bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outsized nutrient contributions from small tributaries to a Great Lake
Authors: Mooney Robert J. , Stanley Emily H. , Rosenthal William C. , Esselman Peter C. , Kendall Anthony D. , McIntyre Peter B. 
Published: October 2020

Significance
Excessive nutrient inputs from tributary streams and rivers contribute to harmful algal blooms and coastal ecosystem degradation worldwide. However, the role that small tributaries play in coastal nutrient dynamics remains unknown because most monitoring and regulatory efforts focus only on the largest tributaries. We combined a 6-d sampling effort with discharge modeling to characterize nutrient inputs from nearly all watersheds draining to the world’s fifth largest lake. We found that streams are particularly likely to promote eutrophication in coastal ecosystems because they deliver water with higher concentrations of nutrients that are readily available to algae. Thus, our findings indicate that efforts to control nutrient loading could be enhanced by looking beyond the largest tributaries to include smaller streams.
Evidence for massive emission of methane from a deep‐water gas field during the Pliocene
Authors: Foschi Martino , Cartwright Joseph A. , MacMinn Christopher W. , Etiope Giuseppe 
Published: October 2020

SignificanceA major uncertainty in the sources of atmospheric methane is the role of geologic seepage from petroleum-bearing sedimentary basins. Hydrocarbon seeps located onshore, shallow offshore, and coastal areas can play a major role. Methane released by deep ocean seeps typically does not reach the atmosphere. Here, we provide evidence for a single, large, and sudden expulsion of methane from a deep‐water reservoir during the Pliocene. We use geophysical evidence and fluid-flow modeling to estimate that this single event would have amounted to ∼10% of present‐day annual natural methane emissions. Although no ultraseepage events, such as this one, have been documented in modern times, the relatively common geologic circumstances of this type of event suggest that they are not exceptional.
Phosphatidylinositol-4-kinase IIα licenses phagosomes for TLR4 signaling and MHC-II presentation in dendritic cells
Authors: López-Haber Cynthia , Levin-Konigsberg Roni , Zhu Yueyao , Bi-Karchin Jing , Balla Tamas , Grinstein Sergio , Marks Michael S. , Mantegazza Adriana R. 
Published: October 2020

Significance
Dendritic cells (DCs) play a key role at the interface between innate and adaptive immunity. DCs continuously sample their microenvironment, respond to microbial cues by signaling through pattern-recognition receptors such as Toll-like receptors (TLRs), and present bacterial antigens to adaptive immune cells. We show that the lipid kinase phosphatidylinositol-4-kinase IIα (PI4KIIα) is required to generate a phosphatidylinositol-4-phosphate pool on DC phagosomes that allows binding of the TLR sorting adaptor TIRAP and promotes TLR4 phagosomal signaling to proinflammatory cytokine production, phagosomal membrane tubule formation, and presentation of phagocytosed antigens. PI4KIIα therefore ensures phagosomal identity and autonomous signaling to initiate antimicrobial immune responses in DCs.
Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants
Authors: Iqbal Sumaiya , Pérez-Palma Eduardo , Jespersen Jakob B. , May Patrick , Hoksza David , Heyne Henrike O. , Ahmed Shehab S. , Rifat Zaara T. , Rahman M. Sohel , Lage Kasper , Palotie Aarno , Cottrell Jeffrey R. , Wagner Florence F. , Daly Mark J. , Campbell Arthur J. , Lal Dennis 
Published: October 2020

Significance
Recent large-scale sequencing efforts have enabled the detection of millions of missense variants. Elucidating their functional effect is of crucial importance but challenging. We approach this problem by performing a wide-scale characterization of missense variants from 1,330 disease-associated genes using >14,000 protein structures. We identify 3D features associated with pathogenic and benign variants that unveiled the mutations’ effect at the molecular level. We further extend our analysis to account for the different essential structural regions in proteins performing different functions. By analyzing variants from 24 gene groups encoding for different protein functional families, we capture function-specific characteristics of missense variants, which match the experimental readouts. We show that our results derived using structural data will effectively inform variant interpretation.
Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function
Authors: Foreman-Ortiz Isabel U. , Liang Dongyue , Laudadio Elizabeth D. , Calderin Jorge D. , Wu Meng , Keshri Puspam , Zhang Xianzhi , Schwartz Michael P. , Hamers Robert J. , Rotello Vincent M. , Murphy Catherine J. , Cui Qiang , Pedersen Joel A. 
Published: October 2020

