bluuebunny/crossref_metadata_2025_split huggingface dataset:
WormSwin: Instance segmentation of C. elegans using vision transformer
Authors: Deserno Maurice , Bozek Katarzyna 
Published: April 2023

AbstractThe possibility to extract motion of a single organism from video recordings at a large-scale provides means for the quantitative study of its behavior, both individual and collective. This task is particularly difficult for organisms that interact with one another, overlap, and occlude parts of their bodies in the recording. Here we propose WormSwin - an approach to extract single animal postures of Caenorhabditis elegans (C. elegans) from recordings of many organisms in a single microscope well. Based on transformer neural network architecture our method segments individual worms across a range of videos and images generated in different labs. Our solutions offers accuracy of 0.990 average precision (AP0.50) and comparable results on the benchmark image dataset BBBC010. Finally, it allows to segment challenging overlapping postures of mating worms with an accuracy sufficient to track the organisms with a simple tracking heuristic. An accurate and efficient method forC. eleganssegmentation opens up new opportunities for studying of its behaviors previously inaccessible due to the difficulty in the worm extraction from the video frames.
Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination
Authors: Zhou Zhao-Hua , Cortese Margaret M. , Fang Jia-Long , Wood Robert , Hummell Donna S. , Risma Kimberly A. , Norton Allison E. , KuKuruga Mark , Kirshner Susan , Rabin Ronald L. , Agarabi Cyrus , Staat Mary A. , Halasa Natasha , Ware Russell , Stahl Anna , McMahon Maureen , Browning Peter , Maniatis Panagiotis , Bolcen Shanna , Edwards Kathryn M. , Su John R. , Dharmarajan Sai , Forshee Richard , Broder Karen R. , Anderson Steven , Kozlowski Steven 
Published: April 2023

AbstractBackgroundThe mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to excipient polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms.MethodsSelected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020 – March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination (“controls”) were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay. Anti-PEG IgG and IgM were measured using two different assays. Laboratorians were blinded to case/control status.ResultsAll 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65%) were hospitalized and 7 (35%) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10%) case-patients vs 8 of 30 (27%) controls (p=0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0%) vs 1 of 30 (3%) controls (p>0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats.ConclusionOur results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.
Abnormal higher-order network interactions in Parkinson’s disease visual hallucinations
Authors: Tan Joshua B. , Müller Eli J. , Orlando Isabella F. , Taylor Natasha L. , Margulies Daniel S. , Szeto Jennifer , Lewis Simon J.G. , Shine James M. , O’Callaghan Claire 
Published: April 2023

AbstractVisual hallucinations in Parkinson’s disease can be viewed from a systems-level perspective, whereby abnormal communication between brain networks responsible for perception predisposes a person to hallucinate. To this end, abnormal functional interactions between higher-order and primary sensory networks have been implicated in the pathophysiology of visual hallucinations in Parkinson’s disease, however the precise signatures remain to be determined. Dimensionality reduction techniques offer a novel means for simplifying the interpretation of multidimensional brain imaging data, identifying hierarchical patterns in the data that are driven by both within- and between-functional network changes. Here, we applied two complementary non-linear dimensionality reduction techniques – diffusion-map embedding and t-distributed Stochastic Neighbour Embedding (t-SNE) – to resting state fMRI data, in order to characterise the altered functional hierarchy associated with susceptibility to visual hallucinations. Our study involved 77 people with Parkinson’s disease (31 with hallucinations; 46 without hallucinations) and 19 age-matched healthy controls. In patients with visual hallucinations, we found compression of the unimodal-heteromodal gradient consistent with increased functional integration between sensory and higher order networks. This was mirrored in a traditional functional connectivity analysis, which showed increased connectivity between the visual and default-mode networks in the hallucinating group. Together, these results suggest a route by which higher-order regions may have excessive influence over earlier sensory processes, as proposed by theoretical models of hallucinations across disorders. By contrast, the t-SNE analysis identified distinct alterations in prefrontal regions that were not apparent in the functional connectivity analysis, suggesting complex reconfigurations in functional brain network architecture as a function of the disease process. Together, the results confirm abnormal brain organisation associated with the hallucinating phenotype in Parkinson’s disease, and highlight the utility of applying convergent dimensionality reduction techniques to investigate complex clinical symptoms. In addition, the patterns we describe in Parkinson’s disease converge with those seen in other conditions, suggesting that reduced hierarchical differentiation across sensory-perceptual systems may be a common transdiagnostic vulnerability in neuropsychiatric disorders with perceptual disturbances.
Environmental, Socioeconomic, and Health Factors Associated with Gut Microbiome Species and Strains in Isolated Honduras Villages
Authors: Shridhar Shivkumar Vishnempet , Beghini Francesco , Alexander Marcus , Singh Adarsh , Juárez Rigoberto Matute , Brito Ilana L. , Christakis Nicholas A. 
Published: April 2023

