bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum bile acids improve prediction of Alzheimer’s progression in a sex-dependent manner
Authors: Chen Tianlu , Wang Lu , Xie Guoxiang , Zheng Xiaojiao , Cristal Bruce S. , Sun Tao , Arnold Matthias , Li Mengci , Dehkordi Siamac Mahmoudian , Sniatynski Matthew J. , Guo Qihao , Wu Lirong , Kuang Junliang , Wang Jieyi , Nho Kwangsik , Ren Zhenxing , Kueider-Paisley Alexandra , Kaddurah-Daouk Rima , Jia Wei ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Alzheimer Disease Metabolomics Consortium
Published: December 2022

AbstractINTRODUCTIONThere is evidence that there are differences in the serum levels of bile acids (BAs) in males and females and their risk of developing Alzheimer’s disease (AD). We previously reported that serum BAs are associated with AD. It remains unclear, however, how changes in serum BAs may relate to the development of AD in a sex-dependent manner.METHODSWe analyzed 33 BAs in the sera of 4219 samples from 1180 subjects in the ADNI cohort. Using linear models, we examined the associations between BAs and mild cognitive impairment (MCI) progression and clinical markers.RESULTSSignificant alterations in BA profiles occurred at an early stage of MCI and were associated with the onset and progression of MCI. These changes were more dramatic in men than in women. BA markers improved the ability of current clinical markers to diagnose MCI and predict its progression.DISCUSSIONOur results highlight the role of BAs in the development of AD and may help improve AD prediction and personalized therapies.Research in contextSystematic review:We examined the relationship between bile acid (BA), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). We previously reported this association. Our findings were consistent with those of other studies, although previous research did not consider sex differences or comprehensively evaluate the potential of BAs as diagnostic markers for AD.Interpretation: Our results suggest that changes in BA profiles may play a role in the development of AD and that sex-specific differences may be important for personalized prediction and management of the disease.Future directions: In the future, it will be important to confirm our findings with other independent samples and further investigate the ways in which BA metabolism, including cholesterol catabolism in the liver and brain, may contribute to AD.
Closing the Bio-Silicon Loop for Cellular Neural Prosthesis using FPGA-based Iono-Neuromorphic Models
Authors: Luo Junwen 
Published: December 2022

AbstractNeural ptosthetic devices offer the ability to develop novel treatments for previously incurable diseases and ailments, such as deafness, blindness and tetraplepia. There is the potential to extend this concept to incorporate cognitive prosthetics, whereby damaged individual neuron cells or larger brain regiops are substituted by silicon neurons, in order to overcome conditions such as stroke or epilepsy. The development of such applications relies heavily upon efficient, scalable and powerful technological platforms, particularly systems capable of running large-scale neural models. The advancemente in fLeld-peogrammable gate array (FPGA) tnchnology provides an excellent foundation for development of these neural models with the same cost of software-based architectures, but with the performance of close to a dedicated hardware system. This paper illustrates the design of a programmable FPGA-based neural model, which is capable of simulating a large range of ion-channel dynamics and delivering biologically realistic network models. Through comparisons with alternative implementations the proposed model is determined to be more scalable and more computationally efficient. We implemented a hybrid bio-silicon syttem to demonstrate thp ability of silicon devices to provide cellular rehabilitation, restoring thn functionality of a damaged biological network.
Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
Authors: Voisin Sarah , Seale Kirsten , Jacques Macsue , Landen Shanie , Harvey Nicholas R , Haupt Larisa M , Griffiths Lyn R , Ashton Kevin J , Coffey Vernon G , Thompson Jamie-Lee M , Doering Thomas M , Lindholm Malene E , Walsh Colum , Davison Gareth , Irwin Rachelle , McBride Catherine , Hansson Ola , Asplund Olof , Heikkinen Aino E , Piirilä Päivi , Pietiläinen Kirsi H , Ollikainen Miina , Blocquiaux Sara , Thomis Martine , Coletta Dawn K , Sharples Adam P , Eynon Nir 
Published: December 2022

AbstractExercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3,176). We show that: 1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, 2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns towards a younger profile, and 3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted towards a younger state after exercise training interventions, while the transcriptome shifted towards an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.
Ultrastructure of Precapillary Sphincters and the Neurovascular Unit
Authors: Grubb Søren 
Published: December 2022

AbstractNeurons communicate with vasculature to regulate blood flow in the brain. The cells that maintain this are collectively named the neurovascular unit (NVU). This communication, known as neurovascular coupling, is thought to involve astrocytes or molecules that can pass through the astrocytic endfeet. However, the exact mechanism is still unclear. Using large 3D electron microscopy datasets, we can now study the entire NVU in context. In this study, I provide evidence for the role of precapillary sphincters as a hub for neurovascular coupling and endothelial transcytosis, as well as the role of collagen synthesized by fibroblasts in strengthening first-order capillaries. I also show how astrocytic endfeet form a barrier for fluid flow and how the microvasculature of the cortex is not innervated but is surrounded by a surprising organization of parenchymal neuronal processes around penetrating arterioles and arterial-end capillaries in both mouse and human brains.Significance statementThe neurovascular unit (NVU) is made up of various types of cells, including neurons, astrocytes, and endothelial cells, which work together to regulate blood flow in response to changes in neural activity. This process, known as neurovascular coupling, is crucial for ensuring that the brain receives an adequate supply of oxygen and nutrients. This study suggests a novel organization of the NVU and neurovascular coupling. Through ultrastructural analysis, I was able to identify previously unknown relationships between the different types of cells in the NVU. These findings provide new insights into the structure of the NVU and how it functions, which may help researchers develop new strategies for preserving cognitive function and promoting healthy aging.
Genetic and phosphoproteomic basis of LysM-mediated immune signaling inMarchantia polymorphahighlights conserved elements and new aspect of pattern-triggered immunity in land plants
Authors: Yotsui Izumi , Matsui Hidenori , Miyauchi Shingo , Iwakawa Hidekazu , Melkonian Katharina , Schlüter Titus , Ibanez Selena Gimenez , Kanazawa Takehiko , Nomura Yuko , Stolze Sara Christina , Jeon Hyung-Woo , Sugano Shigeo , Shirakawa Makoto , Nishihama Ryuichi , Ichihashi Yasunori , Shirasu Ken , Ueda Takashi , Kohchi Takayuki , Nakagami Hirofumi 
Published: December 2022

AbstractPattern-recognition receptor (PRR)-triggered immunity (PTI) wards off a wide range of pathogenic microbes, playing a pivotal role in plant immunity. The model liverwortMarchantia polymorphais emerging as a popular model for investigating the evolution of plant-microbe interactions.M. polymorphatriggers defense-related gene expression upon sensing components of bacterial and fungal extracts, suggesting the existence of PTI in this plant model. However, the molecular components of the putative PTI inM. polymorphahave not yet been described. We show that, inM. polymorpha, which has four LysM receptor homologs, lysin motif (LysM) receptor-like kinase (LYK) MpLYK1 and LYK-related (LYR) MpLYR are required for sensing chitin and peptidoglycan fragments, triggering a series of characteristic immune responses. Comprehensive phosphoproteomic analysis ofM. polymorphain response to chitin treatment identified regulatory proteins that potentially shape LysM-mediated PTI. The identified proteins included homologs of well-described PTI components in angiosperms as well as proteins whose roles in PTI are not yet determined, including the blue-light receptor phototropin MpPHOT. We revealed that MpPHOT is required for a negative feedback of defense-related gene expression during PTI. Taken together, this study outlines the basic framework of LysM-mediated PTI inM. polymorphaand demonstrates the utility ofM. polymorphaas a plant model for discovering novel or fundamental molecular mechanisms underlying PRR-triggered immune signaling in plants.
ERCC1 mice, unlike other premature aging models, display accelerated epigenetic age
Authors: Perez Kevin , Parras Alberto , Rechsteiner Cheyenne , Haghani Amin , Brooke Robert , Mrabti Calida , Schonfeldt Lucas , Horvath Steve , Ocampo Alejandro 
Published: December 2022

