bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserving a threatened North American walnut: a chromosome-scale reference genome for butternut (Juglans cinerea)
Authors: Guzman-Torres Cristopher R. , Trybulec Emily , LeVasseur Hannah , Akella Harshita , Amee Maurice , Strickland Emily , Pauloski Nicole , Williams Martin , Romero-Severson Jeanne , Hoban Sean , Woeste Keith , Pike Carolyn C. , Fetter Karl C. , Webster Cynthia N. , Neitzey Michelle L. , O’Neill Rachel J. , Wegrzyn Jill L. 
Published: May 2023

AbstractWith the advent of affordable and more accurate third generation sequencing technologies and the associated bioinformatic tools, it is now possible to sequence, assemble, and annotate more species of conservation concern than ever before.Juglans cinerea, commonly known as butternut or white walnut, is a member of the walnut family, native to the Eastern United States and Southeastern Canada. The species is currently listed as Endangered on the IUCN Red List due to decline from an invasive fungus known asOphiognomonia clavigignenti-juglandacearum(Oc-j) that causes butternut canker. Oc-j creates visible sores on the trunks of the tree which essentially starves and slowly kills the tree. Natural resistance to this pathogen is rare. Conserving butternut is of utmost priority due to its critical ecosystem role and cultural significance. As part of an integrated undergraduate and graduate student training program in biodiversity and conservation genomics, the first reference genome forJuglans cinereais described here. This chromosome-scale 539 Mb assembly was generated from over 100X coverage of Oxford Nanopore long reads and scaffolded with theJuglans mandshuricagenome. Scaffolding with a closely related species oriented and ordered the sequences in a manner more representative of the structure of the genome without altering the sequence. Comparisons with sequenced Juglandaceae revealed high levels of synteny and further supportedJ. cinerea’srecent phylogenetic placement. Comparative assessment of gene family evolution revealed a significant number of contracting families, including several associated with biotic stress response.
Neuro-Regenerative Behavior of Adipose-Derived Stem Cells in Aligned Collagen I Hydrogels
Authors: Lewis Mackenzie , David Gabriel , Jacobs Danielle , Woessner Alan E. , Kuczwara Patrick , Kim Jin-Woo , Quinn Kyle P. , Song Younghye 
Published: May 2023

AbstractPeripheral nerve injuries persist as a major clinical issue facing the US population and can be caused by stretch, laceration, or crush injuries. Small nerve gaps are simple to treat, and the nerve stumps can be reattached with sutures. In longer nerve gaps, traditional treatment options consist of autografts, hollow nerve guidance conduits, and, more recently, manufactured fibrous scaffolds. These manufactured scaffolds often incorporate stem cells, growth factors, and/or extracellular matrix (ECM) proteins to better mimic the native environment but can have issues with homogenous cell distribution or uniformly oriented neurite outgrowth in scaffolds without fibrous alignment. Here, we utilize a custom device to fabricate collagen I hydrogels with aligned fibers and encapsulated adipose-derived mesenchymal stem cells (ASCs) for potential use as a peripheral nerve repair graft. Analysis of these scaffolds in vitro revealed heightened therapeutic secretome from ASCs, ECM deposition, and dorsal root ganglia (DRG) neurite outgrowth along the axis of fiber alignment. Our platform serves as an in vitro testbed platform to assess neuro-regenerative potential of ASCs in aligned collagen fiber scaffolds and may provide guidance on next-generation nerve repair scaffold design.
Initiation phase cellular reprogramming ameliorates DNA damage in the ERCC1 mouse model of premature aging
Authors: Paine Patrick Treat , Rechsteiner Cheyenne , Morandini Francesco , Desdin Mico Gabriela , Mrabti Calida , Parras Alberto , Haghani Amin , Brooke Robert , Horvath Steve , Seluanov Andrei , Gorbunova Vera , Ocampo Alejandro 
Published: May 2023

