bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decentralized Mixed Effects Modeling in COINSTAC
Authors: Basodi Sunitha , Raja Rajikha , Gazula Harshvardhan , Romero Javier Tomas , Panta Sandeep , Maullin-Sapey Thomas , Nichols Thomas , Calhoun Vince D. 
Published: May 2023

AbstractPerforming group analysis on magnetic resonance imaging (MRI) data with linear mixed-effects (LME) models is challenging due to its large dimensionality and inherent multi-level covariance structure. In addition, as large-scale collaborative projects become commonplace in neuroimaging, data must increasingly be stored and analysed at different locations. In such settings, substantial overheads occur in terms of data transfer and coordination between participating research groups. In some cases, data cannot be pooled together due to privacy or regulatory concerns. In this work, we propose a decentralized LME model to perform a large-scale analysis of data from different collaborations without sharing or pooling. This method is efficient as it overcomes the hurdles of data privacy for sharing and has lower bandwidth and memory requirements for analysis than the centralized modeling approach. We evaluate our model using features extracted from structural magnetic resonance imaging (sMRI) data. Results highlight gray matter reductions in the temporal lobe/insula and medical front regions demonstrate the correctness of decentralized LME models. Our analysis also demonstrates that decentralized LME models achieve similar performance compared to the models trained with all the data in one location. We also implement the decentralized LME approach in COINSTAC, a decentralized platform for federating neuroimaging analysis, to demonstrate its value to the neuroimaging community.
Investigating the developmental onset of regenerative potential in the annelidCapitella teleta
Authors: Boyd Alicia A. , Seaver Elaine C. 
Published: May 2023

AbstractAn animal’s ability to regrow lost tissues or structures can vary greatly during its life cycle. The annelidCapitella teletaexhibits posterior, but not anterior, regeneration as juveniles and adults. In contrast, embryos display only limited replacement of specific tissues. To investigate when during developmentC. teletabecomes capable of regeneration, we assessed the extent to which larvae can regenerate. We hypothesized that larvae exhibit intermediate regeneration potential and demonstrate some features of juvenile regeneration, but do not successfully replace all lost structures. Both anterior and posterior regeneration potential of larvae were evaluated following amputation. Wound sites were analyzed for re-epithelialization, cell proliferation by EdU incorporation, stem cell and differentiation marker expression by in situ hybridization, presence of neurites and muscle fibers by immunohistochemistry and phalloidin staining respectively, and regrowth of structures. Wound healing occurred within 6 hours of amputation for both anterior and posterior amputations. Cell proliferation at both wound sites was observed for up to 7 days following amputation. In addition, the stem cell markervasawas expressed at anterior and posterior wound sites. However, growth of new tissue was observed only in posterior amputations. Neurites from the ventral nerve cord were also observed at posterior wound sites.De novo ashexpression in the ectoderm of anterior wound sites indicated neuronal cell specification, although the absence ofelavexpression indicated an inability to progress to neuronal differentiation. In rare instances, cilia and eyes reformed. Both amputations induced expanded expression of the myogenesis geneMyoDin pre-existing tissues. Our results indicate that amputated larvae complete early, but not late, stages of regeneration, indicating a gradual acquisition of regenerative ability inC. teleta.Furthermore, amputated larvae can metamorphose into burrowing juveniles, including those missing brain and anterior sensory structures. To our knowledge, this is the first study to assess regenerative potential of annelid larvae.
Breaking New Ground in Computational Psychiatry: Model-Based Characterization of Forgetting in Healthy Aging and Mild Cognitive Impairment
Authors: Hake Holly Sue , Leonard Bridget , Ulibarri Sara , Grabowski Thomas , Van Rijn Hedderik , Stocco Andrea 
Published: May 2023

AbstractComputational models of memory used in adaptive learning settings trace a learner’s memory capacities. However, less work has been done on the implementation of these models in the clinical realm. Current assessment tools lack the reliable, convenient, and repeatable qualities needed to capture the individualized and evolving nature of memory decline. The goal of this project was to predict and track memory decline in subjectively- or mildly cognitively impaired (MCI) individuals by using a model-based, adaptive fact-learning system. Here we present data demonstrating that these tools can diagnose mild memory impairment with over 80% accuracy after a single 8-minute learning session. These findings provide new insights into the nature and progression of memory decline and may have implications for the early detection and management of Alzheimer’s disease and other forms of dementia.
Electroconvulsive stimuli reverse neuro-inflammation and behavioral deficits in a mouse model of depression
Authors: Rooney Alasdair G , Kilpatrick Alastair M , ffrench-Constant Charles 
Published: May 2023

