bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay of genotypic and thermal sex determination shapes climatic distribution in herpetofauna
Authors: Nemesházi Edina , Bókony Veronika 
Published: April 2024

AbstractSex is a fundamental trait of all sexually reproducing organisms, and sex-determination systems show a great diversity across the tree of life. A growing body of evidence shows that genotypic and temperature-dependent sex determination (GSD and TSD, respectively) can coexist, which theoretically can have wide-ranging consequences for demography and population persistence, especially under climate change. Temperature-induced sex reversal, resulting from combined effects of sex chromosomes and environmental temperatures on sexual development, can explain the frequent transitions between GSD and TSD, and even between different GSD systems, that happened multiple times in ectothermic vertebrates. However, general lack of empirical data on the prevalence of sex reversal has long constrained the assessment of its evolutionary-ecological significance. Here we analysed an exhaustive compilation of available data to demonstrate that the climatic distribution of extant species is explained by the combination of their sex-chromosome system (GSD) and temperature reaction norm (TSD) across the phylogeny of amphibians and some reptiles. This pattern is in accordance with predictions of the ‘asymmetrical sex reversal’ theory, underscoring the importance of temperature-induced sex reversal in phylogeography, evolution, and species conservation under the threat of climate change, and highlighting the need for more empirical research on sex reversal in nature.
Glia-Mediated Antigen Presentation In The Retina During Degeneration
Authors: Intonti Simona , Kokona Despina , Zinkernagel Martin S. , Stein Jens V. , Enzmann Volker , Conedera Federica M. 
Published: April 2024

ABSTRACTGlia antigen-presenting cells (APCs) are pivotal regulators of immune surveillance within the retina, maintaining tissue homeostasis and promptly responding to insults. The intricate mechanisms underlying their local coordination and activation remain unclear.Our study integrates an animal model of retinal injury, retrospective analysis of human retinas, and in vitro experiments to elucidate insights into the pivotal role of antigen presentation in neuroimmunology during retinal degeneration, uncovering the involvement of various glial cells, notably Müller glia, and microglia. Glial cells act as sentinels, detecting antigens released during degeneration and interacting with T-cells via MHC molecules, which are essential for immune responses. Microglia function as APCs via the MHC class II pathway, upregulating key molecules such as Csf1r and cytokines. In contrast, Müller cells act as atypical APCs through the MHC class I pathway, exhibiting upregulated antigen processing genes and promoting a CD8+T-cell response. Distinct cytokine signaling pathways, including TNF-α and IFN, contribute to the immune balance. Human retinal specimens corroborate these findings, demonstrating glial activation and MHC expression correlating with degenerative changes. In vitro assays also confirmed differential T-cell migration responses to activated microglia and Müller cells, highlighting their role in shaping the immune milieu within the retina. These insights emphasize the complex interplay between glial cells and T-cells, influencing the inflammatory environment and potentially modulating degenerative processes.In summary, our study emphasizes the involvement of retinal glial cells in modulating the immune response after insults to the retinal parenchyma. Thus, unraveling the intricacies of glia-mediated antigen presentation in retinal degeneration is essential for developing precise therapeutic interventions for retinal pathologies.
Coated crystalline essential amino acid supplementation supports high soybean meal inclusion in diets for Nile tilapia (Oreochromis niloticus) with improved protein retention and nutrient assimilation
Authors: Davies Simon J. , Bell Matt E. 
Published: April 2024

