bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSP90 mediates the connection of multiple programmed cell death in diseases
Authors: Peng Caiwang , Zhao Fengyan , Li Hengli , Li Ling , Yang Yantao , Liu Fang 
Published: November 2022

AbstractHeat shock protein (HSP) 90, an important component of the molecular chaperone network, is closely concerned with cellular signaling pathways and stress response by participating in the process of maturation and activation of client proteins, playing a crucial role both in the normal and abnormal operation of the organism. In functionally defective tissues, programmed cell death (PCD) is one of the regulable fundamental mechanisms mediated by HSP90, including apoptosis, autophagy, necroptosis, ferroptosis, and others. Here, we show the complex relationship between HSP90 and different types of PCD in various diseases, and discuss the possibility of HSP90 as the common regulatory nodal in multiple PCD, which would provide a new perspective for the therapeutic approaches in disease.
Analysis of clinically relevant variants from ancestrally diverse Asian genomes
Authors: Chan Sock Hoai , Bylstra Yasmin , Teo Jing Xian , Kuan Jyn Ling , Bertin Nicolas , Gonzalez-Porta Mar , Hebrard Maxime , Tirado-Magallanes Roberto , Tan Joanna Hui Juan , Jeyakani Justin , Li Zhihui , Chai Jin Fang , Chong Yap Seng , Davila Sonia , Goh Liuh Ling , Lee Eng Sing , Wong Eleanor , Wong Tien Yin ,   SG10K_Health Consortium, Aung Tin , Ban Kenneth Hon Kim , Bellis Claire , Chee Miao Li , Chee Miao Ling , Chew Wen Jie , Chin Calvin Woon-Loong , Cook Stuart A. , Dalan Rinkoo , Dorajoo Rajkumar , Drum Chester L. , Elliott Paul , Eriksson Johan G. , Foo Roger , Gardner Daphne , Gluckman Peter D. , Goh Denise Li Meng , Jain Kanika , Kam Sylvia , Kassam Irfahan , Lakshmanan Lakshmi Narayanan , Lee Caroline G. , Lee Jimmy , Lee Soo-Chin , Lee Yung Seng , Li Hengtong , Lim Chia Wei , Lim Tock Han , Loh Marie , Maurer-Stroh Sebastian , Mina Theresia Handayani , Mok Shi Qi , Ng Hong Kiat , Pua Chee Jian , Riboli Elio , Rim Tyler Hyungtaek , Sabanayagam Charumathi , Sim Wey Cheng , Subramaniam Tavintharan , Tan Ee Shien , Tan Eng King , Tantoso Erwin , Tay Darwin , Teo Yik Ying , Tham Yih Chung , Toh Li-xian Grace , Tsai Pi Kuang , van Dam Rob M. , Veeravalli Lavanya , Khin-lin Gervais Wansaicheong , Wilm Andreas , Yang Chengxi , Yap Fabian , Yew Yik Weng , Prabhakar Shyam , Liu Jianjun , Cheng Ching-Yu , Eisenhaber Birgit , Karnani Neerja , Leong Khai Pang , Sim Xueling , Yeo Khung Keong , Chambers John C. , Tai E-Shyong , Tan Patrick , Jamuar Saumya S. , Ngeow Joanne , Lim Weng Khong 
Published: November 2022

AbstractAsian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.
FRET-FISH probes chromatin compaction at individual genomic loci in single cells
Authors: Mota Ana , Berezicki Szymon , Wernersson Erik , Harbers Luuk , Li-Wang Xiaoze , Gradin Katarina , Peuckert Christiane , Crosetto Nicola , Bienko Magda 
Published: November 2022

