bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roseicyclus amphidinii sp. nov., a novel bacterium isolated from the culture of a dinoflagellate Amphidinium carterae
Authors: Cui Yudong , Mo Xueyi , Huang Zhaobin 
Published: February 2025

A Gram-negative, rod-shaped and light pink-pigmented bacterial strain, designated Amp-Y-6T, was isolated from the culture of a dinoflagellate Amphidinium carterae CCMP1314. It can produce bacteriochlorophyll a. The 16S rRNA gene of strain Amp-Y-6T had the highest sequence similarity with Roseicyclus marinus CCMM001T of 98.1%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Amp-Y-6T was affiliated to the genus Roseicyclus and formed a monophyletic clade with R. marinus CCMM001T and Roseicyclus mahoneyensis ML6T. The digital DNA–DNA hybridization, average nucleotide identity and average amino acid identity between strain Amp-Y-6T and the two phylogenetic relatives were 22.7–22.8, 80.4–80.5 and 79.5–80.2%, respectively. The respiratory quinone was Q-10. The major fatty acid composition was summed feature 8 (C18:1
ω7c and/or C18:1
ω6c). The draft genome size was 3.8 Mbp with a genomic G+C content of 68.1 mol%. Gene annotation showed that Amp-Y-6T contained a gene cluster responsible for the C-P degradation, indicating that it had the potential to provide a phosphate source for the dinoflagellate. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain Amp-Y-6T represents a novel species, for which the name Roseicyclus amphidinii sp. nov. is proposed. The type strain is Amp-Y-6T (=MCCC 1K08249T=KCTC 92882T).
T cell-intrinsic lymphoproliferation as a key driver of intestinal autoimmunity in acquired generalized lipodystrophy
Authors: Letizia Marilena , Omar Toka , Weidner Patrick , Jakob Manuel O. , Freise Inka , Krug Susanne M. , Löscher Britt-Sabina , Rosati Elisa , Obermayer Benedikt , Gamez-Belmonte Maria de los Reyes , Hecker Julia , Ziegler Joern-Felix , Weixler Benjamin , Asbach Patrick , Kunkel Desiree , Stumvoll Michael , Miehle Konstanze , Becker Christoph , Klose Christoph S.N. , Glauben Rainer , Beule Dieter , Kühl Anja , Franke Andre , Sanders Ashley , Siegmund Britta , Weidinger Carl 
Published: February 2025

AbstractAcquired generalized lipodystrophy (AGL) is a rare metabolic disorder frequently associated with autoimmunity. Its etiology is incompletely understood and the impact of adipose tissue loss on autoimmunity and intestinal inflammation in AGL remains unclear. Using mass cytometry and single-cell RNA sequencing, we observed an oligoclonal expansion of T cells in the periphery and inflamed intestine in a patient with AGL and Crohn’s disease (AGLCD). To explore if loss of adipose tissue triggers lymphoproliferation, we studied lipodystrophic mice as a model for AGL. Unexpectedly, lipodystrophic mice did not show T-cell expansion, were protected from colitis and displayed a defect in the development of pro-inflammatory T cells, which could be reversed by allogeneic fat transplantations, indicating that clonal T-cell expansion is not primarily caused by lipodystrophy. Instead, gene sequencing revealed a T cell-intrinsic de-novoNRASmutation, pointing towards somatic mosaicism as a driver of clonal T-cell expansion and systemic autoimmunity in AGLCD.
A Quantitative Look at Mitochondrial DNA in Genealogy
Authors: Spencer Robin W. 
Published: February 2025

AbstractMutations occur throughout the 16,569 basepair human mitochondrial genome and most are under strong purifying selection. Archaeologically and genealogically useful mutations, in contrast, are neutral and remain stable for centuries. In new results, multiple lines of evidence show that the latter appear on average every 2900 years and the effective genealogical chromosome is limited to about 4800 basepairs, 28% of its physical length. These mutations are already three-fold oversampled in the haplotree; all those in protein-coding genes are translationally synonymous. This evidence offers a limited prospect that additional testing can significantly increase the branching or temporal resolution of the haplotree.
The role of GATA2 in the expression of the soluble decoy receptor ST2/IL1RL1 in human and mouse mast cells
Authors: Nagata Kazuki , Kasakura Kazumi , Ishii Kenta , Ito Naoto , Hara Mutsuko , Okumura Ko , Nishiyama Chiharu 
Published: February 2025

