bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved modeling of human AD with an automated culturing platform for iPSC neurons, astrocytes and microglia
Authors: Bassil Reina , Shields Kenneth , Granger Kevin , Zein Ivan , Ng Shirley , Chih Ben 
Published: September 2021

AbstractAdvancement in human induced pluripotent stem cell (iPSC) neuron and microglial differentiation protocols allow for disease modeling using physiologically relevant cells. However, iPSC differentiation and culturing protocols have posed challenges to maintaining consistency. Here, we generated an automated, consistent, and long-term culturing platform of human iPSC neurons, astrocytes, and microglia. Using this platform we generated a iPSC AD model using human derived cells, which showed signs of Aβ plaques, dystrophic neurites around plaques, synapse loss, dendrite retraction, axon fragmentation, phospho-Tau induction, and neuronal cell death in one model. We showed that the human iPSC microglia internalized and compacted Aβ to generate and surround the plaques, thereby conferring some neuroprotection. We investigated the mechanism of action of anti-Aβ antibodies protection and found that they protected neurons from these pathologies and were most effective before pTau induction. Taken together, these results suggest that this model can facilitate target discovery and drug development efforts.
Epistatic Net allows the sparse spectral regularization of deep neural networks for inferring fitness functions
Authors: Aghazadeh Amirali , Nisonoff Hunter , Ocal Orhan , Brookes David H. , Huang Yijie , Koyluoglu O. Ozan , Listgarten Jennifer , Ramchandran Kannan 
Published: September 2021

AbstractDespite recent advances in high-throughput combinatorial mutagenesis assays, the number of labeled sequences available to predict molecular functions has remained small for the vastness of the sequence space combined with the ruggedness of many fitness functions. While deep neural networks (DNNs) can capture high-order epistatic interactions among the mutational sites, they tend to overfit to the small number of labeled sequences available for training. Here, we developed Epistatic Net (EN), a method for spectral regularization of DNNs that exploits evidence that epistatic interactions in many fitness functions are sparse. We built a scalable extension of EN, usable for larger sequences, which enables spectral regularization using fast sparse recovery algorithms informed by coding theory. Results on several biological landscapes show that EN consistently improves the prediction accuracy of DNNs and enables them to outperform competing models which assume other priors. EN estimates the higher-order epistatic interactions of DNNs trained on massive sequence spaces-a computational problem that otherwise takes years to solve.
A CDK-regulated chromatin segregase promoting chromosome replication
Authors: Chacin Erika , Bansal Priyanka , Reusswig Karl-Uwe , Diaz-Santin Luis M. , Ortega Pedro , Vizjak Petra , Gómez-González Belen , Müller-Planitz Felix , Aguilera Andrés , Pfander Boris , Cheung Alan C. M. , Kurat Christoph F. 
Published: September 2021

AbstractThe replication of chromosomes during S phase is critical for cellular and organismal function. Replicative stress can result in genome instability, which is a major driver of cancer. Yet how chromatin is made accessible during eukaryotic DNA synthesis is poorly understood. Here, we report the characterization of a chromatin remodeling enzyme—Yta7—entirely distinct from classical SNF2-ATPase family remodelers. Yta7 is a AAA+ -ATPase that assembles into ~1 MDa hexameric complexes capable of segregating histones from DNA. The Yta7 chromatin segregase promotes chromosome replication both in vivo and in vitro. Biochemical reconstitution experiments using purified proteins revealed that the enzymatic activity of Yta7 is regulated by S phase-forms of Cyclin-Dependent Kinase (S-CDK). S-CDK phosphorylation stimulates ATP hydrolysis by Yta7, promoting nucleosome disassembly and chromatin replication. Our results present a mechanism for how cells orchestrate chromatin dynamics in co-ordination with the cell cycle machinery to promote genome duplication during S phase.
Olfactory bulb astrocytes mediate sensory circuit processing through Sox9 in the mouse brain
Authors: Ung Kevin , Huang Teng-Wei , Lozzi Brittney , Woo Junsung , Hanson Elizabeth , Pekarek Brandon , Tepe Burak , Sardar Debosmita , Cheng Yi-Ting , Liu Gary , Deneen Benjamin , Arenkiel Benjamin R. 
Published: September 2021

