bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial functional resilience after TFAM ablation in adult cardiomyocytes
Authors: Ghazal Nasab , Peoples Jessica N. , Mohuiddin Tahmina , Kwong Jennifer Q. 
Published: June 2020

AbstractThe adult heart is a terminally differentiated tissue that depends on mitochondria for its energy supply. Respiratory chain energy supply deficits due to alterations in the mitochondrial genome (mtDNA) or in nuclear genome (nDNA)-encoded mtDNA regulators are associated with cardiac pathologies ranging from primary mitochondrial cardiomyopathies to heart failure. Mitochondrial transcription factor A (TFAM) is an nDNA-encoded regulator of mtDNA transcription, replication, and maintenance. Insufficiency of this protein in embryonic and postnatal cardiomyocytes causes cardiomyopathy and/or lethality, establishing TFAM as indispensable to the developing heart; its role in adult tissue has been inferred from these findings. Here, we provide evidence that challenges this long-standing paradigm usingTfamablation in the adult heart. Unexpectedly, loss ofTfamin adult cardiomyocytes resulted in a prolonged period of functional resilience characterized by preserved mtDNA content, mitochondrial function, and cardiac function despite mitochondrial structural alterations and decreased transcript abundance. Remarkably, TFAM protein levels did not directly dictate mtDNA content in the adult heart, and mitochondrial translation was preserved with acute TFAM inactivation, suggesting a mechanism whereby respiratory chain assembly and function can be sustained, which we term ‘functional resilience’. Finally, long-termTfaminactivation induced a coordinated downregulation of the core mtDNA transcription and replication machinery that ultimately resulted in mitochondrial dysfunction and cardiomyopathy. Taken together, adult-onset cardiomyocyte-specificTfaminactivation reveals a striking resilience of the adult heart to acute insults to mtDNA regulatory mechanisms and provides insight into critical differences between the developing versus differentiated heart.
Brainprints: identifying individuals from magnetoencephalograms
Authors: Wu Shenghao , Ramdas Aaditya , Wehbe Leila 
Published: June 2020

AbstractMagnetoencephalography (MEG) is used to study a wide variety of cognitive processes. Increasingly, researchers are adopting principles of open science and releasing their MEG data. While essential for reproducibility, sharing MEG data has unforeseen privacy risks. Individual differences may make a participant identifiable from their anonymized recordings. However, our ability to identify individuals based on these individual differences has not yet been assessed. Here, we propose interpretable MEG features to characterize individual difference. We term these features brainprints (brain fingerprints). We show through several datasets that brainprints accurately identify individuals across days, tasks, and even between MEG and Electroencephalography (EEG). Furthermore, we identify consistent brainprint components that are important for identification. We study the dependence of identifiability on the amount of data available. We also relate identifiability to the level of preprocessing, the experimental task. Our findings reveal specific aspects of individual variability in MEG. They also raise concerns about unregulated sharing of brain data, even if anonymized.Abstract FigureFigure 1:Graphical abstract.Identifying which subject a segment of MEG data belongs to is strikingly easy when other data from the same session is available for every subject. We propose three types of interpretable features that can also be used to identify individuals across sessions with high accuracy. Identifiability of individuals is influenced by factors such as resting state vs. task state, components of each feature, the sample size and the level of preprocessing. Our results reveal aspects of individual variability in MEG signals and highlight privacy risks associated with MEG data sharing.
Histone H3.3 Hira chaperone complex contributes to zygote formation in mice and humans
Authors: Smith Rowena , Pickering Sue , Kopakaki Anna , Thong K Joo , Anderson Richard A , Lin Chih-Jen 
Published: June 2020

