bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting behavior through dynamic modes in resting-state fMRI data
Authors: Ikeda Shigeyuki , Kawano Koki , Watanabe Soichi , Yamashita Okito , Kawahara Yoshinobu 
Published: May 2021

ABSTRACTDynamic properties of resting-state functional connectivity (FC) provide rich information on brainbehavior relationships. Dynamic mode decomposition (DMD) has been used as a method to characterize FC dynamics. However, it remains unclear whether dynamic modes (DMs), spatial-temporal coherent patterns computed by DMD, provide information about individual behavioral differences. This study established a methodological approach to predict individual differences in behavior using DMs. Furthermore, we investigated the contribution of DMs within each of seven specific frequency bands (0-0.1,…,0.6–0.7 Hz) for prediction. To validate our approach, we confirmed whether each of 59 behavioral measures could be predicted by performing multivariate pattern analysis on a gram matrix, which was created using subject-specific DMs computed from resting-state functional magnetic resonance imaging (rs-fMRI) data of individuals. The prediction was successful, and DMD outperformed temporal independent component analysis, a conventional data decomposition method for extracting spatial activity patterns. Most of the behavioral measures that showed significant prediction accuracies in a permutation test were cognitive-behavioral measures. Our results suggested that DMs within frequency bands <0.2 Hz primarily contributed to prediction. In addition, we found that DMs <0.2 Hz had spatial structures similar to several common resting-state networks. We demonstrated the effectiveness of DMs, indicating that DMD is a key approach for extracting spatiotemporal features from rs-fMRI data.
Gains of 12p13.31 delay WNT-mediated initiation of hPSC differentiation and promote residual pluripotency in a cell cycle dependent manner
Authors: Keller Alexander , Lei Yingnan , Krivec Nuša , de Deckersberg Edouard Couvreu , Dziedzicka Dominika , Markouli Christina , Sermon Karen , Geens Mieke , Spits Claudia 
Published: May 2021

SummaryThough gains of chromosome 12p13.31 are highly recurrent in hPSC, their impact on differentiation is poorly understood. We identify a reduction in differentiation capacity towards all three germ layers and a subpopulation of residual pluripotent cells that appear during hepatic specification. These cells form as a result of the overexpression of NANOG and GDF3, whereby NANOG as the primary driver delays activation of WNT signaling, partly as a result of a direct physical interaction with TCF7. Entry into the residual state is determined by cell cycle position at the onset of differentiation and is maintained by a feedback loop between NANOG and GDF3. These findings highlight the ability of genetically abnormal hPSC to escape correct differentiation and to form residual pluripotent cells, an important risk in the safe clinical translation of hPSC. Our results further refine the molecular mechanisms that underpin the exit from pluripotency and onset of differentiation.
Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing
Authors: Bhattacharya Saikat , Wang Suman , Reddy Divya , Shen Siyuan , Zhang Ying , Zhang Ning , Li Hua , Washburn Michael P. , Florens Laurence , Shi Yunyu , Li Fudong , Workman Jerry L. 
Published: May 2021

ABSTRACTThe RNA recognition motif (RRM) binds to nucleic acids as well as proteins. More than one such domain is found in the pre-mRNA processing hnRNP proteins. While the mode of RNA recognition by RRMs is known, the molecular basis of their protein interaction remains obscure. Here we describe the mode of interaction between hnRNP L and LL with the methyltransferase SETD2. We demonstrate that for the interaction to occur, a leucine pair within a highly conserved stretch of SETD2 insert their side chains in hydrophobic pockets formed by hnRNP L RRM2. Notably, the structure also highlights that RRM2 can form a ternary complex with SETD2 and RNA. Remarkably, mutating the leucine pair in SETD2 also results in its reduced interaction with other hnRNPs. Importantly, the similarity that the mode of SETD2-hnRNP L interaction shares with other related protein-protein interactions reveals a conserved design by which splicing regulators interact with one another.
Comparison of human and mouse tissues with focus on genes with no 1-to-1 homology
Authors: Jeong Jieun , Kellis Manolis 
Published: May 2021

