bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red knots in Europe - a dead end host species or a new niche for highly pathogenic avian influenza?
Authors: King Jacqueline , Pohlmann Anne , Bange Andreas , Horn Elisabeth , Hälterlein Bernd , Breithaupt Angele , Globig Anja , Günther Anne , Kelm Angie , Wiedemann Christian , Grund Christian , Haecker Karena , Garthe Stefan , Harder Timm , Beer Martin , Schwemmer Philipp 
Published: May 2024

AbstractThe 2020/2021 epidemic in Europe of highly pathogenic avian influenza virus (HPAIV) of subtype H5 surpassed all previously recorded European outbreaks in size, genotype constellations and reassortment frequency and continued into 2022 and 2023. The causative 2.3.4.4b viral lineage proved to be highly proficient with respect to reassortment with cocirculating low pathogenic AIV and seems to establish an endemic status in northern Europe. A specific HPAIV reassortant of the subtype H5N3 was detected almost exclusively in red knots (Calidris canutus islandica)in December 2020. It caused systemic and rapidly fatal disease leading to a singular and self-limiting mass mortality affecting about 3.500 birds in the German Wadden Sea, roughly 1% of the entire flyway population ofislandicared knots. Phylogenetic analyses revealed that the H5N3 reassortant very likely had formed in red knots and remained confined to this species. While mechanisms of virus circulation in potential reservoir species, dynamics of spill-over and reassortment events and the roles of environmental virus sources remain to be identified, the year-round infection pressure poses severe threats to endangered avian species, and prompts adaptation of habitat and species conservation practices.One-Sentence SummaryHigh red knot mortality in Europe (December 2020) was associated with infection of a unique genotype of HPAIV H5N3 clade 2.3.4.4b.
Cellular and molecular characterization of peripheral glia in the lung and other organs
Authors: Hall Shaina , Liu Shixuan , Liang Irene , Schulz Shawn , Ezran Camille , Tan Mingqian , Kuo Christin S. 
Published: May 2024

ABSTRACTPeripheral glia are important regulators of diverse physiologic functions yet their molecular distinctions and locations in almost all visceral organs are not well-understood. We performed a systematic analysis of peripheral glia, focusing on the lung and leveraging single cell RNA sequencing (scRNA-seq) analysis to characterize their cellular and molecular features. Using in vivo lineage studies, we characterized the anatomic, cellular, and molecular features of theSox10+glial lineage of the mouse lung. Using high-resolution imaging, we quantified the distribution and cellular morphologies of myelinating, non-myelinating, satellite, and terminal glial cells with their intricate extensions along peripheral nerves, including terminals at specialized neurosensory structures within the lung. Spatial analysis of selectively expressed myelinating (periaxin/Prx, claudin 19/Cldn) or non-myelinating (sodium channel/Scn7a) glial cell genes identified by scRNA-seq analysis revealed molecularly distinct populations surrounding myelinated nerve fibers in the lung. To extend this analysis to primates and other organs, we extracted rare peripheral glial cells in whole organism scRNA-seq atlases of mouse lemur and human. Our cross-species data analysis and integration of scRNA-seq data of ∼700 peripheral glial cells from mouse, mouse lemur, and human glial cells identified conserved gene expression of molecularly distinct peripheral glial cell populations. This foundational knowledge facilitates subsequent functional studies targeting molecularly distinct subsets of peripheral glia and integrating them into organ-specific disorders of autonomic dysregulation. In addition, our cross-species analysis identifying conserved gene expression patterns and glial networks in extrapulmonary organs provides a valuable resource for studying the functional role of peripheral glia in multiorgan human diseases.
“Rapid SARS-CoV-2 Detection Using High-Sensitivity Thickness Shear Mode Sensors”
Authors: Saleh Sahera , Alkalamouni Habib , Antar Karen , Karam Pierre , Muthuswamy Jit , Zaraket Hassan , Khraiche Massoud L 
Published: May 2024

