bluuebunny/crossref_metadata_2025_split huggingface dataset:
A curated collection of transcriptome datasets to study the transcriptional response in blood and nasal samples following viral respiratory inoculation and vaccination
Authors: Lan Zheng , Zhang Tongli , Zhang Yu , Sun Xuejun , Liu Chuwen , Liu Pei , Tang Muyao , Fu Meng , Hagood James S. , Pickles Raymond J , Zou Fei , Zheng Xiaojing 
Published: September 2024

AbstractOur understanding of the human immune system’s response to viral respiratory tract infections (VRTIs) and vaccines, including the molecular mechanisms and correlates of protection, remains incomplete. Extensive transcriptomic data from inoculation and vaccination studies have been deposited in publicly available databases. However, these studies are often separate and difficult to locate. We provide a curated compendium of public gene expression data repositories for researchers to reanalyze transcriptomes from human whole blood, peripheral blood mononuclear cells (PBMCs), and nasal swab samples. This enables the study of transcriptional responses to viral inoculation or vaccination. This collection includes 18 datasets from inoculation studies and 37 datasets from vaccination studies, sourced from the NCBI Gene Expression Omnibus (GEO), ImmPort Shared Data, and ArrayExpress.
A Comprehensive and Accessible Model for Co-Segregation Analysis inBRCA1, BRCA2, andPALB2Variant Classification
Authors: Moghadasi Setareh , Monajemi Ramin , Braspenning Merel E. , Vreeswijk Maaike P.G. , Rodríguez-Girondo Mar 
Published: September 2024

AbstractVariants of uncertain significance (VUS) are genetic variations with unclear clinical implications, often complicating clinical management in genetic testing. The analysis of co-segregation of the variant with the disease in families has been shown to be a powerful tool for the classification of these variants. We present CAL-Leiden (Co-segregation Analysis via Likelihood ratio analysis-Leiden), a comprehensive co-segregation model facilitating the classification of variants inBRCA1, BRCA2andPALB2genes, which can be used as an important component of the ACMG/AMP classification guideline. CAL-Leiden includes an expanded range of cancer types, including pancreatic cancer, in addition to breast and ovarian cancer. It also considers contralateral breast cancer. The model integrates population incidence rates from the Netherlands and the United Kingdom, along with penetrance data from the latest literature. A web-based platform has been developed, making the model accessible and practical for use in diagnostic labs:https://bioexp.net/cosegregation/. We demonstrate the functionality of the tool with multiple pedigrees and compare its performance with alternative approaches. These features in CAL-Leiden collectively contribute to a more comprehensive and accurate assessment of variant pathogenicity, helping lab specialists in classification of the variants of uncertain significance.
Divergent selection and plasticity shape reproductive isolation at the onset of speciation
Authors: Jarrett Benjamin J. M. , Downing Philip A. , Svensson Erik I. 
Published: September 2024

AbstractReproductive isolation is a key process during speciation, but the factors that shape its evolution during the early stages of speciation remain largely unknown. Using a meta-analysis of 34 experimental speciation studies, we show that populations that experience divergent selection evolved stronger reproductive isolation compared to populations that evolved in similar environments, consistent with ecological speciation theory. However, and contrary to predictions, reproductive isolation did not increase with the number of generations. We present evidence that phenotypic plasticity could play a role in explaining these results, as divergent environments induce an increase in reproductive isolation in the first few generations. Our results highlight that adaptation to different environments in conjunction with plasticity can lead to a rapid increase in reproductive isolation at the beginning of speciation.
A minor impact of VGLUT1 expression level on quantal size revealed through the characterization of VGLUT1mEos2knock-down new mouse model
Authors: Zhang Xiao Min , François Urielle , Angelo Maria Florencia , Claverol Stéphane , Mondin Magali , Martin Christelle , Deshors Melissa , Humeau Yann , Lipstein Noa , Herzog Etienne 
Published: September 2024