AbstractThe aquaculture industry has previously relied on high-quality fishmeal (FM) to produce diets of excellent standards. However, plant-based proteins such as soybean are more cost-effective for low-value fish species, for example, tilapia and carp, and fishmeal use has been significantly diminished. Previous studies have mainly addressed standard soybean meal (SBM) sources in aquafeeds. A 55-day feeding trial was conducted to investigate the replacement of fish meal with soybean meal concentrate in Nile tilapia (Oreochromis niloticus)using a semi-purified diet approach against a Low Temperature (LT) fishmeal as a primary reference protein. Four diets with different levels of soybean meal were evaluated and compared to a control diet of 100 % fish meal. Three diets containing 20, 40, and 80 % soybean protein concentrate (SBPC) were examined. The fourth diet consisted of 80 % SBPC and two essential amino acids: lysine and methionine (80SBPCAA) in a coated form. The average daily growth values highlight similar daily growth rates when tilapia was fed 100FM and 40SBPC. No significant differences were observed in the final mean weight for all soybean-fed tilapia, but they were marginally lower than the 100FM control diet group. The 80SBPC diet showed the poorest feed conversion ratio (FCR) at 1.31 and protein efficiency ratio (PER) at 2.19. However, the 80SBPCAAdiet showed a significantly improved result for per cent weight gain compared to the 80SBPC-fed tilapia. Also, protein efficiency ratio was significantly higher at 2.47 and had a better Apparent Net Protein Utilization (ANPU) value of 28.51 % compared to un-supplemented 80SBPC-fed tilapia (25.48 %). These results confirmed that high-quality fishmeal can be substituted by up to 40 % SBPC alone and without any detrimental effects on growth or carcass composition. Further studies on plant proteins and supplementary amino acids as a suitable alternative for replacing high-quality fishmeal may promote a more sustainable aquaculture industry.
A Comprehensive Collection of Pain and Opioid Use Disorder Compounds for High-Throughput Screening and Artificial Intelligence-Driven Drug Discovery
Authors: Hu Xin , Shinn Paul , Itkin Zina , Ye Lin , Zhang Ya-Qin , Shen Min , Ford-Scheimer Stephanie , Hall Matthew D. 
Published: April 2024

AbstractAs part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, the National Center for Advancing Translational Sciences (NCATS) is dedicated to the development of new pharmacological tools and investigational drugs for managing and treating pain, as well as the prevention and treatment of opioid misuse and addiction. In line with these objectives, we created a comprehensive, annotated small molecule library including drugs, probes, and tool compounds that act on published pain and addiction-relevant targets. Nearly 3,000 small molecules associated with approximately 200 known and hypothesized HEAL targets have been assembled, curated, and annotated in one collection. Physical samples of the library compounds have been acquired and plated in 1536-well format, enabling rapid and efficient high throughput screen (HTS) against a wide range of assays. The creation of the HEAL Targets and Compounds Library, coupled with an integrated computational platform for AI-driven machine learning (ML), structural modeling, and virtual screening (VS), provides a valuable source for strategic drug repurposing, innovative profiling, and hypothesis testing of novel targets related to pain and opioid use disorder (OUD). The library is available to investigators for screening pain and OUD-relevant phenotypes.
Tagging of Exo70 at the N-terminus compromises its assembly with the exocyst complex and changes its spatiotemporal behavior at the plasma membrane
Authors: Gosain Hiteshika , Seebohm Guiscard , Holtmannspötter Michael , Kurre Rainer , Busch Karin B. 
Published: April 2024

ABSTRACTThe vesicle-tethering exocyst complex is a key regulator of cell polarity. The subunit Exo70 is required for the targeting of the exocyst complex to the plasma membrane. While the N-terminus of Exo70 is important for its regulation by GTPases, the C-terminus binds to PI(4,5)P2 and Arp2/3. Here, we compare N- and C-terminal tagged Exo70 with respect to subcellular localization, dynamics and function in cell membrane expansion. Using high-resolution imaging, we determined the spatial distribution and dynamics in different sub-compartments of un-polarized and polarized cells. With lattice light-sheet microscopy, we show that HaloTag-Exo70, but not Exo70-HaloTag, promotes the outgrowth of filopodia-like structures from the axon of hippocampal neurons. Fluorescence lifetime imaging of sfGFP-Exo70 and molecular modeling results suggest that the assembly of sfGFP-Exo70 with the exocyst complex is reduced. This is supported by single particle tracking data showing higher mobility of N- than C-terminal tagged Exo70 at the plasma membrane. The distinct spatiotemporal properties of N-terminal tagged Exo70 were correlated with pronounced filopodia formation in unpolarized cells and neurons, a process that is less reliant on exocyst complex formation. We therefore propose that N-terminal tagging of Exo70 shifts its activity to processes that are less exocyst-dependent.Why it mattersIn the life sciences, the high-resolution visualization of processes in living cells is of great interest. To tag proteins, they are fused with fluorescent proteins, usually at the N- or C-terminus of the amino acid sequence. We show here that the position of the tag alters the function and interaction of Exo70, a polypeptide involved in vesicle fusion, but also in membrane bending and expansion. Using state-of-the-art microscopic techniques, single particle localization and tracking, fluorescence lifetime imaging microscopy and co-localization in combination with modeling, we conclude that N-terminal tagging of Exo70 impairs its assembly with the exocyst complex and instead promotes the interaction of free Exo70 with the actin skeleton, which favors controlled membrane expansion into filipodia.
Heart rate changes related to risky selections and outcomes in a rat gambling task
Authors: Fukushima Fumiya , Tamura Atsushi , Kuga Nahoko , Sasaki Takuya 
Published: April 2024