ABSTRACTBackgroundElectroconvulsive therapy is a fast, safe, and effective treatment for severe clinical depression but there is an ongoing search for mechanistic insights.MethodsWe used a mouse neuro-endocrine model of depression to examine behavioral, cellular, and molecular effects of electroconvulsive stimuli (ECS).ResultsThe behavioral response to repeated ECS correlated with adult neurogenesis, more strongly in the ventral than dorsal hippocampus. Subsequent RNA-seq analysis targeting the ventral subgranular zone (SGZ) delineated ECS-responsive molecular pathways that were shared between naive and depressive-state conditions, and which may represent core biological responses to seizure induction. Other pathways responded to ECS preferentially in the depressive state, suggesting further state- specific mechanisms. By comparing gene set pathways reciprocally altered in depressed-state animals then reversed by ECS, we identified and validated neuro-inflammation as a candidate regulator of the antidepressant response. We further identified 56 novel candidate ‘antidepressant response’ genes in the ventral SGZ that may contribute to recovery, half of which have been implicated in human neuropsychiatric phenotypes.ConclusionsElectroconvulsive stimuli reverse neuro-inflammation in a mouse model of depression. The results offer a detailed molecular characterization of potential SGZ antidepressant response-specific genes and pathways in brain regions implicated in depression.
Inactivating Negative Regulators of Cortical Branched Actin Enhances Persistence of Single Cell Migration
Authors: Fokin Artem I. , Boutillon Arthur , James John , Courtois Laura , Vacher Sophie , Simanov Gleb , Wang Yanan , Polesskaya Anna , Bièche Ivan , David Nicolas B. , Gautreau Alexis M. 
Published: May 2023

ABSTRACTThe Rac1-WAVE-Arp2/3 pathway pushes the plasma membrane by polymerizing branched actin at the cell cortex and thereby powering membrane protrusions that mediate cell migration. Here, using knock-down (KD) or knock-out (KO), we combine the inactivation of the Arp2/3 inhibitory protein Arpin, the Arp2/3 subunit ARPC1A and the WAVE complex subunit, CYFIP2, that all enhance the polymerization of cortical branched actin (CBA). Inactivation of the 3 CBA negative regulators increases migration persistence of human breast MCF10A cells, and of endodermal cells in the zebrafish embryo, significantly more than any single or double inactivation. In the triple KO, but not triple KD cells, the “super-migrator” phenotype was associated with a heterogenous down-regulation of vimentin expression and a lack of coordination in collective behaviors, such as wound healing and acinus morphogenesis. Re-expression of vimentin in triple KO cells restored the normal persistence of single cell migration to a large extent, suggesting that vimentin down-regulation is one of the adjustments in gene expression through which the super-migrator phenotype is stably maintained in triple KO cells. Constant excessive production of branched actin at the cell cortex thus commits cells into a motile state through changes in gene expression.
Quantitative flow cytometric selection of tau conformational nanobodies specific for pathological aggregates
Authors: Zupancic Jennifer M. , Smith Matthew D. , Trzeciakiewicz Hanna , Skinner Mary E. , Ferris Sean P. , Makowski Emily K. , Lucas Michael J. , McArthur Nikki , Kane Ravi S. , Paulson Henry L. , Tessier Peter M. 
Published: May 2023