AbstractUnlike aged somatic cells, which exhibit a decline in molecular fidelity and eventually reach a state of replicative senescence, pluripotent stem cells can indefinitely replenish themselves while retaining full homeostatic capacity. The conferment of beneficial-pluripotency related traits via in vivo partial cellular reprogramming (IVPR) significantly extends lifespan and restores aging phenotypes in mouse models. Although the phases of cellular reprogramming are well characterized, details of the rejuvenation processes are poorly defined. To understand whether epigenetic reprogramming can ameliorate DNA damage, we created reprogrammable accelerated aging mouse model with an ERCC1 mutation. Importantly, using enhanced partial reprogramming by combining small molecules with the Yamanaka factors, we observed potent reversion of DNA damage, significant upregulation of multiple DNA damage repair processes, and restoration of the epigenetic clock. In addition, we present evidence that pharmacological inhibition of ALK5 and ALK2 receptors in TGFb pathway is able to phenocopy some benefits including epigenetic clock restoration suggesting a role in the mechanism of rejuvenation by partial reprogramming.
Intermediate basal cell population in prostate homeostasis and cancer initiation
Authors: Guo Wangxin , Zhang Xiaoyu , Li Lin , Shao Pengfei , Zhang Hongjiong , Liu Kuo , Liang Chao , Wang Shuoming , Peng Yunyi , Ju Yi , Yu Chen , Chen Luonan , Zhou Bin , Gao Dong 
Published: May 2023

AbstractMany glandular epithelia are mainly composed of basal cells and luminal cells, including the prostate gland. Adult prostate basal and luminal cells are independently self-sustained by unipotent stem cells that can reactivate multipotency under prostate inflammation and carcinogenesis contexts. However, the defined basal stem cell populations responsible for prostate regeneration and their cell fates in prostate homeostasis, inflammation and carcinogenesis remain unclear. Using a genetic proliferation tracer (ProTracer) system, we found that basal cells exhibited extensive cell loss and proliferation during androgen-mediated prostate regression and regeneration, respectively. A rare intermediate basal cell population that expresses luminal cell markers (Nkx3.1andPbsn) (termed Basal-B) and a large basal cell population (termed Basal-A) were identified in mouse prostates by single-cell RNA sequencing. Basal-B cells exhibited a greater capacity for organoid formation and luminal cell differentiationin vitro. Genetic lineage tracing using dual recombinases showed that prostate homeostasis and regeneration are not driven by specific basal cell types. Fate-mapping results showed that Basal-B cells had a greater tendency to generate luminal cells under bacteria-induced prostate inflammation. Deletion ofPtenin basal cells resulted in Basal-A-to-Basal-B-to-luminal transition and prostatic intraepithelial neoplasia. Moreover, the human Basal-B-cell population was significantly increased in human benign prostate hyperplasia and prostatic intraepithelial neoplasia samples compared with normal prostate samples. This study identifies intermediate Basal-B cells as a potential stem cell population and provides genetic evidence of prostate basal cell lineage plasticity under physiological and pathological contexts.
Clearing the way to the external world: do ants make optimal decisions when removing obstacles from their subterranean galleries?
Authors: Devers Louis E. , Cléradin Clémentine , Bescond-Michel Zoé , Latil Gérard , Fourcassié Vincent 
Published: May 2023

AbstractTransport tasks are simple tasks whose cost can be easily measured and that are thus well suited to test optimality hypotheses. Here we focus on a particular type of transport that occur when ants are clearing obstacles from their subterranean galleries. In the laboratory we studied how they extract an object from a gallery of various inclinations. We expected that if ants behave optimally, they should remove the object by the gallery extremity requiring the lower energetic effort. At the colony-level, we found that the obstacle was more often extracted by the lower end of the tube, even if this required a higher amount of mechanical work. At the individual level however, ants showed mechanically optimal pulling behaviours in 75% of cases. Our results suggest that individual ants take into account both the inclination of the gallery and the position of the obstacle in it to decide in which direction they pull. In addition, they seem to base their decision to release the obstacle on the relative effort they perceive while pulling. Using a simple simulation model, we argue that the suboptimal extraction bias observed at the colony-level can be explained by the sequential nature of the extraction task.
Transcription-directed membrane association organizes the chloroplast nucleoid structure
Authors: Palomar V. Miguel , Fujii Sho , Rothi M. Hafiz , Jaksich Sarah , Coke Adriana N. , Wang Joyful , Wierzbicki Andrzej T. 
Published: May 2023

