bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared and distinct adaptations to early-life exercise training based on inborn fitness
Authors: Sadler Daniel G. , Treas Lillie , Barre Mary , Ross Taylor , Sikes James D. , Zhong Ying , Britton Steven L. , Koch Lauren G. , Wankhade Umesh , Børsheim Elisabet , Porter Craig 
Published: December 2024

AbstractBackgroundLow cardiorespiratory fitness due to genetics increases the risk for cardiometabolic disease. Endurance exercise training promotes cardiorespiratory fitness and improves cardiometabolic risk factors, but with great heterogeneity. Here, we tested the hypothesis that the metabolic phenotype imparted by low parental (inborn) cardiorespiratory fitness would be overcome by early-life exercise training, and that exercise adaptations would be influenced in part by inborn fitness.MethodsAt 26 days of age, male and female rat low-capacity runners (LCR,n=20) and high-capacity runners (HCR,n=20) generated by artificial selection were assigned to either sedentary control (CTRL,n=10) or voluntary wheel running (VWR,n=10) for 6 weeks. Post-intervention, whole-body metabolic phenotyping was performed, and the respiratory function of isolated skeletal muscle and liver mitochondria assayed. Transcriptomics and proteomics were performed on skeletal muscle and liver tissue using RNA-sequencing and mass spectrometry, respectively.ResultsDaily VWR volume was 1.8-fold higher in HCR-VWR compared to LCR-VWR. In LCR, VWR reduced adiposity and enhanced glucose tolerance, coincident with elevated total energy expenditure. While intrinsic skeletal muscle mitochondrial respiratory function was unaffected by VWR, estimated skeletal muscle oxidative capacity increased in VWR groups owing to greater mitochondrial content. In the liver, both maximal oxidative capacity and ATP-linked respiration were higher in HCR-VWR than HCR-CTRL. Transcriptomic and proteomic profiling revealed extensive remodeling of skeletal muscle and liver tissue by VWR, elements of which were both shared and distinct based on inborn fitness.SummaryEarly-life exercise training partially overcomes the metabolic phenotype imparted by low inborn cardiorespiratory fitness. However, molecular adaptations to VWR are partly influenced by inborn fitness, which may have implications for personalized exercise medicine.
Effects of Spatial Constraints of Inhibitory Connectivity on the Dynamical Development of Criticality in Spiking Networks
Authors: Kern Felix Benjamin , Date Takahisa , Chao Zenas C. 
Published: December 2024

AbstractNeural systems are hypothesized to operate near criticality, enhancing their capacity for optimal information processing, transmission and storage capabilities. Criticality has typically been studied in spiking neural networks and related systems organized in random or full connectivity, with the balance of excitation and inhibition being a key determinant of the critical point of the system. However, given that neurons in the brain are spatially distributed, with their distances significantly influencing connectivity and signal timing, it is unclear how the spatial organization of excitatory and inhibitory connectivity influences the network’s self-organization towards criticality. Here, we systematically constrain the distance and density of inhibitory connectivity in two-dimensional spiking networks and allow synaptic weights to self-organize with activity-dependent excitatory and inhibitory plasticity in the presence of a low level of stochastic intrinsic activity. We then investigate the relationship between inhibitory connectivity, synaptic weights, and the resulting network activity during and after development. We find that networks with longer-range inhibitory synapses tend towards more supercritical behavior compared to networks with a similar number of shorter-range inhibitory synapses. We show that this distance dependence is a consequence of weaker long-range synapses after development due to the presence of synaptic delays, which shift most spike pairs outside of the potentiation window of the inhibitory learning rule.
Vasoinhibin is Generated by the Renin-Angiotensin System
Authors: Núñez Francisco Freinet , Siqueiros-Marquez Lourdes , Adán-Castro Elva , Zamora Magdalena , Robles Juan Pablo , Ruiz-Herrera Xarubet , Bertsch Thomas , Triebel Jakob , Martínez de la Escalera Gonzalo , Clapp Carmen 
Published: December 2024

