bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Wnt5a-Cdc42 axis controls aging and rejuvenation of hair-follicle stem cells
Authors: Tiwari Rajiv L , Mishra Pratibha , Martin Nicola , George Nikhil Oommen , Sakk Vadim , Soller Karin , Nalapareddy Kodandaramireddy , Nattamai Kalpana , Scharffetter-Kochanek Karin , Florian Maria Carolina , Geiger Hartmut 
Published: October 2020

SummaryNormal hair growth occurs in cycles, comprising growth (anagen), cessation (catagen) and rest (telogen). Upon aging, the initiation of anagen is significantly delayed, which results in impaired hair regeneration. Hair regeneration is driven by hair follicle stem cells (HFSCs). We show here that aged HFSCs present with a decrease in canonical Wnt signaling and a shift towards non-canonical Wnt5a driven signaling which antagonizes canonical Wnt signaling. Elevated expression of Wnt5a in HFSCs upon aging results in elevated activity of the small RhoGTPase Cdc42 as well as a change in the spatial distribution of Cdc42 within HFSCs. Treatment of aged HFSC with a specific pharmacological inhibitor of Cdc42 activity termed CASIN to suppress the aging-associated elevated activity of Cdc42 restored canonical Wnt signaling in aged HFSCs. Treatment of aged mice in vivo with CASIN induced anagen onset and increased the percentage of anagen skin areas. Aging-associated functional deficits of HFSCs are at least in part intrinsic to HFSCs and can be restored by rational pharmacological approaches.
Mesoscale phase separation of chromatin in the nucleus
Authors: Bajpai Gaurav , Amiad-Pavlov Daria , Lorber Dana , Volk Talila , Safran Samuel 
Published: October 2020

AbstractIntact-organism imaging ofDrosophilalarvae reveals and quantifies chromatin-aqueous phase separation. The chromatin can be organized near the lamina layer of the nuclear envelope, conventionally fill the nucleus, be organized centrally, or as a wetting droplet. These transitions are controlled by changes in nuclear volume and the interaction of chromatin with the lamina (part of the nuclear envelope) at the nuclear periphery. Using a simple polymeric model that includes the key features of chromatin self-attraction and its binding to the lamina, we demonstrate theoretically that it is the competition of these two effects that determines the mode of chromatin distribution. The qualitative trends as well as the compositional profiles obtained in our simulations compare well with the observed intact-organism imaging and quantification. Since the simulations contain only a small number of physical variables we can identify the generic mechanisms underlying the changes in the observed phase separations.
Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice
Authors: Gonzalez-Perez Vivian , Martinez-Espinosa Pedro L. , Sala-Rabanal Monica , Bharadwaj Nikhil , Xia Xiao-Ming , Chen Albert C. , Alvarado David , Gustafsson Jenny K. , Hu Hongzhen , Ciorba Matthew A. , Lingle Christopher J. 
Published: October 2020

