bluuebunny/crossref_metadata_2025 huggingface dataset:
A tactile sensor system with sensory neurons and a perceptual synaptic network based on semivolatile carbon nanotube transistors
Authors: Kim Sungho , Lee Yongwoo , Kim Hee-Dong , Choi Sung-Jin
Published: December 2020

The human sensory system has a fascinating stimulus-detection capability attributed to the fact that the feature (pattern) of an input stimulus can be extracted through perceptual learning. Therefore, sensory information can be organized and identified efficiently based on iterative experiences, whereby the sensing ability is improved. Specifically, the distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. Herein, we demonstrate an artificial tactile sensor system with a sensory neuron and a perceptual synaptic network composed of a single device: a semivolatile carbon nanotube transistor. The system can differentiate the temporal features of tactile patterns, and its recognition accuracy can be improved by an iterative learning process. Furthermore, the developed circuit model of the system provides quantitative analytical and product-level feasibility. This work is a step toward the design and use of a neuromorphic sensory system with a learning capability for potential applications in robotics and prosthetics.
Enhanced analog synaptic behavior of SiNx/a-Si bilayer memristors through Ge implantation
Authors: Kim Keonhee , Park Soojin , Hu Su Man , Song Jonghan , Lim Weoncheol , Jeong Yeonjoo , Kim Jaewook , Lee Suyoun , Kwak Joon Young , Park Jongkil , Park Jong Keuk , Ju Byeong-Kwon , Jeong Doo Seok , Kim Inho
Published: December 2020

Conductive bridging random access memory (CBRAM) has been considered to be a promising emerging device for artificial synapses in neuromorphic computing systems. Good analog synaptic behaviors, such as linear and symmetric synapse updates, are desirable to provide high learning accuracy. Although numerous efforts have been made to develop analog CBRAM for years, the stochastic and abrupt formation of conductive filaments hinders its adoption. In this study, we propose a novel approach to enhance the synaptic behavior of a SiNx/a-Si bilayer memristor through Ge implantation. The SiNx and a-Si layers serve as switching and internal current limiting layers, respectively. Ge implantation induces structural defects in the bulk and surface regions of the a-Si layer, enabling spatially uniform Ag migration and nanocluster formation in the upper SiNx layer and increasing the conductance of the a-Si layer. As a result, the analog synaptic behavior of the SiNx/a-Si bilayer memristor, such as the nonlinearity, on/off ratio, and retention time, is remarkably improved. An artificial neural network simulation shows that the neuromorphic system with the implanted SiNx/a-Si memristor provides a 91.3% learning accuracy mainly due to the improved linearity.
Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system
Authors: Chevalier Grégoire , Siopi Eleni , Guenin-Macé Laure , Pascal Maud , Laval Thomas , Rifflet Aline , Boneca Ivo Gomperts , Demangel Caroline , Colsch Benoit , Pruvost Alain , Chu-Van Emeline , Messager Aurélie , Leulier François , Lepousez Gabriel , Eberl Gérard , Lledo Pierre-Marie
Published: December 2020

Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.
Using metacommunity ecology to understand environmental metabolomes
Authors: Danczak Robert E. , Chu Rosalie K. , Fansler Sarah J. , Goldman Amy E. , Graham Emily B. , Tfaily Malak M. , Toyoda Jason , Stegen James C.
Published: December 2020

Environmental metabolomes are fundamentally coupled to microbially-linked biogeochemical processes within ecosystems. However, significant gaps exist in our understanding of their spatiotemporal organization, limiting our ability to uncover transferrable principles and predict ecosystem function. We propose that a theoretical paradigm, which integrates concepts from metacommunity ecology, is necessary to reveal underlying mechanisms governing metabolomes. We call this synthesis between ecology and metabolomics ‘meta-metabolome ecology’ and demonstrate its utility using a mass spectrometry dataset. We developed three relational metabolite dendrograms using molecular properties and putative biochemical transformations and performed ecological null modeling. Based upon null modeling results, we show that stochastic processes drove molecular properties while biochemical transformations were structured deterministically. We further suggest that potentially biochemically active metabolites were more deterministically assembled than less active metabolites. Understanding variation in the influences of stochasticity and determinism provides a way to focus attention on which meta-metabolomes and which parts of meta-metabolomes are most likely to be important to consider in mechanistic models. We propose that this paradigm will allow researchers to study the connections between ecological systems and their molecular processes in previously inaccessible detail.
Coexistence of distinct skyrmion phases observed in hybrid ferromagnetic/ferrimagnetic multilayers
Authors: Mandru Andrada-Oana , Yıldırım Oğuz , Tomasello Riccardo , Heistracher Paul , Penedo Marcos , Giordano Anna , Suess Dieter , Finocchio Giovanni , Hug Hans Josef
Published: December 2020

