bluuebunny/crossref_metadata_2025_split huggingface dataset:
SlimVar: rapidin vivosingle-molecule tracking of chromatin regulators in plants
Authors: Payne-Dwyer Alex L. , Jang Geng-Jen , Dean Caroline , Leake Mark C. 
Published: May 2024

AbstractEpigenetic regulation maintains gene expression patterns over many rounds of cell division in higher organisms. However, visualization of factors regulating epigenetic switchesin vivois limited by the challenge of imaging cells deep in living tissue, with molecular sensitivity and rapid sampling. We report an easy-to-implement method called Variable-angle Slimfield microscopy (SlimVar), which by simple modification of an inverted optical microscope, enables single-molecule tracking of fluorescent reporters inArabidopsis thaliana. Using SlimVar, we imaged stepwise photobleaching of chromatin-protein assemblies in individual nuclei, 30 µm deep in root tips through multiple cell layers. We find that two homologous proteins key to the epigenetic switch atFLOWERING LOCUS C(FLC) —cold-induced VERNALIZATION INSENSITIVE3 (VIN3) and constitutively expressed VERNALIZATION 5 (VRN5)—exhibit dynamic nuclear assemblies duringFLCsilencing. Upon cold exposure, these assemblies increase in stoichiometry by up to 100% to a median of ∼20 molecules. Larger VRN5 assemblies preferentially co-localize with anFLC lacOtransgenic reporter during prolonged cold, persisting after return to warm conditions. Our findings support a hybrid model of epigenetic memory in which nucleation of histone trimethylation is assisted by dynamic protein assemblies over extended durations. SlimVar therefore has potential to offer molecular insights into proteins expressed at physiological levels in a range of tissues.
Association of Body Index with Fecal Microbiome in Children Cohorts with Ethnic-Geographic Factor Interaction: Accurately Using a Bayesian Zero-inflated Negative Binomial Regression Model
Authors: Huang Jian , Lu Yanzhuan , Tian Fengwei , Ni Yongqing 
Published: May 2024

ABSTRACTThe exponential growth of High-Throughput Sequencing (HTS) data on the microbial communities presents researchers with an unparalleled opportunity to delve deeper into the association of microorganisms with host phenotype. However, this growth also poses a challenge, as microbial data is complex, sparse, discrete, and prone to zero-inflation. Moreover, current methods for integrating microbiome data and other covariates are severely lacking. Hence, we propose a Bayesian zero-inflated negative binomial (ZINB) regression model that is capable of identifying differentially abundant taxa with distinct phenotypes and quantifying the effects of covariates on these taxa. Our model exhibits excellent performance when tested on simulated data. Upon successfully applying our model to a real multi-ethnic cohort study, we discovered that the prevailing understanding of microbial count data from previous research was overly dogmatic, because only a subset of taxa demonstrated zero inflation in real data. Moreover, we have discovered that dispersion parameters significantly influence the accuracy of model results, and increasing sample size can alleviate this issue. In all, we have presented an innovative integrative Bayesian regression model and a comprehensive pipeline for conducting a multi-ethnic cohort study of children, which facilitates bacterial differential abundance analysis and quantification of microbiome-covariate effects. This approach can be applied to general microbiome studies.IMPORTANCEMicrobiome are closely associated with physical indicators of the body, such as height, weight, age and BMI, which can be used as measures of human health. How to accurately identify which taxa in the microbiome are closely related to indicators of physical development is valuable as microbial markers of local child growth. Complex biological systems can be effectively modeled with ZINB model which is a Bayesian Generalized Linear Model. However, the potential of the ZINB model in the microbiome field has not yet been fully utilized in practice. Microbial count data are more complex than other scenarios, and our model captures this complexity. Our study is the first to discuss the effects of zero inflation and the degree of overdispersion in microbiome data on the results of model solutions. Finally, our work successfully applied it to a real multi-ethnic cohort study.
Interactive effects of temperature and salinity on metabolism and activity of the copepodTigriopus californicus
Authors: Terry Caroline E. , Liebzeit Josie A. , Purvis Ella M. , Dowd W. Wesley 
Published: May 2024