AbstractChromatin compaction is a key biophysical property that influences multiple DNA transactions. Lack of chromatin accessibility is frequently used as proxy for chromatin compaction. However, we currently lack tools for directly probing chromatin compaction at individual genomic loci. To fill this gap, here we present FRET-FISH, a method combining fluorescence resonance energy transfer (FRET) with DNA fluorescence in situ hybridization (FISH) to probe chromatin compaction at select loci in single cells. We first validate FRET-FISH by comparing it with ATAC-seq, demonstrating that local compaction and accessibility are strongly correlated. FRET-FISH also detects expected differences in compaction upon treatment with drugs perturbing global chromatin condensation. We then leverage FRET-FISH to study local chromatin compaction on the active and inactive X chromosome, along the nuclear radius, in different cell cycle phases, and during increasing passage number. FRET-FISH is a robust tool for probing local chromatin compaction in single cells.
The assembly of mammalian SWI/SNF chromatin remodeling complexes is regulated by lysine-methylation dependent proteolysis
Authors: Guo Pengfei , Hoang Nam , Sanchez Joseph , Zhang Elaine H. , Rajawasam Keshari , Trinidad Kristiana , Sun Hong , Zhang Hui 
Published: November 2022

AbstractThe assembly of mammalian SWI/SNF chromatin remodeling complexes is developmentally programed, and loss/mutations of SWI/SNF subunits alter the levels of other components through proteolysis, causing cancers. Here, we show that mouse Lsd1/Kdm1a deletion causes dramatic dissolution of SWI/SNF complexes and that LSD1 demethylates the methylated lysine residues in SMARCC1 and SMARCC2 to preserve the structural integrity of SWI/SNF complexes. The methylated SMARCC1/SMARCC2 are targeted for proteolysis by L3MBTL3 and the CRL4DCAF5 ubiquitin ligase complex. We identify SMARCC1 as the critical target of LSD1 and L3MBTL3 to maintain the pluripotency and self-renewal of embryonic stem cells. L3MBTL3 also regulates SMARCC1/SMARCC2 proteolysis induced by the loss of SWI/SNF subunits. Consistently, mouse L3mbtl3 deletion causes striking accumulation of SWI/SNF components, associated with embryonic lethality. Our studies reveal that the assembly/disassembly of SWI/SNF complexes is dynamically controlled by a lysine-methylation dependent proteolytic mechanism to maintain the integrity of the SWI/SNF complexes.
Parent-of-Origin inference for biobanks
Authors: Hofmeister Robin J. , Rubinacci Simone , Ribeiro Diogo M. , Buil Alfonso , Kutalik Zoltán , Delaneau Olivier 
Published: November 2022

AbstractIdentical genetic variations can have different phenotypic effects depending on their parent of origin. Yet, studies focusing on parent-of-origin effects have been limited in terms of sample size due to the lack of parental genomes or known genealogies. We propose a probabilistic approach to infer the parent-of-origin of individual alleles that does not require parental genomes nor prior knowledge of genealogy. Our model uses Identity-By-Descent sharing with second- and third-degree relatives to assign alleles to parental groups and leverages chromosome X data in males to distinguish maternal from paternal groups. We combine this with robust haplotype inference and haploid imputation to infer the parent-of-origin for 26,393 UK Biobank individuals. We screen 99 phenotypes for parent-of-origin effects and replicate the discoveries of 6 GWAS studies, confirming signals on body mass index, type 2 diabetes, standing height and multiple blood biomarkers, including the known maternal effect at the MEG3/DLK1 locus on platelet phenotypes. We also report a novel maternal effect at the TERT gene on telomere length, thereby providing new insights on the heritability of this phenotype. All our summary statistics are publicly available to help the community to better characterize the molecular mechanisms leading to parent-of-origin effects and their implications for human health.
Inducible plasmid copy number control for synthetic biology in commonly used E. coli strains
Authors: Joshi Shivang Hina-Nilesh , Yong Chentao , Gyorgy Andras 
Published: November 2022

AbstractThe ability to externally control gene expression has been paradigm shifting for all areas of biological research, especially for synthetic biology. Such control typically occurs at the transcriptional and translational level, while technologies enabling control at the DNA copy level are limited by either (i) relying on a handful of plasmids with fixed and arbitrary copy numbers; or (ii) require multiple plasmids for replication control; or (iii) are restricted to specialized strains. To overcome these limitations, we present TULIP (TUnable Ligand Inducible Plasmid): a self-contained plasmid with inducible copy number control, designed for portability across various Escherichia coli strains commonly used for cloning, protein expression, and metabolic engineering. Using TULIP, we demonstrate through multiple application examples that flexible plasmid copy number control accelerates the design and optimization of gene circuits, enables efficient probing of metabolic burden, and facilitates the prototyping and recycling of modules in different genetic contexts.
Mapping structure heterogeneities and visualizing moisture degradation of perovskite films with nano-focus WAXS
Authors: Li Nian , Pratap Shambhavi , Körstgens Volker , Vema Sundeep , Song Lin , Liang Suzhe , Davydok Anton , Krywka Christina , Müller-Buschbaum Peter 
Published: November 2022

