bluuebunny/crossref_metadata_2025_split huggingface dataset:
ExploringPorphyromonas gingivalisPathogenesis and Antibody Pool Effect Using a Novel Mouse Reproductive Model
Authors: Shi Xiaoju , Xu Maria 
Published: July 2024

ABSTRACTThis study introduces a novel animal model consisting of two phases. In phase I, Balb/c mice received three intraperitoneal injections of antibodies and two subcutaneous challenges withPorphyromonas gingivalis. The mice were divided into seven groups: G1, G2, and G3 received a single monoclonal antibody targeting the major outer membrane protein RagB ofP. gingivalisand infection; G4 was infected without antibody; G5 and G6 received a mixture of monoclonal antibodies and infection; and G7 served as the healthy control. In phase II, one male was paired with one female from the same group and one healthy female. Fertility was assessed using maximum body weight growth rate (MWGR) and alive pup rate (APR).Results indicated that the APR of neonatal mice in G5+G6 significantly lower than G1-G3 and G7 (P < 0.05). Similarly, the MWGR of G5+G6 significantly lower than G7 (P < 0.05). Notably, the APR and MWGR in G4, which received no antibody, were lower than in G7 but higher than in G5-G6. These findings suggest that a mixture of antibodies coexisting withP. gingivalisinfection leads to more detrimental reproductive damage than infection alone. The so-called Antibody Pool Effect plays a role in the pathogenesis ofP. gingivalis. Understanding the mechanisms of this immunopathological damage may provide insights into the correlation betweenP. gingivalisinfection and systemic diseases.
Population genetic consequences of the seasonal migrations of birds
Authors: Pegan T.M. , Kimmitt A.A. , Benz B.W. , Weeks B.C. , Aubry Y. , Burg T.M. , Hudon J. , Jones A.W. , Kirchman J.J. , Ruegg K. , Winger B.M. 
Published: July 2024

AbstractDifferences in life history can cause co-distributed species to display discordant population genetic patterns. In high-latitude animals, evolutionary processes may be especially influenced by long-distance seasonal migration, a widespread adaptation to seasonality. Although migratory movements are intuitively linked to dispersal, their evolutionary genetic consequences remain poorly understood. Using ∼1700 genomes from 35 co-distributed boreal-breeding bird species, we reveal that most long-distance migrants exhibit spatial genetic structure, revealing evolutionary effects of philopatry rather than dispersal. We further demonstrate that migration distance and genetic diversity are strongly positively correlated in our study species. This striking relationship suggests that the adaptive seasonal shifts in biogeography that long-distance migratory species undergo each year lends them enhanced population stability that preserves genetic diversity relative to shorter-distance migrants that winter at higher latitudes. Our results suggest that the major impact of long-distance seasonal migration on population genetic evolution occurs through promotion of demographic stability, rather than facilitation of dispersal.
Nucleus accumbens sub-regions experience distinct dopamine release responses following acute and chronic morphine exposure
Authors: Gooding Sarah Warren , Lewis Elinor , Chau Christine , Sandhu Suhail , Glienke Julianna , Whistler Jennifer L. 
Published: July 2024