ABSTRACTRisk-taking behavior is crucial for animals to increase their potential outcomes and is considered to alter arousal states in the brain and body represented by heart rates. In this study, we monitored changes in heart rate as rats performed a gambling task in which they selected either a certain outcome with 100% probability (sure option) or a probabilistic double outcome with 50% probability (risky option). We found that when rats selected risky options, they exhibited significantly greater decreases in their instantaneous heart rates immediately before selection than when they selected certain options. In addition, we observed significantly larger increases in instantaneous heart rates when the rats were informed of the larger number of outcomes after selecting the risky options than after selecting the sure options. These results demonstrate that animals can dynamically alter their instantaneous heart rates in response to risky selection and outcomes.
Atlas of Cynomolgus Macaque Hematopoiesis
Authors: Oshima Shinichiro , Sinha Rahul , Takeuchi Kazuhiro , Mizuta Ken , Nakamura Tomonori , Ito Ryoji , Kawamoto Ikuo , Iwatani Chizuru , Nakaya Masataka , Tsuchiya Hideaki , Bhagat Shruti , Tsukiyama Tomoyuki , Takaori-Kondo Akifumi , Saitou Mitinori , Murakawa Yasuhiro , Yamamoto Ryo 
Published: April 2024

SummarySelf-renewal and differentiation are inherent properties of hematopoietic stem cells (HSCs) that are necessary to support hematopoiesis; however, the underlying mechanisms, especially in human, remain unclear. Here, using the cynomolgus macaque as a surrogate model, we develop a new gating strategy to isolate with high purity transplantable cynomolgus HSCs and generated a single-cell transcriptomic map of cynomolgus HSCs and progenitor cells — that covering gestational periods previously not analyzed in human. We show that hematopoietic cells from the late-1stto early-3rdtrimester fetal liver and late-2ndtrimester and thereafter bone marrow have repopulating potential, closely mimicking humans. Unexpectedly however, we found unlike in human, cynomolgus HSCs express CD38 but not CD33, indicating that these cellular counterparts are molecularly distinct. Our transcriptomic analysis reveals the presence of a direct differentiation pathway from HSCs to megakaryocyte lineages, lineage-primed multipotent progenitors and also identified putative HSC surface markers. Taken together, our comprehensive dataset highlights not only the utility of cynomolgus monkeys as model systems to study hematopoiesis but also their potential for translational applications.
Temporal tissue dynamics from a spatial snapshot
Authors: Somer Jonathan , Mannor Shie , Alon Uri 
Published: April 2024

