bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling of driver events in metastatic uveal melanoma
Authors: Karlsson Joakim , Nilsson Lisa M. , Mitra Suman , Alsén Samuel , Shelke Ganesh Vilas , Sah Vasu R. , Forsberg Elin M. V. , Stierner Ulrika , All-Eriksson Charlotta , Einarsdottir Berglind , Jespersen Henrik , Ny Lars , Lindnér Per , Larsson Erik , Olofsson Bagge Roger , Nilsson Jonas A. 
Published: April 2020

AbstractMetastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease.
Observation of edge solitons in photonic graphene
Authors: Zhang Zhaoyang , Wang Rong , Zhang Yiqi , Kartashov Yaroslav V. , Li Feng , Zhong Hua , Guan Hua , Gao Kelin , Li Fuli , Zhang Yanpeng , Xiao Min 
Published: April 2020

AbstractEdge states emerge in diverse areas of science, offering promising opportunities for the development of future electronic or optoelectronic devices, sound and light propagation control in acoustics and photonics. Previous experiments on edge states in photonics were carried out mostly in linear regimes, but the current belief is that nonlinearity introduces more striking features into physics of edge states, leading to the formation of edge solitons, optical isolation, making possible stable lasing in such states, to name a few. Here we report the observation of edge solitons at the zigzag edge of a reconfigurable photonic graphene lattice created via the effect of electromagnetically induced transparency in an atomic vapor cell with controllable nonlinearity. To obtain edge solitons, Raman gain is introduced to compensate strong absorption experienced by the edge state during propagation. Our observations may open the way for future experimental exploration of topological photonics on this nonlinear, reconfigurable platform.
Stochasticity constrained by deterministic effects of diet and age drive rumen microbiome assembly dynamics
Authors: Furman Ori , Shenhav Liat , Sasson Goor , Kokou Fotini , Honig Hen , Jacoby Shamay , Hertz Tomer , Cordero Otto X. , Halperin Eran , Mizrahi Itzhak 
Published: April 2020

AbstractHow complex communities assemble through the animal’s life, and how predictable the process is remains unexplored. Here, we investigate the forces that drive the assembly of rumen microbiomes throughout a cow’s life, with emphasis on the balance between stochastic and deterministic processes. We analyse the development of the rumen microbiome from birth to adulthood using 16S-rRNA amplicon sequencing data and find that the animals shared a group of core successional species that invaded early on and persisted until adulthood. Along with deterministic factors, such as age and diet, early arriving species exerted strong priority effects, whereby dynamics of late successional taxa were strongly dependent on microbiome composition at early life stages. Priority effects also manifest as dramatic changes in microbiome development dynamics between animals delivered by C-section vs. natural birth, with the former undergoing much more rapid species invasion and accelerated microbiome development. Overall, our findings show that together with strong deterministic constrains imposed by diet and age, stochastic colonization in early life has long-lasting impacts on the development of animal microbiomes.
A double-hit of stress and low-grade inflammation on functional brain network mediates posttraumatic stress symptoms
Authors: Kim Jungyoon , Yoon Sujung , Lee Suji , Hong Haejin , Ha Eunji , Joo Yoonji , Lee Eun Hee , Lyoo In Kyoon 
Published: April 2020

AbstractGrowing evidence indicates a reciprocal relationship between low-grade systemic inflammation and stress exposure towards increased vulnerability to neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, the neural correlates of this reciprocity and their influence on the subsequent development of PTSD are largely unknown. Here we investigated alterations in functional connectivity among brain networks related to low-grade inflammation and stress exposure using two large independent data sets. Functional couplings among the higher-order cognitive network system including the salience, default mode, and central executive networks were reduced in association with low-grade inflammation and stress exposure. This reduced functional coupling may also be related to subsequent posttraumatic stress symptom severity. The current findings propose functional couplings among the higher-order cognitive network system as neural correlates of low-grade inflammation and stress exposure, and suggest that low-grade inflammation, alongside with stress, may render individuals more vulnerable to PTSD.
Mouse tracking reveals structure knowledge in the absence of model-based choice
Authors: Konovalov Arkady , Krajbich Ian 
Published: April 2020