Materials hosting magnetic skyrmions at room temperature could enable compact and energetically-efficient storage such as racetrack memories, where information is coded by the presence/absence of skyrmions forming a moving chain through the device. The skyrmion Hall effect leading to their annihilation at the racetrack edges can be suppressed, for example, by antiferromagnetically-coupled skyrmions. However, avoiding modifications of the inter-skyrmion distances remains challenging. As a solution, a chain of bits could also be encoded by two different solitons, such as a skyrmion and a chiral bobber, with the limitation that it has solely been realized in B20-type materials at low temperatures. Here, we demonstrate that a hybrid ferro/ferri/ferromagnetic multilayer system can host two distinct skyrmion phases at room temperature, namely tubular and partial skyrmions. Furthermore, the tubular skyrmion can be converted into a partial skyrmion. Such systems may serve as a platform for designing memory applications using distinct skyrmion types.
AN1-type zinc finger protein 3 (ZFAND3) is a transcriptional regulator that drives Glioblastoma invasion
Authors: Schuster Anne , Klein Eliane , Neirinckx Virginie , Knudsen Arnon Møldrup , Fabian Carina , Hau Ann-Christin , Dieterle Monika , Oudin Anais , Nazarov Petr V. , Golebiewska Anna , Muller Arnaud , Perez-Hernandez Daniel , Rodius Sophie , Dittmar Gunnar , Bjerkvig Rolf , Herold-Mende Christel , Klink Barbara , Kristensen Bjarne Winther , Niclou Simone P.
Published: December 2020

The infiltrative nature of Glioblastoma (GBM), the most aggressive primary brain tumor, critically prevents complete surgical resection and masks tumor cells behind the blood brain barrier reducing the efficacy of systemic treatment. Here, we use a genome-wide interference screen to determine invasion-essential genes and identify the AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of GBM invasion. Using patient-derived cellular models, we show that loss of ZFAND3 hampers the invasive capacity of GBM, whereas ZFAND3 overexpression increases motility in cells that were initially not invasive. At the mechanistic level, we find that ZFAND3 activity requires nuclear localization and integral zinc-finger domains. Our findings indicate that ZFAND3 acts within a nuclear protein complex to activate gene transcription and regulates the promoter of invasion-related genes such as COL6A2, FN1, and NRCAM. Further investigation in ZFAND3 function in GBM and other invasive cancers is warranted.
Ru(II)Porphyrinate-based molecular nanoreactor for carbene insertion reactions and quantitative formation of rotaxanes by active-metal-template syntheses
Authors: Fontana Liniquer A. , Almeida Marlon P. , Alcântara Arthur F. P. , Rigolin Vitor H. , Ribeiro Marcos A. , Barros Wdeson P. , Megiatto Jackson D.
Published: December 2020

Selectivity in N–H and S–H carbene insertion reactions promoted by Ru(II)porphyrinates currently requires slow addition of the diazo precursor and large excess of the primary amine and thiol substrates in the reaction medium. Such conditions are necessary to avoid the undesirable carbene coupling and/or multiple carbene insertions. Here, the authors demonstrate that the synergy between the steric shielding provided by a Ru(II)porphyrinate-based macrocycle with a relatively small central cavity and the kinetic stabilization of otherwise labile coordinative bonds, warranted by formation of the mechanical bond, enables single carbene insertions to occur with quantitative efficiency and perfect selectivity even in the presence of a large excess of the diazo precursor and stoichiometric amounts of the primary amine and thiol substrates. As the Ru(II)porphyrinate-based macrocycle bears a confining nanospace and alters the product distribution of the carbene insertion reactions when compared to that of its acyclic version, the former therefore functions as a nanoreactor.
Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice
Authors: Zhang Zhi , Reis Fernando M. C. V. , He Yanlin , Park Jae W. , DiVittorio Johnathon R. , Sivakumar Nilla , van Veen J. Edward , Maesta-Pereira Sandra , Shum Michael , Nichols India , Massa Megan G. , Anderson Shawn , Paul Ketema , Liesa Marc , Ajijola Olujimi A. , Xu Yong , Adhikari Avishek , Correa Stephanie M.
Published: December 2020