AbstractTheST2/IL1RL1gene encodes a receptor subunit for IL-33. TheST2/IL1RL1gene is transcribed and translated to two splice variants, full-length ST2 (ST2L) and soluble ST2 (sST2). ST2L is expressed on cell surface as membrane bound molecule and forms a heterodimer with IL-1RAcP, which plays an important role in Th2 transduces a signaling of IL-33. In contrast, sST2 blocks the IL-33-signaling via functioning as a decoy receptor of IL-33. In this study, we analyzed the regulatory mechanisms of the gene expression of sST2 in mast cell, the major source of sST2. We found that a hematopoietic cell-specific transcription factor GATA2 is essential for sST2 expression in human mast cells (a cell line and primary cells) and mouse mast cells. Various assays including ChIP assay, reporter assay, and 3C assay revealed that GATA2 binding to the distal promoter of theIL1RL1gene transcriptionally activates proximal promoter-driven expression of sST2 through chromosomal conformation.
Diammonium glycyrrhizinate injection promotes zebrafish angiogenesis through the mTOR/HIF-1 signaling pathway
Authors: Yu Shuqing , Yu Jiahao , Sun Fengzhi , Zhang Xuanming , Sheng Wenlong , Liu Kechun , Li Xiaobin , Li Wei 
Published: February 2025

Abstract(1)BackgroundGlycyrrhizic acid (GA) is the main component of the traditional Chinese medicine Glycyrrhiza glabra. Many GA preparations in the pharmaceutical market have good efficacy in hepatoprotection and the treatment of liver diseases. However, the pro-angiogenic effects for GA-based agents have not been researched specifically. The aim of this study was to investigate the pro-angiogenic activity of GA preparations commonly used in clinical practice and screen the representative angiogenesis promotor to further elucidate the mechanism of action(2)MethodsA zebrafish vascular injury model induced by PTK787 was used to assess the pro-angiogenic effect of GA preparations. The pro-angiogenic activity of diammonium glycyrrhizinate injection (DGI) was further systematically evaluated by detecting the growth of the intersegmental vessels (ISVs) and subintestinal vein vessels (SIVs) in zebrafish. The underlying mechanism of action for DGI was explored by transcriptomics analysis and RT-qPCR validation;(3)ResultsThe results showed that magnesium isoglycyrrhizinate injection (MII), DGI, compound glycyrrhizinate tablets (CGT), and diammonium glycyrrhizinate enteric-coated capsules (DGEC) could demonstrate significantly pro-angiogenic effects. Among them, DGI exhibited the strongest activity. Transcriptomic analysis showed that the pro-angiogenic activity of DGI was closely associated with the mTOR signaling pathway. RT-qPCR results indicated that the expression levels of key genes of the mTOR/HIF-α pathway were significantly upregulated in DGI-treated zebrafish relative to the PTK787 group;(4)ConclusionsGA preparations have an obvious pro-angiogenic effect, in which DGI can exert particularly strong activity by activating the mTOR/HIF-1 signaling pathway. This study broadens the clinical application of GA agents and provides new insights into the pharmacodynamics and potential mechanisms of DGI as a candidate agent for treating ischemic diseases
A computational model elucidates the effect of oncogene induced expression alterations on the energy metabolism of neuroblastoma
Authors: Simon Mareike , Benary Uwe , Baum Katharina , Schramm Alexander , Wolf Jana 
Published: February 2025

AbstractAn altered energy metabolism is recognized as a hallmark of cancer. Experimental evidence shows that oncogenes play a key role in the reprogramming of metabolism. In neuroblastoma the oncogene MYCN, a main risk factor of poor prognosis, has been demonstrated to lead to expression changes in numerous glycolytic enzymes. Since it is not clear whether all these targets are required and how the overall metabolic response is shaped, we here dissect the effect of MYCN targets on the pathway individually and in combination using a computational modeling approach. We develop a first mathematical model of the energy metabolism in neuroblastoma cells based on our published experimental data. The analysis shows that MYCN overexpression overall leads to Warburg-like flux alterations with characteristic changes for the individual MYCN targets highlighting that MYCN targets can have opposing and sometimes unexpected effects. Interestingly, not all described MYCN targets contribute to notable flux alterations, at least in glycolysis. Our model moreover predicts a potential bistability of the cellular metabolism with an occurrence of a low-flux state likely representing quiescence. Overall, our study highlights the importance of analysing perturbations such as expression changes in the context of realistic pathways capturing their specific interactions and complex regulations.
Swiftly squeaky clean: lessons learned from eradicating an overpopulation of rats on an island of constraints
Authors: Micheletti Tatiane , Mello Thayna J. , Verona Carlos , Gasparotto Vinicius P. O. , Krul Ricardo , Araujo Ricardo , Sampaio Thali , Mangini Paulo Rogerio 
Published: February 2025