AbstractExtensive attention has focused on the structure optimization of perovskites, whereas rare research has mapped the structure heterogeneity within mixed hybrid perovskite films. Overlooked aspects include material and structure variations as a function of depth. These depth-dependent local structure heterogeneities dictate their long-term stabilities and efficiencies. Here, we use a nano-focused wide-angle X-ray scattering method for the mapping of film heterogeneities over several micrometers across lateral and vertical directions. The relative variations of characteristic perovskite peak positions show that the top film region bears the tensile strain. Through a texture orientation map of the perovskite (100) peak, we find that the perovskite grains deposited by sequential spray-coating grow along the vertical direction. Moreover, we investigate the moisture-induced degradation products in the perovskite film, and the underlying mechanism for its structure-dependent degradation. The moisture degradation along the lateral direction primarily initiates at the perovskite-air interface and grain boundaries. The tensile strain on the top surface has a profound influence on the moisture degradation.
Sila-spirocyclization involving unstrained C(sp3)−Si bond cleavage
Authors: Shi Yufeng , Shi Xiaonan , Zhang Jinyu , Qin Ying , Li Bo , Zhao Dongbing 
Published: November 2022

AbstractC − Si Bond cleavage is one of the key elemental steps for a wide variety of silicon-based transformations. However, the cleavage of unstrained Si−C(sp3) bonds catalyzed by transition metal are still in their infancy. They generally involve the insertion of a M − C(sp2) species into the C − Si bond and consequent intramolecular C(sp2)‒Si coupling to exclusively produce siloles. Here we report the Pd-catalyzed sila-spirocyclization, in which the Si−C(sp3) bond is activated by the insertion of a M − C(sp3) species and followed by the formation of a new C(sp3)‒Si bond, allowing the construction of diverse spirosilacycles. This reactivity mode, which is strongly supported by DFT calculations may open an avenue for the Si−C(sp3) bond cleavage and silacycle synthesis.
Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops
Authors: Liao Nanqiao , Hu Zhongyuan , Miao Jinshan , Hu Xiaodi , Lyu Xiaolong , Fang Haitian , Zhou Yi-Mei , Mahmoud Ahmed , Deng Guancong , Meng Yi-Qing , Zhang Kejia , Ma Yu-Yuan , Xia Yuelin , Zhao Meng , Yang Haiyang , Zhao Yong , Kang Ling , Wang Yiming , Yang Jing-Hua , Zhou Yan-Hong , Zhang Ming-Fang , Yu Jing-Quan 
Published: November 2022

AbstractThe Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.
Structural basis for the activation of the lipid scramblase TMEM16F
Authors: Arndt Melanie , Alvadia Carolina , Straub Monique S. , Clerico Mosina Vanessa , Paulino Cristina , Dutzler Raimund 
Published: November 2022

AbstractTMEM16F, a member of the conserved TMEM16 family, plays a central role in the initiation of blood coagulation and the fusion of trophoblasts. The protein mediates passive ion and lipid transport in response to an increase in intracellular Ca2+. However, the mechanism of how the protein facilitates both processes has remained elusive. Here we investigate the basis for TMEM16F activation. In a screen of residues lining the proposed site of conduction, we identify mutants with strongly activating phenotype. Structures of these mutants determined herein by cryo-electron microscopy show major rearrangements leading to the exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. The concomitant opening of a pore promotes ion conduction in the same protein conformation. Our work has revealed a mechanism that is distinct for this branch of the family and that will aid the development of a specific pharmacology for a promising drug target.
Soft nanobrush-directed multifunctional MOF nanoarrays
Authors: Wang Shuang , Xie Wenhe , Wu Ping , Lin Geyu , Cui Yan , Tao Jiawei , Zeng Gaofeng , Deng Yonghui , Qiu Huibin 
Published: November 2022

