bluuebunny/crossref_metadata_2025_split huggingface dataset:
GRACEfully Closing the Water Balance: A Data‐Driven Probabilistic Approach Applied to River Basins in Iran
Authors: Schoups Gerrit , Nasseri Mohsen 
Published: May 2021

AbstractTo fully benefit from remotely sensed observations of the terrestrial water cycle, bias and random errors in these data sets need to be quantified. This paper presents a Bayesian hierarchical model that fuses monthly water balance data and estimates the corresponding data errors and error‐corrected water balance components (precipitation, evaporation, river discharge, and water storage). The model combines monthly basin‐scale water balance constraints with probabilistic data error models for each water balance variable. Each data error model includes parameters that are in turn treated as unknown random variables to reflect uncertainty in the errors. Errors in precipitation and evaporation data are parameterized as a function of multiple data sources, while errors in GRACE storage observations are described by a noisy sine wave model with parameters controlling the phase, amplitude, and randomness of the sine wave. Error parameters and water balance variables are estimated using a combination of Markov Chain Monte Carlo sampling and iterative smoothing. Application to semiarid river basins in Iran yields (a) significant reductions in evaporation uncertainty during water‐stressed summers, (b) basin‐specific timing and amplitude corrections of the GRACE water storage dynamics, and (c) posterior water balance estimates with average standard errors of 4–12 mm/month for water storage, 3.5–7 mm/month for precipitation, 2–6 mm/month for evaporation, and 0–2 mm/month for river discharge. The approach is readily extended to other data sets and other (gauged) basins around the world, possibly using customized data error models. The resulting error‐filtered and bias‐corrected water balance estimates can be used to evaluate hydrological models.
Observations of Closed Magnetic Flux Embedded in the Lobes During Periods of Northward IMF
Authors: Fryer L. J. , Fear R. C. , Coxon J. C. , Gingell I. L. 
Published: May 2021

AbstractThe high latitude, lobe regions of the magnetosphere are often assumed to contain cool, low energy plasma populations. However, during periods of northward Interplanetary Magnetic Field, energetic plasma populations have occasionally been observed. We present three cases when Cluster observed uncharacteristically “hot” plasma populations in the lobe. For two of the three events, we present simultaneous observations of the plasma sheet observed by Double Star. The similarity between the plasma in the lobe and the plasma sheet suggests that the mechanism that produces plasma at high latitudes is likely to be tail reconnection, resulting in a trapped “wedge” of closed flux about the noon‐midnight meridian. Complementary images from Imager for Magnetopause to Aurora Global Exploration and DMSP/Special Sensor Ultraviolet Spectrographic Imager show that transpolar arcs, which form in each event in at least one hemisphere, directly intersect the footprint of the Cluster spacecraft in all three events. The intersection of the Cluster footprint with the transpolar arcs is synchronous with the observation of the energetic plasma populations in the lobe. This further supports the conclusion that it is likely this energetic plasma observed in the high latitude lobe regions of magnetosphere is on closed field lines.
PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis
Authors: Huang Wushuang , Zheng Xueqing , Yang Mei , Li Ruiqi , Song Yaling 
Published: May 2021

AbstractCircadian rhythm is involved in the development and diseases of many tissues. However, as an essential environmental regulating factor, its effect on amelogenesis has not been fully elucidated. The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation. Circadian disruption models were constructed in mice for in vivo experiments. An ameloblast-lineage cell (ALC) line was used for in vitro studies. As essential molecules of the circadian system, Bmal1 and Per2 exhibited circadian expression in ALCs. Circadian disruption mice showed reduced amelogenin (AMELX) expression and enamel matrix secretion and downregulated expression of BMAL1, PER2, PPARγ, phosphorylated AKT1 and β-catenin, cytokeratin-14 and F-actin in ameloblasts. According to previous findings and our study, BMAL1 positively regulated PER2. Therefore, the present study focused on PER2-mediated ameloblast differentiation and enamel formation. Per2 knockdown decreased the expression of AMELX, PPARγ, phosphorylated AKT1 and β-catenin, promoted nuclear β-catenin accumulation, inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs. Overexpression of PPARγ partially reversed the above results in Per2-knockdown ALCs. Furthermore, in in vivo experiments, the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group, which was rescued by using a PPARγ agonist in circadian disturbance mice. In conclusion, through regulation of the PPARγ/AKT1/β-catenin signalling axis, PER2 played roles in amelogenin expression, cell junctions and arrangement, enamel matrix secretion and mineralization during ameloblast differentiation, which exert effects on enamel formation.
Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance
Authors: Lodillinsky Catalina , Fuhrmann Laetitia , Irondelle Marie , Pylypenko Olena , Li Xiao-Yan , Bonsang-Kitzis Hélène , Reyal Fabien , Vacher Sophie , Calmel Claire , De Wever Olivier , Bièche Ivan , Lacombe Marie-Lise , Eiján Ana Maria , Houdusse Anne , Vincent-Salomon Anne , Weiss Stephen J. , Chavrier Philippe , Boissan Mathieu 
Published: May 2021

AbstractMembrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is up-regulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anti-correlation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1-MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.
18F-Fluciclovine PET/CT performance in biochemical recurrence of prostate cancer: a systematic review
Authors: Rais-Bahrami Soroush , Efstathiou Jason A. , Turnbull Catriona M. , Camper Stephen B. , Kenwright Andy , Schuster David M. , Scarsbrook Andrew F. 
Published: May 2021

Abstract
Background
A systematic literature review of the performance of 18Fluorine-fluciclovine PET/CT for imaging of men with recurrent prostate cancer was performed.

Methods
Scientific literature databases (MEDLINE, ScienceDirect and Cochrane Libraries) were searched systematically during Oct 2020 using PRISMA criteria. No limit was put on the date of publication. Prospective studies reporting a patient-level 18F-fluciclovine detection rate (DR) from ≥25 patients with recurrent prostate cancer were sought. Proceedings of relevant meetings held from 2018 through Oct 2020 were searched for abstracts meeting criteria.

Results
Searches identified 321 unique articles. In total, nine articles (six papers and three conference abstracts), comprising a total of 850 patients met inclusion criteria. Most studies (n = 6) relied on ASTRO-Phoenix Criteria, EAU-ESTRO-SIOG, and/or ASTRO-AUA guidelines to identify patients with biochemical recurrence. Patients’ PSA levels ranged from 0.02–301.7 ng/mL (median level per study, 0.34–4.10 ng/mL [n = 8]). Approximately 64% of patients had undergone prostatectomy, but three studies focused solely on post-prostatectomy patients. Adherence to imaging protocol guidelines was heterogeneous, with variance seen in administered activity, uptake and scan times. Overall patient-level DR varied between studies from 26% to 83%, with 78% of studies reporting a DR > 50%. DR was proportional to PSA, but even at PSA < 0.5 ng/mL DR of up to 53% were reported. Prostate/bed DR (n = 7) ranged from 18% to 78% and extra-prostatic rates (n = 6) from 8% to 72%. Pelvic node and bone lesion DR ranged from 8% to 47% and 0% to 26%, respectively (n = 5). 18F-Fluciclovine PET/CT was shown to impact patient management and outcomes. Two studies reported 59–63% of patients to have a management change post-scan. A further study showed significant increase in failure-free survival following 18F-fluciclovine-guided compared with conventional imaging-guided radiotherapy planning.

Conclusions
18F-Fluciclovine PET/CT shows good performance in patients with recurrent prostate cancer leading to measurable clinical benefits. Careful adherence to recommended imaging protocols may help optimize DR.
RNAi and chemogenetic reporter co-regulation in primate striatal interneurons
Authors: Lerchner Walter , Adil Abdullah A. , Mumuney Sekinat , Wang Wenliang , Falcone Rossella , Turchi Janita , Richmond Barry J. 
Published: May 2021

AbstractUsing genetic tools to study the functional roles of molecularly specified neuronal populations in the primate brain is challenging, primarily because of specificity and verification of virus-mediated targeting. Here, we report a lentivirus-based system that helps improve specificity and verification by (a) targeting a selected molecular mechanism, (b) in vivo reporting of expression, and (c) allowing the option to independently silence all regional neural activity. Specifically, we modulate cholinergic signaling of striatal interneurons by shRNAmir and pair it with hM4Di_CFP, a chemogenetic receptor that can function as an in vivo and in situ reporter. Quantitative analyses by visual and deep-learning assisted methods show an inverse linear relation between hM4Di_CFP and ChAT protein expression for several shRNAmir constructs. This approach successfully applies shRNAmir to modulating gene expression in the primate brain and shows that hM4Di_CFP can act as a readout for this modulation.
A small climate-amplifying effect of climate-carbon cycle feedback
Authors: Zhang Xuanze , Wang Ying-Ping , Rayner Peter J. , Ciais Philippe , Huang Kun , Luo Yiqi , Piao Shilong , Wang Zhonglei , Xia Jianyang , Zhao Wei , Zheng Xiaogu , Tian Jing , Zhang Yongqiang 
Published: May 2021

