bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonvolatile voltage-controlled magnetization reversal in a spin-valve multiferroic heterostructure
Authors: Liu Mengli , Du Wei , Su Hua , Zhang Huaiwu , Liu Bo , Meng Hao , Tang Xiaoli
Published: October 2021

Pure voltage-controlled magnetism, rather than a spin current or magnetic field, is the goal for next-generation ultralow power consumption spintronic devices. To advance toward this goal, we report a voltage-controlled nonvolatile 90° magnetization rotation and voltage-assisted 180° magnetization reversal in a spin-valve multiferroic heterostructure. Here, a spin valve with a synthetic antiferromagnetic structure was grown on a (110)-cut Pb(Mg1/3Nb2/3)0.7Ti0.3O3 (PMN-PT) substrate, in which only the magnetic moment of the free layer can be manipulated by an electric field (E-field) via the strain-mediated magnetoelectric coupling effect. As a result of selecting a specified PMN-PT substrate with defect dipoles, nonvolatile and stable magnetization switching was achieved by using voltage impulses. Accordingly, a giant, reversible and nonvolatile magnetoresistance modulation was achieved without the assistance of a magnetic field. In addition, by adopting a small voltage impulse, the critical magnetic field required for complete 180° magnetization reversal of the free layer can be tremendously reduced. A magnetoresistance ratio as large as that obtained by a magnetic field or spin current under normal conditions is achieved. These results indicate that E-field-assisted energy-efficient in-plane magnetization switching is a feasible strategy. This work is significant to the development of ultralow-power magnetoresistive memory and spintronic devices.
Tetraketide α-pyrone reductases in sporopollenin synthesis pathway in Gerbera hybrida: diversification of the minor function
Authors: Zhu Lingping , Zhang Teng , Teeri Teemu H
Published: October 2021

The structurally robust biopolymer sporopollenin is the major constituent of the exine layer of pollen wall and plays a vital role in plant reproductive success. The sporopollenin precursors are synthesized through an ancient polyketide biosynthetic pathway consisting of a series of anther-specific enzymes that are widely present in all land plant lineages. Tetraketide α-pyrone reductase 1 (TKPR1) and TKPR2 are two reductases catalyzing the final reduction of the carbonyl group of the polyketide synthase-synthesized tetraketide intermediates to hydroxylated α-pyrone compounds, important precursors of sporopollenin. In contrast to the functional conservation of many sporopollenin biosynthesis associated genes confirmed in diverse plant species, TKPR2’s role has been addressed only in Arabidopsis, where it plays a minor role in sporopollenin biosynthesis. We identified in gerbera two non-anther-specific orthologues of AtTKPR2, Gerbera reductase 1 (GRED1) and GRED2. Their dramatically expanded expression pattern implies involvement in pathways outside of the sporopollenin pathway. In this study, we show that GRED1 and GRED2 are still involved in sporopollenin biosynthesis with a similar secondary role as AtTKPR2 in Arabidopsis. We further show that this secondary role does not relate to the promoter of the gene, AtTKPR2 cannot rescue pollen development in Arabidopsis even when controlled by the AtTKPR1 promoter. We also identified the gerbera orthologue of AtTKPR1, GTKPR1, and characterized its crucial role in gerbera pollen development. GTKPR1 is the predominant TKPR in gerbera pollen wall formation, in contrast to the minor roles GRED1 and GRED2. GTKPR1 is in fact an excellent target for engineering male-sterile gerbera cultivars in horticultural plant breeding.
The NAM/ATAF1/2/CUC2 transcription factor PpNAC.A59 enhances PpERF.A16 expression to promote ethylene biosynthesis during peach fruit ripening
Authors: Guo Zhi-Hua , Zhang You-Jia , Yao Jia-Long , Xie Zhi-Hua , Zhang Yu-Yan , Zhang Shao-Ling , Gu Chao
Published: October 2021

Peach is a typical climacteric fruit that releases ethylene during fruit ripening. Several studies have been conducted on the transcriptional regulation of ethylene biosynthesis in peach fruit. Herein, an ethylene response factor, PpERF.A16, which was induced by exogenous ethylene, could enhance ethylene biosynthesis by directly inducing the expression of1-aminocyclopropane-1-carboxylic acid synthase(PpACS1) and1-aminocyclopropane-1-carboxylic acid oxidase(PpACO1) genes. Moreover, the NAM/ATAF1/2/CUC2 (NAC) transcription factor (TF)PpNAC.A59was coexpressed withPpERF.A16in all tested peach cultivars. Interestingly, PpNAC.A59 can directly interact with the promoter ofPpERF.A16to induce its expression but not enhanceLUCactivity driven by any promoter ofPpACS1orPpACO1. Thus, PpNAC.A59 can indirectly mediate ethylene biosynthesis via the NAC-ERF signaling cascade to induce the expression of bothPpACS1andPpACO1. These results enrich the genetic network of fruit ripening in peach and provide new insight into the ripening mechanism of other perennial fruits.
The role of watermelon caffeic acid O-methyltransferase (ClCOMT1) in melatonin biosynthesis and abiotic stress tolerance
Authors: Chang Jingjing , Guo Yanliang , Yan Jingyi , Zhang Zixing , Yuan Li , Wei Chunhua , Zhang Yong , Ma Jianxiang , Yang Jianqiang , Zhang Xian , Li Hao
Published: October 2021

