bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of amphibian genomes: an emerging resource for basic and applied research
Authors: Kosch Tiffany A. , Crawford Andrew J. , Mueller Rachel Lockridge , Wollenberg Valero Katharina C. , Power Megan L. , Rodríguez Ariel , O’Connell Lauren A. , Young Neil D. , Skerratt Lee F. 
Published: March 2023

ABSTRACTAmphibians are the most threatened group of vertebrates and are in dire need of conservation intervention to ensure their continued survival. They exhibit unique features including a high diversity of reproductive strategies, permeable and specialized skin capable of producing toxins and antimicrobial compounds, multiple genetic mechanisms of sex determination, and in some lineages, the ability to regenerate limbs and organs. Although genomics approaches would shed light on these unique traits and aid conservation, sequencing and assembly of amphibian genomes has lagged behind other taxa due to their comparatively large genome sizes. Fortunately, the development of long-read sequencing technologies and initiatives has led to a recent burst of new amphibian genome assemblies. Although growing, the field of amphibian genomics suffers from the lack of annotation resources, tools for working with challenging genomes, and lack of high-quality assemblies in multiple clades of amphibians. Here we analyze 51 publicly available amphibian genomes to evaluate their usefulness for functional genomics research. We report considerable variation in genome assembly quality and completeness, and report some of the highest transposable element and repeat contents of any vertebrate. Additionally, we detected an association between transposable element content and climatic variables. Our analysis provides evidence of conserved genome synteny despite the long divergence times of this group, but we also highlight inconsistencies in chromosome naming and orientation across genome assemblies. We discuss sequencing gaps in the phylogeny and suggest key targets for future sequencing endeavors. Finally, we propose increased investment in amphibian genomics research to promote their conservation.
A distinct class of pan-cancer susceptibility genes revealed by alternative polyadenylation transcriptome-wide association study
Authors: Chen Hui , Wang Zeyang , Wang Jia , Chen Wenyan , Ma Xuelian , Zou Xudong , Plass Mireya , Lian Cheng , Ni Ting , Wei Gong-Hong , Li Wei , Deng Lin , Li Lei 
Published: March 2023

AbstractAlternative polyadenylation (APA) plays an important role in cancer initiation and progression; however, current genome- and transcriptome-wide association studies (GWAS and TWAS, respectively) mostly ignore APA when identifying putative cancer susceptibility genes. Here, we performed a pan-cancer 3′untranslated region (UTR) APA TWAS (3′aTWAS) by integrating 80 well-powered (n>50,000) GWAS datasets across 23 major cancer types with APA quantification from 17,330 RNA sequencing samples across 49 tissue types and 949 individuals. We found that genetic variants associated with APA represent around 24.4% of cancer GWAS variants and are more likely to be causal variants explaining a large portion of cancer heritability. We further identified 413 significant APA-linked cancer susceptibility genes. Of these, 77.4% have been overlooked by traditional expression- and splicing-studies, given that APA may regulate translation, protein localization, and protein–protein interactions independent of the expression level of the genes or splicing isoforms. As proof of principle validation, modulation of four novel APA-linked breast-cancer susceptibility genes significantly altered cancer cell proliferation. Our study highlights the significant role of APA in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.
A unique symbiosome in an anaerobic single-celled eukaryote
Authors: Jerlström-Hultqvist Jon , Gallot-Lavallée Lucie , Salas-Leiva Dayana E. , Curtis Bruce A. , Záhonová Kristína , Čepička Ivan , Stairs Courtney W. , Pipaliya Shweta , Dacks Joel B. , Archibald John M. , Roger Andrew J. 
Published: March 2023