AbstractControlled growth of well-oriented metal-organic framework nanoarrays on requisite surfaces is of prominent significance for a broad range of applications such as catalysis, sensing, optics and electronics. Herein, we develop a highly flexible soft nanobrush-directed synthesis approach for precise in situ fabrication of MOF nanoarrays on diverse substrates. The soft nanobrushes are constructed via surface-initiated living crystallization-driven self-assembly and their active poly(2-vinylpyridine) corona captures abundant metal cations through coordination interactions. This allows the rapid heterogeneous growth of MOF nanoparticles and the subsequent formation of MIL-100 (Fe), HKUST-1 and CUT-8 (Cu) nanoarrays with tailored heights of 220~1100 nm on silicon wafer, Ni foam and ceramic tube. Auxiliary functional components including metal oxygen clusters and precious metal nanoparticles can be readily incorporated to finely fabricate hybrid structures with synergistic features. Remarkably, the MIL-100 (Fe) nanoarrays doped with Keggin H3PMo10V2O40 dramatically boost formaldehyde selectivity up to 92.8% in catalytic oxidation of methanol. Moreover, the HKUST-1 nanoarrays decorated with Pt nanoparticles show exceptional sensitivity to H2S with a ppb-level detection limit.
Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity
Authors: Wang Yaping , Lang Marion C. , Lu Jinsong , Suo Mingqian , Du Mengcong , Hou Yubin , Wang Xiu-Hong , Wang Pu 
Published: November 2022

AbstractSingle cell analysis is crucial for elucidating cellular diversity and heterogeneity as well as for medical diagnostics operating at the ultimate detection limit. Although superbly sensitive biosensors have been developed using the strongly enhanced evanescent fields provided by optical microcavities, real-time quantification of intracellular molecules remains challenging due to the extreme low quantity and limitations of the current techniques. Here, we introduce an active-mode optical microcavity sensing stage with enhanced sensitivity that operates via Förster resonant energy transferring (FRET) mechanism. The mutual effects of optical microcavity and FRET greatly enhances the sensing performance by four orders of magnitude compared to pure Whispering gallery mode (WGM) microcavity sensing system. We demonstrate distinct sensing mechanism of FRET-WGM from pure WGM. Predicted lasing wavelengths of both donor and acceptor by theoretical calculations are in perfect agreement with the experimental data. The proposed sensor enables quantitative molecular analysis at single cell resolution, and real-time monitoring of intracellular molecules over extended periods while maintaining the cell viability. By achieving high sensitivity at single cell level, our approach provides a path toward FRET-enhanced real-time quantitative analysis of intracellular molecules.
Molecular oxygen enhances H2O2 utilization for the photocatalytic conversion of methane to liquid-phase oxygenates
Authors: Sun Xiao , Chen Xuanye , Fu Cong , Yu Qingbo , Zheng Xu-Sheng , Fang Fei , Liu Yuanxu , Zhu Junfa , Zhang Wenhua , Huang Weixin 
Published: November 2022

AbstractH2O2 is widely used as an oxidant for photocatalytic methane conversion to value-added chemicals over oxide-based photocatalysts under mild conditions, but suffers from low utilization efficiencies. Herein, we report that O2 is an efficient molecular additive to enhance the utilization efficiency of H2O2 by suppressing H2O2 adsorption on oxides and consequent photogenerated holes-mediated H2O2 dissociation into O2. In photocatalytic methane conversion over an anatase TiO2 nanocrystals predominantly enclosed by the {001} facets (denoted as TiO2{001})-C3N4 composite photocatalyst at room temperature and ambient pressure, O2 additive significantly enhances the utilization efficiency of H2O2 up to 93.3%, giving formic acid and liquid-phase oxygenates selectivities respectively of 69.8% and 97% and a formic acid yield of 486 μmolHCOOH·gcatalyst−1·h−1. Efficient charge separation within TiO2{001}-C3N4 heterojunctions, photogenerated holes-mediated activation of CH4 into ·CH3 radicals on TiO2{001} and photogenerated electrons-mediated activation of H2O2 into ·OOH radicals on C3N4, and preferential dissociative adsorption of methanol on TiO2{001} are responsible for the active and selective photocatalytic conversion of methane to formic acid over TiO2{001}-C3N4 composite photocatalyst.
QEnclave - A practical solution for secure quantum cloud computing
Authors: Ma Yao , Kashefi Elham , Arapinis Myrto , Chakraborty Kaushik , Kaplan Marc 
Published: November 2022