AbstractSynaptic vesicles (SVs) are small organelles secreting neurotransmitters at synapses. By fusing a photoactivated fluorescent protein to VGLUT1, we generated a VGLUT1mEos2knock-in mouse. VGLUT1mEos2knock-in mice are viable and healthy, but exhibit a severe reduction in VGLUT1 expression levels. Using VGLUT1mEos2expressing neurons, we established paradigms to trace individual SV mobility at the single-molecule level or via massive photoconversion. Hippocampal neurons with significantly diminished VGLUT1 expression maintain unaltered miniature glutamate release characteristics in terms of quantal size and frequency. We demonstrate that VGLUT1 expression level are not correlated in a linear fashion with the vesicular glutamate content. In conclusion, the VGLUT1mEos2mouse line serves as a powerful tool for exploring SV mobility properties and elucidating the contributions of VGLUT1 to excitatory neurotransmission and cognitive processes.
Accurate non-invasive quantification of astaxanthin content using hyperspectral images and machine learning
Authors: Calderini Marco L. , Pääkkönen Salli , Yli-Tuomola Aliisa , Timilsina Hemanta , Pulkkinen Katja , Pölönen Ilkka , Salmi Pauliina 
Published: September 2024

AbstractCommercial cultivation of the microalgaeHaematococcus pluvialisto produce natural astaxanthin has gained significant traction due to the high antioxidant capacity of this pigment and its application in foods, feed, cosmetics and nutraceuticals. However, monitoring of astaxanthin content in cultures remains challenging and relies on invasive, time consuming and expensive approaches. In this study, we employed reflectance hyperspectral imaging (HSI) ofH. pluvialissuspensions within the visible spectrum, combined with a 1-dimensional convolutional neural network (CNN) to predict the astaxanthin content (μg mg−1) as quantified by high-performance liquid chromatography (HPLC). This approach had low average prediction error (5.9%) across a gradient of astaxanthin contents and was only unreliable at very low contents (<0.6 μg mg−1). In addition, our machine learning model outperformed single or dual wavelength linear regression models even when the spectral data was obtained with a spectrophotometer coupled with an integrating sphere. Overall, this study proposes the use of HSI in combination with a CNN for precise non-invasive quantification of astaxanthin in cell suspensions.
Flexible graphene-based neurotechnology for high-precision deep brain mapping and neuromodulation in Parkinsonian rats
Authors: Ria Nicola , Eladly Ahmed , Masvidal Eduard , Illa Xavi , Guimerà Anton , Hills K. , Garcia Ramon , Flaherty Samuel , Prokop Michal , Wykes Rob. C , Kostarelos Kostas , Garrido Jose A. 
Published: September 2024

AbstractDeep brain stimulation (DBS) is a neuroelectronic therapy for the treatment of a broad range of neurological disorders, including Parkinson’s disease. Current DBS technologies face important limitations that impact their efficacy, such as large electrode size, invasiveness, and lack of adaptive therapy based on biomarker monitoring. The use of novel electrode materials is expected to contribute to overcome these limitations. In a previous study, we reported that nanoporous reduced graphene oxide (rGO) is a promising electrode material due to its high charge injection capacity and low impedance. Here, we investigate the potential benefits of using the rGO technology in DBS. To this end, we implant a flexible high-density array of rGO microelectrodes in the subthalamic nucleus (STN) of healthy and hemi-parkinsonian rats to investigate specific electrophysiological Parkinsonian biomarkers and to assess the effect of microscale stimulation. We demonstrate that these microelectrodes record action potentials with high signal-to-noise ratios (SNR > 6), allowing the precise localization of deep brain structures like the STN, and the tracking of multiunit-based biomarkers such as STN bursts. The bidirectional capability to deliver high-density focal stimulation and to record high-fidelity signals unlocks the visualization of the local neuromodulation of the multiunit biomarker. These findings demonstrate the potential of bidirectional high-resolution neural interfaces to investigate the mechanisms around DBS in preclinical models and suggest new avenues for the use of adaptive closed-loop operation based on electrophysiological biomarkers monitoring.
CX3CR1 modulates migration of resident microglia towards brain injury
Authors: Wagner Jens , Hoyer Cornelia , Antony Henrike , Lundgrén Kristiina , Soliymani Rabah , Crux Sophie , Justus Lena , Keppler Kevin , Steffen Julia , Kurts Christian , Engel Daniel R. , Herms Jochen , Łałowski Maciej , Fuhrmann Martin 
Published: September 2024