AbstractSymbiotic relationships drive evolutionary change and are important sources of novelty. Here we demonstrate a highly structured syntrophic symbiosis between species of the anaerobic protistAnaeramoeba(Anaeramoebae, Metamonada) and bacterial ectosymbionts. We dissected this symbiosis with long-read metagenomics, transcriptomics of host and symbiont cells coupled with fluorescent in situ hybridization (FISH), and microscopy. Genome sequencing, phylogenomic analyses and FISH show that the symbionts belong to theDesulfobacteraceaeand were acquired independently in two differentAnaeramoebaspecies. We show that ectosymbionts likely reside deep within cell surface invaginations in a symbiosomal membrane network that is tightly associated with cytoplasmic hydrogenosomes. Metabolic reconstructions based on the genomes and transcriptomes of the symbionts suggest a highly evolved syntrophic interaction. Host hydrogenosomes likely produce hydrogen, acetate, and propionate that are consumed by the symbionts dissimilatory sulfate reduction, Wood-Ljungdahl and methylmalonyl pathways, respectively. Because the host genome sequences encode several vitamin B12-dependent enzymes but appear to lack the ability to biosynthesize this vitamin, we hypothesize that the symbionts supply their hosts with B12. We detected numerous lateral gene transfers from diverse bacteria toAnaeramoeba, including genes involved in oxygen defense and anaerobic metabolism. Gene families encoding membrane-trafficking components that regulate the phagosomal maturation machinery are notably expanded inAnaeramoebaspp. and may be involved in organizing and/or stabilizing the symbiosomal membrane system. Overall, the Anaeramoebae have evolved a dynamic symbiosome comprised of a vacuolar system that facilitates positioning and maintenance of sulfate-reducing bacterial ectosymbionts.
A role for retro-splenial cortex in the task-related P3 network
Authors: Das Diptyajit , Shaw Marnie E. , Hämäläinen Matti S. , Dykstra Andrew R. , Doll Laura , Gutschalk Alexander 
Published: March 2023

AbstractObjectiveThe P3 is an event-related response observed in relation to task-relevant sensory events. Despite its ubiquitous presence, the neural generators of the P3 are controversial and not well identified.MethodsWe compared source analysis of combined magneto- and electroencephalography (M/EEG) data with functional magnetic resonance imaging (fMRI) and simulation studies to better understand the sources of the P3 in an auditory oddball paradigm.ResultsOur results suggest that the dominant source of the classical, postero-central P3 lies in the retro-splenial cortex of the ventral cingulate gyrus. A second P3 source in the anterior insular cortex contributes little to the postero-central maximum. Multiple other sources in the auditory, somatosensory, and anterior midcingulate cortex are active in an overlapping time window but can be functionally dissociated based on their activation time courses.ConclusionThe retro-splenial cortex is a dominant source of the parietal P3 maximum in EEG.SignificanceThese results provide a new perspective for the interpretation of the extensive research based on the P3 response.
Delayed formation of neural representations of space in aged mice
Authors: McDermott Kelsey D. , Frechou M. Agustina , Jordan Jake T. , Martin Sunaina S. , Gonçalves J. Tiago 
Published: March 2023

AbstractAging is associated with cognitive deficits, with spatial memory being very susceptible to decline. The hippocampal dentate gyrus (DG) is important for processing spatial information in the brain and is particularly vulnerable to aging, yet its sparse activity has led to difficulties in assessing changes in this area. Usingin vivotwo-photon calcium imaging, we compared DG neuronal activity and representations of space in young and aged mice walking on an unfamiliar treadmill. We found that calcium activity was significantly higher and less tuned to location in aged mice, resulting in decreased spatial information encoded in the DG. However, with repeated exposure to the same treadmill, both spatial tuning and information levels in aged mice became similar to young mice, while activity remained elevated. Our results show that spatial representations of novel environments are impaired in the aged hippocampus and gradually improve with increased familiarity. Moreover, while the aged DG is hyperexcitable, this does not disrupt neural representations of familiar environments.
Continuous optical detection of small-molecule analytes in complex biomatrices
Authors: Hariri Amani A. , Cartwright Alyssa P. , Dory Constantin , Gidi Yasser , Yee Steven , Fu Kaiyu , Yang Kiyoul , Wu Diana , Thompson Ian A. P. , Maganzini Nicolò , Feagin Trevor , Young Brian E. , Afshar Behrad Habib , Eisenstein Michael , Digonnet Michel , Vuckovic Jelena , Soh H. Tom 
Published: March 2023

