bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems-level analysis of dynamic total-body PET data reveals complex skeletal energy metabolism networksin vivo
Authors: Suchacki Karla J. , Alcaide-Corral Carlos J. , Nimale Samah , Macaskill Mark G. , Stimson Roland H. , Farquharson Colin , Freeman Tom C. , Tavares Adriana A. S. 
Published: February 2021

AbstractBone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary, limiting our ability to assess systemic mechanisms underlying diseases and develop novel therapeutics.In vitromolecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactionsin vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactionsin vivousing total-body positron emission tomography (PET) network analysis of murine18F-FDG scans, as a biomarker of glucose metabolism signature in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network. These data could have important therapeutic implications in the management of the metabolic syndrome and skeletal disease. The application of our approach to clinical and preclinical total-body PET studies promises to reveal further physiological and pathological tissue interactions, which simplistic PET standard uptake values analysis fail to interrogate, extending beyond skeletal metabolism, due to the diversity of PET radiotracers available and under development as well as the advent of clinical total-body PET systems.One Sentence SummaryBones form a complex metabolic network.
Transcriptome sequence reveals candidate genes involving in the post-harvest hardening of trifoliate yamDioscorea dumetorum
Authors: Siadjeu Christian , Mayland-Quellhorst Eike , Laubinger Sascha , Albach Dirk C. 
Published: February 2021

AbstractStorage ability ofD. dumetorumis restricted by a severe phenomenon of post-harvest hardening which starts 72h after harvest and renders tubers inedible. Previous work has only focused on the biochemistry changes affecting the PHH onD. dumetorum. To the best of our knowledge nobody has identified candidate genes responsible for hardness onD. dumetorum. Here, transcriptome analysis ofD. dumetorumtubers was performed, 4 months after emergence (4MAE), after harvest (AH), 3 days AH (3DAH) and 14 days AH (14DAH) on four accessions using RNA-Seq. In total between AH and 3DAH, 165, 199,128 and 61 differentially expressed genes (DEGs) were detected in Bayangam 2, Fonkouankem 1, Bangou 1 and Ibo sweet 3 respectively. Functional analysis of DEGs revealed that genes encoding for cellulose synthase A, xylan O-acetyltransferase chlorophyll a/b binding protein 1,2,3,4 and transcription factor MYBP were found predominantly and significantly up-regulated 3DAH, implying that genes were potentially involved in the post-harvest hardening. A hypothetical mechanism of this phenomenon and its regulation has been proposed. These findings provide the first comprehensive insights into genes expression in yam tubers after harvest and valuable information for molecular breeding against the post-harvest hardening. A hypothetical mechanism of this phenomenon and its regulation has been proposed. These findings provide the first comprehensive insights into genes expression in yam tubers after harvest and valuable information for molecular breeding against the post-harvest hardening.
Anthracyclins increase free PUFAs and etherPEs with PUFAs as potential hallmarks of lipid peroxidation and ferroptosis
Authors: Balgoma David , Kullenberg Fredrik , Calitz Carlemi , Kopsida Maria , Heindryckx Femke , Lennernäs Hans , Hedeland Mikael 
Published: February 2021

AbstractMetabolic and personalized interventions in cancer treatment require a better under-standing of the relationship between the induction of cell death and metabolism. Consequently, we treated three primary liver cancer cell lines with two anthracyclins (doxorubicin and idarubin) and studied the changes of the lipidome. We found that both anthracyclins in the three cell lines increased the levels of polyunsaturated fatty acids (PUFAs) and alkylacylglycerophosphoethano-lamines (etherPEs) with PUFAs. As PUFAs and alkylacylglycerophospholipids with PUFAs are fundamental in lipid peroxidation during ferroptotic cell death, our results suggests supplementa-tion with PUFAs and/or etherPEs with PUFAs as a potential general adjuvant of anthracyclins. In contrast, neither the markers of de novo lipogenesis nor cholesterol lipids presented the same trend in all cell lines and treatments. In agreement with previous research, this suggests that modulation of the metabolism of cholesterol could be considered a specific adjuvant of anthracyclins depend-ing on the type of tumor and the individual. Finally, we discuss the changes in the lipidome in re-lation to the endoplasmic reticulum stress and the sensitivity to anthracyclins of the different cells. In conclusion, our results suggest that the modulation of different lipid metabolic pathways may be considered for generalized and personalized metabochemotherapies.
Disentangling the relative importance of spatio-temporal parameters and host selectivity in shaping AMF communities in temperate forests
Authors: Grünfeld Leonie , Mola Magkdi , Wulf Monika , Hempel Stefan , Veresoglou Stavros D 
Published: February 2021