AbstractThe COVID-19 pandemic, caused by the SARS-CoV-2 virus, has emphasized the urgent need for accurate and readily available diagnostic tools. Conventional diagnostic methods, such as reverse transcription real-time polymerase chain reaction (RT-qPCR), are often labor-intensive and time-consuming, which highlights the necessity for rapid point-of-care diagnostic solutions. This study introduces an innovative, low-cost, and highly sensitive diagnostic platform for swift COVID-19 detection. Our platform utilizes the mass sensing properties of thickness shear mode (TSM) transducers to detect and quantify the SARS-CoV-2 nucleocapsid protein through polyethylene glycol (PEG)-based chemistry (1). To confirm surface functionalization and evaluate the effects of the virus lysis buffer, we employed surface characterization techniques including Digital Holographic Microscopy (DHM), Scanning Electron Microscopy (SEM) with Energy-Dispersive X-ray spectroscopy (EDX), and Raman spectroscopy. Sensitivity tests with heat-inactivated SARS-CoV-2 samples demonstrated a sensitivity of about 0.256 Hz/TCID50/mL and a limit of detection (LOD) of roughly 150 TCID50/mL. Specificity was verified through cross-reactivity testing. Our detailed characterization and sensitivity analysis underscore the platform’s reliability, making it a promising candidate for efficient and accessible COVID-19 diagnosis at the point of care.
CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of the maternal-to-zygotic transition in teleosts
Authors: Hernandez-Huertas Luis , Moreno-Sanchez Ismael , Crespo-Cuadrado Jesús , Vargas-Baco Ana , da Silva Pescador Gabriel , Santos-Pereira José M. , Bazzini Ariel A. , Moreno-Mateos Miguel A. 
Published: May 2024

SummaryThe Maternal-to-Zygotic transition (MZT) is a reprograming process encompassing zygotic genome activation (ZGA) and the clearance of maternally-provided mRNAs. While some factors regulating MZT have been identified, there are thousands of maternal RNAs whose function has not been ascribed yet. Here, we have performed a proof-of-principle CRISPR-RfxCas13d maternal screening targeting mRNAs encoding protein kinases and phosphatases in zebrafish and identified Bckdk as a novel post-translational regulator of MZT.BckdkmRNA knockdown caused epiboly defects, ZGA deregulation, H3K27ac reduction and a partial impairment of miR-430 processing. Phospho-proteomic analysis revealed that Phf10/Baf45a, a chromatin remodeling factor, is less phosphorylated upon Bckdk depletion. Further,phf10mRNA knockdown also altered ZGA and Phf10 constitutively phosphorylated rescued the developmental defects observed afterbckdkmRNA depletion. Altogether, our results demonstrate the competence of CRISPR-RfxCas13d screenings to uncover new regulators of early vertebrate development and shed light on the post-translational control of MZT mediated by protein phosphorylation.
Biochemical reconstitution of a major age-related cancer mutational signature by heat-induced spontaneous deamination of 5-methylcytosine residues, repair of uracil residues, and DNA replication
Authors: Sugiyama Tomohiko 
Published: May 2024

AbstractNon-enzymatic spontaneous deamination of 5-methylcytosine, producing thymine, is the proposed etiology of cancer mutational signature 1, which is the most predominant signature in all cancers. Here, the proposed mutational process was reconstituted using synthetic DNA and purified proteins. First, single-stranded DNA containing 5-methylcytosine at CpG context was incubated at an elevated temperature to accelerate spontaneous DNA damage. Then, the DNA was treated with uracil DNA glycosylase to remove uracil residues that were formed by deamination of cytosine. The resulting DNA was then used as a template for DNA synthesis by yeast DNA polymerase δ. The DNA products were analyzed by next-generation DNA sequencing, and mutation frequencies were quantified. The observed mutations after this process were exclusively C>T mutations at CpG context, which was very similar to signature 1. When 5-methylcytosine modification and uracil DNA glycosylase were both omitted, C>T mutations were produced on C residues in all sequence contexts, but these mutations were diminished by uracil DNA glycosylase-treatment. These results indicate that the CpG>TpG mutations were produced by the deamination of 5-methylcytosine. Additional mutations, mainly C>G, were introduced by yeast DNA polymerase ζ on the heat-damaged DNA, indicating that G residues of the templates were also damaged. However, the damage on G residues was not converted to mutations with DNA polymerase δ or ε. These results provide biochemical evidence to support that the majority of mutations in cancers are produced by ordinary DNA replication on spontaneously damaged DNA.
Loss of a conserved C-terminal region of theAspergillus fumigatusAtrR transcriptional regulator leads to a gene-specific defect in target gene expression
Authors: Ror Shivani , Stamnes Mark A. , Moye-Rowley W. Scott 
Published: May 2024