AbstractElucidating the underlining mechanisms underpinning successful fertilisation is imperative in optimising IVF treatments, and may lead to a specific diagnosis and therefore potential treatment for some infertile couples. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. This step is critical for the formation of the male pronucleus, without which the zygote contains only 1 pronucleus (1PN), in contrast to normally fertilised zygotes with two-pronuclei (2PN). 1PN zygotes are a frequently observed phenomenon in IVF treatments, therefore aberrant mechanism of action controlling paternal chromatin repackaging may be an important cause of abnormal fertilisation. Hira is the main H3.3 chaperone that governs this protamine-to-histone exchange. In this study, we investigated the maternal functions of two other molecules of the Hira complex, Cabin1 and Ubn1 in the mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed abnormal 1PN zygote phenotypes, similar to the phenotype of Hira mutants. We then studied human 1PN zygotes, and found that the Hira complex was absent in 1PN zygotes which were lacking the male pronucleus. This result confirms that the role of the Hira complex in male pronucleus formation has coherence from mice to humans. Furthermore, rescue experiments showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of Hira in the mouse oocytes. In summary, we have provided evidence of the role of Hira complex in regulating male pronucleus formation in both mice and humans, that both Cabin1 and Ubn1 components of the Hira complex are equally essential for male pronucleus formation, and that this can be rescued. We present a proof-of-concept experiment that could potentially lead to a personalised IVF therapy for oocyte defects.
Evidence for distinct isotopic composition of sap and tissue water in tree stems: consequences for plant water source identification
Authors: Barbeta Adrià , Burlett Régis , Martín-Gómez Paula , Fréjaville Bastien , Devert Nicolas , Wingate Lisa , Domec Jean-Christophe , Ogée Jérôme 
Published: June 2020

AbstractFor decades, theory has upheld that plants do not fractionate water isotopes as they move across the soil-root interface or along plant stems. This theory is now being challenged by several recent studies reporting that the water held in woody stems has an isotopic composition that cannot be attributed to any potential water source. Isotopic offsets between stem and source water still need to be explained, as they prevent identifying unambiguously tree water’s origin from water isotope measurements. Here we show that isotopic offsets between stem and source water can be explained by micrometer-scale water isotope heterogeneity within woody stems and soil micropores. Using a novel technique to extract sap water in xylem conduits separately from the water held in other xylem tissues, we show that these non-conductive xylem tissues are more depleted in deuterium than sap water. We also report that, in cut stems and well-watered potted plants, the isotopic composition of sap water reflects well that of irrigation water, demonstrating that no isotopic fractionation occurs during root water uptake or the sap water extraction process. Previous studies showed that isotopic heterogeneity also exists in soils at the pore scale where water adsorbed onto soil particles is more depleted than capillary/mobile soil water. Data collected at a beech (Fagus sylvatica) forest indicate that sap water matches best the capillary/mobile soil water from deep soil horizons, indicating that micrometer-scale water isotope heterogeneity in soils and stems must be accounted for to unambiguously identify where trees obtain their water within catchments.Significance StatementForests are prime regulators of the water cycle over land. They return, via transpiration, a large fraction of precipitation back to the atmosphere, influence surface runoff, groundwater recharge or stream flow, and enhance the recycling of atmospheric moisture inland from the ocean. The isotopic composition of water in woody stems can provide unique information on the role forests play in the water cycle only if it can be unambiguously related to the isotopic composition of source water. Here, we report a previously overlooked isotopic fractionation of stem water whereby non-conductive tissues are more depleted in deuterium than sap water, and propose a new technique to extract sap water separately from bulk stem water to unambiguously identify plant water sources.
Detection of differential RNA modifications from direct RNA sequencing of human cell lines
Authors: Pratanwanich Ploy N. , Yao Fei , Chen Ying , Koh Casslynn W.Q. , Hendra Christopher , Poon Polly , Goh Yeek Teck , Yap Phoebe M. L. , Yuan Choi Jing , Chng Wee Joo , Ng Sarah , Thiery Alexandre , Goh W.S. Sho , Göke Jonathan 
Published: June 2020

