bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDC42 Inhibitors Alter Patterns of Vessel Arborization in Skin and Tumors in vivo
Authors: Vuong Linh M , Hachey Stephanie , Shiu Jessica , Xie Danny F , Salvador Noel , Brindani Nicoletta , Bertozzi Sine Mandrup , Summa Maria , Bertorelli Rosalia , Armirotti Andrea , Pham Rachel , Ku Vance SH , Nguyen Terry , Choi Bernard , Hughes Christopher CW , De Vivo Marco , Ganesan Anand K 
Published: April 2024

AbstractTumors that arise in the epidermis must develop a vascular supply to grow beyond a millimeter in depth. This process requires CDC42 GTPases such as CDC42, RhoJ and RhoQ. Despite this dependence on angiogenesis for growth, melanoma tumors are minimally responsive to current anti-angiogenesis agents, highlighting the need for more effective drugs in this class. Here we integrate antibody infusion, optical tissue clearing, multiphoton imaging, and three-dimensional semi-automated tracing to develop a quantitative approach to measure changes in vascular architecture in skin and skin tumors. This new approach uncovered differences in vessel arborization in the skin of RhoJ KO mice as compared to wild-type mice. Furthermore, novel small molecules that inhibit CDC42 GTPases inhibited both tumor growth and vessel branching within tumors to a similar degree as Braf inhibitors, which are commonly used to treat melanoma. In contrast to Braf inhibitors, however, which only affected tumor vasculature, CDC42 inhibitors affected vascularization in both tumor and normal skin without apparent toxicity to endothelial or stromal cells. These novel CDC42 inhibitors similarly blocked vessel branching in human cell-based micro-physiological models of normal and tumor vessels. RNA sequencing revealed reduced expression of multiple angiogenesis-related genes in drug-treated skin. Taken together, these studies identify a new class of pharmacologic agents that inhibit vessel branching in both normal skin and tumors with potential utility for treating skin cancer and skin diseases characterized by pathologic angiogenesis.
Metabolite accumulation from oral NMN supplementation drives aging-specific kidney inflammation
Authors: Saleh Tara A. , Whitson Jeremy , Keiser Phoebe , Prasad Praveena , Jenkins Brenita C. , Sodeinde Tori , Mann Carolyn N. , Rabinovitch Peter S. , McReynolds Melanie R. , Sweetwyne Mariya T. 
Published: April 2024

AbstractThe mitochondrial-rich renal tubule cells are key regulators of blood homeostasis via excretion and reabsorption of metabolic waste. With age, tubules are subject to increasing mitochondrial dysfunction and declining nicotinamide adenine dinucleotide (NAD+) levels, both hampering ATP production efficiency. We tested two mitochondrial interventions in young (6-mo) and aged (26-mo) adult male mice: (ELAM), a tetrapeptide in clinical trials that improves mitochondrial structure and function, and nicotinamide mononucleotide (NMN), an NAD+intermediate and commercially available oral supplement. Kidneys were analyzed from young and aged mice after eight weeks of treatment with ELAM (3 mg/kg/day), NMN (300 mg/kg/day), or from aged mice treated with the two interventions combined (ELAM+NMN). We hypothesized that combining pharmacologic treatments to ameliorate mitochondrial dysfunction and boost NAD+levels, would more effectively reduce kidney aging than either intervention alone. Unexpectedly, in aged kidneys, NMN increased expression of genetic markers of inflammation (IL-1β and Ccl2) and tubule injury (Kim-1). Metabolomics of endpoint sera showed that NMN-treated aged mice had higher circulating levels of uremic toxins than either aged controls or young NMN-treated mice. ELAM+NMN- treated aged mice accumulated uremic toxins like NMN-only aged mice, but reduced IL-1β and Ccl2 kidney mRNA. This suggests that pre-existing mitochondrial dysfunction in aged kidney underlies susceptibility to inflammatory signaling with NMN supplementation in aged, but not young, mice. These findings demonstrate age and tissue dependent effects on downstream metabolic accumulation from NMN and highlight the need for targeted analysis of aged kidneys to assess the safety of anti-aging supplements in older populations.Summary StatementDeclining levels of NAD+and increasing mitochondrial dysfunction with age are functionally linked and are popular mechanistic targets of commercially available anti-aging therapeutics. Studies have focused on nicotinamide mononucleotide (NMN), nicotinamide riboside (NR) and nicotinamide (NAM) supplementation to boost cellular NAD+, but a consensus on the dosage and regimen that is beneficial or tolerable has not been reached. We show that although high levels of sustained NMN supplementation are beneficial to liver and heart in aged mice, the same dosing regimen carries age-associated signs of kidney inflammation. Our findings underscore a complex state of age- and tissue-specific metabolic homeostasis and raise questions not only about how much, and for how long, but at what age is NAD+boosting safe.
High-throughput three-dimensional characterization of morphogenetic signals during the formation of the vertebrate retina
Authors: Ledesma-Terrón Mario , Pérez-Dones Diego , Mazó-Durán Diego , Míguez David G. 
Published: April 2024