AbstractTreatment of fungal infections associated with the filamentous fungusAspergillus fumigatusis becoming more problematic as this organism is developing resistance to the main chemotherapeutic drug at an increasing rate. Azole drugs represent the current standard-of-care in treatment of aspergillosis with this drug class acting by inhibiting a key step in biosynthesis of the fungal sterol ergosterol. Azole compounds block the activity of the lanosterol α-14 demethylase, encoded by thecyp51Agene. A common route of azole resistance involves an increase in transcription ofcyp51A. This transcriptional increase requires the function of a Zn2Cys6 DNA-binding domain-containing transcription activator protein called AtrR. AtrR was identified through its action as a positive regulator of expression of an ATP-binding cassette transporter (abcC/cdr1Bhere calledabcG1). Using both deletion and alanine scanning mutagenesis, we demonstrate that a conserved C-terminal domain inA. fumigatusis required for expression ofabcG1but dispensable forcyp51Atranscription. This domain is also found in several other fungal pathogen AtrR homologues consistent with a conserved gene-selective function of this protein segment being conserved. Using RNA-seq, we find that this gene-specific transcriptional defect extends to several other membrane transporter-encoding genes including a second ABC transporter locus. Our data reveal that AtrR uses at least two distinct mechanisms to induce gene expression and that normal susceptibility to azole drugs cannot be provided by maintenance of wild-type expression of the ergosterol biosynthetic pathway when ABC transporter expression is reduced.ImportanceAspergillus fumigatusis the primary human filamentous fungal pathogen. The principal chemotherapeutic drug used to control infections associated withA. fumigatusare the azole compounds. These drugs are well-tolerated and effective but resistance is emerging at an alarming rate. Most resistance is associated with mutations that lead to overexpression of the azole target enzyme, lanosterol α-14 demethylase, encoded by thecyp51Agene. A key regulator ofcyp51Agene expression is the transcription factor AtrR. Very little is known of the molecular mechanisms underlying the effect of AtrR on gene expression. Here we use deletion and clustered amino acid substitution mutagenesis to map a region of AtrR that confers gene-specific activation on target genes of this transcription factor. This region is highly conserved across AtrR homologues from other pathogenic species arguing that its importance in transcriptional regulation is maintained across evolution.
Survival benefit of adjuvant therapy following neoadjuvant therapy in patients with resected esophageal cancer: a retrospective cohort study
Authors: Jia Weiyi , Li Chao , Liu Can , Hu Renwang 
Published: May 2024

AbstractBackgroundThere is controversy about the benefit of administering adjuvant therapy to esophageal cancer (EC) patients after preoperative neoadjuvant therapy and surgical treatment. This study aims to investigate the impact of postoperative adjuvant therapy in EC patients with neoadjuvant therapy and surgery.Materials and methodsThe study included EC patients diagnosed from 2007 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients who received neoadjuvant therapy (NCRT) were defined as those who underwent neoadjuvant chemotherapy or neoadjuvant radiotherapy before surgery, while patients who received adjuvant therapy (ACRT) were defined as those who underwent adjuvant chemotherapy or adjuvant radiotherapy after surgery. Propensity score matching (PSM) method was employed to establish matched cohorts, and Kaplan-Meier analysis, COX regression model, and Fine-Gray model were used for survival analysis.ResultsThe study included a total of 5805 EC patients, with 837 (14.4%) in the ACRT group and 4968 (85.4%) in the no-ACRT group. After PSM, a cohort of 1660 patients who received NCRT was enrolled for analysis, with 830 patients in each group. Kaplan-Meier analysis revealed no significant differences between the two groups in terms of median overall survival (OS) (34.0 vs. 36.0 months, P = 0.89) or cancer-specific survival (CSS) (40.0 vs. 49.0 months, P = 0.16). Multivariate Cox models and Fine-Gray models indicated that ACRT was not a predictive factor for OS or CSS (P > 0.05). Subgroup analysis for CSS suggested a protective effect of ACRT in the N2 (Cox model: HR = 0.640, P = 0.090; Fine-Gray model: HR = 0.636, P = 0.081) and the N3 subgroup (Cox model: HR = 0.302, P = 0.018; Fine-Gray model: HR = 0.306, P = 0.034).ConclusionsOnly for esophageal cancer patients with a more advanced N stage, postoperative adjuvant therapy after completing neoadjuvant therapy and curative surgical treatment may be beneficial.
Stakeholder’s perspective on Brain-Computer Interfaces for children and adolescents with quadriplegic cerebral palsy
Authors: Branco M.P. , Verberne M.S.W. , van Balen B.J. , Bekius A. , Leinders S. , Ketelaar M. , Geytenbeek J. , van Driel-Boerrigter M. , Willems-op het Veld M. , Rabbie-Baauw K. , Vansteensel M.J. 
Published: May 2024