AbstractIn natural environments two or more abiotic parameters often vary simultaneously, and interactions between covarying parameters frequently result in unpredictable, non-additive biological responses. To better understand the mechanisms and consequences of interactions between multiple stressors it is important to study their effects on both survival and performance. The splashpool copepodTigriopus californicustolerates extremely variable abiotic conditions and exhibits a non-additive, antagonistic interaction resulting in higher survival when simultaneously exposed to high salinity and acute heat stress. Here, we investigatedT. californicus’response in activity and oxygen consumption under simultaneous manipulation of salinity and temperature to identify if this interaction also arises in these sublethal measures of performance. Oxygen consumption and activity rates decreased with increasing assay salinity. Oxygen consumption also sharply increased in response to acute transfer to lower salinities, an effect that was absent upon transfer to higher salinities. Elevated temperature led to reduced rates of activity overall, resulting in no discernible impact of increased temperature on routine metabolic rates. This suggests that swimming activity has a non-negligible effect on copepod’s metabolic rates and must be accounted for in metabolic studies. Temperature also interacted with assay salinity to affect activity and with acclimation salinity to affect routine metabolic rates upon acute salinity transfer, implying that the sublethal impacts of these co-varying factors are also not predictable from experiments that study them in isolation.Summary StatementTemperature and salinity interact to affect metabolic rate in the copepodTigriopus californicus, but the stressors’ individual effects and their interaction are complicated by concurrent changes in activity.
Fabrication of mRNA encapsulated Lipid nanoparticles usingState-of-the-artSMART-MaGIC Technology and transfectionin vitro
Authors: Heshmati Niloofar , Chakka Jaidev , Zhang Yu , Maniruzzaman Mohammed 
Published: May 2024

AbstractThe messenger ribose nucleic acid (mRNA)in lieuof Corona virus of 2019 (COVID-19) vaccines were effectively delivered through Lipid nanoparticles (LNP) which were proved effective carriers for clinical applications. In the present work, mRNA (erythropoietin (EPO)) encapsulated LNPs were prepared using a next generation state-of-the-art patented Sprayed Multi Absorbed-droplet Reposing Technology (SMART) coupled with Multi-channeled and Guided Inner-Controlling printheads (MaGIC) technologies. The LNP-mRNA were synthesized at different N/P ratios and the particles were characterized for particle size & zeta potential (Zetasizer), encapsulation or complexation (gel retardation assay) and transfection (Fluorescence microscopy) in MG63 sarcoma cellsin vitro. The results showed a narrow distribution of mRNA-lipid particles of 200 nm when fabricated with SMART alone and then the size was reduced to approximately 50 nm with the combination of SMART-MaGIC technologies. The gel retardation assay showed that the N/P>1 showed strong encapsulation of mRNA with lipid. Thein vitroresults showed the toxicity profile of the lipids where N/P ratio of 5 is the optimized with >50% cell viability. The functional LNP-mRNA were prepared and analyzed with SMART-MaGIC technologies which could be a potential new fabrication method of mRNA loaded LNPs.HighlightsThe particle size was reduced to around 50 nm with implementation of SMART-MaGIC.The loading efficiency is 100%.The functionality of the mRNA is unaffected during the preparation process.The transfection facilitated transient expression of the proteinin vitro.The EPO mRNA is more effective than EPO protein to reduce chemo-toxic effectsin vitro.
Sensitivity to visual features in inattentional blindness
Authors: Nartker Makaela , Firestone Chaz , Egeth Howard , Phillips Ian 
Published: May 2024

