bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkenone Paleothermometry in Coastal Settings: Evaluating the Potential for Highly Resolved Time Series of Sea Surface Temperature
Authors: Salacup J. M. , Farmer J. R. , Herbert T. D. , Prell W. L. 
Published: January 2019

AbstractThe unsaturation ratios of alkenones have been applied widely to reconstruct pelagic sea surface temperatures (SSTs). However, applications to costal settings have been hampered by the effects of salinity and nutrient dynamics. Here we present a 4.5‐year‐long record of alkenones in water column particulate organic matter from sites in Narragansett Bay (RI, USA) spanning wide ranges in salinity and nutrients, and a 300‐year alkenone record from two Narragansett Bay sediment cores. Particulate organic matter results suggest that there are two distinct alkenone producing populations. One is a widespread population that blooms in summer (July–September) and displays alkenones typical of Group III producers—the basis for the widely applied marine Uk’37 temperature index. The other population is confined to brackish waters in the Providence River during spring salinity minima and displays alkenone profiles consistent with Group I production—the first detection of Group I in a brackish nonlacustrine environment. The sedimentary alkenone profiles consist of only Group III alkenone distributions, allowing for the reconstruction of a 300‐year‐long record of Narragansett Bay SST. Comparison of the most recent 100 years of this reconstruction with local and regional instrumental SST records shows excellent agreement, confirming a regional pattern of SST rise in the coastal northeastern United States that exceeds global or hemispheric rates. Group III alkenone production in coastal settings may be common and may open the way to high resolution local and regional SST reconstruction.
“Plasmonics” in free space: observation of giant wavevectors, vortices, and energy backflow in superoscillatory optical fields
Authors: Yuan Guanghui , Rogers Edward T. F. , Zheludev Nikolay I. 
Published: January 2019

AbstractEvanescent light can be localized at the nanoscale by resonant absorption in a plasmonic nanoparticle or taper or by transmission through a nanohole. However, a conventional lens cannot focus free-space light beyond half of the wavelength λ. Nevertheless, precisely tailored interference of multiple waves can form a hotspot in free space of an arbitrarily small size, which is known as superoscillation. Here, we report a new type of integrated metasurface interferometry that allows for the first time mapping of fields with a deep subwavelength resolution ~λ/100. The findings reveal that an electromagnetic field near the superoscillatory hotspot has many features similar to those found near resonant plasmonic nanoparticles or nanoholes: the hotspots are surrounded by nanoscale phase singularities and zones where the phase of the superoscillatory field changes more than tenfold faster than a free-propagating plane wave. Areas with high local wavevectors are pinned to phase vortices and zones of energy backflow (~λ/20 in size) that contribute to tightening of the main focal spot size beyond the Abbe–Rayleigh limit. Our observations reveal some analogy between plasmonic nanofocusing of evanescent waves and superoscillatory nanofocusing of free-space waves and prove the fundamental link between superoscillations and superfocusing, offering new opportunities for nanoscale metrology and imaging.
The CSN3 subunit of the COP9 signalosome interacts with the HD region of Sos1 regulating stability of this GEF protein
Authors: Zarich Natasha , Anta Begoña , Fernández-Medarde Alberto , Ballester Alicia , de Lucas María Pilar , Cámara Ana Belén , Anta Berta , Oliva José Luís , Rojas-Cabañeros José M. , Santos Eugenio 
Published: January 2019

AbstractSos1 is an universal, widely expressed Ras guanine nucleotide-exchange factor (RasGEF) in eukaryotic cells. Its N-terminal HD motif is known to be involved in allosteric regulation of Sos1 GEF activity through intramolecular interaction with the neighboring PH domain. Here, we searched for other cellular proteins also able to interact productively with the Sos1 HD domain. Using a yeast two-hybrid system, we identified the interaction between the Sos1 HD region and CSN3, the third component of the COP9 signalosome, a conserved, multi-subunit protein complex that functions in the ubiquitin–proteasome pathway to control degradation of many cellular proteins. The interaction of CSN3 with the HD of Sos1 was confirmed in vitro by GST pull-down assays using truncated mutants and reproduced in vivo by co-immunoprecipitation with the endogenous, full-length cellular Sos1 protein. In vitro kinase assays showed that PKD, a COP9 signalosome-associated-kinase, is able to phosphorylate Sos1. The intracellular levels of Sos1 protein were clearly diminished following CSN3 or PKD knockdown. A sizable fraction of the endogenous Sos1 protein was found ubiquitinated in different mammalian cell types. A significant reduction of RasGTP formation upon growth factor stimulation was also observed in CSN3-silenced as compared with control cells. Our data suggest that the interaction of Sos1 with the COP9 signalosome and PKD plays a significant role in maintenance of cellular Sos1 protein stability and homeostasis under physiological conditions and raises the possibility of considering the CSN/PKD complex as a potential target for design of novel therapeutic drugs.
Size differences predict niche and relative fitness differences between phytoplankton species but not their coexistence
Authors: Gallego Irene , Venail Patrick , Ibelings Bas W 
Published: January 2019