Significance
Design of nanoscale materials for applications that interface with biological systems requires that mechanisms of nanoparticle interaction with cellular membranes be understood, both to improve performance and to assess nanomaterial safety. We integrated experimental and computational approaches to resolve the outstanding question of whether the function of membrane-embedded ion channels can be perturbed via nanoparticle-induced modulation of membrane mechanical properties. We show that anionic nanoparticles disrupt channel activity indirectly by perturbing local properties of the surrounding lipid bilayer. Our results indicate that nanoparticle effects on membrane protein function do not require direct interaction; effects can be mediated via changes in bilayer mechanical properties. Such indirect effects warrant consideration in nanomaterial safety evaluations and suggest potential applications in modulating cellular function.
Climate drives the geography of marine consumption by changing predator communities
Authors: Whalen Matthew A. , Whippo Ross D. B. , Stachowicz John J. , York Paul H. , Aiello Erin , Alcoverro Teresa , Altieri Andrew H. , Benedetti-Cecchi Lisandro , Bertolini Camilla , Bresch Midoli , Bulleri Fabio , Carnell Paul E. , Cimon Stéphanie , Connolly Rod M. , Cusson Mathieu , Diskin Meredith S. , D’Souza Elrika , Flores Augusto A. V. , Fodrie F. Joel , Galloway Aaron W. E. , Gaskins Leo C. , Graham Olivia J. , Hanley Torrance C. , Henderson Christopher J. , Hereu Clara M. , Hessing-Lewis Margot , Hovel Kevin A. , Hughes Brent B. , Hughes A. Randall , Hultgren Kristin M. , Jänes Holger , Janiak Dean S. , Johnston Lane N. , Jorgensen Pablo , Kelaher Brendan P. , Kruschel Claudia , Lanham Brendan S. , Lee Kun-Seop , Lefcheck Jonathan S. , Lozano-Álvarez Enrique , Macreadie Peter I. , Monteith Zachary L. , O’Connor Nessa E. , Olds Andrew D. , O’Leary Jennifer K. , Patrick Christopher J. , Pino Oscar , Poore Alistair G. B. , Rasheed Michael A. , Raymond Wendel W. , Reiss Katrin , Rhoades O. Kennedy , Robinson Max T. , Ross Paige G. , Rossi Francesca , Schlacher Thomas A. , Seemann Janina , Silliman Brian R. , Smee Delbert L. , Thiel Martin , Unsworth Richard K. F. , van Tussenbroek Brigitta I. , Vergés Adriana , Yeager Mallarie E. , Yednock Bree K. , Ziegler Shelby L. , Duffy J. Emmett 
Published: October 2020

Significance
Consumption transfers energy and materials through food chains and fundamentally influences ecosystem productivity. Therefore, mapping the distribution of consumer feeding intensity is key to understanding how environmental changes influence biodiversity, with consequent effects on trophic transfer and top–down impacts through food webs. Our global comparison of standardized bait consumption in shallow coastal habitats finds a peak in feeding intensity away from the equator that is better explained by the presence of particular consumer families than by latitude or temperature. This study complements recent demonstrations that changes in biodiversity can have similar or larger impacts on ecological processes than those of climate.
Myelination of peripheral nerves is controlled by PI4KB through regulation of Schwann cell Golgi function
Authors: Baba Takashi , Alvarez-Prats Alejandro , Kim Yeun Ju , Abebe Daniel , Wilson Steve , Aldworth Zane , Stopfer Mark A. , Heuser John , Balla Tamas 
Published: October 2020

Significance
We identify PI4KB, a phosphoinositide kinase that controls the functions of the Golgi compartment, as a critical regulator of myelination of peripheral nerves. Genetic inactivation of PI4KB, specifically in Schwann cells in mice, causes hypomyelination of large diameter axons and impairs engulfment of small diameter fibers by nonmyelinating Schwann cells. Sciatic nerves of mutant mice show depletion of cholesterol, sphingomyelin and phosphatidylethanolamine, as well as defects in protein glycosylation.
RNA-binding protein DDX3 mediates posttranscriptional regulation of androgen receptor: A mechanism of castration resistance
Authors: Vellky Jordan E. , McSweeney Sean T. , Ricke Emily A. , Ricke William A. 
Published: October 2020