AbstractCurrent technology for measuring specific biomarkers – continuously in complex samples, without sample preparation – is limited to just handful of molecules such as glucose and blood oxygen. In this work, we present the first optical biosensor system that enables continuous detection of a wide range of biomarkers in complex samples, such as human plasma. Our system employs a modular duplex-bubble switch (DBS) architecture that converts aptamers into structure-switching fluorescence probes whose affinity and kinetics can be readily tuned. These DBS constructs are coupled to a fiber-optic detector that measures the fluorescence change only within an evanescent field, thereby minimizing the impact of background autofluorescence and enabling direct detection of analytes at physiologically relevant concentrations even in interferent-rich sample matrices. Using our system, we achieved continuous detection of dopamine in artificial cerebrospinal fluid for >24 hours with sub-second resolution and a limit of detection (LOD) of 1 µM. We subsequently demonstrated the system’s generalizability by configuring it to detect cortisol with nanomolar sensitivity in undiluted human plasma. Both sensors achieved LODs orders of magnitude lower than theKDof the DBS element, highlighting the potential to achieve sensitive detection even when using aptamers with modest affinity.
Inclusive pedagogy strategies to introduce high schoolers to systems biology
Authors: Watts Kelsey M , Richardson William 
Published: March 2023

AbstractWomen and non-white racial and ethnic groups remain underrepresented in science, technology, engineering, and math (STEM). To achieve a more diverse and equitable STEM workforce, the recruitment and retention of these historically marginalized communities in postsecondary education will also need to increase. Recently, the lens has turned to pedagogy and how creating a more inclusive classroom environment can foster STEM identity in previously marginalized communities. This work focuses on developing and piloting systems biology education modules designed to promote an inclusive learning environment in a summer outreach program for high school students by (1) utilizing a hybrid of unplugged activities with coded simulation and (2) a female-oriented problem statement. Based on initial findings in our pilot program, we anticipate that these techniques will enable students with limited prior computational experience to feel more comfortable and able to complete tasks, thereby increasing their self-efficacy and STEM identity. These modules could be a valuable tool for practitioners teaching high school or early college-level computational courses who instruct students with varied coding experience. Additionally, our analysis of the use of a female-oriented problem statement on female-identifying students’ self-efficacy provides potential evidence of the usefulness of representative problem statements in engaging underrepresented student populations. We believe these techniques could be adapted to address a variety of contexts across STEM disciplines and other fields to foster inclusive learning environments.
Human Cytomegalovirus Induces Significant Structural and Functional Changes in Terminally Differentiated Human Cortical Neurons
Authors: Adelman Jacob W. , Rosas-Rogers Suzette , Schumacher Megan L. , Mokry Rebekah L. , Terhune Scott S. , Ebert Allison D. 
Published: March 2023

ABSTRACTHuman cytomegalovirus (HCMV) is a highly prevalent viral pathogen that typically presents asymptomatically in healthy individuals despite lifelong latency. However, in 10-15% of congenital cases, this beta-herpesvirus demonstrates direct effects on the central nervous system, including microcephaly, cognitive/learning delays, and hearing deficits. HCMV has been widely shown to infect neural progenitor cells, but the permissiveness of fully differentiated neurons to HCMV is controversial and chronically understudied, despite potential associations between HCMV infection with neurodegenerative conditions. Using a model system representative of the human forebrain, we demonstrate that induced pluripotent stem cell (iPSC)-derived, excitatory glutamatergic and inhibitory GABAergic neurons are fully permissive to HCMV, demonstrating complete viral replication, competent virion production, and spread within the culture. Interestingly, while cell proliferation was not induced in these post-mitotic neurons, HCMV did increase expression of proliferative markers Ki67 and PCNA suggesting alterations in cell cycle machinery. These finding are consistent with previous HCMV-mediated changes in various cell types and implicate the virus’ ability to alter proliferative pathways to promote virion production. HCMV also induces significant structural changes in forebrain neurons, such as the formation of syncytia and retraction of neurites. Finally, we demonstrate that HCMV disrupts calcium signaling and decreases neurotransmission, with action potential generation effectively silenced after 15 days post infection. Taken together, our data highlight the potential for forebrain neurons to be permissive to HCMV infection in the CNS, which could have significant implications on overall brain health and function.
Detection of Subclinical Pulmonary Edema After Acute ST-segment Elevation Myocardial Infarction Without Heart Failure by Chest Computed Tomography
Authors: Hua Minghui , Liang Rong , Gao Yufan , Cui Keyi , Liu Yanzhen , Liang Shuo , Li Ximing , Zhang Hong 
Published: March 2023

