bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure
Authors: Oelen Roy , de Vries Dylan H. , Brugge Harm , Gordon M. Grace , Vochteloo Martijn ,   single-cell eQTLGen consortium,   BIOS Consortium, Ye Chun J. , Westra Harm-Jan , Franke Lude , van der Wijst Monique G. P. 
Published: June 2022

AbstractThe host’s gene expression and gene regulatory response to pathogen exposure can be influenced by a combination of the host’s genetic background, the type of and exposure time to pathogens. Here we provide a detailed dissection of this using single-cell RNA-sequencing of 1.3M peripheral blood mononuclear cells from 120 individuals, longitudinally exposed to three different pathogens. These analyses indicate that cell-type-specificity is a more prominent factor than pathogen-specificity regarding contexts that affect how genetics influences gene expression (i.e., eQTL) and co-expression (i.e., co-expression QTL). In monocytes, the strongest responder to pathogen stimulations, 71.4% of the genetic variants whose effect on gene expression is influenced by pathogen exposure (i.e., response QTL) also affect the co-expression between genes. This indicates widespread, context-specific changes in gene expression level and its regulation that are driven by genetics. Pathway analysis on theCLEC12Agene that exemplifies cell-type-, exposure-time- and genetic-background-dependent co-expression interactions, shows enrichment of the interferon (IFN) pathway specifically at 3-h post-exposure in monocytes. Similar genetic background-dependent association between IFN activity andCLEC12Aco-expression patterns is confirmed in systemic lupus erythematosus by in silico analysis, which implies thatCLEC12Amight be an IFN-regulated gene. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.
Cell fate roadmap of human primed-to-naive transition reveals preimplantation cell lineage signatures
Authors: Bi Yan , Tu Zhifen , Zhou Jianfeng , Zhu Xuehao , Wang Hong , Gao Shaorong , Wang Yixuan 
Published: June 2022

AbstractHuman naive pluripotent stem cells offer a unique window into early embryogenesis studies. Recent studies have reported several strategies to obtain cells in the naive state. However, cell fate transitions and the underlying mechanisms remain poorly understood. Here, by a dual fluorescent reporter system, we depict the cell fate dynamics from primed state toward naive pluripotency with ALPG activation followed by the activation of OCT4-distal enhancer. Integration of transcription profiles and the chromatin accessibility landscape reveals the appearance of primitive endoderm and trophectoderm signatures in the transitioning subpopulations, with the capacities for derivation of extra-embryonic endoderm and trophoblast stem cell lines, respectively. Furthermore, despite different fluorescent dynamics, all transitioning intermediates are capable of reaching the naive state with prolonged induction, showing their developmental plasticity and potential. Overall, our study describes a global cell roadmap toward naive pluripotency and provides hints for embryo modeling-related studies.
Adipocyte HIF2α functions as a thermostat via PKA Cα regulation in beige adipocytes
Authors: Han Ji Seul , Jeon Yong Geun , Oh Minsik , Lee Gung , Nahmgoong Hahn , Han Sang Mun , Choi Jeehye , Kim Ye Young , Shin Kyung Cheul , Kim Jiwon , Jo Kyuri , Choe Sung Sik , Park Eun Jung , Kim Sun , Kim Jae Bum 
Published: June 2022

AbstractThermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate that adipocyte hypoxia-inducible factor α (HIFα) plays a key role in calibrating thermogenic function upon cold and re-warming. In beige adipocytes, HIFα attenuates protein kinase A (PKA) activity, leading to suppression of thermogenic activity. Mechanistically, HIF2α suppresses PKA activity by inducing miR-3085-3p expression to downregulate PKA catalytic subunit α (PKA Cα). Ablation of adipocyte HIF2α stimulates retention of beige adipocytes, accompanied by increased PKA Cα during re-warming after cold stimuli. Moreover, administration of miR-3085-3p promotes beige-to-white transition via downregulation of PKA Cα and mitochondrial abundance in adipocyte HIF2α deficient mice. Collectively, these findings suggest that HIF2α-dependent PKA regulation plays an important role as a thermostat through dynamic remodeling of beige adipocytes.
Small reorganization energy acceptors enable low energy losses in non-fullerene organic solar cells
Authors: Shi Yanan , Chang Yilin , Lu Kun , Chen Zhihao , Zhang Jianqi , Yan Yangjun , Qiu Dingding , Liu Yanan , Adil Muhammad Abdullah , Ma Wei , Hao Xiaotao , Zhu Lingyun , Wei Zhixiang 
Published: June 2022

