bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fat body‐derived juvenile hormone acid methyltransferase functions to maintain iron homeostasis in Drosophila melanogaster
Authors: Ye Yun‐Yan , Liu Zhi‐Hua , Wang Hui‐Li 
Published: July 2024

AbstractIron homeostasis is of critical importance to living organisms. Drosophila melanogaster has emerged as an excellent model to study iron homeostasis, while the regulatory mechanism of iron metabolism remains poorly understood. Herein, we accidently found that knockdown of juvenile hormone (JH) acid methyltransferase (Jhamt) specifically in the fat body, a key rate‐limiting enzyme for JH synthesis, led to iron accumulation locally, resulting in serious loss and dysfunction of fat body. Jhamt knockdown‐induced phenotypes were mitigated by iron deprivation, antioxidant and Ferrostatin‐1, a well‐known inhibitor of ferroptosis, suggesting ferroptosis was involved in Jhamt knockdown‐induced defects in the fat body. Further study demonstrated that upregulation of Tsf1 and Malvolio (Mvl, homolog of mammalian DMT1), two iron importers, accounted for Jhamt knockdown‐induced iron accumulation and dysfunction of the fat body. Mechanistically, Kr‐h1, a key transcription factor of JH, acts downstream of Jhamt inhibiting Tsf1 and Mvl transcriptionally. In summary, the findings indicated that fat body‐derived Jhamt is required for the development of Drosophila by maintaining iron homeostasis in the fat body, providing unique insight into the regulatory mechanisms of iron metabolism in Drosophila.
Strength of enemy release from parasitoids is context-dependent in the invasive African Fig Fly,Zaprionus indianus
Authors: Walsh-Antzak Camille R. , Erickson Priscilla A. 
Published: July 2024

AbstractUnderstanding the mechanisms underlying the success of biological invasions is essential to employ effective prediction and management strategies. Escape from natural enemies in invaded regions (enemy release hypothesis, ERH) and increased competitive ability are hallmarks of invasive species; however, these two processes are rarely studied within the same context. Here, we examined the effect of enemy release on the competition outcomes of a successful invasive insect pest in North America, the African fig fly (Zaprionus indianus). Parasitoid wasps such asLeptopilina heterotomathat parasitize drosophilid larvae may seek out established species with known host suitability over a novel species, so we hypothesizedZ. indianusmay have low susceptibility to parasitoids, giving them a competitive advantage over co-occurring drosophilids. We tested this hypothesis by comparing the adult emergence rates fromZ. indianuslarvae reared alone or in competition withDrosophila hydeiorD. simulanslarvae in the presence and absence of parasitoid wasps under low and high larval densities. At low larval densities,Z. indianusemerged at equal rates toD. hydeibut outcompetedD. simulans, and these outcomes were not affected by parasitoids. However, at high densities, the addition of parasitoids shifted competition outcomes in favor ofZ. indianus, suggesting enemy release provides a competitive advantage under some circumstances. These results indicate that the strength of enemy release inZ. indianusis widely dependent on contextual factors such as density and competitor species. This study emphasizes how a community approach to testing the ERH is vital as the overall interpretation of the presence and strength of enemy release differed between intraspecific and interspecific experiments. Further investigation of how these results apply to field environments could offer insight into howZ. indianusalters ecosystems and how productive biological control may limit the spread ofZ. indianus.Short AbstractInvasive species may succeed in new environments in part because they are less susceptible to diseases and parasites that have co-evolved with local hosts, giving invaders a competitive advantage. We tested this hypothesis by competing an invasive fruit fly against established species in the presence of parasitoid wasps that lay their eggs in fruit fly larvae. We found that the invasive species generally outcompeted other species in the presence of parasitoids, but the extent of its advantage depended on the species it was competing against and the number of larvae present.
Sex-related differences in vascular remodeling of sodium overloaded normotensive mice
Authors: Viegas Katia A. S. , Silva Juliane C. S. , Lima Rariane S. , Lima Cintia T. , Peron Natalia N. , Silva Maikon B. , Irigoyen Maria Claudia , Lacchini Silvia 
Published: July 2024