Abstract
Here we aim to incorporate trait-based information into the modern coexistence framework that comprises a balance between stabilizing (niche-based) and equalizing (fitness) mechanisms among interacting species. Taking the modern coexistence framework as our basis, we experimentally tested the effect of size differences among species on coexistence by using fifteen unique pairs of resident vs. invading cyanobacteria, resulting in thirty unique invasibility tests. The cyanobacteria covered two orders of magnitude differences in size. We found that both niche and fitness differences increased with size differences. Niche differences increased faster with size differences than relative fitness differences and whereas coexisting pairs showed larger size differences than non-coexisting pairs, ultimately species coexistence could not be predicted on basis of size differences only. Our findings suggest that size is more than a key trait controlling physiological and population-level aspects of phytoplankton, it is also relevant for community-level phenomena such as niche and fitness differences which influence coexistence and biodiversity.
An interspecies malate–pyruvate shuttle reconciles redox imbalance in an anaerobic microbial community
Authors: Wang Po-Hsiang , Correia Kevin , Ho Han-Chen , Venayak Naveen , Nemr Kayla , Flick Robert , Mahadevan Radhakrishnan , Edwards Elizabeth A 
Published: January 2019

Abstract
Microbes in ecosystems often develop coordinated metabolic interactions. Therefore, understanding metabolic interdependencies between microbes is critical to deciphering ecosystem function. In this study, we sought to deconstruct metabolic interdependencies in organohalide-respiring consortium ACT-3 containing Dehalobacter restrictus using a combination of metabolic modeling and experimental validation. D. restrictus possesses a complete set of genes for amino acid biosynthesis yet when grown in isolation requires amino acid supplementation. We reconciled this discrepancy using flux balance analysis considering cofactor availability, enzyme promiscuity, and shared protein expression patterns for several D. restrictus strains. Experimentally, 13C incorporation assays, growth assays, and metabolite analysis of D. restrictus strain PER-K23 cultures were performed to validate the model predictions. The model resolved that the amino acid dependency of D. restrictus resulted from restricted NADPH regeneration and predicted that malate supplementation would replenish intracellular NADPH. Interestingly, we observed unexpected export of pyruvate and glutamate in parallel to malate consumption in strain PER-K23 cultures. Further experimental analysis using the ACT-3 transfer cultures suggested the occurrence of an interspecies malate–pyruvate shuttle reconciling a redox imbalance, reminiscent of the mitochondrial malate shunt pathway in eukaryotic cells. Altogether, this study suggests that redox imbalance and metabolic complementarity are important driving forces for metabolite exchange in anaerobic microbial communities.
Ant colonies promote the diversity of soil microbial communities
Authors: Delgado-Baquerizo Manuel , Eldridge David J , Hamonts Kelly , Singh Brajesh K 
Published: January 2019

Abstract
Little is known about the role of ant colonies in regulating the distribution and diversity of soil microbial communities across large spatial scales. Here, we conducted a survey across &gt;1000 km in eastern Australia and found that, compared with surrounding bare soils, ant colonies promoted the richness (number of phylotypes) and relative abundance of rare taxa of fungi and bacteria. Ant nests were also an important reservoir for plant pathogens. Our study also provides a portfolio of microbial phylotypes only found in ant nests, and which are associated with high nutrient availability. Together, our work highlights the fact that ant nests are an important refugia for microbial diversity.
Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
Authors: Flores A. , Sandoval-Gonzalez S. , Takahashi R. , Krall A. , Sathe L. , Wei L. , Radu C. , Joly J. H. , Graham N. A. , Christofk H. R. , Lowry W. E. 
Published: January 2019

AbstractAlthough numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.
Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway
Authors: Singh Rajbir , Chandrashekharappa Sandeep , Bodduluri Sobha R. , Baby Becca V. , Hegde Bindu , Kotla Niranjan G. , Hiwale Ankita A. , Saiyed Taslimarif , Patel Paresh , Vijay-Kumar Matam , Langille Morgan G. I. , Douglas Gavin M. , Cheng Xi , Rouchka Eric C. , Waigel Sabine J. , Dryden Gerald W. , Alatassi Houda , Zhang Huang-Ge , Haribabu Bodduluri , Vemula Praveen K. , Jala Venkatakrishna R. 
Published: January 2019