AbstractWe assembled a panel of 28 tissue pairs of human and mouse with RNA-Seq data on gene expression. We focused on genes with no 1-to-1 homology, because they pose special challenges. In this way, we identified expression patterns that identify and explain differences between the two species and suggest target genes for therapeutic applications. Here we mention three examples.One pattern is observed by defining the aggregate expression of immunoglobulin genes (which have no homology) as a measure of different levels of an immune response. In Lung, we used this statistic to find genes that have significantly higher expression in low/moderate response, and thus they may be therapy targets: increasing their expression or mimicking their function with medications may help in recovery from inflammation in the lungs. Some of the observed associations are common to human and mouse; other associations involve genes involved in cell-to-cell signaling or in regeneration but were not known to be important in Lung.Second pattern is that in the Small Intestine, mouse expresses much less antimicrobial defensins, while it has much higher expression of enzymes that are found to improve adaptive immune response. Such enzymes may be tested if they improve probiotic supplements that help in gut inflammation and other diseases.Another pattern involves a many-to-many homology group of defensins that did not have a described function. In human tissues, expression of its genes was found only in a study of a disease of hair covered skin, but several of its genes are highly expressed in two tissues of our panel: mouse Skin and to a lesser degree mouse Vagina. This suggests that those genes or their homologs in other species may provide non-antibiotic medications for hair covered skin and other tissues with microbiome that includes fungi.
Ebola virus glycoprotein domains associated with protective efficacy
Authors: Bhatia Bharti , Furuyama Wakako , Hoenen Thomas , Feldmann Heinz , Marzi Andrea 
Published: May 2021

AbstractEbola virus (EBOV) is the cause of sporadic outbreaks of human hemorrhagic disease in Africa, and the best-characterized virus in the filovirus family. The West Africa epidemic accelerated the clinical development of vaccines and therapeutics leading to licensure of vaccines and antibody-based therapeutics for human use in recent years. The most widely used vaccine is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP)(VSV-EBOV). Due to its favorable immune cell targeting, this vaccine has also been used as base-vector for the development of second generation VSV-based vaccines against Influenza, Nipah, and Zika viruses. However, in these situations it may be beneficial if the immunogenicity against EBOV GP is minimized to induce a better protective immune response against the other foreign immunogen. Here, we analyzed if EBOV GP can be truncated to be less immunogenic yet still able to drive replication of the vaccine vector. We found that the EBOV GP glycan cap and the mucin-like domain are both dispensable for VSV-EBOV replication. The glycan cap domain, however, appears critical for mediating a protective immune response against lethal EBOV challenge in mice.
Reactive/Non-cooperative individuals advance Population’s Synchronization: Modeling ofDictyostelium discoideumConcerted Signaling during Aggregation Phase
Authors: Eidi Zahra , Khorasani Najme , Sadeghi Mehdi 
Published: May 2021

AbstractOrchestrated chemical signaling of single cells sounds to be a linchpin of emerging organization and multicellular life form. The social amoebaDictiostelium discoiudiumis a well-studied model organism to explore overall pictures of grouped behavior in developmental biology. The chemical waves secreted by aggregatingDictiosteliumis a superb example of pattern formation. The waves are either circular or spiral in shape, according to the incremental population density of a self-aggregating community of individuals. Here, we revisit the spatiotemporal patterns that appear in an excitable medium due to synchronization of randomly firing individuals, but with a more parsimonies attitude. According to our model, a fraction of these individuals is refusal to amplify external stimulants. Our simulations indicate that the cells enhance the system’s asymmetry and as a result, nucleate early sustainable spiral territory zones, provided that their relative population does not exceed a tolerable threshold.
Non-coding NFKBIZ 3′ UTR mutations promote cell growth and resistance to targeted therapeutics in diffuse large B-cell lymphoma
Authors: Arthur Sarah E. , Gao Jie , Healy Shannon , Rushton Christopher K. , Thomas Nicole , Hilton Laura K. , Dreval Kostiantyn , Tang Jeffrey , Alcaide Miguel , Cojocaru Razvan , Mottok Anja , Telenius Adèle , Unrau Peter , Wilson Wyndham H. , Staudt Louis M. , Scott David W. , Hodson Daniel J , Steidl Christian , Morin Ryan D. 
Published: May 2021