Homeotherms maintain a stable internal body temperature despite changing environments. During energy deficiency, some species can cease to defend their body temperature and enter a hypothermic and hypometabolic state known as torpor. Recent advances have revealed the medial preoptic area (MPA) as a key site for the regulation of torpor in mice. The MPA is estrogen-sensitive and estrogens also have potent effects on both temperature and metabolism. Here, we demonstrate that estrogen-sensitive neurons in the MPA can coordinate hypothermia and hypometabolism in mice. Selectively activating estrogen-sensitive MPA neurons was sufficient to drive a coordinated depression of metabolic rate and body temperature similar to torpor, as measured by body temperature, physical activity, indirect calorimetry, heart rate, and brain activity. Inducing torpor with a prolonged fast revealed larger and more variable calcium transients from estrogen-sensitive MPA neurons during bouts of hypothermia. Finally, whereas selective ablation of estrogen-sensitive MPA neurons demonstrated that these neurons are required for the full expression of fasting-induced torpor in both female and male mice, their effects on thermoregulation and torpor bout initiation exhibit differences across sex. Together, these findings suggest a role for estrogen-sensitive MPA neurons in directing the thermoregulatory and metabolic responses to energy deficiency.
Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers
Authors: Petrany Michael J. , Swoboda Casey O. , Sun Chengyi , Chetal Kashish , Chen Xiaoting , Weirauch Matthew T. , Salomonis Nathan , Millay Douglas P.
Published: December 2020

While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the presence of distinct myonuclear populations emerging in postnatal development as well as aging muscle. Our datasets also provided a platform for discovery of genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.
Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells
Authors: Kim Minchul , Franke Vedran , Brandt Bettina , Lowenstein Elijah D. , Schöwel Verena , Spuler Simone , Akalin Altuna , Birchmeier Carmen
Published: December 2020

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/).
Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds
Authors: Campinoti Sara , Gjinovci Asllan , Ragazzini Roberta , Zanieri Luca , Ariza-McNaughton Linda , Catucci Marco , Boeing Stefan , Park Jong-Eun , Hutchinson John C. , Muñoz-Ruiz Miguel , Manti Pierluigi G. , Vozza Gianluca , Villa Carlo E. , Phylactopoulos Demetra-Ellie , Maurer Constance , Testa Giuseppe , Stauss Hans J. , Teichmann Sarah A. , Sebire Neil J. , Hayday Adrian C. , Bonnet Dominique , Bonfanti Paola
Published: December 2020

The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases.
Quantifying and addressing the prevalence and bias of study designs in the environmental and social sciences
Authors: Christie Alec P. , Abecasis David , Adjeroud Mehdi , Alonso Juan C. , Amano Tatsuya , Anton Alvaro , Baldigo Barry P. , Barrientos Rafael , Bicknell Jake E. , Buhl Deborah A. , Cebrian Just , Ceia Ricardo S. , Cibils-Martina Luciana , Clarke Sarah , Claudet Joachim , Craig Michael D. , Davoult Dominique , De Backer Annelies , Donovan Mary K. , Eddy Tyler D. , França Filipe M. , Gardner Jonathan P. A. , Harris Bradley P. , Huusko Ari , Jones Ian L. , Kelaher Brendan P. , Kotiaho Janne S. , López-Baucells Adrià , Major Heather L. , Mäki-Petäys Aki , Martín Beatriz , Martín Carlos A. , Martin Philip A. , Mateos-Molina Daniel , McConnaughey Robert A. , Meroni Michele , Meyer Christoph F. J. , Mills Kade , Montefalcone Monica , Noreika Norbertas , Palacín Carlos , Pande Anjali , Pitcher C. Roland , Ponce Carlos , Rinella Matt , Rocha Ricardo , Ruiz-Delgado María C. , Schmitter-Soto Juan J. , Shaffer Jill A. , Sharma Shailesh , Sher Anna A. , Stagnol Doriane , Stanley Thomas R. , Stokesbury Kevin D. E. , Torres Aurora , Tully Oliver , Vehanen Teppo , Watts Corinne , Zhao Qingyuan , Sutherland William J.
Published: December 2020

Building trust in science and evidence-based decision-making depends heavily on the credibility of studies and their findings. Researchers employ many different study designs that vary in their risk of bias to evaluate the true effect of interventions or impacts. Here, we empirically quantify, on a large scale, the prevalence of different study designs and the magnitude of bias in their estimates. Randomised designs and controlled observational designs with pre-intervention sampling were used by just 23% of intervention studies in biodiversity conservation, and 36% of intervention studies in social science. We demonstrate, through pairwise within-study comparisons across 49 environmental datasets, that these types of designs usually give less biased estimates than simpler observational designs. We propose a model-based approach to combine study estimates that may suffer from different levels of study design bias, discuss the implications for evidence synthesis, and how to facilitate the use of more credible study designs.
Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome
Authors: Rychel Kevin , Sastry Anand V. , Palsson Bernhard O.
Published: December 2020