ABSTRACTDNA is organized into chromatin-like structures, which support the maintenance and regulation of genomes. A unique and poorly understood form of DNA packaging exists in chloroplasts, which are endosymbiotic organelles responsible for photosynthesis. Chloroplast genomes, together with associated proteins, form membraneless structures known as nucleoids. The internal arrangement of the nucleoid, molecular mechanisms of DNA packaging, and connections between nucleoid structure and gene expression remain mostly unknown. We show thatArabidopsis thalianachloroplast nucleoids have a unique organization driven by DNA binding to the thylakoid membranes. DNA associated with the membranes has high protein occupancy, reduced DNA accessibility, and is highly transcribed. In contrast, genes with low levels of transcription are further away from the membranes, have lower protein occupancy, and higher DNA accessibility. Disruption of transcription at specific genes in sigma factor mutants causes a corresponding reduction in membrane association, indicating that RNA polymerase activity causes DNA tethering to the membranes. We propose that transcription organizes the chloroplast nucleoid into a transcriptionally active membrane-associated core and a less active periphery.
Selenoprotein synthesis is not induced by hepatotoxic drugs
Authors: Shetty Sumangala P. , He Dongming , Copeland Paul R. 
Published: May 2023

AbstractBackground and AimsMany of the proteins that contain the amino acid selenocysteine are required for optimal defense against cellular stress. As such, one might expect selenoprotein synthesis to persist or be induced upon cellular insult. Because selenocysteine is incorporated by a complex post-transcriptional mechanism, monitoring the transcription of selenoprotein genes is not adequate to understand the regulation of selenoprotein synthesis. We aimed to determine whether selenoprotein synthesis is regulated by the induction of hepatotoxic stress.MethodsWe used hepatotropic clinically relevant drugs to evaluate the regulation of selenoprotein synthesis in human hepatocarcinoma cells.ResultsWe found that two drugs, benzbromarone and sorafenib, caused significant inhibition of selenoprotein synthesis. However, the loss of selenoprotein expression was not specific as total protein synthesis was similarly down-regulated only by benzbromarone and sorafenib.ConclusionsThese results allow us to conclude that these hepatotoxins do not induce or preserve selenoprotein synthesis as a protective mechanism.HighlightsThe treatment of liver cells with hepatotoxic and hepatotropic compounds does not result in increased synthesis of selenoproteins.Compounds that induced the canonical oxidative stress response that features NRF2 activation eliminated selenoprotein synthesis.The downregulation of selenoproteins was accompanied by general inhibition of protein synthesis.
Single cell assessment of human stem cell derived mesolimbic models and their responses to substances of abuse
Authors: Rudibaugh Thomas P. , Tam Ryan W. , Estridge R. Chris , Keung Albert J. 
Published: May 2023

AbstractThe mesolimbic pathway connects ventral tegmental area dopaminergic neurons and striatal medium spiny neurons, playing a critical role in reward and stress behaviors. Exposure to substances of abuse during development and adulthood has been linked to adverse outcomes and molecular changes. The rise of human cell repositories and whole genome sequences enables human functional genomics ‘in a dish’, offering insights into human-specific responses to substances of abuse. Characterizations ofin vitromodels are necessary to ensure appropriate experimental designs and accurate interpretation of results. This study provides a comprehensive characterization of these models and their responses to substances of abuse, introducing new culture conditions for generating medium spiny neurons and dopaminergic neurons from human pluripotent stem cells. Single cell analysis reveals cell type-specific transcriptomic responses to dopamine, cocaine, and morphine, including compound and cell type-specific transcriptomic signatures related to neuroinflammation and alterations in signaling pathways. These findings offer a resource for future genomics studies leveraging human stem cell-derived models.TeaserGeneration and characterization of a novel mesolimbic pathway model and its response to acute dopamine, morphine, and cocaine.
Using multiscale molecular modeling to analyze possible NS2b-NS3 protease inhibitors from medicinal plants endemic to the Philippines
Authors: Cordero Allen Mathew F. , Gonzales Arthur A. 
Published: May 2023

