bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome
Authors: Rychel Kevin , Sastry Anand V. , Palsson Bernhard O. 
Published: December 2020

AbstractThe 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

AbstractLong 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

AbstractAcidothermus 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

AbstractHuman 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

AbstractNew 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

AbstractThe 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

AbstractImmunosuppressive 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

AbstractThe 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

Abstract[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

AbstractThe 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

AbstractAlthough 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

AbstractNeurons 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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractWe 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.