Melatonin is a pleiotropic signaling molecule that regulates plant growth and responses to various abiotic stresses. The last step of melatonin synthesis in plants can be catalyzed by caffeic acid O-methyltransferase (COMT), a multifunctional enzyme reported to have N-acetylserotonin O-methyltransferase (ASMT) activity; however, the ASMT activity of COMT has not yet been characterized in nonmodel plants such as watermelon (Citrullus lanatus). Here, a total of 16 putative O-methyltransferase (ClOMT) genes were identified in watermelon. Among them, ClOMT03 (Cla97C07G144540) was considered a potential COMT gene (renamed ClCOMT1) based on its high identities (60.00–74.93%) to known COMT genes involved in melatonin biosynthesis, expression in almost all tissues, and upregulation under abiotic stresses. The ClCOMT1 protein was localized in the cytoplasm. Overexpression of ClCOMT1 significantly increased melatonin contents, while ClCOMT1 knockout using the CRISPR/Cas-9 system decreased melatonin contents in watermelon calli. These results suggest that ClCOMT1 plays an essential role in melatonin biosynthesis in watermelon. In addition, ClCOMT1 expression in watermelon was upregulated by cold, drought, and salt stress, accompanied by increases in melatonin contents. Overexpression of ClCOMT1 enhanced transgenic Arabidopsis tolerance against such abiotic stresses, indicating that ClCOMT1 is a positive regulator of plant tolerance to abiotic stresses.
The NAC transcription factor ClNAC68 positively regulates sugar content and seed development in watermelon by repressing ClINV and ClGH3.6
Authors: Wang Jinfang , Wang Yanping , Zhang Jie , Ren Yi , Li Maoying , Tian Shaowei , Yu Yongtao , Zuo Yi , Gong Guoyi , Zhang Haiying , Guo Shaogui , Xu Yong
Published: October 2021

NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in fruit ripening and quality. The watermelon genome encodes 80 NAC genes, and 21 of these NAC genes are highly expressed in both the flesh and vascular tissues. Among these genes, ClNAC68 expression was significantly higher in flesh than in rind. However, the intrinsic regulatory mechanism of ClNAC68 in fruit ripening and quality is still unknown. In this study, we found that ClNAC68 is a transcriptional repressor and that the repression domain is located in the C-terminus. Knockout of ClNAC68 by the CRISPR-Cas9 system decreased the soluble solid content and sucrose accumulation in mutant flesh. Development was delayed, germination was inhibited, and the IAA content was significantly decreased in mutant seeds. Transcriptome analysis showed that the invertase gene ClINV was the only gene involved in sucrose metabolism that was upregulated in mutant flesh, and expression of the indole-3-acetic acid-amido synthetase gene ClGH3.6 in the IAA signaling pathway was also induced in mutant seeds. EMSA and dual-luciferase assays showed that ClNAC68 directly bound to the promoters of ClINV and ClGH3.6 to repress their expression. These results indicated that ClNAC68 positively regulated sugar and IAA accumulation by repressing ClINV and ClGH3.6. Our findings provide new insights into the regulatory mechanisms by which NAC transcription factors affect fruit quality and seed development.
The CaCIPK3 gene positively regulates drought tolerance in pepper
Authors: Ma Xiao , Li Yang , Gai Wen-Xian , Li Chuang , Gong Zhen-Hui
Published: October 2021

Drought stress is a major agricultural problem restricting the growth, development, and productivity of plants. Calcineurin B-like proteins (CBLs) and CBL-interacting protein kinases (CIPKs) significantly influence the plant response to different stresses. However, the molecular mechanisms of CBL–CIPK in the drought stress response of pepper are still unknown. Here, the function ofCaCIPK3in the regulation of drought stress in pepper (Capsicum annuumL.) was explored. Transcriptomic data and quantitative real-time PCR (qRT-PCR) analysis revealed thatCaCIPK3participates in the response to multiple stresses. Knockdown ofCaCIPK3in pepper increased the sensitivity to mannitol and methyl jasmonate (MeJA). Transient overexpression ofCaCIPK3improved drought tolerance by enhancing the activities of the antioxidant system and positively regulating jasmonate (JA)-related genes. Ectopic expression ofCaCIPK3in tomato also improved drought and MeJA resistance. As the CaCIPK3-interacting partner, CaCBL2 positively influenced drought resistance. Additionally, CaWRKY1 and CaWRKY41 directly bound theCaCIPK3promoter to influence its expression. This study shows thatCaCIPK3acts as a positive regulator in drought stress resistance via the CBL–CIPK network to regulate MeJA signaling and the antioxidant defense system.
MdVQ37 overexpression reduces basal thermotolerance in transgenic apple by affecting transcription factor activity and salicylic acid homeostasis
Authors: Dong Qinglong , Duan Dingyue , Zheng Wenqian , Huang Dong , Wang Qian , Li Xiaoran , Mao Ke , Ma Fengwang
Published: October 2021