AbstractMicroglia are innate immune cells of the central nervous system (CNS). They extend their processes towards and migrate towards injuriesin vivo. However, whether the fractalkine receptor (CX3CR1) influences microglial migration remains unknown. Label-free proteomic profiling predicted changes in RHO-signaling activity that hint at dysregulated cytoskeleton signaling inCx3cr1-deficient murine cortex tissue. To further investigate microglial migration, we carried out 4-hour interval two-photonin vivoimaging for 72 hours after a laser lesion in the cortex.Cx3cr1-deficient microglia showed enhanced migration towards the lesion. Additionally, length and velocity of microglial fine processes extending towards the lesion were increased inCx3cr1-deficient microglia. Migration remained unchanged inCcr2-deficient mice, indicating that monocyte-derived macrophages/microglia did not contribute to microglia accumulation around the lesion. These results demonstrate microglia migration towards CNS injury and suggest CX3CR1 as a modulator of this. Manipulating microglia migration via CX3CR1 therefore is a potential target for treatment of CNS-injury.
Identification and Diagnostic Potential of Pyroptosis-Related Genes in Endometriosis: A Novel Bioinformatics Analysis
Authors: Teng Piaopiao , Wang Li , Ding Caiyun , Gu Kaili , Luo Xianchen , Su Chang , Ni Guantai , Lyu Yuanyuan , Ding Jin 
Published: September 2024

AbstractObjectiveThis study aimed to identify and analyze potential signatures of pyroptosis-related genes in EMs.MethodsTranscriptomic datasets related to endometriosis were retrieved from the GEO databases (GSE7305, GSE7307, and GSE11691). Differential gene expression analysis was performed to identify pyroptosis-related differentially expressed genes (PRDEGs) by intersecting DEGs with a curated list of PRGs. Various bioinformatics tools were employed to explore the biological functions and pathways associated with PRDEGs.ResultsWe identified 26 PRDEGs from combined datasets and constructed an EMs diagnostic model using LASSO regression based on pyroptosis scores. The model included 5 DEGs: KIF13B, BAG6, MYO5A, HEATR, and AK055981. Additionally, 21 Key Module Genes (KMGs) were identified, leading to the classification of 3 distinct EMs subtypes. These subtypes were analyzed for immune cell infiltration, revealing a complex immune landscape in EMs.ConclusionsThis study reveals pyroptosis’ crucial role in EMs and offers a novel diagnostic model based on pyroptosis-related genes. Modulating pyroptosis may provide a new therapeutic approach for managing EMs.
Building plumbing influences the microdiversity and community assembly of the drinking water microbiome
Authors: He Huanqi , Huo Linxuan , Oosthuizen-Vosloo Solize , Pieper Kelsey J. , Stubbins Aron , Yoon Byungman , Pinto Ameet J. 
Published: September 2024

AbstractBuilding plumbing microbial communities can significantly influence water quality at the point of use, particularly during periods of stagnation. Thus, a fine-scale understanding of factors governing community membership and structure, as well as environmental and ecological factors shaping building plumbing microbial communities is critical. In this study, we utilized full-length 16S ribosomal RNA (rRNA) gene sequencing to investigate the microdiversity and spatial-temporal dynamics of microbial communities in commercial and residential building plumbing systems. Bacterial operational taxonomic units (OTUs) within commercial buildings exhibited much lower microdiversity relative to the same OTUs in residential buildings. Microdiversity was associated with higher persistence and relative abundance of OTUs. Interestingly, amplicon sequencing variants within the same OTUs exhibited habitat preferences based on the building type while also demonstrating varying temporal turnover patterns. Dispersal limitation disproportionately governed community assembly in commercial buildings, whereas heterogeneous selection was the dominant ecological mechanism shaping the microbial community in residential buildings. Dispersal limitation in commercial buildings is consistent with larger building sizes and greater periods of water stagnation. Interestingly, the inability to explain the extent of heterogeneous selection-driven community assembly in residential locations using measured water chemistry may suggest a disproportionately large effect of fine-scale variation in plumbing characteristics on community assembly in residential locations.
Eavesdropping on Herbivores: Using contact microphones to quantify Plant-Insect Interactions
Authors: Mehrotra Dev , Still Laurence , Agrawal Vidit , Gibson Kimberly , Crall James D. , Bick Emily N. 
Published: September 2024