ABSTRACTOver the last decades, several premature aging mouse models have been developed to study aging and identify interventions that can delay age-related diseases. Yet, it is still unclear whether these models truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported mouse models of premature aging (ERCC1, LAKI, POLG and XPG). We estimated DNA methylation (DNAm) age of these samples using the Horvath clock. The most pronounced increase in DNAm age could be observed in ERCC1 mice, a strain which exhibits a deficit in DNA nucleotide excision repair. In line with these results, we detected an increase in epigenetic age in fibroblasts isolated from patients with progeroid syndromes associated with mutations in DNA excision repair genes. These findings highlight ERCC1 as a particularly attractive mouse model to study aging in mammals and suggest a strong connection between DNA damage and epigenetic dysregulation during aging.
A versatile semiautomated image analysis workflow for time-lapsed camera trap image classification
Authors: Celis Gerardo , Ungar Peter , Sokolov Aleksandr , Sokolova Natalia , Böhner Hanna , Liu Desheng , Ziker John , Gilg Olivier , Fufachev Ivan , Pokrovskay Olga , Ims Rolf Anker , Ivanov Valeriy , Ehrich Dorothee 
Published: December 2022

ABSTRACTCamera trap arrays can generate thousands to millions of images that require exorbitant time and effort to classify and annotate by trained observers. Computer vision has evolved as an automated alternative to manual classification. The most popular computer vision solution is the supervised Machine Learning technique, which uses labeled images to train automated classification algorithms.We propose a multi-step semi-automated workflow that consists of (1) identifying and separating bad-from good-quality images, (2) parsing good images into animals, humans, vehicles, and empty, and (3) cropping animals from images and classifying them into species for manual inspection. We trained, validated, and evaluated this approach using 548,627 images from 46 cameras in two regions of the Arctic (northeastern Norway, and Yamal Peninsula, Russia).We obtained an accuracy of 0.959 for all three steps combined with the complete year test data set at Varanger and 0.922 at Yamal, reducing the number of images that required manual inspection to 7.9% of the original set from Varanger and 3.2% from Yamal.Researchers can modify this multi-step process to meet their specific needs for monitoring and surveying wildlife, providing greater flexibility than current options available for image classification.
APOEgenotype or presence of brain amyloid alters the plasma proteome in cognitively normal, elderly subjects
Authors: Philippi Sarah M. , Kailash BP , Raj Towfique , Castellano Joseph M. 
Published: December 2022

ABSTRACTBackgroundProcesses that drive Alzheimer’s disease pathogenesis have long been considered to occur within the central nervous system, yet recent studies have bolstered the possibility that changes in the periphery may be relevant to the disease process. Accumulating evidence has suggested that proteins changing in the blood may be reliable indicators of disease within the brain. Recent advances in geroscience have identified potential mechanisms of blood-brain communication that modulate brain function in ways that could be harnessed for therapy. While blood-borne proteins associated with either youth or old age have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here we investigate whetherAPOEallelic variation or presence of brain amyloid are associated with distinct proteomic changes within the systemic environment and what molecular processes are associated with these changes.MethodsUsing the SOMAscan assay, we measured 1,305 plasma proteins from 53 homozygousAPOE3andAPOE4subjects (mean age = 68 years; minimum = 54 years) who exhibited no cognitive impairment, some of whom can be categorized as harboring cerebral amyloid based on cerebrospinal fluid Aβ42 measurements. Using the Dream R package for linear mixed effects modeling, we investigated possible contributions of either theAPOE-ε4allele or amyloid positivity to changes in the plasma proteome. Ontology-based pathway and module trait correlation analyses were performed to understand disrupted pathways that vary based onAPOEgenotype or amyloid positivity.ResultsWe found that expression of theAPOE-ε4allele produced distinct changes in the composition of the plasma proteome. Using both pathway enrichment analysis and weighted gene co-expression network analysis, we found that plasma proteins associated withAPOE4expression were linked to pathways related to atherosclerosis, lipid transport, the extracellular matrix, and synaptogenesis signaling. Independent ofAPOE4, we found that cognitively normal, amyloid-positive subjects exhibit distinct plasma proteome signatures associated with pathways previously linked to AD pathology, relative to amyloid-negative controls. Harboring brain amyloid was associated with plasma proteomic changes linked to dysfunction in blood-brain barrier and other neural cell types. Our results indicate that changes in the plasma proteome are related to possession of AD risk alleles, as well as the presence of amyloid pathology in subjects prior to the onset of symptoms. This work highlights the possibility that pathways in the systemic environment in certain risk contexts may be plausible targets to explore for modulating disease.
Mapping Tree Cover Expansion in Montana, U.S.A. Rangelands Using High-Resolution Historical Aerial Imagery
Authors: Morford Scott , Allred Brady W. , Jensen Eric R. , Maestas Jeremy D. , Mueller Kristopher R. , Pacholski Catherine L. , Smith Joseph T. , Tack Jason D. , Tackett Kyle N. , Naugle David E. 
Published: December 2022

