bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of natural product modulators of Merkel cell carcinoma cell growth and survival
Authors: Smith Emily A. , Hill Natasha T. , Gelb Tara , Garman Khalid A. , Goncharova Ekaterina I. , Bokesch Heidi R. , Kim Chang-Kwon , Wendt Karen L. , Cichewicz Robert H. , Gustafson Kirk R. , Brownell Isaac , Henrich Curtis J. 
Published: June 2021

AbstractMerkel cell carcinoma (MCC) is a rare, but aggressive skin cancer the incidence of which has increased significantly in recent years. The majority of MCCs have incorporated Merkel cell polyomavirus (VP-MCC) while the remainder are virus-negative (VN-MCC). Although a variety of therapeutic options have shown promise in treating MCC, there remains a need for additional therapeutics as well as probes for better understanding MCC. A high-throughput screening campaign was used to assess the ability of > 25,000 synthetic and natural product compounds as well as > 20,000 natural product extracts to affect growth and survival of VN-MCC and VP-MCC cell lines. Sixteen active compounds were identified that have mechanisms of action reported in the literature along with a number of compounds with unknown mechanisms. Screening results with pure compounds suggest a range of potential targets for MCC including DNA damage, inhibition of DNA or protein synthesis, reactive oxygen species, and proteasome inhibition as well as NFκB inhibition while also suggesting the importance of zinc and/or copper binding. Many of the active compounds, particularly some of the natural products, have multiple reported targets suggesting that this strategy might be a particularly fruitful approach. Processing of several active natural product extracts resulted in the identification of additional MCC-active compounds. Based on these results, further investigations focused on natural products sources, particularly of fungal origin, are expected to yield further potentially useful modulators of MCC.
Association of depressive disorder with biochemical and anthropometric indices in adult men and women
Authors: Lee Bum Ju 
Published: June 2021

AbstractDepression is a common psychiatric disorder. Although many risk factors for depression have been reported, the associations of biochemical and anthropometric indices with depressive disorder remain unclear. The objective of this study was to assess whether there are significant associations of depressive disorder with biochemical and obesity indices. This study was based on data from the Korea National Health and Nutrition Examination Survey from 2007 to 2018, and logistic regression was performed to examine the association of depression with biochemical and obesity indices. A total of 33,993 subjects were included in the analyses. Study subjects consisted of 13,178 men in the control group (mean age of 51.12 years), 509 men in the depression group (53.67), 18,279 women in the control group (50.5), and 2027 women in the depression group (55.39). Among men, the depression group was significantly more likely to have a lower height and weight than the control group. Compared to the control group, the depression group was more likely to have higher triglyceride levels and tended to have lower hematocrit and blood urea nitrogen (BUN) levels. Among women, the depression group was more likely to have higher triglyceride, aspartate aminotransferase (AST), BUN, and creatinine levels and lower high-density lipoprotein cholesterol (HDL-C), hematocrit, and red blood cell counts. Several biochemical and anthropometric indices used in this study were associated with depressive disorder, but these associations may differ according to sex.
Parental selection for growth and early-life low stocking density increase the female-to-male ratio in European sea bass
Authors: Geffroy Benjamin , Gesto Manuel , Clota Fréderic , Aerts Johan , Darias Maria J. , Blanc Marie-Odile , Ruelle François , Allal François , Vandeputte Marc 
Published: June 2021

AbstractIn European sea bass (Dicentrarchus labrax), as in many other fish species, temperature is known to influence the sex of individuals, with more males produced at relatively high temperatures. It is however unclear to what extent growth or stress are involved in such a process, since temperature is known to influence both growth rate and cortisol production. Here, we designed an experiment aiming at reducing stress and affecting early growth rate. We exposed larvae and juveniles originating from both captive and wild parents to three different treatments: low stocking density, food supplemented with tryptophan and a control. Low stocking density and tryptophan treatment respectively increased and decreased early growth rate. Each treatment influenced the stress response depending on the developmental stage, although no clear pattern regarding the whole-body cortisol concentration was found. During sex differentiation, fish in the low-density treatment exhibited lower expression of gr1, gr2, mr, and crf in the hypothalamus when compared to the control group. Fish fed tryptophan displayed lower crf in the hypothalamus and higher level of serotonin in the telencephalon compared to controls. Overall, fish kept at low density produced significantly more females than both control and fish fed tryptophan. Parents that have been selected for growth for three generations also produced significantly more females than parents of wild origin. Our findings did not allow to detect a clear effect of stress at the group level and rather point out a key role of early sexually dimorphic growth rate in sex determination.
Identification of novel QTLs for grain fertility and associated traits to decipher poor grain filling of basal spikelets in dense panicle rice
Authors: Sekhar Sudhanshu , Kumar Jitendra , Mohanty Soumya , Mohanty Niharika , Panda Rudraksh Shovan , Das Swagatika , Shaw Birendra Prasad , Behera Lambodar 
Published: June 2021

