bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Silica and Bioglass Nanomaterials in Pulp-Like Living Materials
Authors: Akoa Daline Mbitta , Avril Anthony , Hélary Christophe , Poliard Anne , Coradin Thibaud 
Published: October 2024

ABSTRACTAlthough silicon is a widespread constituent in dental materials, its possible influence on teeth formation and repair remains largely unexplored. Here we have studied the effect of two silicic acid-releasing nanomaterials, silica and bioglass, on a living model of pulp consisting of dental pulp stem cells seeded in dense type I collagen hydrogels. Silica nanoparticles and released silicic acid had little effect on cell viability and mineralization efficiency but impacted metabolic activity, delayed matrix remodeling and led to heterogeneous cell distribution. Bioglass improved cell metabolic activity and led to a homogenous dispersion of cells and mineral deposits within the scaffold. These results suggest that the presence of calcium ions in bioglass is not only favorable to cell proliferation but can also counter-balance the negative effects of silica and silicic acid. Both chemical and biological processes should therefore be considered when investigating the effect of silicon-containing materials on dental tissues.
Sperm quality metrics exhibit annual fluctuations in a critically endangered amphibian managed under human care
Authors: Julien Allison R. , Burger Isabella J. , Kouba Carrie K. , Barber Diane 
Published: October 2024

AbstractThe Puerto Rican crested toad (PRCT) is Puerto Rico’s only endemic toad and has undergone rapid population decline within the last 40 years. As a hedge against extinction, captive assurance colonies have been established at several zoological institutions for breeding and reintroduction. However, reproductive output has remained low, despite the use of hormone therapies to attempt to bypass missing abiotic cues and stimulate reproductive behaviors. This low output necessitates a better understanding of natural fluctuations in gamete, specifically sperm, quality in captive individuals. To generate an understanding of natural gametic cycles in captive PRCTs, we administered male PRCTs (n = 86) housed under natural temperature and photoperiod cycles with exogenous hormones monthly for one year. Samples were analyzed for motility and concentration to assess variations in sperm quality by month. Spermiation was successfully stimulated every month, but quality fluctuated; sperm motility was highest in June and July, while sperm concentration was highest in December, January, and March. These results indicate that, while hormones can be utilized to stimulate gamete production in PRCTs year-round, sperm quality is not consistent. Furthermore, the seasonal occurrence of peak sperm production of captive males differed from natural peaks reported for wild PRCTs. Our results illustrate the need for more biologically informed strategies for breeding of at-risk anuran populations.
Amygdala Subregion Volumes and Apportionment in Preadolescents — Associations with Age, Sex, and Body Mass Index
Authors: Overholtzer L. Nate , Torgerson Carinna , Morrel Jessica , Ahmadi Hedyeh , Tyszka J. Michael , Herting Megan M. 
Published: October 2024

AbstractImportanceThe amygdala, a key limbic structure, plays a critical role in emotional, social, and appetitive behaviors that develop throughout adolescence. Composed of a heterogeneous group of nuclei, questions remain about potential differences in the maturation of its subregions during development.ObjectiveTo characterize the associations between developmental variables and amygdala subregion volumes during preadolescence.Design, Setting, and ParticipantsCross-sectional Adolescent Brain Cognitive DevelopmentSM(ABCD®) Study data was collected from 3,953 9- and 10-year-old children between September 1, 2016, and October 15, 2018. Data analysis was conducted between June 1, 2023, and July 30, 2024.Main Outcomes and MeasuresUsing theCIT168 Amygdala Atlas, nine amygdala subregion volumes were quantified from high-quality MRI scans. Linear mixed-effects models were used to examine the effects of age, sex, pubertal stage, and body mass index z-score (BMIz) on subregion volumes and their relative apportionment within the amygdala.ResultsThe study population consisted of 3,953 preadolescents (mean [SD] age, 120 [7.41] months; 1,763 [44.6%] female; 57 [1.4%] Asian, 527 [13.3%] Black, 740 [18.7%] Hispanic, 2,279 [57.7%] white, and 350 [8.9%] from other racial/ethnic groups [identified by parents as American Indian/Native American, Alaska Native, Native Hawaiian, Guamanian, Samoan, other Pacific Islander, or other race]). Distinct associations were observed between age, sex, and BMIz and whole amygdala volume, subregion volumes, and subregion apportionment. Pubertal stage was not related to amygdala subregion volumes. Age was associated with near-global expansion of amygdala subregions during this developmental period. Female sex was linked to smaller volumes in most amygdala subregions, with larger relative apportionment in dorsal amygdala subregions and smaller apportionment in the basolateral ventral paralaminar subregion. Higher BMIz was associated with smaller volumes in large laterobasal subregions, with increased relative apportionment in smaller subregions.Conclusions and RelevanceThis cross-sectional study suggests that age, but not pubertal stage, is associated with near-global expansion of the amygdala at ages 9 and 10, while sex and BMIz are linked to distinct changes in amygdala subregions that explain observed differences in total volumes. These findings provide a foundational context for understanding how developmental variables influence amygdala structure in preadolescents, with implications for understanding future risk for brain disorders.
Extending mathematical frameworks to investigate neuronal dynamics in the presence of microglial ensheathment
Authors: Garcia Nellie , Handy Gregory 
Published: October 2024