AbstractMany woody and herbaceous plants in temperate forests cannot establish and survive in the absence of mycorrhizal associations. Here, we address and hierarchize how Glomeromycota, a group of soil-borne fungi, forming a ubiquitous type of mycorrhiza, varied in a temperate forest patch in Germany with time, space, plant hosts but also the proximity to Glomeromycota-associating woody species. The communities of Glomeromycota in our study were non-random. We observed that space had a greater impact on fungal community structure than either time or proximity to Glomeromycota-associating trees but unlike host identity did not alter Glomeromycotan richness. The set of parameters which we addressed has rarely been studied together and we believe that the resulting ranking could ease prioritizing some of them to include in future surveys. Glomeromycota are crucial for the establishment of understory plants in temperate forests making it desirable to further explore how they vary in time and space.
Laminar dynamics of beta bursts in human motor cortex
Authors: Bonaiuto James J , Little Simon , Neymotin Samuel A , Jones Stephanie R , Barnes Gareth R , Bestmann Sven 
Published: February 2021

AbstractModulation of motor cortical activity in the beta frequency range is one of the strongest and most studied movement-related neural signals. At the single trial level, beta band activity is often characterized by transient bursting events rather than slowly modulating oscillations, suggesting a more rapid, information-encoding functional role than previously believed. Insight into how beta bursts are generated in sensorimotor circuits can provide important constraints to theories about their functional role for movement control. To this end, we leverage and extend recent developments in high precision MEG for temporally resolved laminar analysis of burst activity, combined with a neocortical circuit model that simulates the biophysical generators of the electrical currents which drive beta bursts. This approach pinpoints the generation of beta bursts in human motor cortex to distinct excitatory synaptic inputs to deep and superficial cortical layers, which drive current flow in opposite directions. These laminar dynamics of beta bursts in motor cortex align with prior invasive animal recordings within the somatosensory cortex, and suggest a conserved mechanism for somatosensory and motor cortical beta bursts. More generally, we demonstrate the ability for uncovering the laminar dynamics of event-related neural signals in human non-invasive recordings.
A dynamic view of histone tails interaction with clustered abasic sites in a nucleosome core particle
Authors: Bignon Emmanuelle , Gillet Natacha , Jiang Tao , Morell Christophe , Dumont Elise 
Published: February 2021

AbstractApurinic/apyrimidinic sites are the most common DNA damage under physiological conditions. Yet, their structural and dynamical behavior within nucleosome core particles has just begun to be investigated, and show dramatic differences with the one of abasic sites in B-DNA. Clusters of two or more abasic sites are repaired even less efficiently and hence constitute hotspots of high mutagenicity notably due to enhanced double-strand breaks formation. Based on a X-ray structure of a 146-bp DNA wrapped onto a histone core, we investigate the structural behavior of two bistranded abasic sites positioned at mutational hotspots along microsecond-range molecular dynamics simulations. Our simulations allow us to probe histone tails interactions at clustered abasic sites locations, with a definitive assignment of the key residues in-volved in the NCP-catalyzed formation of DNA–protein cross-linking in line with recent experimental findings, and pave the way towards a systematic assessment of histone tails response to DNA lesions.
Constitutive G protein coupling profiles of understudied orphan GPCRs
Authors: Lu Sumin , Jang Wonjo , Inoue Asuka , Lambert Nevin A. 
Published: February 2021

AbstractA large number of GPCRs are potentially valuable drug targets but remain understudied. Many of these lack well-validated activating ligands and are considered “orphan” receptors, and G protein coupling profiles have not been defined for many orphan GPCRs. Here we asked if constitutive receptor activity can be used to determine G protein coupling profiles of orphan GPCRs. We monitored nucleotide-sensitive interactions between 48 understudied orphan GPCRs and five G proteins (240 combinations) using bioluminescence resonance energy transfer (BRET). No receptor ligands were used, but GDP was used as a common G protein ligand to disrupt receptor-G protein complexes. Constitutive BRET between the same receptors and β-arrestins was also measured. We found sufficient GDP-sensitive BRET to generate G protein coupling profiles for 22 of the 48 receptors we studied. Altogether we identified 48 coupled receptor-G protein pairs, many of which have not been described previously. We conclude that receptor-G protein complexes that form spontaneously in the absence of guanine nucleotides can be used to profile G protein coupling of constitutively active GPCRs. This approach may prove useful for studying G protein coupling of other GPCRs for which activating ligands are not available.
Frequent origins of traumatic insemination involve convergent shifts in sperm and genital morphology
Authors: Brand Jeremias N. , Harmon Luke J. , Schärer Lukas 
Published: February 2021