AbstractAmplifications and non-coding 3′ UTR mutations affecting NFKBIZ have been identified as recurrent genetic events in diffuse large B-cell lymphoma (DLBCL). We confirm the prevalence and pattern of NFKBIZ 3′ UTR mutations in independent cohorts and determine they are enriched in the ABC subtype as well as the recently described novel BN2/C1/NOTCH2 classes of DLBCL. Presently, the effects of and mechanism by which non-coding mutations can act as cancer drivers has been relatively unexplored. Here, we provide a functional characterization of these non-coding NFKBIZ 3′ UTR mutations. We demonstrate that the resulting elevated expression of IκB-ζ confers growth advantage in DLBCL cell lines and primary germinal center B-cells as well as nominate novel IκB-ζ target genes with potential therapeutic implications. The limited responses to targeted treatments in DLBCL, particularly those targeting the NF-κB axis, led us to investigate and confirm that NFKBIZ 3′ UTR mutations affect response to therapeutics and suggest it may be a useful predictive biomarker.Statement of SignificanceThrough functional characterization we reveal that non-coding NFKBIZ 3′ UTR mutations are a common driver in DLBCL, and mutation status may be a relevant biomarker to predict poor response to therapeutics targeting the NF-κB pathway.
The endoplasmic reticulum associated degradation adaptor Sel1L regulates T cell homeostasis and function
Authors: Dils Alexander T. , Correa Luis O. , Gronevelt J. Paige , Liu Lu , Kadiyala Padma , Li Qing , Carty Shannon A. 
Published: May 2021

SummarySuppressor/Enhancer of Lin-12-like (Sel1L) is a critical adaptor for endoplasmic reticulum-associated degradation (ERAD), a process that maintains cellular protein quality control through degradation of misfolded proteins. Here we investigate the role of Sel1L in T cell homeostasis and function. T cell-specific deletion of Sel1L profoundly impairs peripheral T cell survival and promotes apoptotic cell death. Furthermore, Sel1L is required to maintain naïve CD8+ T cell homeostasis in a cell-intrinsic manner with loss of quiescence as evidenced by increased proliferation. Sel1L-deficient T cells exhibit enhanced activation of the mammalian target of rapamycin (mTOR) pathway and altered cellular metabolism, including increased cellular reactive oxygen species, mitochondrial mass and mitochondrial membrane potential in the naïve CD8+ T cell compartment. Furthermore, loss of Sel1L impaired CD8+ T cell immune responses following bacterial infection. These results demonstrate a novel role for Sel1L/ERAD in T cell homeostasis and function.
A novel SERPINE1-FOSB fusion gene in a case of pseudomyogenic hemangioendothelioma results in activation of intact FOSB and the PI3K-AKT-mTOR signaling pathway and responsiveness to sirolimus
Authors: Ren Jun , Wang Xiaohui , Zhou Yulin , Yue Xin , Chen Shouhui , Ding Xin , Jiang Xiaoyong , Liu Xiaokun , Guo Qiwei 
Published: May 2021