AbstractHigh grain number is positively correlated with grain yield in rice, but it is compromised because of poor filling of basal spikelets in dense panicle bearing numerous spikelets. The phenomenon that turns the basal spikelets of compact panicle sterile in rice is largely unknown. In order to understand the factor(s) that possibly determines such spikelet sterility in compact panicle cultivars, QTLs and candidate genes were identified for spikelet fertility and associated traits like panicle compactness, and ethylene production that significantly influences the grain filling using recombinant inbred lines developed from a cross between indica rice cultivars, PDK Shriram (compact, high spikelet number) and Heera (lax, low spikelet number). Novel QTLs, qSFP1.1, qSFP3.1, and qSFP6.1 for spikelet fertility percentage; qIGS3.2 and qIGS4.1 for panicle compactness; and qETH1.2, qETH3.1, and qETH4.1 for ethylene production were consistently identified in both kharif seasons of 2017 and 2018. The comparative expression analysis of candidate genes like ERF3, AP2-like ethylene-responsive transcription factor, EREBP, GBSS1, E3 ubiquitin-protein ligase GW2, and LRR receptor-like serine/threonine-protein kinase ERL1 associated with identified QTLs revealed their role in poor grain filling of basal spikelets in a dense panicle. These candidate genes thus could be important for improving grain filling in compact-panicle rice cultivars through biotechnological interventions.
Water quality drives the regional patterns of an algal metacommunity in interconnected lakes
Authors: Kim Min Sung , Ahn Seok Hyun , Jeong In Jae , Lee Tae Kwon 
Published: June 2021

AbstractThe metacommunity approach provides insights into how the biological communities are assembled along the environmental variations. The current study presents the importance of water quality on the metacommunity structure of algal communities in six river-connected lakes using long-term (8 years) monitoring datasets. Elements of metacommunity structure were analyzed to evaluate whether water quality structured the metacommunity across biogeographic regions in the riverine ecosystem. The algal community in all lakes was found to exhibit Clementsian or quasi-Clementsian structure properties such as significant turnover, grouped and species sorting indicating that the communities responded to the environmental gradient. Reciprocal averaging clearly classified the lakes into three clusters according to the geographical region in river flow (upstream, midstream, and downstream). The dispersal patterns of algal genera, including Aulacoseira, Cyclotella, Stephanodiscus, and Chlamydomonas across the regions also supported the spatial-based classification results. Although conductivity, chemical oxygen demand, and biological oxygen demand were found to be important variables (loading > |0.5|) of the entire algal community assembly, water temperature was a critical factor in water quality associated with community assembly in each geographical area. These results support the notion that the structure of algal communities is strongly associated with water quality, but the relative importance of variables in structuring algal communities differed by geological regions.
Low-dose aspirin for primary and secondary prevention of cardiovascular events in Denmark 1998–2018
Authors: Christensen Mikkel B. , Jimenez-Solem Espen , Ernst Martin. T. , Schmidt Morten , Pottegård Anton , Grove Erik L. 
Published: June 2021

