bluuebunny/crossref_metadata_2025_split huggingface dataset:
FGF6 and FGF9 regulate UCP1 expression independent of brown adipogenesis
Authors: Shamsi Farnaz , Xue Ruidan , Huang Tian Lian , Lundh Morten , Liu Yang , Leiria Luiz O. , Lynes Matthew D. , Kempf Elena , Wang Chih-Hao , Sugimoto Satoru , Nigro Pasquale , Landgraf Kathrin , Schulz Tim , Li Yiming , Emanuelli Brice , Kothakota Srinivas , Williams Lewis T. , Jessen Niels , Pedersen Steen Bønløkke , Böttcher Yvonne , Blüher Matthias , Körner Antje , Goodyear Laurie J. , Mohammadi Moosa , Kahn C. Ronald , Tseng Yu-Hua 
Published: March 2020

AbstractUncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue (BAT). Using high-throughput library screening of secreted peptides, we identify two fibroblast growth factors (FGF), FGF6 and FGF9, as potent inducers of UCP1 expression in adipocytes and preadipocytes. Surprisingly, this occurs through a mechanism independent of adipogenesis and involves FGF receptor-3 (FGFR3), prostaglandin-E2 and interaction between estrogen receptor-related alpha, flightless-1 (FLII) and leucine-rich-repeat-(in FLII)-interacting-protein-1 as a regulatory complex for UCP1 transcription. Physiologically, FGF6/9 expression in adipose is upregulated by exercise and cold in mice, and FGF9/FGFR3 expression in human neck fat is significantly associated with UCP1 expression. Loss of FGF9 impairs BAT thermogenesis. In vivo administration of FGF9 increases UCP1 expression and thermogenic capacity. Thus, FGF6 and FGF9 are adipokines that can regulate UCP1 through a transcriptional network that is dissociated from brown adipogenesis, and act to modulate systemic energy metabolism.
A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
Authors: Kodama Manabu , Oshikawa Kiyotaka , Shimizu Hideyuki , Yoshioka Susumu , Takahashi Masatomo , Izumi Yoshihiro , Bamba Takeshi , Tateishi Chisa , Tomonaga Takeshi , Matsumoto Masaki , Nakayama Keiichi I. 
Published: March 2020

AbstractGlucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malignant progression of cancer. The fate of glutamine nitrogen is shifted from the anaplerotic pathway into the TCA cycle to nucleotide biosynthesis, with this shift being controlled by glutaminase (GLS1) and phosphoribosyl pyrophosphate amidotransferase (PPAT). Interventions to reduce the PPAT/GLS1 ratio suppresses tumor growth of many types of cancer. A meta-analysis reveals that PPAT shows the strongest correlation with malignancy among all metabolic enzymes, in particular in neuroendocrine cancer including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. A shift in glutamine fate may thus be required for malignant progression of cancer, with modulation of nitrogen metabolism being a potential approach to SCLC treatment.
Quantifying contributions of chlorofluorocarbon banks to emissions and impacts on the ozone layer and climate
Authors: Lickley Megan , Solomon Susan , Fletcher Sarah , Velders Guus J. M. , Daniel John , Rigby Matthew , Montzka Stephen A. , Kuijpers Lambert J. M. , Stone Kane 
Published: March 2020

AbstractChlorofluorocarbon (CFC) banks from uses such as air conditioners or foams can be emitted after global production stops. Recent reports of unexpected emissions of CFC-11 raise the need to better quantify releases from these banks, and associated impacts on ozone depletion and climate change. Here we develop a Bayesian probabilistic model for CFC-11, 12, and 113 banks and their emissions, incorporating the broadest range of constraints to date. We find that bank sizes of CFC-11 and CFC-12 are larger than recent international scientific assessments suggested, and can account for much of current estimated CFC-11 and 12 emissions (with the exception of increased CFC-11 emissions after 2012). Left unrecovered, these CFC banks could delay Antarctic ozone hole recovery by about six years and contribute 9 billion metric tonnes of equivalent CO2 emission. Derived CFC-113 emissions are subject to uncertainty, but are much larger than expected, raising questions about its sources.
Gating mechanism of hyperpolarization-activated HCN pacemaker channels
Authors: Ramentol Rosamary , Perez Marta E. , Larsson H. Peter 
Published: March 2020

AbstractHyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential for rhythmic activity in the heart and brain, and mutations in HCN channels are linked to heart arrhythmia and epilepsy. HCN channels belong to the family of voltage-gated K+ (Kv) channels. However, why HCN channels are activated by hyperpolarization whereas Kv channels are activated by depolarization is not clear. Here we reverse the voltage dependence of HCN channels by mutating only two residues located at the interface between the voltage sensor and the pore domain such that the channels now open upon depolarization instead of hyperpolarization. Our data indicate that what determines whether HCN channels open by hyperpolarizations or depolarizations are small differences in the energies of the closed and open states, due to different interactions between the voltage sensor and the pore in the different channels.
Structural insights into sequence-dependent Holliday junction resolution by the chloroplast resolvase MOC1
Authors: Yan Junjie , Hong Sixing , Guan Zeyuan , He Wenjing , Zhang Delin , Yin Ping 
Published: March 2020

AbstractHolliday junctions (HJs) are key DNA intermediates in genetic recombination and are eliminated by nuclease, termed resolvase, to ensure genome stability. HJ resolvases have been identified across all kingdoms of life, members of which exhibit sequence-dependent HJ resolution. However, the molecular basis of sequence selectivity remains largely unknown. Here, we present the chloroplast resolvase MOC1, which cleaves HJ in a cytosine-dependent manner. We determine the crystal structure of MOC1 with and without HJs. MOC1 exhibits an RNase H fold, belonging to the retroviral integrase family. MOC1 functions as a dimer, and the HJ is embedded into the basic cleft of the dimeric enzyme. We characterize a base recognition loop (BR loop) that protrudes into and opens the junction. Residues from the BR loop intercalate into the bases, disrupt the C-G base pairing at the crossover and recognize the cytosine, providing the molecular basis for sequence-dependent HJ resolution by a resolvase.
Genome-wide transcriptome profile of rice hybrids with and without Oryza rufipogon introgression reveals candidate genes for yield
Authors: Guttikonda Haritha , Thummala Shashi Rekha , Agarwal Surekha , Mangrauthia Satendra K , Ramanan Rajeshwari , Neelamraju Sarla 
Published: March 2020

AbstractIn this study, we compared genome-wide transcriptome profile of two rice hybrids, one with (test hybrid IR79156A/IL50-13) and the other without (control hybrid IR79156A/KMR3) O. rufipogon introgressions to identify candidate genes related to grain yield in the test hybrid. IL50-13 (Chinsurah Nona2 IET21943) the male parent (restorer) used in the test hybrid, is an elite BC4F8 introgression line of KMR3 with O. rufipogon introgressions. We identified 2798 differentially expressed genes (DEGs) in flag leaf and 3706 DEGs in panicle. Overall, 78 DEGs were within the major yield QTL qyld2.1 and 25 within minor QTL qyld8.2. The DEGs were significantly (p < 0.05) enriched in starch synthesis, phenyl propanoid pathway, ubiquitin degradation and phytohormone related pathways in test hybrid compared to control hybrid. Sequence analysis of 136 DEGs from KMR3 and IL50-13 revealed 19 DEGs with SNP/InDel variations. Of the 19 DEGs only 6 showed both SNP and InDel variations in exon regions. Of these, two DEGs within qyld2.1, Phenylalanine ammonia- lyase (PAL) (Os02t0626400-01, OsPAL2) showed 184 SNPs and 11 InDel variations and Similar to phenylalanine ammonia- lyase (Os02t0627100-01, OsPAL4) showed 205 SNPs and 13 InDel variations. Both PAL genes within qyld2.1 and derived from O. rufipogon are high priority candidate genes for increasing grain yield in rice.
Protection of Permafrost Soils from Thawing by Increasing Herbivore Density
Authors: Beer Christian , Zimov Nikita , Olofsson Johan , Porada Philipp , Zimov Sergey 
Published: March 2020

