bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient Creep in Subduction Zones by Long‐Range Dislocation Interactions in Olivine
Authors: Wallis David , Sep Mike , Hansen Lars N. 
Published: January 2022

AbstractLarge earthquakes transfer stress from the shallow lithosphere to the underlying viscoelastic lower crust and upper mantle, inducing transient creep during the postseismic interval. Recent experiments on olivine have provided a new rheological model for this transient creep based on the accumulation and release of back stresses among dislocations. Here, we test whether natural rocks preserve dislocation‐induced stress heterogeneity consistent with the back‐stress hypothesis by mapping olivine from the palaeosubduction interface of the Oman‐UAE ophiolite with high‐angular resolution electron backscatter diffraction. The olivine preserves heterogeneous residual stresses that vary in magnitude by several hundred megapascals over length scales of a few micrometers. Large stresses are commonly spatially associated with elevated densities of geometrically necessary dislocations within subgrain interiors. These spatial relationships, along with characteristic probability distributions of the stresses, confirm that the stress heterogeneity is generated by the dislocations and records their long‐range elastic interactions. Images of dislocations decorated by oxidation display bands of high and low dislocation density, suggesting that dislocation interactions contributed to the organization of the substructure. These results support the applicability of the back‐stress model of transient creep to deformation in the mantle portion of plate‐boundary shear zones. The model predicts that rapid stress changes, such as those imposed by large earthquakes, can induce order‐of‐magnitude changes in viscosity that depend nonlinearly on the stress change, consistent with inferences of mantle rheology from geodetic observations.
OCO‐2 Satellite‐Imposed Constraints on Terrestrial Biospheric CO2 Fluxes Over South Asia
Authors: Philip Sajeev , Johnson Matthew S. , Baker David F. , Basu Sourish , Tiwari Yogesh K. , Indira Nuggehalli K. , Ramonet Michel , Poulter Benjamin 
Published: January 2022

AbstractThe spatiotemporal variability of terrestrial biospheric carbon dioxide (CO2) fluxes over South Asia has large uncertainty. The Orbiting Carbon Observatory 2 (OCO‐2) satellite provides much‐needed retrievals of column‐average CO2 on a global‐scale, with the highest sensitivity to surface CO2 fluxes and spatiotemporal resolution available to‐date. This study conducted global inverse model simulations, assimilating in situ (IS) data and OCO‐2 retrievals, to assess optimized CO2 net ecosystem exchange (NEE) fluxes for South Asia. Annual Net Biome Exchange (NBE = NEE + biomass burning) fluxes over South Asia were estimated to be near neutral (0.04 ± 0.14 PgC yr−1) using both IS and OCO‐2 observations. The most robust result found by assimilating OCO‐2 observations was the constraint imposed on the seasonal cycle of NBE fluxes. The amplitude of the seasonal cycle of NEE was found to be larger than previously assumed. The OCO‐2 inversion led to an NBE seasonal amplitude of 0.34 PgC month−1, which was larger compared to IS constrained NBE (0.19 PgC month−1) and MsTMIP ensemble mean NEE (0.16 PgC month−1). Moreover, OCO‐2 data imposed a phase shift in the NBE seasonal cycle predicted by the prior model. The larger magnitude of NEE seasonality, and phase shift, simulated when assimilating OCO‐2 observations are in general agreement with previous studies assimilating regional aircraft observations in addition to global IS observations. This result suggests that OCO‐2 provides valuable data that allows for the estimate of NBE on a regional scale in a similar manner as regional in situ aircraft networks.
Improved Quantification of Ocean Carbon Uptake by Using Machine Learning to Merge Global Models and pCO2 Data
Authors: Gloege L. , Yan M. , Zheng T. , McKinley G. A. 
Published: January 2022