High temperature (HT) is one of the most important environmental stress factors and seriously threatens plant growth, development, and production. VQ motif-containing proteins are transcriptional regulators that have been reported to regulate plant growth and developmental processes, including responses to biotic and abiotic stresses. However, the relationships between VQ motif-containing proteins and HT stress have not been studied in depth in plants. In this study, transgenic apple (Malus domestica) plants overexpressing the apple VQ motif-containing protein-coding gene (MdVQ37) were exposed to HT stress, and the transgenic lines exhibited a heat-sensitive phenotype. In addition, physiological and biochemical studies revealed that, compared with WT plants, transgenic lines had lower enzymatic activity and photosynthetic capacity and lower amounts of nonenzymatic antioxidant system metabolites under HT stress. Transcriptome analysis revealed 1379 genes whose expression differed between the transgenic lines and WT plants. GO and KEGG pathway analyses showed that transcription factor activity and plant hormone signaling pathways were differentially influenced and enriched in the transgenic lines. Salicylic acid (SA) content analysis indicated that overexpression of MdVQ37 reduced the content of endogenous SA by regulating the expression of SA catabolism-related genes, which ultimately resulted in disruption of the SA-dependent signaling pathway under HT stress. The application of SA slightly increased the survival rate of the transgenic lines under HT stress. Taken together, our results indicate that apple MdVQ37 has a regulatory function in basal thermotolerance by modulating the activity of transcription factors and SA homeostasis. Overall, this study provides novel insights that improve our understanding of the various functions of VQ motif-containing proteins.
Standardized preservation, extraction and quantification techniques for detection of fecal SARS-CoV-2 RNA
Authors: Natarajan Aravind , Han Alvin , Zlitni Soumaya , Brooks Erin F. , Vance Summer E. , Wolfe Marlene , Singh Upinder , Jagannathan Prasanna , Pinsky Benjamin A. , Boehm Alexandria , Bhatt Ami S.
Published: October 2021

Patients with COVID-19 shed SARS-CoV-2 RNA in stool, sometimes well after their respiratory infection has cleared. This may be significant for patient health, epidemiology, and diagnosis. However, methods to preserve stool, and to extract and quantify viral RNA are not standardized. We test the performance of three preservative approaches at yielding detectable SARS-CoV-2 RNA: the OMNIgene-GUT kit, Zymo DNA/RNA shield kit, and the most commonly applied, storage without preservative. We test these in combination with three extraction kits: QIAamp Viral RNA Mini Kit, Zymo Quick-RNA Viral Kit, and MagMAX Viral/Pathogen Kit. We also test the utility of ddPCR and RT-qPCR for the reliable quantification of SARS-CoV-2 RNA from stool. We identify that the Zymo DNA/RNA preservative and the QiaAMP extraction kit yield more detectable RNA than the others, using both ddPCR and RT-qPCR. Taken together, we recommend a comprehensive methodology for preservation, extraction and detection of RNA from SARS-CoV-2 and other coronaviruses in stool.
A rational blueprint for the design of chemically-controlled protein switches
Authors: Shui Sailan , Gainza Pablo , Scheller Leo , Yang Che , Kurumida Yoichi , Rosset Stéphane , Georgeon Sandrine , Di Roberto Raphaël B. , Castellanos-Rueda Rocío , Reddy Sai T. , Correia Bruno E.
Published: October 2021

Small-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules. To design ON-switches, we converted the CDHs into a multi-domain architecture which we refer to as activation by inhibitor release switches (AIR) that incorporate a rationally designed drug-insensitive receptor protein. CDHs and AIRs showed excellent performance as drug responsive switches to control combinations of synthetic circuits in mammalian cells. This approach effectively expands the chemical space and logic responses in living cells and provides a blueprint to develop new ON- and OFF-switches.
Complex small-world regulatory networks emerge from the 3D organisation of the human genome
Authors: Brackley C. A. , Gilbert N. , Michieletto D. , Papantonis A. , Pereira M. C. F. , Cook P. R. , Marenduzzo D.
Published: October 2021

The discovery that overexpressing one or a few critical transcription factors can switch cell state suggests that gene regulatory networks are relatively simple. In contrast, genome-wide association studies (GWAS) point to complex phenotypes being determined by hundreds of loci that rarely encode transcription factors and which individually have small effects. Here, we use computer simulations and a simple fitting-free polymer model of chromosomes to show that spatial correlations arising from 3D genome organisation naturally lead to stochastic and bursty transcription as well as complex small-world regulatory networks (where the transcriptional activity of each genomic region subtly affects almost all others). These effects require factors to be present at sub-saturating levels; increasing levels dramatically simplifies networks as more transcription units are pressed into use. Consequently, results from GWAS can be reconciled with those involving overexpression. We apply this pan-genomic model to predict patterns of transcriptional activity in whole human chromosomes, and, as an example, the effects of the deletion causing the diGeorge syndrome.
Growth and site-specific organization of micron-scale biomolecular devices on living mammalian cells
Authors: Jia Sisi , Phua Siew Cheng , Nihongaki Yuta , Li Yizeng , Pacella Michael , Li Yi , Mohammed Abdul M. , Sun Sean , Inoue Takanari , Schulman Rebecca
Published: September 2021

