bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care
Authors: Tarocco Anna , Caroccia Natascia , Morciano Giampaolo , Wieckowski Mariusz R. , Ancora Gina , Garani Giampaolo , Pinton Paolo 
Published: April 2019

AbstractMelatonin, more commonly known as the sleep hormone, is mainly secreted by the pineal gland in dark conditions and regulates the circadian rhythm of the organism. Its intrinsic properties, including high cell permeability, the ability to easily cross both the blood–brain and placenta barriers, and its role as an endogenous reservoir of free radical scavengers (with indirect extra activities), confer it beneficial uses as an adjuvant in the biomedical field. Melatonin can exert its effects by acting through specific cellular receptors on the plasma membrane, similar to other hormones, or through receptor-independent mechanisms that involve complex molecular cross talk with other players. There is increasing evidence regarding the extraordinary beneficial effects of melatonin, also via exogenous administration. Here, we summarize molecular pathways in which melatonin is considered a master regulator, with attention to cell death and inflammation mechanisms from basic, translational and clinical points of view in the context of newborn care.
Breast cancer quantitative proteome and proteogenomic landscape
Authors: Johansson Henrik J. , Socciarelli Fabio , Vacanti Nathaniel M. , Haugen Mads H. , Zhu Yafeng , Siavelis Ioannis , Fernandez-Woodbridge Alejandro , Aure Miriam R. , Sennblad Bengt , Vesterlund Mattias , Branca Rui M. , Orre Lukas M. , Huss Mikael , Fredlund Erik , Beraki Elsa , Garred Øystein , Boekel Jorrit , Sauer Torill , Zhao Wei , Nord Silje , Höglander Elen K. , Jans Daniel C. , Brismar Hjalmar , Haukaas Tonje H. , Bathen Tone F. , Schlichting Ellen , Naume Bjørn ,   Consortia Oslo Breast Cancer Research Consortium (OSBREAC), Geisler Jürgen , Hofvind Solveig , Engebråten Olav , Geitvik Gry Aarum , Langerød Anita , Kåresen Rolf , Mælandsmo Gunhild Mari , Sørlie Therese , Skjerven Helle Kristine , Park Daehoon , Hartman-Johnsen Olaf-Johan , Luders Torben , Borgen Elin , Kristensen Vessela N. , Russnes Hege G. , Lingjærde Ole Christian , Mills Gordon B. , Sahlberg Kristine K. , Børresen-Dale Anne-Lise , Lehtiö Janne 
Published: April 2019

AbstractIn the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis
Authors: Zou Yilong , Palte Michael J. , Deik Amy A. , Li Haoxin , Eaton John K. , Wang Wenyu , Tseng Yuen-Yi , Deasy Rebecca , Kost-Alimova Maria , Dančík Vlado , Leshchiner Elizaveta S. , Viswanathan Vasanthi S. , Signoretti Sabina , Choueiri Toni K. , Boehm Jesse S. , Wagner Bridget K. , Doench John G. , Clish Clary B. , Clemons Paul A. , Schreiber Stuart L. 
Published: April 2019

AbstractClear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers.
Nucleobase pairing and photodimerization in a biologically derived metal-organic framework nanoreactor
Authors: Anderson Samantha L. , Boyd Peter G. , Gładysiak Andrzej , Nguyen Tu N. , Palgrave Robert G. , Kubicki Dominik , Emsley Lyndon , Bradshaw Darren , Rosseinsky Matthew J. , Smit Berend , Stylianou Kyriakos C. 
Published: April 2019

AbstractBiologically derived metal-organic frameworks (bio-MOFs) are of great importance as they can be used as models for bio-mimicking and in catalysis, allowing us to gain insights into how large biological molecules function. Through rational design, here we report the synthesis of a novel bio-MOF featuring unobstructed Watson-Crick faces of adenine (Ade) pointing towards the MOF cavities. We show, through a combined experimental and computational approach, that thymine (Thy) molecules diffuse through the pores of the MOF and become base-paired with Ade. The Ade-Thy pair binding at 40–45% loading reveals that Thy molecules are packed within the channels in a way that fulfill both the Woodward-Hoffmann and Schmidt rules, and upon UV irradiation, Thy molecules dimerize into Thy<>Thy. This study highlights the utility of accessible functional groups within the pores of MOFs, and their ability to ‘lock’ molecules in specific positions that can be subsequently dimerized upon light irradiation, extending the use of MOFs as nanoreactors for the synthesis of molecules that are otherwise challenging to isolate.
Specific inhibition of splicing factor activity by decoy RNA oligonucleotides
Authors: Denichenko Polina , Mogilevsky Maxim , Cléry Antoine , Welte Thomas , Biran Jakob , Shimshon Odelia , Barnabas Georgina D. , Danan-Gotthold Miri , Kumar Saran , Yavin Eylon , Levanon Erez Y. , Allain Frédéric H. , Geiger Tamar , Levkowitz Gil , Karni Rotem 
Published: April 2019

AbstractAlternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present an approach to specifically downregulate SF activity in conditions where SFs are either up-regulated or hyperactive.
Bad-metal relaxation dynamics in a Fermi lattice gas
Authors: Xu W. , McGehee W. R. , Morong W. N. , DeMarco B. 
Published: April 2019

AbstractElectrical current in conventional metals is carried by electrons that retain their individual character. Bad metals, such as the normal state of some high-temperature superconductors, violate this scenario, and the complete picture for their behavior remains unresolved. Here, we report phenomena consistent with bad-metal behaviour in an optical-lattice Hubbard model by measuring the transport lifetime for a mass current excited by stimulated Raman transitions. We demonstrate incompatibility with weak-scattering theory and key characteristics of bad metals: anomalous resistivity scaling consistent with T-linear behavior, the onset of incoherent transport, and the approach to the Mott–Ioffe–Regel limit. Our work demonstrates a direct method for determining the transport lifetime, which is critical to theory but difficult to measure in materials, and exposes minimal ingredients for bad-metal behavior.
Contactless measurements of photocarrier transport properties in perovskite single crystals
Authors: Gong Xiwen , Huang Ziru , Sabatini Randy , Tan Chih-Shan , Bappi Golam , Walters Grant , Proppe Andrew , Saidaminov Makhsud I. , Voznyy Oleksandr , Kelley Shana O. , Sargent Edward H. 
Published: April 2019

AbstractThe remarkable properties of metal halide perovskites arising from their impressive charge carrier diffusion lengths have led to rapid advances in solution-processed optoelectronics. Unfortunately, diffusion lengths reported in perovskite single crystals have ranged widely – from 3 μm to 3 mm – for ostensibly similar materials. Here we report a contactless method to measure the carrier mobility and further extract the diffusion length: our approach avoids both the effects of contact resistance and those of high electric field. We vary the density of quenchers – epitaxially included within perovskite single crystals – and report the dependence of excited state lifetime in the perovskite on inter-quencher spacing. Our results are repeatable and self-consistent (i.e. they agree on diffusion length for many different quencher concentrations) to within ± 6%. Using this method, we obtain a diffusion length in metal-halide perovskites of 2.6 μm ± 0.1 μm.
Muscle functions as a connective tissue and source of extracellular matrix in planarians
Authors: Cote Lauren E. , Simental Eric , Reddien Peter W. 
Published: April 2019

AbstractRegeneration and tissue turnover require new cell production and positional information. Planarians are flatworms capable of regenerating all body parts using a population of stem cells called neoblasts. The positional information required for tissue patterning is primarily harbored by muscle cells, which also control body contraction. Here we produce an in silico planarian matrisome and use recent whole-animal single-cell-transcriptome data to determine that muscle is a major source of extracellular matrix (ECM). No other ECM-secreting, fibroblast-like cell type was detected. Instead, muscle cells express core ECM components, including all 19 collagen-encoding genes. Inhibition of muscle-expressed hemicentin-1 (hmcn-1), which encodes a highly conserved ECM glycoprotein, results in ectopic peripheral localization of cells, including neoblasts, outside of the muscle layer. ECM secretion and hmcn-1-dependent maintenance of tissue separation indicate that muscle functions as a planarian connective tissue, raising the possibility of broad roles for connective tissue in adult positional information.
RNA editing is abundant and correlates with task performance in a social bumblebee
Authors: Porath Hagit T. , Hazan Esther , Shpigler Hagai , Cohen Mira , Band Mark , Ben-Shahar Yehuda , Levanon Erez Y. , Eisenberg Eli , Bloch Guy 
Published: April 2019