AbstractPhilippine folkloric medicinal plants likeEuphorbia hirta(locally known as tawa-tawa),Carica papaya(papaya),Psidium guajava(guava), andMomordica charantia(bittermelon) have been used as a treatment for dengue. However, limited studies have been conducted regarding the extensive effects of these plants, especially their anti-dengue activity. This study evaluated 2,944 ligands from phytochemicals found in various medicinal plants as potential dengue inhibitors that could be developed into cost-effective and efficient therapeutic agents. SwissADME and Chembioserver online servers were used to conduct tests on absorption, distribution, metabolism, excretion, and toxicity (ADMET) for all ligands, resulting in 1,265 compounds being pharmacologically viable. By targeting the NS2b-NS3 protease of the dengue virus, specifically its catalytic triad of Asp 75, Ser 135, and His 51 residues, we can inhibit the replication of the virus. Molecular docking results showed ten ligands with comparable docking scores to the reference compounds. Attachment to the binding site is strengthened by electrostatic, polar, and hydrophobic interactions and the formation of hydrogen bonds.Furthermore, we also evaluated their stability using molecular dynamics simulations on GROMACS 2021.3. Molecular dynamics simulations of up to 100 ns of chemical time suggest eight of the ten candidate ligands are stable while binding to the active site. Free energy calculations using molecular mechanics Poisson-Boltzmann surface area also proved that six of the eight stable ligands exceeded the binding energies of the reference compounds. Results showed that veramiline fromVeratrum mengtzeanum(pimacao), etiolin fromLilion martagon(Turk’s cap lily), hydroxyverazine fromEclipta prostrata(false daisy), chlorogenin fromYucca gloriosa(palm lily), cyclobranol fromEuphorbia hirta(tawa-tawa), and ecliptalbine fromEclipta albamaintained their structural stability throughout the simulations. They also displayed good oral bioavailability and potential drug-like characteristics. These six compounds warrant furtherin vitroandin vivoinvestigation as potential dengue therapies.
In depth profiling of the cancer proteome from the flowthrough of standard RNA- preparation kits for precision oncology
Authors: Mundt Madsen Filip , Nielsen Annelaura Bach , Wang Juanjuan , Duel Josephine Kerzel , Yde Christina Westmose , Eriksen Martina Amnitzbøll , Lassen Ulrik , Nielsen Finn Cilius , Rohrberg Kristoffer , Mann Matthias 
Published: May 2023

AbstractCancer is a highly heterogeneous disease, even within the same patient. Biopsies taken from different regions of a tumor may stand in stark molecular contrast to each other. Therefore, the ability to generate meaningful data from multiple platforms using the same biopsy is crucial for translating multi-omics characterizations into the clinic. However, it is generally a cumbersome and lengthy procedure to generate DNA, RNA and protein material from the same biopsy. The Qiagen AllPrep kit is an accessible, straightforward, and widely used kit in clinics worldwide to process biopsies and generate genomic and transcriptomic data from tumors. We aimed to determine if high-quality proteomics data could also be obtained from the remaining material. Here, we investigated procedures for generating deep and quantitatively accurate proteomic information in high throughput from Qiagen AllPrep flowthroughs. With a number of refinements, we obtain in excess of 10,000 quantified proteins, from 60 samples per day, achieving a substantial coverage of the total proteome. Additionally, we successfully characterize the tumors using phosphoproteomics. Combining a standard kit with in-depth proteomics will be an attractive approach for clinics seeking to implement multi-omics-based precision oncology.
Peripheral serotonergic neurons regulate gut motility and anxiety-like behavior
Authors: Zhang Hailong , Leitner Deborah R. , Hasegawa Yuko , Waldor Matthew K. 
Published: May 2023