AbstractThe ocean plays a critical role in modulating climate change by sequestering CO2 from the atmosphere. Quantifying the CO2 flux across the air‐sea interface requires time‐dependent maps of surface ocean partial pressure of CO2 (pCO2), which can be estimated using global ocean biogeochemical models (GOBMs) and observational‐based data products. GOBMs are internally consistent, mechanistic representations of the ocean circulation and carbon cycle, and have long been the standard for making spatio‐temporally resolved estimates of air‐sea CO2 fluxes. However, there are concerns about the fidelity of GOBM flux estimates. Observation‐based products have the strength of being data‐based, but the underlying data are sparse and require significant extrapolation to create global full‐coverage flux estimates. The Lamont Doherty Earth Observatory‐Hybrid Physics Data (LDEO‐HPD) pCO2 product is a new approach to estimating the temporal evolution of surface ocean pCO2 and air‐sea CO2 exchange. LDEO‐HPD uses machine learning to merge high‐quality observations with state‐of‐the‐art GOBMs. We train an eXtreme Gradient Boosting (XGB) algorithm to learn a non‐linear relationship between model‐data mismatch and observed predictors. GOBM fields are then corrected with the predicted model‐data misfit to estimate real‐world pCO2 for 1982–2018. The resulting reconstruction by LDEO‐HPD is in better agreement with independent pCO2 observations than other currently available observation‐based products. Within uncertainties, LDEO‐HPD global ocean uptake of CO2 agrees with other products and the Global Carbon Budget 2020.
Connexin 43 confers chemoresistance through activating PI3K
Authors: Pridham Kevin J. , Shah Farah , Hutchings Kasen R. , Sheng Kevin L. , Guo Sujuan , Liu Min , Kanabur Pratik , Lamouille Samy , Lewis Gabrielle , Morales Marc , Jourdan Jane , Grek Christina L. , Ghatnekar Gautam G. , Varghese Robin , Kelly Deborah F. , Gourdie Robert G. , Sheng Zhi 
Published: January 2022

AbstractCircumventing chemoresistance is crucial for effectively treating cancer including glioblastoma, a lethal brain cancer. The gap junction protein connexin 43 (Cx43) renders glioblastoma resistant to chemotherapy; however, targeting Cx43 is difficult because mechanisms underlying Cx43-mediated chemoresistance remain elusive. Here we report that Cx43, but not other connexins, is highly expressed in a subpopulation of glioblastoma and Cx43 mRNA levels strongly correlate with poor prognosis and chemoresistance in this population, making Cx43 the prime therapeutic target among all connexins. Depleting Cx43 or treating cells with αCT1–a Cx43 peptide inhibitor that sensitizes glioblastoma to the chemotherapy temozolomide–inactivates phosphatidylinositol-3 kinase (PI3K), whereas overexpression of Cx43 activates this signaling. Moreover, αCT1-induced chemo-sensitization is counteracted by a PI3K active mutant. Further research reveals that αCT1 inactivates PI3K without blocking the release of PI3K-activating molecules from membrane channels and that Cx43 selectively binds to the PI3K catalytic subunit β (PIK3CB, also called PI3Kβ or p110β), suggesting that Cx43 activates PIK3CB/p110β independent of its channel functions. To explore the therapeutic potential of simultaneously targeting Cx43 and PIK3CB/p110β, αCT1 is combined with TGX-221 or GSK2636771, two PIK3CB/p110β-selective inhibitors. These two different treatments synergistically inactivate PI3K and sensitize glioblastoma cells to temozolomide in vitro and in vivo. Our study has revealed novel mechanistic insights into Cx43/PI3K-mediated temozolomide resistance in glioblastoma and demonstrated that targeting Cx43 and PIK3CB/p110β together is an effective therapeutic approach for overcoming chemoresistance.
Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours
Authors: Nestler Tim , Dalvi Priya , Haidl Friederike , Wittersheim Maike , von Brandenstein Melanie , Paffenholz Pia , Wagener-Ryczek Svenja , Pfister David , Koitzsch Ulrike , Hellmich Martin , Buettner Reinhard , Odenthal Margarete , Heidenreich Axel 
Published: January 2022

Abstract
Background
Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients.

Methods
Defined areas [invasive tumour front (TF) and tumour centre (TC)] of non-metastatic (with surveillance and recurrence-free follow-up >2 years) and metastatic STGCTs were collected separately using laser capture microdissection. The expression of 760 genes related to tumour progression and metastasis was analysed using nCounter technology and validated with quantitative real-time PCR and enzyme-linked immunosorbent assay.