AbstractThe precise differentiation of neural progenitors during development ensures the correct cognitive, sensory and motor functions of higher organisms. This balance between self-renewal and terminal differentiation is regulated by a complex interplay of signaling pathways, that set the spatial and temporal cues that ultimately shape and organize neurogenic tissues. The developing vertebrate retina is a widely used model to study how these key signaling cascades modulate the mode and rate of division of neural progenitors, despite its complex threedimensional architecture and the asymmetric differentiation dynamics. Here, we present a comprehensive multi-step framework that integratesin totoexperiments with three dimensional image analysis and theoretical tools to provide a quantitative characterization of the dynamics of growth and differentiation of the developing vertebrate retina. Additionally, we use small molecule inhibitors to show that Hh and FGF activation promote differentiation and cell cycle progression, while Wnt and Notch activation respectively increase and decrease the average division rate. These results represent a detailed and accurate quantitative characterization of the development and regulation of the vertebrate retina. We propose that the same framework can be directly used to characterize otherin vitroorin vivotissues.
Do mixed-species groups travel as one? An investigation on large African herbivores using animal-borne video collars
Authors: Dejeante Romain , Valeix Marion , Chamaillé-Jammes Simon 
Published: April 2024

ABSTRACTAlthough prey foraging in mixed-species groups benefit from a reduced risk of predation, whether heterospecific groupmates move together in the landscape, and more generally to what extent mixed-species groups remain cohesive over time and space remains unknown. Here, we used GPS collars with video cameras to investigate the movements of plains zebras (Equus quagga) in mixed-species groups. Blue wildebeest (Connochaetes taurinus), impalas (Aepyceros melampus) and giraffes (Giraffa camelopardalis) commonly form mixed-species groups with zebras in savanna ecosystems. We found that zebras adjust their movement decisions solely to the presence of giraffes, being more likely to move in zebra-giraffe herds, and this was correlated to a higher cohesion of such groups. Additionally, zebras moving with giraffes spent longer time grazing, suggesting that zebras follow giraffes to forage in their proximity. Our results provide new insights on animal movements in mixed-species groups, contributing to a better consideration of mutualism in movement ecology.
Satellite glial cells from adult DRG dedifferentiatein vitroand can be reprogrammed into nociceptor-like neurons
Authors: Sodmann Annemarie , Köhler Niels , Esfahani Nastaran M. , Schukraft Nina , Aue Annemarie , Jager Sara E. , Bischler Thorsten , Imdahl Fabian , Gräfenhan Tom , Leipold Enrico , Rittner Heike L. , Blum Robert 
Published: April 2024