AbstractIt is well established that dopamine neurons of the ventral tegmental area (VTA) play a critical role in reward and aversion as well as pathologies including drug dependence and addiction. The distinct effects of acute and chronic opioid exposure have been previously characterized at VTA synapses. Recent work suggests that distinct VTA projections that target the medial and lateral shell of the nucleus accumbens (NAc), may play opposing roles in modulating behavior. It is possible that these two anatomically and functionally distinct pathways also have disparate roles in opioid reward, tolerance, and withdrawal in the brain. In this study we monitored dopamine release in the medial or lateral shell of the NAc of male mice during a week-long morphine treatment paradigm. We measured dopamine release in response to an intravenous morphine injection both acutely and following a week of repeated morphine. We also measured dopamine in response to a naloxone injection both prior to and following repeated morphine treatment. Morphine induced a transient increase in dopamine in the medial NAc shell that was much larger than the slower rise observed in the lateral shell. Surprisingly, chronic morphine treatment induced a sensitization of the medial dopamine response to morphine that opposed a diminished response observed in the saline-treated control group. This study expands on our current understanding of the medial NAc shell as hub of opioid-induced dopamine fluctuation. It also highlights the need for future opioid studies to appreciate the heterogeneity of dopamine neurons.Significance StatementThe social and economic consequences of the opioid epidemic are tragic and far-reaching. Yet, opioids are indisputably necessary in clinical settings where they remain the most useful treatment for severe pain. To combat this crisis, we must improve our understanding of opioid function in the brain, particularly the neural mechanisms that underlie opioid dependence and addictive behaviors. This study uses fiber photometry to examine dopamine changes that occur in response to repeated morphine, and morphine withdrawal, at multiple stages of a longitudinal opioid-dependence paradigm. We reveal key differences in how dopamine levels respond to opioid administration in distinct sub-regions of the ventral striatum and lay a foundation for future opioid research that appreciates our contemporary understanding of the dopamine system.
A graph-based practice of evaluating collective identities of cell clusters
Authors: Okano Yuji , Kase Yoshitaka , Okano Hideyuki 
Published: July 2024

AbstractThe rise of single-cell RNA-sequencing (scRNA-seq) and evolved computational algorithms have significantly advanced biomedical science by revealing and visualizing the multifaceted and diverse nature of single cells. These technical advancements have also highlighted the pivotal role of cell clusters as representations of biologically universal entities such as cell types and cell states. However, to some extent, these clusterings remain dataset-specific and method-dependent. To improve comparability across different datasets or compositions, we previously introduced a graph-based representation of cell collections that captures the statistical dependencies of their characteristic genes.While our earlier work focused on theoretical insights, it was not sufficiently adapted and fine-tuned for practical implementation. To address this, the present paper introduces an improved practice to define and evaluate cellular identities based on our theory. First, we provide a concise summary of our previous theory and workflow. Then, point-by-point, we highlight the issues that needed fixing and propose solutions. The framework’s utility was enhanced by leveraging alternative formats of cellular features such as gene ontology (GO) terms and effectively handling dropouts. Supplemental techniques are offered to reinforce the versatility and robustness of our method.
Knock out of the intracellular calcium conducting ion channel Mitsugumin 23 (MG23) protects against pressure overload induced left ventricular hypertrophy and cardiac dysfunction
Authors: Dorward Amy M. , Robertson Gavin B. , Sneddon Claire , O’Rourke Chloe L. , Um In Hwa , Harrison David J. , Nishi Miyuki , Takeshima Hiroshi , Murdoch Colin E. , Pitt Samantha J. 
Published: July 2024

AbstractBackgroundIn cardiac dysfunction, intracellular Ca2+-dynamics are disrupted leading to leakage of Ca2+from the sarcoplasmic reticulum (SR). This results in diminished cardiac contractility and impaired cardiac function. In cardiac tissue, the underlying molecular mechanisms responsible for RyR2-independent Ca2+leak are poorly understood. Mitsugumin 23 (MG23) is an intracellular Ca2+-conducting ion channel located on ER/SR and nuclear membranes. We propose that MG23 contributes to regulation of intracellular Ca2+-homeostasis, and that altered MG23 function may drive progression of cardiac dysfunction. The aim of this research was to investigate the role of MG23 in SR Ca2+leak, and whether knock out ofMg23protects the heart against pressure-overload induced left ventricular hypertrophy.MethodsCardiac pressure-overload was induced in wild type (WT) andMg23-knock out (KO) mice through subcutaneous Angiotensin II (AngII, 1.1 mg/kg/day) infusion via osmotic pump. After 10-days infusion,in vivopressure-volume dynamics were measured by insertion of a pressure-volume catheter into the left ventricle. MG23 protein expression was assessed through Western blot analysis. Ventricular fibrosis and cardiomyocyte size were measured using histological and immunofluorescence approaches. Cardiomyocytes were isolated from WT andMg23-KO hearts and intracellular Ca2+dynamics assessed through live cell imaging using the Ca2+indicator Fluo-4.ResultsAngII-induced cardiac pressure-overload increased expression of MG23 in WT mouse hearts. Knock out ofMg23protected hearts against AngII-induced cardiac hypertrophy. Compared to WT animals, AngII treatedMg23-KO mice displayed a significant reduction in left ventricular fibrosis and displayed normal cardiac functioning. InMg23-KO hearts, no alteration in expression of key Ca2+handling proteins was identified, but cardiomyocytes displayed altered Ca2+spark profiles consistent with a role for MG23 in SR Ca2+leak.ConclusionMG23 plays a key role in driving Ca2+dysregulation observed in the early pathological stages of pressure-overload induced heart failure.
The aging musician: Evidence of a downward trend in song tempo as a function of artist age
Authors: Luck Geoff , Ansani Alessandro 
Published: July 2024

