bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain-Body Interactions Influence the Transition from Mind Wandering to Awareness of Ongoing Thought
Authors: Shinagawa Kazushi , Tanaka Yuto , Terasawa Yuri , Umeda Satoshi 
Published: September 2024

AbstractOur thoughts are inherently dynamic and often wander far from our current situation (mind wandering, MW). Although previous research revealed that the ascending arousal system shapes neural dynamics to mediate awareness of ongoing thoughts, the physiological states and afferent signals altered by this activation and its effects on awareness are unknown. In this study, we examined electroencephalography (EEG), electrocardiography (ECG), and respiration data before participants were aware of MW during a task in which they focused on external or internal stimuli. We showed that the transition from MW to awareness was characterized by decreased alpha and beta activity and increased heartbeat-evoked potential (HEP) amplitudes. In addition, the participants were more likely to be in the exhalation phase becoming aware, and in the inhalation phase at the time of MW reports. Moreover, changes in cardiac activity and HEP accompanied this pattern when participants were asked to focus on respiration. Based on these findings, we suggest that the release from the increased cognitive load with sustained MW and catching these changes as physiological alterations supporting awareness of MW; moreover, the modulation of the respiratory cycle by focusing on breathing enhances these changes.
Computer vision guided rapid and precise automated cranial microsurgeries in rodents
Authors: Navabi Zahra S , Peters Ryan , Gulner Beatrice , Cherkkil Arun , Ko Eunsong , Dadashi Farnoosh , Brien Jacob O , Feldkamp Michael , Kodandaramaiah Suhasa B 
Published: September 2024

ABSTRACTNeuroscientists employ various experimental procedures to interface with the brain to study and perturb the neural activity during behavior. A common procedure that allows such physical interfacing is cranial microsurgery, wherein small to large craniotomies are performed in the overlying skull for insertion of neural interfaces or implantation of optically clear windows for long-term cranial observation. Performing craniotomies is, however, a skilled task that requires significant time and practice and further needs to be carried out precisely to ensure that the procedure does not cause damage to the underlying brain and dura. Here, we present a computer vision-guided craniotomy robot (CV-Craniobot) that utilizes machine learning to accurately estimate the dorsal skull anatomy from optical coherence tomography (OCT) images. Instantaneous information of the skull morphology is used by a robotic mill to rapidly and precisely remove the skull from a desired craniotomy location. We show that the CV-Craniobot can perform small (2 - 4 mm diameter) craniotomies with near 100% success rates within 2 minutes and large craniotomies encompassing most of the dorsal cortex in less than 5 minutes. Thus, the CV-Craniobot enables rapid and precise craniotomies, significantly reducing surgery time as compared to human practitioners and eliminating the need for long training.
Prenatal exposure to valproic acid induces sex-specific alterations in cortical and hippocampal neuronal structure and function in rats
Authors: Williams Olivia O. F. , Coppolino Madeleine , Micelli Cecilia B. , McCallum Ryan T. , Henry-Duru Paula T. , Manduca Joshua D. , Lalonde Jasmin , Perreault Melissa L. 
Published: September 2024