AbstractThe importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.
Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase
Authors: Padyana Anil K. , Gross Stefan , Jin Lei , Cianchetta Giovanni , Narayanaswamy Rohini , Wang Feng , Wang Rui , Fang Cheng , Lv Xiaobing , Biller Scott A. , Dang Lenny , Mahoney Christopher E. , Nagaraja Nelamangala , Pirman David , Sui Zhihua , Popovici-Muller Janeta , Smolen Gromoslaw A. 
Published: January 2019

AbstractSqualene epoxidase (SQLE), also known as squalene monooxygenase, catalyzes the stereospecific conversion of squalene to 2,3(S)-oxidosqualene, a key step in cholesterol biosynthesis. SQLE inhibition is targeted for the treatment of hypercholesteremia, cancer, and fungal infections. However, lack of structure-function understanding has hindered further progression of its inhibitors. We have determined the first three-dimensional high-resolution crystal structures of human SQLE catalytic domain with small molecule inhibitors (2.3 Å and 2.5 Å). Comparison with its unliganded state (3.0 Å) reveals conformational rearrangements upon inhibitor binding, thus allowing deeper interpretation of known structure-activity relationships. We use the human SQLE structure to further understand the specificity of terbinafine, an approved agent targeting fungal SQLE, and to provide the structural insights into terbinafine-resistant mutants encountered in the clinic. Collectively, these findings elucidate the structural basis for the specificity of the epoxidation reaction catalyzed by SQLE and enable further rational development of next-generation inhibitors.
Single-cell microRNA-mRNA co-sequencing reveals non-genetic heterogeneity and mechanisms of microRNA regulation
Authors: Wang Nayi , Zheng Ji , Chen Zhuo , Liu Yang , Dura Burak , Kwak Minsuk , Xavier-Ferrucio Juliana , Lu Yi-Chien , Zhang Miaomiao , Roden Christine , Cheng Jijun , Krause Diane S. , Ding Ye , Fan Rong , Lu Jun 
Published: January 2019

AbstractMeasuring multiple omics profiles from the same single cell opens up the opportunity to decode molecular regulation that underlies intercellular heterogeneity in development and disease. Here, we present co-sequencing of microRNAs and mRNAs in the same single cell using a half-cell genomics approach. This method demonstrates good robustness (~95% success rate) and reproducibility (R2 = 0.93 for both microRNAs and mRNAs), yielding paired half-cell microRNA and mRNA profiles, which we can independently validate. By linking the level of microRNAs to the expression of predicted target mRNAs across 19 single cells that are phenotypically identical, we observe that the predicted targets are significantly anti-correlated with the variation of abundantly expressed microRNAs. This suggests that microRNA expression variability alone may lead to non-genetic cell-to-cell heterogeneity. Genome-scale analysis of paired microRNA-mRNA co-profiles further allows us to derive and validate regulatory relationships of cellular pathways controlling microRNA expression and intercellular variability.
Nanoparticle-enabled phase control for arc welding of unweldable aluminum alloy 7075
Authors: Sokoluk Maximilian , Cao Chezheng , Pan Shuaihang , Li Xiaochun 
Published: January 2019

AbstractLightweight materials are of paramount importance to reduce energy consumption and emissions in today’s society. For materials to qualify for widespread use in lightweight structural assembly, they must be weldable or joinable, which has been a long-standing issue for high strength aluminum alloys, such as 7075 (AA7075) due to their hot crack susceptibility during fusion welding. Here, we show that AA7075 can be safely arc welded without hot cracks by introducing nanoparticle-enabled phase control during welding. Joints welded with an AA7075 filler rod containing TiC nanoparticles not only exhibit fine globular grains and a modified secondary phase, both which intrinsically eliminate the materials hot crack susceptibility, but moreover show exceptional tensile strength in both as-welded and post-weld heat-treated conditions. This rather simple twist to the filler material of a fusion weld could be generally applied to a wide range of hot crack susceptible materials.
A novel scaffold for EGFR inhibition: Introducing N-(3-(3-phenylureido)quinoxalin-6-yl) acrylamide derivatives
Authors: do Amaral Daniel Nascimento , Lategahn Jonas , Fokoue Harold Hilarion , da Silva Eduardo Miguez Bastos , Sant’Anna Carlos Mauricio R. , Rauh Daniel , Barreiro Eliezer J. , Laufer Stefan , Lima Lidia Moreira 
Published: January 2019

