bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia
Authors: Marballi Ketan K. , Alganem Khaled , Brunwasser Samuel J. , Barkatullah Arhem , Meyers Kimberly T. , Campbell Janet M. , Ozols Annika B. , Mccullumsmith Robert E. , Gallitano Amelia L. 
Published: August 2022

AbstractBioinformatics and network studies have identified the immediate early gene transcription factor early growth response 3 (EGR3) as a master regulator of genes differentially expressed in the brains of patients with neuropsychiatric illnesses ranging from schizophrenia and bipolar disorder to Alzheimer’s disease. However, few studies have identified and validatedEgr3-dependent genes in the mammalian brain. We have previously shown thatEgr3is required for stress-responsive behavior, memory, and hippocampal long-term depression in mice. To identifyEgr3-dependent genes that may regulate these processes, we conducted an expression microarray on hippocampi from wildtype (WT) andEgr3−/−mice following electroconvulsive seizure (ECS), a stimulus that induces maximal expression of immediate early genes includingEgr3. We identified 69 genes that were differentially expressed between WT andEgr3−/−mice one hour following ECS. Bioinformatic analyses showed that many of these are altered in, or associated with, schizophrenia, includingMef2candCalb2. Enrichr pathway analysis revealed the GADD45 (growth arrest and DNA-damage-inducible) family (Gadd45b,Gadd45g) as a leading group of differentially expressed genes. Together with differentially expressed genes in the AP-1 transcription factor family genes (Fos,Fosb), and the centromere organization proteinCenpa, these results revealed thatEgr3is required for activity-dependent expression of genes involved in the DNA damage response. Our findings show thatEGR3is critical for the expression of genes that are mis-expressed in schizophrenia and reveal a novel requirement for EGR3 in the expression of genes involved in activity-induced DNA damage response.
Predictors of emotional distress in uveal melanoma survivors: a systematic review
Authors: Davies Cari , Brown Stephen Lloyd , Fisher Peter , Hope-Stone Laura , Fisher Debra , Morgan Andrew , Cherry Mary Gemma 
Published: August 2022

AbstractUveal melanoma (UM) survivors can experience significant emotional distress, although the factors underpinning this are poorly understood. Systematic reviews of distress in UM only include cross-sectional studies, thereby limiting our understanding of causal factors. This review identified prospective clinical, demographic, social and psychological predictors of distress in UM survivors. A systematic search of the literature for English language prospective studies was conducted. Thirteen papers, reporting data from seven unique datasets were included in a narrative synthesis of the results. Younger age (3 studies from 3 datasets), physical health (including visual impairment, ocular symptoms, and other UM-related factors; 3 studies from 3 datasets), and psychological factors (mainly baseline distress; 3 studies from 3 datasets and worry about recurrence; 2 studies from 2 datasets), significantly predicted distress. There was no consistent evidence for other demographic, clinical or social variables (significant in <50% of datasets). Generally, the quality of the papers was adequate. However, attrition rates were high or not reported in over half of the included studies. The findings of this review emphasise the importance of attempts to prevent and recognise distress immediately post-diagnosis of UM. Particular focus should be given to younger patients, those with physical and psychological health difficulties at the time of diagnosis, and those who develop adverse treatment symptoms during survivorship. More research into potential social and psychological variables and their role in predicting distress in survivors is recommended.
RALY regulate the proliferation and expression of immune/inflammatory response genes via alternative splicing of FOS
Authors: Liang Zhao , Rehati Aliya , Husaiyin Erhati , Chen Dong , Jiyuan Zhang , Abuduaini Buzukela 
Published: August 2022