ABSTRACTBackground and Aims:Primary hypertension affect about 20% of adults in developed societies and, associated with high salt intake, leads to vascular remodeling, an adaptive physiological response of blood vessels that driven by repair, inflammation, or cell growth, is but may contribute to vascular diseases over time. This study examined vascular remodeling in the aorta and cardiac arteries, focused on gender-specific responses to sodium overload.Methods and Results:Adult male and female C57Bl/6 mice were divided into six groups: control with filtered water (Cont M; Cont F), 1% NaCl for two weeks (Salt-2 M; Salt-2 F), and 1% NaCl for twelve weeks (Salt-12 M; Salt-12 F). Blood pressure (BP) and heart rate (HR) were measured using tail plethysmography, and metabolic cages recorded 24-hour water intake and urine output. Morphometric analysis of the aorta and cardiac arteries included assessments of elastic laminae and collagen fibers, using Weigert van Gieson and Picrosirius staining. No changes in BP and HR were observed. Sodium intake increased water consumption in both genders after two weeks, but only males showed increased urine output. Vascular responses differed: males exhibited delayed increases in aortic elastic lamellae, while females showed earlier changes. Elastic lamellae in cardiac arteries remained unchanged. Collagen deposition increased in aortic walls for both genders but decreased by 50% in male cardiac arteries. Males showed thick collagen fibers, while females had thin and thick fibers.Conclusion:High sodium intake caused arterial stiffness through distinct mechanisms in males and females, even in normotensive animals.
Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis
Authors: Pessenda Gabriela , Ferreira Tiago R. , Paun Andrea , Kabat Juraj , Amaral Eduardo P. , Kamenyeva Olena , Gazzinelli-Guimaraes Pedro Henrique , Perera Shehan R. , Ganesan Sundar , Lee Sang Hun , Sacks David L. 
Published: July 2024

SUMMARYIn murine models of visceral leishmaniasis (VL), parasitization of resident Kupffer cells (resKCs) is responsible for early growth ofLeishmania infantumin the liver, which leads to granuloma formation and eventual parasite control. We employed the chronic VL model, and revealed an open niche established by KCs death and their migration outside of the sinusoids, resulting in their gradual replacement by monocyte-derived KCs (moKCs). While early granulomas were composed of resKCs, late granulomas were found outside of the sinusoids and contained resKC-derived macrophages, and monocyte-derived macrophages (momacs). ResKCs and moKCs within the sinusoids were identified as homeostatic/regulatory cells, while resKC-derived macrophages and momacs within late granulomas were pro-inflammatory. Despite the infection being largely confined to the resKC-derived macrophages, in the absence of monocyte recruitment, parasite control was strongly compromised. Macrophage heterogeneity, involving migration and reprogramming of resKCs, along with recruitment of monocyte-derived cells, is a hallmark of granuloma maturation and hepatic immunity in VL.
Real-time Plasmid Transmission Detection Pipeline
Authors: Scherff Natalie , Rothgänger Jörg , Weniger Thomas , Mellmann Alexander , Harmsen Dag 
Published: July 2024