Mesoscale molecular assemblies on the cell surface, such as cilia and filopodia, integrate information, control transport and amplify signals. Designer cell-surface assemblies could control these cellular functions. Such assemblies could be constructed from synthetic components ex vivo, making it possible to form such structures using modern nanoscale self-assembly and fabrication techniques, and then oriented on the cell surface. Here we integrate synthetic devices, micron-scale DNA nanotubes, with mammalian cells by anchoring them by their ends to specific cell surface receptors. These filaments can measure shear stresses between 0-2 dyn/cm2, a regime important for cell signaling. Nanotubes can also grow while anchored to cells, thus acting as dynamic cell components. This approach to cell surface engineering, in which synthetic biomolecular assemblies are organized with existing cellular architecture, could make it possible to build new types of sensors, machines and scaffolds that can interface with, control and measure properties of cells.
Entropic singularities give rise to quantum transmission
Authors: Siddhu Vikesh
Published: October 2021

When can noiseless quantum information be sent across noisy quantum devices? And at what maximum rate? These questions lie at the heart of quantum technology, but remain unanswered because of non-additivity— a fundamental synergy which allows quantum devices (aka quantum channels) to send more information than expected. Previously, non-additivity was known to occur in very noisy channels with coherent information much smaller than that of a perfect channel; but, our work shows non-additivity in a simple low-noise channel. Our results extend even further. We prove a general theorem concerning positivity of a channel’s coherent information. A corollary of this theorem gives a simple dimensional test for a channel’s capacity. Applying this corollary solves an open problem by characterizing all qubit channels whose complement has non-zero capacity. Another application shows a wide class of zero quantum capacity qubit channels can assist an incomplete erasure channel in sending quantum information. These results arise from introducing and linking logarithmic singularities in the von-Neumann entropy with quantum transmission: changes in entropy caused by this singularity are a mechanism responsible for both positivity and non-additivity of the coherent information. Analysis of such singularities may be useful in other physics problems.
ECNet is an evolutionary context-integrated deep learning framework for protein engineering
Authors: Luo Yunan , Jiang Guangde , Yu Tianhao , Liu Yang , Vo Lam , Ding Hantian , Su Yufeng , Qian Wesley Wei , Zhao Huimin , Peng Jian
Published: September 2021

Machine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 β-lactamase and identified variants with improved ampicillin resistance with high success rates.
Efficient propyne/propadiene separation by microporous crystalline physiadsorbents
Authors: Peng Yun-Lei , Wang Ting , Jin Chaonan , Deng Cheng-Hua , Zhao Yanming , Liu Wansheng , Forrest Katherine A. , Krishna Rajamani , Chen Yao , Pham Tony , Space Brian , Cheng Peng , Zaworotko Michael J. , Zhang Zhenjie
Published: October 2021

Selective separation of propyne/propadiene mixture to obtain pure propadiene (allene), an essential feedstock for organic synthesis, remains an unsolved challenge in the petrochemical industry, thanks mainly to their similar physicochemical properties. We herein introduce a convenient and energy-efficient physisorptive approach to achieve propyne/propadiene separation using microporous metal-organic frameworks (MOFs). Specifically, HKUST-1, one of the most widely studied high surface area MOFs that is available commercially, is found to exhibit benchmark performance (propadiene production up to 69.6 cm3/g, purity > 99.5%) as verified by dynamic breakthrough experiments. Experimental and modeling studies provide insight into the performance of HKUST-1 and indicate that it can be attributed to a synergy between thermodynamics and kinetics that arises from abundant open metal sites and cage-based molecular traps in HKUST-1.
Pentaphosphaferrocene-mediated synthesis of asymmetric organo-phosphines starting from white phosphorus
Authors: Reichl Stephan , Mädl Eric , Riedlberger Felix , Piesch Martin , Balázs Gábor , Seidl Michael , Scheer Manfred
Published: October 2021

The synthesis of phosphines is based on white phosphorus, which is usually converted to PCl3, to be afterwards substituted step by step in a non-atomic efficient manner. Herein, we describe an alternative efficient transition metal-mediated process to form asymmetrically substituted phosphines directly from white phosphorus (P4). Thereby, P4is converted to [Cp*Fe(η5-P5)] (1) (Cp* = η5-C5(CH3)5) in which one of the phosphorus atoms is selectively functionalized to the 1,1-diorgano-substituted complex [Cp*Fe(η4-P5R′R″)] (3). In a subsequent step, the phosphine PR′R″R‴ (R′ ≠ R″ ≠ R‴ = alky, aryl) (4) is released by reacting it with a nucleophile R‴M (M = alkali metal) as racemates. The starting material1can be regenerated with P4and can be reused in multiple reaction cycles without isolation of the intermediates, and only the phosphine is distilled off.
Boson-peak-like anomaly caused by transverse phonon softening in strain glass
Authors: Ren Shuai , Zong Hong-Xiang , Tao Xue-Fei , Sun Yong-Hao , Sun Bao-An , Xue De-Zhen , Ding Xiang-Dong , Wang Wei-Hua
Published: October 2021