AbstractClimate change will cause a substantial future greenhouse gas release from warming and thawing permafrost-affected soils to the atmosphere enabling a positive feedback mechanism. Increasing the population density of big herbivores in northern high-latitude ecosystems will increase snow density and hence decrease the insulation strength of snow during winter. As a consequence, theoretically 80% of current permafrost-affected soils (<10 m) is projected to remain until 2100 even when assuming a strong warming using the Representative Concentration Pathway 8.5. Importantly, permafrost temperature is estimated to remain below −4 °C on average after increasing herbivore population density. Such ecosystem management practices would be therefore theoretically an important additional climate change mitigation strategy. Our results also highlight the importance of new field experiments and observations, and the integration of fauna dynamics into complex Earth System models, in order to reliably project future ecosystem functions and climate.
Longitudinal imaging of T cell-based immunotherapy with multi-spectral, multi-scale optoacoustic tomography
Authors: Kimm Melanie A. , Tzoumas Stratis , Glasl Sarah , Omar Murad , Symvoulidis Panagiotis , Olefir Ivan , Rummeny Ernst J. , Meier Reinhard , Ntziachristos Vasilis 
Published: March 2020

AbstractMost imaging studies of immunotherapy have focused on tracking labeled T cell biodistribution in vivo for understanding trafficking and homing parameters and predicting therapeutic efficacy by the presence of transferred T cells at or in the tumour mass. Conversely, we investigate here a novel concept for longitudinally elucidating anatomical and pathophysiological changes of solid tumours after adoptive T cell transfer in a preclinical set up, using previously unexplored in-tandem macroscopic and mesoscopic optoacoustic (photoacoustic) imaging. We show non-invasive in vivo observations of vessel collapse during tumour rejection across entire tumours and observe for the first time longitudinal tumour rejection in a label-free manner based on optical absorption changes in the tumour mass due to cellular decline. We complement these observations with high resolution episcopic fluorescence imaging of T cell biodistribution using optimized T cell labeling based on two near-infrared dyes targeting the cell membrane and the cytoplasm. We discuss how optoacoustic macroscopy and mesoscopy offer unique contrast and immunotherapy insights, allowing label-free and longitudinal observations of tumour therapy. The results demonstrate optoacoustic imaging as an invaluable tool in understanding and optimizing T cell therapy.
Dynamics for a fractional-order predator-prey model with group defense
Authors: Tang Bingnan 
Published: March 2020

AbstractIn the present article, a new fractional order predator-prey model with group defense is put up. The dynamical properties such as the existence, uniqueness and boundness of solution, the stability of equilibrium point and the existence of Hopf bifurcation of the involved predator-prey model have been discussed. Firstly, we establish the sufficient conditions that guarantee the existence, uniqueness and boundness of solution by applying Lipschitz condition, inequality technique and fractional order differential equation theory. Secondly, we analyze the existence of various equilibrium points by basic mathematical analysis method and obtain some sufficient criteria which guarantee the locally asymptotically stability of various equilibrium points of the involved predator-prey model with the aid of linearization approach. Thirdly, the existence of Hopf bifurcation of the considered predator-prey model is investigated by using the Hopf bifurcation theory of fractional order differential equations. Finally, simulation results are presented to substantiate the theoretical findings.
Bacterial analysis in the early developmental stages of the black tiger shrimp (Penaeus monodon)
Authors: Angthong Pacharaporn , Uengwetwanit Tanaporn , Arayamethakorn Sopacha , Chaitongsakul Panomkorn , Karoonuthaisiri Nitsara , Rungrassamee Wanilada 
Published: March 2020

AbstractMicrobial colonization is an essential process in the early life of animal hosts—a crucial phase that could help influence and determine their health status at the later stages. The establishment of bacterial community in a host has been comprehensively studied in many animal models; however, knowledge on bacterial community associated with the early life stages of Penaeus monodon (the black tiger shrimp) is still limited. Here, we examined the bacterial community structures in four life stages (nauplius, zoea, mysis and postlarva) of two black tiger shrimp families using 16S rRNA amplicon sequencing by a next-generation sequencing. Although the bacterial profiles exhibited different patterns in each developmental stage, Bacteroidetes, Proteobacteria, Actinobacteria and Planctomycetes were identified as common bacterial phyla associated with shrimp. Interestingly, the bacterial diversity became relatively stable once shrimp developed to postlarvae (5-day-old and 15-day-old postlarval stages), suggesting an establishment of the bacterial community in matured shrimp. To our knowledge, this is the first report on bacteria establishment and assembly in early developmental stages of P. monodon. Our findings showed that the bacterial compositions could be shaped by different host developmental stages where the interplay of various host-associated factors, such as physiology, immune status and required diets, could have a strong influence.
Visual liver assessment using Gd-EOB-DTPA–enhanced magnetic resonance imaging of patients in the early post-Fontan period
Authors: Nakajima Kimiko , Seki Mitsuru , Hatakeyama Shinitsu , Arai Shuhei , Asami Yuji , Tanaka Kensuke , Ikeda Kentaro , Shimoyama Shinya , Kobayashi Tomio , Miyamoto Takashi , Okada Yasunori , Arakawa Hirokazu , Takizawa Takumi 
Published: March 2020

