bluuebunny/crossref_metadata_2025_split huggingface dataset:
Milk Exosomes Cross the Blood-Brain Barrier in Murine Cerebral Cortex Endothelial Cells and Promote Dendritic Complexity in the Hippocampus and Brain Function in C57BL/6J Mice
Authors: Zhou Fang , Ebea Pearl , Mutai Ezra , Sukreet Sonal , Navazesh Shya , Dogan Haluk , Li Wenhao , Cui Juan , Ji Peng , Ramirez Denise M. O. , Zempleni Janos 
Published: November 2021

ABSTRACTBackgroundHuman milk contains large amounts of exosomes (MEs) and their regulatory microRNA cargos, whereas infant formulas contain only trace amounts of MEs and microRNAs. Breastfeeding has been implicated in optimal brain development but experimental evidence linking ME intake with brain development is limited.ObjectivesWe assessed the transport of MEs across the blood-brain barrier (BBB) and ME accumulation in distinct regions of the brain in brain endothelial cells and suckling mice. We further assessed BME-dependent gene expression profiles and effects on the dendritic complexity of hippocampal granule cells and phenotypes of BME depletion in neonate, juvenile and adult mice.MethodsThe transfer of MEs across the BBB was assessed by using bovine MEs labeled with FM4-64 or loaded with IRDye-labeled miR-34a in murine brain endothelial bEnd.3 cell monolayers and dual chamber systems, and in wild-type newborn pups fostered to exosome and cargo tracking (ECT) dams that express MEs endogenously labeled with a CD63-eGFP fusion protein for subsequent analysis by serial two-photon tomography and staining with anti-eGFP antibodies. Effects of MEs on gene expression and dendritic architecture of granule cells was analyzed in hippocampi from juvenile mice fed exosome and RNA-depleted (ERD) and exosome and RNA-sufficient (ERS) diets by using RNA-sequencing analysis and Golgi-Cox staining followed by integrated neuronal tracing and morphological analysis of neuronal dendrites, respectively. Spatial learning and severity of kainic acid-induced seizures were assessed in mice fed ERD and ERS diets.ResultsbEnd.3 cells internalized MEs by using a saturable transport mechanism and secreted miR-34a across the basal membrane. MEs penetrated the entire brain in fostering experiments; major regions of accumulation included the hippocampus, cortex and cerebellum. Two hundred ninety-five genes were differentially expressed in hippocampi from male mice fed ERD and ERS diets; high-confidence gene networks included pathways implicated in axon guidance and calcium signaling. Only one gene was differentially expressed in females fed the experimental diets. Juvenile pups fed the ERD diet had reduced dendritic complexity of dentate granule cells in the hippocampus, scored nine-fold lower in the Barnes maze test of spatial learning and memory (P< 0.01), and the severity of seizures was 5-fold higher following kainic acid administration in adult mice fed the ERD diet compared to mice fed the ERS diet (P< 0.01).ConclusionsMEs cross the BBB and contribute toward optimal neuronal development, spatial learning and memory, and resistance to kainic acid-induced seizures in mice.
RyR2/IRBIT regulates insulin gene transcription, insulin content, and secretion in the insulinoma cell line INS-1
Authors: Harvey Kyle E. , LaVigne Emily K. , Dar Mohd Saleem , Salyer Amy E. , Pratt Evan P.S. , Sample Paxton A. , Aryal Uma , Gowher Humaira , Hockerman Gregory H. 
Published: November 2021