AbstractClinical data acquired over the last decade on non-small cell lung cancer (NSCLC) treatment with small molecular weight Epidermal Growth Factor Receptor (EGFR) inhibitors have shown significant influence of EGFR point mutations and in-frame deletions on clinical efficacy. Identification of small molecules capable of inhibiting the clinically relevant EGFR mutant forms is desirable, and novel chemical scaffolds might provide knowledge regarding selectivity among EGFR forms and shed light on new strategies to overcome current clinical limitations. Design, synthesis, docking studies and in vitro evaluation of N-(3-(3-phenylureido)quinoxalin-6-yl) acrylamide derivatives (7a-m) against EGFR mutant forms are described. Compounds 7h and 7l were biochemically active in the nanomolar range against EGFRwt and EGFRL858R. Molecular docking and reaction enthalpy calculations have shown the influence of the combination of reversible and covalent binding modes with EGFR on the inhibitory activity. The inhibitory profile of 7h against a panel of patient-derived tumor cell lines was established, demonstrating selective growth inhibition of EGFR related cells at 10 μM among a panel of 30 cell lines derived from colon, melanoma, breast, bladder, kidney, prostate, pancreas and ovary tumors.
Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor
Authors: Balogh Andrea , Karpati Eva , Schneider Andrea E. , Hetey Szabolcs , Szilagyi Andras , Juhasz Kata , Laszlo Gloria , Hupuczi Petronella , Zavodszky Peter , Papp Zoltan , Matko Janos , Than Nandor Gabor 
Published: January 2019

AbstractThe complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover, the expression of SHBG and its internalization by potential receptors, as well as the influence of SHBG on estradiol uptake and signaling in lymphocytes has remained unexplored. Here, we found that human and mouse T cells expressed SHBG intrinsically. In addition, B lymphoid cell lines as well as both primary B and T lymphocytes bound and internalized external SHBG, and the amount of plasma membrane-bound SHBG decreased in B cells of pregnant compared to non-pregnant women. As potential mediators of this process, SHBG receptor candidates expressed by lymphocytes were identifiedin silico, including estrogen receptor (ER) alpha. Furthermore, cell surface-bound SHBG was detected in close proximity to membrane ERs while highly colocalizing with lipid rafts. The SHBG-membrane ER interaction was found functional since SHBG promoted estradiol uptake by lymphocytes and subsequently influenced Erk1/2 phosphorylation. In conclusion, the SHBG-SHBG receptor-membrane ER complex participates in the rapid estradiol signaling in lymphocytes, and this pathway may be altered in B cells in pregnant women.
Frequency of everyday pro-environmental behaviour is explained by baseline activation in lateral prefrontal cortex
Authors: Baumgartner Thomas , Langenbach Benedikt P. , Gianotti Lorena R. R. , Müri René M. , Knoch Daria 
Published: January 2019

AbstractHumankind faces a plethora of environmental problems, many of which are directly influenced by individual human behaviour. To better understand pro-environmental behaviour, we here try to identify interindividual markers that explain variance in the frequency of every-day pro-environmental behaviour. So far, research on this topic has mainly relied on subjective self-report measures and has yielded mixed results. In this study, we applied a neural trait approach to assess stable, objective individual differences. Using source-localised electroencephalography, we measured cortical activation at rest and combined our neural task-independent data with an ecologically valid assessment of everyday pro-environmental behaviour. We find whole-brain-corrected evidence that task-independent baseline activation in the right lateral prefrontal cortex, a brain area known to be involved in cognitive control and self-control processes, explains individual differences in pro-environmental behaviour. The higher the cortical baseline activation in this area, the higher the frequency of everyday pro-environmental behaviour. Implications for the promotion of pro-environmental behaviour are discussed.
Cell force-mediated matrix reorganization underlies multicellular network assembly
Authors: Davidson Christopher D. , Wang William Y. , Zaimi Ina , Jayco Danica Kristen P. , Baker Brendon M. 
Published: January 2019

AbstractVasculogenesis is the de novo formation of a vascular network from individual endothelial progenitor cells occurring during embryonic development, organogenesis, and adult neovascularization. Vasculogenesis can be mimicked and studied in vitro using network formation assays, in which endothelial cells (ECs) spontaneously form capillary-like structures when seeded in the appropriate microenvironment. While the biochemical regulators of network formation have been well studied using these assays, the role of mechanical and topographical properties of the extracellular matrix (ECM) is less understood. Here, we utilized both natural and synthetic fibrous materials to better understand how physical attributes of the ECM influence the assembly of EC networks. Our results reveal that active cell-mediated matrix recruitment through actomyosin force generation occurs concurrently with network formation on Matrigel, a reconstituted basement membrane matrix regularly used to promote EC networks, and on synthetic matrices composed of electrospun dextran methacrylate (DexMA) fibers. Furthermore, modulating physical attributes of DexMA matrices that impair matrix recruitment consequently inhibited the formation of cellular networks. These results suggest an iterative process in which dynamic cell-induced changes to the physical microenvironment reciprocally modulate cell behavior to guide the formation and stabilization of multicellular networks.