AbstractBackgroundThere are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is the most widely used model for the study of idiopathic ASD, but almost all of the studies have used male rodents.MethodTo fill this knowledge gap, we evaluated sex differences for neuronal activity, morphology, and glycogen synthase kinase-3 (GSK-3) signaling in primary cortical (CTX) and hippocampal (HIP) neurons prepared from rats exposed to VPAin utero.In vivo, sex-specific VPA-induced alterations in the frontal CTX transcriptome at birth were also determined.ResultsOverall, VPA induced more robust changes in neuronal function and structure in the CTX than in the HIP. Male- and female-derived primary CTX neurons from rats exposed to prenatal VPA had elevated activity and showed more disorganized firing. In the HIP, only the female VPA neurons showed elevated firing, while the male VPA neurons exhibited disorganized activity. Dendritic arborization of CTX neurons from VPA rats was less complex in both sexes, though this was more pronounced in the females. Conversely, both female and male HIP neurons from VPA rats showed elevated complexity distal to the soma. Female VPA CTX neurons also had an elevated number of dendritic spines. The relative activity of the α and β isoforms of GSK-3 were suppressed in both female and male VPA CTX neurons, with no changes in the HIP neurons. On postnatal day 0, alterations in CTX genes associated with neuropeptides (e.g.,penk,pdyn) and receptors (e.g.,drd1,adora2a) were seen in both sexes, though they were downregulated in females and upregulated in males.LimitationsPrimary neuron studies may not recapitulate findings performedin vivoor at later stages of development.ConclusionTogether these findings suggest that substantial sex differences in neuronal structure and function in the VPA model may have relevance to the reported sex differences in idiopathic ASD.
A conserved cell-type gradient across the human mediodorsal and paraventricular thalamus
Authors: Schulmann Anton , Feng Ningping , Auluck Pavan K , Mukherjee Arghya , Komal Ruchi , Leng Yan , Gao Claire , Williams Avram Sarah K , Roy Snehashis , Usdin Ted B , Xu Qing , Imamovic Vesna , Patel Yash , Akula Nirmala , Raznahan Armin , Menon Vilas , Roussos Panos , Duncan Laramie , Elkahloun Abdel , Singh Jatinder , Kelly Michael C , Halassa Michael M , Hattar Samer , Penzo Mario A , Marenco Stefano , McMahon Francis J 
Published: September 2024

AbstractThe mediodorsal thalamus (MD) and adjacent midline nuclei are important for cognition and mental illness, but their cellular composition is not well defined. Using single-nucleus and spatial transcriptomics, we identified a conserved excitatory neuron gradient, with distinct spatial mapping of individual clusters. One end of the gradient was expanded in human MD compared to mice, which may be related to the expansion of granular prefrontal cortex in hominids. Moreover, neurons preferentially mapping onto the parvocellular division MD were associated with genetic risk for schizophrenia and bipolar disorder. Midbrain-derived inhibitory interneurons were enriched in human MD and implicated in genetic risk for major depressive disorder.
The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κβ pathway
Authors: Mukherjee Srimoyee , Barua Atish , Wang Luyang , Tian Bin , Moore Claire L. 
Published: September 2024

AbstractMacrophages are required for our body’s development and tissue repair and protect against microbial attacks. We previously reported a crucial role for regulation of mRNA 3’-end cleavage and polyadenylation (C/P) in monocyte to macrophage differentiation. The CFIm25 subunit of the C/P complex showed a striking increase upon differentiation of monocytes with Phorbol Myristate Acetate, suggesting that it promotes this process. To test this hypothesis, CFIm25 was overexpressed in two different monocytic cell lines, followed by differentiation. Both cell lines showed a significant increase in macrophage characteristics and an earlier slowing of the cell cycle. In contrast, depletion of CFIm25 hindered differentiation. Cell cycle slowing upon CFIm25 overexpression was consistent with a greater decrease in the proliferation markers PCNA and cyclin D1, coupled with increased 3’UTR lengthening of cyclin D1 mRNA. Since choice of other poly(A) sites could be affected by manipulating CFIm25, we identified additional genes with altered use of poly(A) sites during differentiation and examined how this changed upon CFIm25 overexpression. The mRNAs of positive regulators of NF-κB signaling, TAB2 and TBL1XR1, and NFKB1, which encodes the NF-κB p50 precursor, underwent 3’UTR shortening that was associated with increased protein expression compared to the control. Cells overexpressing CFIm25 also showed elevated levels of phosphorylated NF-κB-p65 and the NF-κB targets p21, Bcl-XL, ICAM1 and TNF-α at an earlier time and greater resistance to NF-κB chemical inhibition. In conclusion, our study supports a model in which CFIm25 accelerates the monocyte to macrophage transition by promoting alternative polyadenylation events which lead to activation of the NF-κB pathway.
Analysis of C-reactive protein omics-measures associates methylation risk score with sleep health and related health outcomes
Authors: Wang Ziqing , Wallace Danielle A , Spitzer Brian W , Huang Tianyi , Taylor Kent , Rotter Jerome I , Rich Stephen S , Liu Peter Y , Daviglus Martha L. , Hou Lifang , Ramos Alberto R , Kaur Sonya , Durda J Peter , González Hector M , Fornage Myriam , Redline Susan , Isasi Carmen R , Sofer Tamar 
Published: September 2024

