bluuebunny/crossref_metadata_2025_split huggingface dataset:
The coronavirus disease (COVID-19) – A supportive approach with selected micronutrients
Authors: Gröber Uwe , Holick Michael F. 
Published: January 2021

Abstract. Worldwide the pandemic of COVID-19 spreads rapidly and has had an enormous public health impact with substantial morbidity and mortality especially in high-risk groups, such as older people and patients with comorbidities like diabetes, dementia or cancer. In the absence of a vaccine against COVID-19 there is an urgent need to find supportive therapies that can stabilize the immune system and can help to deal with the infection, especially for vulnerable groups such as the elderly. This is especially relevant for our geriatric institutions and nursing homes. A major potential contributing factor for elderly is due to their high incidence of malnutrition: up to 80% among the hospitalized elderly. Malnutrition results when adequate macronutrients and micronutrients are lacking in the diet. Often missing in public health discussions around preventing and treating COVID-19 patients are nutritional strategies to support optimal function of their immune system. This is surprising, given the importance that nutrients play a significant role for immune function. Several micronutrients, such as vitamin D, retinol, vitamin C, selenium and zinc are of special importance supporting both the adaptive and innate immune systems. As suboptimal status or deficiencies in these immune-relevant micronutrients impair immune function and reduces the resistance to infections, micronutrient deficiencies should therefore be corrected as soon as possible, especially in the elderly and other vulnerable groups. According to epidemiological, experimental and observational studies, some case reports and a few intervention studies the supplementation of vitamin D and/or zinc are promising. The multiple anti-inflammatory and immunomodulatory effects of Vitamin D could explain its protective role against immune hyper reaction and cytokine storm in patients with severe COVID-19. A randomized, placebo-controlled intervention study even shows that high dose vitamin D supplementation promotes viral clearance in asymptomatic and mildly symptomatic SARS-CoV-2 positive individuals. Besides, the data of a recent prospective study with COVID-19 patients reveal that a significant number of them were zinc deficient. The zinc deficient patients had more complications and the deficiency was associated with a prolonged hospital stay and increased mortality. Thus, immune-relevant micronutrients may help to increase the physiological resilience against COVID-19.
An Explanation of the Nightside Ionospheric Structure of Venus
Authors: Brecht Stephen H. , Ledvina Stephen A. 
Published: January 2021

AbstractHybrid simulations of Venus have produced nightside structure. It is believed these are the first simulations to produce the structure reported by spacecraft such as the Pioneer Venus Orbiter (PVO). The simulations reveal that the structure is created by the ▽Pe ambipolar electric field when it aligns with local IMF (interplanetary magnetic field) direction. Thus, the orientation of the IMF in and near the ionosphere controls where on the nightside the tail structure will occur. The structure size and density is found to agree well with that measured by the PVO spacecraft. Further, comparisons with ion energy and velocity distributions also agree well with the summary conclusions from a variety of PVO papers and with some nightside observations by Venus Express. The agreement between the data and simulations lends confidence that the simulation results have merit.
Crystal‐Plastic Deformation in Seismically Active Carbonate Fault Rocks
Authors: Ohl Markus , Nzogang Billy , Mussi Alexandre , Wallis David , Drury Martyn , Plümper Oliver 
Published: January 2021