AbstractRecent experimental evidence has shown that glial cells, including microglia and astrocytes, can ensheathe synapses, positioning them to disrupt neurotransmitter flow between pre- and post-synaptic terminals. This study extends micro- and network-scale theoretical models to explore how varying degrees of synaptic ensheathment affect synaptic communication and network dynamics. Consistent with previous studies, our microscale model shows that ensheathment accelerates synaptic transmission while reducing its strength and reliability, with the potential to effectively switch off synaptic connections. Building on these findings, we integrate an “effective” glial cell model into a large-scale neuronal network. Specifically, we analyze a network with highly heterogeneous synaptic strengths and time constants, where glial proximity parametrizes synaptic parameters. Unlike previous models that assumed normal parameter distributions, our model uses parameters drawn from distinct distributions. This framework is applied to large networks of exponential integrate-and-fire neurons, extending linear response theory to analyze not only firing rate distributions but also noise correlations across the network. Despite the significant heterogeneity in the system, a mean-field approximation accurately captures network statistics. We demonstrate the utility of our model by reproducing experimental findings, showing that microglial ensheathment leads to post-anesthesia hyperactivity in excitatory neurons of mice. Furthermore, we explore how glial ensheathment may be used in the visual cortex to target specific neuronal subclasses, tuning higher-order network statistics.
Apollo: A comprehensive GPU-powered within-host simulator for viral evolution and infection dynamics across population, tissue, and cell
Authors: Perera Deshan , Li Evan , van der Meer Frank , Lynch Tarah , Gill John , Church Deirdre L. , Huber Christian D. , van Marle Guido , Platt Alexander , Long Quan 
Published: October 2024

ABSTRACTModern sequencing instruments bring unprecedented opportunity to study within-host viral evolution in conjunction with viral transmissions between hosts. However, no computational simulators are available to assist the characterization of within-host dynamics. This limits our ability to interpret epidemiological predictions incorporating within-host evolution and to validate computational inference tools. To fill this need we developed Apollo, a GPU-accelerated, out-of-core tool for within-host simulation of viral evolution and infection dynamics across population, tissue, and cellular levels. Apollo is scalable to hundreds of millions of viral genomes and can handle complex demographic and population genetic models. Apollo can replicate real within-host viral evolution; accurately recapturing observed viral sequences from an HIV cohort derived from initial population-genetic configurations. For practical applications, using Apollo-simulated viral genomes and transmission networks, we validated and uncovered the limitations of a widely used viral transmission inference tool.
Dopamine and cortical iPSC-derived neurons with different Parkinsonian mutations show variation in lysosomal and mitochondrial dysfunction: implications for protein deposition versus selective cell loss
Authors: Chedid Jessica , Li Yan , Labrador-Garrido Adahir , Abu-Bonsrah Dad , Pavan Chiara , Fraser Tyra , Ovchinnikov Dmitry , Zhong Melanie , Davis Ryan , Strbenac Dario , Johnston Jennifer A. , Thompson Lachlan H. , Kirik Deniz , Parish Clare L. , Halliday Glenda M. , Sue Carolyn M. , Wali Gautam , Dzamko Nicolas 
Published: October 2024