Results
Distinct gene expression patterns were observed in metastatic and non-metastatic seminomas with respect to both the TF and TC. Comprehensive pathway analysis showed enrichment of genes related to tumour functions such as inflammation, angiogenesis and metabolism at the TF compared to the TC. Remarkably, prominent inflammatory and cancer-related pathways, such as interleukin-6 (IL-6) signalling, integrin signalling and nuclear factor-κB signalling, were significantly upregulated in the TF of metastatic vs non-metastatic tumours.

Conclusions
IL-6 signalling was the most significantly upregulated pathway in metastatic vs non-metastatic tumours and therefore could constitute a therapeutic target for future personalised therapy. In addition, this is the first study showing intra- and inter-tumour heterogeneity in STGCT.
Safety, efficacy and delivery of isometric resistance training as an adjunct therapy for blood pressure control: a modified Delphi study
Authors: Baffour-Awuah Biggie , Pearson Melissa J. , Smart Neil A. , Dieberg Gudrun 
Published: January 2022

AbstractUncontrolled hypertension remains the major risk factor for cardiovascular disease. Isometric resistance training (IRT) has been shown to be a useful nonpharmacological therapy for reducing blood pressure (BP); however, some exercise physiologists and other health professionals are uncertain of the efficacy and safety of IRT. Experts’ consensus was sought in light of the current variability of IRT use as an adjunct treatment for hypertension. An expert consensus-building analysis (Delphi study) was conducted on items relevant to the safety, efficacy and delivery of IRT. The study consisted of 3 phases: (1) identification of items and expert participants for inclusion; (2) a two-round modified Delphi exercise involving expert panelists to build consensus; and (3) a study team consensus meeting for a final item review. A list of 50 items was generated, and 42 international experts were invited to join the Delphi panel. Thirteen and 10 experts completed Delphi Rounds 1 and 2, respectively, reaching consensus on 26 items in Round 1 and 10 items in Round 2. The study team consensus meeting conducted a final item review and considered the remaining 14 items for the content list. A final list of 43 items regarding IRT reached expert consensus: 7/10 items on safety, 11/11 items on efficacy, 10/12 items on programming, 8/10 items on delivery, and 7/7 on the mechanism of action. This study highlights that while experts reached a consensus that IRT is efficacious as an antihypertensive therapy, some still have safety concerns, and there is also ongoing conjecture regarding optimal delivery.
Reversing insecticide resistance with allelic-drive in Drosophila melanogaster
Authors: Kaduskar Bhagyashree , Kushwah Raja Babu Singh , Auradkar Ankush , Guichard Annabel , Li Menglin , Bennett Jared B. , Julio Alison Henrique Ferreira , Marshall John M. , Montell Craig , Bier Ethan 
Published: January 2022

AbstractA recurring target-site mutation identified in various pests and disease vectors alters thevoltage gated sodium channel(vgsc) gene (often referred to asknockdown resistanceorkdr) to confer resistance to commonly used insecticides, pyrethroids and DDT. The ubiquity ofkdrmutations poses a major global threat to the continued use of insecticides as a means for vector control. In this study, we generate commonkdrmutations in isogenic laboratoryDrosophilastrains using CRISPR/Cas9 editing. We identify differential sensitivities to permethrin and DDT versus deltamethrin among these mutants as well as contrasting physiological consequences of two differentkdrmutations. Importantly, we apply a CRISPR-based allelic-drive to replace a resistantkdrmutation with a susceptible wild-type counterpart in population cages. This successful proof-of-principle opens-up numerous possibilities including targeted reversion of insecticide-resistant populations to a native susceptible state or replacement of malaria transmitting mosquitoes with those bearing naturally occurring parasite resistant alleles.
Cornering the universal shape of fluctuations
Authors: Estienne Benoit , Stéphan Jean-Marie , Witczak-Krempa William 
Published: January 2022

AbstractUnderstanding the fluctuations of observables is one of the main goals in science, be it theoretical or experimental, quantum or classical. We investigate such fluctuations in a subregion of the full system, focusing on geometries with sharp corners. We report that the angle dependence is super-universal: up to a numerical prefactor, this function does not depend on anything, provided the system under study is uniform, isotropic, and correlations do not decay too slowly. The prefactor contains important physical information: we show in particular that it gives access to the long-wavelength limit of the structure factor. We exemplify our findings with fractional quantum Hall states, topological insulators, scale invariant quantum critical theories, and metals. We suggest experimental tests, and anticipate that our findings can be generalized to other spatial dimensions or geometries. In addition, we highlight the similarities of the fluctuation shape dependence with findings relating to quantum entanglement measures.
Selective ligand removal to improve accessibility of active sites in hierarchical MOFs for heterogeneous photocatalysis
Authors: Naghdi Shaghayegh , Cherevan Alexey , Giesriegl Ariane , Guillet-Nicolas Rémy , Biswas Santu , Gupta Tushar , Wang Jia , Haunold Thomas , Bayer Bernhard Christian , Rupprechter Günther , Toroker Maytal Caspary , Kleitz Freddy , Eder Dominik 
Published: January 2022