ABSTRACTDespite a growing interest in the gut microbiome of non-industrialized countries, data linking microbiome features from such settings to diverse phenotypes remains uncommon. Using metagenomic data from a community-based cohort of 1,871 people from isolated villages in the Mesoamerican highlands of western Honduras, we report novel associations between bacterial species and phenotypes. We also find an uncharacterizedLachnospiraceaespecies associated with 22 different phenotypes, and little overlap with a prior Dutch Microbiome Project. Furthermore, including strain-phylogenetic information modifies the overall relationship between the gut microbiome and the phenotypes, especially in some phenotypes like household wealth. Coincidentally, wealthier individuals also have a higher number of polymorphic sites. Our analysis suggests new roles that gut microbiome surveillance can play in understanding broad features of individual and public health.
Decoding State-Dependent Cortical-Cerebellar Cellular Functional Connectivity in the Mouse Brain
Authors: Yan Yuhao , Murphy Timothy H 
Published: April 2023

ABSTRACTThe cerebellum participates in motor tasks, but also a broad spectrum of cognitive functions. However, cerebellar connections with higher areas such as cortex are not direct and the mechanisms by which the cerebellum integrates and processes diverse information streams are not clear. We investigated the functional connectivity between single cerebellar neurons and population activity of the dorsal cortex using mesoscale imaging. Our findings revealed dynamic coupling between individual cerebellar neurons and diverse cortical networks, and such functional association can be influenced by local excitatory and inhibitory connections. While the cortical representations of individual cerebellar neurons displayed marked changes across different brain states, the overall assignments to specific cortical topographic areas at the population level remained stable. Simple spikes and complex spikes of the same Purkinje cells displayed either similar or distinct cortical functional connectivity patterns. Moreover, the spontaneous functional connectivity patterns aligned with cerebellar neurons’ functional responses to external stimuli in a modality-specific manner. Importantly, the tuning properties of subsets of cerebellar neurons differed between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns. Collectively, our results provide a comprehensive view of the state-dependent cortical-cerebellar functional connectivity landscape and demonstrate that remapping of long-range functional network association could underlie state-dependent change in sensory processing.
Methane formation driven by light and heat prior to the origin of life
Authors: Ernst Leonard , Barayeu Uladzimir , Hädeler Jonas , Dick Tobias P. , Klatt Judith M. , Keppler Frank , Rebelein Johannes G. 
Published: April 2023

AbstractMethane is a potent greenhouse gas, which likely enabled the evolution of life by keeping the early Earth warm. Here, we demonstrate new routes towards abiotic methane formation under early-earth conditions from methylated sulfur and nitrogen compounds with prebiotic origin. These compounds are demethylated in Fenton reactions governed by ferrous iron and reactive oxygen species, produced by light and heat in aqueous environments. The reactions generate methyl radicals and ultimately release methane and ethane. Organic iron chelators enhance reaction rates and recycle ferric to ferrous complexes via ligand-to-metal charge transfer, establishing a light-driven iron redox cycle. This abiotic reaction facilitates methane and ethane formation across Earth’s humid realm, thereby shaping the chemical evolution of the atmosphere prior to the origin of life and beyond.One-Sentence SummaryUnder suboxic and anoxic conditions, iron and reactive oxygen species drive the global formation of methane in aqueous environments.
Oligodendrocyte calcium signaling sculpts myelin sheath morphology
Authors: Iyer Manasi , Kantarci Husniye , Ambiel Nicholas , Novak Sammy W. , Andrade Leonardo R. , Lam Mable , Münch Alexandra E. , Yu Xinzhu , Khakh Baljit S. , Manor Uri , Zuchero J. Bradley 
Published: April 2023

SUMMARYMyelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and can precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. Here, we used genetic tools to attenuate oligodendrocyte calcium signaling during active myelination in the developing mouse CNS. Surprisingly, we found that genetic calcium attenuation did not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation caused striking myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduced actin filaments in oligodendrocytes, and an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a novel cellular mechanism required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to sculpt myelin sheaths throughout the nervous system.
Somatic Calcium Signals from Layer II/III Motor Cortex for Continuous Neural Decoding
Authors: Wang Ruixue , Han Jiawei , Hu Xiaoling , You Heecheon , Zhang Shaomin 
Published: April 2023

