bluuebunny/crossref_metadata_2025_split huggingface dataset:
Striatal Dopamine Binding in Anhedonia: A Simultaneous [11C]Raclopride Positron Emission Tomography and Functional Magnetic Resonance Imaging Investigation
Authors: Phillips Rachel D. , Walsh Erin C. , Zürcher Nicole R. , Lalush David , Kinard Jessica , Tseng Chieh-En , Cernasov Paul , Kan Delia , Cummings Kaitlin , Kelley Lisalynn , Campbell David , Dillon Daniel G. , Pizzagalli Diego A. , Izquierdo-Garcia David , Hooker Jacob , Smoski Moria , Dichter Gabriel S. 
Published: July 2022

AbstractBackgroundAnhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA binding, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample.MethodsParticipants with (n=25) and without (n=12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors.ResultsRelative to controls, the anhedonia group exhibited increased [11C]raclopride binding potential (ΔBPND) in response to rewards, interpreted as decreased task-related DA release, in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions (i.e., bilateral caudate, putamen, pallidum, medial prefrontal cortex, anterior cingulate cortex, and thalamus) in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. We did not find evidence of associations between self-reported stress and striatal DA response to rewards, mesocorticolimbic fMRI activation or GFC in the anhedonic sample.ConclusionsResults provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.
Fragment size and diversity of mulches affect their decomposition, nutrient dynamics, and soil microbiology
Authors: Gaitanis Dimitrios , Lukac Martin , Tibbett Mark 
Published: July 2022

AbstractPlant-based mulch has been proposed as a sustainable way of maintaining soil fertility. However, the role of mulch diversity, quality, and size in decomposition dynamics, and their effect on crop yield are not fully explored. We investigated how mulch quality, proxied by the constituent plant species diversity, and residue size drive mulch decomposition, crop nutrition, and yield.A rhizotron experiment was set up with barley as a model crop, with the addition of mulch of two particle sizes (1.5 and 30 cm) and four different plant residue mixes (17, 12, 6, and 1 species) in a fully factorial design. Soil nutrient dynamics were measured at advanced decomposition stages, together with residue quality, arbuscular mycorrhizal fungal (AMF) root colonization, and crop yield.Residue mass loss was significantly affected by its chemical composition. Long residues retained significantly higher C and N content, than short residues. Crop yield was not affected by residue type or size. Residue size significantly affected barley growth rate, influencing seed protein content. Soil available K was significantly increased by residues with a higher initial C:N ratio. Short residues resulted in higher soil Zn. Residues of higher diversity resulted in higher AMF root colonization of the barley plants.Generally, long residue mulches maintain soil fertility for a longer period than short ones, without a deleterious effect on crop yield. Further investigation should evaluate the effect of continuous application of long residue mulches on soil fertility and microbial populations.
Evolutionary consequences of nascent multicellular life cycles
Authors: Pentz Jennifer T. , MacGillivray Kathryn , DuBose James G. , Conlin Peter L. , Reinhardt Emma , Libby Eric , Ratcliff William C. 
Published: July 2022

AbstractA key step in the evolutionary transition to multicellularity is the origin of multicellular groups as biological individuals capable of adaptation. Comparative work, supported by theory, suggests clonal development should facilitate this transition, though this hypothesis has never been tested in a single model system. We evolved 20 replicate populations of otherwise isogenic clonally-reproducing ‘snowflake’ yeast (Δace2/Δace2) and aggregative ‘floc’ yeast (GAL1p::FLO1/ GAL1p::FLO1) with daily selection for rapid growth in liquid media, which favors faster cell division, followed by selection for rapid sedimentation, which favors larger multicellular groups. While both genotypes adapted to this regime, growing faster and having higher survival during the group-selection phase, there was a stark difference in evolutionary dynamics. Aggregative floc yeast obtained nearly all of their increased fitness from faster growth, not improved group survival; indicating that selection acted primarily at the level of cells. In contrast, clonal snowflake yeast mainly benefited from higher group-dependent fitness, indicating a shift in the level of biological individuality from cells to groups. Through genome sequencing and mathematical modeling, we show that the genetic bottlenecks in a clonal life cycle also drive much higher rates of genetic drift—a result with complex implications for this evolutionary transition. Our results highlight the central role that early multicellular life cycles play in the process of multicellular adaptation.
Buying time: detecting Vocs in SARS-CoV-2 via co-evolutionary signals
Authors: Barrett Christopher , Bura Andrei C. , He Qijun , Huang Fenix W. , Li Thomas J. X. , Reidys Christian M. 
Published: July 2022

