bluuebunny/crossref_metadata_2025_split huggingface dataset:
MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer
Authors: Stramucci Lorenzo , Pranteda Angelina , Stravato Arianna , Amoreo Carla Azzurra , Pennetti Annarita , Diodoro Maria Grazia , Bartolazzi Armando , Milella Michele , Bossi Gianluca 
Published: November 2019

AbstractColorectal cancer (CRC) is one of the most common malignant tumors worldwide and understanding its underlying molecular mechanisms is crucial for the development of therapeutic strategies. The mitogen-activated protein kinase-kinase 3 (MKK3) is a specific activator of p38 MAP kinases (p38 MAPKs), which contributes to the regulation of several cellular functions, such as proliferation, differentiation, apoptosis as well as response to drugs. At present, the exact MKK3/p38 MAPK pathway contribution in cancer is heavily debated because of its pleiotropic function. In this work, we retrospectively explored the prognostic and pathobiologic relevance of MKK3 in a cohort of CRC patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. We found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. Herein, we report that the MKK3 targeting by inducible RNA interference univocally exerts antitumor effects in CRC lines but not in primary colonocytes. While MKK3 depletion per se affects growth and survival by induction of sustained autophagy and death in some CRC lines, it potentiates response to chemotherapeutic drug 5-fluorouracil (5-FU) in all of the tested CRC lines in vitro. Here, we demonstrate for the first time that in CRC the MKK3 specifically activates p38delta MAPK isoform to sustain prosurvival signaling and that such effect is exacerbated upon 5-FU challenge. Indeed, p38delta MAPK silencing recapitulates MKK3 depletion effects in CRC cells in vitro and in vivo. Overall, our data identified a molecular mechanism through which MKK3 supports proliferation and survival signaling in CRC, further supporting MKK3 as a novel and extremely attractive therapeutic target for the development of promising strategies for the management of CRC patients.
Hepatocyte-derived exosomal MiR-194 activates PMVECs and promotes angiogenesis in hepatopulmonary syndrome
Authors: Chen Lin , Han Yi , Li Yujie , Chen Bing , Bai Xuehong , Belguise Karine , Wang Xiaobo , Chen Yang , Yi Bin , Lu Kaizhi 
Published: November 2019

AbstractHepatopulmonary syndrome (HPS) is a serious vascular complication in the setting of liver disease. Factors produced by the liver are essential to regulate pulmonary angiogenesis in the pathogenesis of HPS; however, the pathogenic mechanisms of pulmonary angiogenesis are not fully understood. We investigated the role of HPS rat serum exosomes (HEs) and sham-operated rat serum exosomes (SEs) in the regulation of angiogenesis. We found that HEs significantly enhance PMVEC proliferation, migration, and tube formation. We further identified miR-194 was the most notably increased miRNA in HEs compared to SEs. Once released, hepatocyte-derived exosomal miR-194 was internalized by PMVECs, leading to the promotion of PMVEC proliferation, migration, and tube formation through direct targeting of THBS1, STAT1, and LIF. Importantly, the pathogenic role of exosomal miR-194 in initiating angiogenesis was reversed by P53 inhibition, exosome secretion inhibition or miR-194 inhibition. Additionally, high levels of miR-194 were found in serum exosomes and were positively correlated with P(A-a)O2 in HPS patients and rats. Thus, our results highlight that the exosome/miR-194 axis plays a critical pathologic role in pulmonary angiogenesis, representing a new therapeutic target for HPS.
Emergence of the Ug99 lineage of the wheat stem rust pathogen through somatic hybridisation
Authors: Li Feng , Upadhyaya Narayana M. , Sperschneider Jana , Matny Oadi , Nguyen-Phuc Hoa , Mago Rohit , Raley Castle , Miller Marisa E. , Silverstein Kevin A. T. , Henningsen Eva , Hirsch Cory D. , Visser Botma , Pretorius Zacharias A. , Steffenson Brian J. , Schwessinger Benjamin , Dodds Peter N. , Figueroa Melania 
Published: November 2019