AbstractMinimizing energy loss is of critical importance in the pursuit of attaining high-performance organic solar cells. Interestingly, reorganization energy plays a crucial role in photoelectric conversion processes. However, the understanding of the relationship between reorganization energy and energy losses has rarely been studied. Here, two acceptors, Qx-1 and Qx-2, were developed. The reorganization energies of these two acceptors during photoelectric conversion processes are substantially smaller than the conventional Y6 acceptor, which is beneficial for improving the exciton lifetime and diffusion length, promoting charge transport, and reducing the energy loss originating from exciton dissociation and non-radiative recombination. So, a high efficiency of 18.2% with high open circuit voltage above 0.93 V in the PM6:Qx-2 blend, accompanies a significantly reduced energy loss of 0.48 eV. This work underlines the importance of the reorganization energy in achieving small energy losses and paves a way to obtain high-performance organic solar cells.
The 3D mutational constraint on amino acid sites in the human proteome
Authors: Li Bian , Roden Dan M. , Capra John A. 
Published: June 2022

AbstractQuantification of the tolerance of protein sites to genetic variation has become a cornerstone of variant interpretation. We hypothesize that the constraint on missense variation at individual amino acid sites is largely shaped by direct interactions with 3D neighboring sites. To quantify this constraint, we introduce a framework called COntact Set MISsense tolerance (or COSMIS) and comprehensively map the landscape of 3D mutational constraint on 6.1 million amino acid sites covering 16,533 human proteins. We show that 3D mutational constraint is pervasive and that the level of constraint is strongly associated with disease relevance both at the site and the protein level. We demonstrate that COSMIS performs significantly better at variant interpretation tasks than other population-based constraint metrics while also providing structural insight into the functional roles of constrained sites. We anticipate that COSMIS will facilitate the interpretation of protein-coding variation in evolution and prioritization of sites for mechanistic investigation.
A genome-wide atlas of antibiotic susceptibility targets and pathways to tolerance
Authors: Leshchiner Dmitry , Rosconi Federico , Sundaresh Bharathi , Rudmann Emily , Ramirez Luisa Maria Nieto , Nishimoto Andrew T. , Wood Stephen J. , Jana Bimal , Buján Noemí , Li Kaicheng , Gao Jianmin , Frank Matthew , Reeve Stephanie M. , Lee Richard E. , Rock Charles O. , Rosch Jason W. , van Opijnen Tim 
Published: June 2022

AbstractDetailed knowledge on how bacteria evade antibiotics and eventually develop resistance could open avenues for novel therapeutics and diagnostics. It is thereby key to develop a comprehensive genome-wide understanding of how bacteria process antibiotic stress, and how modulation of the involved processes affects their ability to overcome said stress. Here we undertake a comprehensive genetic analysis of how the human pathogen Streptococcus pneumoniae responds to 20 antibiotics. We build a genome-wide atlas of drug susceptibility determinants and generated a genetic interaction network that connects cellular processes and genes of unknown function, which we show can be used as therapeutic targets. Pathway analysis reveals a genome-wide atlas of cellular processes that can make a bacterium less susceptible, and often tolerant, in an antibiotic specific manner. Importantly, modulation of these processes confers fitness benefits during active infections under antibiotic selection. Moreover, screening of sequenced clinical isolates demonstrates that mutations in genes that decrease antibiotic sensitivity and increase tolerance readily evolve and are frequently associated with resistant strains, indicating such mutations could be harbingers for the emergence of antibiotic resistance.
Elucidating the origin of chiroptical activity in chiral 2D perovskites through nano-confined growth
Authors: Ma Sunihl , Jung Young-Kwang , Ahn Jihoon , Kyhm Jihoon , Tan Jeiwan , Lee Hyungsoo , Jang Gyumin , Lee Chan Uk , Walsh Aron , Moon Jooho 
Published: June 2022