AbstractLoss of sensory neurons in the dorsal root ganglia (DRG) may be a cause of neuropathic pain following traumatic nerve lesion or surgery. To regenerate peripheral sensory neurons, satellite glial cells (SGCs) may be an attractive endogenous cell source. SGCs are known to acquire certain neural progenitor-like properties after injury and are derived from the same neural crest lineage as sensory neurons. Here, we found that adult mouse DRG harbor SGC-like cells that dedifferentiate into glial sensory progenitor cellsin vitro. Surprisingly, forced coexpression of the early developmental transcription factors Neurog1 and Neurog2 was sufficient to induce neuronal and glial cell phenotypes. In the presence of nerve growth factor, the induced neurons developed a nociceptor phenotype characterized by functional expression of marker ion channels such as TrpA1, TrpV1 and TTX-resistant NaVchannels. Our study demonstrates that glial cells harvested from the adult DRG have neural stem cell-like properties, are multipotent, and may be useful for future neural repair strategies in the peripheral nervous system.Summary statementThe adult dorsal root ganglion carries a satellite glial cell source for generation of induced nociceptor-like neurons. The cells dedifferentiatein vitroand acquire properties of a multipotent peripheral neural progenitor.
Differential Proteomic Analysis of Serum and Bone Marrow Supernatant in Acute myeloid leukemia Patients at Low and Intermediate Altitudes after Chemotherapy
Authors: Sun Qi , Zhou Houfa , Wang Aibo , Li Wenqian , Xie Youbang 
Published: April 2024

AbstractChemotherapy is the primary treatment for patients with acute myeloid leukemia (AML). In addition to factors such as patient age, physical condition, and choice of medication, we have noticed that environmental factors such as altitude may also have a significant impact on post-chemotherapy bone marrow suppression in AML patients in clinical practice. The results indicate that there are differences in the proteomics of the two groups of patients during the bone marrow suppression period after chemotherapy. Differentially expressed proteins are primarily located in the cytoplasm, extracellular space, and nucleus, followed by mitochondria and membranes. These differentially expressed proteins mainly participate in biological processes such as cell and metabolism. For differential protein KEGG pathway enrichment analysis, it was found that metabolic pathways were mainly enriched in the metabolic category, while the PI3K-Akt signaling pathway, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway were enriched in the signaling pathways.
The subthalamic nucleus contributes causally to perceptual decision-making in monkeys
Authors: Rogers Kathryn , Gold Joshua I. , Ding Long 
Published: April 2024

AbstractThe subthalamic nucleus (STN) plays critical roles in the motor and cognitive function of the basal ganglia (BG), but the exact nature of these roles is not fully understood, especially in the context of decision-making based on uncertain evidence. Guided by theoretical predictions of specific STN contributions, we used single-unit recording and electrical microstimulation in the STN of healthy monkeys to assess its causal, computational roles in visual-saccadic decisions based on noisy evidence. The recordings identified subpopulations of STN neurons with distinct task-related activity patterns that related to different theoretically predicted functions. Microstimulation caused changes in behavioral choices and response times that reflected multiple contributions to an “accumulate-to-bound”-like decision process, including modulation of decision bounds and evidence accumulation, and to non-perceptual processes. These results provide new insights into the multiple ways that the STN can support higher brain function.
Hypothesis-driven interpretable neural network for interactions between genes
Authors: Wang Shuhui , Allauzen Alexandre , Nghe Philippe , Opuu Vaitea 
Published: April 2024

