bluuebunny/crossref_metadata_2025_split huggingface dataset:
JMJD3 mediated senescence is required to overcome stress induced hematopoietic defects
Authors: Nakata Yuichiro , Ueda Takeshi , Sera Yasuyuki , Kanai Akinori , Ikeda Ken-ichiro , Yamasaki Norimasa , Nagamachi Akiko , Kobatake Kohei , Taguchi Masataka , Sotomaru Yusuke , Ichinohe Tatsuo , Honda Zen-ichiro , Manabe Ichiro , Suda Toshio , Takubo Keiyo , Kaminuma Osamu , Honda Hiroaki 
Published: August 2024

AbstractCellular senescence in stem cells compromises regenerative capacity, promotes chronic inflammation, and is implicated in aging. Hematopoietic stem and progenitor cells (HSPCs) are responsible for producing mature blood cells, however, how cellular senescence influences their function is largely unknown. Here, we show that JMJD3, a histone demethylase, activates cellular senescence viap16Ink4aupregulation in competition with Polycomb group proteins, and reprograms HSPC integrity to overcome hematopoietic defects induced by replicative and oncogenic stresses. JMJD3 deficiency impaired stem cell potential, proper cell cycle regulation, and WNT pathway activation in HSPCs under stress conditions. These impaired phenotypes were rescued through exogenous and retroviral introduction ofp16Ink4a. This JMJD3-p16INK4aaxis in hematopoiesis is age-dependent and is distinct from cellular senescence. Treatment with a JMJD3 selective inhibitor attenuated leukemic potential during cellular senescence. Taken together, these results demonstrate that JMJD3-p16INK4amediates cellular senescence and plays critical roles in the functional integrity of HSPCs under stress conditions, suggesting a new link for aging and anti-cancer therapies.
Coevolution of phenological traits shapes plant-pollinator coexistence
Authors: Duchenne François , Dominguez-García Virginia , Molina Francisco P. , Bartomeus Ignasi 
Published: August 2024

AbstractPrevious research has revealed how species traits determine species interactions, and how species interactions influence species coexistence. However, this hierarchical view ignores the coevolutionary feedback from species interactions to species traits and its consequences for species coexistence. Here, we developed a theoretical model to explore how the coevolution of morphological and phenological traits shape the structure and stability of mutualistic interaction networks. We found phenological traits lead to distinctive coevolutionary opportunities for species and to different emergent properties at community level than morphological traits, because they decouple mutualism and competition. Morphological coevolution led to modular and specialized interaction networks with a low structural stability, while phenological coevolution was required to achieve nested interaction networks with a higher structural stability. This suggested that phenological coevolution is key in the emergence of stable communities. Our theoretical prediction was consistent with empirical observations: across 17 empirical pollination networks we found a high proportion of phenological motifs promoting facilitation over competition, suggesting an important role of phenological coevolution in community assembly. In addition, the phenological structure of the empirical communities was a major determinant of their structural stability. Our results highlight the importance of phenological coevolution in the emergence of diverse and stable communities.
Improved Spectral Inversion of Blood Oxygenation due to Reduced Tissue Scattering: Towards NIR-II Photoacoustic Imaging
Authors: Vincely Vinoin Devpaul , Bayer Carolyn L. 
Published: August 2024