1.ABSTRACTSingle-domain antibodies, also known as nanobodies, are broadly important for studying the structure and conformational states of several classes of proteins, including membrane proteins, enzymes, and amyloidogenic proteins. Conformational nanobodies specific for aggregated conformations of amyloidogenic proteins are particularly needed to better target and study aggregates associated with a growing class of associated diseases, especially neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. However, there are few reported nanobodies with both conformational and sequence specificity for amyloid aggregates, especially for large and complex proteins such as the tau protein associated with Alzheimer’s disease, due to difficulties in selecting nanobodies that bind to complex aggregated proteins. Here, we report the selection of conformational nanobodies that selectively recognize aggregated (fibrillar) tau relative to soluble (monomeric) tau. Notably, we demonstrate that these nanobodies can be directly isolated from immune libraries using quantitative flow cytometric sorting of yeast-displayed libraries against tau aggregates conjugated to quantum dots, and this process eliminates the need for secondary nanobody screening. The isolated nanobodies demonstrate conformational specificity for tau aggregates in brain samples from both transgenic tau mouse models and human tauopathies. We expect that our facile approach will be broadly useful for isolating conformational nanobodies against diverse amyloid aggregates and other complex antigens.
Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine dynamics in VPS35 p.D620N knock-in mice
Authors: Bu Mengfei , Follett Jordan , Tatarnikov Igor , Wall Shannon , Guenther Dylan , Deng Isaac , Wimsatt Genevieve , Milnerwood Austen , Moehle Mark S. , Khoshbouei Habibeh , Farrer Matthew J. 
Published: May 2023

AbstractDysregulation of dopamine neurotransmission profoundly affects motor, motivation and learning behaviors, and is often observed during the prodromal phase of Parkinson’s disease (PD). However, the mechanism underlying these pathophysiological changes remains to be elucidated. Mutations in vacuolar protein sorting 35 (VPS35) and leucine-rich repeat kinase 2 (LRRK2) both lead to autosomal dominant PD, and VPS35 and LRRK2 may physically interact to govern the trafficking of synaptic cargos within the endo-lysosomal network in a kinase-dependent manner. To better understand the functional role of VPS35 and LRRK2 on dopamine physiology, we examined Vps35 haploinsufficient (Haplo) and Vps35 p.D620N knock-in (VKI) mice and how their behavior, dopamine kinetics and biochemistry are influenced by LRRK2 kinase inhibitors. We found Vps35 p.D620N significantly elevates LRRK2-mediated phosphorylation of Rab10, Rab12 and Rab29. In contrast, Vps35 haploinsufficiency reduces phosphorylation of Rab12. While striatal dopamine transporter (DAT) expression and function is similarly impaired in both VKI and Haplo mice, that physiology is normalized in VKI by treatment with the LRRK2 kinase inhibitor, MLi-2. As a corollary, VKI animals show a significant increase in amphetamine induced hyperlocomotion, compared to Haplo mice, that is also abolished by MLi-2. Taken together, these data show Vps35 p.D620N confers a gain-of-function with respect to LRRK2 kinase activation, and VPS35 and LRRK2 functionally interact to regulate DAT trafficking and striatal dopamine neurotransmission.
Allochthonous groundwater microorganisms affect coastal seawater microbial abundance, activity and diversity
Authors: Yanuka-Golub Keren , Belkin Natalia , Weber Nurit , Mayyani Meor , Levy Yehuda , Reznik Itay J. , Rubin-Blum Maxim , Rahav Eyal , Kiro Yael 
Published: May 2023

AbstractSubmarine groundwater discharge (SGD) is a globally important process supplying nutrients and trace elements to the coastal environment, thus playing a pivotal role in sustaining marine primary productivity. Along with nutrients, groundwater also contains allochthonous microbes that are discharged from the terrestrial subsurface into the sea. Currently, little is known about the interactions between groundwater-borne and coastal seawater microbial populations, and their role upon introduction to coastal seawater populations. Here, we investigated seawater microbial abundance, activity and diversity in a site strongly influenced by SGD (in-situobservations), and through laboratory-controlled bottle incubations mimicking different mixing scenarios between SGD (either ambient or filtered through 0.1 µm/0.22 µm) and seawater. Our results demonstrate that the addition of <0.1 µm SGD stimulated heterotrophic activity and increased microbial abundance compared to control, whereas <0.22 µm filtration treatments induced primary productivity rates andSynechococcusgrowth. Amplicon sequencing of the 16S rRNA gene showed a strong shift from a SAR11-rich community in the reference SGD-unaffected coastal samples to aRhodobacteraceae-dominated one in the <0.1 µm treatment, in agreement with theirin-situenrichment in the SGD field site. These results suggest that despite the significant nutrient input, microbes delivered by SGD may affect the abundance, activity and diversity of intrinsic microbes in coastal seawater. Our results highlight the cryptic interplay between groundwater and seawater microbes in coastal environments, which has important implications for carbon cycling and climate.Key Points:Groundwater discharge into the coastal zone delivers both nutrients and allochthonous microbes.Groundwater microbes interact with seawater populations, by which affecting the delicate autotroph-heterotroph balance.Subterranean microbial processes are key drivers of food webs, potentially affecting biogenic carbon fluxes in the ocean and climate.
CRISPRδ: dCas13-mediated translational repression for accurate gene silencing in mammalian cells
Authors: Apostolopoulos Antonios , Tsuiji Hitomi , Shichino Yuichi , Iwasaki Shintaro 
Published: May 2023