AbstractMetal-organic frameworks (MOFs) are commended as photocatalysts for H2 evolution and CO2 reduction as they combine light-harvesting and catalytic functions with excellent reactant adsorption capabilities. For dynamic processes in liquid phase, the accessibility of active sites becomes a critical parameter as reactant diffusion is limited by the inherently small micropores. Our strategy is to introduce additional mesopores by selectively removing one ligand in mixed-ligand MOFs via thermolysis. Here we report photoactive MOFs of the MIL-125-Ti family with two distinct mesopore architectures resembling either large cavities or branching fractures. The ligand removal is highly selective and follows a 2-step process tunable by temperature and time. The introduction of mesopores and the associated formation of new active sites have improved the HER rates of the MOFs by up to 500%. We envision that this strategy will allow the purposeful engineering of hierarchical MOFs and advance their applicability in environmental and energy technologies.
Mammalian brain glycoproteins exhibit diminished glycan complexity compared to other tissues
Authors: Williams Sarah E. , Noel Maxence , Lehoux Sylvain , Cetinbas Murat , Xavier Ramnik J. , Sadreyev Ruslan I. , Scolnick Edward M. , Smoller Jordan W. , Cummings Richard D. , Mealer Robert G. 
Published: January 2022

AbstractGlycosylation is essential to brain development and function, but prior studies have often been limited to a single analytical technique and excluded region- and sex-specific analyses. Here, using several methodologies, we analyze Asn-linked and Ser/Thr/Tyr-linked protein glycosylation between brain regions and sexes in mice. Brain N-glycans are less complex in sequence and variety compared to other tissues, consisting predominantly of high-mannose and fucosylated/bisected structures. Most brain O-glycans are unbranched, sialylated O-GalNAc and O-mannose structures. A consistent pattern is observed between regions, and sex differences are minimal compared to those in plasma. Brain glycans correlate with RNA expression of their synthetic enzymes, and analysis of glycosylation genes in humans show a global downregulation in the brain compared to other tissues. We hypothesize that this restricted repertoire of protein glycans arises from their tight regulation in the brain. These results provide a roadmap for future studies of glycosylation in neurodevelopment and disease.
Biosensor for branched-chain amino acid metabolism in yeast and applications in isobutanol and isopentanol production
Authors: Zhang Yanfei , Cortez Jeremy D. , Hammer Sarah K. , Carrasco-López César , García Echauri Sergio Á. , Wiggins Jessica B. , Wang Wei , Avalos José L. 
Published: January 2022

AbstractBranched-chain amino acid (BCAA) metabolism fulfills numerous physiological roles and can be harnessed to produce valuable chemicals. However, the lack of eukaryotic biosensors specific for BCAA-derived products has limited the ability to develop high-throughput screens for strain engineering and metabolic studies. Here, we harness the transcriptional regulator Leu3p from Saccharomyces cerevisiae to develop a genetically encoded biosensor for BCAA metabolism. In one configuration, we use the biosensor to monitor yeast production of isobutanol, an alcohol derived from valine degradation. Small modifications allow us to redeploy Leu3p in another biosensor configuration that monitors production of the leucine-derived alcohol, isopentanol. These biosensor configurations are effective at isolating high-producing strains and identifying enzymes with enhanced activity from screens for branched-chain higher alcohol (BCHA) biosynthesis in mitochondria as well as cytosol. Furthermore, this biosensor has the potential to assist in metabolic studies involving BCAA pathways, and offers a blueprint to develop biosensors for other products derived from BCAA metabolism.
The formation of avian montane diversity across barriers and along elevational gradients
Authors: Pujolar José Martín , Blom Mozes P. K. , Reeve Andrew Hart , Kennedy Jonathan D. , Marki Petter Zahl , Korneliussen Thorfinn S. , Freeman Benjamin G. , Sam Katerina , Linck Ethan , Haryoko Tri , Iova Bulisa , Koane Bonny , Maiah Gibson , Paul Luda , Irestedt Martin , Jønsson Knud Andreas 
Published: January 2022