AbstractMechanistic models of genetic interactions are rarely feasible due to a lack of information and computational challenges. Alternatively, machine learning (ML) approaches may predict gene interactions if provided with enough data but they lack interpretability. Here, we propose an ML approach for interpretable genotype-to-fitness mapping, the Direct-Latent Interpretable Model (D-LIM). The neural network is built on a strong hypothesis: mutations in different genes cause independent effects in phenotypes, which then interact via non-linear relationships to determine fitness. D-LIM predicts interpretable genotype-to-fitness maps with state-of-the-art accuracy for gene-to-gene and gene-to-environment perturbations in deep mutational scanning of a metabolic pathway, a protein-protein interaction system, and yeast mutants for environmental adaptation. The hypothesis-driven structure of D-LIM offers interpretable features reminiscent of mechanistic models: the inference of phenotypes, identification of trade-offs, and fitness extrapolation outside of the data domain.
Age-Invariant Genes: Multi-Tissue Identification and Characterization of Murine Reference Genes
Authors: González John T. , Thrush Kyra , Meer Margarita , Levine Morgan E. , Higgins-Chen Albert T. 
Published: April 2024

AbstractStudies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes—those that remain unchanged throughout the aging process? These genes also have a practical application: they serve as reference genes (often called housekeeping genes) in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan. Here, we build upon a common pipeline for identifying reference genes in RNA-seq datasets to identify age-invariant genes across seventeen C57BL/6 mouse tissues (brain, lung, bone marrow, muscle, white blood cells, heart, small intestine, kidney, liver, pancreas, skin, brown, gonadal, marrow, and subcutaneous adipose tissue) spanning 1 to 21+ months of age. We identify 9 pan-tissue age-invariant genes and many tissue-specific age-invariant genes. These genes are stable across the lifespan and are validated in independent bulk RNA-seq datasets and RT-qPCR. We find age-invariant genes have shorter transcripts on average and are enriched for CpG islands. Interestingly, pathway enrichment analysis for age-invariant genes identifies an overrepresentation of molecular functions associated with some, but not all, hallmarks of aging. Thus, though hallmarks of aging typically involve changes in cell maintenance mechanisms, select genes associated with these hallmarks resist fluctuations in expression with age. Finally, our analysis concludes no classical reference gene is appropriate for aging studies in all tissues. Instead, we provide tissue-specific and pan-tissue genes for assays utilizing reference gene normalization (i.e., RT-qPCR) that can be applied to animals across the lifespan.
Meta-analysis: a quantitative model of adult neurogenesis in the rodent hippocampus
Authors: Arellano Jon I. , Rakic Pasko 
Published: April 2024

AbstractContrary to humans, adult neurogenesis in rodents is not controversial. And in the last three decades, multiple studies in rodents have deemed adult neurogenesis essential for most hippocampal functions. The functional relevance of new neurons relies on their distinct physiological properties during their maturation before they become indistinguishable from mature granule cells. Most functional studies have used very young animals with robust neurogenesis. However, this trait declines dramatically with age, questioning its functional relevance in aging animals, a caveat that has been mentioned repeatedly, but rarely analyzed quantitatively. In this meta-analysis, we use data from published studies to determine the critical functional window of new neurons and to model their numbers across age in both mice and rats. Our model shows that new neurons with distinct functional profile represent about 3% of the total granule cells in young adult 3-month-old rodents, and their number decline following a power function to reach less than 1% in middle aged animals and less than 0.5% in old mice and rats. These low ratios pose an important logical and computational caveat to the proposed essential role of new neurons in the dentate gyrus, particularly in middle aged and old animals, a factor that needs to be adequately addressed when defining the relevance of adult neurogenesis in hippocampal function.
Three years of insecticide resistance evolution and associated mechanisms inAedes aegyptipopulations of Ouagadougou, Burkina Faso
Authors: Yaméogo Félix , Sombié Aboubacar , Oté Manabu , Saiki Erisha , Sakurai Tatsuya , Wangrawa Dimitri W. , McCall Philip J. , Weetman David , Kanuka Hirotaka , Badolo Athanase 
Published: April 2024