AbstractNo imaging modality can be used to evaluate Fontan-associated liver disease (FALD). We retrospectively reviewed hepatic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) characteristics of patients within 1 year post-Fontan procedure, and we evaluated the association between hepatic imaging abnormalities and clinical parameters, including follow-up cardiac catheterization and laboratory test findings. The EOB-MR images were graded, based on the extent of the decreased enhancement, as “normal” (Grade 1), “segmental” (Grade 2), “regional” (Grade 3), and “diffuse” (Grade 4). We enrolled 37 patients (mean age, 3.5 ± 1.0 years): 9 patients had Grade 1 or 2; 14 patients, Grade 3; and 14 patients, Grade 4. EOB-MRI revealed characteristic reticular or mosaic patterns of diminished enhancement (i.e. “frog spawn” appearance). Ultrasonography did not detect diminished enhancement or “frog spawn” appearance. A trend existed toward increased grade severity in imaging with increased central venous pressure, pulmonary vascular resistance, and gamma-glutamyltransferase levels. Noninvasive EOB-MRI revealed the characteristic pattern of diminished enhancement, which was correlated with certain clinical parameters indicative of Fontan physiology and liver dysfunction. Early-stage FALD may occur soon after the Fontan procedure and is associated with increased pressure in the inferior vena cava and hepatic veins.
Root transcriptome profiling of contrasting wheat genotypes provides an insight to their adaptive strategies to water deficit
Authors: Mia Md. Sultan , Liu Hui , Wang Xingyi , Zhang Chi , Yan Guijun 
Published: March 2020

AbstractWater deficit limits plant growth and productivity in wheat. The effect of water deficit varies considerably in the contrasting genotypes. This study attempted comparative transcriptome profiling of the tolerant (Abura) and susceptible (AUS12671) genotypes under PEG-simulated water stress via genome-wide RNA-seq technology to understand the dynamics of tolerance mechanism. Morphological and physiological analyses indicated that the tolerant genotype Abura had a higher root growth and net photosynthesis, which accounted for its higher root biomass than AUS12671 under stress. Transcriptomic analysis revealed a total of 924 differentially expressed genes (DEGs) that were unique in the contrasting genotypes under stress across time points. The susceptible genotype AUS12671 had slightly more abundant DEGs (505) than the tolerant genotype Abura (419). Gene ontology enrichment and pathway analyses of these DEGs suggested that the two genotypes differed significantly in terms of adaptive mechanism. Predominant upregulation of genes involved in various metabolic pathways was the key adaptive feature of the susceptive genotype AUS12671 indicating its energy-consuming approach in adaptation to water deficit. In contrast, downregulation the expression of genes of key pathways, such as global and overview maps, carbohydrate metabolism, and genetic information processing was the main strategy for the tolerant genotype Abura. Besides, significantly higher number of genes encoding transcription factors (TF) families like MYB and NAC, which were reported to be associated with stress defense, were differentially expressed in the tolerant genotype Abura. Gene encoding transcription factors TIFY were only differentially expressed between stressed and non-stressed conditions in the sensitive genotype. The identified DEGs and the suggested differential adaptive strategies of the contrasting genotypes provided an insight for improving water deficit tolerance in wheat.
The expression level of alpha-synuclein in different neuronal populations is the primary determinant of its prion-like seeding
Authors: Courte Josquin , Bousset Luc , Boxberg Ysander Von , Villard Catherine , Melki Ronald , Peyrin Jean-Michel 
Published: March 2020