AbstractThe climate-carbon cycle feedback is one of the most important climate-amplifying feedbacks of the Earth system, and is quantified as a function of carbon-concentration feedback parameter (β) and carbon-climate feedback parameter (γ). However, the global climate-amplifying effect from this feedback loop (determined by the gain factor, g) has not been quantified from observations. Here we apply a Fourier analysis-based carbon cycle feedback framework to the reconstructed records from 1850 to 2017 and 1000 to 1850 to estimate β and γ. We show that the β-feedback varies by less than 10% with an average of 3.22 ± 0.32 GtC ppm−1 for 1880–2017, whereas the γ-feedback increases from −33 ± 14 GtC K−1 on a decadal scale to −122 ± 60 GtC K−1 on a centennial scale for 1000–1850. Feedback analysis further reveals that the current amplification effect from the carbon cycle feedback is small (g is 0.01 ± 0.05), which is much lower than the estimates by the advanced Earth system models (g is 0.09 ± 0.04 for the historical period and is 0.15 ± 0.08 for the RCP8.5 scenario), implying that the future allowable CO2 emissions could be 9 ± 7% more. Therefore, our findings provide new insights about the strength of climate-carbon cycle feedback and about observational constraints on models for projecting future climate.
Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
Authors: Georgiadis Marios , Schroeter Aileen , Gao Zirui , Guizar-Sicairos Manuel , Liebi Marianne , Leuze Christoph , McNab Jennifer A. , Balolia Aleezah , Veraart Jelle , Ades-Aron Benjamin , Kim Sunglyoung , Shepherd Timothy , Lee Choong H. , Walczak Piotr , Chodankar Shirish , DiGiacomo Phillip , David Gergely , Augath Mark , Zerbi Valerio , Sommer Stefan , Rajkovic Ivan , Weiss Thomas , Bunk Oliver , Yang Lin , Zhang Jiangyang , Novikov Dmitry S. , Zeineh Michael , Fieremans Els , Rudin Markus 
Published: May 2021

AbstractMyelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.
A trimethoprim derivative impedes antibiotic resistance evolution
Authors: Manna Madhu Sudan , Tamer Yusuf Talha , Gaszek Ilona , Poulides Nicole , Ahmed Ayesha , Wang Xiaoyu , Toprak Furkan C. R. , Woodard DaNae R. , Koh Andrew Y. , Williams Noelle S. , Borek Dominika , Atilgan Ali Rana , Hulleman John D. , Atilgan Canan , Tambar Uttam , Toprak Erdal 
Published: May 2021

AbstractThe antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4’-desmethyltrimethoprim (4’-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4’-DTMP than in the presence of TMP. We find that 4’-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to resistance.
FKRP-dependent glycosylation of fibronectin regulates muscle pathology in muscular dystrophy
Authors: Wood A. J. , Lin C. H. , Li M. , Nishtala K. , Alaei S. , Rossello F. , Sonntag C. , Hersey L. , Miles L. B. , Krisp C. , Dudczig S. , Fulcher A. J. , Gibertini S. , Conroy P. J. , Siegel A. , Mora M. , Jusuf P. , Packer N. H. , Currie P. D. 
Published: May 2021

AbstractThe muscular dystrophies encompass a broad range of pathologies with varied clinical outcomes. In the case of patients carrying defects in fukutin-related protein (FKRP), these diverse pathologies arise from mutations within the same gene. This is surprising as FKRP is a glycosyltransferase, whose only identified function is to transfer ribitol-5-phosphate to α-dystroglycan (α-DG). Although this modification is critical for extracellular matrix attachment, α-DG’s glycosylation status relates poorly to disease severity, suggesting the existence of unidentified FKRP targets. Here we reveal that FKRP directs sialylation of fibronectin, a process essential for collagen recruitment to the muscle basement membrane. Thus, our results reveal that FKRP simultaneously regulates the two major muscle-ECM linkages essential for fibre survival, and establishes a new disease axis for the muscular dystrophies.
Cryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding
Authors: Wang Kaituo , Dagil Robert , Lavstsen Thomas , Misra Sandeep K. , Spliid Charlotte B. , Wang Yong , Gustavsson Tobias , Sandoval Daniel R. , Vidal-Calvo Elena Ethel , Choudhary Swati , Agerbaek Mette Ø , Lindorff-Larsen Kresten , Nielsen Morten A. , Theander Thor G. , Sharp Joshua S. , Clausen Thomas Mandel , Gourdon Pontus , Salanti Ali 
Published: May 2021

