bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking the association between circRNAs and Alzheimer’s disease progression by multi-tissue circular RNA characterization
Authors: Lo IJu , Hill Jamie , Vilhjálmsson Bjarni J. , Kjems Jørgen 
Published: January 2020

AbstractAlzheimer’s Disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we mined the published dataset on the AMP-AD Knowledge Portal from the Mount Sinai Brain Bank (MSBB) to describe the circRNA profiles at different AD stage in brain samples from four AD patients brain regions, anterior prefrontal cortex, superior temporal lobe, parahippocampal gyrus, and inferior frontal gyrus. We found in total 147 circRNAs to be differentially expressed (DE) during AD progression in the four regions. We also characterized the mRNA-circRNA co-expression network and annotated the potential function of circRNAs based on the co-expressed modules. Based on our results, we propose that parahippocampal gyrus is the most circRNA-regulated region during the AD progression. The strongest negatively AD stage-correlated module in parahippocampal gyrus were enriched in cognitive disability and pathological-associated pathways such as synapse organization and regulation of membrane potential. Finally, the regression model based on the expression pattern of DE circRNAs in the module could help to distinguish the disease severity of patients, further supported the importance of circRNAs in AD pathology. In conclusion, our finding indicates that circRNAs in parahippocampal gyrus are possible regulators of AD progression and potentially be a therapeutic target or of AD.
Teratogenic Drug Topiramate Upregulates TGFβ1 and SOX9 Expression in Primary Palatal Mesenchyme Cells
Authors: Rafi Syed K. , Goering Jeremy P. , Olm-Shipman Adam J. , Hipp Lauren A. , Ernst Nicholas J. , Wilson Nathan R. , Hall Everett G. , Gunewardena Sumedha , Saadi Irfan 
Published: January 2020

AbstractTopiramate is a commonly prescribed anti-epileptic drug with over 8 million prescriptions dispensed annually. Topiramate use during pregnancy has been linked to significantly increased risk of babies born with orofacial clefts (OFCs). However, the exact molecular mechanism of topiramate teratogenicity is unknown. We used an unbiased antibody array analysis to test the effect of topiramate on human embryonic palatal mesenchyme (HEPM) cells. This analysis identified 40 differentially expressed proteins, showing strong connectivity to known OFC genes. However, among known OFC genes, only TGFβ1 was significantly upregulated in the antibody array analysis. Next, we validated that topiramate could increase expression of TGFβ1 and of downstream target phospho-SMAD2 in primary mouse embryonic palatal mesenchyme (MEPM) cells. Furthermore, we showed that topiramate treatment of primary MEPM cells increased expression of SOX9. SOX9 overexpression in chondrocytes is known to cause cleft palate in mouse. We propose that topiramate mediates upregulation of TGFβ1 signaling through activation of γ-aminobutyric acid (GABA) receptors in the palate. TGFβ1 and SOX9 play critical roles in orofacial morphogenesis, and their abnormal overexpression may underlie the teratogenic effects of topiramate.
Chromosome-level assembly of theCaenorhabditis remaneigenome reveals conserved patterns of nematode genome organization
Authors: Teterina Anastasia A. , Willis John H. , Phillips Patrick C. 
Published: January 2020

AbstractThe nematodeCaenorhabditis elegansis one of the key model systems in biology, including possessing the first fully assembled animal genome. WhereasC. elegansis a self-reproducing hermaphrodite with fairly limited within-population variation, its relativeC. remaneiis an outcrossing species with much more extensive genetic variation, making it an ideal parallel model system for evolutionary genetic investigations. Here, we greatly improve on previous assemblies by generating a chromosome-level assembly of the entireC. remaneigenome (124.8 Mb of total size) using long-read sequencing and chromatin conformation capture data. Like other fully assembled genomes in the genus, we find that theC. remaneigenome displays a high degree of synteny withC. elegansdespite multiple within-chromosome rearrangements. Both genomes have high gene density in central regions of chromosomes relative to chromosome ends and the opposite pattern for the accumulation of repetitive elements.C. elegansandC. remaneialso show similar patterns of inter-chromosome interactions, with the central regions of chromosomes appearing to interact with one another more than the distal ends. The newC. remaneigenome presented here greatly augments the use of theCaenorhabditisas a platform for comparative genomics and serves as a basis for molecular population genetics within this highly diverse species.
Material category of visual objects computed from specular image structure
Authors: Schmid Alexandra C. , Barla Pascal , Doerschner Katja 
Published: January 2020