AbstractPseudomyogenic hemangioendothelioma (PHE) is an extremely rare disease that affects mainly the young and more men than women. PHE are multicentric, locally aggressive, have low metastatic potential, and affect multiple tissue planes. Genetic aberrations are frequently detected in PHE and may play important roles in the occurrence, development, and treatment of this disease. In this study, we report a case of PHE with a novel SERPINE1-FOSB fusion gene. The fusion introduced a strong promoter near the coding region of FOSB, resulting in overexpression of intact FOSB. Immunohistochemical analysis showed overexpression of pAKT and mTOR in tumor cells, suggesting activation of the PI3K-AKT-mTOR signaling pathway. The patient responded well to targeted therapy with sirolimus, an mTOR inhibitor. Our study correlated dysregulation of a specific signaling pathway and the effectiveness of a targeted therapy to a specific genetic aberration. This information may be useful for future investigations of targeted therapeutics and provide a potential predictive biomarker for therapeutic effectiveness in cases of PHE with this genetic aberration.
Tmem138, a photoreceptor connecting cilium (CC) protein, is required for rhodopsin transport across the cilium and outer segment (OS) biogenesis
Authors: Guo Dianlei , Ru Jiali , Xie Lijing , Wu Mingjuan , Su Yingchun , Zhu Shiyong , Xu Shujuan , Wei Yanhong , Liu Xialin , Liu Yizhi , Liu Chunqiao 
Published: May 2021

AbstractPhotoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as non-syndromic retinal degenerations. Despite extensive studies, protein trafficking across the photoreceptor CC is largely unknown. Here we genetically inactivated mouse Tmem138, a gene encoding a ciliary membrane protein localized to the ciliary TZ and linked to Joubert syndrome (JBTS). Germline deletion of Tmem138 abolished OS morphogenesis followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and, accordingly, the molecular compartments of the CC and axoneme of the mutant photoreceptors were altered despite ciliogenesis proceeding normally at the early stage of photoreceptor development. To gain further insights into Tmem138 function in OS biogenesis, we focused on trafficking of rhodopsin, the most abundant protein of the OS. Mislocalization of rhodopsin was readily observed as early as P5 in the mutant photoreceptors prior to growth of the OS. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing well-formed outer segment discs to disintegrate accompanied by mislocalization of rhodopsin in the cell body. Furthermore, Tmem138 interacted with rhodopsin, and two additional CC compartment proteins Ahi1 and Tmem231, which were both altered in the mutant photoreceptors. Taken together, these results suggest that Tmem138 has a distinct role in gating the transport of rhodopsin and likely other OS bound proteins through formation of CC transport complex(es).
The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution
Authors: Nirmal Ajit J. , Maliga Zoltan , Vallius Tuulia , Quattrochi Brian , Chen Alyce A. , Jacobson Connor A. , Pelletier Roxanne J. , Yapp Clarence , Arias-Camison Raquel , Chen Yu-An , Lian Christine G. , Murphy George F. , Santagata Sandro , Sorger Peter K. 
Published: May 2021

ABSTRACTCutaneous melanoma is a highly immunogenic malignancy, surgically curable at early stages, but life- threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially-resolved micro-region transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis involving precursor states, melanomain situ,and invasive tumor. Hallmarks of immunosuppression are already detectable in precursor regions. When tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor-stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1, and by PD1-PDL1 mediated cell contacts involving macrophages, dendritic cells, and T cells. A few millimeters away, cytotoxic T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can co-exist within a few millimeters of each other in a single specimen.STATEMENT OF SIGNIFICANCEThe reorganization of the tumor ecosystem in primary melanoma is an excellent setting in which to study immunoediting and immune evasion. Guided by classical histopathology, spatial profiling of proteins and mRNA reveals recurrent morphological and molecular features of tumor evolution that involve localized paracrine cytokine signaling and direct cell-cell contact.
Biomechanics and Myofibrillar Alignment Enhance Contractile Development and Reproducibility in Stem Cell Derived Cardiac Muscle
Authors: Tsan Yao-Chang , Zhao Yan-Ting , DePalma Samuel J. , Capilnasiu Adela , Wu Yu-Wei , Elder Brynn , Panse Isabella , Friedline Sabrina , O’Leary Thomas S. , Wubshet Nadab , Ho Kenneth K. Y. , Previs Michael J. , Nordsletten David , Baker Brendon M. , Isom Lori L. , Liu Allen P. , Helms Adam S. 
Published: May 2021