AbstractPlacental malaria can have severe consequences for both mother and child and effective vaccines are lacking. Parasite-infected red blood cells sequester in the placenta through interaction between parasite-expressed protein VAR2CSA and the glycosaminoglycan chondroitin sulfate A (CS) abundantly present in the intervillous space. Here, we report cryo-EM structures of the VAR2CSA ectodomain at up to 3.1 Å resolution revealing an overall V-shaped architecture and a complex domain organization. Notably, the surface displays a single significantly electropositive patch, compatible with binding of negatively charged CS. Using molecular docking and molecular dynamics simulations as well as comparative hydroxyl radical protein foot-printing of VAR2CSA in complex with placental CS, we identify the CS-binding groove, intersecting with the positively charged patch of the central VAR2CSA structure. We identify distinctive conserved structural features upholding the macro-molecular domain complex and CS binding capacity of VAR2CSA as well as divergent elements possibly allowing immune escape at or near the CS binding site. These observations will support rational design of second-generation placental malaria vaccines.
Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin
Authors: Lee Young-Tae , Ayoub Alex , Park Sang-Ho , Sha Liang , Xu Jing , Mao Fengbiao , Zheng Wei , Zhang Yang , Cho Uhn-Soo , Dou Yali 
Published: May 2021

AbstractRecent cryo-EM structures show the highly dynamic nature of the MLL1-NCP (nucleosome core particle) interaction. Functional implication and regulation of such dynamics remain unclear. Here we show that DPY30 and the intrinsically disordered regions (IDRs) of ASH2L work together in restricting the rotational dynamics of the MLL1 complex on the NCP. We show that DPY30 binding to ASH2L leads to stabilization and integration of ASH2L IDRs into the MLL1 complex and establishes new ASH2L-NCP contacts. The significance of ASH2L-DPY30 interactions is demonstrated by requirement of both ASH2L IDRs and DPY30 for dramatic increase of processivity and activity of the MLL1 complex. This DPY30 and ASH2L-IDR dependent regulation is NCP-specific and applies to all members of the MLL/SET1 family of enzymes. We further show that DPY30 is causal for de novo establishment of H3K4me3 in ESCs. Our study provides a paradigm of how H3K4me3 is regulated on chromatin and how H3K4me3 heterogeneity can be modulated by ASH2L IDR interacting proteins.
Cardiomyocyte contractile impairment in heart failure results from reduced BAG3-mediated sarcomeric protein turnover
Authors: Martin Thomas G. , Myers Valerie D. , Dubey Praveen , Dubey Shubham , Perez Edith , Moravec Christine S. , Willis Monte S. , Feldman Arthur M. , Kirk Jonathan A. 
Published: May 2021

AbstractThe association between reduced myofilament force-generating capacity (Fmax) and heart failure (HF) is clear, however the underlying molecular mechanisms are poorly understood. Here, we show impaired Fmax arises from reduced BAG3-mediated sarcomere turnover. Myofilament BAG3 expression decreases in human HF and positively correlates with Fmax. We confirm this relationship using BAG3 haploinsufficient mice, which display reduced Fmax and increased myofilament ubiquitination, suggesting impaired protein turnover. We show cardiac BAG3 operates via chaperone-assisted selective autophagy (CASA), conserved from skeletal muscle, and confirm sarcomeric CASA complex localization is BAG3/proteotoxic stress-dependent. Using mass spectrometry, we characterize the myofilament CASA interactome in the human heart and identify eight clients of BAG3-mediated turnover. To determine if increasing BAG3 expression in HF can restore sarcomere proteostasis/Fmax, HF mice were treated with rAAV9-BAG3. Gene therapy fully rescued Fmax and CASA protein turnover after four weeks. Our findings indicate BAG3-mediated sarcomere turnover is fundamental for myofilament functional maintenance.
The kaolinite shuttle links the Great Oxidation and Lomagundi events
Authors: Hao Weiduo , Mänd Kaarel , Li Yuhao , Alessi Daniel S. , Somelar Peeter , Moussavou Mathieu , Romashkin Alexander E. , Lepland Aivo , Kirsimäe Kalle , Planavsky Noah J. , Konhauser Kurt O. 
Published: May 2021

AbstractThe ~2.22–2.06 Ga Lomagundi Event was the longest positive carbon isotope excursion in Earth’s history and is commonly interpreted to reflect perturbations in continental weathering and the phosphorous cycle. Previous models have focused on mechanisms of increasing phosphorous solubilization during weathering without focusing on transport to the oceans and its dispersion in seawater. Building from new experimental results, here we report kaolinite readily absorbs phosphorous under acidic freshwater conditions, but quantitatively releases phosphorous under seawater conditions where it becomes bioavailable to phytoplankton. The strong likelihood of high weathering intensities and associated high kaolinite content in post-Great-Oxidation-Event paleosols suggests there would have been enhanced phosphorus shuttling from the continents into marine environments. A kaolinite phosphorous shuttle introduces the potential for nonlinearity in the fluxes of phosphorous to the oceans with increases in chemical weathering intensity.