AbstractHerbivorous insects are major crop pests whose feeding often results in significant economic damage. Detecting and monitoring insect herbivory is crucial for effective pest management, but manual methods can be time-consuming, inefficient, and destructive. This study investigates the use of contact microphones as a non-invasive and efficient tool for detecting, identifying, and monitoring insects feeding on plants.Approach and methods: Contact microphones connected to a Raspberry Pi were clipped onto plant stems and programmed to record sounds made by the feeding insects. Three combinations of herbivorous insects and plants were evaluated: tobacco hornworm (Manduca sextaLinnaeus) on tobacco, Colorado potato beetle (Leptinotarsa decemlineataSay) on potato, and European corn borer (Ostrinia nubilalisHübner) and Northern corn rootworm (Diabrotica barberiSmith & Lawrence) on corn (Zea maysLinnaeus). Sound recordings were analyzed to determine the presence and absence of insects and to quantify differences in feeding activity between different insects. The laboratory study was repeated in a corn field to observe corn rootworms (Diabroticaspp.).Main results: Contact microphones successfully detected insect herbivory on the tobacco, potato, and corn plants in the lab and field, demonstrating the use of substrate-born acoustic signals for detecting both large and small-bodied insect pests. The recordings also revealed differences in the feeding patterns, frequency, and amplitude between insect species. Field experiments indicate low background noise relative to lab experiments.Conclusions and implications: Contact microphones offer a promising cost-effective, non-destructive, and efficient method for monitoring insect herbivory. This approach has the potential to improve scientific observations of insect herbivores and pest management strategies by enabling early pest detection and measuring the success of interventions. Early field results indicate the viability of this approach under realistic conditions in the field. The results highlight the importance of considering the acoustic environment in agricultural ecosystems, suggesting sound can be used to better understand the behavior of insects and their interactions with plant hosts. Contact microphones could have widespread applications in agriculture and ecology by providing a simple and effective tool for detecting and monitoring insect activity.
PDZ-directed substrate recruitment is the primary determinant of specific 4E- BP1 dephosphorylation by PP1-Neurabin
Authors: Fedoryshchak Roman O , El-Bouri Karim , Joshi Dhira , Mouilleron Stephane , Treisman Richard 
Published: September 2024

ABSTRACTProtein Phosphatase 1 (PP1) relies on association with PP1-interacting proteins (PIPs) to generate substrate-specific PIP/PP1 holoenzymes, but the lack of well-defined substrates has hindered elucidation of the mechanisms involved. We previously demonstrated that the Phactr1 PIP confers sequence specificity on the Phactr1/PP1 holoenzyme by remodelling the PP1 hydrophobic substrate groove. Phactr1 defines a group of “RVxF-ΦΦ-R-W” PIPs that all interact with PP1 in a similar fashion. Here we use a PP1-PIP fusion approach to address sequence specificity and identify substrates of the RVxF-ΦΦ-R-W family PIPs. We show that the four Phactr proteins confer identical sequence specificities on their holoenzymes. We identify the 4E-BP and p70 S6K translational regulators as substrates for the Neurabin/Spinophilin PIPs, implicated in neuronal plasticity, pointing to a role for their holoenzymes in mTORC1-dependent translational control. Biochemical and structural experiments show that in contrast to the Phactrs, substrate recruitment and catalytic efficiency of the PP1-Neurabin and PP1-Spinophilin fusions is primarily determined by substrate interaction with the PDZ domain adjoining their RVxF-ΦΦ-R-W motifs, rather than by recognition of the remodelled PP1 hydrophobic groove. Thus, even PIPs that interact with PP1 in a similar manner use different mechanisms to ensure substrate selectivity.
Whisker deprivation triggers a distinct form of cortical homeostatic plasticity that is impaired in theFmr1KO
Authors: Lakhani Alishah , Huang Washington , Rodgers Chris C. , Wenner Peter 
Published: September 2024

SUMMARYMouse models of Fragile X Syndrome (FXS) have demonstrated impairments in excitatory and inhibitory sensory-evoked neuronal firing. Homeostatic plasticity, which encompasses a set of mechanisms to stabilize baseline activity levels, does not compensate for these changes in activity. Previous work has shown that impairments in homeostatic plasticity are observed in FXS, including deficits in synaptic scaling and intrinsic excitability. Here, we aimed to examine how homeostatic plasticity is alteredin vivoin anFmr1KO mouse model following unilateral whisker deprivation (WD). We show that WD in the wild type leads to an increase in the proportion of L5/6 somatosensory neurons that are recruited, but this does not occur in the KO. In addition, we observed a change in the threshold of excitatory neurons at a later developmental stage in the KO. Compromised homeostatic plasticity in development could influence sensory processing and long-term cortical organization.
Versatile Cell Penetrating Peptide for Multimodal CRISPR Gene Editing in Primary Stem Cells
Authors: Graham Josh P. , Castro Jose Gabriel , Werba Lisette C. , Fardone Luke C. , Francis Kevin P. , Ramamurthi Anand , Layden Michael , McCarthy Helen O. , Gonzalez-Fernandez Tomas 
Published: September 2024