Strain glass is a glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, yet its nature remains unclear. Here, we report a glassy feature in strain glass that was thought to be only present in structural glasses. An abnormal hump is observed in strain glass around 10 K upon normalizing the specific heat by cubed temperature, similar to the boson peak in metallic glass. The simulation studies show that this boson-peak-like anomaly is caused by the phonon softening of the non-transforming matrix surrounding martensitic domains, which occurs in a transverse acoustic branch not associated with the martensitic transformation displacements. Therefore, this anomaly neither is a relic of van Hove singularity nor can be explained by other theories relying on structural disorder, while it verifies a recent theoretical model without any assumptions of disorder. This work might provide fresh insights in understanding the nature of glassy states and associated vibrational properties.
Subtype heterogeneity and epigenetic convergence in neuroendocrine prostate cancer
Authors: Cejas Paloma , Xie Yingtian , Font-Tello Alba , Lim Klothilda , Syamala Sudeepa , Qiu Xintao , Tewari Alok K. , Shah Neel , Nguyen Holly M. , Patel Radhika A. , Brown Lisha , Coleman Ilsa , Hackeng Wenzel M. , Brosens Lodewijk , Dreijerink Koen M. A. , Ellis Leigh , Alaiwi Sarah Abou , Seo Ji-Heui , Baca Sylvan , Beltran Himisha , Khani Francesca , Pomerantz Mark , Dall’Agnese Alessandra , Crowdis Jett , Van Allen Eliezer M. , Bellmunt Joaquim , Morrisey Colm , Nelson Peter S. , DeCaprio James , Farago Anna , Dyson Nicholas , Drapkin Benjamin , Liu X. Shirley , Freedman Matthew , Haffner Michael C. , Corey Eva , Brown Myles , Long Henry W.
Published: October 2021

Neuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes of a range of human NECs and show convergence to the activation of a common epigenetic program. With a particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), we analyze cell lines, patient-derived xenograft (PDX) models and human clinical samples to show the existence of two distinct NEPC subtypes based on the expression of the neuronal transcription factors ASCL1 and NEUROD1. While in cell lines and PDX models these subtypes are mutually exclusive, single-cell analysis of human clinical samples exhibits a more complex tumor structure with subtypes coexisting as separate sub-populations within the same tumor. These tumor sub-populations differ genetically and epigenetically contributing to intra- and inter-tumoral heterogeneity in human metastases. Overall, our results provide a deeper understanding of the shared clinicopathological characteristics shown by NECs. Furthermore, the intratumoral heterogeneity of human NEPCs suggests the requirement of simultaneous targeting of coexisting tumor populations as a therapeutic strategy.
SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition
Authors: Ma Jian , Shi Qing , Cui Gaofeng , Sheng Haoyue , Botuyan Maria Victoria , Zhou Yingke , Yan Yuqian , He Yundong , Wang Liguo , Wang Yuzhuo , Mer Georges , Ye Dingwei , Wang Chenji , Huang Haojie
Published: October 2021

Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy.
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
Authors: Thery Fabien , Martina Lia , Asselman Caroline , Zhang Yifeng , Vessely Madeleine , Repo Heidi , Sedeyn Koen , Moschonas George D. , Bredow Clara , Teo Qi Wen , Zhang Jingshu , Leandro Kevin , Eggermont Denzel , De Sutter Delphine , Boucher Katie , Hochepied Tino , Festjens Nele , Callewaert Nico , Saelens Xavier , Dermaut Bart , Knobeloch Klaus-Peter , Beling Antje , Sanyal Sumana , Radoshevich Lilliana , Eyckerman Sven , Impens Francis
Published: October 2021

ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection withListeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.
Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models
Authors: Jiang Yan , Fu Xing , Zhang Yuhan , Wang Shen-Fei , Zhu Hong , Wang Wei-Kang , Zhang Lin , Wu Ping , Wong Catherine C. L. , Li Jinsong , Ma Jinbiao , Guan Ji-Song , Huang Ying , Hui Jingyi
Published: October 2021

Rett syndrome (RTT) is a severe neurological disorder and a leading cause of intellectual disability in young females. RTT is mainly caused by mutations found in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Despite extensive studies, the molecular mechanism underlying RTT pathogenesis is still poorly understood. Here, we report MeCP2 as a key subunit of a higher-order multiunit protein complex Rbfox/LASR. Defective MeCP2 in RTT mouse models disrupts the assembly of the MeCP2/Rbfox/LASR complex, leading to reduced binding of Rbfox proteins to target pre-mRNAs and aberrant splicing of Nrxns and Nlgn1 critical for synaptic plasticity. We further show that MeCP2 disease mutants display defective condensate properties and fail to promote phase-separated condensates with Rbfox proteins in vitro and in cultured cells. These data link an impaired function of MeCP2 with disease mutation in splicing control to its defective properties in mediating the higher-order assembly of the MeCP2/Rbfox/LASR complex.
Experimental study of quantum coherence decomposition and trade-off relations in a tripartite system
Authors: Ding Zhe , Liu Ran , Radhakrishnan Chandrashekar , Ma Wenchao , Peng Xinhua , Wang Ya , Byrnes Tim , Shi Fazhan , Du Jiangfeng
Published: October 2021