AbstractTraumatic insemination is a mating behaviour during which the (sperm) donor uses a traumatic intromittent organ to inject an ejaculate through the epidermis of the (sperm) recipient, thereby frequently circumventing the female genitalia. Traumatic insemination occurs widely across animals, but the frequency of its evolution, the intermediate stages via which it originates, and the morphological changes that such shifts involve remain poorly understood. Based on observations in 145 species of the free-living flatworm genusMacrostomum, we identify at least nine independent evolutionary origins of traumatic insemination from reciprocal copulation, but no clear indication of reversals. These origins involve convergent shifts in multivariate morphospace of male and female reproductive traits, suggesting that traumatic insemination has a canalising effect on morphology. Signatures of male-female coevolution across the genus indicate that sexual selection and sexual conflict drive the evolution of traumatic insemination, because it allows donors to bypass postcopulatory control mechanisms of recipients.
Input–Output Slope Curve Estimation in Neural Stimulation Based on Optimal Sampling Principles
Authors: Mahdi Alavi Seyed Mohammad , Goetz Stefan M. , Saif Mehrdad 
Published: February 2021

AbstractThis paper discusses some of the practical limitations and issues, which exist for the input–output (IO) slope curve estimation (SCE) in neural, brain and spinal, stimulation techniques. The drawbacks of the SCE techniques by using existing uniform sampling and Fisher-information-based optimal IO curve estimation (FO-IOCE) methods are elaborated. A novel IO SCE technique is proposed with a modified sampling strategy and stopping rule which improve the SCE performance compared to these methods. The effectiveness of the proposed IO SCE is tested on 1000 simulation runs in transcranial magnetic stimulation (TMS), with a realistic model of motor evoked potentials (MEPs). The results show that the proposed IO SCE method successfully satisfies the stopping rule, before reaching the maximum number of TMS pulses in 79.5% of runs, while the estimation based on the uniform sampling technique never converges and satisfies the stopping rule. At the time of successful termination, the proposed IO SCE method decreases the 95th percentile (mean value in the parentheses) of the absolute relative estimation errors (AREs) of the slope curve parameters up to 7.45% (2.2%), with only 18 additional pulses on average compared to that of the FO-IOCE technique. It also decreases the 95th percentile (mean value in the parentheses) of the AREs of the IO slope curve parameters up to 59.33% (16.71%), compared to that of the uniform sampling method. The proposed IO SCE also identifies the peak slope with higher accuracy, with the 95th percentile (mean value in the parentheses) of AREs reduced by up to 9.96% (2.01%) compared to that of the FO-IOCE method, and by up to 46.29% (13.13%) compared to that of the uniform sampling method.
PAMP-triggered Genetic Reprogramming Involves Widespread Alternative Transcription Initiation and an Immediate Transcription Factor Wave
Authors: Thieffry Axel , Bornholdt Jette , Barghetti Andrea , Sandelin Albin , Brodersen Peter 
Published: February 2021

ABSTRACTImmune responses triggered by pathogen-associated molecular patterns (PAMPs) are key to pathogen defense, but drivers of the genetic reprogramming required to reach the immune state remain incompletely understood in plants. Here, we report a time-course study of the establishment of PAMP-triggered immunity (PTI) using cap analysis of gene expression (CAGE). Our results show that as much as 15% of all PAMP response genes display alternative transcription initiation. In several cases, use of alternative TSSs may be regulatory as it determines inclusion of target peptides or protein domains, or occurrence of upstream open reading frames (uORFs) in mRNA leader sequences. We also find that 60% of PAMP-response genes respond much earlier than previously thought. In particular, a previously unnoticed cluster of rapidly and transiently PAMP-induced genes is enriched in transcription factors whose functions, previously associated with biological processes as diverse as abiotic stress adaptation and stem cell activity, appear to converge on growth restriction. Furthermore, some examples of known potentiators of PTI, in one case under direct MAP kinase control, support the notion that the rapidly induced transcription factors could constitute direct links to PTI signaling pathways and drive gene expression changes underlying establishment of the immune state.
AGL16 negatively modulates stress response to balance with growth
Authors: Zhao Ping-Xia , Zhang Jing , Chen Si-Yan , Wu Jie , Xia Jing-Qiu , Sun Liang-Qi , Ma Shi-Song , Xiang Cheng-Bin 
Published: February 2021

ABSTRACTSensile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS-box transcription factor AGL16 acting as a negative regulator in stress response. Loss-of-AGL16confers resistance to salt stress in seed germination, root elongation, and soil-grown plants, while elevatedAGL16expression confers the opposite phenotypes compared with wild type. However, the sensitivity to ABA in seed germination is inversely correlated withAGL16expression level. Transcriptomic comparison revealed that the improved salt resistance ofagl16mutant was largely attributed to enhanced expression of stress responsive transcriptional factors and genes involved in ABA signaling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter ofHKT1;1,HsfA6a,andMYB102and represses their expression. Genetic analyses with double mutants also support thatHsfA6aandMYB102are target genes of AGL16. Taken together, our results show that AGL16 acts as negative regulator transcriptionally suppressing key components in stress response and may play a critical role in balancing stress response with growth.
Plant trait heterosis is quantitatively associated with expression heterosis of the plastid ribosomal proteins
Authors: Birdseye Devon , de Boer Laura A. , Bai Hua , Zhou Peng , Shen Zhouxin , Schmelz Eric A. , Springer Nathan M. , Briggs Steven P. 
Published: February 2021