AbstractConverging evidence has demonstrated that humans exhibit two distinct strategies when learning in complex environments. One is model-free learning, i.e., simple reinforcement of rewarded actions, and the other is model-based learning, which considers the structure of the environment. Recent work has argued that people exhibit little model-based behavior unless it leads to higher rewards. Here we use mouse tracking to study model-based learning in stochastic and deterministic (pattern-based) environments of varying difficulty. In both tasks participants’ mouse movements reveal that they learned the structures of their environments, despite the fact that standard behavior-based estimates suggested no such learning in the stochastic task. Thus, we argue that mouse tracking can reveal whether subjects have structure knowledge, which is necessary but not sufficient for model-based choice.
Scavenger receptor-A is a biomarker and effector of rheumatoid arthritis: A large-scale multicenter study
Authors: Hu Fanlei , Jiang Xiang , Guo Chunqing , Li Yingni , Chen Shixian , Zhang Wei , Du Yan , Wang Ping , Zheng Xi , Fang Xiangyu , Li Xin , Song Jing , Xie Yang , Huang Fei , Xue Jimeng , Bai Mingxin , Jia Yuan , Liu Xu , Ren Limin , Zhang Xiaoying , Guo Jianping , Pan Hudan , Su Yin , Yi Huanfa , Ye Hua , Zuo Daming , Li Juan , Wu Huaxiang , Wang Yongfu , Li Ru , Liu Liang , Wang Xiang-Yang , Li Zhanguo 
Published: April 2020

AbstractEarly diagnosis is critical to improve outcomes in rheumatoid arthritis (RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A (sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy.
Transcriptional downregulation of MHC class I and melanoma de- differentiation in resistance to PD-1 inhibition
Authors: Lee Jenny H. , Shklovskaya Elena , Lim Su Yin , Carlino Matteo S. , Menzies Alexander M. , Stewart Ashleigh , Pedersen Bernadette , Irvine Malama , Alavi Sara , Yang Jean Y. H. , Strbenac Dario , Saw Robyn P. M. , Thompson John F. , Wilmott James S. , Scolyer Richard A. , Long Georgina V. , Kefford Richard F. , Rizos Helen 
Published: April 2020

AbstractTranscriptomic signatures designed to predict melanoma patient responses to PD-1 blockade have been reported but rarely validated. We now show that intra-patient heterogeneity of tumor responses to PD-1 inhibition limit the predictive performance of these signatures. We reasoned that resistance mechanisms will reflect the tumor microenvironment, and thus we examined PD-1 inhibitor resistance relative to T-cell activity in 94 melanoma tumors collected at baseline and at time of PD-1 inhibitor progression. Tumors were analyzed using RNA sequencing and flow cytometry, and validated functionally. These analyses confirm that major histocompatibility complex (MHC) class I downregulation is a hallmark of resistance to PD-1 inhibitors and is associated with the MITFlow/AXLhigh de-differentiated phenotype and cancer-associated fibroblast signatures. We demonstrate that TGFß drives the treatment resistant phenotype (MITFlow/AXLhigh) and contributes to MHC class I downregulation in melanoma. Combinations of anti-PD-1 with drugs that target the TGFß signaling pathway and/or which reverse melanoma de-differentiation may be effective future therapeutic strategies.
Transformable hybrid semiconducting polymer nanozyme for second near-infrared photothermal ferrotherapy
Authors: Jiang Yuyan , Zhao Xuhui , Huang Jiaguo , Li Jingchao , Upputuri Paul Kumar , Sun He , Han Xiao , Pramanik Manojit , Miao Yansong , Duan Hongwei , Pu Kanyi , Zhang Ruiping 
Published: April 2020

AbstractDespite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression.
Resonant nanostructures for highly confined and ultra-sensitive surface phonon-polaritons
Authors: Dubrovkin Alexander M. , Qiang Bo , Salim Teddy , Nam Donguk , Zheludev Nikolay I. , Wang Qi Jie 
Published: April 2020

AbstractPlasmonics on metal-dielectric interfaces was widely seen as the main route for miniaturization of components and interconnect of photonic circuits. However recently, ultra-confined surface phonon-polaritonics in high-index chalcogenide films of nanometric thickness has emerged as an important alternative to plasmonics. Here, using mid-IR near-field imaging we demonstrate tunable surface phonon-polaritons in CMOS-compatible interfaces of few-nm thick germanium on silicon carbide. We show that Ge-SiC resonators with nanoscale footprint can support sheet and edge surface modes excited at the free space wavelength hundred times larger than their physical dimensions. Owing to the surface nature of the modes, the sensitivity of real-space polaritonic patterns provides pathway for local detection of the interface composition change at sub-nanometer level. Such deeply subwavelength resonators are of interest for high-density optoelectronic applications, filters, dispersion control and optical delay devices.
Intramolecular chaperone-mediated secretion of an Rhs effector toxin by a type VI secretion system
Authors: Pei Tong-Tong , Li Hao , Liang Xiaoye , Wang Zeng-Hang , Liu Guangfeng , Wu Li-Li , Kim Haeun , Xie Zhiping , Yu Ming , Lin Shuangjun , Xu Ping , Dong Tao G. 
Published: April 2020