AbstractBackgroundMutations causing Parkinson’s disease (PD) give diverse pathological phenotypes whose cellular correlates remain to be determined. For example, those withPRKNloss of function mutations have significantly earlier selective vulnerability of dopamine neurons, those withSNCAmutations have increased alpha-synuclein deposition, while those withLRRK2mutations have additional deposition of tau. Yet all three mutation types are implicated in mitochondrial and/or lysosomal dysfunction. Direct comparison of cell models with these mutations would clarify the relative cellular dysfunctions associated with these different pathological phenotypes.MethodsAn unbiased high-content imaging platform using orthogonal probes to assess both lysosomal and mitochondrial dysfunction, along with alpha-synuclein and tau protein deposition was established using induced pluripotent stem cell (iPSC) derived cortical and ventral midbrain neurons. Three mutation types,SNCAA53T,LRRK2R1441G andPRKNloss of function (lof), were selected as exemplars of divergent PD pathological phenotypes and compared to each other, and to control iPSC from subjects without PD.ResultsDifferent PD mutations caused cell type specific dysfunctions, likely to impact on both selective neuronal vulnerability and the pathologies observed in PD. Comparison of dopamine neurons identified that both lysosomal and mitochondrial dysfunction were predominant withPRKNlof mutations, whereas immunofluorescent staining revealed thatSNCAA53T andLRRK2R1441G mutations had increased tau deposition. In contrast, cortical neurons withSNCAandLRRK2mutations both had mitochondrial and autophagy impairments without protein deposition, withLRRK2cells additionally showing decreased glucocerebrosidase activity and increased alpha-synuclein phosphorylation.ConclusionsLysosomal and mitochondrial dysfunction are predominant in dopamine neurons withPRKNlof mutations, and may drive the early selective loss of dopamine neurons inPRKNmutation carriers. More subtle cellular abnormalities in theSNCAA53T cell lines are likely to predispose to alpha-synuclein aggregation and tau protein deposition over time. TheLRRK2R1441G may also predispose to tau deposition, but despite substantial lysosomal dysfunction with increased alpha-synuclein phosphorylation, pathological alpha-synuclein accumulations were not observed. Understanding the mechanistic differences in how lysosomal and mitochondrial dysfunction impact on PD pathogenesis in different disease subtypes may be important for therapeutic development.
Metabolomic Profiling Reveals Potential of Fatty Acids as Regulators of Stem-like Exhausted CD8 T Cells During Chronic Viral Infection
Authors: Kazane Katelynn R , Labarta-Bajo Lara , Zangwill Dina R , Liimatta Kalle , Vargas Fernando , Weldon Kelly C , Dorrestein Pieter C , Zúñiga Elina I 
Published: October 2024

AbstractChronic infections drive a CD8 T cell program termed T cell exhaustion, characterized by reduced effector functions. While cell-intrinsic mechanisms underlying CD8 T cell exhaustion have been extensively studied, the impact of the metabolic environment in which exhausted CD8 T cells (Tex) operate remains less clear. Using untargeted metabolomics and the murine lymphocytic choriomeningitis virus infection model we investigated systemic metabolite changes early and late following acute versus chronic viral infections. We identified distinct short-term and persistent metabolite shifts, with the most significant differences occurring transiently during the acute phase of the sustained infection. This included nutrient changes that were independent of viral loads and partially associated with CD8 T cell-induced anorexia and lipolysis. One remarkable observation was the elevation of medium- and long-chain fatty acid (FA) and acylcarnitines during the early phase after chronic infection. During this time, virus-specific CD8 T cells from chronically infected mice exhibited increased lipid accumulation and uptake compared to their counterparts from acute infection, particularly stem-like Tex (TexSTEM), a subset that generates effector-like TexINTwhich directly limit viral replication. Notably, only TexSTEMincreased oxidative metabolism and ATP production upon FA exposure. Consistently, short-term reintroduction of FA during late chronic infection exclusively improved TexSTEMmitochondrial fitness, percentages and numbers. This treatment, however, also reduced TexINT, resulting in compromised viral control. Our study offers a valuable resource for investigating the role of specific metabolites in regulating immune responses during acute and chronic viral infections and highlights the potential of long-chain FA to influence TexSTEMand viral control during a protracted infection.SignificanceThis study examines systemic metabolite changes during acute and chronic viral infections. Notably, we identified an early, transient nutrient shift in chronic infection, marked by an increase in medium- and long-chain fatty acid related species. Concomitantly, a virus-specific stem-like T cell population, essential for maintaining other T cells, displayed high lipid avidity and was capable of metabolizing exogenous fatty acids. Administering fatty acids late in chronic infection, when endogenous lipid levels had normalized, expanded this stem-like T cell population and enhanced their mitochondrial fitness. These findings highlight the potential role of fatty acids in regulating stem-like T cells in chronic settings and offer a valuable resource for studying other metabolic signatures in both acute and persistent infections.
FIThe Effects of Curcumin Supplementation on Body Weight, Body Mass Index, and Waist Circumference in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Alivand Noorbakhsh , Alivand Soleyman , masoumi Seyed jalil , foshati Sahar , Abbasi Ebrahim 
Published: October 2024