AbstractThe role of ER Ca2+ release via ryanodine receptors (RyR) in pancreatic β-cell function is not well defined. Deletion of RyR2 from the rat insulinoma INS-1 (RyR2KO) enhanced the Ca2+ integral (AUC) stimulated by 7.5 mM glucose, and rendered it sensitive to block by the IP3 receptor inhibitor xestospongin C, coincident with reduced levels of the protein IP3Receptor Binding protein released with Inositol 1,4,5 Trisphosphate (IRBIT; aka AHCYL1). Deletion of IRBIT from INS-1 cells (IRBITKO) increased the Ca2+ AUC in response to 7.5 mM glucose and induced xestospongin sensitivity. Insulin content and basal (2.5 mM glucose) and 7.5 mM glucose-stimulated insulin secretion were reduced in RyR2KO cells and more modestly reduced in IRBITKO cells compared to controls. INS2 mRNA levels were reduced in both RyR2KO and IRBITKO cells, but INS1 mRNA levels were specifically decreased in RyR2KO cells. Nuclear localization of S-adenosylhomocysteinase (AHCY) was increased in RyR2KO and IRBITKO cells. DNA methylation of the INS1 and INS2 gene promotor regions was very low, and not different among RyR2KO, IRBITKO, and controls. In contrast, exon 2 of the INS1 and INS2 genes was more extensively methylated in RyR2KO and IRBITKO cells than in controls. Proteomics analysis using LC-MS/MS revealed that deletion of RyR2 or IRBIT resulted in differential regulation of 314 and 137 proteins, respectively, with 41 in common. These results suggest that RyR2 regulates IRBIT levels and activity in INS-1 cells, and together maintain insulin content and secretion, and regulate the proteome, perhaps via DNA methylation.One sentence SummaryDeletion of RyR2 from INS-1 cells had the unanticipated effect of reducing IRBIT proteins levels, and both RyR2 and IRBIT contribute to maintenance of glucose- stimulated insulin secretion.
A Complete Pedigree-Based Graph Workflow for Rare Candidate Variant Analysis
Authors: Markello Charles , Huang Charles , Rodriguez Alex , Carroll Andrew , Chang Pi-Chuan , Eizenga Jordan , Markello Thomas , Haussler David , Paten Benedict 
Published: November 2021

AbstractMethods that use a linear genome reference for genome sequencing data analysis are reference biased. In the field of clinical genetics for rare diseases, a resulting reduction in genotyping accuracy in some regions has likely prevented the resolution of some cases. Pangenome graphs embed population variation into a reference structure. While pangenome graphs have helped to reduce reference mapping bias, further performance improvements are possible. We introduce VG-Pedigree, a pedigree-aware workflow based on the pangenome-mapping tool of Giraffe (Sirén et al. 2021) and the variant-calling toolDeepTrio(Kolesnikov et al. 2021) using a specially-trained model for Giraffe-based alignments. We demonstrate mapping and variant calling improvements in both single-nucleotide variants (SNVs) and insertion and deletion (INDEL) variants over those produced by alignments created using BWA-MEM to a linear-reference and Giraffe mapping to a pangenome graph containing data from the 1000 Genomes Project. We have also adapted and upgraded the deleterious-variant (DV) detecting methods and programs of Gu et al. into a streamlined workflow (Gu et al. 2019). We used these workflows in combination to detect small lists of candidate DVs among 15 family quartets and quintets of the Undiagnosed Diseases Program (UDP). All candidate DVs that were previously diagnosed using the mendelian models covered by the previously published Gu et al. methods were recapitulated by these workflows. The results of these experiments indicate a slightly greater absolute count of DVs are detected in the proband population than in their matched unaffected siblings.
Automated methodology for optimal selection of minimum electrode subsets for accurate EEG source estimation based on Genetic Algorithm optimization
Authors: Soler A. , Moctezuma L. , Giraldo E. , Molinas M. 
Published: November 2021

ABSTRACTHigh-density Electroencephalography (HD-EEG) has been proven to be the most accurate option to estimate the neural activity inside the brain. Multiple studies report the effect of electrode number on source localization for specific sources and specific electrode configurations. The electrodes for these configurations have been manually selected to uniformly cover the entire head, going from 32 to 128 electrodes, but electrodes were not selected according to their contribution to accuracy. In this work, an optimization-based study is proposed to determine the minimum number of electrodes and identify optimal combinations of electrodes that can retain the localization accuracy of HD-EEG reconstructions. This optimization approach incorporates scalp landmark positions of widely used EEG montages. In this way, a systematic search for the minimum electrode subset is performed for single and multiple source localization problems. The Non-dominated Sorting Genetic Algorithm II (NSGA-II) combined with source reconstruction methods is used to formulate a multi-objective optimization problem that concurrently minimizes 1) the localization error for each source and 2) the number of required EEG electrodes. The method can be used for evaluating the source localization quality of low-density EEG systems (e.g. consumer-grade wearable EEG). We performed an evaluation over synthetic and real EEG dataset with known ground-truth. The experimental results show that optimal subsets with 6 electrodes can obtain an equal or better accuracy than HD-EEG (with more than 200 channels) for a single source case. This happened when reconstructing a particular brain activity in more than 88% of the cases (in synthetic signals) and 63% (in real signals), and in more than 88% and 73% of the cases when considering optimal combinations with 8 channels. For a multiple-source case of three sources (only with synthetic signals), it was found that optimized combinations of 8, 12 and 16 electrodes attained an equal or better accuracy than HD-EEG with 231 electrodes in at least 58%, 76%, and 82% of the cases respectively. Additionally, for such electrode numbers, a lower mean error and standard deviation than with 231 electrodes were obtained.HighlightsThe number of EEG electrodes and their locations can be optimized for reconstructing the brain source activity.Optimally selected EEG electrodes can retain the accuracy of high density montages (256, 128 chs) for brain source estimation, when electrodes are selected according to their contribution to accuracy.With optimization, selected combinations of EEG electrodes will flexibilize the estimation of the source activity.
A structural dynamics model for how CPEB3 binding to SUMO2 can regulate translational control in dendritic spines
Authors: Gu Xinyu , Schafer Nicholas P. , Bueno Carlos , Lu Wei , Wolynes Peter G. 
Published: November 2021