SummaryThe relation between attention, perception and awareness is among the most fundamental problems in the science of the mind. One of the most striking and well-known phenomena bearing on this question isinattentional blindness(IB; Neisser & Becklen, 1975; Mack & Rock, 1998; Most et al., 2001, 2005). In IB, naïve observers fail to report clearly visible stimuli when their attention is otherwise engaged—famously even missing a gorilla parading before their eyes (Simons & Chabris, 1999). This phenomenon and the research programs it has motivated carry tremendous theoretical significance, both as crucial evidence that awareness requires attention (Cohen et al., 2012; Prinz, 2012; Noah & Mangun, 2020) and as a key tool in seeking the neural correlates of consciousness (Rees et al., 1999; Pitts et al., 2014; Hutchinson, 2019). However, these and other implications critically rest on a notoriously biased measure: asking participants whether they noticed anything unusual (and interpreting negative answers as reflecting a complete lack of perception). Here, in the largest ever set of IB studies, we show that, as a group, inattentionally blind participants can successfully report the location, color and shape of the stimuli they deny noticing. This residual visual sensitivity shows that perceptual information remains accessible in IB. We further show that subjective reports in IB are conservative, by introducing absent trials where no IB stimulus is presented; this approach allows us to show for the first time that observers collectively show a systematic bias to report not noticing in IB—essentially ‘playing it safe’ in reporting their sensitivity. This pair of results is consistent with an alternative hypothesis about IB, namely that inattentionally blind subjects retain some degree of awareness of the stimuli they fail to report. Overall, these data provide the strongest evidence to date of significant residual visual sensitivity in IB. They also challenge the use of inattentional blindness to argue that awareness requires attention.
Generating Synthetic Single Cell Data from Bulk RNA-seq Using a Pretrained Variational Autoencoder
Authors: Cho Hyun Jae , Xie Eric , Zhang Aidong , Bekiranov Stefan 
Published: May 2024

AbstractSingle cell RNA sequencing (scRNA-seq) is a powerful approach which generates genome-wide gene expression profiles at single cell resolution. Among its many applications, it enables determination of the transcriptional states of distinct cell types in complex tissues, thereby allowing the precise cell type and set of genes driving a disease to be identified. However, scRNA-seq remains costly, and there are extremely limited samples generated in even the most extensive human disease studies. In sharp contrast, there is a wealth of publicly available bulk RNA-seq data, in which single cell and cell type information are effectively averaged. To further leverage this wealth of RNA-seq data, methods have been developed to infer the fraction of cell types from bulk RNA-seq data using single cell data to train models. Additionally, generative AI models have been developed to generate more of an existing scRNA-seq dataset. In this study, we develop an innovative framework that takes full advantage of powerful generative AI approaches and existing scRNA-seq data to generate representative scRNA-seq data from bulk RNA-seq. Our bulk to single cell variational autoencoder-based model, termedbulk2sc, is trained to deconvolve pseudo-bulk RNA-seq datasets back into their constituent single-cell transcriptomes by learning the specific distributions and proportions related to each cell type. We assess the performance of bulk2sc by comparing synthetically generated scRNA-seq to actual scRNA-seq data. Application of bulk2sc to large-scale bulk RNA-seq human disease datasets could yield single cell level insights into disease processes and suggest targeted scRNA-seq experiments.
Multivariate Analysis of the Impact of Demographic and Clinical Factors on Cardiovascular Health
Authors: Benfallah Youssef , Guo Wanru , Sarfraz Shoaib , Yang Yanyu 
Published: May 2024

AbstractBackgroundThis study investigates the influence of demographic and clinical factors on cardiovascular health using a multivariate analysis approach. We analyzed data from one of the largest heart-related disease datasets, merging variables such as age, sex, chest pain type, to determine their association with resting blood pressure, cholesterol, and maximum heart rate.MethodsTwo-means comparison is used to investigate the effect of heart disease with response variables, One-way and two-way MANOVA are used to study the relationship between chest pain type, as well as sex and heart disease on the response variables, respectively. Profile analysis and MANCOVA were also conducted to determine a final model.ResultsOur findings indicate significant effects of heart disease on resting blood pressure, cholesterol and maximum heart rate. Chest pain type also has a significant effect on maximum heart rate achieved, but not blood pressure and cholesterol. There are also notable interactions between sex and heart disease status on all response variables. Finally, we formulized a multivariate regression model with age, sex, chest pain type, heart disease, and the interaction between heart disease and sex as predictors.ConclusionThese findings can inform physicians on possible treatment strategies in cardiovascular diseases.
Signatures of social pain empathy: general and process-specific brain-wide representations of social exclusion and separation
Authors: Zhang Xiaodong , Qing Peng , Liu Qi , Liu Can , Liu Lei , Gan Xianyang , Fu Kun , Lan Chunmei , Zhou Xinqi , Kendrick Keith M. , Becker Benjamin , Zhao Weihua 
Published: May 2024