AbstractThe role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. Less is known about astrocytes contributions towards circuits and behavior in the adult brain. Astrocytes play important roles in synaptic development and modulation, however their contributions towards neuronal sensory function and maintenance of neuronal circuit architecture remain unclear. Here, we show that loss of the transcription factor Sox9 results in both anatomical and functional changes in adult mouse olfactory bulb (OB) astrocytes, affecting sensory processing. Indeed, astrocyte-specific deletion of Sox9 in the OB results in decreased odor detection thresholds and discrimination and it is associated with aberrant neuronal sensory response maps. At functional level, loss of astrocytic Sox9 impairs the electrophysiological properties of mitral and tufted neurons. RNA-sequencing analysis reveals widespread changes in the gene expression profiles of OB astrocytes. In particular, we observe reduced GLT-1 expression and consequential alterations in glutamate transport. Our findings reveal that astrocytes are required for physiological sensory processing and we identify astrocytic Sox9 as an essential transcriptional regulator of mature astrocyte function in the mouse OB.
Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation
Authors: Lioy Virginia S. , Lorenzi Jean-Noël , Najah Soumaya , Poinsignon Thibault , Leh Hervé , Saulnier Corinne , Aigle Bertrand , Lautru Sylvie , Thibessard Annabelle , Lespinet Olivier , Leblond Pierre , Jaszczyszyn Yan , Gorrichon Kevin , Varoquaux Nelle , Junier Ivan , Boccard Frédéric , Pernodet Jean-Luc , Bury-Moné Stéphanie 
Published: September 2021

AbstractBacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics. The linear chromosome includes a central region harboring core genes, as well as extremities enriched in specialized metabolite biosynthetic gene clusters. Here, we show that chromosome structure in Streptomyces ambofaciens correlates with genetic compartmentalization during exponential phase. Conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends tend to be transcriptionally quiescent compartments with different structural features. The onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture, from a rather ‘open’ to a ‘closed’ conformation, in which highly expressed specialized metabolite biosynthetic genes form new boundaries. Thus, our results indicate that the linear chromosome of S. ambofaciens is partitioned into structurally distinct entities, suggesting a link between chromosome folding, gene expression and genome evolution.
Aurora kinase A inhibition reverses the Warburg effect and elicits unique metabolic vulnerabilities in glioblastoma
Authors: Nguyen Trang T. T. , Shang Enyuan , Shu Chang , Kim Sungsoo , Mela Angeliki , Humala Nelson , Mahajan Aayushi , Yang Hee Won , Akman Hasan Orhan , Quinzii Catarina M. , Zhang Guoan , Westhoff Mike-Andrew , Karpel-Massler Georg , Bruce Jeffrey N. , Canoll Peter , Siegelin Markus D. 
Published: September 2021

AbstractAurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling. While glycolysis is suppressed by AURKA inhibition, we note an increase in the oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO), which was accompanied by an increase of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α). Combining AURKA inhibitors with inhibitors of FAO extends overall survival in orthotopic GBM PDX models. Taken together, these data suggest that simultaneous targeting of oxidative metabolism and AURKAi might be a potential novel therapy against recalcitrant malignancies.
The basis of easy controllability in Boolean networks
Authors: Borriello Enrico , Daniels Bryan C. 
Published: September 2021

AbstractEffective control of biological systems can often be achieved through the control of a surprisingly small number of distinct variables. We bring clarity to such results using the formalism of Boolean dynamical networks, analyzing the effectiveness of external control in selecting a desired final state when that state is among the original attractors of the dynamics. Analyzing 49 existing biological network models, we find strong numerical evidence that the average number of nodes that must be forced scales logarithmically with the number of original attractors. This suggests that biological networks may be typically easy to control even when the number of interacting components is large. We provide a theoretical explanation of the scaling by separating controlling nodes into three types: those that act as inputs, those that distinguish among attractors, and any remaining nodes. We further identify characteristics of dynamics that can invalidate this scaling, and speculate about how this relates more broadly to non-biological systems.
Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice
Authors: Kim Kwang-eun , Park Isaac , Kim Jeesoo , Kang Myeong-Gyun , Choi Won Gun , Shin Hyemi , Kim Jong-Seo , Rhee Hyun-Woo , Suh Jae Myoung 
Published: September 2021

AbstractSecretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describeiSLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validateiSLET in a whole-body system, we expressiSLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liveriSLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together,iSLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets.
Correlation of bone density to screw loosening in dynamic stabilization: an analysis of 176 patients
Authors: Chang Hsuan-Kan , Ku Jason , Ku Johnson , Kuo Yi-Hsuan , Chang Chih-Chang , Wu Ching-Lan , Lirng Jiing-Feng , Wu Jau-Ching , Huang Wen-Cheng , Cheng Henrich , Hsu Shih-Ming 
Published: September 2021