AbstractCommunication Brain-Computer Interfaces (cBCIs) use neural signals to control a computer and are of interest as a communication tool for people with motor and speech impairment. Whereas the majority of cBCI research focuses on adults, the technology may also benefit children and adolescents with communication impairments, for example as a result of cerebral palsy (CP). Here we aimed to create a solid basis for the user centered design of cBCIs for children and adolescents with CP and complex communication needs by investigating the perspectives of their parents/caregivers and health care professionals on communication and cBCIs. We conducted an online survey on 1) current communication problems and usability of used aids, 2) interest in cBCIs, and 3) preference for specific types of cBCIs. A total of 19 parents/caregivers and 36 health care professionals who live(d) or work(ed) directly with children and adolescents (8-25 years old) with quadriplegic CP participated. Both groups of respondents indicated that, of 12 potential communication-limiting factors, motor impairment occurred the most frequently and also had the greatest impact on communication. The currently used communication aids included mainly no/low- tech aids (e.g., letter card) and high-tech aids (e.g., tablet or computer). Mid-tech aids (e.g., systems with static displays) were less frequently used. The majority of health care professionals and parents/caregivers reported an interest in cBCIs for children and adolescents with severe CP, with a slight preference for implanted electrodes over non-implanted ones, and no preference for either of the two proposed mental BCI control strategies (visual stimuli and imagined/attempted movement). These results indicate that cBCIs should be considered for a subpopulation of children and adolescents with severe CP, and that in the development of cBCIs for this group both P300 and sensorimotor rhythms, as well as the use of implanted electrodes, should be considered.
QRS prolongation is associated with structural remodeling in hypertrophic cardiomyopathy
Authors: Vera-Sarmiento Hernan L. , Tanriverdi Talha , Hurtado-de-Mendoza David , Sivalokanathan Sanjay , Ketty Dolores , Lu Daiyin , Zimmerman Stefan , Sinha Sunil , Scheinman Melvin , Abraham M. Roselle 
Published: May 2024

ABSTRACTBackgroundSignal-averaged electrocardiogram (SAECG) records myocardial depolarization, and can detect inhomogeneous/slow conduction in fibrotic myocardium, which promotes reentrant ventricular arrhythmias (VAs). Hypertrophic cardiomyopathy (HCM) is associated with a high prevalence of cardiac fibrosis and VAs, but abnormal SAECG has low predictive power for VAs. We hypothesized that HCM-specific structural/electrical remodeling underlies this result.MethodsWe tested our hypothesis by retrospectively studying HCM patients (n=73) who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG and 12-lead ECG. Patients were divided into 2 groups (normal-SAECG, abnormal-SAECG) based on filtered-QRS duration (fQRSd), root-mean-square-voltage (RMS40) and low-amplitude (<40μV) signal of terminal 40ms of filtered-QRS (late potentials). Abnormal SAECG was defined asfQRSd>114ms, RMS40<20μVorLAS40>38ms.ResultsAbnormal SAECG was seen in ∼50% of HCM patients (37/73). In the abnormal-SAECG group, 78% (n=29) only had prolongedfQRSd, and 22% (n=8) had prolongedfQRSd plus late potentials (RMS40<20μVorLAS40>38ms). MeanfQRSd andLAS40were significantly higher in the abnormal-SAECG group. The abnormal-SAECG group had significantly larger LA size, lower global-LV longitudinal systolic strain/strain rate and early-diastolic strain rate by TTE; higher LV-mass index (LVMI) and LV-scar burden by CMR; higher prevalence of repolarization abnormalities on 12-lead ECG. LVEF and adverse outcomes (VT/VF, heart failure, death) were similar in the 2 groups. Univariate analysis showed thatfQRSd is positively correlated with LVMI, LV-scar mass, and negatively correlated with global-LV early diastolic strain rate.ConclusionsIn HCM, abnormal SAECG is associated with greater structural/electrical LV-remodeling, reflecting a severe global myopathy.
Human neural dynamics of real-world and imagined navigation
Authors: Seeber Martin , Stangl Matthias , Vallejo Mauricio , Topalovic Uros , Hiller Sonja , Halpern Casey H. , Langevin Jean-Philippe , Rao Vikram R. , Fried Itzhak , Eliashiv Dawn , Suthana Nanthia 
Published: May 2024