AbstractSignificanceConventional spectral photoacoustic imaging (sPAI) to assess tissue oxygenation (sO2) uses optical wavelengths in the first near infrared window (NIR-I). This limits the maximum imaging depth (∼1 cm) due to high spectral coloring of biological tissues.AimSecond near infrared or short-wave infrared (NIR-II or SWIR) wavelengths (950-1400 nm) show potential for deep tissue sPAI due to the exponentially reduced tissue scattering and higher maximum exposure threshold (MPE) in this wavelength range. However, to date, a systematic assessment of NIR-II wavelengths for sPAI of tissue sO2has yet to be performed.ApproachThe NIR-II PA spectra of oxygenated and deoxygenated hemoglobin was first characterized using a phantom. Optimal wavelengths to minimize spectral coloring were identified. The resulting NIR-II PA imaging methods were then validatedin vivoby measuring renal sO2in adult female rats.ResultssPAI of whole blood under a phantom and of circulating renal blood in vivo, demonstrated PA spectra proportional to wavelength-dependent optical absorption. NIR-II wavelengths had a ∼50% decrease in error of spectrally unmixed blood sO2compared to conventional NIR-I wavelengths. In vivo measurements of renal sO2validated these findings and demonstrated a ∼30% decrease in error of estimated renal sO2when using NIR-II wavelengths for spectral unmixing in comparison to NIR-I wavelengths.ConclusionssPAI using NIR-II wavelengths improved the accuracy of tissue sO2measurements. This is likely due to the overall reduced spectral coloring in this wavelength range. Combined with the increased safe skin exposure fluence limits in this wavelength range, demonstrate the potential to use NIR-II wavelengths for quantitative sPAI of sO2from deep heterogeneous tissues.
An orphan gene is essential for efficient sperm entry into eggs inDrosophila melanogaster
Authors: Guay Sara Y. , Patel Prajal H. , Thomalla Jonathon M. , McDermott Kerry L. , O’Toole Jillian M. , Arnold Sarah E. , Obrycki Sarah J. , Wolfner Mariana F. , Findlay Geoffrey D. 
Published: August 2024

AbstractWhile spermatogenesis has been extensively characterized in theDrosophila melanogastermodel system, very little is known about the genes required for fly sperm entry into eggs. We identified a lineage-specific gene, which we namedkatherine johnson(kj), that is required for efficient fertilization. Males that do not expresskjproduce and transfer sperm that are stored normally in females, but sperm from these males enter eggs with severely reduced efficiency. Using a tagged transgenic rescue construct, we observed that the KJ protein localizes around the edge of the nucleus at various stages of spermatogenesis but is undetectable in mature sperm. These data suggest thatkjexerts an effect on sperm development, the loss of which results in reduced fertilization ability. Interestingly, KJ protein lacks detectable sequence similarity to any other known protein, suggesting thatkjcould be a lineage-specific orphan gene. While previous bioinformatic analyses indicated thatkjwas restricted to themelanogastergroup ofDrosophila, we identified putative orthologs with conserved synteny, male-biased expression, and predicted protein features across the genus, as well as likely instances of gene loss in some lineages. Thus,kjwas likely present in theDrosophilacommon ancestor and subsequently evolved an essential role in fertility inD. melanogaster. Our results demonstrate a new aspect of male reproduction that has been shaped by a lineage-specific gene and provide a molecular foothold for further investigating the mechanism of sperm entry into eggs inDrosophila.Article SummaryHow fruit fly sperm enter eggs is poorly understood. Here, we identify a gene required for efficient fertilization. Sperm from males lacking this gene’s function cannot enter eggs. The gene appears to act during sperm production, rather than in mature sperm. Interestingly, the gene is undetectable outside of genusDrosophila, and its encoded protein shows no discernable similarity to other proteins. This study provides insights into sperm-egg interactions and illustrates how lineage-specific genes can impact important aspects of reproduction.
The repertoire of short tandem repeats across the tree of life
Authors: Chantzi Nikol , Georgakopoulos-Soares Ilias 
Published: August 2024

AbstractShort tandem repeats (STRs) are widespread, dynamic repetitive elements with a number of biological functions and relevance to human diseases. However, their prevalence across taxa remains poorly characterized. Here we examined the impact of STRs in the genomes of 117,253 organisms spanning the tree of life. We find that there are large differences in the frequencies of STRs between organismal genomes and these differences are largely driven by the taxonomic group an organism belongs to. Using simulated genomes, we find that on average there is no enrichment of STRs in bacterial and archaeal genomes, suggesting that these genomes are not particularly repetitive. In contrast, we find that eukaryotic genomes are orders of magnitude more repetitive than expected. STRs are preferentially located at functional loci at specific taxa. Finally, we utilize the recently completed Telomere-to-Telomere genomes of human and other great apes, and find that STRs are highly abundant and variable between primate species, particularly in peri/centromeric regions. We conclude that STRs have expanded in eukaryotic and viral lineages and not in archaea or bacteria, resulting in large discrepancies in genomic composition.
Tritrichomonas murissensitizes the intestinal epithelium to doxorubicin-induced apoptosis
Authors: Janto Nicolas V. , Gleizes Antoine R. , Sun Siyang , Ari Gurel , Gracz Adam D. 
Published: August 2024