AbstractEmpathy can be elicited by physiological pain, as well as in social contexts. Although physiological and different social contexts induce a strong subjective experience of empathy, the general and context-specific neural representations remain elusive. Here, we combine fMRI with multivariate pattern analysis to establish neurofunctional models for pain empathy triggered by social exclusion and separation. Our findings revealed both overlapping and distinct neural representations for social exclusion and separation empathy across cortical and subcortical regions. This study established an evolutionary model that traces the progression from social pain to physiological pain empathy. In conclusion, this study establishes neural decoding models for pain empathy evoked by social exclusion and social separation, revealing their neural foundations and interconnectedness of empathy induced by social and physiological stimuli. These findings deepen our understanding of the neurobiological mechanisms underlying social pain empathy and provide robust neuromarkers to precisely evaluate empathy across physiological and social domains.
Systemic migrations in enucleated cells
Authors: De la Fuente Ildefonso M. , Carrasco-Pujante Jose , Camino-Pontes Borja , Fedetz Maria , Bringas Carlos , Pérez-Samartín Alberto , Pérez-Yarza Gorka , López José I. , Cortes Jesus M , Malaina Iker 
Published: May 2024

AbstractDirectional locomotion is a fundamental characteristic of many cells with great relevance in essential physiological and human pathological processes. For decades, research efforts have focused on studying specific individual processes and their corresponding biomolecular components involved in cellular locomotion movements. However, the notion that migratory displacements are functionally integrated and regulated at the systemic level has never been recognized. Recently, we have shown that locomotion movements correspond to an emergent systemic behavior which depends on a complex integrated self-organized system carefully regulated at a global cellular level. Here, to study the forces driving the locomotion movement of the cell, and to corroborate the thesis on the systemic character of the cellular migratory responses we have carried out an extensive study of locomotion movements with enucleated cells (cytoplasts) belonging toAmoeba proteus. The migratory behavior of both enucleated and non-enucleated cells has been individually studied in four different scenarios: in absence of stimuli, under a galvanotactic field, in chemotactic gradient, and under very complex conditions such as simultaneous galvanotactic and chemotactic stimuli. All these experimental displacement trajectories, obtained on flat two-dimensional surfaces, have been analyzed using advanced non-linear quantitative approaches. Our results show that both non-enucleated amoebas and cytoplasts display the same complex kind of dynamic structure in their migratory trajectories. The locomotion displacements of enucleated cells are regulated by complex self-organized integrative dynamics, modulated at a global-systemic level which seems to depend on the cooperative interaction of most, if not all, molecular components of cells.
CONSTITUTIVE OPENING OF THE Kv7.2 PORE ACTIVATION GATE CAUSESKCNQ2-DEVELOPMENTAL ENCEPHALOPATHY
Authors: Nappi Mario , Alberini Giulio , Berselli Alessandro , Roscioni Agnese , Soldovieri Maria Virginia , Barrese Vincenzo , Weckhuysen Sarah , Chiu Ting-Gee Annie , Scheffer Ingrid E. , Benfenati Fabio , Maragliano Luca , Miceli Francesco , Taglialatela Maurizio 
Published: May 2024