AbstractRandomised controlled trials have shown a neutral or even unfavourable risk–benefit balance of aspirin for primary prevention of cardiovascular events. Using Danish nationwide registries, we investigated aspirin use and associated risks during the past two decades (1998–2018). We linked individual patient data on repeated aspirin redemptions with registered hospital ICD-10 diagnoses of atherosclerotic cardiovascular disease and bleedings. The prevalence of aspirin use among 1.1 million Danish adults fluctuated over the 20-year study period peaking in 2008 with 8.5% (5.4% primary prevention) and dropping to 5.1% (3.1% primary prevention) in 2018. Aspirin use showed strong age dependency, and 21% of individuals > 80 years were treated with aspirin for primary prevention in 2018. Medication adding to bleeding risk was used concurrently by 21% of all aspirin users in 2018. The incidence of major bleedings were similar with primary and secondary prevention aspirin use and highest in elderly (2 per 100 patient years among individuals > 80 years in 2018). In conclusion, low-dose aspirin use for primary prevention of cardiovascular events remains prevalent. The widespread use of aspirin, especially among older adults, and substantial concomitant use of medications adding to bleeding risk warrant increased focus on discontinuation of inappropriate aspirin use.
A yeast-optimized single-cell transcriptomics platform elucidates how mycophenolic acid and guanine alter global mRNA levels
Authors: Urbonaite Guste , Lee Jimmy Tsz Hang , Liu Ping , Parada Guillermo E. , Hemberg Martin , Acar Murat 
Published: June 2021

AbstractStochastic gene expression leads to inherent variability in expression outcomes even in isogenic single-celled organisms grown in the same environment. The Drop-Seq technology facilitates transcriptomic studies of individual mammalian cells, and it has had transformative effects on the characterization of cell identity and function based on single-cell transcript counts. However, application of this technology to organisms with different cell size and morphology characteristics has been challenging. Here we present yeastDrop-Seq, a yeast-optimized platform for quantifying the number of distinct mRNA molecules in a cell-specific manner in individual yeast cells. Using yeastDrop-Seq, we measured the transcriptomic impact of the lifespan-extending compound mycophenolic acid and its epistatic agent guanine. Each treatment condition had a distinct transcriptomic footprint on isogenic yeast cells as indicated by distinct clustering with clear separations among the different groups. The yeastDrop-Seq platform facilitates transcriptomic profiling of yeast cells for basic science and biotechnology applications.
Structure-based insights into evolution of rhodopsins
Authors: Zabelskii Dmitrii , Dmitrieva Natalia , Volkov Oleksandr , Shevchenko Vitaly , Kovalev Kirill , Balandin Taras , Soloviov Dmytro , Astashkin Roman , Zinovev Egor , Alekseev Alexey , Round Ekaterina , Polovinkin Vitaly , Chizhov Igor , Rogachev Andrey , Okhrimenko Ivan , Borshchevskiy Valentin , Chupin Vladimir , Büldt Georg , Yutin Natalia , Bamberg Ernst , Koonin Eugene , Gordeliy Valentin 
Published: June 2021

AbstractRhodopsins, most of which are proton pumps generating transmembrane electrochemical proton gradients, span all three domains of life, are abundant in the biosphere, and could play a crucial role in the early evolution of life on earth. Whereas archaeal and bacterial proton pumps are among the best structurally characterized proteins, rhodopsins from unicellular eukaryotes have not been well characterized. To fill this gap in the current understanding of the proton pumps and to gain insight into the evolution of rhodopsins using a structure-based approach, we performed a structural and functional analysis of the light-driven proton pump LR (Mac) from the pathogenic fungus Leptosphaeria maculans. The first high-resolution structure of fungi rhodopsin and its functional properties reveal the striking similarity of its membrane part to archaeal but not to bacterial rhodopsins. We show that an unusually long N-terminal region stabilizes the protein through direct interaction with its extracellular loop (ECL2). We compare to our knowledge all available structures and sequences of outward light-driven proton pumps and show that eukaryotic and archaeal proton pumps, most likely, share a common ancestor.
Atomic-state-dependent screening model for hot and warm dense plasmas
Authors: Zhou Fuyang , Qu Yizhi , Gao Junwen , Ma Yulong , Wu Yong , Wang Jianguo 
Published: June 2021