ABSTRACTRecognising materials and their properties from visual information is vital for successful interactions with our environment, from avoiding slippery floors to handling fragile objects. Yet there is no simple mapping of retinal image intensities to the physical properties that define materials. While studies have investigated how material properties like surface gloss are perceived from regularities in image structure, such as the size, sharpness, contrast, and position of bright patches caused by specular reflections, little is known how this translates to the recognition of different material classes like plastic, pearl, satin, or steel, and the underlying mechanisms involved. We investigated this by collecting human psychophysical judgments about complex glossy objects rendered in natural illumination fields. We found that variations in specular image structure – produced either by different reflectance properties or direct manipulation of image features – caused categorical shifts in material appearance, suggesting that specular reflections provide diagnostic information about a wide range of material classes, including many that should be defined by more complex scattering functions. Moreover, differences in material category were predicted by, but also appeared to mediate, cues for surface gloss, providing evidence against a traditional feedforward view of neural processing that assumes combinations of mid-level properties mediate our holistic, categorical impressions. Instead, our results suggest that the image structure that triggers our perception of surface gloss plays a direct role in visual categorisation and, importantly, that the perception and neural processing of stimulus properties should not be studied in isolation but rather in the context of recognition.
Cell shape, and not 2D migration, predicts ECM-driven 3D cell invasion in breast cancer
Authors: Baskaran Janani P. , Weldy Anna , Guarin Justinne , Munoz Gabrielle , Kotlik Michael , Subbiah Nandita , Wishart Andrew , Peng Yifan , Miller Miles A. , Cowen Lenore , Oudin Madeleine J. 
Published: January 2020

AbstractMetastasis, the leading cause of death in cancer patients, requires the invasion of tumor cells through the stroma in response to migratory cues, such as those provided by the extracellular matrix (ECM). Recent advances in proteomics have led to the identification of hundreds of ECM proteins which are more abundant in tumors relative to healthy tissue. Our goal was to develop a pipeline to easily predict which of these ECM proteins is more likely to have an effect on cancer invasion and metastasis. We evaluated the effect of 4 ECM proteins upregulated in breast tumor tissue in multiple human breast cancer cell lines in 3 assays. We found there was no linear relationship between the 11 cell shape parameters we quantified when cells adhere to ECM proteins and 2D cell migration speed, persistence or 3D invasion. We then used classifiers and partial-least squares regression analysis to identify which metrics best predicted ECM-driven 2D migration and 3D invasion responses. ECM-driven 2D cell migration speed or persistence did not correlate with or predict 3D invasion in response to that same cue. However, cell adhesion, and in particular cell elongation and irregularity accurately predicted the magnitude of ECM-driven 2D migration and 3D invasion in all cell lines. Testing predictions revealed that our models are good at predicting the effect of novel ECM proteins within a given cell line, but that ECM responses are cell-line specific. Overall, our studies identify the cell morphological features that determine 3D invasion responses to individual ECM proteins. This platform will help provide insight into the functional role of ECM proteins abundant tumor tissue and help prioritize strategies for targeting tumor-ECM interactions to treat metastasis.FundingThis work was supported by the National Institutes of Health [R00-CA207866-04 to M.J.O.]; Tufts University [Start-up funds from the School of Engineering to M.J.O.] and funds from NSF REU to A.W.Conflict-of-interest: None.Insight BoxMetastasis, the dissemination of tumor cells, is driven by the interaction of invading tumor cells with their local environment, in particular with the ECM, which provides structure and support to our tissues. This study presents an integrated approach to predict the effect of individual ECM proteins on 3D invasion and metastasis based on simple adhesion assays which quantify cell shape. Machine learning classification and partial-least squares regression models reveal that ECM-driven 2D cell migration metrics are not predictive of 3D invasion, and that cell shape of cells adhered to ECM can predict that protein’s effect on 3D invasion. These data provide a pipeline for predicting the effect of ECM proteins on breast cancer cell invasion and metastasis.
Multilevel integrative transcriptome analyses in humans and humanized mice define in vivo human lncRNA metabolic regulators
Authors: Ruan Xiangbo , Li Ping , Ma Yonghe , Jiang Cheng-fei , Chen Yi , Shi Yu , Gupta Nikhil , Seifuddin Fayaz , Pirooznia Mehdi , Suemizu Hiroshi , Ohnishi Yasuyuki , Yoneda Nao , Nishiwaki Megumi , Cao Haiming 
Published: January 2020