Significance
Little is known regarding the mechanisms involved in loss of androgen receptor (AR) function in the development of castration resistance. Recently, the clinical use of new potent AR therapies has led to the emergence of a new lethal subtype of castration-resistant prostate cancer (CRPC) lacking AR protein and signaling, termed ARL/negative CRPC. We discovered that DDX3 (DEAD-box helicase 3 X-linked) is a key repressor of AR protein translation—a mechanism that leads to development of castration resistance. Inhibition of DDX3 in ARL/negative CRPC promotes the expression of AR protein/signaling and hence sensitivity to hormone therapy. These data provide a molecular mechanism for hormone action and describe a synthetic lethality approach to the clinical treatment of therapy-resistant diseases such as CRPC.
Harnessing
64
Cu/
67
Cu for a theranostic approach to pretargeted radioimmunotherapy
Authors: Keinänen Outi , Fung Kimberly , Brennan James M. , Zia Nicholas , Harris Matt , van Dam Ellen , Biggin Colin , Hedt Amos , Stoner Jon , Donnelly Paul S. , Lewis Jason S. , Zeglis Brian M. 
Published: October 2020

Significance
Radioimmunotherapy is predicated on harnessing the exquisite specificity of antibodies to deliver cytotoxic radiation to tumors. Yet the long circulation time of radioimmunoconjugates leads to high radiation doses to healthy tissues. Pretargeted radioimmunotherapy (PRIT) circumvents this problem by decoupling the antibody and radionuclide, injecting the former prior to the latter, and empowering the two components to combine at the tumor. We have leveraged bioorthogonal click chemistry, a colorectal cancer-targeting antibody, and a pair radioligands bearing radioisotopes of copper—positron-emitting copper-64 and beta particle-emitting copper-67—to create a pretargeting system that enables both theranostic positron emission tomography and PRIT. We believe that the incorporation of theranostic imaging into PRIT regimens could be instrumental in the clinical success of the modality.
Characterization of systemic genomic instability in budding yeast
Authors: Sampaio Nadia M. V. , Ajith V. P. , Watson Ruth A. , Heasley Lydia R. , Chakraborty Parijat , Rodrigues-Prause Aline , Malc Ewa P. , Mieczkowski Piotr A. , Nishant Koodali T. , Argueso Juan Lucas 
Published: October 2020

Significance
Mutations are generally thought to accumulate independently and gradually over many generations. Here, we combined complementary experimental approaches in budding yeast to track the appearance of chromosomal changes resulting in loss-of-heterozygosity. In contrast to the prevailing model, our results provide evidence for the existence of a path for nonindependent accumulation of multiple chromosomal alteration events over a few generations. These results are analogous to recent reports of bursts of genomic instability in human cells. The experimental model we describe provides a system to further dissect the fundamental biological processes underlying such punctuated bursts of mutation accumulation.
Floristic evidence for alternative biome states in tropical Africa
Authors: Aleman J. C. , Fayolle A. , Favier C. , Staver A. C. , Dexter K. G. , Ryan C. M. , Azihou A. F. , Bauman D. , te Beest M. , Chidumayo E. N. , Comiskey J. A. , Cromsigt J. P. G. M. , Dessard H. , Doucet J.-L. , Finckh M. , Gillet J.-F. , Gourlet-Fleury S. , Hempson G. P. , Holdo R. M. , Kirunda B. , Kouame F. N. , Mahy G. , Gonçalves F. Maiato P. , McNicol I. , Quintano P. Nieto , Plumptre A. J. , Pritchard R. C. , Revermann R. , Schmitt C. B. , Swemmer A. M. , Talila H. , Woollen E. , Swaine M. D. 
Published: October 2020

Significance
We develop a biogeographic approach to analyzing the presence of alternative stable states in tropical biomes. Whilst forest–savanna bistability has been widely hypothesized and modeled, empirical evidence has remained scarce and controversial, and here, applying our method to Africa, we provide large-scale evidence that there are alternative states in tree species composition of tropical vegetation. Furthermore, our results have produced more accurate maps of the forest and savanna distributions in Africa, which take into account differences in tree species composition, and a complex suite of determinants. This result is not only important for understanding the biogeography of the continent but also, to guide large-scaled tree planting and restoration efforts planned for the region.
USP7 regulates ALS-associated proteotoxicity and quality control through the NEDD4L–SMAD pathway
Authors: Zhang Tao , Periz Goran , Lu Yu-Ning , Wang Jiou 
Published: October 2020