ABSTRACTDoxorubicin (DXR) is a widely used chemotherapy drug that can induce severe intestinal mucositis. While the influence of gut bacteria on DXR-induced damage has been documented, the role of eukaryotic commensals remains unexplored. We discoveredTritrichomonas muris(Tmu) in one of our mouse colonies exhibiting abnormal tuft cell hyperplasia, prompting an investigation into its impact on DXR-induced intestinal injury. Mice fromTmu-colonized andTmu-excluded facilities were injected with DXR, and tissue morphology and gene expression were evaluated at acute injury (6 h) and peak regeneration (120 h) phases. Contrary to previous reports, DXR did not significantly alter villus height, crypt depth, or crypt density in any mice. However, we did observe apoptosis, measured by cleaved caspase 3 (CC3) staining, in intestinal crypts at 6 h post-DXR that was significantly higher in mice colonized byTmu. Interestingly, while DXR did not alter the expression of active and facultative intestinal stem cell (ISC) marker genes in control mice, it significantly reduced their expression inTmu+mice.Tmu, but not DXR, is also associated with increased inflammation and expression of the type 2 cytokines IL-5 and IL-13. However, pre-treatment of intestinal organoids with these cytokines is not sufficient to drive elevated DXR-induced apoptosis. These findings highlight the significant influence of commensal microbiota, particularly eukaryotic organisms likeTmu, on intestinal biology and response to chemotherapy, underscoring the complexity of gut microbiota interactions in drug-induced mucositis.NEW & NOTEWORTHYOur study found that the eukaryotic commensalTritrichomonas muris(Tmu) significantly increases DXR-induced intestinal apoptosis in mice, despite no changes in tissue morphology.Tmualso reduces intestinal stem cell gene expression post-DXR injury, and elevates inflammation and type 2 cytokine expression in the absence of injury.In vitroorganoid assays suggest that type 2 cytokines alone are insufficient to promote increased DXR-associated apoptosis. These findings emphasize the complex role of gut microbiota in drug-induced intestinal damage.
A honey bee-associated virus remains infectious and quantifiable in postmortem hosts
Authors: Payne Alexandria N. , Prayugo Vincent , Dolezal Adam G. 
Published: August 2024

ABSTRACTCorpse-mediated transmission is a potentially viable route through which naïve hosts can become infected, but its likelihood for honey bee-associated viruses is largely unknown. While these viruses can be easily detected in deceased bees, it remains unclear if they stay infectious within postmortem hosts or if enough viral RNA degradation—and subsequently virus inactivation—occurs post-host death to render these viruses inviable. This knowledge gap has important implications for how researchers perform honey bee virus studies and for our general understanding of honey bee virus transmission. To better understand the resiliency of honey bee-associated viruses within deceased hosts, we first tested the hypothesis that postmortem specimens, stored in colony-normal temperature and humidity conditions, can be reliably used to quantify virus abundance. To determine this, we experimentally-infected adult honey bees with Israeli acute paralysis virus (IAPV) and then measured the virus levels of individuals sampled live or at different postmortem timepoints (4–, 12–, 24–, and 48–hours post-death) using RT-qPCR and a standard curve absolute quantification method. We found no significant differences based on when bees were sampled, indicating that postmortem honey bees are statistically comparable to using live-sampled bees and can be reliably used to quantify absolute IAPV abundance. We then performed a follow-up experiment that determined whether or not the IAPV detected in postmortem bees remained infectious over time. We found that IAPV extracted from postmortem bees remained highly infectious for at least 48–hours post-death, indicating that any viral RNA degradation that may have occurred during the postmortem interval did not adversely affect IAPV’s overall infectivity. The results from this study suggest that IAPV is more resilient to degradation than previously assumed, support the use of postmortem bees for downstream IAPV analyses, and indicate that postmortem hosts can act as sources of IAPV infection for susceptible individuals.
Multi-modal, Label-free, Optical Mapping of Cellular Metabolic Function and Oxidative Stress in 3D Engineered Brain Tissue Models
Authors: Zhang Yang , Savvidou Maria , Liaudanskaya Volha , Ramanathan Varshini , Bui Thi , Lindley Matthew , Sze Ash , Ugwu Ugochukwu O. , Fu Yuhang , Dilsizian Matthew E. , Chen Xinjie , Nasritdinova Sevara , Dey Aonkon , Miller Eric L. , Kaplan David L. , Georgakoudi Irene 
Published: August 2024