ABSTRACTVasoinhibin is a fragment of the hormone prolactin (PRL) that inhibits angiogenesis, vasopermeability, and vasodilation. Cathepsin D (CTSD) cleaves the N-teminal of PRL to generate vasoinhibin in the retina of neonate mice as revealed by the CTSD inhibitor, pepstatin A (PA). However, PA also inhibits renin. Because renin is expressed in the retina and the renin-angiotensin system (RAS) gives rise to peptides with positive and negative effects on blood vessel growth and function, we investigated whether renin cleaves PRL to vasoinhibin in the newborn mouse retina and in the circulation. Newborn mouse retinal extracts from wild-type and CTSD-null newborn mice cleaved PRL to a 14 kDa vasoinhibin and such cleavage was prevented by heat-inactivation, PA, and the selective renin inhibitor VTP-27999 suggesting the contribution of renin. In agreement, recombinant renin cleaved different species PRLs to the expected 14 kDa vasoinhibin, a mass consistent with a consensus renin cleavage site located at Leu124-Leu125 in rat and mouse PRLs and at Leu126-Leu127 in human, bovine, and ovine PRLs. Dehydration and rehydration (D/R) in rats increased the levels of renin and PRL in plasma. Further increase in PRL circulating levels by the dopamine D2 receptor blocker, sulpiride, enabled detection of 14 kDa vasoinhibin in D/R rats. Moreover, the incubation of PRL with plasma from D/R rats generated a 14 kDa vasoinhibin that was prevented by VTP-27999. These findings add renin to the list of PRL-cleaving proteases and introduce vasoinhibin as a RAS-mediated mechanism for regulating blood vessel growth and function.
Solar UVB Radiation for the Synthesis of Vitamin D3in Four Skin Types – Model Propagation Studies
Authors: Pasricha Pradeep K. , Upadhayaya Arun K. 
Published: December 2024

AbstractThe study presents model computations of the wavelength of absorption of radiation energy in the ultraviolet (UV) band in the epidermis cells keratinocytes for four skin types: White-skin, Pale Yellow-skin, Brown-skin and Black-skin. Keratinocytes cells are idealized as spherical dielectric microcavities, with central melanin granule and a layer of keratin molecules surrounding the cell. Refractive indices of epidermis tissue, melanin and keratin are obtained from the published data. The size distribution of keratinocytes in the epidermis is obtained with the conjecture that the differentiated keratinocytes grow exponentially in the process of cell differentiation. The mole concept is used to calculate the size of melanin granules, one each for four skin types, using the published data of melanin content of the four skin types. The thickness of keratin layer around the cell keratinocyte does not occur in the model computations. In White-skin, the model solar UVB radiation wavelength range of 296 – 300 nm is close to the maximal range of 295 – 300 nm, of the range 290 – ∼317 nm, of the synthesis of vitamin D3 by the compound 7-dehydrocholesterol in skin cells. In Pale Yellow-skin, Brown-skin and Black-skin, the model solar UVB/(limited UVA) radiation wavelength ranges for the synthesis of vitamin D3are 290 – 295 nm, 290 – 297 nm and 307 – 314 nm, and 313 – ∼317 nm, respectively. The solar UVB radiation synthesizes vitamin D3to the maximum in White-skin and the least in Black-skin. The synthesis of vitamin D3is to a lesser extent in Pale Yellow-skin compared to White-skin. The solar UVB radiation synthesizes ample levels of vitamin D3in the pigmented Brown-skin. The solar UVB radiation is more effective to synthesize vitamin D3in Pale Yellow-skin compared to Brown-skin, since the Brown-skin is prone to pigmentation. The UVA radiation wavelength ranges that cause tanning of skin are analyzed. In Brown-skin, in particular, the wavelength range is 315 – 342 nm. Also, the physical mechanism of the UVA-caused tanning is similar to that of the UVB-caused tanning of skin. The UVA radiation phototherapies toward tanning of skin may be applied in the wavelength range of 340 – 370 nm. A sunscreen gel, in Brown-skin, in particular, may have the formulation to absorb the effective solar UVB and UVA radiation of wavelengths of 290 – 310 nm and 315 – 340 nm, respectively. The UVB radiation phototherapies to synthesize vitamin D3, especially for individuals allergic to medicinal vitamin D3, have varied model wavelength ranges for the four skin types. The study emphasizes the specific role of UV radiation toward synthesis of vitamin D3and therapeutic use in skin tanning for different skin types. The preparation of a sunscreen gel for skin protection may vary with skin type.
Cardiomyocyte STIM1 downregulation exacerbates post-Myocardial Infarction remodeling by dysregulating mitochondrial ultrastructure and metabolic signaling
Authors: Cacheux Marine , Velasco Juan , Wu Xiaohong , Strauss Benjamin , Akar Fadi G. 
Published: December 2024