AbstractA growing number of long non-coding RNAs (lncRNAs) have emerged as vital metabolic regulators in research animals suggesting that lncRNAs could also play an important role in human metabolism. However, most human lncRNAs are non-conserved, vastly limiting our ability to identify human lncRNA metabolic regulators (hLMRs). As the sequence-function relation of lncRNAs has yet to be established, the identification of lncRNA metabolic regulators in animals often relies on their regulations by experimental metabolic conditions. But it is very challenging to apply this strategy to human lncRNAs because well-controlled human data are much limited in scope and often confounded by genetic heterogeneity. In this study, we establish an efficient pipeline to identify putative hLMRs that are metabolically sensitive, disease-relevant, and population applicable. We first progressively processed human transcriptome data to select human liver lncRNAs that exhibit highly dynamic expression in the general population, show differential expression in a metabolic disease population, and response to dietary intervention in a small disease cohort. We then experimentally demonstrated the responsiveness of selected hepatic lncRNAs to defined metabolic milieus in a liver-specific humanized mouse model. Furthermore, by extracting a concise list of protein-coding genes that are persistently correlated with lncRNAs in general and metabolic disease populations, we predicted the specific function for each hLMR. Using gain- and loss-of-function approaches in humanized mice as well as ectopic expression in conventional mice, we were able to validate the regulatory role of one non-conserved hLMR in cholesterol metabolism. Mechanistically, this hLMR binds to an RNA-binding protein, PTBP1, to modulate the transcription of cholesterol synthesis genes. In summary, our study provides a pipeline to overcome the variabilities intrinsic to human data to enable the efficient identification and functional definition of hLMRs. The combination of this bioinformatic framework and humanized murine model will enable broader systematic investigation of the physiological role of disease-relevant human lncRNAs in metabolic homeostasis.
Histone modification dynamics as revealed by a multicolor immunofluorescence-based single-cell analysis
Authors: Hayashi-Takanaka Yoko , Kina Yuto , Nakamura Fumiaki , Becking Leontine E. , Nakao Yoichi , Nagase Takahiro , Nozaki Naohito , Kimura Hiroshi 
Published: January 2020