AbstractDifferences in RNA expression can provide insights into the molecular identity of a cell, pathways involved in human diseases, and variation in RNA levels across patients associated with clinical phenotypes. RNA modifications such as m6A have been found to contribute to molecular functions of RNAs. However, quantification of differences in RNA modifications has been challenging. Here we develop a computational method (xPore) to identify differential RNA modifications from direct RNA sequencing data. We evaluate our method on transcriptome-wide m6A profiling data, demonstrating that xPore identifies positions of m6A sites at single base resolution, estimates the fraction of modified RNAs in the cell, and quantifies the differential modification rate across conditions. We apply the method to direct RNA-Sequencing data from 6 cell lines and find that many m6A sites are preserved, while a subset of m6A sites show significant differences in their modification rates across cell types. Together, we show that RNA modifications can be identified from direct RNA-sequencing with high accuracy, enabling the analysis of differential modifications and expression from a single high throughput experiment.AvailabilityxPore is available as open source software (https://github.com/GoekeLab/xpore)
Short-lived plants have stronger demographic responses to climate
Authors: Compagnoni Aldo , Levin Sam , Childs Dylan Z. , Harpole Stan , Paniw Maria , Römer Gesa , Burns Jean H. , Che-Castaldo Judy , Rüger Nadja , Kunstler Georges , Bennett Joanne M , Archer C. Ruth , Jones Owen R. , Salguero-Gómez Roberto , Knight Tiffany M. 
Published: June 2020

AbstractTo mitigate and adapt to climate change, there is an urgent need to synthesize the state of our knowledge on plant responses to climate. The availability of open-access data, combined with our understanding of plant physiology and life history theory provide opportunities to examine quantitative generalizations regarding which biomes and species are most responsive to climate drivers. Here, we synthesized time series of structured population models from 165 populations from 62 plants around the globe to link plant population growth rates to precipitation and temperature drivers. We expected: (1) more pronounced demographic responses to precipitation than temperature, especially in arid biomes; (2) a higher climate sensitivity in short-lived rather than long-lived species; and (3) a stronger response to climate by species that reproduce more frequently. We found that precipitation anomalies have a nearly three-fold larger effect onλthan temperature. Precipitation has substantially more pronounced effects in more arid sites, but large noise makes this relationship non-significant. Species with shorter generation time have much stronger absolute responses to climate anomalies, while the degree of iteroparity does not correlate with population responses to climate. We conclude that key species-level traits can predict plant population responses to climate, and discuss the relevance of this generalization for conservation planning and evolutionary theory.
miR156-independent repression of the ageing pathway by longevity-promoting AHL proteins in Arabidopsis
Authors: Rahimi Arezoo , Karami Omid , Offringa Remko 
Published: June 2020

AbstractPlants age by transition through distinct developmental phases, with the juvenile- to adult vegetative and the adult vegetative to reproductive phase change as two consecutive important post-embryonic phase transitions. During the transition from the juvenile- to adult vegetative phase, also known as the vegetative phase change (VPC), many plants undergo specific morphological and physiological changes. In the model plantArabidopsis thaliana(Arabidopsis), for example, the VPC is marked by clear heteroblastic changes in leaf shape and size and the appearance of trichomes on the abaxial side of leaves. The VPC and the vegetative to reproductive transition are promoted by the SQUAMOSA PROMOTOR BINDING PROTEIN-LIKE (SPL) family of transcription factors and repressed by miR156 and miR157 that target theSPLtranscripts. Here we present data that the plant longevity promoting AT-HOOK MOTIF NUCLEAR LOCALIZED protein 15 (AHL15) and family members also repress the SPL-driven ageing pathway. Arabidopsisahlloss-of-function mutants showed an accelerated VPC and flowering time, whereasAHL15overexpression dramatically delayed the VPC and flowering time in both Arabidopsis andNicotiana tabacum. Expression analysis and tissue-specificAHL15overexpression revealed thatAHL15affects the VPC and flowering time directly through its expression in the shoot apical meristem and young leaves. In addition, we found evidence that AHL15 repressesSPLgene expression in a miR156/157-independent manner. The juvenile traits ofsplloss-of-function mutants appeared to be dependent on the enhanced expression of theAHL15gene, providing evidence for a reciprocal negative feedback betweenAHL15andSPLgenes. Antagonistically to AHLs, SPLs promote axillary meristem (AM) maturation and thus prevent vegetative growth from these meristems by repressingAHL15expression. Taken together, our results place AHL15 and family members at a central position in the SPL-driven ageing pathway as suppressors of the VPC, flowering time and AM maturation.
Neuronal Classification from Network Connectivity via Adjacency Spectral Embedding
Authors: Mehta Ketan , Goldin Rebecca F. , Marchette David , Vogelstein Joshua T. , Priebe Carey E. , Ascoli Giorgio A. 
Published: June 2020