AbstractBacterial Rhs proteins containing toxic domains are often secreted by type VI secretion systems (T6SSs) through unclear mechanisms. Here, we show that the T6SS Rhs-family effector TseI of Aeromonas dhakensis is subject to self-cleavage at both the N- and the C-terminus, releasing the middle Rhs core and two VgrG-interacting domains (which we name VIRN and VIRC). VIRC is an endonuclease, and the immunity protein TsiI protects against VIRC toxicity through direct interaction. Proteolytic release of VIRC and VIRN is mediated, respectively, by an internal aspartic protease activity and by two conserved glutamic residues in the Rhs core. Mutations abolishing self-cleavage do not block secretion, but reduce TseI toxicity. Deletion of VIRN or the Rhs core abolishes secretion. TseI homologs from Pseudomonas syringae, P. aeruginosa, and Vibrio parahaemolyticus are also self-cleaved. VIRN and VIRC interact with protein VgrG1, while the Rhs core interacts with protein TecI. We propose that VIRN and the Rhs core act as T6SS intramolecular chaperones to facilitate toxin secretion and function.
Large scale active-learning-guided exploration for in vitro protein production optimization
Authors: Borkowski Olivier , Koch Mathilde , Zettor Agnès , Pandi Amir , Batista Angelo Cardoso , Soudier Paul , Faulon Jean-Loup 
Published: April 2020

AbstractLysate-based cell-free systems have become a major platform to study gene expression but batch-to-batch variation makes protein production difficult to predict. Here we describe an active learning approach to explore a combinatorial space of ~4,000,000 cell-free buffer compositions, maximizing protein production and identifying critical parameters involved in cell-free productivity. We also provide a one-step-method to achieve high quality predictions for protein production using minimal experimental effort regardless of the lysate quality.
Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones
Authors: Chen Jiachang , Wang Yiming , Ding Zhengtian , Kong Wangqing 
Published: April 2020

AbstractThe restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.01,5]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.01,5]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio- and enantioselectivities (92–99% ee).
Cool White Polymer Coatings based on Glass Bubbles for Buildings
Authors: Nie Xiao , Yoo Youngjae , Hewakuruppu Hasitha , Sullivan Jonathan , Krishna Anirudh , Lee Jaeho 
Published: April 2020

AbstractWhile most selective emitter materials are inadequate or inappropriate for building applications, here we present a techno-economically viable optical coating by integrating glass bubbles within a polymer film. A controlled glass bubble volume concentration from 0 to 70% leads to a selective solar reflectivity increase from 0.06 to 0.92 while the mid-infrared emissivity remains above 0.85. Outdoor measurements show the polymer coating on a concrete surface can provide a temperature reduction up to 25 °C during the day when conduction and convection are limited and a net cooling power greater than 78 W/m2 at a cost less than $0.005/W. The impact of polymer coating on common buildings is estimated as potential annual energy savings of 2–12 MJ/m2 and CO2 emission savings of 0.3–1.5 kg/m2. More savings are expected for higher surface-area-to-volume-ratio buildings, and the polymer coating is also expected to resolve cooling issues for old buildings with no air conditioning.
The non-receptor tyrosine kinase Pyk2 modulates acute locomotor effects of cocaine in D1 receptor-expressing neurons of the nucleus accumbens
Authors: de Pins Benoit , Montalban Enrica , Vanhoutte Peter , Giralt Albert , Girault Jean-Antoine 
Published: April 2020

AbstractThe striatum is critical for cocaine-induced locomotor responses. Although the role of D1 receptor-expressing neurons is established, underlying molecular pathways are not fully understood. We studied the role of Pyk2, a non-receptor, calcium-dependent protein-tyrosine kinase. The locomotor coordination and basal activity of Pyk2 knock-out mice were not altered and major striatal protein markers were normal. Cocaine injection increased Pyk2 tyrosine phosphorylation in mouse striatum. Pyk2-deficient mice displayed decreased locomotor response to acute cocaine injection. In contrast, locomotor sensitization and conditioned place preference were normal. Cocaine-activated ERK phosphorylation, a signaling pathway essential for these late responses, was unaltered. Conditional deletion of Pyk2 in the nucleus accumbens or in D1 neurons reproduced decreased locomotor response to cocaine, whereas deletion of Pyk2 in the dorsal striatum or in A2A receptor-expressing neurons did not. In mice lacking Pyk2 in D1-neurons locomotor response to D1 agonist SKF-81297, but not to an anticholinergic drug, was blunted. Our results identify Pyk2 as a regulator of acute locomotor responses to psychostimulants. They highlight the role of tyrosine phosphorylation pathways in striatal neurons and suggest that changes in Pyk2 expression or activation may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine action.
Effectiveness of decontamination by litter removal in Japanese forest ecosystems affected by the Fukushima nuclear accident
Authors: Koarashi Jun , Atarashi-Andoh Mariko , Nishimura Syusaku , Muto Kotomi 
Published: April 2020