AbstractThe spatial separation of macroscopic rheological behaviors has led to independent conceptual treatments of frictional failure, often referred to as brittle, and viscous deformation. Detailed microstructural investigations of naturally deformed carbonate rocks indicate that both frictional failure and viscous mechanisms might operate during seismic deformation of carbonates. Here, we investigate the deformation mechanisms that were active in two carbonate fault zones in Greece by performing detailed slip‐system analyses on data from automated crystal‐orientation mapping transmission electron microscopy and electron‐backscatter diffraction. We combine the slip‐system analyses with interpretations of nanostructures and predictions from deformation mechanism maps for calcite. The nanometric grains at the principal slip surface should deform by diffusion creep but the activation of the (0001)<20> slip system is evidence for a contribution of crystal plasticity. A similar crystallographic preferred orientation appears in the cataclastic parts of the fault rocks despite exhibiting a larger grain size and a different fractal dimension, compared to the principal slip surface. The cataclastic region exhibits microstructures consistent with activation of the (0001)<20> and {104}<021> slip systems. Postdeformational, static recrystallization, and annealing produce an equilibrium microstructure with triple junctions and equant grain size. We propose that repeated introduction of plastic strain and recrystallization reduces the grain size and offers a mechanism to form a cohesive nanogranular material. This formation mechanism leads to a grain‐boundary strengthening effect resulting in slip delocalization which is observed over 6 orders of magnitude (μm‐m) and is expressed by multiple faults planes, suggesting cyclic repetition of deformation and annealing.
Efficient dilution-to-extinction isolation of novel virus–host model systems for fastidious heterotrophic bacteria
Authors: Buchholz Holger H , Michelsen Michelle L , Bolaños Luis M , Browne Emily , Allen Michael J , Temperton Ben 
Published: January 2021

Abstract
Microbes and their associated viruses are key drivers of biogeochemical processes in marine and soil biomes. While viruses of phototrophic cyanobacteria are well-represented in model systems, challenges of isolating marine microbial heterotrophs and their viruses have hampered experimental approaches to quantify the importance of viruses in nutrient recycling. A resurgence in cultivation efforts has improved the availability of fastidious bacteria for hypothesis testing, but this has not been matched by similar efforts to cultivate their associated bacteriophages. Here, we describe a high-throughput method for isolating important virus–host systems for fastidious heterotrophic bacteria that couples advances in culturing of hosts with sequential enrichment and isolation of associated phages. Applied to six monthly samples from the Western English Channel, we first isolated one new member of the globally dominant bacterial SAR11 clade and three new members of the methylotrophic bacterial clade OM43. We used these as bait to isolate 117 new phages, including the first known siphophage-infecting SAR11, and the first isolated phage for OM43. Genomic analyses of 13 novel viruses revealed representatives of three new viral genera, and infection assays showed that the viruses infecting SAR11 have ecotype-specific host ranges. Similar to the abundant human-associated phage ɸCrAss001, infection dynamics within the majority of isolates suggested either prevalent lysogeny or chronic infection, despite a lack of associated genes, or host phenotypic bistability with lysis putatively maintained within a susceptible subpopulation. Broader representation of important virus–host systems in culture collections and genomic databases will improve both our understanding of virus–host interactions, and accuracy of computational approaches to evaluate ecological patterns from metagenomic data.
SCA-1 micro-heterogeneity in the fate decision of dystrophic fibro/adipogenic progenitors
Authors: Giuliani Giulio , Vumbaca Simone , Fuoco Claudia , Gargioli Cesare , Giorda Ezio , Massacci Giorgia , Palma Alessandro , Reggio Alessio , Riccio Federica , Rosina Marco , Vinci Maria , Castagnoli Luisa , Cesareni Gianni 
Published: January 2021

AbstractThe term micro-heterogeneity refers to non-genetic cell to cell variability observed in a bell-shaped distribution of the expression of a trait within a population. The contribution of micro-heterogeneity to physiology and pathology remains largely uncharacterised. To address such an issue, we investigated the impact of heterogeneity in skeletal muscle fibro/adipogenic progenitors (FAPs) isolated from an animal model of Duchenne muscular dystrophy (DMD), the mdx mouse. FAPs play an essential role in muscle homoeostasis. However, in pathological conditions or ageing, they are the source of intramuscular infiltrations of fibrotic or adipose tissue. By applying a multiplex flow cytometry assay, we characterised and purified from mdx muscles two FAP cell states expressing different levels of SCA-1. The two cell states are morphologically identical and repopulate each other after several growth cycles. However, they differ in their in vitro behaviour. Cells expressing higher levels of SCA-1 (SCA1-High-FAPs) differentiate more readily into adipocytes while, when exposed to a fibrogenic stimulation, increase the expression of Col1a1 and Timp1 mRNA. A transcriptomic analysis confirmed the adipogenic propensity of SCA1-High-FAPs. In addition, SCA1-High-FAPs proliferate more extensively ex vivo and display more proliferating cells in dystrophic muscles in comparison to SCA1-Low-FAPs. Adipogenesis of both FAP cell states is inhibited in vitro by leucocytes from young dystrophic mice, while leucocytes isolated from aged dystrophic mice are less effective in limiting the adipogenesis of SCA1-High-FAPs suggesting a differential regulatory effect of the microenvironment on micro-heterogeneity. Our data suggest that FAP micro-heterogeneity is modulated in pathological conditions and that this heterogeneity in turn may impact on the behaviour of interstitial mesenchymal cells in genetic diseases.
Sequential targeting of YAP1 and p21 enhances the elimination of senescent cells induced by the BET inhibitor JQ1
Authors: Zhang Huan-Tian , Gui Tao , Liu Ri-Xu , Tong Kui-Leung , Wu Chong-Jie , Li Zhenyan , Huang Xun , Xu Qiu-Tong , Yang Jie , Tang Wang , Sang Yuan , Liu Wanting , Liu Ning , Ross Ryan D. , He Qing-Yu , Zha Zhen-Gang 
Published: January 2021