ABSTRACTBACKGROUNDPulmonary edema is a severe complication in patients with acute myocardial infarction which indicates the development of heart failure (HF) and poor prognosis. However, subclinical pulmonary edema after acute ST-segment elevation myocardial infarction (STEMI) without HF has not received enough attention in clinical practice. We aimed to investigate the prognostic value and associated clinical characteristics of subclinical pulmonary edema after acute STEMI without HF detected by chest computed tomography (CT).METHODSA total of 276 patients with acute STEMI without HF who underwent chest CT were included in this study. K-means clustering analysis was performed to classify the patients into different subgroups based on the mean lung density. Clinical characteristics of the different subgroups were compared and used to establish a machine learning model for discriminating between them. Relative risk (RR) for major adverse cardiovascular events (MACEs) during hospitalization was compared between the subgroups.RESULTSThe patients were classified into two subgroups. Subgroup 2 showed higher mean lung density than subgroup 1 (median [IQR], −727 [−747, −704] vs. −806 [−826, −785] HU, P < 0.001), with significantly higher levels of cardiac enzymes and numbers of inflammatory cells and significantly worse left ventricular function than subgroup 1. In the model analysis, the most important clinical characteristics were the levels of cardiac enzymes, numbers of inflammatory cells, and left ventricular function. The risk for MACEs was higher in subgroup 2 than in subgroup 1 (RR, 2.12; P = 0.002).CONCLUSIONSSubclinical pulmonary edema after acute STEMI without HF was mainly associated with elevated levels of cardiac enzymes, followed by increased numbers of inflammatory cells and worse left ventricular function. In addition, subclinical pulmonary edema provided crucial prognostic information for patients during hospitalization.
Cell-free quorum sensing to drive feedback and communication within populations of droplet interface bilayers
Authors: Gonzales David T. , Suraritdechachai Surased , Zechner Christoph , Tang T-Y Dora 
Published: March 2023

AbstractBuilding synthetic multicellular systems using non-living molecular components is a grand challenge in the field of bottom-up synthetic biology. Towards this goal, a diverse range of chemistries have been developed to provide mechanisms of intercellular communication and methods to assemble multicellular compartments. However, building bottom-up synthetic multicellular systems is still challenging because it requires the integration of intercellular reaction networks with compatible cellular compartment properties. In this study, we encapsulated cell-free expression systems (CFES) expressing two quorum sensing genetic circuits into droplet interface bilayer (DIB) synthetic cells to demonstrate intercellular communication and feedback. We further develop a method of generating custom DIB multicellular structures by acoustic liquid handling to automatically dispense the CFES droplets and show the potential for multiplexing compartmentalized gene circuits for generating heterogeneous populations of cells. Our work provides a step towards building more complex multicellular systems with feedback mechanisms from the bottom-up to study and experimentally model biological multiscalar processes.
Bibliometric analysis on cannibalism/infanticide and maternal aggression towards pups in laboratory animals
Authors: Bravo José C. , Ugartemendia Lierni , Barman Arko , Rodríguez Ana B. , Pariente José A. , Bravo Rafael 
Published: March 2023