AbstractWe present a novel framework facilitating the rapid detection of variants of interest (VOI) and concern (VOC) in a viral multiple sequence alignment (MSA). The framework is purely based on the genomic sequence data, without requiring prior established biological analysis. The framework’s building blocks are sets of co-evolving sites (motifs), identified via co-evolutionary signals within the MSA. Motifs form a weighted simplicial complex, whose vertices are sites that satisfy a certain nucleotide diversity. Higher dimensional simplices are constructed using distances quantifying the co-evolutionary coupling of pairs and in the context of our method maximal motifs manifest as clusters. The framework triggers an alert via a cluster with a significant fraction of newly emerging polymorphic sites. We apply our method to SARS-CoV-2, analyzing all alerts issued from November 2020 through August 2021 with weekly resolution for England, USA, India and South America. Within a week at most a handful of alerts, each of which involving on the order of 10 sites are triggered. Cross referencing alerts with a posteriori knowledge of VOI/VOC-designations and lineages, motif-induced alerts detect VOIs/VOCs rapidly, typically weeks earlier than current methods. We show how motifs provide insight into the organization of the characteristic mutations of a VOI/VOC, organizing them as co-evolving blocks. Finally we study the dependency of the motif reconstruction on metric and clustering method and provide the receiver operating characteristic (ROC) of our alert criterion.
Genetic variation in correlated regulatory region of Immunity
Authors: Avalos Diana , Rey Guillaume , Ribeiro Diogo M. , Ramisch Anna , Dermitzakis Emmanouil T. , Delaneau Olivier 
Published: July 2022

AbstractStudying the interplay between genetic variation, epigenetic changes and regulation of gene expression in immune cells is important to understand the modification of cellular states in various conditions, including immune diseases. Here, we built cis maps of regulatory regions with coordinated activity – Cis Regulatory Domains (CRDs) – in neutrophils, monocytes and T cells. For this, we leveraged (i) whole-genome sequencing (WGS), (ii) chromatin immunoprecipitation sequencing (ChIP-seq), (iii) DNA methylation (450k arrays), and (iv) transcriptional profiles (RNA-seq) from the BLUEPRINT consortium, for up to 200 individuals.Our study uncovers 9287, 7666 and 5480 histone CRDs (hCRDs) and 6053, 6112, 5701 methyl CRDs (mCRDs) in monocytes, neutrophils and T-cells, respectively. We discovered 15294 hCRD-gene and 6185 mCRD-gene associations (5% FDR). Only 33% of hCRD-gene associations and 37% of mCRD-gene associations were shared between cell-types, revealing the dynamic nature of regulatory interactions and how similarly located regulatory regions modulate the activity of different genes on different cell types. We mapped Quantitative Trait Loci associated with CRD activity (CRD-QTLs) and found that 89% and 70% of these hCRDs and mCRDs are under genetic control highlighting the importance of genetic variation to study the coordination of cellular regulatory programs. We found CRD-QTLs to be enriched in celltype-specific transcription factor binding sites, such as SPI1, STAT3, RFX1, SOX4, ATF3 for neutrophils and monocytes and TCF4 and BCL11A for T-cells, in line with the Human protein Atlas.We integrated PCHi-C data, which showed that most significant associations discovered within gene-CRD associations and co-expressed genes associated with the same CRD, involving large genomic distances, tend to happen between genomic regions in close spatial proximity. Finally, we mapped trans regulatory associations between CRDs, which enabled the discovery of 207 trans-eQTLs across cell types. Overlapping our hits with trans eQTLs from eQTLGen Consortium meta-analysis in whole blood revealed 52 trans-eQTLs shared between the two studies. Overall, we show that mapping functional regulatory units using population genomics data allows discovering important mechanisms in the regulation of gene expression in immune cells and gain a greater understanding of cell-type specific regulatory mechanisms of immunity.
PTPN22 R620W Gene Editing in T Cells Enhances Low Avidity TCR Responses
Authors: Anderson Warren , Barahmand-pour-Whitman Fariba , Linsley Peter S , Cerosaletti Karen , Buckner Jane H , Rawlings David J 
Published: July 2022

AbstractA genetic variant in the genePTPN22(R620W, rs2476601) is strongly associated with increased risk for multiple autoimmune diseases and has been linked to altered TCR regulation. Here, we utilize Crispr/Cas9 gene editing with donor DNA repair templates in human cord blood-derived, naive T cells to generatePTPN22risk edited, non-risk edited (silent modification), or knock out T cells from the same donor.PTPN22risk edited cells exhibited increased activation marker expression following non-specific TCR engagement, findings that mimicked PTPN22 KO cells. Next, using lentiviral delivery of T1D patient-derived islet-antigen specific TCRs, we demonstrate that loss of PTPN22 function led to enhanced signaling in T cells expressing a lower avidity self-reactive TCR. In this setting, loss of PTPN22 mediated enhanced proliferation and Th1 skewing. Importantly, expression of the risk variant in association with a lower avidity TCR also increased proliferation relative to PTPN22 non-risk T cells. Together, these findings suggest that, in primary human T cells,PTPN22rs2476601 contributes to autoimmunity risk by permitting increased TCR signaling in mildly self-reactive T cells, thereby potentially expanding the self-reactive T cell pool and skewing this population toward an inflammatory phenotype.
Prophages and plasmids display opposite trends in the types of accessory genes they carry
Authors: Takeuchi Nobuto , Hamada-Zhu Sophia , Suzuki Haruo 
Published: July 2022