AbstractThe spread of antimicrobial resistance among bacteria by horizontal plasmid transmissions poses a major challenge for clinical microbiology. Here, we evaluate a new real-time plasmid transmission detection pipeline implemented in the SeqSphere+(Ridom GmbH, Münster, Germany) software.Within the pipeline, a local Mash plasmid database is created and Mash searches with a distance threshold of 0.001 are used to trigger plasmid transmission early warning alerts (EWA). Clonal transmissions are detected using cgMLST allelic differences. The integrated tools MOB-suite, NCBI AMRFinderPlus, CGE MobileElementFinder, pyGenomeViz, and MUMmer are used to characterize plasmids and for visual pairwise plasmid comparisons, respectively. We evaluated the pipeline using published hybrid assemblies (Oxford Nanopore Technology/Illumina) of a surveillance and outbreak dataset with plasmid transmissions. To emulate prospective usage, samples were imported in chronological order of sampling date. Different combinations of the user-adjustable parameters sketch size (1,000 vs 10,000) and plasmid size correction were tested and discrepancies between resulting clusters were analyzed with Quast.When using a sketch size of 1,000 with size correction turned on, the SeqSphere+pipeline agreed with the published data and produced the same clonal and carbapenemase-carrying plasmid clusters. EWAs were in the correct chronological order.In summary, the developed pipeline presented here is suitable for integration into clinical microbiology settings with limited bioinformatics knowledge due to its automated analyses and alert system, which are combined with the GUI-based SeqSphere+platform. Thus, with its integrated sample database, (near) real-time plasmid transmission detection is within reach in bacterial routine-diagnostic settings when long-read sequencing is employed.ImportancePlasmid-mediated spread of antimicrobial resistance (AMR) is a major challenge for clinical microbiology and monitoring of potential plasmid transmissions is essential to combat further dissemination. Whole-genome sequencing (WGS) is often used to surveil nosocomial transmissions but usually limited to the detection of clonal transmissions (based on chromosomal markers). Recent advances in long-read sequencing technologies enable full reconstruction of plasmids and the detection of very similar plasmids but so far easy-to-use bioinformatic tools for this purpose were missing. Here we present an evaluation of an innovative real-time plasmid transmission detection pipeline. It is integrated into the GUI-based SeqSphere+software, which already offers cgMLST based pathogen outbreak detection. It requires very limited bioinformatics knowledge, and its database, automated analyses, and alert system make it well suited for prospective clinical application.
Where the patterns are: repetition-aware compression for colored de Bruijn graphs⋆
Authors: Campanelli Alessio , Pibiri Giulio Ermanno , Fan Jason , Patro Rob 
Published: July 2024

AbstractWe describe lossless compressed data structures for thecoloredde Bruijn graph (or, c-dBG). Given a collection of reference sequences, a c-dBG can be essentially regarded as a map fromk-mers to theircolor sets. The color set of ak-mer is the set of all identifiers, orcolors, of the references that contain thek-mer. While these maps find countless applications in computational biology (e.g., basic query, reading mapping, abundance estimation, etc.), their memory usage represents a serious challenge for large-scale sequence indexing. Our solutions leverage on the intrinsic repetitiveness of the color sets when indexing large collections of related genomes. Hence, the described algorithms factorize the color sets into patterns that repeat across the entire collection and represent these patterns once, instead of redundantly replicating their representation as would happen if the sets were encoded as atomic lists of integers. Experimental results across a range of datasets and query workloads show that these representations substantially improve over the space effectiveness of the best previous solutions (sometimes, even dramatically, yielding indexes that are smaller by an order of magnitude). Despite the space reduction, these indexes only moderately impact the efficiency of the queries compared to the fastest indexes.SoftwareThe implementation of the indexes used for all experiments in this work is written inC++17and is available athttps://github.com/jermp/fulgor.
A Powered Simple Walking Model Modifies the Rate of Recovery Definition: Human Walking Deviates Drastically from Pendular Motion During the Double Support Phase
Authors: Hosseini-Yazdi Seyed-Saleh 
Published: July 2024