AbstractAlthough osteoporosis has negative impacts on lumbar fusion, its effects on screw loosening in dynamic stabilization remain elusive. We aimed to correlate bone mineral density (BMD) with screw loosening in Dynesys dynamic stabilization (DDS). Consecutive patients who underwent 2- or 3-level DDS for spondylosis, recurrent disc herniations, or low-grade spondylolisthesis at L3-5 were retrospectively reviewed. BMD was assessed by the Hounsfield Unit (HU) in vertebral bodies (VB) and pedicles with and without cortical bone (CB) on pre-operative computed tomography (CT). Screw loosening was assessed by radiographs and confirmed by CT. HU values were compared between the loosened and intact screws. 176 patients and 918 screws were analyzed with 78 loosened screws found in 36 patients (mean follow-up: 43.4 months). The HU values of VB were similar in loosened and intact screws (p = 0.14). The HU values of pedicles were insignificantly less in loosened than intact screws (including CB: 286.70 ± 118.97 vs. 297.31 ± 110.99, p = 0.45; excluding CB: 238.48 ± 114.90 vs. 240.51 ± 108.91, p = 0.88). All patients had clinical improvements. In conclusion, the HU values, as a surrogate for BMD, were unrelated to screw loosening in DDS. Therefore, patients with compromised BMD might be potential candidates for dynamic stabilization rather than fusion.
Impact of shredding degree on papermaking potential of recycled waste
Authors: Lipkiewicz Aneta , Małachowska Edyta , Dubowik Marcin , Przybysz Piotr 
Published: September 2021

AbstractThe properties of paper products depend on the structure of the cellulose fibres therein. Although fibre properties in virgin pulps can be modified by a refining process, this is more difficult in pulp from recovered fibre, particularly waste from office shredders that tend to shorten fibres during shredding. The shorter fibres in shredded paper make it difficult to easily reconstitute them into high-quality paper products. Moreover, because of high energy usage during the recycling process and transportation inefficiencies, there is a need to determine how to responsibly shred paper to alleviate this environmental burden. With this in mind, the influence of initial fibre length on the tensile properties of paper was investigated. Changes in initial fibre length significantly influenced many pulp and paper properties. It was found that cutting the paper into pieces with an area less than 25 mm2caused significant changes in the important morphological parameters of the fibres and a sharp decrease in the tensile properties of the reconstituted paper.
20 Years nitrogen dynamics study by using APSIM nitrogen model simulation for sustainable management in Jilin China
Authors: Tahir Nazia , Li Jumei , Ma Yibing , Ullah Aman , Zhu Ping , Peng Chang , Hussain Babar , Danish Subhan 
Published: September 2021

AbstractThe tremendous increase in industrial development and urbanization has become a severe threat to the Chinese climate and food security. The Agricultural Production System Simulator model was used to simulate soil nitrogen in black soil in Yangling Jilin Province for 20 years. The observed values are consistent with the simulated values. The predicted values of total soil NO3−–N and NH4+–N nitrogen are 10 kg ha−1 and 5 kg ha−1 higher than the observed values. The total soil NO3−–N loss has the same trend as the rainfall, and it increases with the number of rainfall days over the years. The average 20 years losses of NO3−–N and NH4+–N observed were 1375.91 kg ha−1, and 9.24 kg ha−1, while in the simulation increase was 1387.01 kg ha−1 and 9.28 kg ha−1, respectively. The difference between the observed and simulated values of NO3−–N and NH4+–N of mean loss was 11.15 kg ha−1 and 0.04 kg ha−1 respectively. Moreover, our findings highlight the opportunity further to improve management policies (especially for nitrogen) to maintain crop yield.
Predictive value of m5C regulatory gene expression in pancreatic adenocarcinoma
Authors: Yu Xiao , Zhang Qiyao , Gao Fang , Zhang Menggang , Zheng Qingyuan , He Yuting , Guo Wenzhi 
Published: September 2021

AbstractPancreatic adenocarcinoma (PAAD) is the most malignant digestive tumor. The global incidence of pancreatic cancer has been rapidly trending upwards, necessitating an exploration of potential prognostic biomarkers and mechanisms of disease development. One of the most prevalent RNA modifications is 5-methylcytosine (m5C); however, its contribution to PAAD remains unclear. Data from The Cancer Genome Atlas (TCGA) database, including genes, copy number variations (CNVs), and simple nucleotide variations (SNVs), were obtained in the present study to identify gene signatures and prognostic values for m5C regulators in PAAD. Regulatory gene m5C changes were significantly correlated with TP53, BRCA1, CDKN2A, and ATM genes, which play important roles in PAAD pathogenesis. In particular, there was a significant relationship between m5C regulatory gene CNVs, especially in genes encoding epigenetic “writers”. According to m5C-regulated gene expression in clinically graded cases, one m5C-regulated genes, DNMT3A, showed both a strong effect on CNVs and a significant correlation between expression level and clinical grade (P < 0.05). Furthermore, low DNMT3A expression was not only associated with poor PAAD patient prognosis but also with the ribosomal processing. The relationship between low DNMT3A expression and poor prognosis was confirmed in an International Cancer Genome Consortium (ICGC) validation dataset.
Transcriptome analysis reveals key genes associated with root-lesion nematode Pratylenchus thornei resistance in chickpea
Authors: Channale Sonal , Kalavikatte Danamma , Thompson John P. , Kudapa Himabindu , Bajaj Prasad , Varshney Rajeev K. , Zwart Rebecca S. , Thudi Mahendar 
Published: September 2021