AbstractThe study investigates the effects of curcumin on obesity and its related factors in diabetic patients, given that obesity can lead to insulin resistance and complicate diabetes management. An analysis of nine randomized controlled trials (RCTs) involving 699 participants was conducted to evaluate curcumin’s impact on body weight (BW), body mass index (BMI), and waist circumference (WC). The results indicated a significant reduction in BW (WMD: −1.65 kg), BMI (WMD: −0.69 kg/m2), and WC (WMD: - 0.93 cm) with curcumin consumption compared to controls. Higher doses of curcumin (>1000 mg/day) were notably more effective in reducing BW, BMI, and WC than lower doses. The study concludes that curcumin supplementation effectively reduces BW, BMI, and WC in diabetic patients, especially at higher doses, and suggests the need for further studies to explore these benefits.
CRISPR tiling deletion screens reveal functional enhancers of neuropsychiatric risk genes and allelic compensation effects (ACE) on transcription
Authors: Ren Xingjie , Zheng Lina , Maliskova Lenka , Tam Tsz Wai , Sun Yifan , Liu Hongjiang , Lee Jerry , Takagi Maya Asami , Li Bin , Ren Bing , Wang Wei , Shen Yin 
Published: October 2024

AbstractPrecise transcriptional regulation is critical for cellular function and development, yet the mechanism of this process remains poorly understood for many genes. To gain a deeper understanding of the regulation of neuropsychiatric disease risk genes, we identified a total of 39 functional enhancers for four dosage-sensitive genes,APP,FMR1,MECP2, andSIN3A, using CRISPR tiling deletion screening in human induced pluripotent stem cell (iPSC)-induced excitatory neurons. We found that enhancer annotation provides potential pathological insights into disease-associated copy number variants. More importantly, we discovered that allelic enhancer deletions atSIN3Acould be compensated by increased transcriptional activities from the other intact allele. Such allelic compensation effects (ACE) on transcription is stably maintained during differentiation and, once established, cannot be reversed by ectopicSIN3Aexpression. Further, ACE atSIN3Aoccurs through dosage sensing by the promoter. Together, our findings unravel a regulatory compensation mechanism that ensures stable and precise transcriptional output forSIN3A, and potentially other dosage-sensitive genes.
A Novel Genus of Virulent Phage TargetingAcinetobacter baumannii: Efficacy and Safety in a Murine Model of Pulmonary Infection
Authors: Wang JiaWang , Hu Huan , Wang QingQing , Zhu TianZhu , Ren XiaoHan , Jiang WenQian , Hou XueMei , Lin Jun , Yu XiaoLing 
Published: October 2024