AbstractChiral perovskites are being extensively studied as a promising candidate for spintronic- and polarization-based optoelectronic devices due to their interesting spin-polarization properties. However, the origin of chiroptical activity in chiral perovskites is still unknown, as the chirality transfer mechanism has been rarely explored. Here, through the nano-confined growth of chiral perovskites (MBA2PbI4(1-x)Br4x), we verified that the asymmetric hydrogen-bonding interaction between chiral molecular spacers and the inorganic framework plays a key role in promoting the chiroptical activity of chiral perovskites. Based on this understanding, we observed remarkable asymmetry behavior (absorption dissymmetry of 2.0 × 10−3 and anisotropy factor of photoluminescence of 6.4 × 10−2 for left- and right-handed circularly polarized light) in nanoconfined chiral perovskites even at room temperature. Our findings suggest that electronic interactions between building blocks should be considered when interpreting the chirality transfer phenomena and designing hybrid materials for future spintronic and polarization-based devices.
Engineered non-covalent π interactions as key elements for chiral recognition
Authors: Jin Ming Yu , Zhen Qianqian , Xiao Dengmengfei , Tao Guanyu , Xing Xiangyou , Yu Peiyuan , Xu Chen 
Published: June 2022

AbstractMolecular recognition and self-assembly are often mediated by intermolecular forces involving aromatic π-systems. Despite the ubiquity of such interactions in biological systems and in the design of functional materials, the elusive nature of aromatic π interaction results in that they have been seldom used as a design element for promoting challenging chemical reactions. Described here is a well-engineered catalytic system into which non-covalent π interactions are directly incorporated. Enabled by a lone pair-π interaction and a π-π stacking interaction operating collectively, efficient chiral recognition is successfully achieved in the long-pursued dihydroxylation-based kinetic resolution. Density functional theory calculations shed light on the crucial role played by the lone pair-π interaction between the carbonyl oxygen of the cinchona alkaloid ligand and the electron-deficient phthalazine π moiety of the substrate in the stereoselectivity-determining transition states. This discovery serves as a proof-of-principle example showing how the weak non-covalent π interactions, if ingeniously designed, could be a powerful guide in attaining highly enantioselective catalysis.
Scrutinizing pathogenicity of the USH2A c.2276 G > T; p.(Cys759Phe) variant
Authors: Reurink Janine , de Vrieze Erik , Li Catherina H. Z. , van Berkel Emma , Broekman Sanne , Aben Marco , Peters Theo , Oostrik Jaap , Neveling Kornelia , Venselaar Hanka , Ramos Mariana Guimarães , Gilissen Christian , Astuti Galuh D. N. , Galbany Jordi Corominas , van Lith-Verhoeven Janneke J. C. , Ockeloen Charlotte W. , Haer-Wigman Lonneke , Hoyng Carel B. , Cremers Frans P. M. , Kremer Hannie , Roosing Susanne , van Wijk Erwin 
Published: June 2022

AbstractThe USH2A variant c.2276 G > T (p.(Cys759Phe)) has been described by many authors as a frequent cause of autosomal recessive retinitis pigmentosa (arRP). However, this is in contrast with the description of two asymptomatic individuals homozygous for this variant. We therefore assessed pathogenicity of the USH2A c.2276 G > T variant using extensive genetic and functional analyses. Whole genome sequencing and optical genome mapping were performed for three arRP cases homozygous for USH2A c.2276 G > T to exclude alternative genetic causes. A minigene splice assay was designed to investigate the effect of c.2276 G > T on pre-mRNA splicing, in presence or absence of the nearby c.2256 T > C variant. Moreover, an ush2ap.(Cys771Phe) zebrafish knock-in model mimicking human p.(Cys759Phe) was generated and characterized using functional and immunohistochemical analyses. Besides the homozygous c.2276 G > T USH2A variant, no alternative genetic causes were identified. Evaluation of the ush2ap.(Cys771Phe) zebrafish model revealed strongly reduced levels of usherin expression at the photoreceptor periciliary membrane, increased levels of rhodopsin localization in the photoreceptor cell body and decreased electroretinogram (ERG) b-wave amplitudes compared to wildtype controls. In conclusion, we confirmed pathogenicity of USH2A c.2276 G > T (p.(Cys759Phe)). Consequently, cases homozygous for c.2276 G > T can now receive a definite genetic diagnosis and can be considered eligible for receiving future QR-421a-mediated exon 13 skipping therapy.
Highly efficient fiber-shaped organic solar cells toward wearable flexible electronics
Authors: Lv Dan , Jiang Qianqing , Shang Yuanyuan , Liu Dianyi 
Published: June 2022

