bluuebunny/crossref_metadata_2025_split huggingface dataset:
CG6015 controls spermatogonia transit-amplifying divisions by epidermal growth factor receptor signaling in Drosophila testes
Authors: Yu Jun , Zheng Qianwen , Li Zhiran , Wu Yunhao , Fu Yangbo , Wu Xiaolong , Lin Dengfeng , Shen Cong , Zheng Bo , Sun Fei 
Published: May 2021

AbstractSpermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development inDrosophilamelanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia ofDsor1RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions inDrosophilatestes.
Magneto-active elastic shells with tunable buckling strength
Authors: Yan Dong , Pezzulla Matteo , Cruveiller Lilian , Abbasi Arefeh , Reis Pedro M. 
Published: May 2021

AbstractShell buckling is central in many biological structures and advanced functional materials, even if, traditionally, this elastic instability has been regarded as a catastrophic phenomenon to be avoided for engineering structures. Either way, predicting critical buckling conditions remains a long-standing challenge. The subcritical nature of shell buckling imparts extreme sensitivity to material and geometric imperfections. Consequently, measured critical loads are inevitably lower than classic theoretical predictions. Here, we present a robust mechanism to dynamically tune the buckling strength of shells, exploiting the coupling between mechanics and magnetism. Our experiments on pressurized spherical shells made of a hard-magnetic elastomer demonstrate the tunability of their buckling pressure via magnetic actuation. We develop a theoretical model for thin magnetic elastic shells, which rationalizes the underlying mechanism, in excellent agreement with experiments. A dimensionless magneto-elastic buckling number is recognized as the key governing parameter, combining the geometric, mechanical, and magnetic properties of the system.
Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice
Authors: Kesner Andrew J. , Shin Rick , Calva Coleman B. , Don Reuben F. , Junn Sue , Potter Christian T. , Ramsey Leslie A. , Abou-Elnaga Ahmed F. , Cover Christopher G. , Wang Dong V. , Lu Hanbing , Yang Yihong , Ikemoto Satoshi 
Published: May 2021

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.
Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer
Authors: Shi Wengui , Zhang Gengyuan , Ma Zhijian , Li Lianshun , Liu Miaomiao , Qin Long , Yu Zeyuan , Zhao Lei , Liu Yang , Zhang Xue , Qin Junjie , Ye Huili , Jiang Xiangyan , Zhou Huinian , Sun Hui , Jiao Zuoyi 
Published: May 2021

AbstractTrastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3’-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer.
Rapid synchronized fabrication of vascularized thermosets and composites
Authors: Garg Mayank , Aw Jia En , Zhang Xiang , Centellas Polette J. , Dean Leon M. , Lloyd Evan M. , Robertson Ian D. , Liu Yiqiao , Yourdkhani Mostafa , Moore Jeffrey S. , Geubelle Philippe H. , Sottos Nancy R. 
Published: May 2021

AbstractBioinspired vascular networks transport heat and mass in hydrogels, microfluidic devices, self-healing and self-cooling structures, filters, and flow batteries. Lengthy, multistep fabrication processes involving solvents, external heat, and vacuum hinder large-scale application of vascular networks in structural materials. Here, we report the rapid (seconds to minutes), scalable, and synchronized fabrication of vascular thermosets and fiber-reinforced composites under ambient conditions. The exothermic frontal polymerization (FP) of a liquid or gelled resin facilitates coordinated depolymerization of an embedded sacrificial template to create host structures with high-fidelity interconnected microchannels. The chemical energy released during matrix polymerization eliminates the need for a sustained external heat source and greatly reduces external energy consumption for processing. Programming the rate of depolymerization of the sacrificial thermoplastic to match the kinetics of FP has the potential to significantly expedite the fabrication of vascular structures with extended lifetimes, microreactors, and imaging phantoms for understanding capillary flow in biological systems.
Electromechanical coupling mechanism for activation and inactivation of an HCN channel
Authors: Dai Gucan , Aman Teresa K. , DiMaio Frank , Zagotta William N. 
Published: May 2021