AbstractIntroductionDNA methylation (DNAm) predictors of high sensitivity C-reactive protein (CRP) offer a stable and accurate means of assessing chronic inflammation, bypassing the CRP protein fluctuations secondary to acute illness. Poor sleep health is associated with elevated inflammation (including elevated blood CRP levels) which may explain associations of sleep insufficiency with metabolic, cardiovascular and neurological diseases. Our study aims to characterize the relationships among sleep health phenotypes and CRP markers —blood, genetic, and epigenetic indicators— within the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).MethodsIn HCHS/SOL, methylation risk scores (MRS)-CRP and polygenetic risk score (PRS)-CRP were constructed separately as weighted sums of methylation beta values or allele counts, respectively, for each individual. Sleep health phenotypes were measured using self-reported questionnaires and objective measurements. Survey-weighted linear regression established the association between the multiple sleep phenotypes (obstructive sleep apnea (OSA), sleep duration, insomnia and excessive sleepiness symptom), cognitive assessments, diabetes and hypertension with CRP markers while adjusting for age, sex, BMI, study center, and the first five principal components of genetic ancestry in HCHS/SOL.ResultsWe included 2221 HCHS/SOL participants (age range 37-76 yrs, 65.7% female) in the analysis. Both the MRS-CRP (95% confidence interval (CI): 0.32-0.42, p = 3.3 x 10-38) and the PRS-CRP (95% CI: 0.15-0.25, p = 1 x 10-14) were associated with blood CRP level. Moreover, MRS-CRP was associated with sleep health phenotypes (OSA, long sleep duration) and related conditions (diabetes and hypertension), while PRS-CRP markers were not associated with these traits. Circulating CRP level was associated with sleep duration and diabetes. Associations between OSA traits and metabolic comorbidities weakened after adjusting for MRS-CRP, most strongly for diabetes, and least for hypertension.ConclusionsMRS-CRP is a promising estimate for systemic and chronic inflammation as reflected by circulating CRP levels, which either mediates or serves as a common cause of the association between sleep phenotypes and related comorbidities, especially in the presence of diabetes.
Reproducible comparison and interpretation of machine learning classifiers to predict autism on the ABIDE multimodal dataset
Authors: Dong Yilan , Batalle Dafnis , Deprez Maria 
Published: September 2024

AbstractAutism is a neurodevelopmental condition affecting ∼1% of the population. Recently, machine learning models have been trained to classify participants with autism using their neuroimaging features, though the performance of these models varies in the literature. Differences in experimental setup hamper the direct comparison of different machine-learning approaches. In this paper, five of the most widely used and best-performing machine learning models in the field were trained to classify participants with autism and typically developing (TD) participants, using functional connectivity matrices, structural volumetric measures and phenotypic information from the Autism Brain Imaging Data Exchange (ABIDE) dataset. Their performance was compared under the same evaluation standard. The models implemented included: graph convolutional networks (GCN), edge-variational graph convolutional networks (EV-GCN), fully connected networks (FCN), auto-encoder followed by a fully connected network (AE-FCN) and support vector machine (SVM). Our results show that all models performed similarly, achieving a classification accuracy around 70%. Our results suggest that different inclusion criteria, data modalities and evaluation pipelines rather than different machine learning models may explain variations in accuracy in published literature. The highest accuracy in our framework was obtained by an ensemble of GCN models trained on combination of functional MRI and structural MRI features, reaching classification accuracy of 72.2% and AUC = 0.78 on the test set. The combined structural and functional modalities exhibited higher predictive ability compared to using single modality features alone. Ensemble methods were found to be helpful to improve the performance of the models. Furthermore, we also investigated the stability of features identified by the different machine learning models using the SmoothGrad interpretation method. The FCN model demonstrated the highest stability selecting relevant features contributing to model decision making. Code available at:https://github.com/YilanDong19/Machine-learning-with-ABIDE.
Meta-analysis study of the therapeutic impact of Mesenchymal stem cells derived exosomes for chronic kidney diseases
Authors: Himanshu k , Gunjan k , Pandey Ramendera Pati , Mukherjee Riya , Chang Chung-Ming 
Published: September 2024