AbstractRALY is a multifunctional RNA-binding protein involved in cancer metastasis, prognosis, and chemotherapy resistance in various cancers. However, the molecular mechanism of which is still unclear. We have established RALY overexpression cell lines and studied the effect of RALY on proliferation and apoptosis in HeLa cells. Then we used RNA-seq to analyze the transcriptomes data. Lastly, RT-qPCR experiments had performed to confirm the RNA-seq results. We found that the overexpression of RALY in HeLa cells inhibited proliferation. Moreover, the overexpression of RALY changed the gene expression profile, and the significant upregulation of genes involved immune/inflammatory response related biological process by NOD-like receptor signaling pathway cytokine-cytokine receptor interaction. The significant downregulation genes involved innate immune response by the Primary immunodeficiency pathway. Notably, IFIT1, IFIT2, IFTI3, IFI44, HERC4, and OASL expression had inhibited by the overexpression of RALY. Furthermore, RALY negatively regulates the expression of transcription factors FOS and FOSB. Notably, we found that 645 alternative splicing events had regulated by overexpression of RALY, which is highly enriched in transcription regulation, RNA splicing, and cell proliferation biological process by the metabolic pathway. We show that RALY regulates the expression of immune/inflammatory response-related genes via alternative splicing of FOS in HeLa cells. The novel role of RALY in regulating immune/inflammatory gene expression may explain its function in regulating chemotherapy resistance and provides novel insights into further exploring the molecular mechanism of RALY in regulating cancer immunity and chemo/immune therapies.
Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis
Authors: Koren Elle , Feldman Alona , Yusupova Marianna , Kadosh Avihay , Sedov Egor , Ankawa Roi , Yosefzon Yahav , Nasser Waseem , Gerstberger Stefanie , Kimel Liam B. , Priselac Noa , Brown Samara , Sharma Sam , Gorenc Travis , Shalom-Feuerstein Ruby , Steller Hermann , Shemesh Tom , Fuchs Yaron 
Published: August 2022

AbstractThe presence of distinct stem cells that maintain the interfollicular epidermis is highly debated. Here, we report a population of keratinocytes, marked by Thy1, in the basal layer of the interfollicular epidermis. We find that epidermal cells expressing differential levels of Thy1 display distinct transcriptional signatures. Thy1+ keratinocytes do not express T cell markers, express a unique transcriptional profile, cycle significantly slower than basal epidermal progenitors and display significant expansion potential in vitro. Multicolor lineage tracing analyses and mathematical modeling reveal that Thy1+ basal keratinocytes do not compete neutrally alike interfollicular progenitors and contribute long-term to both epidermal replenishment and wound repair. Importantly, ablation of Thy1+ cells strongly impairs these processes, thus indicating the non-redundant function of Thy1+ stem cells in the epidermis. Collectively, these results reveal a distinct stem cell population that plays a critical role in epidermal homeostasis and repair.
Scarf enables a highly memory-efficient analysis of large-scale single-cell genomics data
Authors: Dhapola Parashar , Rodhe Johan , Olofzon Rasmus , Bonald Thomas , Erlandsson Eva , Soneji Shamit , Karlsson Göran 
Published: August 2022

AbstractAs the scale of single-cell genomics experiments grows into the millions, the computational requirements to process this data are beyond the reach of many. Herein we present Scarf, a modularly designed Python package that seamlessly interoperates with other single-cell toolkits and allows for memory-efficient single-cell analysis of millions of cells on a laptop or low-cost devices like single-board computers. We demonstrate Scarf’s memory and compute-time efficiency by applying it to the largest existing single-cell RNA-Seq and ATAC-Seq datasets. Scarf wraps memory-efficient implementations of a graph-based t-stochastic neighbour embedding and hierarchical clustering algorithm. Moreover, Scarf performs accurate reference-anchored mapping of datasets while maintaining memory efficiency. By implementing a subsampling algorithm, Scarf additionally has the capacity to generate representative sampling of cells from a given dataset wherein rare cell populations and lineage differentiation trajectories are conserved. Together, Scarf provides a framework wherein any researcher can perform advanced processing, subsampling, reanalysis, and integration of atlas-scale datasets on standard laptop computers. Scarf is available on Github: https://github.com/parashardhapola/scarf.
Unified classification and risk-stratification in Acute Myeloid Leukemia
Authors: Tazi Yanis , Arango-Ossa Juan E. , Zhou Yangyu , Bernard Elsa , Thomas Ian , Gilkes Amanda , Freeman Sylvie , Pradat Yoann , Johnson Sean J. , Hills Robert , Dillon Richard , Levine Max F. , Leongamornlert Daniel , Butler Adam , Ganser Arnold , Bullinger Lars , Döhner Konstanze , Ottmann Oliver , Adams Richard , Döhner Hartmut , Campbell Peter J. , Burnett Alan K. , Dennis Michael , Russell Nigel H. , Devlin Sean M. , Huntly Brian J. P. , Papaemmanuil Elli 
Published: August 2022