AbstractThe root-lesion nematode, Pratylenchus thornei, is one of the major plant-parasitic nematode species causing significant yield losses in chickpea (Cicer arietinum). In order to identify the underlying mechanisms of resistance to P. thornei, the transcriptomes of control and inoculated roots of three chickpea genotypes viz. D05253 > F3TMWR2AB001 (resistant advanced breeding line), PBA HatTrick (moderately resistant cultivar), and Kyabra (susceptible cultivar) were studied at 20 and 50 days post inoculation using the RNA-seq approach. On analyzing the 633.3 million reads generated, 962 differentially expressed genes (DEGs) were identified. Comparative analysis revealed that the majority of DEGs upregulated in the resistant genotype were downregulated in the moderately resistant and susceptible genotypes. Transcription factor families WRKY and bZIP were uniquely expressed in the resistant genotype. The genes Cysteine-rich receptor-like protein kinase 10, Protein lifeguard-like, Protein detoxification, Bidirectional sugar transporter Sugars Will Eventually be Exported Transporters1 (SWEET1), and Subtilisin-like protease were found to play cross-functional roles in the resistant chickpea genotype against P. thornei. The identified candidate genes for resistance to P. thornei in chickpea can be explored further to develop markers and accelerate the introgression of P. thornei resistance into elite chickpea cultivars.
Long-term data reveal unimodal responses of ground beetle abundance to precipitation and land use but no changes in taxonomic and functional diversity
Authors: Zajicek Petr , Welti Ellen A. R. , Baker Nathan J. , Januschke Kathrin , Brauner Oliver , Haase Peter 
Published: September 2021

AbstractWhile much of global biodiversity is undoubtedly under threat, the responses of ecological communities to changing climate, land use intensification, and long-term changes in both taxonomic and functional diversity over time, has still not been fully explored for many taxonomic groups, especially invertebrates. We compiled time series of ground beetles covering the past two decades from 40 sites located in five regions across Germany. We calculated site-based trends for 21 community metrics representing taxonomic and functional diversity of ground beetles, activity density (a proxy for abundance), and activity densities of functional groups. We assessed both overall and regional temporal trends and the influence of the global change drivers of temperature, precipitation, and land use on ground beetle communities. While we did not detect overall temporal changes in ground beetle taxonomic and functional diversity, taxonomic turnover changed within two regions, illustrating that community change at the local scale does not always correspond to patterns at broader spatial scales. Additionally, ground beetle activity density had a unimodal response to both annual precipitation and land use. Limited temporal change in ground beetle communities may indicate a shifting baseline, where community degradation was reached prior to the start of our observation in 1999. In addition, nonlinear responses of animal communities to environmental change present a challenge when quantifying temporal trends.
Lower extremity energy absorption strategies at different phases during single and double-leg landings with knee valgus in pubertal female athletes
Authors: Dadfar Mahdis , Soltani M. , Novinzad Mohammadreza Basohbat , Raahemifar Kaamran 
Published: September 2021

AbstractDynamic knee valgus (DKV) malalignment affects the biomechanical characteristic during sports activities. This cross-sectional study was conducted to evaluate mechanical energy absorption (MEA) strategies at initial contact (IC) and total landing (TL) phases during single-leg landing (SLL), and double-leg landing (DLL). Twenty-eight female athletes with DKV (age 10–14) were invited. MEA analysis of lower extremity joints was done in sagittal and frontal motion planes employing 8 Vicon motion capture cameras and 2 Kistler force plates. Statistical analysis was done using IBM Statistics (version24) by Bivariate Pearson Correlation Coefficient test. Knee extensors MEA during SLL (IC: P = 0.008, R = 0.522/TL: P < 0.001, R = 0.642) and DLL (IC: P < 0.001, R = 0.611/TL: P = 0.011, R = 0.525), and knee abductors during SLL (IC: P = 0.021, R = 0.474) were positively correlated with increased DKV angle. Ankle plantar flexors during SLL (TL: P = 0.017, R = − 0.477) and DLL (TL: P = 0.028, R = − 0.404), and hip extensors during SLL (TL: P = 0.006, R = − 0.5120) were negatively correlated with increased DKV angle. Compensated MEA in knee extensors was correlated with less ankle plantar flexion MEA during SLL (IC: P = 0.027, R = − 0.514/TL: P = 0.007, R = − 0.637) and DLL (IC: P = 0.033, R = − 00.412/TL: P = 0.025, R = − 0.485). These outcomes indicated a knee-reliant MEA strategy in female athletes with DKV during puberty, putting them at higher risks of ACL injuries during landing.