ABSTRACTCorrespondences between the timing of motor behavior and that of musical performance are well-established. Motor behavior, however, is known to degrade across the adult lifespan due to neurobiological decay. In particular, performance on speed-dependent motor tasks deteriorates, spontaneous motor tempo (SMT) slows, and upper motor rate limit falls. Here, we examine whether this slowdown in motor behavior impacts tempo of musical performance as a function of age. We analyzed 14,556 songs released between 1956 and 2020 by artists with careers spanning at least 20 years. Generalized Additive Mixed Models (GAMMs) and Linear Mixed Models (LMMs) were employed to assess the effects of age, operationalized by subtracting birth year from release year of each track, on musical tempo. Results revealed a slight tempo increase from early adulthood to age 30, followed by a marked, linear slowdown with age across the remainder of the lifespan. From artists’ thirties to their eighties, tempo decreased by almost 10 bpm, averaging around 2 bpm per decade. This decrease aligns with the slowing-with-age hypothesis and mirrors rates of decline observed in studies of spontaneous motor tempo (SMT) and gait speed. Our findings highlight a significant gap in understanding of creative performance across the lifespan, particularly the role of age as a mediating factor in musical tempo. Moreover, that a discernible decrease in tempo is apparent even in commercial recordings further emphasizes the inescapable connection between dynamics of motor behavior and timing of musical performance.
TGFβ-ANGPT2-Tie2 axis in cancer-associated fibroblasts reprograms oral cancer cells to embryonic-like cell state with predictive significance of poor prognosis
Authors: Mitra Paromita , Saha Uday , Stephen Kingsly Joshua , Prasad Priyanka , Patel Ankit Kumar , Harshvardhan BV , Mondal Santosh Kumar , Kurkalang Sillarine , Roy Sumitava , Ghosh Arnab , Roy Shantanu Saha , Das Sarma Jayasri , Biswas Nidhan Kumar , Acharya Moulinath , Sharan Rajeev , Arun Pattatheyil , Jolly Mohit Kumar , Maitra Arindam , Singh Sandeep 
Published: July 2024

AbstractMyofibroblastic cancer-associated fibroblasts (CAFs) in tumor stroma is identified as poor-prognostic indicator in oral cancer; however, biological mechanisms are largely unexplored. Here, we discovered the role of autocrine or exogenous transforming growth factor beta (TGFβ) in inducing Tunica Interna Endothelial cell kinase 2 (Tie2) -signaling through histone deacetylase-mediated downregulation of Tie2-antagonist, Angiopoietin-2 in CAFs, responsible for induction and maintenance of myofibroblastic differentiation. To understand the influence of CAF-specific Tie2-signaling on cancer cell properties, we performed CAF-Cancer cell co-culture and its single-cell RNA sequencing (scRNA-Seq). Distinct clustering of CAFs suggested their transcriptional heterogeneity, driven by TGFβ-Tie2 activation. Interestingly, CAF-specific Tie2-signaling was responsible to reprogram cancer cells, producing embryonic-like cell state with increased stemness and EMT signatures. Importantly, both the Tie2-specific gene expression signature as well as reprogrammed cancer cell specific gene expression modules were validated respectively in fibroblasts clusters and malignant cell clusters in two independent earlier reported scRNAseq studies of HNSCC tumors. Highlighting the translatability of our study, the gene expression signature derived from reprogrammed cancer cells showed significant association with poor prognosis in HNSCC patient of TCGA cohort. Pharmacological inhibition of Tie2-signaling in CAFs, significantly abrogated the tumor initiating ability of co-cultured oral cancer cell lines. Overall, combining our molecular and computational analysis, we may propose Tie2 as a novel factor responsible for CAF mediated cancer cell plasticity, associated with aggressive nature of oral cancer.TeaserTie2-signaling is activated in myofibroblasts which impacts the behaviour of malignant cells by inducing cancer cell plasticity to acquire stemness.
Autoimmunity and clinical pathology amelioration in SLE by Dexamethasone primed Mesenchymal Stem Cell derived conditioned media
Authors: Priya Khushbu , Rawat Sonali , Das Doli , Chaubey Manaswi , Thacker Hiral , Giri Kiran , Singh Shambhavi , Rai Madhukar , Mohanty Sujata , Rai Geeta 
Published: July 2024