AbstractParasexuality contributes to diversity and adaptive evolution of haploid (monokaryotic) fungi. However, non-sexual genetic exchange mechanisms are not defined in dikaryotic fungi (containing two distinct haploid nuclei). Newly emerged strains of the wheat stem rust pathogen, Puccinia graminis f. sp. tritici (Pgt), such as Ug99, are a major threat to global food security. Here, we provide genomics-based evidence supporting that Ug99 arose by somatic hybridisation and nuclear exchange between dikaryons. Fully haplotype-resolved genome assembly and DNA proximity analysis reveal that Ug99 shares one haploid nucleus genotype with a much older African lineage of Pgt, with no recombination or chromosome reassortment. These findings indicate that nuclear exchange between dikaryotes can generate genetic diversity and facilitate the emergence of new lineages in asexual fungal populations.
Complex I is bypassed during high intensity exercise
Authors: Nilsson Avlant , Björnson Elias , Flockhart Mikael , Larsen Filip J. , Nielsen Jens 
Published: November 2019

AbstractHuman muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.
Global mycorrhizal plant distribution linked to terrestrial carbon stocks
Authors: Soudzilovskaia Nadejda A. , van Bodegom Peter M. , Terrer César , Zelfde Maarten van’t , McCallum Ian , Luke McCormack M. , Fisher Joshua B. , Brundrett Mark C. , de Sá Nuno César , Tedersoo Leho 
Published: November 2019

AbstractVegetation impacts on ecosystem functioning are mediated by mycorrhizas, plant–fungal associations formed by most plant species. Ecosystems dominated by distinct mycorrhizal types differ strongly in their biogeochemistry. Quantitative analyses of mycorrhizal impacts on ecosystem functioning are hindered by the scarcity of information on mycorrhizal distributions. Here we present global, high-resolution maps of vegetation biomass distribution by dominant mycorrhizal associations. Arbuscular, ectomycorrhizal, and ericoid mycorrhizal vegetation store, respectively, 241 ± 15, 100 ± 17, and 7 ± 1.8 GT carbon in aboveground biomass, whereas non-mycorrhizal vegetation stores 29 ± 5.5 GT carbon. Soil carbon stocks in both topsoil and subsoil are positively related to the community-level biomass fraction of ectomycorrhizal plants, though the strength of this relationship varies across biomes. We show that human-induced transformations of Earth’s ecosystems have reduced ectomycorrhizal vegetation, with potential ramifications to terrestrial carbon stocks. Our work provides a benchmark for spatially explicit and globally quantitative assessments of mycorrhizal impacts on ecosystem functioning and biogeochemical cycling.
A bio-inspired coordination polymer as outstanding water oxidation catalyst via second coordination sphere engineering
Authors: Li Wenlong , Li Fusheng , Yang Hao , Wu Xiujuan , Zhang Peili , Shan Yu , Sun Licheng 
Published: November 2019

AbstractFirst-row transition metal-based catalysts have been developed for the oxygen evolution reaction (OER) during the past years, however, such catalysts typically operate at overpotentials (η) significantly above thermodynamic requirements. Here, we report an iron/nickel terephthalate coordination polymer on nickel form (NiFeCP/NF) as catalyst for OER, in which both coordinated and uncoordinated carboxylates were maintained after electrolysis. NiFeCP/NF exhibits outstanding electro-catalytic OER activity with a low overpotential of 188 mV at 10 mA cm−2 in 1.0 KOH, with a small Tafel slope and excellent stability. The pH-independent OER activity of NiFeCP/NF on the reversible hydrogen electrode scale suggests that a concerted proton-coupled electron transfer (c-PET) process is the rate-determining step (RDS) during water oxidation. Deuterium kinetic isotope effects, proton inventory studies and atom-proton-transfer measurements indicate that the uncoordinated carboxylates are serving as the proton transfer relays, with a similar function as amino acid residues in photosystem II (PSII), accelerating the proton-transfer rate.
Chemo-enzymatic cascades to produce cycloalkenes from bio-based resources
Authors: Wu Shuke , Zhou Yi , Gerngross Daniel , Jeschek Markus , Ward Thomas R. 
Published: November 2019