SummaryThe ability to form episodic memories and later imagine them is integral to the human experience, influencing our recollection of the past and our ability to envision the future. While research on spatial navigation in rodents suggests the involvement of the medial temporal lobe (MTL), especially the hippocampus, in these cognitive functions, it is uncertain if these insights apply to the human MTL, especially regarding imagination and the reliving of events. Importantly, by involving human participants, imaginations can be explicitly instructed and their mental experiences verbally reported. In this study, we investigated the role of hippocampal theta oscillations in both real-world and imagined navigation, leveraging motion capture and intracranial electroencephalographic recordings from individuals with chronically implanted MTL electrodes who could move freely. Our results revealed intermittent theta dynamics, particularly within the hippocampus, which encoded spatial geometry and partitioned navigational routes into linear segments during real-world navigation. During imagined navigation, theta dynamics exhibited similar, repetitive patterns despite the absence of external environmental cues. Furthermore, a computational model, generalizing from real-world to imagined navigation, successfully reconstructed participants’ imagined positions using neural data. These findings offer unique insights into the neural mechanisms underlying human navigation and imagination, with implications for understanding episodic memory formation and retrieval in real-world settings.
Pseudomonas fluorescens 15small RNA Pfs1 mediates transgenerational epigenetic inheritance of pathogen avoidance inC. elegansthrough the Ephrin receptor VAB-1
Authors: Seto Renee , Brown Rachel , Kaletsky Rachel , Parsons Lance R. , Moore Rebecca S. , Murphy Coleen T. 
Published: May 2024

AbstractC. elegansare exposed to a variety of pathogenic and non-pathogenic bacteria species in their natural environment. Correspondingly,C. eleganshas evolved an ability to discern between nutritive and infectious bacterial food sources. Here we show thatC. eleganscan learn to avoid the pathogenic bacteriaPseudomonas fluorescens 15(PF15), and that this learned avoidance behavior is passed on to progeny for four generations, as we previously demonstrated forPseudomonas aeruginosa(PA14) andPseudomonas vranovensis, using similar mechanisms, including the involvement of both the TGF-β ligand DAF-7 andCer1retrotransposon-encoded virus-like particles. PF15 small RNAs are both necessary and sufficient to induce this transgenerational avoidance behavior. Unlike PA14 orP. vranovensis, PF15 does not use P11, Pv1, or a small RNA withmaco-1homology for this avoidance; instead, an unrelated PF15 small RNA, Pfs1, that targets theC. elegans vab-1Ephrin receptor gene is necessary and sufficient for learned avoidance, suggesting the evolution of yet another bacterial sRNA/C. elegansgene target pair involved in transgenerational inheritance of pathogen avoidance. As VAB-2 Ephrin receptor ligand and MACO-1 knockdown also induce PF15 avoidance, we have begun to understand the genetic pathway involved in small RNA targeted pathogenic avoidance. Moreover, these data show that axon guidance pathway genes (VAB-1 and VAB-2) have previously unknown adult roles in regulating neuronal function.C. elegansmay have evolved multiple bacterial specificity-encoded small RNA-dependent mechanisms to avoid different pathogenic bacteria species, thereby providing progeny with a survival advantage in a dynamic environment.
NMDA receptor activation drives early synapse formationin vivo
Authors: Leibold Noah S. , Higgs Nathalie F. , Kandler Steffen , Khan Adil , Donato Flavio , Andreae Laura C. 
Published: May 2024

AbstractThe rules governing neural circuit formation in mammalian central nervous systems are poorly understood. NMDA receptors are involved in synaptic plasticity mechanisms in mature neurons, but their contribution to circuit formation and dendritic maturation remains controversial. Using pharmacological and genetic interventions to disrupt NMDA receptor signaling in hippocampal CA1 pyramidal neuronsin vitroandin vivo, we identify an early critical window for a synapse-specific function in wiring Schaffer collateral connections and dendritic arborization. Throughin vivoimaging, we show that NMDA receptors are frequently activated during early development and elicit minute-long calcium transients, which immediately precede the emergence of filopodia. These results demonstrate that NMDA receptors drive synapto- and dendritogenesis during development, challenging the view that these processes are primarily mediated by molecular cues.