AbstractThis work presents a novel strategy for classifying neurons, represented by nodes of a directed graph, based on their circuitry (edge connectivity). We assume a stochastic block model (SBM) where neurons belong together if they connect to neurons of other groups according to the same probability distributions. Following adjacency spectral embedding (ASE) of the SBM graph, we derive the number of classes and assign each neuron to a class with a Gaussian mixture model-based expectation-maximization (EM) clustering algorithm. To improve accuracy, we introduce a simple variation using random hierarchical agglomerative clustering to initialize the EM algorithm and picking the best solution over multiple EM restarts. We test this procedure on a large (n~ 212− 215neurons), sparse, biologically inspired connectome with eight neuron classes. The simulation results demonstrate that the proposed approach is broadly stable to the choice of dimensional embedding and scales extremely well as the number of neurons in the network increases. Clustering accuracy is robust to variations in model parameters and highly tolerant to simulated experimental noise, achieving perfect classifications with up to 40% of swapped edges. Thus, this approach may be useful to analyze and interpret large-scale brain connectomics data in terms of underlying cellular components.
Long-read RNA sequencing of human and animal filarial parasites improves gene models and discovers operons
Authors: Wheeler Nicolas J , Airs Paul M. , Zamanian Mostafa 
Published: June 2020

AbstractFilarial nematodes (Filarioidea) cause substantial disease burden to humans and animals around the world. Recently there has been a coordinated global effort to generate and curate genomic data from nematode species of medical and veterinary importance. This has resulted in two chromosome-level assemblies (Brugia malayiandOnchocerca volvulus) and 10 additional draft genomes from Filarioidea. These reference assemblies facilitate comparative genomics to explore basic helminth biology and prioritize new drug and vaccine targets. While the continual improvement of genome contiguity and completeness advances these goals, experimental functional annotation of genes is often hindered by poor gene models. Short-read RNA sequencing data and expressed sequence tags, in cooperation withab initioprediction algorithms, are employed for gene prediction, but these can result in missing clade-specific genes, fragmented models, imperfect mapping of gene ends, and lack of isoform resolution. Long-read RNA sequencing can overcome these drawbacks and greatly improve gene model quality. Here, we present Iso-Seq data forB. malayiandDirofilaria immitis, etiological agents of lymphatic filariasis and canine heartworm disease, respectively. These data cover approximately half of the known coding genomes and substantially improve gene models by extending untranslated regions, cataloging novel splice junctions from novel isoforms, and correcting mispredicted junctions. Furthermore, we validated computationally predicted operons, identified new operons, and merged fragmented gene models. We carried out analyses of poly(A) tails in both species, leading to the identification of non-canonical poly(A) signals. Finally, we prioritized and assessed known and putative anthelmintic targets, correcting or validating gene models for molecular cloning and target-based antiparasitic screening efforts. Overall, these data significantly improve the catalog of gene models for two important parasites, and they demonstrate how long-read RNA sequencing should be prioritized for future improvement of parasitic nematode genome assemblies.
Wolbachiaand virus alter the host transcriptome at the interface of nucleotide metabolism pathways
Authors: Lindsey Amelia RI , Bhattacharya Tamanash , Hardy Richard W , Newton Irene LG 
Published: June 2020