AbstractWorldwide, trees are colonizing rangelands with high conservation value. The introduction of trees into grasslands and shrublands causes large-scale changes in ecosystem structure and function, which have cascading impacts to ecosystem services, biodiversity, and agricultural economies. Satellites are increasingly being used to track tree cover at continental to global scales, but these methods can only provide reliable estimates of change over recent decades. Given the slow pace of tree cover expansion, remote sensing techniques that can extend this historical record provide critical insights into the magnitude of environmental change. Here, we estimate conifer expansion in rangelands of the northern Great Plains, United States, North America, using historical aerial imagery from the mid-20th century and modern aerial imagery. We analyzed 19.3 million hectares of rangelands in Montana, USA, using a convolutional neural network (U-Net architecture) and cloud computing to detect tree features and tree cover change. Our bias-corrected results estimate 3.0 ± 0.2 million hectares of conifer tree cover expansion in Montana rangelands, which accounts for 15.4% of the total study area. Overall accuracy was greater than 91%, but producer accuracy was lower than user accuracy (0.60 vs. 0.88). Nonetheless, the omission errors were not spatially correlated, indicating that the method is reliable for estimating the spatial extent of tree cover expansion. Using the model results in conjunction with historical and modern imagery allows for effective communication of the scale of tree expansion while overcoming the recency effect caused by shifting environmental baselines.
Towards reliable reconstruction of the mouse brain thalamocortical connectivity using diffusion MRI
Authors: Arefin Tanzil Mahmud , Lee Choong Heon , Liang Zifei , Rallapalli Harikrishna , Wadghiri Youssef Z. , Turnbull Daniel H. , Zhang Jiangyang 
Published: December 2022

AbstractDiffusion magnetic resonance imaging (dMRI) tractography has yielded intriguing insights into brain circuits and their relationship to behavior in response to gene mutations or neurological diseases across a number of species. Still, existing tractography approaches suffer from limited sensitivity and specificity, leading to uncertain interpretation of the reconstructed connections. Hence, in this study, we aimed to optimize the imaging and computational pipeline for reliable reconstruction of the mouse brain thalamocortical network. We developed a dMRI-based atlas of the mouse forebrain with structural labels imported from the Allen Mouse Brain Atlas (AMBA). Using the atlas and tracer data from the Allen Mouse Brain Connectivity Atlas (AMBCA) as ground truth, we investigated the accuracy of reconstructed node-to-node thalamocortical structural connectivity and effects of imaging and tractography parameters. Our results suggest that these parameters significantly affect tractography outcomes and our atlas can be used to investigate macroscopic structural connectivity in the mouse brain. Furthermore, tractography in mouse brain gray matter still face challenges and need improved imaging and tractography methods.
An updated end-to-end ecosystem model of the Northern California Current reflecting ecosystem changes due to recent marine heat waves
Authors: Gomes Dylan G.E. , Ruzicka James J. , Crozier Lisa G. , Huff David D. , Phillips Elizabeth M. , Hernvann Pierre-Yves , Morgan Cheryl A. , Brodeur Richard D. , Zamon Jen E. , Daly Elizabeth A. , Bizzarro Joseph. J. , Fisher Jennifer L. , Auth Toby D. 
Published: December 2022