ABSTRACTAnimal welfare has evolved during the past decades to improve not only the quality of life of laboratory animals but also the quality and reproducibility of scientific investigations. Bibliometric analysis has become an important tool to complete the current knowledge with academic databases. Our objective was to investigate whether scientific research on cannibalism/infanticide is connected with maternal aggression towards the offspring in laboratory animals. To carry out our research, we performed a specific search for published articles on each concept. Results were analyzed in the opensource environment RStudio with the package Bibliometrix. We obtained 228 and 134 articles for the first search (cannibalism/infanticide) and the second search (maternal aggression towards the pups) respectively. We observed that the interest in infanticide cannibalism started in the 1950s, while researchers started showing interest in maternal aggression towards the pups 30 years later. Our analyses indicated that maternal aggression had better citations in scientific literature. In addition, although our results showed some common features (e.g., oxytocin or medial preoptic area in the brain), we observed a gap between cannibalism/infanticide and maternal aggression towards the pups with only 18 published articles in common for both the searches. Therefore, we recommend researchers to combine both concepts in further investigations in the context of cannibalism for better dissemination and higher impact in laboratory animals’ welfare research.Highlights- Cannibalism/Infanticide and maternal aggression have been investigated separately.- Maternal aggression has a higher impact on scientific literature.- Combining both topics may increase cannibalism/infanticide impact.
Combining experiments and simulations to examine the temperature-dependent behaviour of a disordered protein
Authors: Pesce Francesco , Lindorff-Larsen Kresten 
Published: March 2023

AbstractIntrinsically disordered proteins are a class of proteins that lack stable folded conformations and instead adopt a range of conformations that determine their biochemical functions. The temperature-dependent behaviour of such disordered proteins is complex and can vary depending on the specific protein and environment. Here, we have used molecular dynamics simulations and previously published experimental data to investigate the temperature-dependent behaviour of Histatin 5, a 24-residue-long polypeptide. We examined the hypothesis that Histatin 5 undergoes a loss of polyproline II structure with increasing temperature, leading to more compact conformations. We found that the conformational ensembles generated by the simulations generally agree with small-angle X-ray scattering data for Histatin 5, but show some discrepancies with the hydrodynamic radius as probed by pulsed-field gradient nuclear magnetic resonance spectroscopy, and with the secondary structure information derived from circular dichroism. We attempted to reconcile these differences by reweighting the conformational ensembles against the scattering and NMR data. By doing so, we were in part able to capture the temperature-dependent behaviour of Histatin 5 and to link the observed decrease in hydrodynamic radius with increasing temperature to a loss of polyproline II structure. We were, however, unable to achieve agreement with both the scattering and NMR data within experimental errors. We discuss different possibilities for this outcome including inaccuracies in the force field, differences in conditions of the NMR and scattering experiments, and issues related to the calculation of the hydrodynamic radius from conformational ensembles. Our study highlights the importance of integrating multiple types of experimental data when modelling conformational ensembles of disordered proteins and how environmental factors such as the temperature influence them.
Using double cutin vitroassembled CRISPR/Cas9 to modify the genome ofCoccidioides posadasii
Authors: Mead Heather L. , Kollath Daniel R. , Itogawa Ashley N. , Blackmon Austin V. , Morales Matthew M. , Bryant Mitchell L. , de Melo Teixeira Marcus , Barker Bridget M. 
Published: March 2023

ABSTRACTAlthough the genusCoccidioidesis divided into two closely related and putatively allopatric species, analysis shows that hybridization has occurred between species and at least oneC. posadasiiconserved fragment has introgressed into severalC. immitisgenomes in a population-specific manner. Transcript abundancein vitroandin vivofor ten ORFs in this introgressed region were measured for several isolates. We used signals of introgression and high mRNA transcript levels in the spherule as indicators of selection for genes related to critical biological processes involved inCoccidioidespathogenesis. The only transcript in the introgression region with significant expression was a gene that encodes for a betadefensin-like (DEFBL) peptide rich in serines and cysteines. Few virulence factors have been identified inCoccidioides, and we employed the CRISPR-Cas9 mediated gene deletion tool to delete this gene inCoccidioides.