AbstractPacemaker hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels exhibit a reversed voltage-dependent gating, activating by membrane hyperpolarization instead of depolarization. Sea urchin HCN (spHCN) channels also undergo inactivation with hyperpolarization which occurs only in the absence of cyclic nucleotide. Here we applied transition metal ion FRET, patch-clamp fluorometry and Rosetta modeling to measure differences in the structural rearrangements between activation and inactivation of spHCN channels. We found that removing cAMP produced a largely rigid-body rotation of the C-linker relative to the transmembrane domain, bringing the A’ helix of the C-linker in close proximity to the voltage-sensing S4 helix. In addition, rotation of the C-linker was elicited by hyperpolarization in the absence but not the presence of cAMP. These results suggest that — in contrast to electromechanical coupling for channel activation — the A’ helix serves to couple the S4-helix movement for channel inactivation, which is likely a conserved mechanism for CNBD-family channels.
Context-specific action of macrolide antibiotics on the eukaryotic ribosome
Authors: Svetlov Maxim S. , Koller Timm O. , Meydan Sezen , Shankar Vaishnavi , Klepacki Dorota , Polacek Norbert , Guydosh Nicholas R. , Vázquez-Laslop Nora , Wilson Daniel N. , Mankin Alexander S. 
Published: May 2021

AbstractMacrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells.
Chemoselective catalytic hydrodefluorination of trifluoromethylalkenes towards mono-/gem-di-fluoroalkenes under metal-free conditions
Authors: Zhang Jingjing , Yang Jin-Dong , Cheng Jin-Pei 
Published: May 2021

AbstractFluorine-containing moieties show significant effects in improving the properties of functional molecules. Consequently, efficient methods for installing them into target compounds are in great demand, especially those enabled by metal-free catalysis. Here we show a diazaphospholene-catalyzed hydrodefluorination of trifluoromethylalkenes to chemoselectively constructgem-difluoroalkenes and terminal monofluoroalkenes by simple adjustment of the reactant stoichiometry. This metal-free hydrodefluorination features mild reaction conditions, good group compatibility, and almost quantitative yields for both product types. Stoichiometric experiments indicated a stepwise mechanism: hydridic addition to fluoroalkenes and subsequentβ-F elimination from hydrophosphination intermediates. Density functional theory calculations disclosed the origin of chemoselectivity, regioselectivity and stereoselectivity, suggesting an electron-donating effect of the alkene-terminal fluorine atom.
Spectroscopic evidence of superconductivity pairing at 83 K in single-layer FeSe/SrTiO3 films
Authors: Xu Yu , Rong Hongtao , Wang Qingyan , Wu Dingsong , Hu Yong , Cai Yongqing , Gao Qiang , Yan Hongtao , Li Cong , Yin Chaohui , Chen Hao , Huang Jianwei , Zhu Zhihai , Huang Yuan , Liu Guodong , Xu Zuyan , Zhao Lin , Zhou X. J. 
Published: May 2021

AbstractSingle-layer FeSe films grown on the SrTiO3 substrate (FeSe/STO) have attracted much attention because of their possible record-high superconducting critical temperature (Tc) and distinct electronic structures. However, it has been under debate on how high its Tc can really reach due to the inconsistency of the results from different measurements. Here we report spectroscopic evidence of superconductivity pairing at 83 K in single-layer FeSe/STO films. By preparing high-quality single-layer FeSe/STO films, we observe strong superconductivity-induced Bogoliubov back-bending bands that extend to rather high binding energy ~ 100 meV by high-resolution angle-resolved photoemission measurements. They provide a new definitive benchmark of superconductivity pairing that is directly observed up to 83 K. Moreover, we find that the pairing state can be further divided into two temperature regions. These results indicate that either Tc as high as 83 K is achievable, or there is a pseudogap formation from superconductivity fluctuation in single-layer FeSe/STO films.
The membrane-localized protein kinase MAP4K4/TOT3 regulates thermomorphogenesis
Authors: Vu Lam Dai , Xu Xiangyu , Zhu Tingting , Pan Lixia , van Zanten Martijn , de Jong Dorrit , Wang Yaowei , Vanremoortele Tim , Locke Anna M. , van de Cotte Brigitte , De Winne Nancy , Stes Elisabeth , Russinova Eugenia , De Jaeger Geert , Van Damme Daniël , Uauy Cristobal , Gevaert Kris , De Smet Ive 
Published: May 2021