AbstractColonies of the bumblebee Bombus terrestris are characterized by wide phenotypic variability among genetically similar full-sister workers, suggesting a major role for epigenetic processes. Here, we report a high level of ADAR-mediated RNA editing in the bumblebee, despite the lack of an ADAR1-homolog. We identify 1.15 million unique genomic sites, and 164 recoding sites residing in 100 protein coding genes, including ion channels, transporters, and receptors predicted to affect brain function and behavior. Some edited sites are similarly edited in other insects, cephalopods and even mammals. The global editing level of protein coding and non-coding transcripts weakly correlates with task performance (brood care vs. foraging), but not affected by dominance rank or juvenile hormone known to influence physiology and behavior. Taken together, our findings show that brain editing levels are high in naturally behaving bees, and may be regulated by relatively short-term effects associated with brood care or foraging activities.
Surface melt driven summer diurnal and winter multi-day stick-slip motion and till sedimentology
Authors: Hart Jane K. , Martinez Kirk , Basford Philip J. , Clayton Alexander I. , Robson Benjamin A. , Young David S. 
Published: April 2019

AbstractFluctuations in glacier motion are very common and are thought to be controlled by subglacial hydrology and till deformation. There are few instrumented studies that have monitored seasonal changes. We use the innovative Glacsweb subglacial in situ wireless probes, combined with dGPS and custom geophone data from an Icelandic soft-bedded temperate glacier, to show that there are two distinct seasonal styles of speed-up events. Relatively small diurnal events occur during the melt season, whilst during winter there are larger multi-day events related to positive degree days. These events are accompanied by a distinct pattern of till deformation and basal icequakes. We argue these reflect stick-slip motion which occurs when the glacier hydrological system is unable to accommodate the melt water flux generated by surface melt episodes. We show a rare fully instrumented coupled glacier/till record of contrasting summer and winter stick-slip motion and discuss its implication for till sedimentology.
Boosting the efficiency of organic persistent room-temperature phosphorescence by intramolecular triplet-triplet energy transfer
Authors: Zhao Weijun , Cheung Tsz Shing , Jiang Nan , Huang Wenbin , Lam Jacky W. Y. , Zhang Xuepeng , He Zikai , Tang Ben Zhong 
Published: April 2019

AbstractPersistent luminescence is a fascinating phenomenon with exceptional applications. However, the development of organic materials capable of persistent luminescence, such as organic persistent room-temperature phosphorescence, lags behind for their normally low efficiency. Moreover, enhancing the phosphorescence efficiency of organic luminophores often results in short lifetime, which sets an irreconcilable obstacle. Here we report a strategy to boost the efficiency of phosphorescence by intramolecular triplet-triplet energy transfer. Incorpotation of (bromo)dibenzofuran or (bromo)dibenzothiophene to carbazole has boosted the intersystem crossing and provided an intramolecular triplet-state bridge to offer a near quantitative exothermic triplet–triplet energy transfer to repopulate the lowest triplet-state of carbazole. All these factors work together to contribute the efficient phosphorescence. The generation and transfer of triplet excitons within a single molecule is revealed by low-temperature spectra, energy level and lifetime investigations. The strategy developed here will enable the development of efficient phosphorescent materials for potential high-tech applications.
Cycles of external dependency drive evolution of avian carotenoid networks
Authors: Badyaev Alexander V. , Posner Alexander B. , Morrison Erin S. , Higginson Dawn M. 
Published: April 2019

AbstractAll organisms depend on input of exogenous compounds that cannot be internally produced. Gain and loss of such dependencies structure ecological communities and drive species’ evolution, yet the evolution of mechanisms that accommodate these variable dependencies remain elusive. Here, we show that historical cycles of gains and losses of external dependencies in avian carotenoid-producing networks are linked to their evolutionary diversification. This occurs because internalization of metabolic controls—produced when gains in redundancy of dietary inputs coincide with increased branching of their derived products—enables rapid and sustainable exploration of an existing network by shielding it from environmental fluctuations in inputs. Correspondingly, loss of internal controls constrains evolution to the rate of the gains and losses of dietary precursors. Because internalization of a network’s controls necessarily bridges diet-specific enzymatic modules within a network, it structurally links local adaptation and continuous evolution even for traits fully dependent on contingent external inputs.
Coordinated host-pathogen transcriptional dynamics revealed using sorted subpopulations and single macrophages infected with Candida albicans
Authors: Muñoz José F. , Delorey Toni , Ford Christopher B. , Li Bi Yu , Thompson Dawn A. , Rao Reeta P. , Cuomo Christina A. 
Published: April 2019