Significance
Protein homeostasis is fundamental to the functioning of all living cells. Perturbation of the homeostasis, or proteotoxicity, plays an important role in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative diseases. To guard against proteotoxicity, cells have evolved sophisticated quality-control mechanisms that make adaptations including enhanced turnover of misfolded proteins. However, how the quality-control systems are coordinated through higher-order regulatory pathways is not fully understood. We have discovered a unique suppressor of proteotoxicity, the ubiquitin-specific protease USP7, whose action is conserved from invertebrate to mammalian systems and mediated by a substrate cascade involving NEDD4L and SMAD2. These findings reveal a previously unknown regulatory pathway for protein quality control and provide new strategies for developing interventions for neurodegenerative diseases.
An allosteric peptide inhibitor of HIF-1α regulates hypoxia-induced retinal neovascularization
Authors: Usui-Ouchi Ayumi , Aguilar Edith , Murinello Salome , Prins Mitchell , Gantner Marin L. , Wright Peter E. , Berlow Rebecca B. , Friedlander Martin 
Published: October 2020

Significance
Retinal ischemia causes hypoxia-induced neovascularization that stimulates production of proangiogenic cytokines such as VEGF by the hypoxia-inducible transcription factors HIF-1 and HIF-2. Current therapies for ischemic retinal diseases target circulating VEGF but do not modulate the activity of the transcription factors that control its production. We demonstrate that inhibiting HIF-mediated transcription with a peptide derived from the intrinsically disordered protein CITED2, a negative feedback regulator of HIF-1α, reduces pathological angiogenesis in a mouse model of ischemic retinopathy. Combining the CITED2 peptide with the VEGF-Trap aflibercept causes potent suppression of neovascularization and promotes revascularization of the ischemic retina, an outcome not observed for anti-VEGF agents alone, suggesting that dual targeting of the HIF transcription factors and VEGF may be advantageous.
Primordial black holes as a dark matter candidate
Authors: Green Anne M , Kavanagh Bradley J 
Published: October 2020

Abstract
The detection of gravitational waves from mergers of tens of Solar mass black hole binaries has led to a surge in interest in primordial black holes (PBHs) as a dark matter candidate. We aim to provide a (relatively) concise overview of the status of PBHs as a dark matter candidate, circa Summer 2020. First we review the formation of PBHs in the early Universe, focussing mainly on PBHs formed via the collapse of large density perturbations generated by inflation. Then we review the various current and future constraints on the present day abundance of PBHs. We conclude with a discussion of the key open questions in this field.
Anisotropic reduced diffusion in dilute liquid 3He–4He mixture in ordered aerogel
Authors: Safiullin K , Kuzmin V , Stanislavovas A , Alakshin E , Klochkov A , Tagirov M 
Published: October 2020

Abstract
We report on the first observation of 3He diffusion anisotropy in 3He–4He liquid mixture confined in ordered aerogels at 1.5–4.2 K temperatures. The used aerogels are arrays of long Al2O3 parallel 8 nm strands. The possible origins of diffusion anisotropy are considered and the changes of roton properties introduced by parallel aerogel strands are discussed. Among the responsible mechanisms we account for Knudsen diffusion, potential anisotropy of layer mode excitations or of bulklike excitations, and helium vortices. The observed reduced 3He diffusion in aerogels is discussed and suggested to appear due to helium excitations at strong confinement conditions. These observations pave the way for future experiments to gain insight into the crossover regime expected at lower temperatures (below 1 K) for which roton density is lower and 3He collisions with strands play significant role.
Evaluation of CBCT scatter correction using deep convolutional neural networks for head and neck adaptive proton therapy
Authors: Lalonde Arthur , Winey Brian , Verburg Joost , Paganetti Harald , Sharp Gregory C 
Published: October 2020

