bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering of an electrically charged hydrogel implanted into a traumatic brain injury model for stepwise neuronal tissue reconstruction
Authors: Tanikawa Satoshi , Ebisu Yuki , Sedlačík Tomáš , Semba Shingo , Nonoyama Takayuki , Hirota Akira , Takahashi Taiga , Yamaguchi Kazushi , Imajo Masamichi , Kato Hinako , Nishimura Takuya , Tanei Zen-ichi , Tsuda Masumi , Nemoto Tomomi , Gong Jian Ping , Tanaka Shinya 
Published: February 2022

AbstractNeural regeneration is extremely difficult to achieve. In traumatic brain injuries, the loss of brain parenchyma volume hinders neural regeneration. In this study, neuronal tissue engineering was performed by using electrically charged hydrogels composed of cationic and anionic monomers in a 1:1 ratio (C1A1 hydrogel), which served as an effective scaffold for the attachment of neural stem cells (NSCs). In the 3D environment of porous C1A1 hydrogels engineered by the cryogelation technique, NSCs differentiated into neuroglial cells. The C1A1 porous hydrogel was implanted into brain defects in a mouse traumatic damage model. The VEGF-immersed C1A1 porous hydrogel promoted host-derived vascular network formation together with the infiltration of macrophages/microglia and astrocytes into the gel. Furthermore, the stepwise transplantation of GFP-labeled NSCs supported differentiation to glial and neuronal cells. Therefore, this two-step method for neural regeneration may become a new approach for therapeutic brain tissue reconstruction after brain damage in the future.One Sentence SummaryBrain tissue reconstruction using charged hydrogel and stepwise NCS injection
AAV2/9-mediated gene transfer into murine lacrimal gland leads to a long-term targeted tear film modification
Authors: Gautier Benoit , Meneux Lena , Feret Nadège , Audrain Christine , Hudecek Laetitia , Kuony Alison , Bourdon Audrey , Guiner Caroline Le , Blouin Véronique , Delettre Cécile , Michon Frédéric 
Published: February 2022

AbstractCorneal blindness is the fourth leading cause of blindness worldwide. Since the corneal epithelium is constantly renewed, non-integrative gene transfer cannot be used to treat corneal diseases. In numerous of these diseases, the tear film has been reported to be defective. Tears are a complex biological fluid secreted by the lacrimal apparatus. Their composition is modulated according to the context. For instance, after a corneal wound, the lacrimal gland secretes reflex tears, which contain specific growth factors supporting the wound healing process. In specific pathological contexts, such as dry eye diseases, the tear composition can support neither corneal homeostasis, nor wound healing. Here, we propose to use the lacrimal gland as bioreactor to produce and secrete specific factors to support corneal physiology. In this study, we used an AAV2/9-mediated gene transfer to supplement the tear film. First, we demonstrate that a single injection of AAV2/9 is sufficient to transduce all epithelial cell types of the lacrimal gland efficiently and widely. Then, we show that lacrimal gland physiology and corneal integrity are maintained after the injection of an AAV2/9-mediated nerve growth factor expression in the lacrimal gland. Remarkably, this injection induces an important and long-lasting secretion of this growth factor in the tear film. Altogether, our findings provide a new clinically applicable approach to tackle corneal blindness.
Salt Induced Transitions in the Conformational Ensembles of Intrinsically Disordered Proteins
Authors: Maity Hiranmay , Baidya Lipika , Reddy Govardhan 
Published: February 2022