AbstractFiber-shaped solar cells (FSCs) show great potential to act as the power source in the wearable electronics field. Due to the unique advantages of the fiber-shaped organic solar cells (FOSCs), such as all-solid-state, ease of fabrication, and environmental friendliness, FOSCs are the strongest candidate among all types of FSCs for wearable electronics. However, the development of FOSCs is seriously lagging behind other types of FSCs. In this work, we demonstrate the efficient FOSCs with non-fullerene-acceptors (NFAs)-based light-harvesting materials. The FOSCs present efficiencies exceeding 9% under AM 1.5 G irradiation conditions. The performance influence factors including hole/electron transport layers, active layer, counter electrodes, solvents, and especially, the environmental humidity is systematically studied. The FOSCs not only can easily drive the electrical devices but also can be woven into the textile to charge the smartwatch. The study exhibits the great potential to apply the FOSCs as the power supply source in the wearable electronic field.
Balancing efficiency and transparency in organic transparent photovoltaics
Authors: Meng Ruiqian , Jiang Qianqing , Liu Dianyi 
Published: June 2022

AbstractThe challenges in transparent photovoltaic (TPV) fields are still that the device transparency and efficiency are difficult to be balanced to meet the requirements of practical applications. In this study, we systematically investigated the interrelationship between photovoltaic film properties, optical transmission, and photovoltaic performances in the near-infrared harvesting organic TPVs. The results indicate that the photovoltaic film thickness determines the TPV’s transparency and meanwhile affects the device efficiency; by contrast, the donor–acceptor ratio only affects device efficiency and has little effect on transparency. By controlling the film thickness and donor–acceptor ratio, the average visible transmission (AVT) of TPVs can be precisely managed in the range of 40% - 85%, and the device efficiency can achieve as high as 4.06% and 2.38% while the AVT exceeds 70% and 80%, respectively. Importantly, the large area (~10 cm2) TPV modules and ultra-flexible devices were then successfully prepared based on the systematical study.
Performance fluctuations and evaluation of a piston type integrated high pressure pump-energy recovery device
Authors: Zhang Yin , Song Daiwang , Wang Haitao , Wang Xiaoli , Jiang Lidong , Wang Chengpeng , Fan Man , Zhao Jingzhou 
Published: June 2022

AbstractThe development of energy recovery device (ERD) is a decisive factor for the recent prevalence of reverse osmosis (RO) technology in the seawater desalination field. Unlike broadly studied large scale ERDs, the investigations of small scale ERDs are scarcely reported, especially on the performance fluctuations under variable operating conditions. Based on an authors’ exploratory research on a piston type integrated high pressure pump-energy recovery device (HPP-ERD), further performance exploitation of the HPP-ERD is conducted. With a constructed experiment platform, the influences of inlet seawater temperature, inlet seawater salinity, as well as the operating frequency on the performance of the HPP-ERD coupled with seawater reverse osmosis (SWRO) desalination system are investigated. The temperature and salinity of the inlet seawater are numerically correlated with the specific energy consumption (SEC) of the HPP-ERD. With the correlated equation, the marine hydrological data of two observatories acquired from a national authoritative database, and the annualized life cycle cost approach incorporated, annual performance assessment is proposed for an SWRO desalination system equipped with the HPP-ERD in the light of energy and economic indices. The study results indicate that the proposed HPP-ERD is competent under various operating conditions for SWRO desalination systems.
QMugs, quantum mechanical properties of drug-like molecules
Authors: Isert Clemens , Atz Kenneth , Jiménez-Luna José , Schneider Gisbert 
Published: June 2022