AbstractThe Fukushima Daiichi nuclear power plant accident caused serious radiocesium (137Cs) contamination of forest ecosystems over a wide area. The removal of the forest floor litter layer has been considered a potential method for forest decontamination; however, its effectiveness remains largely unknown. We conducted a pilot-scale decontamination study in a deciduous broadleaved forest in Fukushima. The entire forest was decontaminated by removing the litter layer in July 2014, approximately 3.3 years after the accident, with the exception of two untreated plots. For three years after decontamination, we quantified 137Cs contamination levels in the litter and topsoil layers and in the tree leaves, in the untreated and decontaminated areas. The decreased inventories of litter materials and the litter-associated 137Cs in the decontaminated areas were observed only in the first year after decontamination. Generally, no decontamination effects were observed on the 137Cs transfer in tree leaves. The primary reason for this was the rapid shift in the main reservoir of 137Cs from litter layers to the underlying mineral soil, which differs from the observations in post-Chernobyl studies of European forest ecosystems. The results suggest that litter-removal decontamination can only be successful if it is implemented more quickly (within 1–2 years after the accident) for Japanese forest ecosystems.
Epigenetics and Mitochondrial Stability in the Metabolic Memory Phenomenon Associated with Continued Progression of Diabetic Retinopathy
Authors: Kowluru Renu A. , Mohammad Ghulam 
Published: April 2020

AbstractRetinopathy continues to progress even when diabetic patients try to control their blood sugar, but the molecular mechanism of this ‘metabolic memory’ phenomenon remains elusive. Retinal mitochondria remain damaged and vicious cycle of free radicals continues to self-propagate. DNA methylation suppresses gene expression, and diabetes activates DNA methylation machinery. Our aim was to investigate the role of DNA methylation in continued compromised mitochondrial dynamics and genomic stability in diabetic retinopathy. Using retinal endothelial cells, incubated in 20 mM glucose for four days, followed by 5 mM glucose for four days, and retinal microvessels from streptozotocin-induced diabetic rats in poor glycemia for four months, followed by normal glycemia for four additional months, DNA methylation of mitochondrial fusion and mismatch repair proteins, Mfn2 and Mlh1 respectively, was determined. Retinopathy was detected in trypsin-digested microvasculature. Re-institution of good glycemia had no beneficial effect on hypermethylation of Mfn2 and Mlh1 and retinal function (electroretinogram), and the retinopathy continued to progress. However, intervention of good glycemia directly with DNA methylation inhibitors (Azacytidine or Dnmt1-siRNA), prevented Mfn2 and Mlh1 hypermethylation, and ameliorated retinal dysfunction and diabetic retinopathy. Thus, direct regulation of DNA methylation can prevent/reverse diabetic retinopathy by maintaining mitochondrial dynamics and DNA stability, and prevent retinal functional damage.
RNA Sequence Analyses throughout the Course of Mouse Cardiac Laminopathy Identify Differentially Expressed Genes for Cell Cycle Control and Mitochondrial Function
Authors: Shao Zhili , Koh Wonshill , Ni Ying , Li Wei , Agatisa-Boyle Brendan , Merkurjev Daria , Tang Wai Hong Wilson 
Published: April 2020

AbstractLamin A/C (LMNA) gene mutations are a known cause of familial dilated cardiomyopathy, but the precise mechanisms triggering disease progression remain unknown. We hypothesize that analysis of differentially expressed genes (DEGs) throughout the course of Lmna knockout (Lmna−/−)-induced cardiomyopathy may reveal novel Lmna-mediated alterations of signaling pathways leading to dilated cardiomyopathy. Although Lmna was the only DEG down-regulated at 1 week of age, we identified 730 and 1004 DEGs in Lmna−/− mice at 2 weeks and 1 month of age, respectively. At 2 weeks, Lmna−/− mice demonstrated both down- and up-regulation of the key genes involving cell cycle control, mitochondrial dysfunction, and oxidative phosphorylation, as well as down-regulated genes governing DNA damage repair and up-regulated genes involved in oxidative stress response, cell survival, and cardiac hypertrophy. At 1 month, the down-regulated genes included those involved in oxidative phosphorylation, mitochondrial dysfunction, nutrient metabolism, cardiac β-adrenergic signaling, action potential generation, and cell survival. We also found 96 overlapping DEGs at both ages involved in oxidative phosphorylation, mitochondrial function, and calcium signaling. Impaired oxidative phosphorylation was observed at early disease stage, even before the appearance of disease phenotypes, and worsened with disease progression, suggesting its importance in the pathogenesis and progression of LMNA cardiomyopathy. Reduction of oxidative stress might therefore prevent or delay the development from Lmna mutation to LMNA cardiomyopathy.