AbstractSerotonergic circuits in the central nervous system play important roles in regulating mood and behavior, yet the functions of peripheral serotonergic neurons are less understood. Here, we engineered mice lacking the serotonin-producing enzymeTph2in peripheral neurons but with intactTph2in central neurons. In contrast to mice lackingTph2in all neurons, mice lackingTph2in peripheral serotonergic neurons did not exhibit increased territorial aggression. However, similar to the total bodyTph2KO mice, the conditional KO animals, exhibited reduced gut motility and decreased anxiety-like behavior. These observations reveal that peripheral serotonergic neurons contribute to control of intestinal motility and anxiety-like behavior and suggest that therapeutics targeting this subset of peripheral neurons could be beneficial.
Characterizing the microbial metagenome of calcareous stromatolite formations in the San Felipe Creek in Anza Borrego Desert
Authors: Stancheva Rosalina , Sethuraman Arun , Khadivar Hossein , Archambeau Jenna , Caughran Ella , Chang Ashley , Hunter Brad , Ihenyen Christian , Onwukwe Marvin , Palacios Dariana , Prairie Chloe La , Read Nicole , Tsang Julianna , Vega Brianna , Velasquez Cristina , Zhang Xiaoyu , Becket Elinne , Read Betsy 
Published: May 2023

AbstractHere we describe the metagenome composition, community functional annotation, and diversity of prokaryotic microbial species derived from calcareous stromatolite formations discovered in the dry stream bed of the open-canopy, ephemeral San Felipe Creek in the Anza Borrego Desert. In this environment, resident microbes must be able to adapt to the harsh conditions of extreme heat, high UV light, desiccation and fluctuating solubilization/precipitation and hydration/evaporation. Metagenomic analysis revealed a community capable of carrying out complete nitrogen fixation and assimilatory nitrate reduction, forming biofilms and quorum sensing, and potentially forming thick-walled akinetes as desiccation-resistant stages. Nitrogen cycling is likely to play a fundamental role in mediating both the structure of the stromatolite microbial community and the mineral precipitation/dissolution. The viruses present in the stromatolites, particularlyNodulariaandMycobacteriumphages are also likely to impact community population dynamics and activity. Stromatolite community members possess different morphological and physiological strategies to cope with desiccation stress.Metagenomic signatures were found for scytonemin, carotenoids, synthesis of potential microsporine-like amino acids; genes involved in microalgal desiccation tolerance, including those encoding aquaporins, chaperones, antioxidants; and enzymes responsible for the synthesis of trehalose, sucrose, and polyamines.The stromatolite ecosystem provides a diverse array of microniches where different functional guilds can develop complex metabolite exchange with the substrate supporting their life in extreme conditions. Metagenome analyses revealed several genes that might enable a specialized and unique group of endolithic cyanobacteria includingChroococcidiopsis, Hyella, Myxosarcina, andPleurocapsato derive metals and important nutrients from rocks, being potentially destructive for the calcareous formations. Our study revealed environmental adaptations of freshwater microbial communities in desert stream stromatolites which may provide valuable insights into Precambrian paleoenvironments, which are little known.
Hippocampome.org v2.0: a knowledge base enabling data-driven spiking neural network simulations of rodent hippocampal circuits
Authors: Wheeler Diek W. , Kopsick Jeffrey D. , Sutton Nate , Tecuatl Carolina , Komendantov Alexander O. , Nadella Kasturi , Ascoli Giorgio A. 
Published: May 2023

AbstractHippocampome.orgis a mature open-access knowledge base of the rodent hippocampal formation focusing on neuron types and their properties.Hippocampome.orgv1.0 established a foundational classification system identifying 122 hippocampal neuron types based on their axonal and dendritic morphologies, main neurotransmitter, membrane biophysics, and molecular expression. Releases v1.1 through v1.12 furthered the aggregation of literature-mined data, including among others neuron counts, spiking patterns, synaptic physiology,in vivofiring phases, and connection probabilities. Those additional properties increased the online information content of this public resource over 100-fold, enabling numerous independent discoveries by the scientific community.Hippocampome.orgv2.0, introduced here, besides incorporating over 50 new neuron types, now recenters its focus on extending the functionality to build real-scale, biologically detailed, data-driven computational simulations. In all cases, the freely downloadable model parameters are directly linked to the specific peer-reviewed empirical evidence from which they were derived. Possible research applications include quantitative, multiscale analyses of circuit connectivity and spiking neural network simulations of activity dynamics. These advances can help generate precise, experimentally testable hypotheses and shed light on the neural mechanisms underlying associative memory and spatial navigation.