AbstractPhysiological and pathological processes such as inflammation or cancer emerge from the interactions between cells over time. However, methods to follow cell populations over time within the native context of a human tissue are lacking, because a biopsy offers only a single snapshot. Here we present one-shot tissue dynamics reconstruction (OSDR), an approach to estimate a dynamical model of cell populations based on a single tissue sample. OSDR uses spatial proteomics to learn how the composition of cellular neighborhoods influences division rate, providing a dynamical model of cell population change over time. We apply OSDR to human breast cancer data, and reconstruct two fixed points of fibroblasts and macrophage interactions. These fixed points correspond to hot and cold fibrosis, in agreement with co-culture experiments that measured these dynamics directly. We then use OSDR to discover a pulse-generating excitable circuit of T and B cells in the tumor microenvironment, suggesting temporal flares of adaptive anti-cancer responses. Finally, we study longitudinal biopsies from a triple negative breast cancer clinical trial, where OSDR predicts the collapse of the tumor cell population in responders versus non-responders based on early treatment biopsies. OSDR can be applied to a wide range of spatial proteomics assays to enable analysis of tissue dynamics based on patient biopsies.
Chromosome level genome reference of the Caucasian dwarf gobyKnipowitschiacf.caucasica, a new alien Gobiidae invading the River Rhine
Authors: Schoenle Alexandra , Guiglielmoni Nadège , Mainz Tobias , Greve Carola , Hamadou Alexander Ben , Heermann Lisa , Borcherding Jost , Waldvogel Ann-Marie 
Published: April 2024

AbstractThe Caucasian dwarf gobyKnipowitschiacf.caucasicais a new invasive alien Gobiidae spreading in the Lower Rhine since 2019. Little is known about the invasion biology of the species and further investigations to reconstruct the invasion history are lacking genomic resources. We assembled a high-quality chromosome-scale reference genome ofKnipowitschiacf.caucasicaby combining PacBio, Omni-C and Illumina technologies. The size of the assembled genome is 956.58 Mb with a N50 scaffold length of 43 Mb, which includes 92.3 % complete Actinopterygii Benchmarking Universal Single-Copy Orthologs. 98.96 % of the assembly sequence was assigned to 23 chromosome-level scaffolds, with a GC-content of 42.83 %. Repetitive elements account for 53.08 % of the genome. The chromosome-level genome contained 26,404 transcripts with 23,210 multi-exons, of which 26,260 genes were functionally annotated. In summary, the high-quality genome assembly provides a fundamental basis to understand the adaptive advantage of the species.
Predicting organoid morphology through a phase field model: insights into cell division and lumenal pressure
Authors: Tanida Sakurako , Fuji Kana , Lu Linjie , Guyomar Tristan , Lee Byung Ho , Honigmann Alf , Grapin-Botton Anne , Riveline Daniel , Hiraiwa Tetsuya , Nonomura Makiko , Sano Masaki 
Published: April 2024

AbstractOrganoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack of understanding regarding the generalized rules that enable use of simple cellular principles to make morphological predictions of entire organoids. Therefore, we employed a phase field model with the following basic components: the minimum conditions for the timing and volume of cell division, lumen nucleation rules, and lumenal pressure. Through our model, we could compute and generate a myriad of organoid phenotypes observed till date. We propose morphological indices necessary to characterize the shapes and construct phase diagrams and show their dependencies on proliferation time and lumen pressure. Additionally, we introduced the lumen-index parameter, which helped in examining the criteria to maintain organoids as spherical structures comprising a single layer of cells and enclosing an intact lumen. Finally, we predict a star-like organoid phenotype that did not undergo differentiation, suggesting that the volume constraint during cell division may determine the final phenotype. In summary, our approach provides researchers with guidelines to test the mechanisms of self-organization and predict the shape of organoid.Author summaryIn nature, a wide variety of organ morphologies are observed. Owing to the complexity of the process underlying the acquisition of organs’ morphology, it is challenging to investigate the mechanisms that lead to such variations. A promising approach to study these variations is the use of “computational organoid” study, which is the computational-based study of self-organizing shapes in multicellular assemblies and fluid-filled cavities called lumens that develop from a few proliferating cells. This study explores general mechanisms that dictate how various mechanical factors affect the growing self-organized multicellular assembly. We relied on computer simulations of the mathematical model called multicellular phase-field model with lumens and explored the mechanical factor effects, such as the lumen pressure while considering the time and volume conditions required for cell division. These simulations generated and categorized a wide range of organoid phenotypes based on the varying lumen pressure and cell division conditions. These phenotypes were characterized into seven distinct classes, based on the morphological index sets, including a cellular monolayer/multilayer surrounding single or multiple lumens and branch formation. These phenotypes were obtained without the assumption of differentiation. Our study elucidates the mechanisms underlying the organoid and organ formation with different shapes, thereby highlighting the significance of mechanical forces in shaping these complex biological structures.
EEG Analyses of visual cue effects on executed movements
Authors: Suwandjieff Patrick , Müller-Putz Gernot R. 
Published: April 2024

