bluuebunny/crossref_metadata_2025_split huggingface dataset:
The quantitative metabolome is shaped by abiotic constraints
Authors: Akbari Amir , Yurkovich James T. , Zielinski Daniel C. , Palsson Bernhard O. 
Published: May 2021

AbstractLiving systems formed and evolved under constraints that govern their interactions with the inorganic world. These interactions are definable using basic physico-chemical principles. Here, we formulate a comprehensive set of ten governing abiotic constraints that define possible quantitative metabolomes. We apply these constraints to a metabolic network ofEscherichia colithat represents 90% of its metabolome. We show that the quantitative metabolomes allowed by the abiotic constraints are consistent with metabolomic and isotope-labeling data. We find that: (i) abiotic constraints drive the evolution of high-affinity phosphate transporters; (ii) Charge-, hydrogen- and magnesium-related constraints underlie transcriptional regulatory responses to osmotic stress; and (iii) hydrogen-ion and charge imbalance underlie transcriptional regulatory responses to acid stress. Thus, quantifying the constraints that the inorganic world imposes on living systems provides insights into their key characteristics, helps understand the outcomes of evolutionary adaptation, and should be considered as a fundamental part of theoretical biology and for understanding the constraints on evolution.
TAPBPR promotes antigen loading on MHC-I molecules using a peptide trap
Authors: McShan Andrew C. , Devlin Christine A. , Morozov Giora I. , Overall Sarah A. , Moschidi Danai , Akella Neha , Procko Erik , Sgourakis Nikolaos G. 
Published: May 2021

AbstractChaperones Tapasin and TAP-binding protein related (TAPBPR) perform the important functions of stabilizing nascent MHC-I molecules (chaperoning) and selecting high-affinity peptides in the MHC-I groove (editing). While X-ray and cryo-EM snapshots of MHC-I in complex with TAPBPR and Tapasin, respectively, have provided important insights into the peptide-deficient MHC-I groove structure, the molecular mechanism through which these chaperones influence the selection of specific amino acid sequences remains incompletely characterized. Based on structural and functional data, a loop sequence of variable lengths has been proposed to stabilize empty MHC-I molecules through direct interactions with the floor of the groove. Using deep mutagenesis on two complementary expression systems, we find that important residues for the Tapasin/TAPBPR chaperoning activity are located on a large scaffolding surface, excluding the loop. Conversely, loop mutations influence TAPBPR interactions with properly conformed MHC-I molecules, relevant for peptide editing. Detailed biophysical characterization by solution NMR, ITC and FP-based assays shows that the loop hovers above the MHC-I groove to promote the capture of incoming peptides. Our results suggest that the longer loop of TAPBPR lowers the affinity requirements for peptide selection to facilitate peptide loading under conditions and subcellular compartments of reduced ligand concentration, and to prevent disassembly of high-affinity peptide-MHC-I complexes that are transiently interrogated by TAPBPR during editing.
Reversible modulation of circadian time with chronophotopharmacology
Authors: Kolarski Dušan , Miró-Vinyals Carla , Sugiyama Akiko , Srivastava Ashutosh , Ono Daisuke , Nagai Yoshiko , Iida Mui , Itami Kenichiro , Tama Florence , Szymanski Wiktor , Hirota Tsuyoshi , Feringa Ben L. 
Published: May 2021

AbstractThe circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology.
Structure-based protein function prediction using graph convolutional networks
Authors: Gligorijević Vladimir , Renfrew P. Douglas , Kosciolek Tomasz , Leman Julia Koehler , Berenberg Daniel , Vatanen Tommi , Chandler Chris , Taylor Bryn C. , Fisk Ian M. , Vlamakis Hera , Xavier Ramnik J. , Knight Rob , Cho Kyunghyun , Bonneau Richard 
Published: May 2021

AbstractThe rapid increase in the number of proteins in sequence databases and the diversity of their functions challenge computational approaches for automated function prediction. Here, we introduce DeepFRI, a Graph Convolutional Network for predicting protein functions by leveraging sequence features extracted from a protein language model and protein structures. It outperforms current leading methods and sequence-based Convolutional Neural Networks and scales to the size of current sequence repositories. Augmenting the training set of experimental structures with homology models allows us to significantly expand the number of predictable functions. DeepFRI has significant de-noising capability, with only a minor drop in performance when experimental structures are replaced by protein models. Class activation mapping allows function predictions at an unprecedented resolution, allowing site-specific annotations at the residue-level in an automated manner. We show the utility and high performance of our method by annotating structures from the PDB and SWISS-MODEL, making several new confident function predictions. DeepFRI is available as a webserver at https://beta.deepfri.flatironinstitute.org/.
Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells
Authors: Funakoshi Shunsuke , Fernandes Ian , Mastikhina Olya , Wilkinson Dan , Tran Thinh , Dhahri Wahiba , Mazine Amine , Yang Donghe , Burnett Benjamin , Lee Jeehoon , Protze Stephanie , Bader Gary D. , Nunes Sara S. , Laflamme Michael , Keller Gordon 
Published: May 2021