AbstractAlpha-synuclein (aSyn)-rich aggregates propagate in neuronal networks and compromise cellular homeostasis leading to synucleinopathies such as Parkinson’s disease. Aggregated aSyn spread follows a conserved spatio-temporal pattern that is not solely dependent on connectivity. Hence, the differential tropism of aSyn-rich aggregates to distinct brain regions, or their ability to amplify within those regions, must contribute to this process. To better understand what underlies aSyn-rich aggregates distribution within the brain, we generated primary neuronal cultures from various brain regions of wild-type mice and mice expressing a reduced level of aSyn, and exposed them to fibrillar aSyn. We then assessed exogenous fibrillar aSyn uptake, endogenous aSyn seeding, and endogenous aSyn physiological expression levels. Despite a similar uptake of exogenous fibrils by neuronal cells from distinct brain regions, the seeded aggregation of endogenous aSyn differed greatly from one neuronal population to another. The different susceptibility of neuronal populations was linked to their aSyn expression level. Our data establish that endogenous aSyn expression level plays a key role in fibrillar aSyn prion-like seeding, supporting that endogenous aSyn expression level participates in selective regional brain vulnerability.
Horizontal and vertical movements of humpback whales inform the use of critical pelagic habitats in the western South Pacific
Authors: Derville Solène , Torres Leigh G. , Zerbini Alexandre N. , Oremus Marc , Garrigue Claire 
Published: March 2020

AbstractHumpback whales (Megaptera novaeangliae) are known for their nearshore distribution during the breeding season, but their pelagic habitat use patterns remain mostly unexplored. From 2016 to 2018, 18 humpback whales were equipped with depth-recording satellite tags (SPLASH10) to shed light on environmental and social drivers of seamount association around New Caledonia in the western South Pacific. Movement paths were spatially structured around shallow seamounts (<200 m). Indeed, two males stopped over the Lord Howe seamount chain during the first-ever recorded longitudinal transit between New Caledonia and the east coast of Australia. Residence time significantly increased with proximity to shallow seamounts, while dive depth increased in the vicinity of seafloor ridges. Most of the 7,986 recorded dives occurred above 80 m (88.5%), but deep dives (>80 m, max 616 m) were also recorded (11.5%), including by maternal females. Deep dives often occurred in series and were characterized by U-shapes suggesting high energy expenditure. This study provides new insights into the formerly overlooked use of pelagic habitats by humpback whales during the breeding season. Given increasing anthropogenic threats on deep sea habitats worldwide, this work has implications for the conservation of vulnerable marine ecosystems.
Slco2a1 deficiency exacerbates experimental colitis via inflammasome activation in macrophages: a possible mechanism of chronic enteropathy associated with SLCO2A1 gene
Authors: Nakata Rieko , Nakamura Yoshinobu , Hosomi Shuhei , Okuda Hiroaki , Nishida Yu , Sugita Naoko , Itani Shigehiro , Nadatani Yuji , Otani Koji , Tanaka Fumio , Kamata Noriko , Taira Koichi , Nagami Yasuaki , Tanigawa Tetsuya , Watanabe Toshio , Yamagami Hirokazu , Nakanishi Takeo , Fujiwara Yasuhiro 
Published: March 2020

AbstractLoss-of-function mutations in the solute carrier organic anion transporter family, member 2a1 gene (SLCO2A1), which encodes a prostaglandin (PG) transporter, have been identified as causes of chronic nonspecific multiple ulcers in the small intestine; however, the underlying mechanisms have not been revealed. We, therefore, evaluated the effects of systemic knockout of Slco2a1 (Slco2a1−/−) and conditional knockout in intestinal epithelial cells (Slco2a1ΔIEC) and macrophages (Slco2a1ΔMP) in mice with dextran sodium sulphate (DSS)-induced acute colitis. Slco2a−/− mice were more susceptible to DSS-induced colitis than wild-type (WT) mice, but did not spontaneously develop enteritis or colitis. The nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3) inflammasome was more strongly upregulated in colon tissues of Slco2a−/− mice administered DSS and in macrophages isolated from Slco2a1−/− mice than in the WT counterparts. Slco2a1ΔMP, but not Slco2a1ΔIEC mice, were more susceptible to DSS-induced colitis than WT mice, partly phenocopying Slco2a−/− mice. Concentrations of PGE2 in colon tissues and macrophages from Slco2a1−/− mice were significantly higher than those of WT mice. Blockade of inflammasome activation suppressed the exacerbation of colitis. These results indicated that Slco2a1-deficiency increases the PGE2 concentration, resulting in NLRP3 inflammasome activation in macrophages, thus exacerbating intestinal inflammation.