AbstractCRISPR gene editing offers unprecedented genomic and transcriptomic control for precise regulation of cell function and phenotype. However, delivering the necessary CRISPR components to therapeutically relevant cell types without cytotoxicity or unexpected side effects remains challenging. Viral vectors risk genomic integration and immunogenicity while non-viral delivery systems are challenging to adapt to different CRISPR cargos, and many are highly cytotoxic. The arginine-alanine-leucine-alanine (RALA) cell penetrating peptide is an amphiphilic peptide that self-assembles into nanoparticles through electrostatic interactions with negatively charged molecules before delivering them across the cell membrane. This system has been used to deliver DNAs, RNAs, and small anionic molecules to primary cells with lower cytotoxicity compared to alternative non-viral approaches. Given the low cytotoxicity, versatility, and competitive transfection rates of RALA, we aimed to establish this peptide as a new CRISPR delivery system in a wide range of molecular formats across different editing modalities. We report that RALA was able to effectively encapsulate and deliver CRISPR in DNA, RNA, and ribonucleic protein (RNP) formats to primary mesenchymal stem cells (MSCs). Comparisons between RALA and commercially available reagents revealed superior cell viability leading to higher numbers of transfected cells and the maintenance of cell proliferative capacity. We then used the RALA peptide for the knock-in and knock-out of reporter genes into the MSC genome as well as for the transcriptional activation of therapeutically relevant genes. In summary, we establish RALA as a powerful tool for safer and effective delivery of CRISPR machinery in multiple cargo formats for a wide range of gene editing strategies.
The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles
Authors: Straub Verena M. , Barti Benjamin , Tandar Sebastian T. , Stevens A. Floor , van der Wel Tom , Zhu Na , Rüegger Joel , van der Horst Cas , Heitman Laura H. , Li Yulong , Stella Nephi , van Hasselt J. G. Coen , Katona István , van der Stelt Mario 
Published: September 2024

AbstractWhile it is known that endocannabinoids (eCB) modulate multiple neuronal functions, the molecular mechanism governing their release and transport remains elusive. Here, we propose an “on-demand release” model, wherein the formation of microvesicles, a specific group of extracellular vesicles (EVs) containing the eCB, 2-arachidonoylglycerol (2-AG), is the rate-limiting step. A co-culture model system that combines a reporter cell line expressing the fluorescent eCB sensor, GRABeCB2.0, and neuronal cells revealed that neurons release EVs containing 2-AG, but not anandamide, in a stimulus-dependent process regulated by PKC, DAGL, Arf6, and which was sensitive to inhibitors of eCB facilitated diffusion. A vesicle contained approximately 2000 2-AG molecules. Accordingly, hippocampal eCB-mediated synaptic plasticity was modulated by Arf6 and transport inhibitors. This “on demand release” model, supported by mathematical analysis, offers a cohesive framework for understanding eCB signaling at the molecular level and suggests that microvesicles carrying signaling lipids regulate neuronal functions in parallel to canonical synaptic vesicles.
Cytotoxicity of Activator Expression in CRISPR-based Transcriptional Activation Systems
Authors: Maddineni Aakaanksha , Liang Ziyan , Jambardi Shreya , Roy Subrata , Tycko Josh , Patil Ajinkya , Manzano Mark , Gottwein Eva 
Published: September 2024

AbstractCRISPR-based transcriptional activation (CRISPRa) has extensive research and clinical potential. Here, we show that commonly used CRISPRa systems can exhibit pronounced cytotoxicity. We demonstrate the toxicity of published and new CRISPRa vectors expressing the activation domains (ADs) of the transcription factors p65 and HSF1, components of the synergistic activation mediator (SAM) CRISPRa system. Based on our findings for the SAM system, we extended our studies to additional ADs and the p300 acetyltransferase core domain. We show that the expression of potent transcriptional activators in lentiviral producer cells leads to low lentiviral titers, while their expression in the transduced target cells leads to cell death. Using inducible lentiviral vectors, we could not identify an activator expression window for effective SAM-based CRISPRa without measurable toxicity. The toxicity of current SAM-based CRISPRa systems hinders their wide adoption in biomedical research and introduces selection bottlenecks that may confound genetic screens. Our results suggest that the further development of CRISPRa technology should consider both the efficiency of gene activation and activator toxicity.