AbstractThe latest research shows that calcium signals can provide a new signal source for brain-machine interfaces (BMI). However, it remains a question whether the calcium signals from layer 2/3 motor cortex can be used for continuous neural decoding. And how they are involved in movement coding is also worth investigating. Here we collect the somatic signals in M1 layer 2/3 while mice performed a lever-press task under the one-photon imaging. We first present the potential of somatic calcium signals from layer 2/3 in continuous neural decoding through an improved recurrent neural network. Layer 2/3 neurons exhibit three types of calcium dynamics with distinct spatiotemporal coding patterns involved in the movement. Pre-pressing and pressing neurons enable sparse coding of movement through complementary spatiotemporal information. While post-pressing neurons predict the lever movement most accurately through the calcium dynamics with higher fidelity. These results demonstrate the capability of calcium signals from layer 2/3 neurons as a motor BMI driver and underscore their diversity in motor coding, opening a new avenue for studying the motor cortex and designing optical BMIs.
Strong purifying selection in haploid tissue-specific genes of Scots pine supports the masking theory
Authors: Cervantes Sandra , Kesälahti Robert , Kumpula Timo A. , Mattila Tiina M. , Helanterä Heikki , Pyhäjärvi Tanja 
Published: April 2023

AbstractThe masking theory states that genes expressed in haploid stage will be under more efficient selection. In contrast, selection will be less efficient in genes expressed in diploid stage, where the fitness effects of recessive deleterious or beneficial mutations can be hidden from selection in heterozygous form. This difference can influence several evolutionary processes such as maintenance of genetic variation, adaptation rate, and genetic load. Masking theory expectations have been confirmed in single-cell haploid and diploid organisms. However, in multicellular organisms, such as plants, the effects of haploid selection are not clear-cut. In plants, the great majority of studies indicating haploid selection have been carried out using male haploid tissues in angiosperms. Hence, evidence in these systems is confounded with the effects of sexual selection and intra-specific competition. Evidence from other plant groups is scarce and results show no support for the masking theory.Here we have used a gymnosperm Scots pine megagametophyte, a maternally-derived seed haploid tissue, and four diploid tissues to test the strength of purifying selection on a set of genes with tissue-specific expression. By using targeted resequencing data of those genes, we obtained estimates of genetic diversity, the site frequency spectrum of 0-fold and 4-fold sites, and inferred the distribution of fitness effects (DFE) of new mutations in haploid and diploid tissue-specific genes. Our results show that purifying selection is stronger for tissue-specific genes expressed in the haploid megagametophyte tissue, and that this signal of strong selection is not an artifact driven by high expression levels
Activation of peroxisome proliferator-activated receptor-γ prevents monocrotaline-induced pulmonary arterial hypertension by suppressing of nuclear factor-kappa B mediated autophagy
Authors: Zhang Peng , Shi Congcong , Song Juntao , Dong Tongbao , Zhang Kaixiao 
Published: April 2023

AbstractTo investigate the molecular mechanisms underlying autophagy inducing pulmonary vascular remodeling and rosiglitazone inhibiting pulmonary arterial hypertension (PAH). Monocrotaline (MCT) was intraperitoneally injection to induce the rat PAH model. The right ventricular hypertrophy index (RVHI), right ventricle systolic pressure (RVSP), percentage of medial wall thickness (%MT) and histomorphologic analyses were performed to evaluate the development of PAH. The translocation of nuclear factor-kappa B (NF-κB) p65 subunit from cytosol to nucleus, the protein expression levels of LC3B, Beclin 1 and RND3 were determined by western blot. Furthermore, NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) and peroxisome proliferator-activated receptor-γ (PPARγ) activator, rosiglitazone, were used to inhibit the activation of NF-κB and activate PPARγ signaling, respectively. MCT injection dramatically induced PAH models in rats as manifested by the increased RVSP, RVHI, and %MT. In addition, the activation of NF-κB and autophagy were significantly enhanced and the RND3 were markedly decreased in MCT-induced PAH in rat. However, these effects could be significantly suppressed either by the supplementation of PDTC or rosiglitazone. NF-κB promotes the development of PAH by activation of autophagy and consequent down-regulation of RND3 expression. Activation of PPARγ suppresses autophagy by inhibiting NF-κB in MCT-induced PAH. Our results not only uncovered the mechanisms of PPARγ activator in the protection of PAH but also provided potential therapeutic target for PAH treatment.
An in vitro model for vitamin A transport across the human blood-brain barrier
Authors: Est Chandler B. , Murphy Regina M. 
Published: April 2023