AbstractThe Northern California Current is a highly productive marine upwelling ecosystem that is economically and ecologically important. It is home to both commercially harvested species and those that are federally listed under the U.S. Endangered Species Act. Recently, there has been a global shift from single-species fisheries management to ecosystem-based fisheries management, which acknowledges that more complex dynamics can reverberate through a food web. Here, we have integrated new research into an end-to-end ecosystem model (i.e., physics to fisheries) using data from long-term ocean surveys, phytoplankton satellite imagery paired with a vertically generalized production model, a recently assembled diet database, fishery catch information, species distribution models, and existing literature. This spatially-explicit model includes 90 living and detrital functional groups ranging from phytoplankton, krill, and forage fish to salmon, seabirds, and marine mammals, and nine fisheries that occur off the coast of Washington, Oregon, and Northern California. This model was updated from previous regional models to account for more recent changes in the Northern California Current (e.g., increases in market squid and some gelatinous zooplankton such as pyrosomes and salps), to expand the previous domain to increase the spatial resolution, to include data from previously unincorporated surveys, and to add improved characterization of endangered species, such as Chinook salmon (Oncorhynchus tshawytscha) and southern resident killer whales (Orcinus orca). Our model is mass-balanced, ecologically plausible, without extinctions, and stable over 150-year simulations. Ammonium and nitrate availability, total primary production rates, and model-derived phytoplankton time series are within realistic ranges. As we move towards holistic ecosystem-based fisheries management, we must continue to openly and collaboratively integrate our disparate datasets and collective knowledge to solve the intricate problems we face. As a tool for future research, we provide the data and code to use our ecosystem model.
Evaluating the efficacy of commercially available antisense oligonucleotides to reduce mouse and human tauin vivo
Authors: Vemula Pranav , Schoch Kathleen M. , Miller Timothy M. 
Published: December 2022

AbstractTauopathies, including Alzheimer’s disease (AD), are neurodegenerative diseases characterized by the accumulation of tau protein encoded by theMAPT(Microtubule Associated Protein Tau) gene. Various strategies targeting mechanisms to reduce tau pathology have been proposed and several tau-directed therapies are being investigated in clinical trials. Our lab previously developed a novel strategy to lower tau protein levels using antisense oligonucleotides (ASOs), showing that human tau (hTau) reduction in aged PS19 tauopathy mice reversed phosphorylated tau pathology, spared neurons, and prolonged survival. Currently, the tau-lowering ASO is being evaluated in the clinical trials with successful phase 1b results. Similarly, preclinical and clinical studies have demonstrated the use of other ASOs as effective therapeutic strategies. Acquiring ASOs for research purposes may be limited by partnerships with pharmaceutical companies. However, ASOs can be obtained through commercial vendors. The current study evaluates the efficacy of mouse and human tau-targeting ASOs obtained from a commercial vendor in various mouse models. We show that mice treated with purchased ASOs distribute among various brain cell types including neurons, microglia, and astrocytes. Mice treated with tau lowering ASOs show decreased mouse or human tau mRNA and protein levels. In addition, human tau lowering ASO-treated PS19 mice showed decreased phosphorylated tau (AT8) and gliosis relative to saline-treated PS19 mice. The results obtained in PS19 mice are consistent with data obtained from our previous study using a non-commercial tau-lowering ASO. Overall, the present study demonstrates the efficacy of commercially-available tau targeting ASOsin vivoto support their broad use by researchers.