AbstractBackgroundIn electroencephalographic (EEG) or electrocorticographic (ECoG) experiments, visual cues are commonly used for timing synchronization but may inadvertently induce neural activity and cognitive processing, posing challenges when decoding self-initiated tasks.New MethodTo address this concern, we introduced four new visual cues (Fade, Rotation, Reference, and Star) and investigated their impact on brain signals. Our objective was to identify a cue that minimizes its influence on brain activity, facilitating cue-effect free classifier training for asynchronous applications, particularly aiding individuals with severe paralysis.Results22 able-bodied, right-handed participants aged 18-30 performed hand movements upon presentation of the visual cues. Analysis of time-variability between movement onset and cue-aligned data, grand average MRCPs, and classification outcomes revealed significant differences among cues. Rotation and Reference cue exhibited favorable results in minimizing temporal variability, maintaining MRCP patterns, and achieving comparable accuracy to self-paced signals in classification.Comparison with Existing MethodsOur study contrasts with traditional cue-based paradigms by introducing novel visual cues designed to mitigate unintended neural activity. We demonstrate the effectiveness of Rotation and Reference cue in eliciting consistent and accurate MRCPs during motor tasks, surpassing previous methods in achieving precise timing and high discriminability for classifier training.ConclusionsPrecision in cue timing is crucial for training classifiers, where both Rotation and Reference cue demonstrate minimal variability and high discriminability, highlighting their potential for accurate classifications in online scenarios. These findings offer promising avenues for refining brain-computer interface systems, particularly for individuals with motor impairments, by enabling more reliable and intuitive control mechanisms.
Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis
Authors: Yang Luting , Hu Chunqing , Chen Xiaowen , Zhang Jie , Feng Zhe , Xiao Yanxin , He Weitai , Cui Tingting , Zhang Xin , Yang Yang , Zhang Yaling , Yan Yaping 
Published: April 2024

AbstractReactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. However, the role and molecular mechanism of metabolic reprogramming in activation of astrocytes have not been clarified. Here, we found that PKM2, a notoriously known rate-limiting enzyme of glycolysis, displayed nuclear translocation in astrocytes of EAE (experimental autoimmune encephalomyelitis) mice, an animal model of multiple sclerosis. Prevention of PKM2 nuclear import by DASA-58 significantly reduced the activation of primary astrocytes, which was observed by decreased proliferation, glycolysis and secretion of inflammatory cytokines. Most importantly, we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. TRIM21 interacted with PKM2, promoted its nuclear translocation and stimulated its nuclear activity to phosphorylate STAT3, NF-κB and interact with c-myc. Further single-cell RNA sequencing and immunofluorescence staining demonstrated that TRIM21 expression was upregulated in astrocytes of EAE. TRIM21 overexpressing in primary astrocytes enhanced PKM2-dependent glycolysis and proliferation, which could be reversed by DASA-58. Moreover, intracerebroventricular injection of a lentiviral vector to knockdown TRIM21 in astrocytes or intraperitoneal injection of TEPP-46, which inhibit the nuclear translocation of PKM2, effectively decreased disease severity, CNS inflammation and demyelination in EAE. Collectively, our study provides novel insights into the pathological function of nuclear glycolytic enzyme PKM2 and ubiquitination-mediated regulatory mechanism that are involved in astrocyte activation. Targeting this axis may be a potential therapeutic strategy for the treatment of astrocyte-involved neurological disease.