AbstractClinical recommendations for Acute Myeloid Leukemia (AML) classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow Minimal Residual Disease (MRD) negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool.
Tectonically-driven oxidant production in the hot biosphere
Authors: Stone Jordan , Edgar John O. , Gould Jamie A. , Telling Jon 
Published: August 2022

AbstractGenomic reconstructions of the common ancestor to all life have identified genes involved in H2O2 and O2 cycling. Commonly dismissed as an artefact of lateral gene transfer after oxygenic photosynthesis evolved, an alternative is a geological source of H2O2 and O2 on the early Earth. Here, we show that under oxygen-free conditions high concentrations of H2O2 can be released from defects on crushed silicate rocks when water is added and heated to temperatures close to boiling point, but little is released at temperatures <80 °C. This temperature window overlaps the growth ranges of evolutionary ancient heat-loving and oxygen-respiring Bacteria and Archaea near the root of the Universal Tree of Life. We propose that the thermal activation of mineral surface defects during geological fault movements and associated stresses in the Earth’s crust was a source of oxidants that helped drive the (bio)geochemistry of hot fractures where life first evolved.
Blocking ActRIIB and restoring appetite reverses cachexia and improves survival in mice with lung cancer
Authors: Queiroz Andre Lima , Dantas Ezequiel , Ramsamooj Shakti , Murthy Anirudh , Ahmed Mujmmail , Zunica Elizabeth R. M. , Liang Roger J. , Murphy Jessica , Holman Corey D. , Bare Curtis J. , Ghahramani Gregory , Wu Zhidan , Cohen David E. , Kirwan John P. , Cantley Lewis C. , Axelrod Christopher L. , Goncalves Marcus D. 
Published: August 2022

AbstractCancer cachexia is a common, debilitating condition with limited therapeutic options. Using an established mouse model of lung cancer, we find that cachexia is characterized by reduced food intake, spontaneous activity, and energy expenditure accompanied by muscle metabolic dysfunction and atrophy. We identify Activin A as a purported driver of cachexia and treat with ActRIIB-Fc, a decoy ligand for TGF-β/activin family members, together with anamorelin (Ana), a ghrelin receptor agonist, to reverse muscle dysfunction and anorexia, respectively. Ana effectively increases food intake but only the combination of drugs increases lean mass, restores spontaneous activity, and improves overall survival. These beneficial effects are limited to female mice and are dependent on ovarian function. In agreement, high expression of Activin A in human lung adenocarcinoma correlates with unfavorable prognosis only in female patients, despite similar expression levels in both sexes. This study suggests that multimodal, sex-specific, therapies are needed to reverse cachexia.
Space-time monitoring of groundwater fluctuations with passive seismic interferometry
Authors: Mao Shujuan , Lecointre Albanne , van der Hilst Robert D. , Campillo Michel 
Published: August 2022