Quantum coherence is the most fundamental of all quantum quantifiers, underlying other well-known quantities such as entanglement. It can be distributed in a multipartite system in various ways—for example, in a bipartite system it can exist within subsystems (local coherence) or collectively between the subsystems (global coherence), and exhibits a trade-off relation. In this paper, we experimentally verify these coherence trade-off relations in adiabatically evolved nuclear spin systems using an NMR spectrometer. We study the full set of coherence trade-off relations between the original state, the bipartite product state, the tripartite product state, and the decohered product state. We also experimentally verify the monogamy inequality and show that both the quantum systems are polygamous during the evolution. We find that the properties of the state in terms of coherence and monogamy are equivalent. This illustrates the utility of using coherence as a characterization tool for quantum states.
Terahertz signatures of ultrafast Dirac fermion relaxation at the surface of topological insulators
Authors: Kovalev S. , Tielrooij K.-J. , Deinert J.-C. , Ilyakov I. , Awari N. , Chen M. , Ponomaryov A. , Bawatna M. , de Oliveira T. V. A. G. , Eng L. M. , Kuznetsov K. A. , Safronenkov D. A. , Kitaeva G. Kh. , Kuznetsov P. I. , Hafez H. A. , Turchinovich D. , Gensch M.
Published: October 2021

Topologically protected surface states present rich physics and promising spintronic, optoelectronic, and photonic applications that require a proper understanding of their ultrafast carrier dynamics. Here, we investigate these dynamics in topological insulators (TIs) of the bismuth and antimony chalcogenide family, where we isolate the response of Dirac fermions at the surface from the response of bulk carriers by combining photoexcitation with below-bandgap terahertz (THz) photons and TI samples with varying Fermi level, including one sample with the Fermi level located within the bandgap. We identify distinctly faster relaxation of charge carriers in the topologically protected Dirac surface states (few hundred femtoseconds), compared to bulk carriers (few picoseconds). In agreement with such fast cooling dynamics, we observe THz harmonic generation without any saturation effects for increasing incident fields, unlike graphene which exhibits strong saturation. This opens up promising avenues for increased THz nonlinear conversion efficiencies, and high-bandwidth optoelectronic and spintronic information and communication applications.
Multimodal dataset of real-time 2D and static 3D MRI of healthy French speakers
Authors: Isaieva Karyna , Laprie Yves , Leclère Justine , Douros Ioannis K. , Felblinger Jacques , Vuissoz Pierre-André
Published: October 2021

The study of articulatory gestures has a wide spectrum of applications, notably in speech production and recognition. Sets of phonemes, as well as their articulation, are language-specific; however, existing MRI databases mostly include English speakers. In our present work, we introduce a dataset acquired with MRI from 10 healthy native French speakers. A corpus consisting of synthetic sentences was used to ensure a good coverage of the French phonetic context. A real-time MRI technology with temporal resolution of 20 ms was used to acquire vocal tract images of the participants speaking. The sound was recorded simultaneously with MRI, denoised and temporally aligned with the images. The speech was transcribed to obtain phoneme-wise segmentation of sound. We also acquired static 3D MR images for a wide list of French phonemes. In addition, we include annotations of spontaneous swallowing.
Aphids harbouring different endosymbionts exhibit differences in cuticular hydrocarbon profiles that can be recognized by ant mutualists
Authors: Hertaeg Corinne , Risse Marion , Vorburger Christoph , De Moraes Consuelo M. , Mescher Mark C.
Published: October 2021

Cuticular hydrocarbons (CHCs) have important communicative functions for ants, which use CHC profiles to recognize mutualistic aphid partners. Aphid endosymbionts can influence the quality of their hosts as ant mutualists, via effects on honeydew composition, and might also affect CHC profiles, suggesting that ants could potentially use CHC cues to discriminate among aphid lines harbouring different endosymbionts. We explored how several strains of Hamiltonella defensa and Regiella insecticola influence the CHC profiles of host aphids (Aphis fabae) and the ability of aphid-tending ants (Lasius niger) to distinguish the profiles of aphids hosting different endosymbionts. We found significant compositional differences between the CHCs of aphids with different infections. Some endosymbionts changed the proportions of odd-chain linear alkanes, while others changed primarily methyl-branched compounds, which may be particularly important for communication. Behavioural assays, in which we trained ants to associate CHC profiles of endosymbiont infected or uninfected aphids with food rewards, revealed that ants readily learned to distinguish differences in aphid CHC profiles associated with variation in endosymbiont strains. While previous work has documented endosymbiont effects on aphid interactions with antagonists, the current findings support the hypothesis that endosymbionts also alter traits that influence communicative interactions with ant mutualists.
Development of an aerogenous Escherichia coli infection model in adult broiler breeders
Authors: Kromann Sofie , Olsen Rikke Heidemann , Bojesen Anders Miki , Jensen Henrik Elvang , Thøfner Ida
Published: October 2021