AbstractBrain metabolism is essential for the function of organisms. While established imaging methods provide valuable insights into brain metabolic function, they lack the resolution to capture important metabolic interactions and heterogeneity at the cellular level. Label-free, two-photon excited fluorescence imaging addresses this issue by enabling dynamic metabolic assessments at the single-cell level without manipulations. In this study, we demonstrate the impact of spectral imaging on the development of rigorous intensity and lifetime label-free imaging protocols to assess dynamically metabolic functions over time in 3D engineered brain tissue models comprised of human induced neural stem cells, astrocytes, and microglia. Specifically, we rely on multi-wavelength spectral imaging to identify the excitation/emission profiles of key cellular fluorophores within human brain cells, including NAD(P)H, LipDH, FAD, and lipofuscin. These enable the development of methods to mitigate lipofuscin’s overlap with NAD(P)H and flavin autofluorescence to extract reliable optical metabolic function metrics from images acquired at two excitation wavelengths over two emission bands. We present fluorescence intensity and lifetime metrics reporting on redox state, mitochondrial fragmentation, and NAD(P)H binding status in neuronal monoculture and the triculture systems to highlight the functional impact of metabolic interactions between different cell types. Our findings reveal significant metabolic differences between neurons and glial cells, shedding light on metabolic pathway utilization, including the glutathione pathway, OXPHOS, glycolysis, and fatty acid oxidation. Collectively, our studies establish a label-free, non-destructive approach to assess the metabolic function and interactions among different brain cell types relying on endogenous fluorescence and illustrate the complementary nature of the information that is gained by combining intensity and lifetime-based images. Such methods can improve understanding of physiological brain function and dysfunction that occurs at the onset of cancers, traumatic injuries and neurodegenerative diseases.
Integrating gene expression and imaging data across Visium capture areas with visiumStitched
Authors: Eagles Nicholas J. , Bach Svitlana V. , Tippani Madhavi , Ravichandran Prashanthi , Du Yufeng , Miller Ryan A. , Hyde Thomas M. , Page Stephanie C. , Martinowich Keri , Collado-Torres Leonardo 
Published: August 2024

AbstractBackgroundVisium is a widely-used spatially-resolved transcriptomics assay available from 10x Genomics. Standard Visium capture areas (6.5mm by 6.5mm) limit the survey of larger tissue structures, but combining overlapping images and associated gene expression data allow for more complex study designs. Current software can handle nested or partial image overlaps, but is designed for merging up to two capture areas, and cannot account for some technical scenarios related to capture area alignment.ResultsWe generated Visium data from a postmortem human tissue sample such that two capture areas were partially overlapping and a third one was adjacent. We developed the R/Bioconductor packagevisiumStitched, which facilitates stitching the images together withFiji(ImageJ), and constructingSpatialExperimentR objects with the stitched images and gene expression data.visiumStitchedconstructs an artificial hexagonal array grid which allows seamless downstream analyses such as spatially-aware clustering without discarding data from overlapping spots. Data stitched withvisiumStitchedcan then be interactively visualized withspatialLIBD.ConclusionsvisiumStitchedprovides a simple, but flexible framework to handle various multi-capture area study design scenarios. Specifically, it resolves a data processing step without disrupting analysis workflows and without discarding data from overlapping spots.visiumStichedrelies on affine transformations byFiji, which have limitations and are less accurate when aligning against an atlas or other situations.visiumStichedprovides an easy-to-use solution which expands possibilities for designing multi-capture area study designs.
Overexpression of theApoegene in the frontal cortex of mice causes sex-dependent changes in learning, attention, and anxiety-like behavior
Authors: Ramos Lizbeth , Harr Abigail E. , Zakas Finian L. , Essig Samuel R. , Kempskie Griffen J. , Fadil Nelly A. , Schmid Makayla G. , Pompy Madison D. , Curley Michael C. , Gabel Lisa A. , Hallock Henry L. 
Published: August 2024