AbstractWe introduce a secure hardware device named a QEnclave that can secure the remote execution of quantum operations while only using classical controls. This device extends to quantum computing from the classical concept of a secure enclave that isolates a computation from its environment to provide privacy and tamper-resistance. Remarkably, our QEnclave only performs single qubit rotations but can nevertheless be used to secure an arbitrary quantum computation even if the qubit source is controlled by an adversary. More precisely, by attaching a QEnclave to a quantum computer, a remote client controlling the QEnclave can securely delegate its computation to the server solely using classical communication. We investigate the security of our QEnclave by modeling it as an ideal functionality named remote state rotation (RSR). We show that this resource, similar to the previously introduced functionality of remote state preparation, allows blind delegated quantum computing with perfect security. Our proof under the Abstract Cryptography framework shows the construction of remote state preparation from remote state rotation while preserving security. An immediate consequence is the weakening of the requirements for blind delegated computation. While previous delegated protocols relied on a client that can either generate or measure quantum states, we show that this same functionality can be achieved with a client that only transforms quantum states without generating or measuring them.
LINC00839 promotes malignancy of liver cancer via binding FMNL2 under hypoxia
Authors: Xie Yangyi , Lin Hongsheng , Wei Wei , Kong Yinzhi , Fang Qiaoling , Chen Enran , Liu Jianghua , Li Mingfen 
Published: November 2022

AbstractLiver cancer is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with liver cancer. Hypoxia is a common feature of solid tumors and enhances malignant character of cancer cells. However, the exact mechanisms involved in hypoxia-driven liver cancer progression and metastasis have not been well clarified so far. The aim of this study was to investigate the contribution of long non-coding RNA (lncRNA) in hypoxia promoting liver cancer progression. We screened and revealed LINC00839 as a novel hypoxia-responsive lncRNA in liver cancer. LINC00839 expression was up-regulated in liver cancer tissues and cell lines, and the patients with high LINC00839 expression had shortened overall survival. LINC00839 further overexpressed under hypoxia and promoted liver cancer cell proliferation, migration, and invasion. Mechanistically, LINC00839 bound multiple proteins that were primarily associated with the metabolism and RNA transport, and positively regulated the expression of Formin-like protein 2 (FMNL2). LINC00839 could promote hypoxia-mediated liver cancer progression, suggesting it may be a clinically valuable biomarker and serve as a molecular target for the diagnosis, prognosis, and therapy of liver cancer.
A preliminary deep learning study on automatic segmentation of contrast-enhanced bolus in videofluorography of swallowing
Authors: Ariji Yoshiko , Gotoh Masakazu , Fukuda Motoki , Watanabe Satoshi , Nagao Toru , Katsumata Akitoshi , Ariji Eiichiro 
Published: November 2022

AbstractAlthough videofluorography (VFG) is an effective tool for evaluating swallowing functions, its accurate evaluation requires considerable time and effort. This study aimed to create a deep learning model for automated bolus segmentation on VFG images of patients with healthy swallowing and dysphagia using the artificial intelligence deep learning segmentation method, and to assess the performance of the method. VFG images of 72 swallowing of 12 patients were continuously converted into 15 static images per second. In total, 3910 images were arbitrarily assigned to the training, validation, test 1, and test 2 datasets. In the training and validation datasets, images of colored bolus areas were prepared, along with original images. Using a U-Net neural network, a trained model was created after 500 epochs of training. The test datasets were applied to the trained model, and the performances of automatic segmentation (Jaccard index, Sørensen–Dice coefficient, and sensitivity) were calculated. All performance values for the segmentation of the test 1 and 2 datasets were high, exceeding 0.9. Using an artificial intelligence deep learning segmentation method, we automatically segmented the bolus areas on VFG images; our method exhibited high performance. This model also allowed assessment of aspiration and laryngeal invasion.