The transcriptional regulatory network (TRN) of Bacillus subtilis coordinates cellular functions of fundamental interest, including metabolism, biofilm formation, and sporulation. Here, we use unsupervised machine learning to modularize the transcriptome and quantitatively describe regulatory activity under diverse conditions, creating an unbiased summary of gene expression. We obtain 83 independently modulated gene sets that explain most of the variance in expression and demonstrate that 76% of them represent the effects of known regulators. The TRN structure and its condition-dependent activity uncover putative or recently discovered roles for at least five regulons, such as a relationship between histidine utilization and quorum sensing. The TRN also facilitates quantification of population-level sporulation states. As this TRN covers the majority of the transcriptome and concisely characterizes the global expression state, it could inform research on nearly every aspect of transcriptional regulation in B. subtilis.
The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans
Authors: Agarwal Shiuli , Vierbuchen Tim , Ghosh Sreya , Chan Jennie , Jiang Zhaozhao , Kandasamy Richard K. , Ricci Emiliano , Fitzgerald Katherine A.
Published: December 2020

Long non-coding RNAs are important regulators of biological processes including immune responses. The immunoregulatory functions of lncRNAs have been revealed primarily in murine models with limited understanding of lncRNAs in human immune responses. Here, we identify lncRNA LUCAT1 which is upregulated in human myeloid cells stimulated with lipopolysaccharide and other innate immune stimuli. Targeted deletion of LUCAT1 in myeloid cells increases expression of type I interferon stimulated genes in response to LPS. By contrast, increased LUCAT1 expression results in a reduction of the inducible ISG response. In activated cells, LUCAT1 is enriched in the nucleus where it associates with chromatin. Further, LUCAT1 limits transcription of interferon stimulated genes by interacting with STAT1 in the nucleus. Together, our study highlights the role of the lncRNA LUCAT1 as a post-induction feedback regulator which functions to restrain the immune response in human cells.
The molecular basis for recognition of 5′-NNNCC-3′ PAM and its methylation state by Acidothermus cellulolyticus Cas9
Authors: Das Anuska , Hand Travis H. , Smith Chardasia L. , Wickline Ethan , Zawrotny Michael , Li Hong
Published: December 2020

Acidothermus cellulolyticus CRISPR-Cas9 (AceCas9) is a thermophilic Type II-C enzyme that has potential genome editing applications in extreme environments. It cleaves DNA with a 5′-NNNCC-3′ Protospacer Adjacent Motif (PAM) and is sensitive to its methylation status. To understand the molecular basis for the high specificity of AceCas9 for its PAM, we determined two crystal structures of AceCas9 lacking its HNH domain (AceCas9-ΔHNH) bound with a single guide RNA and DNA substrates, one with the correct and the other with an incorrect PAM. Three residues, Glu1044, Arg1088, Arg1091, form an intricate hydrogen bond network with the first cytosine and the two opposing guanine nucleotides to confer specificity. Methylation of the first but not the second cytosine base abolishes AceCas9 activity, consistent with the observed PAM recognition pattern. The high sensitivity of AceCas9 to the modified cytosine makes it a potential device for detecting epigenomic changes in genomes.
The nuclear localization sequence mediates hnRNPA1 amyloid fibril formation revealed by cryoEM structure
Authors: Sun Yunpeng , Zhao Kun , Xia Wencheng , Feng Guoqin , Gu Jinge , Ma Yeyang , Gui Xinrui , Zhang Xia , Fang Yanshan , Sun Bo , Wang Renxiao , Liu Cong , Li Dan
Published: December 2020

Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-β2 (Kapβ2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapβ2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminates structural understandings of the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapβ2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.
Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand
Authors: Geoghegan Jemma L. , Ren Xiaoyun , Storey Matthew , Hadfield James , Jelley Lauren , Jefferies Sarah , Sherwood Jill , Paine Shevaun , Huang Sue , Douglas Jordan , Mendes Fábio K. , Sporle Andrew , Baker Michael G. , Murdoch David R. , French Nigel , Simpson Colin R. , Welch David , Drummond Alexei J. , Holmes Edward C. , Duchêne Sebastián , de Ligt Joep
Published: December 2020