ABSTRACTInvasive rats threaten island biodiversity, disrupting ecosystems and endangering native species. While rat eradication has succeeded on many islands, tropical islands present unique management challenges. Strict regulations and financial constraints on some tropical islands further limit proven eradication methods, complicating rodent management. This study addresses these challenges by demonstrating a real-time active adaptive management (RAM) approach, providing a cautious, cost-efficient, scientifically grounded, and adaptive pathway to eradication, while adhering to strict environmental regulations. We implemented RAM on a Brazilian island at USD 3,300 per hectare, integrating rodenticide (brodifacoum) application, population monitoring, and iterative management adjustments. This approach eradicated a rat overpopulation within five months, with early population increases observed in the threatened masked booby and the endemic Noronha elaenia and Noronha skink. Despite logistical constraints, RAM proved effective and cost-efficient, marking its first application in a biological system. Our findings highlight the value of innovation, interdisciplinary collaboration, and adaptive decision-making when the application of best-practice methods is constrained.
Fiber photometry analysis of spontaneous dopamine signals: The z-scored data are not the data
Authors: Wallace Conner W , Slinkard Clare Y , Shaughnessy Rachael , Holleran Katherine M , Centanni Samuel W , Lapish Christopher C , Jones Sara R 
Published: February 2025

AbstractFluorescent sensors have revolutionized the measurement of molecules in the brain, and the dLight dopamine sensor has been used extensively to examine reward- and cue-evoked dopamine release, but only recently has the field turned its attention to spontaneous release events. Analysis of spontaneous events typically requires evaluation of hundreds of events over minutes to hours, and the most common method of analysis, z-scoring, was not designed for this purpose. Here, we compare the accuracy and reliability of three different analysis methods to identify pharmacologically induced changes in dopamine release and uptake in freely moving C57BL/6J mice. The D1-like receptor antagonist SCH23390 was used to prevent dLight sensors from interacting with dopamine in the extracellular space, while cocaine was used to inhibit uptake and raclopride to increase release of dopamine in the nucleus accumbens. We examined peak-to-peak frequency, peak amplitude, and width, the time spent above an established cutoff. The three methods were 1) the widely-used “Z-Score Method”, which automatically smooths baseline drift and normalizes recordings using signal-to-noise ratios, 2) a “Manual Method”, in which local baselines were adjusted manually and individual cutoffs were determined for each subject, and 3) the “Prominence Method” that combines z-scoring with prominence assessment to tag individual peaks, then returns to the preprocessed data for kinetic analysis. First, SCH23390 drastically reduced the number of signals detected as expected, but only when the Manual Method was used. Z-scoring failed to identify any changes, due to its amplification of noise when signals were diminished. Cocaine increased signal width as expected using the Manual and Prominence Methods, but not the Z-Score Method. Finally, raclopride- induced increases in amplitude were correctly identified by the Manual and Prominence Methods. The Z-Score Method failed to identify any of the changes in dopamine release and uptake kinetics. Thus, analysis of spontaneous dopamine signals requires assessment of the %ΔF/F values, ideally using the Manual Method, and the use of z- scoring is not appropriate.
Pericellular oxygen dynamics in human cardiac fibroblasts and iPSC-cardiomyocytes in high-throughput plates: insights from experiments and modeling
Authors: Li Weizhen , McLeod David , Antonevich Sarah , Li Zhenyu , Entcheva Emilia 
Published: February 2025