AbstractGoblet cells (GCs) are specialized cells of the intestinal epithelium contributing critically to mucosal homeostasis. One of the functions of GCs is to produce and secrete MUC2, the mucin that forms the scaffold of the intestinal mucus layer coating the epithelium and separates the luminal pathogens and commensal microbiota from the host tissues. Although a variety of ion channels and transporters are thought to impact on MUC2 secretion, the specific cellular mechanisms that regulate GC function remain incompletely understood. Previously, we demonstrated that leucine-rich-repeat-containing protein 26 (LRRC26), a known regulatory subunit of the Ca2+-and voltage-activated K+channel (BK channel), localizes specifically to secretory cells within the intestinal tract. Here, utilizing a mouse model in which MUC2 is fluorescently tagged allowing visualization of single GCs in intact colonic crypts, we show that murine colonic GCs have functional LRRC26-associated BK channels. In the absence of LRRC26, BK channels are present in GCs, but are not activated at physiological conditions. In contrast, all tested MUC2-negative cells completely lacked BK channels. Moreover, LRRC26-associated BK channels underlie the BK channel contribution to the resting transepithelial current across mouse distal colonic mucosa. Genetic ablation of either LRRC26 or BK-pore forming α-subunit in mice results in a dramatically enhanced susceptibility to colitis induced by dextran sodium sulfate (DSS). These results demonstrate that normal potassium flux through LRRC26-associated BK channels in GCs has protective effects against colitis in mice.SignificanceA primary function of goblet cells (GCs) of the intestinal epithelium is to generate a protective mucus layer lining the intestinal lumen. GC dysfunction is linked to Inflammatory Bowel Disease (IBD). GC mucus secretion is thought to be dependent on contributions of an ensemble of anion and cation fluxes, although understanding remains limited. Here, it is shown in mouse colon that the Ca2+- and voltage-dependent BK-type K+channel, specifically in association with the LRRC26 regulatory subunit, plays a critical role in normal GC function, protecting mice against chemically-induced colitis. The results demonstrate that normal K+fluxes mediated by LRRC26-containing BK channels are required for normal GC function, potentially providing insights into the potential role of BK channels in IBD.
Surfactant-free production of biomimetic artificial cells using PDMS-based microfluidics
Authors: Yandrapalli Naresh , Petit Julien , Bäumchen Oliver , Robinson Tom 
Published: October 2020

AbstractMicrofluidic-based production of cellular mimics (e.g. giant vesicles) presents a paradigm-shift in the development of artificial cells. While encapsulation rates are high and vesicles are mono-disperse compared to swelling-based techniques, current microfluidic emulsion-based methods heavily rely on the addition of additives such as surfactants, glycerol and even ethanol to produce stable vesicles. In this work, we present a microfluidic platform designed for the production of cellular mimics in the form of giant unilamellar vesicles (GUVs). Our PDMS-based device comprises a double cross-junction and a serpentine-shaped shear inducing module to produce surfactant-free and additive-free monodisperse biomimetic GUVs. Vesicles can be made with neutral and charged lipids in physiological buffers and, unlike previous works, it is possible to produce them with pure water both inside and outside. By not employing surfactants such as block co-polymers, additives like glycerol, and long-chain poly-vinyl alcohol that are known to alter the properties of lipid membranes, the vesicles are rendered truly biomimetic. The membrane functionality and stability are validated by lipid diffusion, membrane protein incorporation, and leakage assays. To demonstrate the usability of the GUVs using this method, various macromolecules such as DNA, smaller liposomes, mammalian cells and even microspheres are encapsulated within the GUVs.
Habitat patch size and tree species richness shape the bird community in urban green spaces of rapidly urbanizing region of India
Authors: Kaushik Monica , Tiwari Samakshi , Manisha Kumari 
Published: October 2020

AbstractRapid urbanization and associated biodiversity loss is rampant globally but especially a cause of concern for developing countries. However, numerous studies investigating the role of urban green spaces have established their key role in conserving larger suites of species in urban area. Yet our knowledge is lopsided due to lag in research in developing countries. We examined how landscape and local scale features of urban green spaces influence bird species richness, density, fine-foraging guild richness and composition during breeding and non-breeding season. This is the first study of this nature in one the Himalayan states of India. We quantified landscape level variables in the 250m buffer around 18 urban green spaces. We sampled vegetation and bird community during breeding and non-breeding season through 52 intensive sampling point spread across 18 urban green spaces. Size of the urban green space at landscape level and tree richness at the local scale emerged as important predictor variables influencing bird species richness, density and richness of imperiled insectivorous guild across seasons. Urban green spaces within education institutions and offices experiencing much less management supported higher bird richness and density whereas city parks were the most species poor. Community composition was affected more strongly by built-up cover and barren area in the matrix and also by tree species richness within urban green spaces. City planners should focus on establishing larger city parks during design stage whereas biodiversity potential of the existing urban green spaces could be enhanced by selecting native tree and shrub species to increase overall habitat complexity.
Complete and haplotype-specific sequence assembly of segmental duplication-mediated genome rearrangements using CRISPR-targeted ultra-long read sequencing (CTLR-Seq)
Authors: Zhou Bo , Shin GiWon , Greer Stephanie U. , Vervoort Lisanne , Huang Yiling , Pattni Reenal , Ho Marcus , Wong Wing H. , Vermeesch Joris R. , Ji Hanlee P. , Urban Alexander E. 
Published: October 2020