AbstractA prion-like RNA-binding protein, CPEB3, can regulate local translation in dendritic spines. CPEB3 monomers repress translation, whereas CPEB3 aggregates activate translation of its target mRNAs. However, the CPEB3 aggregates, as long-lasting prions, may raise the problem of unregulated translational activation. Here, we propose a computational model of the complex structure between CPEB3 RNA-binding domain (CPEB3-RBD) and small ubiquitin-like modifier protein 2 (SUMO2). Free energy calculations suggest that the allosteric effect of CPEB3-RBD/SUMO2 interaction can amplify the RNA-binding affinity of CPEB3. Combining with previous experimental observations on the SUMOylation mode of CPEB3, this model suggests an equilibrium shift of mRNA from binding to deSUMOylated CPEB3 aggregates to binding to SUMOylated CPEB3 monomers in basal synapses. This work shows how a burst of local translation in synapses can be silenced following a stimulation pulse, and explores the CPEB3/SUMO2 interplay underlying the structural change of synapses and the formation of long-term memories.
Lateralization of autonomic activity in response to limb-specific threat
Authors: Kryklywy James H. , Lu Amy , Roberts Kevin H. , Rowan Matt , Todd Rebecca M. 
Published: November 2021

AbstractIn times of stress or danger, the autonomic nervous system (ANS) signals the fight or flight response. A canonical function of ANS activity is to globally mobilize metabolic resources, preparing the organism to respond to threat. Yet a body of research has demonstrated that, rather than displaying a homogenous pattern across the body, autonomic responses to arousing events — as measured through changes in electrodermal activity (EDA) — can differ between right and left body locations. Surprisingly, the metabolic function of such ANS asymmetry has not been investigated. In the current study, we investigated whether asymmetric autonomic responses could be induced through limb-specific aversive stimulation. Participants were given mild electric stimulation to either the left or right arm while EDA was monitored bilaterally. Across participants, a strong ipsilateral EDA response bias was observed, with increased EDA response in the hand adjacent to the stimulation. This effect was observable in over 50% of individual subjects. These results demonstrate that autonomic output is more complex than canonical interpretations suggest. We suggest that, in stressful situations, autonomic outputs can prepare either the whole-body fight or flight response, or a simply a limb-localized flick, which can effectively neutralize the threat while minimizing global resource consumption. These findings provide insight into the evolutionary pathway of neural systems processing general arousal by linking observed asymmetry in the peripheral arousal response to a historical leveraging of neural structures organized to mediate responses to localized threat.
The dynamics of HD-ZIP III - ZPR protein interactions play essential roles in embryogenesis, meristem function and organ development
Authors: Gruber Anna Vitlin , Kosty Melissa , Jami-Alahmadi Yasaman , Wohlschlegel James A. , Long Jeff A. 
Published: November 2021