AbstractThis study proposes a modified definition of the original rate of recovery (ROR) in human walking, derived from a powered simple walking model and center of mass work. The metric captures the proportion of energy transferred from one step to the next by incorporating total step mechanical dissipation. Our simulation results show that the modified ROR decreases nearly linearly with increasing walking speed on even terrain due to collision impulses scaling with velocity (𝑐𝑜∼𝑣ave) and energy dissipation scaling quadratically. For nominal even walking at 1.25 m. s-1, the analytical ROR was 85%, depicting higher rates than previously proposed. Empirical data, however, reveal lower ROR values due to additional energy dissipation factors, such as elevated collision dissipation or negative net single support work, which are not captured by the analytical model. In contrast to the analytical model, the experimental results also show a maximum rate of recovery occurring at 1.21 m. s-1(59.4%). This peak appeared when total step dissipation was considered. We also demonstrated that the ROR trajectory was not symmetrical as previously presented but depended on the total step dissipation. For uneven terrains with step height variations of ±0.036 m, the average analytical model ROR was 82%, suggesting that a completely random uneven terrain may be analytically approximated by even walking. However, the elevated energetic demands of uneven walking, primarily due to suboptimal pre-emptive push-offs (timing or magnitude), must further decrease the ROR. Similarly, other walking conditions associated with increased metabolic costs, such as aging or when vision about the coming terrain is denied (restricted lookahead: max rate 58.5%), are also expected to result in reduced RORs.
Neuronal GPCR NMUR-1 regulates energy homeostasis in response to pathogen infection
Authors: Wibisono Phillip , Liu Yiyong , Roberts Kenneth P , Baluya Dodge , Sun Jingru 
Published: July 2024

SUMMARYA key question in current immunology is how the innate immune system generates high levels of specificity. Our previous study inCaenorhabditis elegansrevealed that NMUR-1, a neuronal G protein-coupled receptor homologous to mammalian receptors for the neuropeptide neuromedin U (NMU), regulates distinct innate immune responses to different bacterial pathogens. Here, by using quantitative proteomics and functional assays, we discovered that NMUR-1 regulates F1FOATP synthase and ATP production in response to pathogen infection, and that such regulation contributes to NMUR-1-mediated specificity of innate immunity. We further demonstrated that ATP biosynthesis and its contribution to defense is neurally controlled by the NMUR-1 ligand CAPA-1 and its expressing neurons ASG. These findings indicate that NMUR-1 neural signaling regulates the specificity of innate immunity by controlling energy homeostasis as part of defense against pathogens. Our study provides mechanistic insights into the emerging roles of NMU signaling in immunity across animal phyla.
From histology to macroscale function in the human amygdala
Authors: Auer Hans , Cabalo Donna Gift , Rodriguez-Cruces Raul , Benkarim Oualid , Paquola Casey , DeKraker Jordan , Wang Yezhou , Valk Sofie , Bernhardt Boris C. , Royer Jessica 
Published: July 2024

ABSTRACTThe amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integratingpost mortemhistology andin vivoMRI at ultrahigh fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3Dpost mortemhistological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as medio-lateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach toin vivoMRI data acquired at 7 Tesla, we could demonstrate generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological andin vivoimaging techniques.
Pseudo-perplexity in One Fell Swoop for Protein Fitness Estimation
Authors: Kantroo Pranav , Wagner Günter P. , Machta Benjamin B. 
Published: July 2024

AbstractProtein language models trained on the masked language modeling objective learn to predict the identity of hidden amino acid residues within a sequence using the remaining observable sequence as context. They do so by embedding the residues into a high dimensional space that encapsulates the relevant contextual cues. These embedding vectors serve as an informative context-sensitive representation that not only aids with the defined training objective, but can also be used for other tasks by downstream models. We propose a scheme to use the embeddings of an unmasked sequence to estimate the corresponding masked probability vectors for all the positions in a single forward pass through the language model. This One Fell Swoop (OFS) approach allows us to efficiently estimate the pseudo-perplexity of the sequence, a measure of the model’s uncertainty in its predictions, that can also serve as a fitness estimate. We find that ESM2 OFS pseudo-perplexity performs nearly as well as the true pseudo-perplexity at fitness estimation, and more notably it defines a new state of the art on the ProteinGym Indels benchmark. The strong performance of the fitness measure prompted us to investigate if it could be used to detect the elevated stability reported in reconstructed ancestral sequences. We find that this measure ranks ancestral reconstructions as more fit than extant sequences. Finally, we show that the computational efficiency of the technique allows for the use of Monte Carlo methods that can rapidly explore functional sequence space.
Antiviral immunity within neural stem cells distinguishes viral strain differences in forebrain organoids
Authors: Vazquez Christine , Negatu Seble G. , Bannerman Carl D. , Sriram Sowmya , Ming Guo-Li , Jurado Kellie A. 
Published: July 2024