AbstractChondrosarcoma (CHS) is the second most common bone malignancy with limited therapeutic approaches. Our previous study has found that Yes associated protein 1 (YAP1) is downregulated in CHS cells treated with bromodomain and extraterminal domain (BET) inhibitor JQ1. However, the precise role of YAP1 in CHS is largely unknown. Herein, we found that YAP1 expression was upregulated in CHS tissues, and positively correlated with its grading score. Loss of YAP1 inhibited CHS proliferation and induced cellular senescence, while expression of YAP1 mutants revealed YAP1/TEA domain family member (TEAD)-dependent negative regulation of p21 and subsequent cellular senescence. These results were validated by in vivo experiments using stable shYAP1 cell lines. Mechanistically, negative regulation of p21 by YAP1 occurred post-transcriptionally via Dicer-regulated miRNA networks, specifically, the miR-17 family. Furthermore, we demonstrated that sequential targeting of YAP1 and p21 enhanced the elimination of JQ1-induced senescent cells in a Bcl-2-like 1 (Bcl-XL)/Caspase-3 dependent manner. Altogether, we unveil a novel role of YAP1 signaling in mediating CHS cell senescence and propose a one-two punch approach that sequentially targets the YAP1/p21 axis to eliminate senescent cells.
Mechanism of membrane-curvature generation by ER-tubule shaping proteins
Authors: Wang Ning , Clark Lindsay D. , Gao Yuan , Kozlov Michael M. , Shemesh Tom , Rapoport Tom A. 
Published: January 2021

AbstractThe endoplasmic reticulum (ER) network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs. These proteins have two pairs of trans-membrane (TM) segments, followed by an amphipathic helix (APH), but how they induce curvature is poorly understood. Here, we show that REEPs form homodimers by interaction within the membrane. When overexpressed or reconstituted at high concentrations with phospholipids, REEPs cause extreme curvature through their TMs, generating lipoprotein particles instead of vesicles. The APH facilitates curvature generation, as its mutation prevents ER network formation of reconstituted proteoliposomes, and synthetic L- or D-amino acid peptides abolish ER network formation in Xenopus egg extracts. In Schizosaccharomyces japonicus, the APH is required for reticulon’s exclusive ER-tubule localization and restricted mobility. Thus, the TMs and APH cooperate to generate high membrane curvature. We propose that the formation of splayed REEP/reticulon dimers is responsible for ER tubule formation.
Mineral phosphorus drives glacier algal blooms on the Greenland Ice Sheet
Authors: McCutcheon Jenine , Lutz Stefanie , Williamson Christopher , Cook Joseph M. , Tedstone Andrew J. , Vanderstraeten Aubry , Wilson Sasha , Stockdale Anthony , Bonneville Steeve , Anesio Alexandre M. , Yallop Marian L. , McQuaid James B. , Tranter Martyn , Benning Liane G. 
Published: January 2021

