions. Remote recognition of such a rock on Mars will not be easy. We do know, however, that present in the Martian crust—especially in the “Southern highlands”—is rock carrying strong natural remanent magnetization (NRM). Characterization of such magnetized rock has profound implications for adding to our knowledge about the origin and early evolution of the Martian interior, lithosphere, atmosphere, and possibly even Martian life forms [Ward and Brownlee, 2000]. Moreover, it should be possible to recognize such rocks by use of a simple magnetic compass mounted on a Rover.
Bonn's Climate Summit
Authors: Showstack Randy
Published: September 2022

Accusations, warnings, and predictions flew around in a flurry prior to the U.N. Conference on Climate Change negotiations that began in Bonn, Germany on July 19.

Glenn Kelly, executive director of the industry‐supported Global Climate Coalition (GCC), predicted that a coordinated bashing of the United States for President George W. Bush's opposition to the Kyoto Protocol on greenhouse gas reductions would be followed by cooler thinking. “It has to play out,” he said. “I liken it to a World Wrestling Federation match: it looks painful, but in the end it's all show and drama.”
Agreement reached on Kyoto Protocol
Authors: Showstack Randy
Published: September 2022

Environment ministers from 178 nations meeting in Bonn, Germany, reached a broad political agreement July 23 on the rules for the Kyoto Protocol on climate change. The agreement, which came despite United States opposition to the treaty, keeps the protocol alive and on track for potential final approval later this year by the signatories.

Japanese Prime Minister Junichiro Koizumi, who indicated he prefers U.S. participation, said he was basically pleased with the outcome of the negotiations. “I welcome the basic agreement on ‘core elements’ which has been consequently reached,’ he said.
Pursuing science and math proficiency
Authors: Showstack Randy
Published: September 2022

The U.S. House of Representatives on July 30 passed two bills to help increase science and math proficiency among students. The first bill, House Resolution 1858, would provide $200 million per year for fiscal years 2002–2006 to establish Mathematics and Science Partnerships among universities, school districts, and possibly businesses, to help improve math and science education from kindergarten through 12th grade. Other funds would expand the scope of the National Science Foundation's digital library program, and set up four university research centers on teaching and learning.
Ocean commission holds initial meeting
Authors: Showstack Randy
Published: September 2022

The U.S. Commission on Ocean Policy held its first organizational meeting on September 17 and 18 in Washington, D.C., and appointed James Watkins, a retired U.S. Navy admiral and former secretary of energy under (former) President George Bush, to chair the commission.

Created through the Oceans Act of 2000, the commission is charged with reviewing the effects of federal ocean‐related laws and programs, and with assessing the relationship of various governmental and private sector groups in carrying out ocean‐ and coastal‐related activities. The commission is considered to be a new “Stratton Commission.” The original Stratton Commission completed a similar broad review of U.S. ocean laws and policies in 1969 under the authority of the Marine Resources and Engineering Development Act of 1966.
In Memoriam
Authors: Anonymous
Published: September 2022

Weibin Wang died on September 11, 2001, at age 41. He was killed in the North Tower of the World Trade Center in New York City. He had been an AGU member (Tectonophysics) since 1988.
U.S. air quality generally improves
Authors: Showstack Randy
Published: September 2022

Air quality in the United States continues to gradually improve, according to a recent report entitled, “Latest Findings on National Air Quality: 2000 Status and Trends.”

The report was released by the Environmental Protection Agency (EPA).
New efforts on global change recommended
Authors: Showstack Randy
Published: September 2022

With the Bush administration working to finalize its initiatives on climate change research and technology, a new report criticizes several major federal and other climate reports and assessments, while also calling for improved research, climate data, and assessment efforts that are “not distorted by political pressures.”