SummaryCurrent gene silencing tools based on RNA interference (RNAi) or, more recently, clustered regularly interspaced short palindromic repeats (CRISPR)⃩Cas13 systems, have critical drawbacks, such as off-target effects (RNAi) or collateral mRNA cleavage (CRISPR⃩Cas13). Thus, a more specific method of gene knockdown is needed. Here, we developed “CRISPRδ”, an approach for translational silencing, harnessing catalytically inactive Cas13 proteins (dCas13). Owing to its tight association with mRNA, dCas13 serves as a physical roadblock for scanning ribosomes during translation initiation and does not affect mRNA stability. Guide RNAs covering the start codon lead to the highest efficacy regardless of the translation initiation mechanism: cap-dependent or internal ribosome entry site (IRES)-dependent translation. Strikingly, genome-wide ribosome profiling revealed the extremely high gene knockdown specificity of CRISPRδ. Moreover, fusion of a translational repressor to dCas13 ensured further improvement of the knockdown efficacy. Our method provides a framework for translational repression-based gene silencing in eukaryotes.
A real-time colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the rapid detection of highly pathogenic H5 clade 2.3.4.4b avian influenza viruses
Authors: Filaire Fabien , Sécula Aurélie , Lebre Laetitia , Croville Guillaume , Guerin Jean-Luc 
Published: May 2023

AbstractHighly pathogenic avian influenza viruses (HPAIV) are a major threat to the global poultry industry and public health due to their zoonotic potential. Since 2016, Europe and France have faced major epizootics caused by clade 2.3.4.4b H5 HPAIV. To reduce sample-to-result times, point-of-care testing is urgently needed to help prevent further outbreaks and the propagation of the virus. This study presents the design of a novel real-time colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of clade 2.3.4.4b H5 HPAIV. A clinical validation of this RT-LAMP assay was performed on 198 pools of clinical swabs sampled in 52 poultry flocks during the H5 HPAI 2020-2022 epizootics in France. This RT-LAMP assay allowed the specific detection of HPAIV H5Nx clade 2.3.4.4b within 30 minutes with a sensitivity of 86.11%. This rapid, easy-to-perform, inexpensive, molecular detection assay could be included in the HPAIV surveillance toolbox.
An automated interface for sedimentation velocity analysis in SEDFIT
Authors: Schuck Peter , To Samuel C. , Zhao Huaying 
Published: May 2023

AbstractSedimentation velocity analytical ultracentrifugation (SV-AUC) is an indispensable tool for the study of particle size distributions in biopharmaceutical industry, for example, to characterize protein therapeutics and vaccine products. In particular, the diffusion-deconvoluted sedimentation coefficient distribution analysis, in the software SEDFIT, has found widespread applications due to its relatively high resolution and sensitivity. However, a lack of available software compatible with Good Manufacturing Practices (GMP) has hampered the use of SV-AUC in this regulatory environment. To address this, we have created an interface for SEDFIT so that it can serve as an automatically spawned module with controlled data input through command line parameters and output of key results in files. The interface can be integrated in custom GMP compatible software, and in scripts that provide documentation and meta-analyses for replicate or related samples, for example, to streamline analysis of large families of experimental data, such as binding isotherm analyses in the study of protein interactions. To test and demonstrate this approach we provide a MATLAB script mlSEDFIT.
Wnt/β-catenin signaling controls mouse eyelid growth by mediating epithelial-mesenchymal interactions
Authors: Zhu Xuming , Senoo Makoto , Millar Sarah E. , Ma Gang 
Published: May 2023