AbstractCompact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.
Interplay of spin–orbit coupling and Coulomb interaction in ZnO-based electron system
Authors: Maryenko D. , Kawamura M. , Ernst A. , Dugaev V. K. , Sherman E. Ya. , Kriener M. , Bahramy M. S. , Kozuka Y. , Kawasaki M. 
Published: May 2021

AbstractSpin–orbit coupling (SOC) is pivotal for various fundamental spin-dependent phenomena in solids and their technological applications. In semiconductors, these phenomena have been so far studied in relatively weak electron–electron interaction regimes, where the single electron picture holds. However, SOC can profoundly compete against Coulomb interaction, which could lead to the emergence of unconventional electronic phases. Since SOC depends on the electric field in the crystal including contributions of itinerant electrons, electron–electron interactions can modify this coupling. Here we demonstrate the emergence of the SOC effect in a high-mobility two-dimensional electron system in a simple band structure MgZnO/ZnO semiconductor. This electron system also features strong electron–electron interaction effects. By changing the carrier density with Mg-content, we tune the SOC strength and achieve its interplay with electron–electron interaction. These systems pave a way to emergent spintronic phenomena in strong electron correlation regimes and to the formation of quasiparticles with the electron spin strongly coupled to the density.
Dual-atom Pt heterogeneous catalyst with excellent catalytic performances for the selective hydrogenation and epoxidation
Authors: Tian Shubo , Wang Bingxue , Gong Wanbing , He Zizhan , Xu Qi , Chen Wenxing , Zhang Qinghua , Zhu Youqi , Yang Jiarui , Fu Qiang , Chen Chun , Bu Yuxiang , Gu Lin , Sun Xiaoming , Zhao Huijun , Wang Dingsheng , Li Yadong 
Published: May 2021

AbstractAtomically monodispersed heterogeneous catalysts with uniform active sites and high atom utilization efficiency are ideal heterogeneous catalytic materials. Designing such type of catalysts, however, remains a formidable challenge. Herein, using a wet-chemical method, we successfully achieved a mesoporous graphitic carbon nitride (mpg-C3N4) supported dual-atom Pt2 catalyst, which exhibited excellent catalytic performance for the highly selective hydrogenation of nitrobenzene to aniline. The conversion of ˃99% is significantly superior to the corresponding values of mpg-C3N4-supported single Pt atoms and ultra-small Pt nanoparticles (~2 nm). First-principles calculations revealed that the excellent and unique catalytic performance of the Pt2 species originates from the facile H2 dissociation induced by the diatomic characteristics of Pt and the easy desorption of the aniline product. The produced Pt2/mpg-C3N4 samples are versatile and can be applied in catalyzing other important reactions, such as the selective hydrogenation of benzaldehyde and the epoxidation of styrene.
CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution
Authors: Wang Qinchuan , Hernández-Ochoa Erick O. , Viswanathan Meera C. , Blum Ian D. , Do Danh C. , Granger Jonathan M. , Murphy Kevin R. , Wei An-Chi , Aja Susan , Liu Naili , Antonescu Corina M. , Florea Liliana D. , Talbot C. Conover , Mohr David , Wagner Kathryn R. , Regot Sergi , Lovering Richard M. , Gao Peisong , Bianchet Mario A. , Wu Mark N. , Cammarato Anthony , Schneider Martin F. , Bever Gabriel S. , Anderson Mark E. 
Published: May 2021

AbstractAntagonistic pleiotropy is a foundational theory that predicts aging-related diseases are the result of evolved genetic traits conferring advantages early in life. Here we examine CaMKII, a pluripotent signaling molecule that contributes to common aging-related diseases, and find that its activation by reactive oxygen species (ROS) was acquired more than half-a-billion years ago along the vertebrate stem lineage. Functional experiments using genetically engineered mice and flies reveal ancestral vertebrates were poised to benefit from the union of ROS and CaMKII, which conferred physiological advantage by allowing ROS to increase intracellular Ca2+ and activate transcriptional programs important for exercise and immunity. Enhanced sensitivity to the adverse effects of ROS in diseases and aging is thus a trade-off for positive traits that facilitated the early and continued evolutionary success of vertebrates.
The SUN1-SPDYA interaction plays an essential role in meiosis prophase I
Authors: Chen Yanyan , Wang Yan , Chen Juan , Zuo Wu , Fan Yong , Huang Sijia , Liu Yongmei , Chen Guangming , Li Qing , Li Jinsong , Wu Jian , Bian Qian , Huang Chenhui , Lei Ming 
Published: May 2021

AbstractChromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division. Association of telomeres with the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex composed of SUN1 and KASH5 enables telomere-led chromosome movements and telomere bouquet formation, facilitating precise pairwise alignment of homologs. Here, we identify a direct interaction between SUN1 and Speedy A (SPDYA) and determine the crystal structure of human SUN1-SPDYA-CDK2 ternary complex. Analysis of meiosis prophase I process in SPDYA-binding-deficient SUN1 mutant mice reveals that the SUN1-SPDYA interaction is required for the telomere-LINC complex connection and the assembly of a ring-shaped telomere supramolecular architecture at the nuclear envelope, which is critical for efficient homologous pairing and synapsis. Overall, our results provide structural insights into meiotic telomere structure that is essential for meiotic prophase I progression.
Cell morphology-based machine learning models for human cell state classification
Authors: Li Yi , Nowak Chance M. , Pham Uyen , Nguyen Khai , Bleris Leonidas 
Published: May 2021

AbstractHerein, we implement and access machine learning architectures to ascertain models that differentiate healthy from apoptotic cells using exclusively forward (FSC) and side (SSC) scatter flow cytometry information. To generate training data, colorectal cancer HCT116 cells were subjected to miR-34a treatment and then classified using a conventional Annexin V/propidium iodide (PI)-staining assay. The apoptotic cells were defined as Annexin V-positive cells, which include early and late apoptotic cells, necrotic cells, as well as other dying or dead cells. In addition to fluorescent signal, we collected cell size and granularity information from the FSC and SSC parameters. Both parameters are subdivided into area, height, and width, thus providing a total of six numerical features that informed and trained our models. A collection of logistical regression, random forest, k-nearest neighbor, multilayer perceptron, and support vector machine was trained and tested for classification performance in predicting cell states using only the six aforementioned numerical features. Out of 1046 candidate models, a multilayer perceptron was chosen with 0.91 live precision, 0.93 live recall, 0.92 live f value and 0.97 live area under the ROC curve when applied on standardized data. We discuss and highlight differences in classifier performance and compare the results to the standard practice of forward and side scatter gating, typically performed to select cells based on size and/or complexity. We demonstrate that our model, a ready-to-use module for any flow cytometry-based analysis, can provide automated, reliable, and stain-free classification of healthy and apoptotic cells using exclusively size and granularity information.
Heat impact during laser ablation extraction of mineralised tissue micropillars
Authors: McPhee Samuel , Groetsch Alexander , Shephard Jonathan D. , Wolfram Uwe 
Published: May 2021

AbstractThe underlying constraint of ultrashort pulsed laser ablation in both the clinical and micromachining setting is the uncertainty regarding the impact on the composition of material surrounding the ablated region. A heat model representing the laser-tissue interaction was implemented into a finite element suite to assess the cumulative temperature response of bone during ultrashort pulsed laser ablation. As an example, we focus on the extraction of mineralised collagen fibre micropillars. Laser induced heating can cause denaturation of the collagen, resulting in ultrastructural loss which could affect mechanical testing results. Laser parameters were taken from a used micropillar extraction protocol. The laser scanning pattern consisted of 4085 pulses, with a final radial pass being 22 $$\upmu {\text {m}}$$μmaway from the micropillar. The micropillar temperature was elevated to 70.58 $$^{\circ }{\text {C}}$$∘C, remaining 79.42 $$^{\circ }{\text {C}}$$∘Clower than that of which we interpret as an onset for denaturation. We verified the results by means of Raman microscopy and Energy Dispersive X-ray Microanalysis and found the laser-material interaction had no effect on the collagen molecules or mineral nanocrystals that constitute the micropillars. We, thus, show that ultrashort pulsed laser ablation is a safe and viable tool to fabricate bone specimens for mechanical testing at the micro- and nanoscale and we provide a computational model to efficiently assess this.
PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma
Authors: Vidarsdottir Linda , Azimi Alireza , Das Ishani , Sigvaldadottir Ingibjorg , Suryo Rahmanto Aldwin , Petri Andreas , Kauppinen Sakari , Ingvar Christian , Jönsson Göran , Olsson Håkan , Frostvik Stolt Marianne , Tuominen Rainer , Sangfelt Olle , Pokrovskaja Tamm Katja , Hansson Johan , Grandér Dan , Egyházi Brage Suzanne , Johnsson Per 
Published: May 2021