Abstract
Adaptive proton therapy (APT) is a promising approach for the treatment of head and neck cancers. One crucial element of APT is daily volumetric imaging of the patient in the treatment position. Such data can be acquired with cone-beam computed tomography (CBCT), although scatter artifacts make uncorrected CBCT images unsuitable for proton therapy dose calculation. The purpose of this work is to evaluate the performance of a U-shape deep convolutive neural network (U-Net) to perform projection-based scatter correction and enable fast and accurate dose calculation on CBCT images in the context of head and neck APT. CBCT projections are simulated for a cohort of 48 head and neck patients using a GPU accelerated Monte Carlo (MC) code . A U-Net is trained to reproduce MC projection-based scatter correction from raw projections. The accuracy of the scatter correction is experimentally evaluated using CT and CBCT images of an anthropomorphic head phantom. The potential of the method for head and neck APT is assessed by comparing proton therapy dose distributions calculated on scatter-free, uncorrected and scatter-corrected CBCT images. Finally, dose calculation accuracy is estimated in experimental patient images using a previously validated empirical scatter correction as reference. The mean and mean absolute HU differences between scatter-free and scatter-corrected images are -0.8 and 13.4 HU, compared to -28.6 and 69.6 HU for the uncorrected images. In the head phantom, the root-mean square difference of proton ranges calculated in the reference CT and corrected CBCT is 0.73 mm. The average 2%/2 mm gamma pass rate for proton therapy plans optimized in the scatter free images and re-calculated in the scatter-corrected ones is 98.89%. In experimental CBCT patient images, a 3%/3 mm passing rate of 98.72% is achieved between the proposed method and the reference one. All CBCT projection volume could be corrected in less than 5 seconds.
Measurements of the energy distribution of W atoms sputtered by low energy Ar ions using high-resolution Doppler spectroscopy
Authors: Ertmer S , Marchuk O , Dickheuer S , Brezinsek S , Boerner P , Schmitz J , Kreter A 
Published: October 2020

Abstract
Emission spectra of neural tungsten (W) sputtered by impact of argon (Ar) ions in a weakly magnetized (<0.1 T) Ar plasma were measured using a high resolution spectrometer at normal incidence angle to the surface. The measurements were performed for the mono-energetic impact energies between 70 and 150 eV using the neutral tungsten (W I) line at 4982.593 Å. The line shape of this line was simulated using a Doppler-shifted emission model to determine the energy distribution. Additional broadening mechanisms were taken into account: instrumental broadening, Zeeman effect and finally the photon or light reflectance at the W surface.
The obtained energy distribution was found in a very good agreement with the Thompson distribution, even though deviations for lower impact energies are observed, e.g. the high-energy tail of sputtered particles demonstrates a faster drop compared to 1/E
2 at energies below 100 eV. Moreover, the standard cosine (Knudsen cosine law) distribution provides a rather good description of emission spectra in the energy range of study. Finally, the energy distribution was also compared with simulations carried out with the binary collision approximation (BCA) based Monte-Carlo code SDTrimSP. It shows a marginally worse description at low energies and better description of the high energy tail compared to the Thompson one. Furthermore, the model was used to determine in-situ the degree of light reflection at the W surface. The results are in excellent agreement with the literature data.
Multi-source domain adaptation for decoder calibration of intracortical brain-machine interface
Authors: Li Wei , Ji Shaohua , Chen Xi , Kuai Bo , He Jiping , Zhang Peng , Li Qiang 
Published: October 2020

Abstract

Objective. For nonstationarity of neural recordings, daily retraining is required in the decoder calibration of intracortical brain-machine interfaces (iBMIs). Domain adaptation (DA) has started to be applied in iBMIs to solve the problem of daily retraining by taking advantage of historical data. However, previous DA studies used only a single source domain, which might lead to performance instability. In this study, we proposed a multi-source DA algorithm, by fully utilizing the historical data, to achieve a better and more robust decoding performance while reducing the decoder calibration time. Approach. The neural signals were recorded from two rhesus macaques using intracortical electrodes to decode the reaching and grasping movements. A principal component analysis (PCA)-based multi-source domain adaptation (PMDA) algorithm was proposed to apply the feature transfer to diminish the disparities between the target domain and each source domain. Moreover, the multiple weighted sub-classifiers based on multi-source domain data and small current sample set were constructed to accomplish the decoding. Main results. Our algorithm was able to make use of the multi-source domain data and achieve better and more robust decoding performance compared with other methods. Only a small current sample set was needed by our algorithm in order for the decoder calibration time to be effectively reduced. Significance. (1) The idea of the multi-source DA was introduced into the iBMIs to solve the problem of time consumption in the daily decoder retraining. (2) Instead of using only single-source domain data in the previous study, our algorithm made use of multi-day historical data, resulting in better and more robust decoding performance. (3) Our algorithm could be accomplished with only a small current sample set, and it can effectively reduce the decoder calibration time, which is important for further clinical applications.