New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nationwide ‘lockdown’ of all non-essential services to curb the spread of COVID-19. Here, we generate 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected during the ‘first wave’, representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. These data helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, Re of New Zealand’s largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in ongoing transmission of more than one additional case. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.
PRC2 and EHMT1 regulate H3K27me2 and H3K27me3 establishment across the zygote genome
Authors: Meng Tie-Gang , Zhou Qian , Ma Xue-Shan , Liu Xiao-Yu , Meng Qing-Ren , Huang Xian-Ju , Liu Hong-Lin , Lei Wen-Long , Zhao Zheng-Hui , Ouyang Ying-Chun , Hou Yi , Schatten Heide , Ou Xiang-Hong , Wang Zhen-Bo , Gao Shao-Rong , Sun Qing-Yuan
Published: December 2020

The formation of zygote is the beginning of mammalian life, and dynamic epigenetic modifications are essential for mammalian normal development. H3K27 di-methylation (H3K27me2) and H3K27 tri-methylation (H3K27me3) are marks of facultative heterochromatin which maintains transcriptional repression established during early development in many eukaryotes. However, the mechanism underlying establishment and regulation of epigenetic asymmetry in the zygote remains obscure. Here we show that maternal EZH2 is required for the establishment of H3K27me3 in mouse zygotes. However, combined immunostaining with ULI-NChIP-seq (ultra-low-input micrococcal nuclease-based native ChIP-seq) shows that EZH1 could partially safeguard the role of EZH2 in the formation of H3K27me2. Meanwhile, we identify that EHMT1 is involved in the establishment of H3K27me2, and that H3K27me2 might be an essential prerequisite for the following de novo H3K27me3 modification on the male pronucleus. In this work, we clarify the establishment and regulatory mechanisms of H3K27me2 and H3K27me3 in mouse zygotes.
An immune checkpoint score system for prognostic evaluation and adjuvant chemotherapy selection in gastric cancer
Authors: Wang Jia-Bin , Li Ping , Liu Xiao-Long , Zheng Qiao-Ling , Ma Yu-Bin , Zhao Ya-Jun , Xie Jian-Wei , Lin Jian-Xian , Lu Jun , Chen Qi-Yue , Cao Long-Long , Lin Mi , Liu Li-Chao , Lian Ning-Zi , Yang Ying-Hong , Huang Chang-Ming , Zheng Chao-Hui
Published: December 2020

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISSGC) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISSGCis an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISSGCcan also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.
Sessile volatile drop evaporation under microgravity
Authors: Kumar Sanjeev , Medale Marc , Marco Paolo Di , Brutin David
Published: December 2020

The evaporation of sessile drops of various volatile and non-volatile liquids, and their internal flow patterns with or without instabilities have been the subject of many investigations. The current experiment is a preparatory one for a space experiment planned to be installed in the European Drawer Rack 2 (EDR-2) of the International Space Station (ISS), to investigate drop evaporation in weightlessness. In this work, we concentrate on preliminary experimental results for the evaporation of hydrofluoroether (HFE-7100) sessile drops in a sounding rocket that has been performed in the frame of the MASER-14 Sounding Rocket Campaign, providing the science team with the opportunity to test the module and perform the experiment in microgravity for six consecutive minutes. The focus is on the evaporation rate, experimentally observed thermo-capillary instabilities, and the de-pinning process. The experimental results provide evidence for the relationship between thermo-capillary instabilities and the measured critical height of the sessile drop interface. There is also evidence of the effects of microgravity and Earth conditions on the sessile drop evaporation rate, and the shape of the sessile drop interface and its influence on the de-pinning process.
Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy
Authors: Brumberg Joachim , Schröter Nils , Blazhenets Ganna , Frings Lars , Volkmann Jens , Lapa Constantin , Jost Wolfgang H. , Isaias Ioannis U. , Meyer Philipp T.
Published: December 2020

[18F]fluorodeoxyglucose (FDG) PET and [123I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 ± 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson’s disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.
Probing embedded topological modes in bulk-like GeTe-Sb2Te3 heterostructures
Authors: Nakamura Hisao , Hofmann Johannes , Inoue Nobuki , Koelling Sebastian , Koenraad Paul M. , Mussler Gregor , Grützmacher Detlev , Narayan Vijay
Published: December 2020

The interface between topological and normal insulators hosts metallic states that appear due to the change in band topology. While topological states at a surface, i.e., a topological insulator-air/vacuum interface, have been studied intensely, topological states at a solid-solid interface have been less explored. Here we combine experiment and theory to study such embedded topological states (ETSs) in heterostructures of GeTe (normal insulator) and $$\hbox {Sb}_2$$

Sb
2

$$\hbox {Te}_3$$

Te
3

(topological insulator). We analyse their dependence on the interface and their confinement characteristics. First, to characterise the heterostructures, we evaluate the GeTe-Sb$$_2$$