AbstractThis study proposes a novel approach, utilizing cell-free dexamethasone (Dex) primed Whartons jelly mesenchymal stem cells derived conditioned media (DW), offering improved efficacy, simplicity, and alternative medicine for addressing complications associated with systemic lupus erythematosus (SLE). This study explores the immunomodulatory effects of DW treatment on immune cell populations in SLE patients and a pristane-induced lupus (PIL) mouse model. DW induces significant expansion of Tregs, Bregs, suppressing Th17, double-negative T cells, and inflammatory neutrophils through modulating IL-10 and IL-17A production. Comparisons with the standard drug hydroxychloroquine reveal similar effects, suggesting TGF beta; pathway mediation in DW’s actions. Compared with the immunosuppressive drug Dex, DW better attenuated autoantibody production, increased anti-inflammatory cytokines and maintained a balanced Th17/Treg ratio. In the preclinical in vivo studies, DW exhibits therapeutic efficacy, reducing mortality, preventing proteinuria, and reversing limb inflammation, seizure and alopecia. Organ specific evaluations using advanced live imaging or histopathological analysis highlighted DW’s protective effects on kidneys, liver, lungs, heart, and spleen. This provided insight into the immunomodulatory benefits of DW at various levels and suggested that it could be a potential therapeutic avenue for managing complications related to SLE.
Temporally resolved growth patterns reveal novel information about the polygenic nature of complex quantitative traits
Authors: Sweet Dorothy D. , Tirado Sara B. , Cooper Julian , Springer Nathan M. , Hirsch Cory D. , Hirsch Candice N. 
Published: July 2024

AbstractPlant height can be an indicator of plant health across environments and used to identify superior genotypes or evaluate abiotic stress factors. Typically plant height is measured at a single time point when plants have reached terminal height for the season. Evaluating plant height using unoccupied aerial vehicles (UAVs) is faster, allowing for measurements throughout the growing season, which facilitates a better understanding of plant-environment interactions and the genetic basis of this complex trait. To assess variation throughout development, plant height data was collected weekly for a panel of ∼500 diverse maize inbred lines over four growing seasons. The variation in plant height throughout the season was significantly explained by genotype, year, and genotype-by-year interactions to varying extents throughout development. Genome-wide association studies revealed significant SNPs associated with plant height and growth rate at different parts of the growing season specific to certain phases of vegetative growth that would not be identified by terminal height associations alone. When plant height growth rates were compared to growth rates estimated from canopy cover, greater Fréchet distance stability was observed in plant height growth curves than for canopy cover. This indicated canopy cover may be more useful for understanding environmental modulation of overall plant growth and plant height better for understanding genotypic modulation of overall plant growth. This study demonstrated that substantial information can be gained from high temporal resolution data to understand how plants differentially interact with the environment and can enhance our understanding of the genetic basis of complex polygenic traits.
Feeders and Expellers, Two Types of Animalcules With Outboard Cilia, Have Distinct Surface Interactions
Authors: Prakash Praneet , Vona Marco , Goldstein Raymond E. 
Published: July 2024

