bluuebunny/crossref_metadata_2025_split huggingface dataset:
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).
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.
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.
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.
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.
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.
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 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

Abstract
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

Abstract
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

AbstractCarrier 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

AbstractOne 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

AbstractPhysical 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

AbstractThe 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

AbstractAmino 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

AbstractMany 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

AbstractComing 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

AbstractThe 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.