2

Te$$_3$$

3

band offset using X-ray photoemission spectroscopy, and chart the elemental composition using atom probe tomography. We then use first-principles to independently calculate the band offset and also parametrise the band structure within a four-band continuum model. Our analysis reveals, strikingly, that under realistic conditions, the interfacial topological modes are delocalised over many lattice spacings. In addition, the first-principles calculations indicate that the ETSs are relatively robust to disorder and this may have practical ramifications. Our study provides insights into how to manipulate topological modes in heterostructures and also provides a basis for recent experimental findings [Nguyen et al. Sci. Rep. 6, 27716 (2016)] where ETSs were seen to couple over thick layers.
A nomogram for estimating intracranial pressure using acute subdural hematoma thickness and midline shift
Authors: Liao Chun-Chih , Liao Heng-Chun , Lai Feipei , Xiao Furen
Published: December 2020

Although criteria for surgical treatment of acute subdural hematoma (SDH) have been proposed, interaction exists between SDH, midline shift (MLS), and intracranial pressure (ICP). Based on our half sphere finite-element model (FEM) of the supratentorial brain parenchyma, tools for ICP estimation using SDH thickness (SDHx) and MLS were developed. We performed 60 single load step, structural static analyses, simulating a left-sided SDH compressing the cerebral hemispheres. The Young's modulus was taken as 10,000 Pa. The ICP loads ranged from 10 to 80 mmHg with Poisson's ratios between 0.25 and 0.49. The SDHx and the MLS results were stored in a lookup table. An ICP estimation equation was derived from these data and then was converted into a nomogram. Numerical convergence was achieved in 49 model analyses. Their SDHx ranged from 0.79 to 28.3 mm, and the MLS ranged from 1.5 to 16.9 mm. The estimation formula was log(ICP) = 0.614–0.520 log(SDHx) + 1.584 log(MLS). Good correlations were observed between invasive ICP measurements and those estimated from preoperative SDHx and MLS data on images using our model. These tools can be used to estimate ICP noninvasively, providing additional information for selecting the treatment strategy in patients with SDH.
Characterization of HA-tagged α9 and α10 nAChRs in the mouse cochlea
Authors: Vyas Pankhuri , Wood Megan Beers , Zhang Yuanyuan , Goldring Adam C. , Chakir Fatima-Zahra , Fuchs Paul Albert , Hiel Hakim
Published: December 2020

Neurons of the medial olivary complex inhibit cochlear hair cells through the activation of α9α10-containing nicotinic acetylcholine receptors (nAChRs). Efforts to study the localization of these proteins have been hampered by the absence of reliable antibodies. To overcome this obstacle, CRISPR-Cas9 gene editing was used to generate mice in which a hemagglutinin tag (HA) was attached to the C-terminus of either α9 or α10 proteins. Immunodetection of the HA tag on either subunit in the organ of Corti of adult mice revealed immunopuncta clustered at the synaptic pole of outer hair cells. These puncta were juxtaposed to immunolabeled presynaptic efferent terminals. HA immunopuncta also occurred in inner hair cells of pre-hearing (P7) but not in adult mice. These immunolabeling patterns were similar for both homozygous and heterozygous mice. All HA-tagged genotypes had auditory brainstem responses not significantly different from those of wild type littermates. The activation of efferent neurons in heterozygous mice evoked biphasic postsynaptic currents not significantly different from those of wild type hair cells. However, efferent synaptic responses were significantly smaller and less frequent in the homozygous mice. We show that HA-tagged nAChRs introduced in the mouse by a CRISPR knock-in are regulated and expressed like the native protein, and in the heterozygous condition mediate normal synaptic function. The animals thus generated have clear advantages for localization studies.
Determinants of activity of brown adipose tissue in lymphoma patients
Authors: Brendle Cornelia , Stefan Norbert , Grams Eva , Soekler Martin , la Fougère Christian , Pfannenberg Christina
Published: December 2020