AbstractSalts modulate the behavior of intrinsically disordered proteins (IDPs). In low ionic strength solutions, IDP conformations are primarily perturbed by the screening of electrostatic interactions, independent of the identity of the salt. In this regime, insight into the IDP behavior can be obtained using the theory for salt-induced transitions in charged polymers. However, in high ionic strength solutions, salt-specific interactions with the charged and uncharged residues, known as the Hofmeister effect, influence IDP behavior. There is a lack of reliable theoretical models in high salt concentration regimes to predict the salt effect on IDPs. Using a coarse-grained simulation model for the IDPs and experimentally measured water to salt solution transfer free-energies of various chemical groups, we studied the salt-specific transitions induced in the IDPs conformational ensemble. We probed the effect of three different salts, ranging from protective osmolyte to denaturant, on five IDPs belonging to various polymer classes classified based on charge content. The transitions observed in the IDP conformational ensembles are dependent on the salt used and the IDP polymer class. An important implication of these results is that a suitable salt can be identified to induce condensation of an IDP through liquid–liquid phase separation.
Benchmarking methods for detecting differential states between conditions from multi-subject single-cell RNA-seq data
Authors: Junttila Sini , Smolander Johannes , Elo Laura L 
Published: February 2022

AbstractSingle-cell RNA-sequencing (scRNA-seq) enables researchers to quantify transcriptomes of thousands of cells simultaneously and study transcriptomic changes between cells. scRNA-seq datasets increasingly include multi-subject, multi-condition experiments to investigate cell-type-specific differential states (DS) between conditions. This can be performed by first identifying the cell types in all the subjects and then by performing a DS analysis between the conditions within each cell type. Naïve single-cell DS analysis methods that treat cells statistically independent are subject to false positives in the presence of variation between biological replicates, an issue known as the pseudo-replicate bias. While several methods have already been introduced to carry out the statistical testing in multi-subject scRNA-seq analysis, comparisons that include all these methods are currently lacking. Here, we performed a comprehensive comparison of 18 methods for the identification of DS changes between conditions from multi-subject scRNA-seq data. Our results suggest that the pseudo-bulk methods performed generally best. Both pseudo-bulks and mixed models that model the subjects as a random effect were superior compared with the naive single-cell methods that do not model the subjects in any way. While the naive models achieved higher sensitivity than the pseudo-bulk methods and the mixed models, they were subject to a high number of false positives. In addition, accounting for subjects through latent variable modeling did not improve the performance of the naive methods.
Inhibition of Glycogen Metabolism Induces Reactive Oxygen Species-Dependent Apoptosis in Anaplastic Thyroid Cancer
Authors: Davidson Cole D. , Tomczak Jennifer A. , Amiel Eyal , Carr Frances E. 
Published: February 2022

AbstractAnaplastic thyroid cancer (ATC) is one of the most lethal solid tumors, yet there are no effective, long-lasting treatments for ATC patients. Most tumors, including tumors of the endocrine system, exhibit an increased consumption of glucose to fuel cancer progression, and some cancers meet this high glucose requirement by metabolizing glycogen. Our goal was to determine if ATC cells metabolize glycogen and if this could be exploited for treatment. We detected glycogen synthase and glycogen phosphorylase (PYG) isoforms in normal thyroid and thyroid cancer cell lines and patient-derived biopsy samples. Inhibition of PYG using CP-91,149 induced apoptosis in ATC cells but not normal thyroid cells. CP-91,149 decreased NADPH levels and induced reactive oxygen species accumulation. CP-91,149 severely blunted ATC tumor growth in vivo. Our work establishes glycogen metabolism as a novel metabolic process in thyroid cells that presents a unique, oncogenic target that could offer an improved clinical outcome.SignificanceGlycogen metabolism plays an important role in combating reactive oxygen species and apoptosis in anaplastic thyroid cancer. Glycogen phosphorylase was inhibited with small molecule inhibitors that limited cell proliferation in vitro and blunted tumor growth in a nude mouse xenograft. This study demonstrates that glycogen metabolism is a viable target in one of the most lethal solid tumors.
Hypoxia modulates cellular endocytic pathways and organelles with enhanced cell migration and 3D cell invasion
Authors: Naveena A Hema , Bhatia Dhiraj 
Published: February 2022