AbstractPost-translational modifications on histones can be stable epigenetic marks and transient signals that can occur in response to internal and external stimuli. Levels of histone modifications fluctuate during the cell cycle and vary among different cell types. Here we describe a simple system to monitor the levels of multiple histone modifications in single cells by multicolor immunofluorescence using directly labeled modification-specific antibodies. We first analyzed histone H3 and H4 modifications during the cell cycle. Levels of active marks, such as acetylation and H3K4 methylation, were increased during the S phase, in association with chromatin duplication. By contrast, levels of some repressive modifications gradually increased during the G2 and the next G1 phases. We applied this method to validate the target modifications of various histone demethylases in cells using a transient overexpression system. We also screened chemical compounds in marine organism extracts that affect histone modifications and identified psammaplin A, which was previously reported to inhibit histone deacetylases. Thus, the method presented here is a powerful and convenient tool for analyzing the changes in histone modifications.
Single cell atlas of trisomy 21 cerebral cortex
Authors: Zhang Jingxuan , Wang Shiyou , Xu Zaoxu , Ding Xiangning , Li Chen , Zhang Yonghong , Chen Yin , Zhong Jixing , Liang Langchao , Chai Chaochao , Wang Xiaoling , Xiang Rong , Zhu Jiacheng , Lin Xiumei , Ding Peiwen , Zhang Qiang , Wang Mingyue , Feng Qikai , Zhang Zhijun , Guo Guangling , Xue Shen , Jin Lin , He Zhikai , Yan Li , Xiao Bing , Zhang Changjun , Xu Yan , Li Wei , Zhang Yichi , Wu Weiying , Jiang Sanjie , Xia Jun , Gao Ya , Wang Lei , Dong Shichen , Liu Si , Zhu Shida , Chen Fang , Chen Dongsheng , Xu Xun 
Published: January 2020

AbstractDown syndrome (DS) is one of the most common human birth defects caused by trisomy 21 (T21), leading to a variety of cognitive impairments. The cellular composition of human brain has been explored using single cell RNA sequencing in both physiological and pathological conditions. However, the cellular heterogeneity of human brain with chromosome aneuploidy is largely unknown. Here, we profiled the transcriptome of 36046 cells in cerebral cortex of T21 human fetus, covering frontal lobe, parietal lobe, occipital lobe and temporal lobe. Intriguingly, we detected several genes positively associated with neurons maturation was dysregulated in T21 frontal cortex (HIC2, POU2F2, ZGLP1andFOXK1). To share, explore and utilized the data resources of T21 cerebral cortex, we developed a comprehensive platform named T21atlas, composing of two functional modules (T21cluster and T21talk). Overall, our study provides, as far as we know, the first single cell atlas for T21 cerebral cortex, which could promote our understanding of the molecular mechanism of DS at an unprecedented resolution and could potentially facilitate the development of novel clinical therapeutics against T21.
An antigenic diversification threshold for falciparum malaria transmission at high endemicity
Authors: He Qixin , Pascual Mercedes 
Published: January 2020

AbstractIn malaria and several other important infectious diseases, high prevalence occurs concomitantly with incomplete immunity. This apparent paradox poses major challenges to malaria elimination in highly endemic regions, where asymptomaticPlasmodium falciparuminfections are present across all age classes creating a large reservoir that maintains transmission. This reservoir is in turn enabled by extreme antigenic diversity of the parasite and turnover of new variants. We present here the concept of a threshold in local pathogen diversification that defines a sharp transition in transmission intensity below which new antigen-encoding genes generated by either recombination or migration cannot establish. Transmission still occurs below this threshold, but diversity of these genes can neither accumulate nor recover from interventions that further reduce it. An analytical expectation for this threshold is derived and compared to numerical results from a stochastic individual-based model of malaria transmission that incorporates the major antigen-encoding multigene family known asvar. This threshold corresponds to an “innovation” number we callRdiv; it is different from, and complementary to, the one defined by the classic basic reproductive number of infectious diseases,R0, which does not easily apply under large and dynamic strain diversity. This new threshold concept can be exploited for effective malaria control and applied more broadly to other pathogens with large multilocus antigenic diversity.Author summaryThe vast diversity of the falciparum malaria parasite as seen by the immune system of hosts in high transmission regions, underlies both high prevalence of asymptomatic infections and partial protection to re-infection despite previous exposure. This large antigenic diversity of the parasite challenges control and elimination efforts. We propose a threshold quantity for antigenic innovation, we callRdiv, measuring the potential of transmission to accumulate new antigenic variants over time. WhenRdivis pushed below one by reduced transmission intensity, new genes encoding this variation can no longer accumulate, resulting in a lower number of strains and facilitating further intervention. This innovation number can be applied to other infectious diseases with fast turnover of antigens, where large standing diversity similarly opposes successful intervention.
A Waddington Epigenetic Landscape for theC. elegansembryo
Authors: Elewa Ahmed 
Published: January 2020