AbstractVitamin A, supplied by the diet, is critical for brain health, but little is known about its delivery across the blood-brain barrier (BBB). Brain microvascular endothelial-like cells (BMECs) differentiated from human-derived induced pluripotent stem cells (iPSC) form a tight barrier that recapitulates many of the properties of the human BBB. We paired iPSC-derived BMECs with recombinant vitamin A serum transport proteins, retinol binding protein (RBP) and transthyretin (TTR), to create anin vitromodel for the study of vitamin A (retinol) delivery across the human BBB. iPSC-derived BMECs display a strong barrier phenotype, express key vitamin A metabolism markers and can be used for quantitative modeling of retinol accumulation and permeation. Manipulation of retinol, RBP and TTR concentrations, and the use of mutant RBP and TTR, yielded novel insights into the patterns of retinol accumulation in, and permeation across, the BBB. The results described herein provide a platform for deeper exploration of the regulatory mechanisms of retinol trafficking to the human brain.
“Shin in the eye”: Au-CS@FNDs as contact lens additives for blocking UV irradiation, bacterial keratitis, and corneal neovascularization therapies
Authors: Nie Linyan , Hu Xiaowen , Zhao Yunxiao , Wu Fan , Wang Yaran , Chen Lei , Wang Yi , Liu Yong 
Published: April 2023

ABSTRACTOphthalmic disease treatment remains a significant problem globally, resulting in poor vision and blindness. UV irradiation and bacterial infection may cause severe damage to the corneal, leading to vision loss within a few days. Corneal neovascular abnormally growth that bock lights reach to eyes, causes low vision. Thus it requires urgent and efficient clinical treatment. Contact lenses play an essential role in treating ophthalmic issues. In this work, we synthesized the chitosan-stabilized Au nanoparticles with a simple method. The Au nanoparticles were further physically adsorbed with negatively charged fluorescent nanodiamonds, yielding Au-CS@FNDs. These Au-CS@FNDs particles were proven with excellent UV adsorption, antibacterial properties, and photothermal conversation ability. Furthermore, we embedded Au-CS@FNDs particles into contact lenses to prevent corneal damage from UV light and bacterial infection. Moreover, the Au-CS@FNDs embedded contact lenses were used to inhibit the neovascularization in the Human Vascular Endothelial Cells via the photodynamic effect of Au nanoparticles. To the best of our knowledge, it is the first time that gold and diamond nanoparticles were used as additives in contact lenses, aiming at clinically corneal neovascular. Our results suggest that the controllable photothermal effect of Au-CS@FNDs embedded contact lenses may provide a unique way to intervene the neovascular-induced vision loss.Abstract Figure
A potential patient stratification biomarker for Parkinso’s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells
Authors: Naaldijk Yahaira , Fernández Belén , Fasiczka Rachel , Fdez Elena , Leghay Coline , Croitoru Ioana , Kwok John B. , Boulesnane Yanisse , Vizeneux Amelie , Mutez Eugenie , Calvez Camille , Destée Alain , Taymans Jean-Marc , Aragon Ana Vinagre , Yarza Alberto Bergareche , Padmanabhan Shalini , Delgado Mario , Alcalay Roy N. , Chatterton Zac , Dzamko Nicolas , Halliday Glenda , Ruiz-Martínez Javier , Chartier-Harlin Marie-Christine , Hilfiker Sabine 
Published: April 2023

AbstractParkinso’s disease (PD) is a common neurodegenerative movement disorder and leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for disease intervention. However, the ability to stratify patients who will benefit from such treatment modalities based on shared etiology is critical for the success of disease-modifying therapies. Ciliary and centrosomal alterations are commonly associated with pathogenic LRRK2 kinase activity and can be detected in many cell types. We previously found centrosomal deficits in immortalized lymphocytes fromG2019S-LRRK2PD patients. Here, to investigate whether such deficits may serve as a potential blood biomarker for PD which is susceptible to LRKK2 inhibitor treatment, we characterized patient-derived cells from distinct PD cohorts. We report centrosomal alterations in peripheral cells from a subset of early-stage idiopathic PD patients which is mitigated by LRRK2 kinase inhibition, supporting a role for aberrant LRRK2 activity in idiopathic PD. Centrosomal defects are detected inR1441G-LRRK2andG2019S-LRRK2PD patients and in non-manifestingLRRK2mutation carriers, indicating that they acumulate prior to a clinical PD diagnosis. They are present in immortalized cells as well as in primary lymphocytes from peripheral blood. These findings indicate that analysis of centrosomal defects as a blood-based patient stratification biomarker may help nominate PD patients who will benefit from LRRK2-related therapeutics.One-sentence summaryPeripheral blood-derived cells can be employed to stratify Parkinso’s disease patients most likely to respond to LRRK2-related therapeutics.