AbstractEngineered enzyme cascades offer powerful tools to convert renewable resources into value-added products. Man-made catalysts give access to new-to-nature reactivities that may complement the enzyme’s repertoire. Their mutual incompatibility, however, challenges their integration into concurrent chemo-enzymatic cascades. Herein we show that compartmentalization of complex enzyme cascades within E. coli whole cells enables the simultaneous use of a metathesis catalyst, thus allowing the sustainable one-pot production of cycloalkenes from oleic acid. Cycloheptene is produced from oleic acid via a concurrent enzymatic oxidative decarboxylation and ring-closing metathesis. Cyclohexene and cyclopentene are produced from oleic acid via either a six- or eight-step enzyme cascade involving hydration, oxidation, hydrolysis and decarboxylation, followed by ring-closing metathesis. Integration of an upstream hydrolase enables the usage of olive oil as the substrate for the production of cycloalkenes. This work highlights the potential of integrating organometallic catalysis with whole-cell enzyme cascades of high complexity to enable sustainable chemistry.
Light-fuelled freestyle self-oscillators
Authors: Zeng Hao , Lahikainen Markus , Liu Li , Ahmed Zafar , Wani Owies M. , Wang Meng , Yang Hong , Priimagi Arri 
Published: November 2019

AbstractSelf-oscillation is a phenomenon where an object sustains periodic motion upon non-periodic stimulus. It occurs commonly in nature, a few examples being heartbeat, sea waves and fluttering of leaves. Stimuli-responsive materials allow creating synthetic self-oscillators fuelled by different forms of energy, e.g. heat, light and chemicals, showing great potential for applications in power generation, autonomous mass transport, and self-propelled micro-robotics. However, most of the self-oscillators are based on bending deformation, thereby limiting their possibilities of being implemented in practical applications. Here, we report light-fuelled self-oscillators based on liquid crystal network actuators that can exhibit three basic oscillation modes: bending, twisting and contraction-expansion. We show that a time delay in material response dictates the self-oscillation dynamics, and realize a freestyle self-oscillator that combines numerous oscillation modes simultaneously by adjusting the excitation beam position. The results provide new insights into understanding of self-oscillation phenomenon and offer new designs for future self-propelling micro-robots.
Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP
Authors: Gowravaram Manjeera , Schwarz Juliane , Khilji Sana K. , Urlaub Henning , Chakrabarti Sutapa 
Published: November 2019

AbstractThe mammalian Staufen proteins (Stau1 and Stau2) mediate degradation of mRNA containing complex secondary structures in their 3’-untranslated region (UTR) through a pathway known as Staufen-mediated mRNA decay (SMD). This pathway also involves the RNA helicase UPF1, which is best known for its role in the nonsense-mediated mRNA decay (NMD) pathway. Here we present a biochemical reconstitution of the recruitment and activation of UPF1 in context of the SMD pathway. We demonstrate the involvement of UPF2, a core NMD factor and a known activator of UPF1, in SMD. UPF2 acts as an adaptor between Stau1 and UPF1, stimulates the catalytic activity of UPF1 and plays a central role in the formation of an SMD-competent mRNP. Our study elucidates the molecular mechanisms of SMD and points towards extensive cross-talk between UPF1-mediated mRNA decay pathways in cells.
Isotopic composition of oceanic dissolved black carbon reveals non-riverine source
Authors: Wagner Sasha , Brandes Jay , Spencer Robert G. M. , Ma Kun , Rosengard Sarah Z. , Moura Jose Mauro S. , Stubbins Aron 
Published: November 2019

AbstractA portion of the charcoal and soot produced during combustion processes on land (e.g., wildfire, burning of fossil fuels) enters aquatic systems as dissolved black carbon (DBC). In terms of mass flux, rivers are the main identified source of DBC to the oceans. Since DBC is believed to be representative of the refractory carbon pool, constraining sources of marine DBC is key to understanding the long-term persistence of carbon in our global oceans. Here, we use compound-specific stable carbon isotopes (δ13C) to reveal that DBC in the oceans is ~6‰ enriched in 13C compared to DBC exported by major rivers. This isotopic discrepancy indicates most riverine DBC is sequestered and/or rapidly degraded before it reaches the open ocean. Thus, we suggest that oceanic DBC does not predominantly originate from rivers and instead may be derived from another source with an isotopic signature similar to that of marine phytoplankton.
A simulated Northern Hemisphere terrestrial climate dataset for the past 60,000 years
Authors: Armstrong Edward , Hopcroft Peter O. , Valdes Paul J. 
Published: November 2019