AbstractAcinetobacter baumannii(A.baumannii) is a notable opportunistic pathogen responsible for severe hospital-acquired infections, with multidrug-resistant strains posing significant treatment challenges. Phage therapy, which employs bacteriophages as natural bacterial antagonists, has gained renewed attention as a promising solution to combat antibiotic-resistant infections. In this study, we isolated and characterized a novel virulent phage, vB_AbaS_qsb1, which specifically lysesA.baumannii. Phylogenetic and genomic analyses indicate that vB_AbaS_qsb1 is the founding member of a previously unreported genus, which we have named asAcinibactriovirus, withAcinibactriovirus lysinusas the type species. vB_AbaS_qsb1 demonstrated robust stability across diverse temperature and pH ranges, a short latent period, and no known virulence or antibiotic resistance genes within its 54,713 bp dsDNA genome. Safety assessments showed that high-dose vB_AbaS_qsb1 induced no adverse effects in mice, with histopathology confirming its safety profile. Therapeutic experiments further indicated that vB_AbaS_qsb1 provided at least 50% protection againstA.baumannii-induced pneumonia, significantly reducing bacterial loads and inflammation markers, while maintaining high phage titers in lung tissue.This study introduces vB_AbaS_qsb1 as a promising candidate for phage therapy againstA.baumannii, offering both innovative insights and a valuable framework for future isolation, genomic characterization, and efficacy evaluation of phages targeting antibiotic-resistant bacteria.Graphical abstract
Can We Ever Develop an Ideal RNA Force Field? Lessons Learned from Simulations of UUCG RNA Tetraloop and Other Systems
Authors: Mlýnský Vojtěch , Kührová Petra , Pykal Martin , Krepl Miroslav , Stadlbauer Petr , Otyepka Michal , Banáš Pavel , Šponer Jiří 
Published: October 2024

ABSTRACTMolecular dynamics (MD) simulations are an important and well-established tool for investigating RNA structural dynamics, but their accuracy relies heavily on the quality of the employed force field (ff). In this work, we present a comprehensive evaluation of widely used pair-additive and polarizable RNAffs using the challenging UUCG tetraloop (TL) benchmark system. Extensive standard MD simulations, initiated from the NMR structure of the 14-mer UUCG TL, revealed that mostffs did not maintain the native state, instead favoring alternative loop conformations. Notably, three very recent variants of pair-additiveffs, OL3CP–gHBfix21, DESAMBER, and OL3R2.7, successfully preserved the native structure over a 10 × 20 µs timescale. To further assess theseffs, we performed enhanced sampling folding simulations of the shorter 8-mer UUCG TL, starting from the single-stranded conformation. Estimated folding free energies (ΔG°fold) varied significantly among these threeffs, with values of 0.0 ± 0.6 kcal/mol, 2.4 ± 0.8 kcal/mol, and 7.4 ± 0.2 kcal/mol for OL3CP–gHBfix21, DESAMBER, and OL3R2.7, respectively. The ΔG°foldvalue from OL3CP–gHBfix21 was closest to experimental data, while the higher ΔG°foldvalues from DESAMBER and OL3R2.7were unexpected, suggesting an over- or underestimation of key interactions within the folded and mis(un)folded ensembles. These discrepancies led us to further test DESAMBER and OL3R2.7ffs on additional RNA and DNA systems, where further performance issues were observed. Our results emphasize the complexity of accurately modeling RNA dynamics and suggest that creating an RNAffcapable of reliably performing across a wide range of RNA motifs remains extremely challenging. In conclusion, our study provides valuable insights into the capabilities of current RNAffs and highlights key areas for futureffdevelopment.
A novel model to quantify blood transit time in cerebral arteries using ASL-based 4D magnetic resonance angiography with example clinical application in moyamoya disease
Authors: Bhogal Alex A. , Uniken-Venema Simone M. , Deckers Pieter , Versluis Maarten , Braun Kees P. , van der Zwan Albert , Siero Jeroen C.W. 
Published: October 2024

AbstractAngiography is critical for visualizing cerebral blood flow in intracranial steno-occlusive diseases. Current 4D magnetic resonance angiography (MRA) techniques primarily focus on macrovascular structures, yet few have quantified hemodynamic timing. This study introduces a novel model to estimate macrovascular arterial transit time (mATT) derived from arterial spin labeling (ASL)-based 4D-MRA. We provide examples of our method that visualize mATT differences in patients with intracranial steno-occlusive disease (moyamoya and atherosclerosis) and changes in mATT resulting from the cerebrovascular reactivity response to an acetazolamide (ACZ) injection. Furthermore, we present a method that projects sparse arterial signals into a 3D native brain-region atlas space and correlate regional mATT with other hemodynamic parameters of interest such as tissue transit time and cerebrovascular reactivity. This approach offers a non-invasive, quantitative assessment of macrovascular dynamics, with potential to enhance understanding of large-vessel and tissue-level hemodynamics and augment monitoring of treatment outcomes in steno-occlusive disease patients. Furthermore, it sets the stage for more in-depth investigations of the macrovascular contribution to brain hemodynamics.