ABSTRACTAdequate oxygen supply is crucial for proper cellular function. The emergence of high-throughput (HT) expansion of human stem-cell-derived cells and HTin vitrocellular assays for drug testing necessitate monitoring and understanding of the oxygenation conditions, yet virtually no data exists for such settings. For metabolically active cells like cardiomyocytes, variations in oxygenation may significantly impact their maturation and function; conversely, electromechanical activity can drive oxygen demands. We used HT label-free optical measurements and computational modeling to gain insights about oxygen availability (peri-cellular oxygen dynamics) in syncytia of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) and human cardiac fibroblasts (cFB) grown in glass-bottom 96-well plates under static conditions. Our experimental results highlight the critical role of cell density and solution height (oxygen delivery path) in peri-cellular oxygen dynamics. The developed 3D reaction-diffusion model with Michaelis-Menten kinetics, trained on the obtained comprehensive data set, revealed that time-variant maximum oxygen consumption rate, Vmax, is needed to faithfully capture the complex peri-cellular oxygen dynamics in the excitable hiPSC-CMs, but not in the cFB. For the latter, accounting for cell proliferation was needed. Interestingly, we found both hypoxic (< 2%) and hyperoxic (> 7%) conditions can easily emerge in these standard HT plates in static culture and that peri-cellular oxygen dynamics evolves with days in culture. Our results and the developed computational model can directly be used to optimize cardiac cell growth in HT plates to achieve desired physiological conditions, important in cellular assays for cardiotoxicity, drug development, personalized medicine and heart regeneration applications.
Topologically Optimized Intrinsic Brain Networks
Authors: Lewis Noah , Iraji Armin , Miller Robyn , Agcaoglu Oktay , Calhoun Vince 
Published: February 2025

AbstractThe estimation of brain networks is instrumental in quantifying and evaluating brain function. Nevertheless, achieving precise estimations of subject-level networks has proven to be a formidable task. In response to this challenge, researchers have developed group-inference frameworks that leverage robust group-level estimations as a common reference point to infer corresponding subject-level networks. Generally, existing approaches either leverage the common reference as a strict, voxel-wise spatial constraint (i.e., strong constraints at the voxel level) or impose no constraints. Here, we propose a targeted approach that harnesses the topological information of group-level networks to encode a high-level representation of spatial properties to be used as constraints, which we refer to as Topologically Optimized Intrinsic Brain Networks (TOIBN). Consequently, our method inherits the significant advantages of constraint-based approaches, such as enhancing estimation efficacy in noisy data or small sample sizes. On the other hand, our method provides a softer constraint than voxel-wise penalties, which can result in the loss of individual variation, increased susceptibility to model biases, and potentially missing important subject-specific information. Our analyses show that the subject maps from our method are less noisy and true to the group networks while promoting subject variability that can be lost from strict constraints. We also find that the topological properties resulting from the TOIBN maps are more expressive of differences between individuals with schizophrenia and controls in the default mode, subcortical, and visual networks.
Consequences of training data composition for deep learning models in single-cell biology
Authors: Nadig Ajay , Thoutam Akshaya , Hughes Madeline , Gupta Anay , Navia Andrew W. , Fusi Nicolo , Raghavan Srivatsan , Winter Peter S. , Amini Ava P. , Crawford Lorin 
Published: February 2025

ABSTRACTFoundation models for single-cell transcriptomics have the potential to augment (or replace) purpose-built tools for a variety of common analyses, especially when data are sparse. Recent work with large language models has shown that training data composition greatly shapes performance; however, to date, single-cell foundation models have ignored this aspect, opting instead to train on the largest possible corpus. We systematically investigate the consequences of training dataset composition on the behavior of deep learning models of single-cell transcriptomics, focusing on human hematopoiesis as a tractable model system and including cells from adult and developing tissues, disease states, and perturbation atlases. We find that (1) these models generalize poorly to unseen cell types, (2) adding malignant cells to a healthy cell training corpus does not necessarily improve modeling of unseen malignant cells, and (3) including an embryonic stem cell differentiation atlas during training improves performance on out-of-distribution tasks. Our results emphasize the importance of diverse training data and suggest strategies to optimize future single-cell foundation models.
Single-nuclei RNA Sequencing Reveals Distinct Transcriptomic Signatures of Rat Dorsal Root Ganglia in a Chronic Discogenic Low Back Pain Model
Authors: Caparaso Sydney M. , Sankaranarayanan Ishwarya , Lillyman David J. , Price Theodore J. , Wachs Rebecca A. 
Published: February 2025