AbstractThe outcome of fungal infections depends on interactions with innate immune cells. Within a population of macrophages encountering Candida albicans, there are distinct host-pathogen trajectories; however, little is known about the molecular heterogeneity that governs these fates. Here we developed an experimental system to separate interaction stages and single macrophage cells infected with C. albicans from uninfected cells and assessed transcriptional variability in the host and fungus. Macrophages displayed an initial up-regulation of pathways involved in phagocytosis and proinflammatory response after C. albicans exposure that declined during later time points. Phagocytosed C. albicans shifted expression programs to survive the nutrient poor phagosome and remodeled the cell wall. The transcriptomes of single infected macrophages and phagocytosed C. albicans displayed a tightly coordinated shift in gene expression co-stages and revealed expression bimodality and differential splicing that may drive infection outcome. This work establishes an approach for studying host-pathogen trajectories to resolve heterogeneity in dynamic populations.
Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation
Authors: Zheng Jun , Fan Rong , Wu Huiqiong , Yao Honghui , Yan Yujie , Liu Jiamiao , Ran Lu , Sun Zhifang , Yi Lunzhao , Dang Li , Gan Pingping , Zheng Piao , Yang Tilong , Zhang Yi , Tang Tao , Wang Yang 
Published: April 2019

AbstractSelf-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.
Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting
Authors: Zhang Yiming , Higgins Cassandra B. , Fortune Hannah M. , Chen Phillip , Stothard Alicyn I. , Mayer Allyson L. , Swarts Benjamin M. , DeBosch Brian J. 
Published: April 2019

AbstractCaloric restriction and intermittent fasting are emerging therapeutic strategies against obesity, insulin resistance and their complications. However, the effectors that drive this response are not completely defined. Here we identify arginase 2 (Arg2) as a fasting-induced hepatocyte factor that protects against hepatic and peripheral fat accumulation, hepatic inflammatory responses, and insulin and glucose intolerance in obese murine models. Arg2 is upregulated in fasting conditions and upon treatment with the hepatocyte glucose transporter inhibitor trehalose. Hepatocyte-specific Arg2 overexpression enhances basal thermogenesis, and protects from weight gain, insulin resistance, glucose intolerance, hepatic steatosis and hepatic inflammation in diabetic mouse models. Arg2 suppresses expression of the regulator of G-protein signalling (RGS) 16, and genetic RGS16 reconstitution reverses the effects of Arg2 overexpression. We conclude that hepatocyte Arg2 is a critical effector of the hepatic glucose fasting response and define a therapeutic target to mitigate the complications of obesity and non-alcoholic fatty liver disease.
Taming the stability of Pd active phases through a compartmentalizing strategy toward nanostructured catalyst supports
Authors: Yang Xinwei , Li Qing , Lu Erjun , Wang Zhiqiang , Gong Xueqing , Yu Zhiyang , Guo Yun , Wang Li , Guo Yanglong , Zhan Wangcheng , Zhang Jinshui , Dai Sheng 
Published: April 2019

AbstractThe design and synthesis of robust sintering-resistant nanocatalysts for high-temperature oxidation reactions is ubiquitous in many industrial catalytic processes and still a big challenge in implementing nanostructured metal catalyst systems. Herein, we demonstrate a strategy for designing robust nanocatalysts through a sintering-resistant support via compartmentalization. Ultrafine palladium active phases can be highly dispersed and thermally stabilized by nanosheet-assembled γ-Al2O3 (NA-Al2O3) architectures. The NA-Al2O3 architectures with unique flowerlike morphologies not only efficiently suppress the lamellar aggregation and irreversible phase transformation of γ-Al2O3 nanosheets at elevated temperatures to avoid the sintering and encapsulation of metal phases, but also exhibit significant structural advantages for heterogeneous reactions, such as fast mass transport and easy access to active sites. This is a facile stabilization strategy that can be further extended to improve the thermal stability of other Al2O3-supported nanocatalysts for industrial catalytic applications, in particular for those involving high-temperature reactions.
Ecological and geographical overlap drive plumage evolution and mimicry in woodpeckers
Authors: Miller Eliot T. , Leighton Gavin M. , Freeman Benjamin G. , Lees Alexander C. , Ligon Russell A. 
Published: April 2019

AbstractOrganismal appearances are shaped by selection from both biotic and abiotic drivers. For example, Gloger’s rule describes the pervasive pattern that more pigmented populations are found in more humid areas. However, species may also converge on nearly identical colours and patterns in sympatry, often to avoid predation by mimicking noxious species. Here we leverage a massive global citizen-science database to determine how biotic and abiotic factors act in concert to shape plumage in the world’s 230 species of woodpeckers. We find that habitat and climate profoundly influence woodpecker plumage, and we recover support for the generality of Gloger’s rule. However, many species exhibit remarkable convergence explained neither by these factors nor by shared ancestry. Instead, this convergence is associated with geographic overlap between species, suggesting occasional strong selection for interspecific mimicry.