A December 4 report by the George C. Marshall Institute, “Climate Science and Policy: Making the Connection,” recommends that better climate models will need improvements in areas including the knowledge of key climate processes, such as the role of clouds and water vapor.
A model study of the influence of the quasi‐biennial oscillation on trace gas distributions in the middle and upper stratosphere
Authors: Gray Lesley J.
Published: September 2022

The dominant tracer transport processes in the equatorial and subtropical latitudes of the middle and upper stratosphere are investigated. Distributions of water vapor in Northern Hemisphere winter from the Microwave Limb Sounder onboard the Upper Atmosphere Research Satellite are employed, together with a three‐dimensional Stratosphere Mesosphere Model that incorporates a representation of the quasi‐biennial oscillation (QBO). The model reproduces the observed tracer distributions, in particular a “staircase” feature that is present in northern winter of 1992 (easterly QBO phase) but not in 1993 (westerly QBO phase). This feature is highly asymmetric about the equator. The model circulation is diagnosed to show that while the induced QBO circulation in the lower stratosphere of the model is relatively symmetric about the equator, in the middle and upper stratosphere it is highly asymmetric and in the correct sense to give rise to the staircase feature. Model experiments are compared in which trajectories are advected by (1) the full three‐dimensional circulation and (2) the residual mean circulation only, thereby removing the local effects of isentropic mixing by planetary waves on the trajectory distributions. These confirm the importance of advection by the QBO circulation at equatorial and subtropical latitudes. However, sharpening of the tracer gradients at the subtropical edge of the surf zone by the action of planetary waves is shown to be important in the formation of a subtropical “cliff ” between 10 and 20 mbar at 20°–30°N. The model results also suggest that the prominence of the summer subtropical peak in easterly phase years compared with westerly phase years is not entirely due to increased summer upwelling of the large‐scale global circulation caused by the stronger planetary wave driving. The depression of the winter half of the equatorial peak by the local asymmetric QBO circulation is also shown to be important.
A mechanistic mathematical model of initiation and malignant transformation in sporadic vestibular schwannoma
Authors: Paterson Chay , Bozic Ivana , Smith Miriam J. , Hoad Xanthe , Evans D. Gareth R.
Published: September 2022

Background

A vestibular schwannoma (VS) is a relatively rare, benign tumour of the eighth cranial nerve, often involving alterations to the gene NF2. Previous mathematical models of schwannoma incidence have not attempted to account for alterations in specific genes, and could not distinguish between nonsense mutations and loss of heterozygosity (LOH).

Methods

Here, we present a mechanistic approach to modelling initiation and malignant transformation in schwannoma. Each parameter is associated with a specific gene or mechanism operative in Schwann cells, and can be determined by combining incidence data with empirical frequencies of pathogenic variants and LOH.

Results

This results in new estimates for the base-pair mutation rate u = 4.48 × 10−10 and the rate of LOH = 2.03 × 10−6/yr in Schwann cells. In addition to new parameter estimates, we extend the approach to estimate the risk of both spontaneous and radiation-induced malignant transformation.

Discussion

We conclude that radiotherapy is likely to have a negligible excess risk of malignancy for sporadic VS, with a possible exception of rapidly growing tumours.
Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma
Authors: Fiorito Elisa , Szybowska Patrycja , Haugsten Ellen M. , Kostas Michal , Øy Geir F. , Wiedlocha Antoni , Singh Sachin , Nakken Sigve , Mælandsmo Gunhild M. , Fletcher Jonathan A. , Meza-Zepeda Leonardo A. , Wesche Jørgen
Published: September 2022

Background

Rhabdomyosarcoma (RMS) is a paediatric cancer driven either by fusion proteins (e.g., PAX3-FOXO1) or by mutations in key signalling molecules (e.g., RAS or FGFR4). Despite the latter providing opportunities for precision medicine approaches in RMS, there are currently no such treatments implemented in the clinic.

Methods

We evaluated biologic properties and targeting strategies for the FGFR4 V550L activating mutation in RMS559 cells, which have a high allelic fraction of this mutation and are oncogenically dependent on FGFR4 signalling. Signalling and trafficking of FGFR4 V550L were characterised by confocal microscopy and proteomics. Drug effects were determined by live-cell imaging, MTS assay, and in a mouse model.