AbstractTropical mountains harbor exceptional concentrations of Earth’s biodiversity. In topographically complex landscapes, montane species typically inhabit multiple mountainous regions, but are absent in intervening lowland environments. Here we report a comparative analysis of genome-wide DNA polymorphism data for population pairs from eighteen Indo-Pacific bird species from the Moluccan islands of Buru and Seram and from across the island of New Guinea. We test how barrier strength and relative elevational distribution predict population differentiation, rates of historical gene flow, and changes in effective population sizes through time. We find population differentiation to be consistently and positively correlated with barrier strength and a species’ altitudinal floor. Additionally, we find that Pleistocene climate oscillations have had a dramatic influence on the demographics of all species but were most pronounced in regions of smaller geographic area. Surprisingly, even the most divergent taxon pairs at the highest elevations experience gene flow across barriers, implying that dispersal between montane regions is important for the formation of montane assemblages.
Single particle cryo-EM structure of the outer hair cell motor protein prestin
Authors: Butan Carmen , Song Qiang , Bai Jun-Ping , Tan Winston J. T. , Navaratnam Dhasakumar , Santos-Sacchi Joseph 
Published: January 2022

AbstractThe mammalian outer hair cell (OHC) protein prestin (Slc26a5) differs from other Slc26 family members due to its unique piezoelectric-like property that drives OHC electromotility, the putative mechanism for cochlear amplification. Here, we use cryo-electron microscopy to determine prestin’s structure at 3.6 Å resolution. Prestin is structurally similar to the anion transporter Slc26a9. It is captured in an inward-open state which may reflect prestin’s contracted state. Two well-separated transmembrane (TM) domains and two cytoplasmic sulfate transporter and anti-sigma factor antagonist (STAS) domains form a swapped dimer. The transmembrane domains consist of 14 transmembrane segments organized in two 7+7 inverted repeats, an architecture first observed in the bacterial symporter UraA. Mutation of prestin’s chloride binding site removes salicylate competition with anions while retaining the prestin characteristic displacement currents (Nonlinear Capacitance), undermining the extrinsic voltage sensor hypothesis for prestin function.
Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors
Authors: Tanaka Yosuke , Takeda Reina , Fukushima Tsuyoshi , Mikami Keiko , Tsuchiya Shun , Tamura Moe , Adachi Keito , Umemoto Terumasa , Asada Shuhei , Watanabe Naoki , Morishita Soji , Imai Misa , Nagata Masayoshi , Araki Marito , Takizawa Hitoshi , Fukuyama Tomofusa , Lamagna Chrystelle , Masuda Esteban S. , Ito Ryoji , Goyama Susumu , Komatsu Norio , Takaku Tomoiku , Kitamura Toshio 
Published: January 2022

AbstractLeukemia stem cells (LSCs) in chronic myeloid leukemia (CML) are quiescent, insensitive to BCR-ABL1 tyrosine kinase inhibitors (TKIs) and responsible for CML relapse. Therefore, eradicating quiescent CML LSCs is a major goal in CML therapy. Here, using a G0 marker (G0M), we narrow down CML LSCs as G0M- and CD27- double positive cells among the conventional CML LSCs. Whole transcriptome analysis reveals NF-κB activation via inflammatory signals in imatinib-insensitive quiescent CML LSCs. Blocking NF-κB signals by inhibitors of interleukin-1 receptor-associated kinase 1/4 (IRAK1/4 inhibitors) together with imatinib eliminates mouse and human CML LSCs. Intriguingly, IRAK1/4 inhibitors attenuate PD-L1 expression on CML LSCs, and blocking PD-L1 together with imatinib also effectively eliminates CML LSCs in the presence of T cell immunity. Thus, IRAK1/4 inhibitors can eliminate CML LSCs through inhibiting NF-κB activity and reducing PD-L1 expression. Collectively, the combination of TKIs and IRAK1/4 inhibitors is an attractive strategy to achieve a radical cure of CML.