AbstractMachine learning approaches in drug discovery, as well as in other areas of the chemical sciences, benefit from curated datasets of physical molecular properties. However, there currently is a lack of data collections featuring large bioactive molecules alongside first-principle quantum chemical information. The open-access QMugs (Quantum-Mechanical Properties of Drug-like Molecules) dataset fills this void. The QMugs collection comprises quantum mechanical properties of more than 665 k biologically and pharmacologically relevant molecules extracted from the ChEMBL database, totaling ~2 M conformers. QMugs contains optimized molecular geometries and thermodynamic data obtained via the semi-empirical method GFN2-xTB. Atomic and molecular properties are provided on both the GFN2-xTB and on the density-functional levels of theory (DFT, ωB97X-D/def2-SVP). QMugs features molecules of significantly larger size than previously-reported collections and comprises their respective quantum mechanical wave functions, including DFT density and orbital matrices. This dataset is intended to facilitate the development of models that learn from molecular data on different levels of theory while also providing insight into the corresponding relationships between molecular structure and biological activity.
DoE-derived continuous and robust process for manufacturing of pharmaceutical-grade wide-range LNPs for RNA-vaccine/drug delivery
Authors: Nag Kakon , Sarker Md. Enamul Haq , Kumar Samir , Khan Habiba , Chakraborty Sourav , Islam Md. Jikrul , Baray Juwel Chandra , Khan Maksudur Rahman , Mahmud Asif , Barman Uttam , Bhuiya Eleus Hussain , Mohiuddin Mohammad , Sultana Naznin 
Published: June 2022

AbstractLipid nanoparticle (LNP) technology has become extremely demanding for delivering RNA-products and other drugs. However, there is no platform to manufacture pharmaceutical-grade LNPs with desired particle size from a wide range in continuous mode. We have developed a unique platform to obtain any specific size-range of LNPs from 60 to 180 nm satisfying pharmaceutical regulatory requirements for polydispersity index, sterility, dose uniformity and bio-functionality. We applied design of experiment (DoE) methodology and identified the critical process parameters to establish the process for global application. Cross-point validation within the response map of DoE confirmed that the platform is robust to produce specific size (± 10 nm) of LNPs within the design-range. The technology is successfully transformed to production scale and validated. Products from R&D, pilot and production batches for a candidate SARS-CoV-2 mRNA-vaccine generated equivalent biological responses. The data collectively established the robustness and bio-uniformity of doses for global RNA-vaccine/drug formulation.
Pingers are effective in reducing net entanglement of river dolphins
Authors: Kolipakam Vishnupriya , Jacob Merin , Gayathri Aaranya , Deori Sunny , Sarma Hiyashri , Tasfia Syeda Tabassum , Rokade Anurag , Negi Ranjana , Wakid Abdul , Qureshi Qamar 
Published: June 2022

AbstractGanges River dolphins echolocate, but this mechanism is inadequate for poor sonar-echoing objects such as the monofilament gillnets, causing considerable net entanglement related mortalities. Net entanglement related deaths are one of the major causes of cetacean population decline around the world. Experiments were carried out to understand the use of pingers—an acoustic deterrent, in aiding the deterrence of dolphins from fishing nets. Based on the dolphin clicks recorded, in an experimental setup spanning 36 days, a 90% deterrence was found; 22.87 ± 0.71 SE dolphin detection positive minutes per hour near non-pingered nets versus 2.20 ± 0.33 SE per hour near pingered net. Within 30 m radii of nets, visual encounters of non-calf reduced by 52% and calf by 9%, in the presence of pingers. No evidence of habituation to pingers, habitat avoidance in dolphins after pinger removal or a change in fish catch in nets because of pingers was found during the study. While the effectiveness of pingers on calves and fish catch needs further experimentation, the use of pingers to minimize net entanglement mortalities in the Ganges River dolphins seems to be the most promising solution currently available. These results have critical implications for the conservation of other species of river dolphins around the world.