AbstractChronic low back pain (LBP), often correlated with intervertebral disc degeneration, is a leading source of disability worldwide yet remains poorly understood. Current treatments often fail to provide sustained relief, highlighting the need to better understand the mechanisms driving discogenic LBP. During disc degeneration, the extracellular matrix degrades, allowing nociceptive nerve fibers to innervate previously aneural disc regions. Persistent mechanical and inflammatory stimulation of nociceptors can induce plastic changes within dorsal root ganglia (DRG) neurons, characterized by altered gene expression, enhanced excitability, and lowered activation thresholds. Although these transcriptional changes have been described in other pain states, including osteoarthritis, they remain underexplored in discogenic LBP. To address this gap, this study represents the first application of comprehensive single-nuclei RNA sequencing of DRG neurons in a rat model of chronic discogenic LBP. Eighteen distinct DRG subpopulations were identified and mapped to existing mouse and cross-species atlases revealing strong similarities in neuronal populations with the mouse. Differential expression analysis revealed increased expression of pain-associated genes, includingScn9aandPiezo2, and neuroinflammatory mediators such asFstl1andNgfr, in LBP animals. Axial hypersensitivity, measured using grip strength, significantly correlated with increased expression ofScn9a, Fstl1, and Ngfr,which suggests their role in maintaining axial hypersensitivity in this model. These findings establish a relationship between DRG transcriptomic changes and axial hypersensitivity in a discogenic LBP model, identifying potential molecular targets for non-opioid treatments and advancing understanding of discogenic LBP mechanisms.
Autophagy Suppresses CCL2 to Preserve Appetite and Prevent Lethal Cachexia
Authors: Ibrahim Maria , Gomez-Jenkins Maria , Scheinfeld Adina , Zhao Zhengqiao , Lopes Eduardo Cararo , Sawant Akshada , Hu Zhixian , Dharani Aditya , Sun Michael , Siddiqui Sarah , Mirek Emily T. , Abram-Saliba Johan , Lattime Edmund C. , Su Xiaoyang , Janowitz Tobias , Goncalves Marcus D. , Dunn Steven M. , Pritykin Yuri , Anthony Tracy G. , Rabinowitz Joshua D. , White Eileen 
Published: February 2025

AbstractMacroautophagy (autophagy hereafter) captures intracellular components and delivers them to lysosomes for degradation and recycling1. In adult mice, autophagy sustains metabolism to prevent wasting by cachexia and to survive fasting, and also suppresses inflammation, liver steatosis, neurodegeneration, and lethality2,3. Defects in autophagy contribute to metabolic, inflammatory and degenerative diseases, however, the specific mechanisms involved were unclear4. Here we profiled metabolism and inflammation in adult mice with conditional, whole-body deficiency in an essential autophagy gene and found that autophagy deficiency altered fuel usage, and reduced ambulatory activity, energy expenditure, and food intake, and elevated circulating GDF15, CXCL10, and CCL2. While deletion ofGdf15orCxcl10provided no or mild benefit, deletion ofCcl2restored food intake, suppressed cachexia and rescued lethality of autophagy-deficient mice. To test if appetite suppression by CCL2 was responsible for lethal cachexia we performed single nucleus RNA sequencing of the hypothalamus, the center of appetite control in the brain. Notably, we found that autophagy deficiency was specifically toxic to PMCH and HCRT neurons that produce orexigenic neuropeptides that promote food intake, which was rescued by deficiency in CCL2. Finally, the restoration of food intake via leptin deficiency prevented lethal cachexia in autophagy-deficient mice. Our findings demonstrate a novel mechanism where autophagy prevents induction of a cachexia factor, CCL2, which damages neurons that maintain appetite, the destruction of which may be central to degenerative wasting conditions.Key points of paper1) Autophagy-deficient mice have reduced food intake, systemic inflammation, and cachexia2) CCL2, but not GDF15 or CXCL10, induces lethal cachexia caused by autophagy defect3) Autophagy-deficient mice have CCL2-dependent destruction of appetite-promoting neurons in the hypothalamus4) Leptin deficiency restores appetite and rescues lethal cachexia in autophagy-deficient mice5) Autophagy-deficient mice die from cachexia mediated by appetite loss6) Degenerative conditions due to impaired autophagy are caused by the inflammatory response to the damage7) Targeting CCL2 may be a viable approach to prevent degenerative wasting disorders