The determinants of brown adipose tissue (BAT) activity are not yet known in detail but might serve as future therapeutic targets against obesity and the metabolic syndrome. We analyzed 235 datasets of lymphoma patients with two PET/CT examinations at different time points retrospectively. We assessed the anthropometric characteristics, features related to the metabolic syndrome, thyroid dysfunction, season of the PET/CT examination, weight change, prior cancer history, lymphoma subgroups, disease activity, and specific lymphoma-related therapies, and evaluated their association with BAT activity. We found BAT activity in 12% of all examinations, and the incidence of BAT activity after initially negative examinations was 10%. In multivariate regression analysis, the prevalence of BAT activity was associated with age, body mass index, sex, the season of the examination, diabetes mellitus, arterial hypertension, and medication on the beta-receptors. New BAT activity arose more often in patients without preceding lymphoma-related therapy. No specific medication was associated with BAT activity. In conclusion, this study confirms the potential connection of BAT with the metabolic syndrome. Preceding lymphoma-related therapy might have an inhibitory effect on the recruitment of BAT.
Physical activity and screen time of children and adolescents before and during the COVID-19 lockdown in Germany: a natural experiment
Authors: Schmidt Steffen C. E. , Anedda Bastian , Burchartz Alexander , Eichsteller Ana , Kolb Simon , Nigg Carina , Niessner Claudia , Oriwol Doris , Worth Annette , Woll Alexander
Published: December 2020

The impact of COVID-19 on social life has been drastic and global. However, the different numbers of cases and different actions in different countries have been leading to various interesting yet unexplored effects on human behavior. In the present study, we compare the physical activity and recreational screen time of a representative sample of 1711 4- to 17-year-olds before and during the strictest time of the first COVID-19 lockdown in Germany. We found that sports activity declined whereas recreational screen time increased. However, a substantial increase in habitual physical activities leads to an overall increase in physical activity among children and adolescents in Germany. The effects differ in size but not in their direction between age groups and are stable for boys and girls. We conclude from this natural experiment that physical activity among children and adolescents is highly context-driven and mutual and does not act as a functional opposite to recreational screen time.
Assessing the evolution of wheat grain traits during the last 166 years using archived samples
Authors: Mariem Sinda Ben , Gámez Angie L. , Larraya Luis , Fuertes-Mendizabal Teresa , Cañameras Nuria , Araus José L. , McGrath Steve P. , Hawkesford Malcolm J. , Murua Carmen Gonzalez , Gaudeul Myriam , Medina Leopoldo , Paton Alan , Cattivelli Luigi , Fangmeier Andreas , Bunce James , Tausz-Posch Sabine , Macdonald Andy J. , Aranjuelo Iker
Published: December 2020

The current study focuses on yield and nutritional quality changes of wheat grain over the last 166 years. It is based on wheat grain quality analyses carried out on samples collected between 1850 and 2016. Samples were obtained from the Broadbalk Continuous Wheat Experiment (UK) and from herbaria from 16 different countries around the world. Our study showed that, together with an increase in carbohydrate content, an impoverishment of mineral composition and protein content occurred. The imbalance in carbohydrate/protein content was specially marked after the 1960’s, coinciding with strong increases in ambient [CO2] and temperature and the introduction of progressively shorter straw varieties. The implications of altered crop physiology are discussed.
An easy to construct sub-micron resolution imaging system
Authors: Sharma Lakhi , Roy A. , Panja S. , De S.
Published: December 2020

We report an easy to construct imaging system that can resolve particles separated by $$\ge $$
≥
0.68 $$\upmu $$
μ
m with minimum aberrations. Its first photon collecting lens is placed at a distance of 31.6 mm giving wide optical access. The microscope has a Numerical Aperture (NA) of 0.33, which is able to collect signal over 0.36 sr. The diffraction limited objective and magnifier recollects 77% photons into the central disc of the image with a transverse spherical aberration of 0.05 mm and magnification upto 238. The system has a depth of field of 142 $$\upmu $$
μ
m and a field of view of 56 $$\upmu $$
μ
m which images a large ensemble of atoms. The imaging system gives a diffraction limited performance over visible to near-infrared wavelengths on optimization of the working distance and the distance between the objective and magnifier.
DNA metabarcoding of fungal diversity in air and snow of Livingston Island, South Shetland Islands, Antarctica
Authors: Rosa Luiz Henrique , Pinto Otávio Henrique Bezerra , Šantl-Temkiv Tina , Convey Peter , Carvalho-Silva Micheline , Rosa Carlos Augusto , Câmara Paulo E. A. S.
Published: December 2020