AbstractMelting of the Greenland Ice Sheet is a leading cause of land-ice mass
loss and cryosphere-attributed sea level rise. Blooms of pigmented glacier ice algae
lower ice albedo and accelerate surface melting in the ice sheet’s southwest sector.
Although glacier ice algae cause up to 13% of the surface melting in this region,
the controls on bloom development remain poorly understood. Here we show a direct
link between mineral phosphorus in surface ice and glacier ice algae biomass through
the quantification of solid and fluid phase phosphorus reservoirs in surface
habitats across the southwest ablation zone of the ice sheet. We demonstrate that
nutrients from mineral dust likely drive glacier ice algal growth, and thereby
identify mineral dust as a secondary control on ice sheet melting.
Tailoring the resolution of single-cell RNA sequencing for primary cytotoxic T cells
Authors: Kanev Kristiyan , Roelli Patrick , Wu Ming , Wurmser Christine , Delorenzi Mauro , Pfaffl Michael W. , Zehn Dietmar 
Published: January 2021

AbstractSingle-cell RNA sequencing in principle offers unique opportunities to improve the efficacy of contemporary T-cell based immunotherapy against cancer. The use of high-quality single-cell data will aid our incomplete understanding of molecular programs determining the differentiation and functional heterogeneity of cytotoxic T lymphocytes (CTLs), allowing for optimal therapeutic design. So far, a major obstacle to high depth single-cell analysis of CTLs is the minute amount of RNA available, leading to low capturing efficacy. Here, to overcome this, we tailor a droplet-based approach for high-throughput analysis (tDrop-seq) and a plate-based method for high-performance in-depth CTL analysis (tSCRB-seq). The latter gives, on average, a 15-fold higher number of captured transcripts per gene compared to droplet-based technologies. The improved dynamic range of gene detection gives tSCRB-seq an edge in resolution sensitive downstream applications such as graded high confidence gene expression measurements and cluster characterization. We demonstrate the power of tSCRB-seq by revealing the subpopulation-specific expression of co-inhibitory and co-stimulatory receptor targets of key importance for immunotherapy.
Anomalous transport due to Weyl fermions in the chiral antiferromagnets Mn3X, X = Sn, Ge
Authors: Chen Taishi , Tomita Takahiro , Minami Susumu , Fu Mingxuan , Koretsune Takashi , Kitatani Motoharu , Muhammad Ikhlas , Nishio-Hamane Daisuke , Ishii Rieko , Ishii Fumiyuki , Arita Ryotaro , Nakatsuji Satoru 
Published: January 2021

AbstractThe recent discoveries of strikingly large zero-field Hall and Nernst effects in antiferromagnets Mn3X (X = Sn, Ge) have brought the study of magnetic topological states to the forefront of condensed matter research and technological innovation. These effects are considered fingerprints of Weyl nodes residing near the Fermi energy, promoting Mn3X (X = Sn, Ge) as a fascinating platform to explore the elusive magnetic Weyl fermions. In this review, we provide recent updates on the insights drawn from experimental and theoretical studies of Mn3X (X = Sn, Ge) by combining previous reports with our new, comprehensive set of transport measurements of high-quality Mn3Sn and Mn3Ge single crystals. In particular, we report magnetotransport signatures specific to chiral anomalies in Mn3Ge and planar Hall effect in Mn3Sn, which have not yet been found in earlier studies. The results summarized here indicate the essential role of magnetic Weyl fermions in producing the large transverse responses in the absence of magnetization.
Dual mechanism β-amino acid polymers promoting cell adhesion
Authors: Chen Qi , Zhang Donghui , Zhang Wenjing , Zhang Haodong , Zou Jingcheng , Chen Mingjiao , Li Jin , Yuan Yuan , Liu Runhui 
Published: January 2021