AbstractMesenchymal stem cell-derived exosomes (EXOs) represent a promising avenue for treating chronic kidney diseases (CKD), though their precise impact remains somewhat elusive. To address this gap, we conducted a systematic analysis, scouring databases and clinical trial repositories for relevant studies from 2019 to 2023. Seventeen papers were meticulously selected for their focus on mesenchymal stem cell-derived exosomes (MSC-EXOs) and their potential in CKD treatment. Our comprehensive meta-analysis, incorporating 15 preclinical and 6 clinical studies, underscores the efficacy of MSC-EXOs in improving renal function while attenuating tubular injury, inflammation, apoptosis, collagen deposition, and renal fibrosis. Notably, post-treatment with MSC-EXOs exhibited significant associations with various CKD markers, with pooled proportions indicating a considerable impact on blood urea nitrogen (BUN) and serum creatinine (SCR) levels. Subgroup analyses based on animal models further elucidated heterogeneity within the studies. In conclusion, MSC-EXOs demonstrate promise in enhancing renal function and reducing CKD risk, as evidenced by both preclinical and clinical data. Their efficacy in lowering SCR and BUN levels while enhancing filtration rate suggests MSC-EXOs as a viable and secure alternative to cell-based therapies, thereby providing valuable insights for personalized CKD treatments despite inherent limitations.Graphical abstractGraphical highlight:MSC-EXOs show promise in improving renal function and reducing CKD risk, as evidenced by comprehensive meta-analysis findings.Pooled proportions indicate significant associations between MSC-EXO treatment and reduced BUN and SCR levels and increased GFR rate, highlighting their potential therapeutic efficacy.Exosomes show a significant effect on renal function, as indicated by the study findings.
Mitochondrial transplantation: A novel therapy for liver ischemia/reperfusion injury
Authors: Mukkala Avinash Naraiah , David Bruna Araujo , Ailenberg Menachem , Liang Jady , Vaswani Chirag Manoj , Karakas Danielle , Goldfarb Rachel , Barbour William , Gasner Avishai , Wu Ruoxian Scarlet , Petrut Raluca , Jerkic Mirjana , Andreazza Ana C. , Santos Claudia dos , Ni Heyu , Zhang Haibo , Kapus Andras , Kubes Paul , Rotstein Ori David 
Published: September 2024