ABSTRACTWe have developed a generally applicable method based on CRISPR/Cas9-targeted ultra-long read sequencing (CTLR-Seq) to completely and haplotype-specifically resolve, at base-pair resolution, large, complex, and highly repetitive genomic regions that had been previously impenetrable to next-generation sequencing analysis such as large segmental duplication (SegDup) regions and their associated genome rearrangements that stretch hundreds of kilobases. Our method combinesin vitroCas9-mediated cutting of the genome and pulse-field gel electrophoresis to haplotype-specifically isolate intact large (200-550 kb) target regions that encompass previously unresolvable genomic sequences. These target fragments are then sequenced (amplification-free) to produce ultra-long reads at up to 40x on-target coverage using Oxford nanopore technology, allowing for the complete assembly of the complex genomic regions of interest at single base-pair resolution. We applied CTLR-Seq to resolve the exact sequence of SegDup rearrangements that constitute the boundary regions of the 22q11.2 deletion CNV and of the 16p11.2 deletion and duplication CNVs. These CNVs are among the strongest known risk factors for schizophrenia and autism. We then performde novoassembly to resolve, for the first time, at single base-pair resolution, the sequence rearrangements of the 22q11.2 and 16p11.2 CNVs, mapping out exactly the genes and non-coding regions that are affected by the CNV for different carriers.
Imaging α-synuclein pathologies in animal models and patients with Parkinson’s and related diseases
Authors: Endo Hironobu , Ono Maiko , Takado Yuhei , Matsuoka Kiwamu , Takahashi Manami , Tagai Kenji , Kataoka Yuko , Hirata Kosei , Takahata Keisuke , Seki Chie , Kokubo Naomi , Fujinaga Masayuki , Mori Wakana , Nagai Yuji , Mimura Koki , Kumata Katsushi , Kikuchi Tatsuya , Shimozawa Aki , Mishra Sushil K. , Yamaguchi Yoshiki , Shimizu Hiroshi , Kakita Akiyoshi , Takuwa Hiroyuki , Shinotoh Hitoshi , Shimada Hitoshi , Kimura Yasuyuki , Ichise Masanori , Suhara Tetsuya , Minamimoto Takafumi , Sahara Naruhiko , Kawamura Kazunori , Zhang Ming-Rong , Hasegawa Masato , Higuchi Makoto 
Published: October 2020

SUMMARYDeposition of α-synuclein fibrils is implicated in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), whilein vivodetection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects.In vivooptical and positron emission tomography (PET) imaging of mouse and marmoset models demonstrated that C05-05 captured a dynamic propagation of fibrillogenesis along neural pathways followed by disruptions of these structures. High-affinity binding of18F-C05-05 to α-synuclein aggregates in human brain tissues was also proven byin vitroassays. Notably, PET-detectable18F-C05-05 signals were intensified in the midbrains of PD and DLB patients as compared to healthy controls, providing the first demonstration of visualizing α-synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders towards diagnostic and therapeutic research and development.
Transferrin receptor is another receptor for SARS-CoV-2 entry
Authors: Tang Xiaopeng , Yang Mengli , Duan Zilei , Liao Zhiyi , Liu Lei , Cheng Ruomei , Fang Mingqian , Wang Gan , Liu Hongqi , Xu Jingwen , Kamau Peter M , Zhang Zhiye , Yang Lian , Zhao Xudong , Peng Xiaozhong , Lai Ren 
Published: October 2020