Results

Among recently developed FGFR4-specific inhibitors, FGF401 inhibited FGFR4 V550L-dependent signalling and cell proliferation at low nanomolar concentrations. Two other FGFR4 inhibitors, BLU9931 and H3B6527, lacked potent activity against FGFR4 V550L. Alternate targeting strategies were identified by RMS559 phosphoproteomic analyses, demonstrating that RAS/MAPK and PI3K/AKT are essential druggable pathways downstream of FGFR4 V550L. Furthermore, we found that FGFR4 V550L is HSP90-dependent, and HSP90 inhibitors efficiently impeded RMS559 proliferation. In a RMS559 mouse xenograft model, the pan-FGFR inhibitor, LY2874455, did not efficiently inhibit growth, whereas FGF401 potently abrogated growth.

Conclusions

Our results pave the way for precision medicine approaches against FGFR4 V550L-driven RMS.
Societal implications of expanded universal carrier screening: a scoping review
Authors: van den Heuvel Lieke M. , van den Berg Nina , Janssens A. Cecile J. W. , Birnie Erwin , Henneman Lidewij , Dondorp Wybo J. , Plantinga Mirjam , van Langen Irene M.
Published: September 2022

Carrier screening aims to identify couples at risk of conceiving children with a recessive condition. Until recently, carrier screening was primarily offered ancestry-based. Technological advances now facilitate expanded universal carrier screening (EUCS). This scoping review aimed to map EUCS’s potential societal implications based on both theoretical studies and empirical evidence. To this aim, we performed a CoCites search to find relevant articles, including articles describing carrier screening for at-risk populations, based on five selected query articles. Forty articles were included. Three main potential societal implications were identified: (1) unwanted medicalization, (2) stigmatization and discrimination of carriers and people affected with the conditions screened and (3) challenges in achieving equitable access. Within these themes, potential positive implications are reduction of ethnic stigmatization in ancestry-based offers and increased equity. Potential negative implications are reinforcement of disability-based stigmatization, less possibility for developing expertise in healthcare and societal pressure to partake in screening. Empirical evidence on all these implications is however scarce. In conclusion, both positive and negative potential societal implications of implementing EUCS, primarily theoretical, were identified, even in at-risk groups where evidence is mostly lacking. Empirical research in EUCS pilots is needed to identify which societal implications are likely to occur and therefore should be overcome when implementing EUCS.
Identification of a binding site on soluble RANKL that can be targeted to inhibit soluble RANK-RANKL interactions and treat osteoporosis
Authors: Huang Dane , Zhao Chao , Li Ruyue , Chen Bingyi , Zhang Yuting , Sun Zhejun , Wei Junkang , Zhou Huihao , Gu Qiong , Xu Jun
Published: September 2022

One of the major challenges for discovering protein-protein interaction inhibitors is identifying selective and druggable binding sites at the protein surface. Here, we report an approach to identify a small molecular binding site to selectively inhibit the interaction of soluble RANKL and RANK for designing anti-osteoporosis drugs without undesirable immunosuppressive effects. Through molecular dynamic simulations, we discovered a binding site that allows a small molecule to selectively interrupt soluble RANKL-RANK interaction and without interfering with the membrane RANKL-RANK interaction. We describe a highly potent inhibitor, S3-15, and demonstrate its specificity to inhibit the soluble RANKL-RANK interaction with in vitro and in vivo studies. S3-15 exhibits anti-osteoporotic effects without causing immunosuppression. Through in silico and in vitro experiments we further confirm the binding model of S3-15 and soluble RANKL. This work might inspire structure-based drug discovery for targeting protein-protein interactions.
Kinetic compartmentalization by unnatural reaction for itaconate production
Authors: Ye Dae-yeol , Noh Myung Hyun , Moon Jo Hyun , Milito Alfonsina , Kim Minsun , Lee Jeong Wook , Yang Jae-Seong , Jung Gyoo Yeol
Published: September 2022