AbstractThe use of hybrids is widespread in agriculture, yet the molecular basis for hybrid vigor (heterosis) remains obscure. To identify molecular components that may contribute to the known higher photosynthetic capacity of maize hybrids, we analyzed proteomic and transcriptomic data from seedling leaf tissues of the hybrid, B73×Mo17, and its inbred parents. Subunits of complexes required for protein synthesis in the chloroplast and for the light reactions of photosynthesis were expressed above mid-parent and high-parent levels, respectively. Nuclear and plastid-encoded subunits were expressed similarly and in a dominant pattern with B73 as the high-parent for most proteins. The reciprocal hybrid displayed the same pattern with B73 still the dominant parent. Protein expression patterns were mostly the same in the adult leaf blade. To rank the relevance of expression differences to trait heterosis, we compared seedling leaf protein levels to adult plant heights of 15 hybrids. Expression heterosis (hybrid/mid-parent expression levels) was most positively correlated with plant height heterosis (hybrid/mid-parent plant height) for the plastid-encoded and nuclear-encoded chloroplast ribosomal proteins; the cytosolic ribosomal proteins were slightly less correlated. Ethylene biosynthetic enzymes were expressed below mid-parent levels in the hybrids, and the ethylene biosynthesis mutant,acs2/acs6, largely phenocopied the hybrid proteome, indicating that a reduction in ethylene biosynthesis may mediate the differences between inbreds and their hybrids. Levels of jasmonic acid biosynthetic enzymes were reduced in bothacs2/acs6and the hybrid, and expression heterosis levels of these proteins were the most negatively correlated with plant height heterosis.Significance StatementHeterosis (hybrid vigor) boosts the productivity and resilience of crops and livestock above the levels of both parents, yet its underlying mechanisms remain unknown. We analyzed expression patterns of proteins in maize hybrids and their inbred parents. Differences in several molecular machines and biochemical pathways were found and quantitatively assessed using a panel of 15 hybrids. Seedling leaf chloroplast ribosomal proteins were able to quantitatively infer levels of adult plant heterosis. Expression levels of biosynthetic enzymes for the stress hormone, ethylene, were reduced in hybrids as was previously reported for the dicot Arabidopsis. Mutation of these genes in a maize inbred caused the proteome to resemble a hybrid. Repression of ethylene biosynthesis may be a conserved component of heterosis physiology.
Association ofCXCR6with COVID-19 severity: Delineating the host genetic factors in transcriptomic regulation
Authors: Dai Yulin , Wang Junke , Jeong Hyun-Hwan , Chen Wenhao , Jia Peilin , Zhao Zhongming 
Published: February 2021

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) is an infectious disease that mainly affects the host respiratory system with ∼80% asymptomatic or mild cases and ∼5% severe cases. Recent genome-wide association studies (GWAS) have identified several genetic loci associated with the severe COVID-19 symptoms. Delineating the genetic variants and genes is important for better understanding its biological mechanisms.MethodsWe implemented integrative approaches, including transcriptome-wide association studies (TWAS), colocalization analysis and functional element prediction analysis, to interpret the genetic risks using two independent GWAS datasets in lung and immune cells. To understand the context-specific molecular alteration, we further performed deep learning-based single cell transcriptomic analyses on a bronchoalveolar lavage fluid (BALF) dataset from moderate and severe COVID-19 patients.ResultsWe discovered and replicated the genetically regulated expression ofCXCR6andCCR9genes. These two genes have a protective effect on the lung and a risk effect on whole blood, respectively. The colocalization analysis of GWAS andcis-expression quantitative trait loci highlighted the regulatory effect onCXCR6expression in lung and immune cells. In the lung resident memory CD8+T (TRM) cells, we found a 3.32-fold decrease of cell proportion and lower expression ofCXCR6in the severe than moderate patients using the BALF transcriptomic dataset. Pro-inflammatory transcriptional programs were highlighted in TRMcells trajectory from moderate to severe patients.ConclusionsCXCR6from the3p21.31locus is associated with severe COVID-19.CXCR6tends to have a lower expression in lung TRMcells of severe patients, which aligns with the protective effect ofCXCR6from TWAS analysis. We illustrate one potential mechanism of host genetic factor impacting the severity of COVID-19 through regulating the expression ofCXCR6and TRMcell proportion and stability. Our results shed light on potential therapeutic targets for severe COVID-19.