AbstractHypoxia, a decrease in cellular or tissue level oxygen content, is characteristic of most tumours and shown to drive cancer progression by altering multiple subcellular processes. We hypothesized that the cancer cells in a hypoxic environment might have slower proliferation rates and increased invasion and migration rate with altered endocytosis when compared to the cancer cells in the periphery of the tumour mass that experiences normoxic condition. Using chemically induced hypoxia, a short hypoxic exposure increased the uptake of clathrin independent endocytic marker Galectin-3, but a prolonged hypoxic exposure decreased clathrin-independent endocytic uptake, while clathrin mediated endocytosis remained unaffected. Subcellular organelles such as mitochondria showed enhanced intensity to withstand the hypoxic stress, while other organelles such as ER were significantly decreased. The proliferation rates decreased, and the migration and invasion rate increased in cancer cells in hypoxic condition compared to normoxic cancer cells.These data suggest that hypoxia modulates cellular endocytic pathways with decreased proliferation and enhanced cell migration and invasion.Abstract Figure
Transglutaminase 2 associated with PI3K and PTEN in a putative membrane-bound signalosome platform blunts cell death
Authors: Jambrovics Károly , Botó Pál , Pap Attila , Sarang Zsolt , Kolostyák Zsuzsanna , Czimmerer Zsolt , Szatmari Istvan , Fésüs László , Uray Iván P. , Balajthy Zoltán 
Published: February 2022

ABSTRACTAtypically expressed transglutaminase 2 (TG2) has been identified as a poor prognostic factor in a variety of cancers. In this study, we evaluated the contribution of TG2 to the prolonged cell survival of differentiated acute promyelocytic leukaemia (APL) cells in response to the standard treatment with combined retinoic acid (ATRA) and arsenic trioxide (ATO). We report that one advantage of ATRA + ATO treatment compared to ATRA alone diminishes the amount of activated and non-activated CD11b/CD18 and CD11c/CD18 cell surface integrin receptors. These changes suppress ATRA-induced TG2 docking on the cytosolic part of CD18 β2-integrin subunits and reduce cell survival. In addition, TG2 overexpresses and hyperactivates the phosphatidylinositol-3-kinase (PI3K), phospho-AKT S473, and phospho-mTOR S2481 signalling axis. mTORC2 acts as a functional switch between cell survival and death by promoting the full activation of AKT. We show that TG2 presumably triggers the formation of a signalosome platform, hyperactivates downstream mTORC2-AKT signalling, which in turn phosphorylates and inhibits the activity of FOXO3, a key pro-apoptotic transcription factor. In contrast, the absence of TG2 restores basic phospho-mTOR S2481, phospho-AKT S473, PI3K, and PTEN expression and activity, thereby sensitising APL cells to ATO-induced cell death. We conclude, that atypically expressed TG2 may serve as a hub, facilitating signal transduction via signalosome formation by the CD18 subunit with both PI3K hyperactivation and PTEN inactivation through the PI3K PTEN cycle in ATRA-treated APL cells.
Detecting clonemates in multicellular clonal species based on “Shared Heterozygosity (SH)” and technical replicates
Authors: Yu Lei , Stachowicz John J. , DuBois Katie , Reusch Thorsten B. H. 
Published: February 2022