Escherichia coli constitutes an immense challenge to the poultry industry due to its devastating effect on productivity, mortality, and carcass condemnations. To aid future studies on disease mechanisms and interventions, an aerogenous infection model was established in adult broiler breeders. Hens (n = 120) were randomly allocated into six groups receiving either aerosolised E. coli or vehicle, or intratracheal E. coli or vehicle. Replication of aerosol inoculation was performed on distinct days. Alternating euthanasia time points were predetermined in order to evaluate the progression of the disease. All animals were thoroughly necropsied, and bacteriological samples were collected as well as tissues for histopathology. Birds inoculated with E. coli exhibited clinical signs and developed characteristic gross and histopathological lesions of colibacillosis, including splenic fibrinoid necrosis, folliculitis, polyserositis and impaction of parabronchi with fibrinoheterophilic exudate and necrotic debris, as well as positive in situ localisation of intralesional E. coli by immunohistochemistry. This study presents a successful development of a discriminative colibacillosis model through aerosol inoculation of adult broiler breeders. Gross and histopathological lesions characteristic of colibacillosis were established in two independent experiments.
Computational modeling of thermal combination therapies by magneto-ultrasonic heating to enhance drug delivery to solid tumors
Authors: Souri Mohammad , Soltani Madjid , Moradi Kashkooli Farshad
Published: October 2021

For the first time, inspired by magnetic resonance imaging-guidance high intensity focused ultrasound (MR-HIFU) technology, i.e., medication therapy and thermal ablation in one session, in a preclinical setting based on a developed mathematical model, the performance of doxorubicin (Dox) and its encapsulation have been investigated in this study. Five different treatment methods, that combine medication therapy with mild hyperthermia by MRI contrast ($$\gamma -{Fe}_{2}{O}_{3}$$

γ
-

Fe

2

O
3

) and thermal ablation via HIFU, are investigated in detail. A comparison between classical chemotherapy and thermochemistry shows that temperature can improve the therapeutic outcome by stimulating biological properties. On the other hand, the intravascular release of ThermoDox increases the concentration of free drug by 2.6 times compared to classical chemotherapy. The transport of drug in interstitium relies mainly on the diffusion mechanism to be able to penetrate deeper and reach the cancer cells in the inner regions of the tumor. Due to the low drug penetration into the tumor center, thermal ablation has been used for necrosis of the central areas before thermochemotherapy and ThermoDox therapy. Perfusion of the region around the necrotic zone is found to be damaged, while cells in the region are alive and not affected by medication therapy; so, there is a risk of tumor recurrence. Therefore, it is recommended that ablation be performed after the medication therapy. Our model describes a comprehensive assessment of MR-HIFU technology, taking into account many effective details, which can be a reliable guide towards the optimal use of drug delivery systems.
Warming events projected to become more frequent and last longer across Antarctica
Authors: Feron Sarah , Cordero Raúl R. , Damiani Alessandro , Malhotra Avni , Seckmeyer Gunther , Llanillo Pedro
Published: October 2021

Summer temperatures are often above freezing along the Antarctic coastline, which makes ice shelves and coastal snowpacks vulnerable to warming events (understood as periods of consecutive days with warmer than usual conditions). Here, we project changes in the frequency, duration and amplitude of summertime warming events expected until end of century according to two emission scenarios. By using both global and regional climate models, we found that these events are expected to be more frequent and last longer, continent-wide. By end of century, the number of warming events is projected to double in most of West Antarctica and to triple in the vast interior of East Antarctica, even under a moderate-emission scenario. We also found that the expected rise of warming events in coastal areas surrounding the continent will likely lead to enhanced surface melt, which may pose a risk for the future stability of several Antarctic ice shelves.
Strontium and oxygen isotopes to trace mobility routes during the Bell Beaker period in the north of Spain
Authors: Ortega L. A. , Alonso-Fernández C. , Guede I. , Zuluaga M. C. , Alonso-Olazabal A. , Jiménez-Echevarría J.
Published: October 2021

Strontium and oxygen isotopes of individuals from El Hundido and Valdescusa (north of Spain) sites, corresponding to the Bell Beaker culture, were analysed in order to determine mobility patterns and provenance areas. Strontium and oxygen isotope ratios in three teeth from two individuals at El Hundido and two teeth from the five individuals at Valdescusa were studied. The analyses were performed in both dentine and enamel fractions. 87Sr/86Sr ratios of El Hundido individuals indicate one was of foreign origin and the other was local whereas at Valdescusa were all of foreign provenance. Calculated δ18Ow values of El Hundido suggest a provenance from the geographical area close to the site while the Valdescusa would come from a warmer region. The comparison of oxygen and strontium isotope signatures indicate the west of the Iberian Peninsula (Zamora or the east of Leon regions) as the provenance area for the foreign individual at El Hundido and southwest France (Garonne basin) as the region of provenance for the Valdescusa.
Crossing design shapes patterns of genetic variation in synthetic recombinant populations of Saccharomyces cerevisiae
Authors: Phillips Mark A. , Kutch Ian C. , McHugh Kaitlin M. , Taggard Savannah K. , Burke Molly K.
Published: October 2021