ABSTRACTBackgroundLoss of stromal interaction molecule 1 (STIM1) expression in smooth muscle cells protects against ischemia-reperfusion (I/R) injury. Whether and how decreased STIM1 expression in cardiomyocytes (CM) impacts cardiac remodeling in response to I/R injury remains unknown.ObjectiveTo examine mechanisms by which decreased CM-STIM1 expression in the adult heart modulates cardiac function before and after I/R injury.Methods8-week old mice underwent cardiotropic AAV9-mediated gene transfer of shRNA directed against STIM1 (shSTIM1). Control (Ctrl) mice underwent shRNA luciferase or PBS injections. Ctrl and shSTIM1 mice were then challenged by 30-min coronary occlusion to induce MI,in-vivo. Mechanical, structural and electrophysiological (EP) properties were compared 1-week following MI. In a second cohort of mice, the impact of CM-STIM1 knockdownper seon upstream metabolic signaling, mitochondrial ultrastructure, and electrophysiological properties were studied.ResultsCM-STIM1 expression was markedly decreased in shSTIM1 vs Ctrl hearts. Challenge within-vivoI/R injury resulted in more pronounced (p<0.0001) LV dysfunction indexed by % drop in fractional shortening in shSTIM1 (44.3%) vs Ctrl (12.2%) hearts 1-week post-MI. Similarly, post-MI structural remodeling and the extent of fibrosis were more severe in shSTIM1 vs Ctrl despite comparable infarct size (p=0.514). Consistently, shSTIM1 exhibited greater impairment in post-MI EP function including predisposition to spatially-discordant action potential alternans. To understand mechanisms underlying this differential remodeling, we examined the impact of CM-STIM1 downregulation on mitochondrial ultrastructure and regulation by metabolic signaling. Quantification of mitochondrial morphology revealed smaller, more rounded mitochondria caused by CM-STIM1 downregulationper se. Underlying these changes was a marked (by 55%, p=0.0057) increase in phosphorylated (p)DRP1 at S616 along with reduced OPA1 expression. Mitochondrial alterations were associated with significant decreases in AMPK downstream signaling with loss of phosphorylated-to-total Raptor and ACC expression in shSTIM1-vs-Ctrl hearts consistent with impaired fatty acid oxidation. These MI-independent metabolic alterations coincided with higher pro-arrhythmic vulnerability under conditions of elevated heart rate.ConclusionsOur findings reveal that decreased CM-STIM1 expression exacerbates post-MI remodeling likely by altering metabolic processes and mitochondrial network dynamics.Functionally, STIM1-dependent mitochondrial alterations impact EP function during conditions of elevated heart rate even without the confounding influence of MI.
Development of the “EASY-HSV (Efficient And Simple high-Yield Herpes Simplex virus Vector) system” based on HSV-1 genome-maintaining HEK293 cells
Authors: Maeda Fumio , Adachi Shungo , Natsume Tohru 
Published: December 2024

AbstractHerpes simplex virus (HSV) amplicon vector is a promising molecular tool with a large transgene capacity of 150 kb. However, the conventional vector production method is labor-intensive and expensive, limiting its application. Here, we generated HEK293 cells harboring the HSV genome (293/HSV) and developed an EASY-HSV (Efficient And Simple high-Yield Herpes Simplex virus Vector) system in which 293/HSV cells are transfected with only two plasmids.
Bridging species boundaries: eDNA and genetic analysis reveal hybrid settlement at the very end of American eel distribution
Authors: Jacobsen Magnus Wulff , Nygaard Rasmus , Frankowski Jens , Buur Tengstedt Aja Noersgaard , Nielsen Julius , Hansen Michael M. , Hedeholm Rasmus , Retzel Anja , Hedal Ida , Urban Paulina , Jørgensen Casper Gundelund , Larsen Rasmus Stenbak , Maggini Sara , Rask Peter , Nielsen Einar Eg 
Published: December 2024