Physical compartmentalization of metabolism using membranous organelles in eukaryotes is helpful for chemical biosynthesis to ensure the availability of substrates from competitive metabolic reactions. Bacterial hosts lack such a membranous system, which is one of the major limitations for efficient metabolic engineering. Here, we employ kinetic compartmentalization with the introduction of an unnatural enzymatic reaction by an engineered enzyme as an alternative strategy to enable substrate availability from competitive reactions through kinetic isolation of metabolic pathways. As a proof of concept, we kinetically isolate the itaconate synthetic pathway from the tricarboxylic acid cycle in Escherichia coli, which is natively separated by mitochondrial membranes in Aspergillus terreus. Specifically, 2-methylcitrate dehydratase is engineered to alternatively catalyze citrate and kinetically secure cis-aconitate for efficient production using a high-throughput screening system. Itaconate production can be significantly improved with kinetic compartmentalization and its strategy has the potential to be widely applicable.
SREBP2-dependent lipid gene transcription enhances the infection of human dendritic cells by Zika virus
Authors: Branche Emilie , Wang Ying-Ting , Viramontes Karla M. , Valls Cuevas Joan M. , Xie Jialei , Ana-Sosa-Batiz Fernanda , Shafee Norazizah , Duttke Sascha H. , McMillan Rachel E. , Clark Alex E. , Nguyen Michael N. , Garretson Aaron F. , Crames Jan J. , Spann Nathan J. , Zhu Zhe , Rich Jeremy N. , Spector Deborah H. , Benner Christopher , Shresta Sujan , Carlin Aaron F.
Published: September 2022

The emergence of Zika virus (ZIKV) as a global health threat has highlighted the unmet need for ZIKV-specific vaccines and antiviral treatments. ZIKV infects dendritic cells (DC), which have pivotal functions in activating innate and adaptive antiviral responses; however, the mechanisms by which DC function is subverted to establish ZIKV infection are unclear. Here we develop a genomics profiling method that enables discrete analysis of ZIKV-infected versus neighboring, uninfected primary human DCs to increase the sensitivity and specificity with which ZIKV-modulated pathways can be identified. The results show that ZIKV infection specifically increases the expression of genes enriched for lipid metabolism-related functions. ZIKV infection also increases the recruitment of sterol regulatory element-binding protein (SREBP) transcription factors to lipid gene promoters, while pharmacologic inhibition or genetic silencing of SREBP2 suppresses ZIKV infection of DCs. Our data thus identify SREBP2-activated transcription as a mechanism for promoting ZIKV infection amenable to therapeutic targeting.
A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids
Authors: Gollwitzer Peter , Grützmacher Nina , Wilhelm Sabine , Kümmel Daniel , Demetriades Constantinos
Published: September 2022

Amino acid availability controls mTORC1 activity via a heterodimeric Rag GTPase complex that functions as a scaffold at the lysosomal surface, bringing together mTORC1 with its activators and effectors. Mammalian cells express four Rag proteins (RagA–D) that form dimers composed of RagA/B bound to RagC/D. Traditionally, the Rag paralogue pairs (RagA/B and RagC/D) are referred to as functionally redundant, with the four dimer combinations used interchangeably in most studies. Here, by using genetically modified cell lines that express single Rag heterodimers, we uncover a Rag dimer code that determines how amino acids regulate mTORC1. First, RagC/D differentially define the substrate specificity downstream of mTORC1, with RagD promoting phosphorylation of its lysosomal substrates TFEB/TFE3, while both Rags are involved in the phosphorylation of non-lysosomal substrates such as S6K. Mechanistically, RagD recruits mTORC1 more potently to lysosomes through increased affinity to the anchoring LAMTOR complex. Furthermore, RagA/B specify the signalling response to amino acid removal, with RagB-expressing cells maintaining lysosomal and active mTORC1 even upon starvation. Overall, our findings reveal key qualitative differences between Rag paralogues in the regulation of mTORC1, and underscore Rag gene duplication and diversification as a potentially impactful event in mammalian evolution.
A bacterial pan-genome makes gene essentiality strain-dependent and evolvable
Authors: Rosconi Federico , Rudmann Emily , Li Jien , Surujon Defne , Anthony Jon , Frank Matthew , Jones Dakota S. , Rock Charles , Rosch Jason W. , Johnston Christopher D. , van Opijnen Tim
Published: September 2022