AbstractHuman pluripotent stem cell derived cardiomyocytes (hPSC-CMs) allow novel investigations of human cardiac disease, but disorganized mechanics and immaturity of hPSC-CMs on two-dimensional (2D) surfaces have been hurdles for efficient and reproducible study of these cells. Here, we developed a platform of micron-scale 2D cardiac tissues (M2DCTs) to precisely control biomechanics in arrays of thousands of purified, independently contracting cardiac muscle strips in 2D. By defining geometry and workload in M2DCTs in this reductionist platform that does not incorporate other cell types, we show that myofibrillar alignment and auxotonic contractions at physiologic workload critically drive maturation of cardiac contractile function, calcium handling, and electrophysiology. Additionally, the organized biomechanics in this system facilitates rapid and automated extraction of contractile kinetic parameters from brightfield microscopy images, increasing the reproducibility and throughput of pharmacologic testing. Finally, we show that M2DCTs enable precise and efficient dissection of contractile kinetics in cardiomyopathy disease models.
Resource levelling in projects considering different activity execution modes and splitting
Authors: Khalilzadeh Mohammad 
Published: May 2021

Purpose
This study aims to develop a mathematical programming model for preemptive multi-mode resource-constrained project scheduling problems in construction with the objective of levelling resources considering renewable and non-renewable resources.

Design/methodology/approach
The proposed model was solved by the exact method and the genetic algorithm integrated with the solution modification procedure coded with MATLAB software. The Taguchi method was applied for setting the parameters of the genetic algorithm. Different numerical examples were used to show the validation of the proposed model and the capability of the genetic algorithm in solving large-sized problems. In addition, the sensitivity analysis of two parameters, including resource factor and order strength, was conducted to investigate their impact on computational time.

Findings
The results showed that preemptive activities obtained better results than non-preemptive activities. In addition, the validity of the genetic algorithm was evaluated by comparing its solutions to the ones of the exact methods. Although the exact method could not find the optimal solution for large-scale problems, the genetic algorithm obtained close to optimal solutions within a short computational time. Moreover, the findings demonstrated that the genetic algorithm was capable of achieving optimal solutions for small-sized problems. The proposed model assists construction project practitioners with developing a realistic project schedule to better estimate the project completion time and minimize fluctuations in resource usage during the entire project horizon.

Originality/value
There has been no study considering the interruption of multi-mode activities with fluctuations in resource usage over an entire project horizon. In this regard, fluctuations in resource consumption are an important issue that needs the attention of project planners.
Technology options to help people with dementia or acquired cognitive impairment perform multistep daily tasks: a scoping review
Authors: Lancioni Giulio , Desideri Lorenzo , Singh Nirbhay , O'Reilly Mark , Sigafoos Jeff 
Published: May 2021

Purpose
The purpose of this paper is to review studies that evaluated technology-based prompting systems for supporting participants with dementia or acquired cognitive impairment in their performance of multistep daily tasks.

Design/methodology/approach
A scoping review was conducted to identify eligible studies through a search of four electronic databases, that is, PubMed, PsycINFO, Web of Science and Institute of Electrical and Electronics Engineers.

Findings
The search, which covered the 2010–2020 period, led to the identification of 1,311 articles, 30 of which were included in the review. These articles evaluated six different types of prompting systems: context-aware, automatic computer prompting, context-aware, mediated computer prompting, teleoperated robot prompting, self-operated augmented reality prompting, self-operated computer or tablet prompting and time-based (preset) computer, tablet or smartphone prompting.

Originality/value
Technology-aided prompting to help people with dementia or acquired cognitive impairment perform relevant multistep daily tasks is considered increasingly important. This review provides a picture of the different prompting options available and of their level of readiness for application in daily contexts.