AbstractWe present a continuous land-based climate reconstruction dataset extending back 60 kyr from 0 BP (1950) at 0.5° resolution on a monthly timestep for 0°N to 90°N. It has been generated from 42 discrete snapshot simulations using the HadCM3B-M2.1 coupled general circulation model. We incorporate Dansgaard-Oeschger (DO) and Heinrich events to represent millennial scale variability, based on a temperature reconstruction from Greenland ice-cores, with a spatial fingerprint based on a freshwater hosing simulation with HadCM3B-M2.1. Interannual variability is also added and derived from the initial snapshot simulations. Model output has been downscaled to 0.5° resolution (using simple bilinear interpolation) and bias corrected. Here we present surface air temperature, precipitation, incoming shortwave energy, minimum monthly temperature, snow depth, wind chill and number of rainy days per month. This is one of the first open access climate datasets of this kind and can be used to study the impact of millennial to orbital-scale climate change on terrestrial greenhouse gas cycling, northern extra-tropical vegetation, and megaflora and megafauna population dynamics.
MicroRNA-495 downregulates AQP1 and facilitates proliferation and differentiation of osteoblasts in mice with tibial fracture through activation of p38 MAPK signaling pathway
Authors: Zhu Lei , Lin Zun-Wen , Wang Gang , Zhang Hong , Liu Ben , Xu Qing-Jia 
Published: November 2019

AbstractOsteoblasts are implicated in the building of the vertebrate skeleton. The current study aimed to investigate the role of microRNA-495 (miR-495) in the osteoblasts of mice with tibial fractures and the underlying mechanism involving in aquaporin-1 (AQP1) and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Initially, a microarray-based analysis was performed to screen the differentially expressed genes and miRNAs associated with tibial fracture. Following the establishment of a tibial fracture mouse model, the positive rate of the AQP1 protein in the fracture tissue was detected by immunohistochemistry (IHC). Next, to verify the binding site between miR-495 on AQP1, bioinformatics data were employed in addition to the application of a dual-luciferase reporter gene assay. The osteoblast cell line MC3T3-E1 was treated with miR-495 mimic, miR-495 inhibitor and Anisomycin to explore the potent effects of miR-495 on proliferation and differentiation of osteoblasts in mice with tibial fracture. The expression of miR-495, AQP1, p38 MAPK, PCNA, Cyclin D1, OCN, and OPN was subsequently evaluated by RT-qPCR and Western blot analysis. Cell viability, the number of calcium nodules and alkaline phosphatase (ALP) activity were detected by MTT assay, alizarin red staining, and ALP activity assay, respectively. Our results revealed that miR-495 was down-regulated while AQP1 was up-regulated in the mice with tibial fractures. AQP1 was verified as a target gene of miR-495. When the cells were treated with overexpressed miR-495 or activated p38 MAPK signaling pathway, elevated expression of PCNA, Cyclin, D1, OCN, and OPN along with an increased amount of calcium nodules, higher cell viability, and enhanced ALP activity was detected, while the expression of AQP1 was reduced. Collectively, the key findings of the present study support the notion that overexpressed miR-495 may activate the p38 MAPK signaling pathway to inhibit AQP1 and to promote the proliferation and differentiation of osteoblasts in mice with tibial fracture.
Bone Anabolic Response in the Calvaria Following Mild Traumatic Brain Injury is Mediated by the Cannabinoid-1 Receptor
Authors: Eger Michal , Bader Miaad , Bree Dara , Hadar Rivka , Nemirovski Alina , Tam Joseph , Levy Dan , Pick Chaim G. , Gabet Yankel 
Published: November 2019