AbstractBRAF inhibitors (BRAFi) selectively target oncogenic BRAFV600E/K and are effective in 80% of advanced cutaneous malignant melanoma cases carrying the V600 mutation. However, the development of drug resistance limits their clinical efficacy. Better characterization of the underlying molecular processes is needed to further improve treatments. We previously demonstrated that transcription of PTEN is negatively regulated by the PTEN pseudogene antisense RNA, PTENP1-AS, and here we investigated the impact of this transcript on clinical outcome and BRAFi resistance in melanoma. We observed that increased expression levels of PTENP1-AS in BRAFi resistant cells associated with enrichment of EZH2 and H3K27me3 at the PTEN promoter, consequently reducing the expression levels of PTEN. Further, we showed that targeting of the PTENP1-AS transcript sensitized resistant cells to BRAFi treatment and that high expression of PTENP1-AS in stage III melanoma correlated with poor survival. Collectively, the data presented here show that PTENP1-AS is a promising target for re-sensitizing cells to BRAFi and also a possible prognostic marker for clinical outcome in stage III melanoma.
Leaky and waveguide modes in biperiodic holograms
Authors: Keshmiri Hamid , Armin Fahimeh , Elsayad Kareem , Schreiber Frank , Moreno Mauricio 
Published: May 2021

AbstractThis study details a theoretical analysis of leaky and waveguide modes in biperiodic all-dielectric holograms. By tuning diffraction orders and subsequently confining local density of optical states at two distinct resonance wavelengths, we present a new class of highly sensitive refractive index biosensing platforms that are capable of resolving 35.5 to 41.3 nm/RIU of spectral shift for two separate biological analytes.
Environmental DNA detection of an invasive ant species (Linepithema humile) from soil samples
Authors: Yasashimoto Tetsu , Sakata Masayuki K. , Sakita Tomoya , Nakajima Satoko , Ozaki Mamiko , Minamoto Toshifumi 
Published: May 2021

AbstractAlien ant species (Formicidae, Hymenoptera) cause serious damage worldwide. Early detection of invasion and rapid management are significant for controlling these species. However, these attempts are sometimes hindered by the need for direct detection techniques, such as capture, visual observation, or morphological identification. In this study, we demonstrated that environmental DNA (eDNA) analysis can be used as a monitoring tool for alien ants using Linepithema humile (Argentine ant), one of the most invasive ants, as a model species. We designed a new real-time PCR assay specific to L. humile and successfully detected eDNA from the surface soil. The reliability of eDNA analysis was substantiated by comparing eDNA detection results with traditional survey results. Additionally, we examined the relationship between eDNA concentration and distance from nests and trails. Our results support the effectiveness of eDNA for alien ant monitoring and suggest that this new method could improve our ability to detect invasive ant species.
Ndufs4 ablation decreases synaptophysin expression in hippocampus
Authors: Shil Subrata Kumar , Kagawa Yoshiteru , Umaru Banlanjo Abdulaziz , Nanto-Hara Fumika , Miyazaki Hirofumi , Yamamoto Yui , Kobayashi Shuhei , Suzuki Chitose , Abe Takaaki , Owada Yuji 
Published: May 2021

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.
Visibility and attractiveness of Fritillaria (Liliaceae) flowers to potential pollinators
Authors: Roguz Katarzyna , Hill Laurence , Koethe Sebastian , Lunau Klaus , Roguz Agata , Zych Marcin 
Published: May 2021

AbstractVisual floral characters play an important role in shaping plant-pollinator interactions. The genus Fritillaria L. (Liliaceae), comprising approximately 140 species, is described as displaying a remarkable variety of flower colours and sizes. Despite this variation in visual floral traits of fritillaries, little is known about the potential role of these features in shaping plant-pollinator interactions. Here, we seek to clarify the role of visual attraction in species offering a robust food reward for pollinators early in the spring, which is the case for Fritillaria. We also searched for potential tendencies in the evolution of floral traits crucial for plant-pollinator communication. The generality of species with green and purple flowers may indicate an influence of environmental factors other than pollinators. The flowers of the studied species seem to be visible but not very visually attractive to potential pollinators. The food rewards are hidden within the nodding perianth, and both traits are conserved among fritillaries. Additionally, visual floral traits are not good predictors of nectar properties. When in the flowers, pollinators are navigated by nectar guides in the form of contrasting nectary area colouration. Flower colour does not serve as a phenotypic filter against illegitimate pollinators—red and orange bird-pollinated fritillaries are visible to bees.