AbstractPlants respond to mild warm temperature conditions by increased elongation growth of organs to enhance cooling capacity, in a process called thermomorphogenesis. To this date, the regulation of thermomorphogenesis has been exclusively shown to intersect with light signalling pathways. To identify regulators of thermomorphogenesis that are conserved in flowering plants, we map changes in protein phosphorylation in both dicots and monocots exposed to warm temperature. We identify MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE KINASE4 (MAP4K4)/TARGET OF TEMPERATURE3 (TOT3) as a regulator of thermomorphogenesis that impinges on brassinosteroid signalling inArabidopsis thaliana. In addition, we show that TOT3 plays a role in thermal response in wheat, a monocot crop. Altogether, the conserved thermal regulation by TOT3 expands our knowledge of thermomorphogenesis beyond the well-studied pathways and can contribute to ensuring food security under a changing climate.
Multifunctional antiferromagnetic materials with giant piezomagnetism and noncollinear spin current
Authors: Ma Hai-Yang , Hu Mengli , Li Nana , Liu Jianpeng , Yao Wang , Jia Jin-Feng , Liu Junwei 
Published: May 2021

AbstractWe propose a new type of spin-valley locking (SVL), named C-paired SVL, in antiferromagnetic systems, which directly connects the spin/valley space with the real space, and hence enables both static and dynamical controls of spin and valley to realize a multifunctional antiferromagnetic material. The new emergent quantum degree of freedom in the C-paired SVL is comprised of spin-polarized valleys related by a crystal symmetry instead of the time-reversal symmetry. Thus, both spin and valley can be accessed by simply breaking the corresponding crystal symmetry. Typically, one can use a strain field to induce a large net valley polarization/magnetization and use a charge current to generate a large noncollinear spin current. We predict the realization of the C-paired SVL in monolayer V2Se2O, which indeed exhibits giant piezomagnetism and can generate a large transverse spin current. Our findings provide unprecedented opportunities to integrate various controls of spin and valley with nonvolatile information storage in a single material, which is highly desirable for versatile fundamental research and device applications.
Hierarchical progressive learning of cell identities in single-cell data
Authors: Michielsen Lieke , Reinders Marcel J. T. , Mahfouz Ahmed 
Published: May 2021

AbstractSupervised methods are increasingly used to identify cell populations in single-cell data. Yet, current methods are limited in their ability to learn from multiple datasets simultaneously, are hampered by the annotation of datasets at different resolutions, and do not preserve annotations when retrained on new datasets. The latter point is especially important as researchers cannot rely on downstream analysis performed using earlier versions of the dataset. Here, we present scHPL, a hierarchical progressive learning method which allows continuous learning from single-cell data by leveraging the different resolutions of annotations across multiple datasets to learn and continuously update a classification tree. We evaluate the classification and tree learning performance using simulated as well as real datasets and show that scHPL can successfully learn known cellular hierarchies from multiple datasets while preserving the original annotations. scHPL is available at https://github.com/lcmmichielsen/scHPL.
STAT1 gain-of-function heterozygous cell models reveal diverse interferon-signature gene transcriptional responses
Authors: Scott Ori , Lindsay Kyle , Erwood Steven , Mollica Antonio , Roifman Chaim M. , Cohn Ronald D. , Ivakine Evgueni A. 
Published: May 2021

AbstractSignal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) is an autosomal dominant immune disorder marked by wide infectious predisposition, autoimmunity, vascular disease, and malignancy. Its molecular hallmark, elevated phospho-STAT1 (pSTAT1) following interferon (IFN) stimulation, is seen consistently in all patients and may not fully account for the broad phenotypic spectrum associated with this disorder. While over 100 mutations have been implicated in STAT1 GOF, genotype–phenotype correlation remains limited, and current overexpression models may be of limited use in gene expression studies. We generated heterozygous mutants in diploid HAP1 cells using CRISPR/Cas9 base-editing, targeting the endogenous STAT1 gene. Our models recapitulated the molecular phenotype of elevated pSTAT1, and were used to characterize the expression of five IFN-stimulated genes under a number of conditions. At baseline, transcriptional polarization was evident among mutants compared with wild type, and this was maintained following prolonged serum starvation. This suggests a possible role for unphosphorylated STAT1 in the pathogenesis of STAT1 GOF. Following stimulation with IFNα or IFNγ, differential patterns of gene expression emerged among mutants, including both gain and loss of transcriptional function. This work highlights the importance of modeling heterozygous conditions, and in particular transcription factor-related disorders, in a manner which accurately reflects patient genotype and molecular signature. Furthermore, we propose a complex and multifactorial transcriptional profile associated with various STAT1 mutations, adding to global efforts in establishing STAT1 GOF genotype–phenotype correlation and enhancing our understanding of disease pathogenesis.
Negative thermal expansion in YbMn2Ge2 induced by the dual effect of magnetism and valence transition
Authors: Qiao Yongqiang , Song Yuzhu , Sanson Andrea , Fan Longlong , Sun Qiang , Hu Shuxian , He Lunhua , Zhang Hongjie , Xing Xianran , Chen Jun 
Published: May 2021