AbstractDocumenting species distributions and hybridization patterns is paramount for elucidating biogeography and understanding speciation processes. Here we combined genetic specimen analysis and environmental DNA (eDNA) to investigate the presence of American eel (Anguilla rotrata) and American × European eel (Anguilla anguilla) hybrids in Greenland freshwater. We further tested the use of eDNA to document hybridization by using European eel mtDNA as a proxy for hybrid occurrence. Overall, eDNA analysis detected mainly American eel but also European eel mtDNA. This finding was validated by DNA sequencing, which identified 3 out of 26 captured eels (14.3%) carrying European eel mtDNA. Five eels (19.2%), including all three with European mtDNA, were heterozygous for species-specific nuclear gene variants, supporting a hybrid ancestry. Further, eDNA successfully identified eels in lakes where they were caught by fyke net fishing, extending their confirmed northern range by 40 km, and indicated eel presence >200km further north. The study provides an empirical demonstration of the use of eDNA to document hybrid occurrence and extends the reported northern distribution of eels in Greenland significantly beyond previous observations. Further, the existence of hybrid eels in Greenland may be key for understanding the complex mechanisms of hybridization between American and European eels.
Dysregulated calcium signaling in the aged macaque entorhinal cortex associated with tau hyperphosphorylation
Authors: Bathla S , Datta D , Bolat D , Woo E , Duque A , Arellano J , Arnsten AFT , Nairn AC 
Published: December 2024

AbstractTau pathology in sporadic Alzheimer’s disease (AD) follows a distinct pattern, beginning in the entorhinal cortex (ERC) and spreading to interconnected brain regions. Early-stage tau pathology, characterized by soluble phosphorylated tau, is difficult to study in human brains post-mortem due to rapid dephosphorylation. Rhesus macaques, which naturally develop age-related tau pathology resembling human AD, provide an ideal model for investigating early tau etiology. This study examines the molecular processes underlying tau pathology in the macaque ERC, focusing on calcium and inflammatory signaling pathways. Our findings reveal age-related decreases in PDE4 phosphodiesterases that hydrolyze cAMP and increases in calpain-2 and GCPII that occur in parallel with early-stage tau hyperphosphorylation at multiple epitopes (pS214-tau, pT181-tau, pT217-tau). These findings suggest that dysregulated calcium signaling in ERC, beginning in middle-age, primes tau for hyperphosphorylation, potentially driving the early stages of AD, advancing our understanding of how ERC vulnerabilities contribute to neurodegeneration in AD.
Biofabrication of a filtration barrier by integrating electrospun membranes and flow in a glomerular co-culture
Authors: Mussoni Camilla , Rederer Anna , Stepanenko Vladimir , Würthner Frank , Stahlhut Philipp , Groll Jürgen , Schiffer Mario , Ahmad Taufiq , Müller-Deile Janina 
Published: December 2024

AbstractThe glomerulus is the functional unit of the kidney, where urine is filtered from blood. This process happens through the glomerular filtration barrier (GFB) which is composed of glomerular endothelial cells, podocytes, and glomerular basement membrane (GBM). Damage to any component of GFB results in failure of the barrier’s function, causing proteinuria that can lead to end-stage kidney failure. There is a high need for reliablein vitromodels of the GFB to study pathological conditions and to test potential novel therapeutic options. We established an artificial GBM generated by electrospinning of poly-L-lactic acid fibers that were coated with polydopamine and gelatin and seeded with human glomerular endothelial cells and podocytes onto different sides. The orientation of fibers in the artificial GBM, their surface chemistry and effects on glomerular cells were characterized in depth. Glomerular endothelial cells and podocytes, including hiPSC-derived podocytes formed monolayers on the artificial GBM and revealed cell type-specific marker expression and morphology. Cell-cell communication was possible between podocytes and glomerular endothelial cells in both directions though the artificial membrane. Different molecular dextrans showed size selective permeability of theex vivoGFB model. Introduction of shear stress by applying flow with a 3D printed micro-bioreactor improved cellular ultrastructure with formation of glomerular endothelial cell fenestrae-like structures and long podocyte foot process-like protrusions that both are usually absent in otherin vitromodels. Personalized hiPSC-derived podocytes within our model will allow to study the role of patient-specific podocyte mutations or individual treatment responseex vivoin the future.
A subset of mouse hippocampus CA1 pyramidal neurons learns sparse synaptic input patterns
Authors: Shahul Anzal K , Bhalla Upinder Singh 
Published: December 2024