AbstractClonal reproduction, the formation of new individuals that are genetically nearly identical to the parent via mitosis in the absence of genetic recombination, is a very common reproductive mode across plants, fungi, and animals. Current genetic marker based methods fail to detect clonal structure when all collected samples belong to one single clone, which seems to be more common than previously thought. Here we propose a new similarity index, “Shared Heterozygosity (SH)” based on the number of genetic markers (typically SNPs, single-nucleotide polymorphisms) that are identically heterozygous among two or more genomes (i.e., NSH). Ideally NSH should be on the order of approximately >=3,000, which can be easily achieved nowadays via Restriction-site Associated DNA (RAD) sequencing or whole-genome resequencing. One should be careful when NSH is small (roughly <1,000). We analyze two large seagrass clones (Posidonia australis, Zostera marina) along with two Z. marina clones of known age (17-yrs), and show that SH can potentially extend the detection of clonemates to any pair of samples with the aid of technical replicates. Another potential application of SH is to detect possible parent-descendant pairs under selfing, because the heterozygous loci in the selfing-produced descendants represent a subset of those in the parent. Our proposed workflow takes advantage of the availability of the larger number of genetic markers in the genomic era, and fills a gap in detecting clonemates in the growing number of cases where many or all samples at a location belong to one single clone.
First record of anti-predator behavior in the gall-forming aphidMordwilkoja vagabunda
Authors: Legan Andrew Wesley 
Published: February 2022

AbstractThe gall-forming aphidMordwilkoja vagabundahas been an outgroup in molecular studies of the evolution of social behavior in thePemphigusgenus, butMordwilkojaaphids have not previously been assayed for social behavior, such as altruistic defense. This study reports experiments carried out in July in Ithaca, NY, USA, in which nymphs (immature aphids) ofM. vagabundawere video recorded under a stereo microscope while they encountered pyralid moth larvae in a plastic arena.M. vagabundanymphs of all instars used their legs to claw moth larvae while pressing their rostrums against the larvae, possibly to pierce the cuticle. Many of the attacking aphids were alatoid nymphs, rather than the specialized first instar soldiers typically observed inPemphigusspecies.M. vagabundanymphs moved in bursts that sometimes became synchronized among several aphids in the same vicinity. These synchronized, rhythmic movements may be anti-predator defense strategies comparable to the collective twitching and kicking response observed in colonies ofAphis neriiand other aphid species. Defensive behaviors byM. vagabundanymphs may be altruistic fortress defense strategies which maximize inclusive fitness of the clone.Open Research statementVideo data are shared publicly on a repository, Zenodo, at this DOI:https://doi.org/10.5281/zenodo.5636845
The infiltration pattern of microenvironmental cells and different immune escape mechanisms in colorectal cancer
Authors: Mao Yihao , Feng Qingyang , Chang Wenju , Lv Yang , Xu Yuqiu , Chang Jiang , Zheng Peng , Yu Shanchao , Zhang Zhiyuan , Li Zhiqiang , Lin Qi , Tang Wentao , Zhu Dexiang , Ji Meiling , Ren Li , Wei Ye , He Guodong , Xu Jianmin 
Published: February 2022

AbstractBackgroundThe tumour microenvironment (TME) plays a crucial role in tumour progression and metastasis. However, the infiltration pattern of TME cells in CRC samples and the immune escape mechanism underneath have not been studied sufficiently.MethodsTranscriptomic data from public datasets were retrieved online. In total, 1802 samples from the microarray dataset and 619 samples from the TCGA dataset were enrolled. The ssGSEA algorithm and unsupervised clustering were used for TME cells infiltration speculation and infiltration pattern recognition.ResultsCRC samples can be classified into three distinct TME cell subtypes. Subtype 1, the immune-active subtype, was characterised by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumour purity and low infiltration of immune and stromal cells. And subtype 3, stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. Three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and the defective antigen presentation. And the stroma-rich subtype lacked activated immune cells.ConclusionsDistinct TME cell subtypes and immune escape mechanisms may provide inspiration and direction for further researches on CRC immunotherapy.
pycoMeth: A toolbox for differential methylation testing from Nanopore methylation calls
Authors: Snajder Rene , Leger Adrien , Stegle Oliver , Bonder Marc Jan 
Published: February 2022