AbstractBackgroundResistance to insecticides is spreading among populations ofAedes aegypti, the primary vector of important human arboviruses. The escalating insecticide resistance poses a significant threat to dengue vector control, with an expanding number of countries affected by the disease.To gain a deeper insight into the evolution of insecticide resistance, it is essential to have longitudinal surveillance results, which are currently lacking, particularly from AfricanAe. aegyptipopulations.Here we report on three-years of surveillance ofAe. aegyptisusceptibility to insecticide resistance phenotypes and associated kdr mutations in Burkina Faso, a country with regular dengue outbreaks.MethodsAe.aegyptisusceptibility to insecticides and the V410L, V1016I, and F1534Ckdrtarget site mutations linked to pyrethroid insecticide resistance were monitored in Ouagadougou from 2016 to 2018. Larvae were collected from artificial containers at two sites and reared to adulthood in an insectary. Bioassays were conducted on female adults, alongside with a laboratory-susceptible strain, following standard WHO protocols. Allele-specific PCR genotyping assays were utilized to identify the V410L, V1016I, and F1534Ckdrpyrethroid target site mutations.ResultsBioassays revealed a high level of resistance to permethrin and deltamethrin that progressively increased over the three-year period in both localities. The 1534C mutation was nearly fixed throughout the three years at each locality, and while the closely related 410L and 1016I mutations did not vary between localities, their frequency notably increased from 2016 to 2018. Interestingly,Ae. aegyptipopulations in both areas remained susceptible to bendiocarb, fenitrothion, and malathion. Modeling the mortality data further confirmed the escalating resistance trend over the years and emphasized the significant role played by the three kdr mutations in conferring resistance to pyrethroids.ConclusionMortality rates indicate thatAe. aegyptipopulations from Ouagadougou are becoming increasingly resistant to pyrethroid insecticides, likely due to an increase in the frequencies of the 410L and 1016Ikdr mutations. Organophosphate insecticides are likely to be better alternative options for control.
An inferotemporal coding strategy robust to partial object occlusion
Authors: Cheng Andrew , Sokol Sach , Connor Charles E. 
Published: April 2024

SummaryObject coding in primate ventral pathway cortex progresses in sparseness/compression/efficiency, from many orientation signals in V1, to fewer 2D/3D part signals in V4, to still fewer multi-part configuration signals in AIT (anterior inferotemporal cortex).1–11This progression could lead to individual neurons exclusively selective for unique objects, the sparsest code for identity, especially for highly familiar, important objects.12–18To test this, we trained macaque monkeys to discriminate 8 simple letter-like shapes in a match-to-sample task, a design in which one-to-one coding of letters by neurons could streamline behavior. Performance increased from chance to >80% correct over a period of weeks, after which AIT neurons showed clear learning effects, with increased selectivity for multi-part configurations within the trained alphabet shapes. But these neurons were not exclusively tuned for unique letters based on training, since their responsiveness generalized to different, non-trained shapes containing the same configurations. This multi-part configuration coding limit in AIT is not maximally sparse, but it could explain the robustness of primate vision to partial object occlusion, which is common in the natural world and problematic for computer vision. Multi-part configurations are highly diagnostic of identity, and neural signals for various partial object structures can provide different but equally sufficient evidence for whole object identity across most occlusion conditions.
A dataset containing speciation rates, uncertainty, and presence-absence matrices for more than 34,000 vertebrate species
Authors: Vásquez-Restrepo Juan D. 
Published: April 2024

AbstractThe increasing availability of phylogenetic data has facilitated the exploration of macroecological and macroevolutionary patterns across diverse spatial and temporal scales. However, calculating some model-based diversification metrics often requires significant computational power and time. To address this, I present a comprehensive dataset of Bayesian diversification rates for over 34,000 vertebrate species, spanning five major groups: amphibians, birds, mammals, reptiles, and sharks. This is the first large-scale dataset of its kind, providing both continuous and binary data for speciation rates and presence-absence matrices, respectively, with global coverage. The dataset not only enables analyses of evolutionary and spatial diversity patterns but also democratizes access to data-intensive studies. Additionally, as it is based on Markov chains, the dataset can be customized and extended without the need to start from scratch, offering flexibility for future research on diversification dynamics.