ABSTRACTPathogenic variants inKCNQ2encoding for Kv7.2 voltage-gated potassium channel subunits cause developmental encephalopathies (KCNQ2-encephalopathies), both with and without epilepsy. We herein describe the clinical,in vitroandin silicofeatures of two encephalopathy-causing variants (A317T, L318V) in Kv7.2 affecting two consecutive residues in the S6activation gate undergoing large structural rearrangements during pore opening. Currents through these mutant channels displayed increased density, hyperpolarizing shifts in activation gating, and insensitivity to phosphatidylinositol 4,5-bisphosphate (PIP2), a critical regulator of Kv7 channel function; all these features are consistent with a strong gain-of-function effect. An increase in single-channel open probability, with no change in membrane abundance or single-channel conductance, was responsible for the observed gain-of-function effects. All-atoms Molecular Dynamics simulations revealed that the mutations widened the inner pore gate and stabilized a constitutively open channel configuration in the closed state, with minimal effects on the open conformation. Thus, a PIP2-independent stabilization of the inner pore gate open configuration is a novel molecular pathogenetic mechanism forKCNQ2-developmental encephalopathies.
A Sap Peptide Conserved across Flowering Plants Positively Regulates Lignin Biosynthesis, Biomass and Immunity
Authors: Chen Chang-Hung , Liou Pin-Chien , Hsu Yi-Fan , Wang I-Fan , Kuo Chun-Yu , Huang Kuan-Hao , Yu Jhong-He , Chen Chin-Wen , Wu Chia-Chen , Lin Da-Gin , Li Cheng-Bin , Tu Yuan-Kai , Hsu Chuan-Chih , Su Jung-Chen , Xia Kai , Tsai Isheng Jason , Lin Ying-Chung Jimmy , Chen Ying-Lan 
Published: May 2024

AbstractSignaling peptides act as hormones to deliver short- or long-distance intercellular signals to govern complex developmental processes. Identifying endogenous signaling peptides is challenging due to their low abundance and the unknown cleavage sites required for release from precursor proteins, not to mention the investigation of their evolutionary roles across species. Consequently, very few peptides were evolutionarily characterizedin vivo, especially long-distance signaling peptides. Here we present current largest peptidomic datasets from six species (maize, camphor tree, tomato, rose gum, soybean and poplar), totaling 12,242 peptides, selected from all representative evolutionary clades of angiosperms, including monocots, magnoliids, rosid eudicots, and asterid eudicots. A sap peptide was found to be identical across all six species and named as ASAP (angiospermsappeptide), emerging as the most conserved peptide family discovered thus far. ASAP rapidly induces a series of protein phosphorylation involved in a signaling cascade previously reported to regulate lignin biosynthesis, plant growth and plant immunity. Functional assays on ASAP activity demonstrated its capability on the induction of monolignol biosynthesis and lignin deposition. High-throughput phenomic analyses showed that ASAP significantly increased plant above- and below-ground biomass. In addition, ASAP treatment enhanced plant immunity and reduced the number of galls and egg masses against nematode invasion. This study provides insights into the conservation and functional significance of plant long-distance mobile signaling peptides, offering potential applications in crop improvement and disease management strategies.
Novel cell-to-cell interactions revealed by cryotomography of a DPANN coculture system
Authors: Johnson Matthew D , Shepherd Doulin C , Sakai Hiroyuki D. , Mudaliyar Manasi , Pandurangan Arun Prasad , Short Francesca L , Veith Paul D. , Scott Nichollas E , Kurosawa Norio , Ghosal Debnath 
Published: May 2024

AbstractDPANN is a widespread and highly diverse group of archaea characterised by their small size, reduced genome, limited metabolic pathways, and symbiotic existence. Known DPANN species are predominantly obligate ectosymbionts that depend on their host for their survival and proliferation. Despite the recent expansion in this clade, the structural and molecular details of host recognition, host-DPANN intercellular communication, and host adaptation in response to DPANN attachment remain unknown. Here, we used electron cryotomography (cryo-ET) to reveal that theCandidatusMicrarchaeota (ARM-1) interacts with its host,Metallosphaera javensisthrough intercellular proteinaceous nanotubes. These tubes (∼4.5 nm wide) originate in the host, extend all the way to the DPANN cytoplasm and act like tunnels for intercellular exchange. Combining cryo-ET and sub-tomogram averaging, we revealed thein situarchitectures of host and DPANN S-layers and the structures of the nanotubes in their primed and extended states, providing mechanistic insights into substrate exchange. Additionally, we performed comparative proteomics and genomic analyses to identify host proteomic changes in response to the DPANN attachment. Our results showed striking alterations in host-proteome during symbiosis and upregulation/downregulation of key cellular pathways. Collectively, these results provided unprecedented insights into the structural basis of host-DPANN communication and deepen our understanding of the host ectosymbiotic relationships.