AbstractAngiotensin-converting enzyme 2 (ACE2) has been suggested as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry to cause coronavirus disease 2019 (COVID-19). However, no ACE2 inhibitors have shown definite beneficiaries for COVID-19 patients, applying the presence of another receptor for SARS-CoV-2 entry. Here we show that ACE2 knockout dose not completely block virus entry, while TfR directly interacts with virus Spike protein to mediate virus entry and SARS-CoV-2 can infect mice with over-expressed humanized transferrin receptor (TfR) and without humanized ACE2. TfR-virus co-localization is found both on the membranes and in the cytoplasma, suggesting SARS-CoV-2 transporting by TfR, the iron-transporting receptor shuttling between cell membranes and cytoplasma. Interfering TfR-Spike interaction blocks virus entry to exert significant anti-viral effects. Anti-TfR antibody (EC50 ~16.6 nM) shows promising anti-viral effects in mouse model. Collectively, this report indicates that TfR is another receptor for SARS-CoV-2 entry and a promising anti-COVID-19 target.
Patient iPSC-astrocytes show transcriptional and functional dysregulation in schizophrenia
Authors: Koskuvi Marja , Lehtonen Šárka , Trontti Kalevi , Keuters Meike , Wu Ying Chieh , Koivisto Hennariikka , Ludwig Anastasia , Plotnikova Lidiia , Virtanen Pekka L. J. , Räsänen Noora , Kaipainen Satu , Hyötyläinen Ida , Dhungana Hiramani , Giniatullina Raisa , Ojansuu Ilkka , Vaurio Olli , Cannon Tyrone D. , Lönnqvist Jouko , Therman Sebastian , Suvisaari Jaana , Kaprio Jaakko , Lähteenvuo Markku , Tohka Jussi , Giniatullin Rashid , Rivera Claudio , Hovatta Iiris , Tanila Heikki , Tiihonen Jari , Koistinaho Jari 
Published: October 2020

AbstractHuman astrocytes are multifunctional brain cells and may contribute to the pathophysiology of schizophrenia (SCZ). We differentiated astrocytes from induced pluripotent stem cells of monozygotic twins discordant for SCZ, and found sex-specific gene expression and signaling pathway alterations related particularly to inflammation and synaptic functions. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins, and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in demyelination, synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Altogether, our results show that astrocytes contribute to both familial risk and clinical manifestation of SCZ in a sex-specific manner.
An extended reconstruction of human gut microbiota metabolism for personalized nutrition
Authors: Blasco Telmo , Pérez-Burillo Sergio , Balzerani Francesco , Lerma-Aguilera Alberto , Hinojosa-Nogueira Daniel , Pastoriza Silvia , Gosalbes María José , Jiménez-Hernández Nuria , Francino M. Pilar , Rufián-Henares José Ángel , Apaolaza Iñigo , Planes Francisco J. 
Published: October 2020

ABSTRACTUnderstanding how diet and gut microbiota interact in the context of human health is a key question in personalized nutrition. Genome-scale metabolic networks and constraint-based modeling approaches are promising to systematically address this complex question. However, when applied to nutritional questions, a major issue in existing reconstructions is the lack of information about degradation pathways of relevant nutrients in the diet that are metabolized by the gut microbiota. Here, we present AGREDA, an extended reconstruction of the human gut microbiota metabolism for personalized nutrition. AGREDA includes the degradation pathways of 231 nutrients present in the human diet and allows us to more comprehensively simulate the interplay between food and gut microbiota. We show that AGREDA is more accurate than existing reconstructions in predicting output metabolites of the gut microbiota. Finally, using AGREDA, we established relevant metabolic differences among clinical subgroups of Spanish children: lean, obese, allergic to foods and celiac.
Structural classification of proteins based on the computationally efficient recurrence quantification analysis and horizontal visibility graphs
Authors: Areti Zervou Michaela , Doutsi Effrosyni , Pavlidis Pavlos , Tsakalides Panagiotis 
Published: October 2020