We assessed fungal diversity present in air and freshly deposited snow samples obtained from Livingston Island, Antarctica, using DNA metabarcoding through high throughput sequencing (HTS). A total of 740 m3 of air were pumped through a 0.22 µm membrane. Snow obtained shortly after deposition was kept at room temperature and yielded 3.760 L of water, which was filtered using Sterivex membranes of 0.22 µm mesh size. The total DNA present was extracted and sequenced. We detected 171 fungal amplicon sequence variants (ASVs), 70 from the air and 142 from the snow. They were dominated by the phyla Ascomycota, Basidiomycota, Mortierellomycota and Mucoromycota. Pseudogymnoascus, Cladosporium, Mortierella and Penicillium sp. were the most dominant ASVs detected in the air in rank order. In snow, Cladosporium, Pseudogymnoascus, Penicillium, Meyerozyma, Lecidea, Malassezia, Hanseniaspora, Austroplaca, Mortierella, Rhodotorula, Penicillium, Thelebolus, Aspergillus, Poaceicola, Glarea and Lecanora were the dominant ASVs present. In general, the two fungal assemblages displayed high diversity, richness, and dominance indices, with the assemblage found in snow having the highest diversity indices. Of the total fungal ASVs detected, 29 were only present in the air sample and 101 in the snow sample, with only 41 present in both samples; however, when only the dominant taxa from both samples were compared none occurred only in the air and, among the rare portion, 26 taxa occurred in both air and snow. Application of HTS revealed the presence of a more diverse fungal community in the air and snow of Livingston Island in comparison with studies using traditional isolation methods. The assemblages were dominated by cold-adapted and cosmopolitan fungal taxa, including members of the genera Pseudogymnoascus, Malassezia and Rhodotorula, which include some taxa reported as opportunistic. Our results support the hypothesis that the presence of microbiota in the airspora indicates the possibility of dispersal around Antarctica in the air column. However, further aeromycology studies are required to understand the dynamics of fungal dispersal within and beyond Antarctica.
Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats
Authors: Moreira Nathalia Juocys Dias , dos Santos Fernando , Moreira Edson Dias , Farah Daniela , de Souza Leandro Eziquiel , da Silva Maikon Barbosa , Moraes-Silva Ivana Cinthya , Lincevicius Gisele Silvério , Caldini Elia Garcia , Irigoyen Maria Cláudia Costa
Published: December 2020

Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. We assessed urinary volume, autonomic control and aorta vascular reactivity after acute RDN. Male normotensive Wistar rats and spontaneously hypertensive rats (SHR) were divided into normotensive + RDN (ND) or sham surgery (NS), and hypertensive + RDN (HD) or sham surgery (HS). Metabolic parameters and hemodynamic measurements were recorded 72h and 4 days after intervention, respectively. Aortic rings were studied 7 days post RDN in an isometric myograph. Concentration–response curves to phenylephrine, sodium nitroprusside and acetylcholine (10–10–10−5 M) were performed. Two-way ANOVA was used for group comparisons and differences reported when p < 0.05. Results are presented as mean ± SEM. Urinary volume was 112% higher in HD vs. HS (HS = 14.94 ± 2.5 mL; HD = 31.69 ± 2.2 mL) and remained unchanged in normotensive rats. Systolic BP was lower in HD rats (HS = 201 ± 12 vs. HD = 172 ± 3 mmHg) without changes in normotensive group. HD group showed increased HF and LF modulation (HS = 5.8 ± 0.7 ms2vs. HD = 13.4 ± 1.4 ms2; HS = 3.5 ± 0.7 ms2vs. HD = 10.5 ± 1.7 ms2, respectively). RDN normalized vascular reactivity in HD rats and increased phenylephrine response in ND rats. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may also have contributed to functional changes of the aorta.
NKT cells promote both type 1 and type 2 inflammatory responses in a mouse model of liver fibrosis
Authors: Nilsson Julia , Hörnberg Maria , Schmidt-Christensen Anja , Linde Kajsa , Nilsson Maria , Carlus Marine , Erttmann Saskia F. , Mayans Sofia , Holmberg Dan
Published: December 2020

Sterile liver inflammation and fibrosis are associated with many liver disorders of different etiologies. Both type 1 and type 2 inflammatory responses have been reported to contribute to liver pathology. However, the mechanisms controlling the balance between these responses are largely unknown. Natural killer T (NKT) cells can be activated to rapidly secrete cytokines and chemokines associated with both type 1 and type 2 inflammatory responses. As these proteins have been reported to accumulate in different types of sterile liver inflammation, we hypothesized that these cells may play a role in this pathological process. We have found that a transgenic NKT (tgNKT) cell population produced in the immunodeficient 2,4αβNOD.Rag2−/− mice, but not in 2,4αβNOD.Rag2+/− control mice, promoted a type 1 inflammatory response with engagement of the NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome. The induction of the type 1 inflammatory response was followed by an altered cytokine profile of the tgNKT cell population with a biased production of anti-inflammatory/profibrotic cytokines and development of liver fibrosis. These findings illustrate how the plasticity of NKT cells modulates the inflammatory response, suggesting a key role for the NKT cell population in the control of sterile liver inflammation.