“Synthetic recombinant” populations have emerged as a useful tool for dissecting the genetics of complex traits. They can be used to derive inbred lines for fine QTL mapping, or the populations themselves can be sampled for experimental evolution. In the latter application, investigators generally value maximizing genetic variation in constructed populations. This is because in evolution experiments initiated from such populations, adaptation is primarily fueled by standing genetic variation. Despite this reality, little has been done to systematically evaluate how different methods of constructing synthetic populations shape initial patterns of variation. Here we seek to address this issue by comparing outcomes in synthetic recombinant Saccharomyces cerevisiae populations created using one of two strategies: pairwise crossing of isogenic strains or simple mixing of strains in equal proportion. We also explore the impact of the varying the number of parental strains. We find that more genetic variation is initially present and maintained when population construction includes a round of pairwise crossing. As perhaps expected, we also observe that increasing the number of parental strains typically increases genetic diversity. In summary, we suggest that when constructing populations for use in evolution experiments, simply mixing founder strains in equal proportion may limit the adaptive potential.
Increased decision latency in alcohol use disorder reflects altered resting-state synchrony in the anterior salience network
Authors: Canessa Nicola , Basso Gianpaolo , Carne Irene , Poggi Paolo , Gianelli Claudia
Published: October 2021

Increased decision latency in alcohol use disorder (AUD) has been generally explained in terms of psychomotor slowing. Recent results suggest that AUD patients’ slowed decision-making might rather reflect alterations in the neural circuitry underlying the engagement of controlled processing by salient stimuli. We addressed this hypothesis by testing a relationship between decision latency at the Cambridge Gambling Task (CGT) and intrinsic brain activity in 22 individuals with AUD and 19 matched controls. CGT deliberation time was related to two complementary facets of resting-state fMRI activity, i.e. coherence and intensity, representing early biomarkers of functional changes in the intrinsic brain architecture. For both metrics, we assessed a multiple regression (to test a relationship with deliberation time in the whole sample), and an interaction analysis (to test a significantly different relationship with decision latency across groups). AUD patients’ slowed deliberation time (p < 0.025) reflected distinct facets of altered intrinsic activity in the cingulate node of the anterior salience network previously associated with the “output” motor stage of response selection. Its heightened activity in AUD patients compared with controls, tracking choice latency (p < 0.025 corrected), might represent a compensation mechanism counterbalancing the concurrent decrease of its internal coherent activity (p < 0.025 corrected). These findings provide novel insights into the intrinsic neural mechanisms underlying increased decision latency in AUD, involving decreased temporal synchronicity in networks promoting executive control by behaviourally relevant stimuli. These results pave the way to further studies assessing more subtle facets of decision-making in AUD, and their possible changes with rehabilitative treatment.
Rapid quantitation of three synthetic cathinones in urine by magnetic dispersive solid-phase extraction combined with DART-HRMS
Authors: Li Yawen , Lian Ru , Yang Feiyu , Xu Zhiru , Cao Fangqi , Wang Rong , Liang Chen , Zhang Yurong
Published: October 2021

Synthetic cathinones in urine can be quickly quantified by the combination of magnetic dispersive solid-phase extraction and DART-HRMS.
In situ identification of TATP and DADP particles collected with transparent tape by Raman spectroscopy and imaging
Authors: Sun Zhenwen , Zhang Guannan , Li Yonggang , Qiao Ting , Liu Zhanfang , Wang Ping , Li Guangyao , Zhou Zheng , Zheng Jili , Li Yajun , Zhu Jun , Liu Yao
Published: October 2021

The collection of peroxide explosives by transparent tapes and in situ identification of explosive particles by Raman spectroscopy and imaging.
Assessment of minimal active space CASSCF-SO methods for calculation of atomic Slater–Condon and spin–orbit coupling parameters in d- and f-block ions
Authors: Walisinghe Alvin J. , Chilton Nicholas F.
Published: October 2021

CASSCF-SO calculations in OpenMolcas are used to determine Slater-Condon and SOC parameters for 3dn, 4dn, 5dn and 4fn ions. We quantify the error of minimal active space approaches and compare to other similar methods.
Di(hydroperoxy)adamantane adducts: synthesis, characterization and application as oxidizers for the direct esterification of aldehydes
Authors: Arp Fabian F. , Ashirov Rahym , Bhuvanesh Nattamai , Blümel Janet
Published: October 2021

Four new Ahn adducts, incorporating di(hydroperoxy)adamantane moieties like the displayedo-Tol3PO·(HOO)2C9H14, have been synthesized and applied for the fast, selective, direct esterification of aliphatic and aromatic aldehydes in non-aqueous media.
A comparative study of open and closed-air cycles for desalination system using the humidification–dehumidification method
Authors: Mohamed A. S. A. , Shahdy Abanob G. , Ahmed M. Salem
Published: October 2021

Humidification dehumidification water desalination system using two cycles of air flow (open and closed-air cycles).
Gut microbiota mediates the effects of inulin on enhancing sulfomucin production and mucosal barrier function in a pig model
Authors: Xia Bing , Wu Weida , Zhang Li , Wen Xiaobin , Xie Jingjing , Zhang Hongfu
Published: October 2021

Diet supplemented with 5% INU but not MCC enhanced the colonic barrier function and sulfomucin production in pigs. INU-induced changes in bacterial genera. SCFAs were significantly associated with these alterations.