AbstractWaddington’s Epigenetic Landscape provides a visual model for both robust and adaptable development. Generating and exploring a Waddington epigenetic landscape for the earlyC. elegansembryo suggests that the key shapers of the landscape are genes that lie at the nexus between stress response and behavior and include genes that are regulated by transgenerational neuronal small RNAs. Curiously, several genes shape the early landscape of one lineage and then pattern, differentiate or are enriched in another lineage. Additionally, paralogs with similar expression profiles contribute differently to shaping the modeled landscape. This work suggests that robust embryonic development is initialized by differential deployment of redundant genes and by transgenerational cues that configure the epigenetic landscape to adapt to a changing world.
Adhesion force spectroscopy with nanostructured colloidal probes reveals nanotopography-dependent early mechanotransductive interactions at the cell membrane level
Authors: Chighizola M. , Previdi A. , Dini T. , Piazzoni C. , Lenardi C. , Milani P. , Schulte C. , Podestà A. 
Published: January 2020

ABSTRACTMechanosensing, the ability of cells to perceive and interpret the microenvironmental biophysical cues (such as the nanotopography), impacts strongly on cellular behaviour through mechanotransductive processes and signalling. These events are predominantly mediated by integrins, the principal cellular adhesion receptors located at the cell/extracellular matrix (ECM) interface.Because of the typical piconewton force range and nanometre length scale of mechanotransductive interactions, achieving a detailed understanding of the spatiotemporal dynamics occurring at the cell/microenvironment interface is challenging; sophisticated interdisciplinary methodologies are required. Moreover, an accurate control over the nanotopographical features of the microenvironment is essential, in order to systematically investigate and precisely assess the influence of the different nanotopographical motifs on the mechanotransductive process.In this framework, we were able to study and quantify the impact of microenvironmental nanotopography on early cellular adhesion events by means of adhesion force spectroscopy based on innovative colloidal probes mimicking the nanotopography of natural ECMs.These probes provided the opportunity to detect nanotopography-specific modulations of the molecular force loading dynamics and integrin clustering at the level of single binding events, in the critical time window of nascent adhesion formation. Following this approach, we found that the nanotopographical features are responsible for an excessive force loading in single adhesion sites after 20 – 60 s of interaction, causing a drop in the number of adhesion sites. However, by manganese treatment we demonstrated that the availability of activated integrins is a critical regulatory factor for these nanotopography-dependent dynamics.
The preservation of news archives: the case of Asia Television (ATV) in Hong Kong
Authors: Li Simon K. , Lee Hang Lai Samman 
Published: January 2020

Purpose
The purpose of this paper is to discuss the urgency to ensure the preservation of the news archives of the crisis-packed Hong Kong-based Asia Television (ATV), the first Chinese television station in the world. This paper also explores the life and times as well as the future of the historical collections of the ATV archives, which is a treasure trove that covers key events in Hong Kong’s history since 1957, a decade before its major rival Television Broadcasts Limited began to go on air.

Design/methodology/approach
Adopting the qualitative approach with in-depth face-to-face interviews, the now defunct ATV News’ longest-serving as well as its very last Chief Librarians discusses the bleeding of priceless history in the 62-year-old news archives which contain Hong Kong’s collective memories.

Findings
An important role of the old news footage is to capture the public’s memories and to take people back to the actual unfolding of landmark events. The interview answers open the way for readers to understand the ways television archives hold immense historical value for a city’s memory and what could be done and preserved before their disappearance.

Originality/value
This paper will be of interest to those historians, journalists, scholars and archivists, including news librarians, who are interested in learning how the ATV’s half-a-century-old archival news footage is a significant asset and cultural record to the former colony.