SUMMARYWolbachiais a maternally transmitted bacterium that manipulates arthropod and nematode biology in myriad ways. TheWolbachiastrain colonizingDrosophila melanogastercreates sperm-egg incompatibilities and protects its host against RNA viruses, making it a promising tool for vector control. Despite successful trials usingWolbachia-transfected mosquitoes for Dengue control, knowledge of howWolbachiaand viruses jointly affect insect biology remains limited. Using theDrosophilamodel, transcriptomics and gene expression network analyses revealed pathways with altered expression and splicing due toWolbachiacolonization and virus infection. Included are metabolic pathways previously unknown to be important forWolbachia-host interactions. Additionally,Wolbachia-colonized flies exhibit a dampened transcriptomic response to virus infection, consistent with early blocking of virus replication. Finally, usingDrosophilagenetics, we showWolbachiaand expression of nucleotide metabolism genes have interactive effects on virus replication. Understanding the mechanisms of pathogen blocking will contribute to the effective development ofWolbachia-mediated vector control programs.
Evaluation of cytotoxic, antiviral effect and mutagenic potential of a micronutrient combination in vitro cell culture
Authors: Matti Nazish , Ashraf Muhammad , Rasheed Muhammad Adil , Altaf Imran , Carvalho Isabel , Nadeem Muhammad Faisal 
Published: June 2020

AbstractBackgroundMicronutrients are essential for the body to produce enzymes, hormones and other substances essential for proper growth and development. Iodine, potassium iodide and ascorbic acid are ones of the most important in global public health terms. However, their lack represents a major threat to the human and animal health.MethodologyAntiviral, cytotoxic and mutagenic activity of commercially available micronutrient combination consisting of iodine, ascorbic acid, potassium iodide and excipients was evaluated. Commercial preparation of micronutrient combination was compared with self-prepared micronutrient preparation. MTT assay was used to evaluate the cytotoxicity of all the preparation. Confluent monolayer of Chicken Embryo Fibroblasts grown in 96-well cell culture plates were treated with ten concentrations of each preparation in triplicate manner and was used to determine the viability of the cells and cell survival percentage. Antiviral efficacy was determined against influenza virus H9N1 strain by virus infection and subsequent cell viability assay. Furthermore, mutagenicity was measured by bacterial reverse mutation analysis by Ames test using two strains ofSalmonella typhimuriumTA100 and TA 98 with and without S9. After appropriate incubation, number of revertant colonies per plate were counted in triplicate manner and MF was calculated.ResultsOur combination showed cytotoxicity at doses higher than 11.71ug/ml while showed significant antiviral efficacy at concentrations of 11.71ug/ml, 5.86ug/ml, 2.93ug/ml and 1.4ug/ml which faded away at lower dilutions. Commercially available preparation was found to be non-mutagenic in our experiment.ConclusionsCombination consisting of iodine, ascorbic acid, potassium iodide is effective in the treatment of viral infections.
Generation and utilization of a HEK-293T murine GM-CSF expressing cell line
Authors: Robinson Elektra K. , Covarrubias Sergio , Zhou Simon , Carpenter Susan 
Published: June 2020

AbstractMacrophages and dendritic cells (DCs) are innate immune cells that play a key role in defense against pathogens.In vitrocultures of bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) are well-established and valuable methods for immunological studies. Typically, commercially available recombinant GMCSF is utilized to generate BMDCs and is also used to culture alveolar macrophages. We have generated a new HEK-293T cell line expressing murine GM-CSF that secretes high levels of GM-CSF (∼180ng/ml) into complete media as an alternative to commercial GM-CSF. Differentiation of dendritic cells and expression of various markers were kinetically assessed using the GM-CSF HEK293T cell line, termed supGM-CSF and compared directly to purified commercial GMCSF. After 7-9 days of cell culture the supGM-CSF yielded twice as many viable cells compared to the commercial purified GM-CSF. In addition to differentiating BMDCs, the supGM-CSF can be utilized to culture alveolar macrophages without an altering inflammatory activation cascade. Collectively, our results show that supernatant from our GM-CSF HEK293T cell line supports the differentiation of mouse BMDCs or alveolar macrophage culturing, providing an economical alternative to purified GM-CSF.