AbstractNegative thermal expansion (NTE) is an intriguing property, which is generally triggered by a single NTE mechanism. In this work, an enhanced NTE (αv = −32.9 × 10−6 K−1, ΔT = 175 K) is achieved in YbMn2Ge2 intermetallic compound to be caused by a dual effect of magnetism and valence transition. In YbMn2Ge2, the Mn sublattice that forms the antiferromagnetic structure induces the magnetovolume effect, which contributes to the NTE below the Néel temperature (525 K). Concomitantly, the valence state of Yb increases from 2.40 to 2.82 in the temperature range of 300–700 K, which simultaneously causes the contraction of the unit cell volume due to smaller volume of Yb3+ than that of Yb2+. As a result, such combined effect gives rise to an enhanced NTE. The present study not only sheds light on the peculiar NTE mechanism of YbMn2Ge2, but also indicates the dual effect as a possible promising method to produce enhanced NTE materials.
Natural language processing methods are sensitive to sub-clinical linguistic differences in schizophrenia spectrum disorders
Authors: Tang Sunny X. , Kriz Reno , Cho Sunghye , Park Suh Jung , Harowitz Jenna , Gur Raquel E. , Bhati Mahendra T. , Wolf Daniel H. , Sedoc João , Liberman Mark Y. 
Published: May 2021

AbstractComputerized natural language processing (NLP) allows for objective and sensitive detection of speech disturbance, a hallmark of schizophrenia spectrum disorders (SSD). We explored several methods for characterizing speech changes in SSD (n = 20) compared to healthy control (HC) participants (n = 11) and approached linguistic phenotyping on three levels: individual words, parts-of-speech (POS), and sentence-level coherence. NLP features were compared with a clinical gold standard, the Scale for the Assessment of Thought, Language and Communication (TLC). We utilized Bidirectional Encoder Representations from Transformers (BERT), a state-of-the-art embedding algorithm incorporating bidirectional context. Through the POS approach, we found that SSD used more pronouns but fewer adverbs, adjectives, and determiners (e.g., “the,” “a,”). Analysis of individual word usage was notable for more frequent use of first-person singular pronouns among individuals with SSD and first-person plural pronouns among HC. There was a striking increase in incomplete words among SSD. Sentence-level analysis using BERT reflected increased tangentiality among SSD with greater sentence embedding distances. The SSD sample had low speech disturbance on average and there was no difference in group means for TLC scores. However, NLP measures of language disturbance appear to be sensitive to these subclinical differences and showed greater ability to discriminate between HC and SSD than a model based on clinical ratings alone. These intriguing exploratory results from a small sample prompt further inquiry into NLP methods for characterizing language disturbance in SSD and suggest that NLP measures may yield clinically relevant and informative biomarkers.
Comprehensive dataset of shotgun metagenomes from oxygen stratified freshwater lakes and ponds
Authors: Buck Moritz , Garcia Sarahi L. , Fernandez Leyden , Martin Gaëtan , Martinez-Rodriguez Gustavo A. , Saarenheimo Jatta , Zopfi Jakob , Bertilsson Stefan , Peura Sari 
Published: May 2021

AbstractStratified lakes and ponds featuring steep oxygen gradients are significant net sources of greenhouse gases and hotspots in the carbon cycle. Despite their significant biogeochemical roles, the microbial communities, especially in the oxygen depleted compartments, are poorly known. Here, we present a comprehensive dataset including 267 shotgun metagenomes from 41 stratified lakes and ponds mainly located in the boreal and subarctic regions, but also including one tropical reservoir and one temperate lake. For most lakes and ponds, the data includes a vertical sample set spanning from the oxic surface to the anoxic bottom layer. The majority of the samples were collected during the open water period, but also a total of 29 samples were collected from under the ice. In addition to the metagenomic sequences, the dataset includes environmental variables for the samples, such as oxygen, nutrient and organic carbon concentrations. The dataset is ideal for further exploring the microbial taxonomic and functional diversity in freshwater environments and potential climate change impacts on the functioning of these ecosystems.