AbstractCell adhesion has tremendous impact on the function of culture platforms and implants. Cell-adhesive proteins and peptides have been extensively used for decades to promote cell adhesion, however, their application suffers from their easy enzymatic degradation, difficulty in large-scale preparation and expensiveness. To develop the next-generation cell-adhesive materials, we mimic the cell adhesion functions and mechanisms of RGD and KRSR peptides and design cell-adhesive cationic-hydrophobic amphiphilic β-amino acid polymers that are stable upon proteolysis and easily prepared in large scale at low cost. The optimal polymer strongly promotes cell adhesion, using preosteoblast cell as a model, by following dual mechanisms that are independent of sequence and chirality of the statistic copolymer. Our strategy opens avenues in designing the next-generation cell-adhesive materials and may guide future studies and applications.
Whole genome sequencing of metastatic colorectal cancer reveals prior treatment effects and specific metastasis features
Authors: Mendelaar Pauline A. J. , Smid Marcel , van Riet Job , Angus Lindsay , Labots Mariette , Steeghs Neeltje , Hendriks Mathijs P. , Cirkel Geert A. , van Rooijen Johan M. , Ten Tije Albert J. , Lolkema Martijn P. , Cuppen Edwin , Sleijfer Stefan , Martens John W. M. , Wilting Saskia M. 
Published: January 2021

AbstractIn contrast to primary colorectal cancer (CRC) little is known about the genomic landscape of metastasized CRC. Here we present whole genome sequencing data of metastases of 429 CRC patients participating in the pan-cancer CPCT-02 study (NCT01855477). Unsupervised clustering using mutational signature patterns highlights three major patient groups characterized by signatures known from primary CRC, signatures associated with received prior treatments, and metastasis-specific signatures. Compared to primary CRC, we identify additional putative (non-coding) driver genes and increased frequencies in driver gene mutations. In addition, we identify specific genes preferentially affected by microsatellite instability. CRC-specific 1kb-10Mb deletions, enriched for common fragile sites, and LINC00672 mutations are associated with response to treatment in general, whereas FBXW7 mutations predict poor response specifically to EGFR-targeted treatment. In conclusion, the genomic landscape of mCRC shows defined changes compared to primary CRC, is affected by prior treatments and contains features with potential clinical relevance.
Human organoid biofilm model for assessing antibiofilm activity of novel agents
Authors: Wu Bing , Haney Evan F. , Akhoundsadegh Noushin , Pletzer Daniel , Trimble Michael J. , Adriaans Alwin E. , Nibbering Peter H. , Hancock Robert E. W. 
Published: January 2021

AbstractBacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.
A general and transferable deep learning framework for predicting phase formation in materials
Authors: Feng Shuo , Fu Huadong , Zhou Huiyu , Wu Yuan , Lu Zhaoping , Dong Hongbiao 
Published: January 2021

AbstractMachine learning has been widely exploited in developing new materials. However, challenges still exist: small dataset is common for most tasks; new datasets, special descriptors and specific models need to be built from scratch when facing a new task; knowledge cannot be readily transferred between independent models. In this paper we propose a general and transferable deep learning (GTDL) framework for predicting phase formation in materials. The proposed GTDL framework maps raw data to pseudo-images with some special 2-D structure, e.g., periodic table, automatically extracts features and gains knowledge through convolutional neural network, and then transfers knowledge by sharing features extractors between models. Application of the GTDL framework in case studies on glass-forming ability and high-entropy alloys show that the GTDL framework for glass-forming ability outperformed previous models and can correctly predicted the newly reported amorphous alloy systems; for high-entropy alloys the GTDL framework can discriminate five types phases (BCC, FCC, HCP, amorphous, mixture) with accuracy and recall above 94% in fivefold cross-validation. In addition, periodic table knowledge embedded in data representations and knowledge shared between models is beneficial for tasks with small dataset. This method can be easily applied to new materials development with small dataset by reusing well-trained models for related materials.
The plant AlcR-pAlcA ethanol-inducible system displays gross growth artefacts independently of downstream pAlcA-regulated inducible constructs
Authors: Randall Ricardo S. 
Published: January 2021

AbstractThe AlcR fungal protein responds to ethanol and binds to the fungal pAlcA promoter in its presence. This system was transferred to plants over twenty years ago and was claimed to function in the same manner in plants. However, never has the control experiment with plants containing the AlcR gene alone, with no downstream inducible construct, been made. In this paper, I conduct several experiments with this control, growing p35:AlcR plants in the presence or absence of ethanol. I found that when these plants were grown in the presence of ethanol, growth in several tissues and several stages of growth was retarded. This demonstrates that this system is not suitable for use in the plant sciences, and casts doubt on the conclusions of papers that have published phenotypes using this system.