AbstractSynaptic plasticity in the hippocampus is fundamental to learning and memory, yet few studies examine how pattern learning occurs across multiple synapses. Such cross-synapse learning is fundamental to emergent properties of pattern discrimination and generalisation, which depend on assumptions about independence of plasticity and linearity of summation. We used sparse optogenetic spatio-temporal ‘pattern stimulation in the CA3 coupled with postsynaptic depolarization to elicit plasticity on CA1 pyramidal neurons, and found that ‘trained’ patterns were selectively strengthened, but only in a subset of postsynaptic cells. Increased resting membrane potential and background mini-EPSP rates were predictive of learner cells. Summation following plasticity became more linear in learners compared to non-learners, consistent with the observed elevated post-stimulus hyperpolarization on non-learner cells. Thus our exploration of biologically plausible sparse activity supports pattern-selective learning, but in a heterogeneous manner modulated by both cell-intrinsic and network features.
More than 2,500 coding genes in the human reference gene set still have unsettled status
Authors: Maquedano Miguel , Cerdán-Vélez Daniel , Tress Michael L. 
Published: December 2024

AbstractIn 2018 we analysed the three main repositories for the human proteome, Ensembl/GENCODE, RefSeq and UniProtKB. They disagreed on the coding status of one of every eight annotated coding genes. The analysis inspired bilateral collaborations between annotation groups.Here we have repeated our analysis with updated versions of the three reference coding gene sets. Superficially, little appears to have changed. Although there are slightly fewer genes predicted as coding overall, the three groups still disagree on the status of 2,606 annotated genes. However, a comparison without read-through genes and immunoglobulin fragments shows that the three reference sets have merged or reclassified more than 700 genes since the last analysis and that just 0.6% of Ensembl/GENCODE coding genes are not also annotated by the other two reference sets.We used eight features indicative of non-coding genes to examine the 21,873 coding genes annotated across the three reference sets. We found that more than 2,000 had one or more potential non-coding features. While some of these genes will be protein coding, we believe that most are likely to be non-coding genes or pseudogenes. Our results suggest that annotators still vastly overestimate the number of true coding genes.
A Novel Taxonomic Database for eukaryotic Mitochondrial Cytochrome Oxidase subunit I Gene (eKOI): Enhancing taxonomic resolution at community-level in metabarcoding analyses
Authors: González-Miguéns Rubén , Gàlvez-Morante Alex , Skamnelou Margarita , Antó Meritxell , Casacuberta Elena , Richter Daniel J. , Vaulot Daniel , del Campo Javier , Ruiz-Trillo Iñaki 
Published: December 2024

AbstractMetabarcoding has emerged as a robust method for understanding biodiversity patterns by retrieving environmental DNA (eDNA) directly from ecosystems. Its low cost and accessibility have extended its use across biological topics, from symbiosis to biogeography, and ecology. A successful metabarcoding application depends on accurate and comprehensive reference databases for proper taxonomic assignment. The 18S rRNA gene is the primary genetic marker used for general/broad eukaryotic metabarcoding due to its combination of conserved and hypervariable regions, and the availability of extensive taxonomically-informed reference databases like PR2 and SILVA. Despite its advantages, 18S rRNA has certain limitations at lower taxonomic levels, depending on the lineage. Alternative fast-evolving molecular markers, such as the mitochondrial cytochrome oxidase subunit I (COI) gene, have been adopted as widely used "barcoding genes" for eukaryotes due to their resolution to the species level. However, the COI gene lacks a curated taxonomically-informed database covering all eukaryotes, including protists, comparable to those available for 18S rRNA. To address this gap, we introduce eKOI, a curated COI gene database aimed at enhancing the taxonomic annotation and primer design for COI-based metabarcoding at the community level. This database integrates COI gene data from GenBank and mitochondrial genomes that are publicly available, followed by rigorous manual curation to eliminate redundancies and contaminants and to correct taxonomic annotations. We validate using the eKOI database for taxonomic annotation of protists by re-annotating several COI-based metabarcoding studies, revealing previously unidentified biodiversity. Phylogenetic analyses confirmed the accuracy of the taxonomic annotations, highlighting the potential of eKOI to uncover new biodiversity in various eukaryotic lineages.