AbstractBrain trauma was clinically associated with increased osteogenesis in the appendicular skeleton. We showed previously in C57BL/6J mice that mild traumatic brain injury (mTBI) transiently induced bone formation in the femur via the cannabinoid-1 (CB1) receptor. Here, we subjected ICR mice to mTBI and examined the bone response in the skull using microCT. We also measured mast cell degranulation (MCD)72 h post-injury. Finally, we measured brain and calvarial endocannabinoids levels post-mTBI. mTBI led to decreased bone porosity on the contralateral (untouched) side. This effect was apparent both in young and mature mice. Administration of rimonabant (CB1 inverse agonist) completely abrogated the effect of mTBI on calvarial porosity and significantly reduced MCD, compared with vehicle-treated controls. We also found that mTBI resulted in elevated levels of anandamide, but not 2-arachidonoylglycerol, in the contralateral calvarial bone, whereas brain levels remained unchanged. In C57BL/6J CB1 knockout mice, mTBI did not reduce porosity but in general the porosity was significantly lower than in WT controls. Our findings suggest that mTBI induces a strain-specific CB1-dependent bone anabolic response in the skull, probably mediated by anandamide, but seemingly unrelated to inflammation. The endocannabinoid system is therefore a plausible target in management of bone response following head trauma.
Comparison of upper sublethal and lethal temperatures in three species of rice planthoppers
Authors: Ali Shahbaz , Li Pei , Ali Asad , Hou Maolin 
Published: November 2019

AbstractTemperature is an important environmental factor for ectotherms’ fitness and survival. The upper sublethal and lethal temperatures were compared between adults of three closely related destructive planthopper species, the small brown planthopper (Laodelphax striatellus, SBPH), the brown planthopper (Nilaparvata lugens, BPH), and the white-backed planthopper (Sogatella furcifera, WBPH) in the absence and presence of the host plant (Oryza sativa, var. Taichong1). Values of the critical thermal maxima (CTmax) were higher in SBPH than in both BPH and WBPH and higher in BPH than in WBPH, and values of the heat coma temperatures (HCT) were higher in both BPH and SBPH than in WBPH. CTmax and HCT values were higher in the presence than in the absence of plant material. Between sexes, females generally showed higher CTmax and HCT than males. The upper lethal temperatures (ULT50) measured in the absence of plant material were not significantly different among the planthopper species. The planthoppers also exhibited different behaviors in an increasing temperature regime, with fewer insects dropping-off from the plant in SBPH than in BPH and WBPH. These results indicate that SBPH and BPH are more heat tolerant than WBPH. The findings highlight the biological divergence in closely related planthopper species and the importance of performing the heat tolerance measurement in an ecologically relevant setting, which serves to predict seasonal and spatial occurrence patterns of the destructive planthopper species.
Rigid fusions of designed helical repeat binding proteins efficiently protect a binding surface from crystal contacts
Authors: Ernst Patrick , Honegger Annemarie , van der Valk Floor , Ewald Christina , Mittl Peer R. E. , Plückthun Andreas 
Published: November 2019

AbstractDesigned armadillo repeat proteins (dArmRPs) bind extended peptides in a modular way. The consensus version recognises alternating arginines and lysines, with one dipeptide per repeat. For generating new binding specificities, the rapid and robust analysis by crystallography is key. Yet, we have previously found that crystal contacts can strongly influence this analysis, by displacing the peptide and potentially distorting the overall geometry of the scaffold. Therefore, we now used protein design to minimise these effects and expand the previously described concept of shared helices to rigidly connect dArmRPs and designed ankyrin repeat proteins (DARPins), which serve as a crystallisation chaperone. To shield the peptide-binding surface from crystal contacts, we rigidly fused two DARPins to the N- and C-terminal repeat of the dArmRP and linked the two DARPins by a disulfide bond. In this ring-like structure, peptide binding, on the inside of the ring, is very regular and undistorted, highlighting the truly modular binding mode. Thus, protein design was utilised to construct a well crystallising scaffold that prevents interference from crystal contacts with peptide binding and maintains the equilibrium structure of the dArmRP. Rigid DARPin-dArmRPs fusions will also be useful when chimeric binding proteins with predefined geometries are required.