AbstractMaintaining a stem cell population while developing lateral organs is a crucial aspect of plant development. Studies have shown that a family of micro proteins, the LITTLE ZIPPERS (ZPR), are involved in this process by repressing the activity of HD-ZIP III transcription factors. However, the unique role of each ZPR has not been thoroughly characterized. In this work, we use genetics, imaging, and biochemistry to create a detailed picture of ZPR family expression and their specific interactions with HD-ZIP IIIs. CRISPR/Cas9 was implemented to isolate single loss-of-function ZPR alleles as well as higher-order mutant combinations. A single mutation in ZPR1, ZPR3, and ZPR4 affects the development of the cotyledons during embryogenesis. Additionally, double mutant analyses indicates both unique roles for each ZPR protein as well as redundancy. Using ZPR tagged lines we show that while ZPR3 and ZPR4 have a similar pattern of accumulation as the HD-ZIP IIIs, ZPR1 and ZPR2 accumulation is more limited. Immuno-precipitations (IP) with tagged ZPR proteins are mainly enriched with the anticipated HD-ZIP III partners. Although ZPRs interact with all HD-ZIP IIIs, an apparent preference of heterodimer formation with REVOLUTA is observed. Our work highlights that the dynamics of ZPR protein accumulation together with the strength of ZPR-HD-ZIP III interactions provide an added layer of complexity to the regulation of HD-ZIP IIIs during plant development.
A glycosylphosphatidylinositol-anchored α-amylase encoded by amyD contributes to a decrease in the molecular mass of cell wall α-1,3-glucan in Aspergillus nidulans
Authors: Miyazawa Ken , Yamashita Takaaki , Takeuchi Ayumu , Kamachi Yuka , Yoshimi Akira , Tashiro Yuto , Koizumi Ami , Yano Shigekazu , Kasahara Shin , Sano Motoaki , Yamagata Youhei , Nakajima Tasuku , Abe Keietsu 
Published: November 2021

Abstractα-1,3-Glucan is one of the main polysaccharides in the cell wall of Aspergillus nidulans. We previously revealed that it plays a role in hyphal aggregation in liquid culture, and that its molecular mass (MM) in an agsA-overexpressing (agsAOE) strain was larger than that in an agsB-overexpressing (agsBOE) strain. The mechanism that regulates the MM of α-1,3-glucan is poorly understood. Although the gene amyD, which encodes glycosyl-phosphatidylinositol (GPI)-anchored α-amylase (AmyD), is involved in the biosynthesis of α-1,3-glucan in A. nidulans, how it regulates this biosynthesis remains unclear. Here we constructed strains with disrupted amyD (ΔamyD) or overexpressed amyD (amyDOE) in the genetic background of the ABPU1 (wild-type), agsAOE, or agsBOE strain, and characterized the chemical structure of α-1,3-glucans in the cell wall of each strain, focusing on their MM. The MM of α-1,3-glucan from the agsBOE amyDOE strain was smaller than that in the parental agsBOE strain. In addition, the MM of α-1,3-glucan from the agsAOE ΔamyD strain was greater than that in the agsAOE strain. These results suggest that AmyD is involved in decreasing the MM of α-1,3-glucan. We also found that the C-terminal GPI-anchoring region is important for these functions.
Precise identification of cancer cells from allelic imbalances in single cell transcriptomes
Authors: Trinh Mi K. , Pacyna Clarissa N. , Kildisiute Gerda , Anderson Nathaniel D. , Khabirova Eleonora , Behjati Sam , Young Matthew D. 
Published: November 2021

ABSTRACTA fundamental step of tumour single cell mRNA analysis is separating cancer and non-cancer cells. We show that the common approach to separation, using shifts in average expression, can lead to erroneous biological conclusions. By contrast, allelic imbalances representing copy number changes directly detect the cancer genotype and accurately separate cancer from non-cancer cells. Our findings provide a definitive approach to identifying cancer cells from single cell mRNA sequencing data.
Seasonal and spatial variability of antibiotic resistance genes and Class I integrons in rivers of the Mekong Delta, Vietnam
Authors: Pham Thi Thu Hang , Dang Khoa Dinh Hoang , Rohrbach Emmanuelle , Breider Florian , Rossi Pierre 
Published: November 2021