AbstractHistoric levels of drought, globally, call for sustainable freshwater management. Under pressing demand is a refined understanding of the structures and dynamics of groundwater systems. Here we present an unconventional, cost-effective approach to aquifer monitoring using seismograph arrays. Employing advanced seismic interferometry techniques, we calculate the space-time evolution of relative changes in seismic velocity, as a measure of hydrological properties. During 2000–2020 in basins near Los Angeles, seismic velocity variations match groundwater tables measured in wells and surface deformations inferred from satellite sensing, but the seismological approach adds temporal and depth resolutions for deep structures and processes. Maps of long-term seismic velocity changes reveal distinct patterns (decline or recovery) of groundwater storage in basins that are adjacent but adjudicated to water districts conducting different pumping practices. This pilot application bridges the gap between seismology and hydrology, and shows the promise of leveraging seismometers worldwide to provide 4D characterizations of groundwater and other near-surface systems.
COVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation
Authors: Reinscheid Matthias , Luxenburger Hendrik , Karl Vivien , Graeser Anne , Giese Sebastian , Ciminski Kevin , Reeg David B. , Oberhardt Valerie , Roehlen Natascha , Lang-Meli Julia , Heim Kathrin , Gross Nina , Baum Christina , Rieg Siegbert , Speer Claudius , Emmerich Florian , Breisinger Susanne , Steinmann Daniel , Bengsch Bertram , Boettler Tobias , Kochs Georg , Schwemmle Martin , Thimme Robert , Neumann-Haefelin Christoph , Hofmann Maike 
Published: August 2022

AbstractImmunization with two mRNA vaccine doses elicits robust spike-specific CD8+ T cell responses, but reports of waning immunity after COVID-19 vaccination prompt the introduction of booster vaccination campaigns. However, the effect of mRNA booster vaccination on the spike-specific CD8+ T cell response remains unclear. Here we show that spike-specific CD8+ T cells are activated and expanded in all analyzed individuals receiving the 3rd and 4th mRNA vaccine shots. This CD8+ T cell boost response is followed by a contraction phase and lasts only for about 30-60 days. The spike-specific CD8+ T memory stem cell pool is not affected by the 3rd vaccination. Both 4th vaccination and breakthrough infections with Delta and Omicron rapidly reactivate CD8+ T memory cells. In contrast, neutralizing antibody responses display little boost effect towards Omicron. Thus, COVID-19 mRNA booster vaccination elicits a transient T effector cell response while long-term spike-specific CD8+ T cell immunity is conserved to mount robust memory recall targeting emerging variants of concern.
A quantitative analysis of various patterns applied in lattice light sheet microscopy
Authors: Shi Yu , Daugird Timothy A. , Legant Wesley R. 
Published: August 2022

AbstractLight sheet microscopes reduce phototoxicity and background and improve imaging speed compared to widefield and confocal microscopes. However, when equipped with Gaussian beams, the axial resolving power of a light sheet microscope and the observable field of view are inversely related. Light sheets based on dithered optical lattices improve axial resolution and beam uniformity compared Gaussian beams by using axially structured illumination patterns. However, these advantages come at the expense of an increased total illumination to the specimen and a decreased axial confinement of the illumination pattern. Using simulations and experimental measurements in fixed and live cells, we quantify the differences between Gaussian and lattice light sheets on beam uniformity, axial resolution, lateral resolution, and photobleaching. We demonstrate how different optical lattice illumination patterns can be tuned to prioritize either axial resolution or optical sectioning. Finally, we introduce an approach to spectrally fuse sequential acquisitions of different lattice light sheet patterns with complementary optical properties to achieve both high resolution and low background images.
Topological superfluid defects with discrete point group symmetries
Authors: Xiao Y. , Borgh M. O. , Blinova A. , Ollikainen T. , Ruostekoski J. , Hall D. S. 
Published: August 2022

AbstractDiscrete symmetries are spatially ubiquitous but are often hidden in internal states of systems where they can have especially profound consequences. In this work we create and verify exotic magnetic phases of atomic spinor Bose–Einstein condensates that, despite their continuous character and intrinsic spatial isotropy, exhibit complex discrete polytope symmetries in their topological defects. Using carefully tailored spinor rotations and microwave transitions, we engineer singular line defects whose quantization conditions, exchange statistics, and dynamics are fundamentally determined by these underlying symmetries. We show how filling the vortex line singularities with atoms in a variety of different phases leads to core structures that possess magnetic interfaces with rich combinations of discrete and continuous symmetries. Such defects, with their non-commutative properties, could provide unconventional realizations of quantum information and interferometry.
FERARI and cargo adaptors coordinate cargo flow through sorting endosomes
Authors: Solinger Jachen A. , Rashid Harun-Or , Spang Anne 
Published: August 2022