AbstractMotivationProtein structure prediction is one of the most significant problems in bioinformatics, as it has a prominent role in understanding the function and evolution of proteins. Designing a computationally efficient but at the same time accurate prediction method remains a pressing issue, especially for sequences that we cannot obtain a sufficient amount of homologous information from existing protein sequence databases. Several studies demonstrate the potential of utilizing chaos game representation (CGR) along with time series analysis tools such as recurrence quantification analysis (RQA), complex networks, horizontal visibility graphs (HVG) and others. However, the majority of existing works involve a large amount of features and they require an exhaustive, time consuming search of the optimal parameters. To address the aforementioned problems, this work adopts the generalized multidimensional recurrence quantification analysis (GmdRQA) as an efficient tool that enables to process concurrently a multidimensional time series and reduce the number of features. In addition, two data-driven algorithms, namely average mutual information (AMI) and false nearest neighbors (FNN), are utilized to define in a fast yet precise manner the optimal GmdRQA parameters.ResultsThe classification accuracy is improved by the combination of GmdRQA with the HVG. Experimental evaluation on a real benchmark dataset demonstrates that our methods achieve similar performance with the state-of-the-art but with a smaller computational cost.AvailabilityThe code to reproduce all the results is available athttps://github.com/aretiz/protein_structure_classification/tree/main.Contactedoutsi@ics.forth.grSupplementary informationSupplementary data are available atBioinformaticsonline.
Motor variability prior to learning is a poor predictor of the ability to adopt new movement solutions
Authors: Ranganathan Rajiv , Lin Marco , Carey Samuel , Lokesh Rakshith , Lee Mei-Hua , Krishnan Chandramouli 
Published: October 2020

AbstractMany contexts in motor learning require a learner to change from an existing movement solution to a novel movement solution to perform the same task. Recent evidence has pointed to motor variability prior to learning as a potential marker for predicting individual differences in motor learning. However, it is not known if this variability is predictive of the ability to adopt a new movement solution for the same task. Here, we examined this question in the context of a redundant precision task requiring control of motor variability. Fifty young adults learned a precision task that involved throwing a virtual puck toward a target using both hands. Because the speed of the puck depended on the sum of speeds of both hands, this task could be achieved using multiple solutions. Participants initially performed a baseline task where there was no constraint on the movement solution, and then performed a novel task where they were constrained to adopt a specific movement solution requiring asymmetric left and right hand speeds. Results showed that participants were able to learn the new solution, and this change was associated with changes in both the amount and structure of variability. However, individual differences in baseline motor variability were only weakly correlated with initial and final task performance when using the new solution, with greater variability being associated with higher errors. We also found a strong specificity component – initial variability when using the new solution was highly correlated with final task performance with the new solution, but once again, higher variability was associated with greater errors. These results suggest that motor variability is not necessarily indicative of flexibility and highlight the need to consider the task context in determining the relation between motor variability and learning.
Protein hyperacylation links mitochondrial dysfunction with nuclear organization
Authors: Smestad John , McCauley Micah , Amato Matthew , Xiong Yuning , Liu Juan , Sin Yi-Cheng , Ellingson Jake , Chen Yue , Al Khazal Fatimah , Wilbanks Brandon , Lee Jeong-Heon , Ordog Tamas , Rouzina Ioulia , Williams Mark , Locasale Jason W. , Maher L. James 
Published: October 2020

SummaryCellular metabolism is linked to epigenetics, but the biophysical effects of metabolism on chromatin structure and implications for gene regulation remain largely unknown. Here, using a broken tricarboxylic acid (TCA) cycle and disrupted electron transport chain (ETC) exemplified by succinate dehydrogenase subunit C (SDHC) deficiency, we investigated the effects of metabolism on chromatin architecture over multiple distance scales [nucleosomes (∼102bp), topologically-associated domains (TADs; ∼105– 106bp), and chromatin compartments (106– 108bp)]. Metabolically-driven hyperacylation of histones led to weakened nucleosome positioning in multiple types of chromatin, and we further demonstrate that lysine acylation directly destabilizes histone octamer-DNA interactions. Hyperacylation of cohesin subunits correlated with decreased mobility on interphase chromatin and increased TAD boundary strength, suggesting that cohesin is metabolically regulated. Erosion of chromatin compartment distinctions reveals metabolic regulation of chromatin liquid-liquid phase separation. The TCA cycle and ETC thus modulate chromatin structure over multiple distance scales.