AbstractApolipoprotein E (ApoE) is a protein that is important for lipid storage, transport, and metabolism.APOEgene variants are associated with Alzheimer’s disease (AD), as well as attentional function in healthy humans. Previous research has shown thatApoetranscription is increased following stimulation of the pathway between the locus coeruleus (LC) and frontal cortex (FC) in mice. This result suggests thatApoemay affect attentional function by virtue of its expression in circuits that control attention. DoesApoecausally regulate attention, or is its expression simply a byproduct of neuronal activity in the LC and FC? To answer this question, we synthetically inducedApoetranscription in the FC of male and female mice, and subsequently tested their ability to learn a touchscreen-based rodent version of the continuous performance test of sustained attention (the rCPT). We found that increasedApoetranscription impaired performance when attentional demand was increased in male mice, while in female mice, increasedApoetranscription significantly accelerated rCPT learning. We further found that this increase inApoetranscription affected subsequent anxiety-like behavior and cellular activity in the FC in a sex-dependent manner. The results of this study provide insight into howApoecausally regulates translationally relevant behaviors in rodent models.
Geometric eigenmode brain fingerprinting and its longitudinal associations with adolescent mental health and wellbeing
Authors: Boyes Amanda , Schwenn Paul E. , Shan Zack Y. , Korgaonkar Mayuresh , Pang James , Prince Taliah , Mills Lia , Kennedy Michelle F. , Hermens Daniel F. 
Published: August 2024

AbstractBackground‘Brain fingerprinting’ research posits that individual uniqueness can be identified by structural and functional features that may also be linked to mental health outcomes. Global structural features of the brain can be succinctly and directly captured from magnetic resonance imaging (MRI) via the eigenmodes of the cortical surface - known asgeometric eigenmodes. This research investigates how the uniqueness of geometric eigenmodes changes across adolescence and their longitudinal relation to mental health and wellbeing.MethodsThe current study utilised n=613 MRI, self-report and demographic datasets from N=116 community-recruited adolescents enrolled in the Longitudinal Adolescent Brain Study (LABS), between the ages of 12-17 years. MPRAGE scans at each participant’s visit were used to derive 225 left-hemisphere geometric eigenmodes. Eigenmodes were clustered into 14 eigengroups and developmental trajectories of their uniqueness and longitudinal associations with mental wellbeing and psychological distress were examined.ResultsAll eigengroups become significantly more unique longitudinally, and higher mode (shorter wavelength) eigengroups were more unique than lower mode groups in adolescence. Less uniqueness in ‘eigengroup 6’ was significantly associated with higher psychological distress and lower mental wellbeing at concurrent and future timepoints.ConclusionGeometric eigengroup brain fingerprinting offers a novel way to examine neurodevelopment. This study provides evidence that eigengroups have distinct trajectories from adolescence to adulthood, consistent with other imaging studies demonstrating increasing uniqueness in this period. Importantly, they are associated with mental health state and thus may represent neurobiological markers for mental illness onset, building on previous LABS research demonstrating that the functional uniqueness of the ‘cognitive control network’ predicts psychological distress four months later.
noSpliceVelo infers gene expression dynamics without separating unspliced and spliced transcripts
Authors: Mahajan Tarun , Maslov Sergei 
Published: August 2024

AbstractModern single-cell transcriptomics has revolutionized biological research, but because of its destructive nature, it provides only static snapshots. Computational approaches that infer RNA velocity from the ratio of unspliced to spliced mRNA levels can be used to predict how gene expression changes over time. However, information about unspliced and spliced transcripts is not always available and may change on a timescale too short to accurately infer transitions between cellular states. Here we present noSpliceVelo, a novel technique for reconstructing RNA velocity without relying on unspliced and spliced transcripts. Instead, it exploits the temporal relationship between the variance and mean of bursty gene expression using a well-established biophysical model. When evaluated on datasets describing mouse pancreatic endocrinogenesis, mouse and human erythroid maturation, and neuronal stimulation in mouse embryonic cortex, noSpliceVelo performed comparably or better than scVelo, a splicing-based approach. In addition, noSpliceVelo inferred key biophysical parameters of gene regulation, specifically burst size and frequency, potentially distinguishing between transcriptional and epigenetic regulation.