AbstractAdvances in base and methylation calling of Oxford Nanopore Technologies (ONT) sequencing data have opened up the possibility for joint profiling of genomic and epigenetic variation on the same long reads. Existing data storage and analysis frameworks that were developed for CpG-methylation arrays or short-read bisulfite sequencing data have severe shortcomings for handling of ONT data, failing to fully exploit methylation profiles obtained from long read technologies. To address these issues, we present pycoMeth, a toolbox to store, manage and analyse DNA methylation data obtained from long-read ONT sequencing data. Our toolbox centers around a new storage format called MetH5, which allows simultaneously for efficient storage of and rapid data access for read-level and reference-anchored methylation call data. Building on this storage format, we propose efficient algorithms for the segmentation and differential methylation testing of methylation calls from ONT data. Our methods draw from read-group and read-level information, as well as methylation call uncertainties, and allow for de novo discovery of methylation patterns and differentially methylated regions in a haplotyped multi-sample setting. We show that MetH5 is more efficient than existing solutions for storing ONT methylation calls, and carry out benchmarking for segmentation and differential methylation analysis, demonstrating increased performance and sensitivity of pycoMeth compared to existing solutions.
Multi-ancestry genome-wide analysis identifies common genetic variants for self-reported sleep duration and shared genetic effects
Authors: Scammell Ben H , Song Yanwei , Tchio Cynthia , Nishiyama Takeshi , Louie Tin L , Dashti Hassan S , Nakatochi Masahiro , Zee Phyllis C , Daghlas Iyas , Momozawa Yukihide , Cai Jianwen , Ollila Hanna M. , Redline Susan , Wakai Kenji , Sofer Tamar , Suzuki Sadao , Lane Jacqueline M , Saxena Richa 
Published: February 2022

AbstractBoth short and long sleep duration are associated with increased risk of chronic diseases, but the genetic determinants of sleep duration are largely unknown outside of European populations. Here we report transferability of a polygenic score of 78 European ancestry sleep duration SNPs to an African (n=7,288; p=0.003), a South Asian (n=7,485; p=0.025), and a Japanese (n=13,618; p=6x10-4) cohort, but not to a cohort of Hispanic/Latino (n- XXX; p=0.71) participants. Furthermore, in a pan-ancestry (N = 483,235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 5 novel and 68 known loci are associated with genome-wide significance. For the novel loci, sleep duration signals colocalize with expression-QTLs for PRR12 and COG5 in brain tissues, and pleiotropic associations are observed with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.
Dissecting the Genetic Architecture of Carbon Partitioning in Sorghum using Multiscale Phenotypes
Authors: Boatwright J. Lucas , Sapkota Sirjan , Myers Matthew , Kumar Neeraj , Cox Alex , Kresovich Stephen 
Published: February 2022

AbstractCarbon partitioning in plants may be viewed as a dynamic process composed of the many interactions between sources and sinks. The accumulation and distribution of fixed carbon is not dictated simply by the sink strength and number but is dependent upon the source, pathways, and interactions of the system. As such, the study of carbon partitioning through perturbations to the system or through focus on individual traits may fail to produce actionable developments or a comprehensive understanding of the mechanisms underlying this complex process. Using the recently published sorghum carbon-partitioning panel, we collected both macroscale phenotypic characteristics such as plant height, above-ground biomass, and dry weight along with microscale compositional traits to deconvolute the carbon-partitioning pathways in this multipurpose crop. Multivariate analyses of traits resulted in the identification of numerous loci associated with several distinct carbon-partitioning traits, which putatively regulate sugar content, manganese homeostasis, and nitrate transportation. Using a multivariate adaptive shrinkage approach, we identified several loci associated with multiple traits suggesting that pleiotropic and/or interactive effects may positively influence multiple carbon-partitioning traits, or these overlaps may represent molecular switches mediating basal carbon allocating or partitioning networks. Conversely, we also identify a carbon tradeoff where reduced lignin content is associated with increased sugar content. The results presented here support previous studies demonstrating the convoluted nature of carbon partitioning in sorghum and emphasize the importance of taking a holistic approach to the study of carbon partitioning by utilizing multiscale phenotypes.