Many bacterial species are represented by a pan-genome, whose genetic repertoire far outstrips that of any single bacterial genome. Here we investigate how a bacterial pan-genome might influence gene essentiality and whether essential genes that are initially critical for the survival of an organism can evolve to become non-essential. By using Transposon insertion sequencing (Tn-seq), whole-genome sequencing and RNA-seq on a set of 36 clinicalStreptococcus pneumoniaestrains representative of >68% of the species’ pan-genome, we identify a species-wide ‘essentialome’ that can be subdivided into universal, core strain-specific and accessory essential genes. By employing ‘forced-evolution experiments’, we show that specific genetic changes allow bacteria to bypass essentiality. Moreover, by untangling several genetic mechanisms, we show that gene essentiality can be highly influenced by and/or be dependent on: (1) the composition of the accessory genome, (2) the accumulation of toxic intermediates, (3) functional redundancy, (4) efficient recycling of critical metabolites and (5) pathway rewiring. While this functional characterization underscores the evolvability potential of many essential genes, we also show that genes with differential essentiality remain important antimicrobial drug target candidates, as their inactivation almost always has a severe fitness cost in vivo.
Large harvested energy with non-linear pyroelectric modules
Authors: Lheritier Pierre , Torelló Alvar , Usui Tomoyasu , Nouchokgwe Youri , Aravindhan Ashwath , Li Junning , Prah Uros , Kovacova Veronika , Bouton Olivier , Hirose Sakyo , Defay Emmanuel
Published: September 2022

Coming up with sustainable sources of electricity is one of the grand challenges of this century. The research field of materials for energy harvesting stems from this motivation, including thermoelectrics1, photovoltaics2 and thermophotovoltaics3. Pyroelectric materials, converting temperature periodic variations in electricity, have been considered as sensors4 and energy harvesters5–7, although we lack materials and devices able to harvest in the joule range. Here we develop a macroscopic thermal energy harvester made of 42 g of lead scandium tantalate in the form of multilayer capacitors that produces 11.2 J of electricity per thermodynamic cycle. Each pyroelectric module can generate up to 4.43 J cm−3 of electric energy density per cycle. We also show that two of these modules weighing 0.3 g are sufficient to sustainably supply an autonomous energy harvester embedding microcontrollers and temperature sensors. Finally, we show that for a 10 K temperature span these multilayer capacitors can reach 40% of Carnot efficiency. These performances stem from (1) a ferroelectric phase transition enabling large efficiency, (2) low leakage current preventing losses and (3) high breakdown voltage. These macroscopic, scalable and highly efficient pyroelectric energy harvesters enable the reconsideration of the production of electricity from heat.
Genetic risk factors have a substantial impact on healthy life years
Authors: Jukarainen Sakari , Kiiskinen Tuomo , Kuitunen Sara , Havulinna Aki S. , Karjalainen Juha , Cordioli Mattia , Rämö Joel T. , Mars Nina ,   FinnGen, Samocha Kaitlin E. , Ollila Hanna M. , Pirinen Matti , Ganna Andrea
Published: September 2022

The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; ‘lost healthy life years’). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.
Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial
Authors: Chaft Jamie E. , Oezkan Filiz , Kris Mark G. , Bunn Paul A. , Wistuba Ignacio I. , Kwiatkowski David J. , Owen Dwight H. , Tang Yan , Johnson Bruce E. , Lee Jay M. , Lozanski Gerard , Pietrzak Maciej , Seweryn Michal , Byun Woo Yul , Schulze Katja , Nicholas Alan , Johnson Ann , Grindheim Jessica , Hilz Stephanie , Shames David S. , Rivard Chris , Toloza Eric , Haura Eric B. , McNamee Ciaran J. , Patterson G. Alexander , Waqar Saiama N. , Rusch Valerie W. , Carbone David P. ,   LCMC study investigators, Waqar Saiama N. , Shum Elaine , Nagasaka Misako , Koczywas Marianna , Garon Edward B. , Finley David J. , Camidge David R. , Carlisle Jennifer W. , Blasberg Justin D.
Published: September 2022

In an ongoing, open-label, single-arm phase II study (NCT02927301), 181 patients with untreated, resectable, stage IB–IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14–28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.