AbstractAn ion embedded in warm/hot dense plasmas will greatly alter its microscopic structure and dynamics, as well as the macroscopic radiation transport properties of the plasmas, due to complicated many-body interactions with surrounding particles. Accurate theoretically modeling of such kind of quantum many-body interactions is essential but very challenging. In this work, we propose an atomic-state-dependent screening model for treating the plasmas with a wide range of temperatures and densities, in which the contributions of three-body recombination processes are included. We show that the electron distributions around an ion are strongly correlated with the ionic state studied due to the contributions of three-body recombination processes. The feasibility and validation of the proposed model are demonstrated by reproducing the experimental result of the line-shift of hot-dense plasmas as well as the classical molecular dynamic simulations of moderately coupled ultra-cold neutral plasmas. Our work opens a promising way to treat the screening effect of hot and warm dense plasma, which is a bottleneck of those extensive studies in high-energy-density physics, such as atomic processes in plasma, plasma spectra and radiation transport properties, among others.
High SARS-CoV-2 seroprevalence in children and adults in the Austrian ski resort of Ischgl
Authors: Knabl Ludwig , Mitra Tanmay , Kimpel Janine , Rössler Annika , Volland André , Walser Andreas , Ulmer Hanno , Pipperger Lisa , Binder Sebastian C. , Riepler Lydia , Bates Katie , Bandyopadhyay Arnab , Schips Marta , Ranjan Mrinalini , Falkensammer Barbara , Borena Wegene , Meyer-Hermann Michael , von Laer Dorothee 
Published: June 2021

Abstract
Background
In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe.

Methods
Between April 21st and 27th 2020, a cross-sectional epidemiologic study targeting the full population of Ischgl (n = 1867), of which 79% could be included (n = 1473, incl. 214 children), was performed. For each individual, the study involved a SARS-CoV-2 PCR, antibody testing and structured questionnaires. A mathematical model was used to help understand the influence of the determined seroprevalence on virus transmission.

Results
The seroprevalence was 42.4% (95% confidence interval (CI) 39.8–44.7). Individuals under 18 showed a significantly lower seroprevalence of 27.1% (95% CI 21.3-33.6) than adults (45%; 95% CI 42.2–47.7; OR of 0.455, 95% CI 0.356–0.682, p < 0.001). Of the seropositive individuals, 83.7% had not been diagnosed to have had SARS-CoV-2 infection previously. The clinical course was generally mild. Over the previous two months, two COVID-19-related deaths had been recorded, corresponding to an infection fatality rate of 0.25% (95% CI 0.03–0.91). Only 8 (0.5 %) individuals were newly diagnosed to be infected with SARS-CoV-2 during this study.

Conclusions
Ischgl was hit early and hard by SARS-CoV-2 leading to a high local seroprevalence of 42.4%, which was lower in individuals below the age of 18 than in adults. Mathematical modeling suggests that a drastic decline of newly infected individuals in Ischgl by the end of April occurred due to the dual impact from the non-pharmacological interventions and a high immunization of the Ischgl population.
High-efficiency electrochemical nitrite reduction to ammonium using a Cu3P nanowire array under ambient conditions
Authors: Liang Jie , Deng Biao , Liu Qin , Wen Guilai , Liu Qian , Li Tingshuai , Luo Yonglan , Alshehri Abdulmohsen Ali , Alzahrani Khalid Ahmed , Ma Dongwei , Sun Xuping 
Published: June 2021

Cu3P enables ambient electrosynthesis of ammonium via selective NO2− reduction, achieving a yield rate of 1626.6 ± 36.1 μg h−1 cm−2 and a Faradaic efficiency of 91.2 ± 2.5%. The catalytic mechanism is investigated by theoretical calculations.
RNA sequencing reveals potential interacting networks between the altered transcriptome and ncRNome in the skeletal muscle of diabetic mice
Authors: Kesharwani Devesh , Kumar Amit , Poojary Mukta , Scaria Vinod , Datta Malabika 
Published: June 2021

Abstract
For a global epidemic like Type 2 diabetes mellitus (T2DM), while impaired gene regulation is identified as a primary cause of aberrant cellular physiology; in the past few years, non-coding RNAs (ncRNAs) have emerged as important regulators of cellular metabolism. However, there are no reports of comprehensive in-depth cross-talk between these regulatory elements and the potential consequences in the skeletal muscle during diabetes. Here, using RNA sequencing, we identified 465 mRNAs and 12 long non-coding RNAs (lncRNAs), to be differentially regulated in the skeletal muscle of diabetic mice and pathway enrichment analysis of these altered transcripts revealed pathways of insulin, FOXO and AMP-activated protein kinase (AMPK) signaling to be majorly over-represented. Construction of networks showed that these pathways significantly interact with each other that might underlie aberrant skeletal muscle metabolism during diabetes. Gene–gene interaction network depicted strong interactions among several differentially expressed genes (DEGs) namely, Prkab2, Irs1, Pfkfb3, Socs2 etc. Seven altered lncRNAs depicted multiple interactions with the altered transcripts, suggesting possible regulatory roles of these lncRNAs. Inverse patterns of expression were observed between several of the deregulated microRNAs (miRNAs) and the differentially expressed transcripts in the tissues. Towards validation, overexpression of miR-381-3p and miR-539-5p in skeletal muscle C2C12 cells significantly decreased the transcript levels of their targets, Nfkbia, Pik3r1 and Pi3kr1, Cdkn2d, respectively. Collectively, the findings provide a comprehensive understanding of the interactions and cross-talk between the ncRNome and transcriptome in the skeletal muscle during diabetes and put forth potential therapeutic options for improving insulin sensitivity.
Probing galactic double-mode RR Lyrae stars against Gaia EDR3
Authors: Kovacs Geza , Karamiqucham Behrooz 
Published: June 2021