MINI-ABSTRACTMitochondrial transplantation prevented liver ischemia/reperfusion-induced hepatocellular injury and inflammation.In vivointravital microscopy demonstrated that liver resident macrophages, namely Kupffer cells, rapidly sequestered, internalized and acidified transplanted mitochondria through the CRIg immunoreceptor. Mechanistically, both Kupffer cells and CRIg were necessary for the hepatoprotective and anti-inflammatory effects of mitochondrial transplantation.STRUCTURED ABSTRACTObjectiveTo investigate the hepatoprotective effects of mitochondrial transplantation in a murine liver ischemia/reperfusion (I/R) model.Summary background dataSequential liver ischemia followed by reperfusion (I/R) is a pathophysiological process underlying hepatocellular injury in a number of clinical contexts, such as hemorrhagic shock/resuscitation, major elective liver surgery and organ transplantation. A unifying pathogenic consequence of I/R is mitochondrial dysfunction. Restoration of mitochondria via transplantation (MTx) has emerged as potential therapeutic in I/R. However, its role in liver I/R and its mechanisms of action remain poorly defined.MethodsWe investigated the hepatoprotective effects of MTx in anin vivomouse model of liver I/R and usedin vivoimaging and various knockout and transgenic mouse models to determine the mechanism of protection.ResultsWe found that I/R-induced hepatocellular injury was prevented by MTx, as measured by plasma ALT, AST and liver histology. Additionally, I/R-induced pro-inflammatory cytokine release (IL-6, TNFα) was dampened by MTx, and anti-inflammatory IL-10 was enhanced. Moreover, MTx lowered neutrophil infiltration into both the liver sinusoids and lung BALF, suggesting a local and distant reduction in inflammation. Usingin vivointravital imaging, we found that I/R-subjected Kupffer cells (KCs), rapidly sequestered transplanted mitochondria, and acidified mitochondria within lysosomal compartments. To specifically interrogate the role of KCs, we depleted KCs using the diphtheria toxin-inducible Clec4f/iDTR transgenic mouse, then induced I/R, and discovered that KCs are necessary for the beneficial effects of MTx. Finally, we induced I/R in complement receptor of the immunoglobulin superfamily (CRIg) knockout mice and found that CRIg was required for mitochondria capture by KCs and mitochondrial-mediated hepatoprotection.ConclusionsIn this study, we demonstrated that CRIg-dependent capture of mitochondria by I/R-subjected Kupffer cells is a hepatoprotective mechanismin vivo. These data progress knowledge on the mechanisms of MTx and opens new avenues for clinical translation.
Arc/Arg3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles
Authors: Kanhema Tambudzai , Parobczak Kamil , Patil Sudarshan , Holm-Kaczmarek Dagmara , Hallin Erik , Ludwiczak Jan , Szczepankiewicz Andrzej A. , Pauzin Francois P. , Szum Adrian , Ishizuka Yuta , Dunin-Horkawicz Stanisław , Kursula Petri , Wilczynski Grzegorz , Magalska Adriana , Bramham Clive R. 
Published: September 2024

SummaryArc is a neuronal activity-induced protein interaction hub with critical roles in synaptic plasticity and memory. Arc localizes to synapses and the nucleus, but its nuclear functions are little known. We show that Arc accumulates in the interchromatin space of dentate granule cell nuclei and the nucleosol subcellular fraction following seizure activity and in vivo dentate gyrus LTP. Proteomic analysis of affinity-purified Arc complexes identified proteins with functions in post-transcriptional mRNA processing. During LTP, Arc undergoes enhanced complex formation with polyadenylate binding protein nuclear 1 (PABPN1) and paraspeckle splicing factor (PSF) in the nucleosol. In vitro peptide binding arrays show selective binding of Arc to the PABPN1 polyA RNA recognition motif. In hippocampal neuronal cultures, Arc knockdown increases formation of PABPN1 nuclear speckles and blocks chemical-LTP associated increases in small PABPN1 foci. These results implicate Arc in basal and neuronal activity-dependent regulation of PABPN1 speckles involved in mRNA processing and polyadenylation.
Characterization of the genome editing with miniature nucleases TnpB, IscB and enIscB inEscherichia colistrains
Authors: Tang Hongjie , Gao Jie , Sun Mingjun , Zhang Suyi , Li Qi 
Published: September 2024

AbstractDNA nucleases TnpB and IscB were regarded as new antibacterial strategy to combat the drug-resistant bacteria represented byEscherichia colidue to its specificity in targeting DNA and smallest size, but the genome-editing of TnpB/IscB inE. coliremains unclear. This study characterized the genome-editing of TnpB/IscB inE. colistrains. First, the toxicity and cleavage results showed TnpB only worked inE. coliMG1655, while IscB and enIscB could perform in ATCC9637 and BL21(DE3). Next, TnpB-based genome-editing tool was established in MG1655, while IscB/enIscB achieved in ATCC9637/BL21(DE3). The copy number of TnpB/IscB/enIscB were changed to explore the impact of editing efficiency. Moreover, the editing plasmids were successfully cured. Finally, the escaping mechanism ofE. coliunder editing of TnpB/IscB was revealed. Overall, this study successfully applied TnpB/IscB/enIscB to genome-editing inE. coli, which will broaden genetic manipulation toolbox inE. coliand facilitate the development of new antimicrobial drugs.