ABSTRACTAquaculture activities continue to expand in Vietnam, covering an estimated 700,000 ha, with 89% of these culture ponds located in the Mekong Delta. Since 2009, large-scale bacterial outbreaks have spread in response to this intensive farming. Antibiotics, even those considered a last resort, have only partially mitigated this problem. A side effect of the massive use of these chemicals is the appearance of mobile genetic elements associated with antibiotic resistance genes (ARGs). The large-scale emergence of a diverse bacterial resistome, accompanied by severe economic losses, has posed significant health risks to local residents. In this study, the seasonal and spatial distributions of the class I integrase (CL1) intl1 and the ARGs sul2 (sulfonamide), BLA-oxa1 (ß-lactams), and ermB (erythromycin) were quantified from water and sediment samples collected during two consecutive seasons along the Vam Co River and its tributary (Long An province, Vietnam). Results showed that CL1 was present in all river compartments, reaching 2.98×104 copies/mL and 1.07×106 copies/g of sediment, respectively. The highest relative copy abundances to the 16S rDNA gene were measured in water samples, with up to 3.02% for BLA-oxa1, followed by sul2 (1.16%) and ermB (0.46%). Strong seasonal (dry season vs. rainy season) and spatial trends were recorded for all resistance genes. Higher amounts of ARGs in river water could be associated with higher antibiotic use during the rainy season. In contrast, higher amounts of ARGs were recorded in river sediments during the dry season, making this habitat a potential reservoir of transient genes. Finally, the observations made in this study allowed us to clarify the environmental and anthropogenic influences that may promote the dispersal and persistence of ARGS in this riverine ecosystem.ABSTRACT ARTHIGHLIGHTSIn Vietnam, inland aquaculture massively relies on antibiotics to prevent epidemicsResistance genes were quantified along two rivers of the Mekong deltaSeasonal (dry and rainy seasons) and spatial distributions were registered by qPCRBLA-oxa1and sul2 reached highest abundances among bacterial communitiesStrong seasonal patterns and local variabilities were measured for CL1s and ARGs
Cryptocurrency as a safe haven for investment portfolios amid COVID-19 panic cases of Bitcoin, Ethereum and Litecoin
Authors: Marobhe Mutaju Isaack 
Published: November 2021

PurposeThis article examines the susceptibility of cryptocurrencies to coronavirus disease 2019 (COVID-19) induced panic in comparison with major stock indices.Design/methodology/approachThe author employs the Bayesian structural vector autoregression to examine the phenomenon in Bitcoin, Ethereum and Litecoin from 2nd January 2020 to 30th June 2021. A similar analysis is conducted for major stock indices, namely S&P 500, FTSE 100 and SSE Composite for comparison purposes.FindingsThe results suggest that cryptocurrencies returns suffered immensely in the early days of the COVID-19 outbreak following declarations of the disease as a global health emergency and eventually a pandemic in March 2020. However, the returns for all three cryptocurrencies recovered by April 2020 and remained resistant to further COVID-19 panic shocks. The results are dissimilar to those of S&P 500, FTSE 100 and SSE Composite values which were vulnerable to COVID-19 panic throughout the timeframe to June 2021. The results further reveal strong predictive power of Bitcoin on prices of other cryptocurrencies.Research limitations/implicationsThe article provides evidence to support the cryptocurrency as a safe haven during COVID-19 school of thought given their resistance to subsequent shocks during COVID-19. Thus, the author stresses the need for diversification of investment portfolios by including cryptocurrencies given their uniqueness and resistance to shocks during crises.Originality/valueThe author makes use of the novel corona virus panic index to examine the magnitude of shocks in prices of cryptocurrencies during COVID-19.
Untangling the role of CEOs' political ideology in the provision and inclusiveness of work–family policies: a multi-level conceptual model
Authors: Roumpi Dorothea 
Published: November 2021

PurposeAcknowledging the importance of work–family practices that extend beyond what is legally mandated and that cover the needs of a diverse workforce, this paper offers a conceptual model that explores the factors that can influence the provision and inclusiveness of work–family policies in organizations.Design/methodology/approachThe conceptual model is based on a thorough literature review of relevant articles in the fields of management and political science.FindingsIn line with the upper echelons perspective, chief executive officers’ (CEOs') political ideology is a multidimensional concept, comprising two main dimensions (financial and social) that can influence the provision and inclusiveness of work–family practices. Moreover, the proposed conceptual model considers other important factors, such as the centrality of the CEO's political ideology, as potential moderating factors, as well as the conditional role of institutional pressures. Finally, the proposed model takes into account the important role of line managers/supervisors in the implementation of work–family policies and shows the importance of the provision and inclusiveness of work–family practices for critical organizational outcomes (organizational attraction and turnover).Originality/valueThe proposed conceptual model offers a more in-depth understanding of the factors that influence the provision and inclusiveness of work–family policies.