Context. Classical double-mode pulsators (RR Lyrae stars and δ Cepheids) are important because of their simultaneous pulsation in low-order radial modes. This enables us to place stringent constraints on their physical parameters.
Aims. We use 30 bright galactic double-mode RR Lyrae (RRd) stars to estimate their luminosities and compare these luminosities with those derived from the parallaxes of the recent data release (EDR3) of the Gaia survey.
Methods. We employed pulsation and evolutionary models together with observationally determined effective temperatures to derive the basic stellar parameters.
Results. When we exclude six outlying stars (e.g., those with blending issues), the RRd and Gaia luminosities correlate well. With the adopted temperature zeropoint from one of the works based on the infrared flux method, we find it necessary to increase the Gaia parallaxes by 0.02 mas to bring the RRd and Gaia luminosities into agreement. This value is consonant with those derived from studies on binary stars in the context of Gaia. We also examined the resulting period-luminosity-metallicity (PLZ) relation in the 2MASS K band as follows from the RRd parameters. This leads to the verification of two independently derived other PLZs. No significant zeropoint differences are found. Furthermore, the predicted K absolute magnitudes agree within σ = 0.005 − 0.01 mag.
Untargeted Plasma Metabolomics and Gut Microbiome Profiling Provide Novel Insights into the Regulation of Platelet Reactivity in Healthy Individuals
Authors: Vadaq Nadira , Schirmer Melanie , Tunjungputri Rahajeng N. , Vlamakis Hera , Chiriac Cecilia , Ardiansyah Edwin , Gasem M. Hussein , Joosten Leo A. B. , de Groot Philip G. , Xavier Ramnik J. , Netea Mihai G. , van der Ven Andre J. , de Mast Quirijn 
Published: June 2021

Abstract
Background Considerable variation exists in platelet reactivity to stimulation among healthy individuals. Various metabolites and metabolic pathways influence platelet reactivity, but a comprehensive overview of these associations is missing. The gut microbiome has a strong influence on the plasma metabolome. Here, we investigated the association of platelet reactivity with results of untargeted plasma metabolomics and gut microbiome profiling.
Methods We used data from a cohort of 534 healthy adult Dutch volunteers (the 500 Functional Genomics study). Platelet activation and reactivity were measured by the expression of the alpha-granule protein P-selectin and the binding of fibrinogen to the activated integrin αIIbβ3, both in unstimulated blood and after ex vivo stimulation with platelet agonists. Plasma metabolome was measured using an untargeted metabolic profiling approach by quadrupole time-of-flight mass spectrometry. Gut microbiome data were measured by shotgun metagenomic sequencing from stool samples.
Results Untargeted metabolomics yielded 1,979 metabolites, of which 422 were identified to play a role in a human metabolic pathway. Overall, 92/422 (21.8%) metabolites were significantly associated with at least one readout of platelet reactivity. The majority of associations involved lipids, especially members of eicosanoids, including prostaglandins and leukotrienes. Dietary-derived polyphenols were also found to inhibit platelet reactivity. Validation of metabolic pathways with functional microbial profiles revealed two overlapping metabolic pathways (“alanine, aspartate, and glutamate metabolism” and “arginine biosynthesis”) that were associated with platelet reactivity.
Conclusion This comprehensive overview is an resource for understanding the regulation of platelet reactivity by the plasma metabolome and the possible contribution of the gut microbiota.