AbstractEyelid closure is required for the development of multiple ocular tissues. Interactions between the epithelium and underlying mesenchyme play a pivotal role in regulating eyelid development. However, the molecular mechanisms underlying these interactions remain unclear. Wnt signaling pathways regulate the development of ocular tissues, but their functions in eyelid development are not fully defined. In this study, we find that deletion of β-catenin in supraorbital mesenchyme abolishes eyelid growth by causing decreased proliferation in supraorbital epithelium and underlying mesenchyme. Inhibition of Wnt secretion by deletingWlsin supraorbital epithelium results in failure of eyelid developing, similar to the effects of deleting mesenchymal β-catenin, suggesting that mesenchymal Wnt/β- catenin signaling is controlled by epithelial Wnt ligands during eyelid development. We also found that deletion ofp63results in formation of hypoplastic eyelids and reduced expression of several Wnt ligands in eyelid epithelium, indicating that expression of Wnt ligands in eyelid development is at least partially regulated by p63. Taken together, our data indicate that Wnt/β-catenin signaling controls eyelid growth by orchestrating epithelial- mesenchymal interactions.
Carotenoid assembly regulates quinone diffusion and theRoseiflexus castenholziireaction center-light harvesting complex architecture
Authors: Xin Jiyu , Shi Yang , Zhang Xin , Yuan Xinyi , Xin Yueyong , He Huimin , Shen Jiejie , Blankenship Robert E. , Xu Xiaoling 
Published: May 2023

AbstractCarotenoid (Car) pigments perform central roles in photosynthesis-related light harvesting (LH), photoprotection, and assembly of functional pigment-protein complexes. However, the relationships between Car depletion in the LH, assembly of the prokaryotic reaction center (RC)-LH complex, and quinone exchange are not fully understood. Here, we analyzed native RC-LH (nRC-LH) and Car-depleted RC-LH (dRC-LH) complexes in Roseiflexus castenholzii, a chlorosome-less filamentous anoxygenic phototroph that forms the deepest branch of photosynthetic bacteria. Newly identified exterior Cars functioned with the bacteriochlorophyll B800 to block the proposed quinone channel between LHαβ subunits in the nRC-LH, forming a sealed LH ring that was disrupted by transmembrane helices from cytochrome c and subunit X to allow quinone shuttling. dRC-LH lacked subunit X, leading to an exposed LH ring with a larger opening, which together accelerated the quinone exchange rate. We also assigned amino acid sequences of subunit X and two hypothetical proteins Y and Z that functioned in forming the quinone channel and stabilizing the RC-LH interactions. This study reveals the structural basis by which Cars assembly regulates the architecture and quinone exchange of bacterial RC-LH complexes. These findings mark an important step forward in understanding the evolution and diversity of prokaryotic photosynthetic apparatus.
In vivo Ontogeny of human forebrain neural progenitor cell grafts in adult rats: an immunohistological study
Authors: Liu Chunhua , Lin Aiping , Xing Qi , Zhang Di , Meng Wei , Wu Rui , Shi Heng , Huang Wenhao , Huang Xiaofen , Qin Dajiang , Wang Xiaoyun , Zhong Xiaofen , Guo Yiping 
Published: May 2023

AbstractA thorough understanding of the cell behaviors of the human neural grafts is fundamental to exploit them to achieve cell therapy for recovering brain functions. Here by using immunohistological staining, we trace the cell fate of the intrastriatal human neural progenitor cell (NPC) grafts up to 9 months in adult rats, with multiple examining time points to provide a unified working time frame for future transplantation study. Lots of Nestin+/Sox2+ human cells continuously migrate along the white matter tracts into distal brain parenchyma even long time after transplantation, providing a potential for curing diffuse brain damage. Further analysis reveals a significant heterogeneity of the long-term sustained neural stem cells (NSC)/NPCs that progressing throughout different stages, mimicking the neural development of human forebrain. More importantly, the initial GFAP expression in human grafts marks the NSC progression instead of terminal astrocyte differentiation. The distally migrating human cells continuously show the capability to produce new neurons, albeit at a low efficiency in the intact brain. Further investigations in neural disease models are needed. Such study would benefit neural cell therapy with regarding to the optimization of the transplantation strategy and choosing of acting mode by neural grafts (e.g. via cell replacement orex vivogene therapy).