AbstractCellular organization, compartmentalization and cell-to-cell communication are crucially dependent on endosomal pathways. Sorting endosomes provide a transit point for various trafficking pathways and decide the fate of proteins: recycling, secretion or degradation. FERARI (Factors for Endosome Recycling and Rab Interactions) play a key role in shaping these compartments and coordinate Rab GTPase function with membrane fusion and fission of vesicles through a kiss-and-run mechanism. Here, we show that FERARI also mediate kiss-and-run of Rab5-positive vesicles with sorting endosomes. During these encounters, cargo flows from Rab5-positive vesicles into sorting endosomes and from there in Rab11-positive vesicles. Cargo flow from sorting endosomes into Rab11 structures relies on the cargo adaptor SNX6, while cargo retention in the Rab11 compartment is dependent on AP1. The available cargo amount appears to regulate the duration of kisses. We propose that FERARI, together with cargo adaptors, coordinate the vectorial flow of cargo through sorting endosomes.
Optimization, kinetics and thermodynamics studies for photocatalytic degradation of Methylene Blue using cadmium selenide nanoparticles
Authors: Gharbani Parvin , Mehrizad Ali , Mosavi Seyyed Amir 
Published: August 2022

AbstractIn this study, the photocatalytic degradation of Methylene Blue was investigated using CdSe nanoparticles. CdSe nanoparticles were synthesized via a simple method and were characterized by FTIR, XRD, FESEM, BET, DRS and EDS techniques. The photocatalytic performance of the CdSe nanoparticles was optimized using Response Surface Methodology (RSM) under visible light. The independent variables involved initial pH, MB concentration, photocatalyst dosage, and irradiation time were evaluated and the optimum photodegradation efficiency of MB dye removal was achieved ˜ 92.80% at pH = 8, 20 mgL−1 of MB concentration, 0.02 g 50 mL−1 of CdSe dosage, and 20 min of irradiation time. Also, the photodegradation of MB by CdSe is obeyed pseudo-first-order kinetic model (k = 0.038 min−1). The thermodynamic results revealed that the photocatalytic degradation of MB is spontaneous and endothermic. Also, the evaluation of various scavengers confirmed that the MB photodegradation was mainly done by photogenerated holes and hydroxyl radicals.
Repeated series learning revisited with a novel prediction on the reduced effect of item frequency in dyslexia
Authors: Kimel Eva , Lieder Itay , Ahissar Merav 
Published: August 2022

AbstractDevelopmental dyslexia, a difficulty with acquiring fluent reading, has also been characterized by reduced short-term memory (STM) capacity, which is often operationalized with span tasks. The low performance of individuals with dyslexia (IDDs) in such tasks is commonly attributed to poor phonological memory. However, we suggest an alternative explanation based on the observation that many times the items that are used in spans tasks are high-frequency items (e.g., digit words). We suggest that IDDs do not enjoy the benefit of item frequency to the same extent as controls, and thus their performance in span tasks is especially hampered. On the contrary, learning of repeated sequences was shown to be largely independent of item frequency, and therefore this type of learning may be unimpaired in dyslexia. To test both predictions, we used the Hebb-learning paradigm. We found that IDDs’ performance is especially poor compared to controls’ when high-frequency items are used, and that their repeated series learning does not differ from that of controls. Taken together with existing literature, our findings suggest that impaired learning of repeated series is not a core characteristic of dyslexia, and that the reports on reduced STM in dyslexia may to a large extent be explained by reduced benefit of item frequency.