SummaryNeural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such responses to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified that neural stem cells, in particular radial glia, are basally primed to respond to virus infection by upregulating several antiviral interferon-stimulated genes. Infection of these organoids with a neuropathogenic Enterovirus-D68 strain, demonstrated the ability of this virus to impede immune activation by blocking interferon responses. Together, our data highlight immune gene signatures present in different types of neural stem cells and differential viral capacity to block neural-specific immune induction.
LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia
Authors: Weindel Chi G. , Ellzey Lily M. , Coleman Aja K. , Patrick Kristin L. , Watson Robert O. 
Published: July 2024

ABSTRACTMounting evidence supports a critical role for central nervous system (CNS) glial cells in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS), as well as neurovascular ischemic stroke. Previously, we found that loss of the PD-associated gene leucine-rich repeat kinase 2 (Lrrk2) in macrophages, peripheral innate immune cells, induced mitochondrial stress and elevated basal expression of type I interferon (IFN) stimulated genes (ISGs) due to chronic mitochondrial DNA engagement with the cGAS/STING DNA sensing pathway. Here, we report that loss of LRRK2 results in a paradoxical response in microglial cells, a CNS-specific macrophage population. In primary murine microglia and microglial cell lines, loss ofLrrk2reduces tonic IFN signaling leading to a reduction in ISG expression. Consistent with reduced type I IFN, mitochondria fromLrrk2KO microglia are protected from stress and have elevated metabolism. These protective phenotypes involve upregulation of NRF2, an important transcription factor in the response to oxidative stress and are restricted by LRRK2 kinase activity. Collectively, these findings illustrate a dichotomous role for LRRK2 within different immune cell populations and give insight into the fundamental differences between immune regulation in the CNS and the periphery.
Silicon Nitride Induces Osteoconduction Via Activated Mitochondrial Oxidative Phosphorylation and Neovascularization
Authors: Gonzales Wayne , Khade Ronit , Kondo Takeru , Arimoto Satomi , Inagaki Taro , Hokugo Akishige , Kaczor-Urbanowicz Karolina Elżbieta , McEntire Bryan , Bock Ryan , Ogawa Takahiro , Pezzotti Giuseppe , Nishimura Ichiro 
Published: July 2024

AbstractSilicon nitride (Si3N4: SiN) is a thermodynamically stable ceramic material with excellent mechanical properties, and wear and corrosion resistance for industrial applications. SiN has been proposed for orthopedic and dental implant applications owing to its enhanced osteoconduction. However, the biological mechanisms underlying SiN-induced bone formation have not been fully elucidated. In this study, SiN significantly increasedin vitromineralization of human bone marrow mesenchymal stromal cells (BM-MSC) andin vivoperi-implant bone volume in mouse femurs compared to conventionally used titanium (Ti) implants. RNA sequencing of BM-MSC cultured on SiN disks revealed that functional gene clusters associated with mitochondrial oxidative phosphorylation were significantly elevated. SiN in an aqueous solution has been shown to release ammonium/ammonia, which may provide a source for glutamine-dependent energy production, and BM-MSC upregulated the expression of a key enzyme, glutamate-ammonia ligase under osteogenic conditions. Additionally, SiN increased the expression of functional gene clusters involved in vascular formation. The upregulation ofHIF1a in vitroand increased VEGFR3-positive blanching vascular structuresin vivoimplied that SiN induced neovascularization. This study revealed an important mechanism through which SiN stimulated osteoconduction by unique glutamine-driven mitochondrial oxidative phosphorylation and established oxygen and nutrient supply by neovascularization, leading to stable osseointegration.