AbstractWithin biological fluid dynamics, it is conventional to distinguish between “puller” and “pusher” microswimmers on the basis of the forward or aft location of the flagella relative to the cell body: typically, bacteria are pushers and algae are pullers. Here we note that since many pullers have “outboard” cilia or flagella displaced laterally from the cell centerline on both sides of the organism, there are two important subclasses whose far-field is that of a stresslet, but whose near field is qualitatively more complex. The ciliary beat creates not only a propulsive force but also swirling flows that can be represented by paired rotlets with two possible senses of rotation, either “feeders” that sweep fluid toward the cell apex, or “expellers” that push fluid away. Experimental studies of the rotiferBrachionus plicatilisin combination with earlier work on the green algaeChlamydomonas reinhardtiishow that the two classes have markedly different interactions with surfaces. When swimming near a surface, expellers such asC. reinhardtiiscatter from the wall, whereas a feeder likeB. plicatilisstably attaches. This results in a stochastic “run-and-stick” locomotion, with periods of ballistic motion parallel to the surface interrupted by trapping at the surface.
Chromosome X Dosage Modulates Development of Aneuploidy in Genetically Diverse Mouse Embryonic Stem Cells
Authors: Stanton Alexander , Aydin Selcan , Skelly Daniel A. , Stavish Dylan , Leonhard Kim , Taapken Seth , McIntire Erik , Pankratz Matthew , Czechanski Anne , Ludwig Tenneille , Choi Ted , Gygi Steven P. , Barbaric Ivana , Munger Steven C. , Reinholdt Laura G. , Pera Martin F. 
Published: July 2024

SUMMARYThe genetic integrity of pluripotent stem cells (PSC) is critical to their applications in research and therapy, but it is compromised by frequent development of structural chromosome variants associated with malignancy. Many cell lines exhibit remarkable genetic stability, but little is known about the basis of the known variation in genomic integrity amongst different PSC isolates. Here we identify aneuploidies using RNA-seq and proteomics data from a panel of mouse embryonic stem cell (mESC) lines derived from 170 Diversity Outbred mice. We found 62 lines with detectable aneuploid subpopulations and a subset of originally XX lines that lost one Chromosome X (XO). Strikingly, a much lower proportion of XX lines were aneuploid, compared to XY or XO lines. Two single-cell RNA-seq data sets demonstrated that aneuploid XY DO mESC also show lower Chromosome X gene expression, and a prospective study confirmed that XY mESC accumulate higher aneuploid proportions in culture than isogenic XX lines. We identify potential mechanisms for this protective effect of X chromosome dosage, including our findings that the lines with two active X Chromosomes have a higher proportion of 2-cell-like cells, a state associated with maintenance of genetic integrity of mESC, and that they show differential expression of X-linked tumor suppressor genes associated with the DNA damage response.HighlightsFirst genetic analysis of predisposition to aneuploidy in pluripotent stem cell culturesChromosomal regions duplicated in aneuploid mouse embryonic stem cells are syntenic with regions overrepresented in human pluripotent stem cell lines bearing recurrent genetic abnormalitiesX-Chromosome dosage strongly influences susceptibility to aneuploidy in mouse embryonic stem cells and to a lesser degree in human pluripotent stem cellsXX mouse embryonic stem cell lines show a higher proportion of cells in 2 cell-like state and higher expression of tumor suppressor genes associated with DNA damage response
A positive list administered immunity system restricts the body size of insects
Authors: Ogata Norichika , Matsuda Tomoko 
Published: July 2024

AbstractThere are several explanations for the extinction of ancient giant insects. Here, we present a new hypothesis suggesting that the innate immune system limits the body sizes of insects. In this study, we co-cultured bacteria, fungi, and insect blood cells, and performed single-cell RNA sequencing analyses of insect blood cells to determine their division of labor. In the innate immune system, prohibited molecules are listed as signals of invasion. The increasing diversity of organisms makes this list extensive. The burden of managing such an extensive list leads to a division of labor among blood cells and reduces the effective number of blood cells. Our simulation indicates that a reduced number of effective blood cells cannot protect a giant body from invaders.