2AbstractMobile genetic elements (MGEs), such as phages and plasmids, often possess accessory genes encoding bacterial functions, facilitating bacterial evolution. Are there evolutionary rules governing the arsenal of accessory genes MGEs carry? If such rules exist, they might be reflected in the types of accessory genes different MGEs carry. To test this hypothesis, we compare prophages and plasmids with respect to the frequencies at which they carry antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) in the genomes of 21 pathogenic bacterial species using public databases. Our results indicate that prophages tend to carry VFGs more frequently than ARGs in three species, whereas plasmids tend to carry ARGs more frequently than VFGs in nine species. InEscherichia coli, where these trends are detected, prophage-borne VFGs encode a much narrower range of functions than do plasmid-borne VFGs, typically involved in damaging host cells or modulating host immunity. In the species where the above trends were not detected, ARGs and VFGs are barely found in prophages and plasmids. These results indicate that MGEs differentiate in the types of accessory genes they carry depending on their infection strategies, suggesting an evolutionary rule governing horizontal gene transfer mediated by MGEs.
Arabidopsis latent virus 1, a comovirus widely spread in Arabidopsis thaliana collections
Authors: Verhoeven Ava , Kloth Karen J. , Kupczok Anne , Oymans Geert H. , Damen Janna , Rijnsburger Karin , Jiang Zhang , Deelen Cas , Sasidharan Rashmi , van Zanten Martijn , van der Vlugt René A.A. 
Published: July 2022

SummaryTranscriptome studies of Illumina RNA-seq datasets of different Arabidopsis thaliana natural accessions and T-DNA mutants revealed the presence of two virus-like RNA sequences which showed the typical two segmented genome characteristics of a comovirus.This comovirus did not induce any visible symptoms in infected Arabidopsis plants cultivated under standard laboratory conditions. Hence it was named Arabidopsis latent virus 1 (ArLV1). Virus infectivity in Arabidopsis plants was confirmed by RT-qPCR, transmission electron microscopy and mechanical inoculation. ArLV1 can also mechanically infect Nicotiana benthamiana, causing distinct mosaic symptoms.A bioinformatics investigation of Arabidopsis RNA-Seq repositories, including nearly 6500 Sequence Read Archives (SRAs) in the NCBI SRA database, revealed the presence of ArLV1 in 25% of all archived natural Arabidopsis accessions and in 8.5% of all analyzed SRAs. ArLV1 could also be detected in Arabidopsis plants collected from the wild.ArLV1 is highly seed-transmissible with up to 40% incidence on the progeny derived from infected Arabidopsis plants. This has likely led to a worldwide distribution in the model plant Arabidopsis with yet unknown effects on plant performance in a substantial number of studies.Plain language summaryWe identified Arabidopsis latent virus 1 (ArLV1), a comovirus that infects the model plant Arabidopsis thaliana without causing any visible symptoms. It is efficiently spread by transmission via seeds to the plant progeny. ArLV1 is infectious to Arabidopsis plants and another model plant, Nicotiana benthamiana. By analyzing public sequencing data, we found that ArLV1 is widely spread in Arabidopsis laboratory collections worldwide. Moreover, it was also detected in wild Arabidopsis plants collected from different locations in the Netherlands and Spain, suggesting that it is a virus that naturally occurs in Arabidopsis.
Nodulin 16 of Lotus japonicus (Nlj16) regulates the recruitment of Leghemoglobin (LegH) to the infected nodule cell membrane during symbiotic nitrogen fixation
Authors: Ghosh Amit , Das Aniruddho , Ashrafi Md Azimuddin , Saha Sudeshna , Molla Firoz , DasGupta Maitrayee , Siddhanta Anirban 
Published: July 2022

AbstractNitrogenase that catalyses anaerobic symbiotic nitrogen fixation (SNF) in legumes is synthesized by rhizobium. Legume root cells express nodulin proteins after infection with rhizobia. Nodulins have been classified as early and late, reflecting the time points of their expression. Leghemoglobin (LegH), which is a classic example of a late nodulin, sequesters oxygen inside the nodule to protect the nitrogenase from oxygen toxicity to sustain SNF. Previous data from our laboratory demonstrated that phosphorylated LegH at S45 showed compromised oxygen sequestration in vitro due to structural disruption of the porphyrin binding pocket responsible for its oxygen binding. Moreover, we have demonstrated by using co-immunoprecipitation that LegH interacts both in vitro with Nodulin 16 of Lotus japonicus (Nlj16), another late nodulin. Fluorescence Immunohistochemistry (IHC) data shows that both LegH and Nlj16 are localized in the membrane and cytosol of infected cells. Notably, serine phosphorylation of LegH and interaction of Nlj16 with LegH respectively reduces and increases its in vitro oxygen sequestration ability. In this report, to further elucidate the spatio-temporal regulation of this interaction, we generated hairy root transgenic Lotus japonicus plants where Nlj16 has been knocked down by using siRNA. Most interestingly, our data shows that the membrane localization of LegH is obliterated in the Nlj16 knocked-down root cells infected with the cognate Rhizobia suggesting a distinct role of Nlj16 in its recruitment to the membrane of nodule cells.
Shared and distinct neural activity during anticipation and outcome of win and loss: A meta-analysis of the monetary incentive delay task
Authors: Chen Yu , Chaudhary Shefali , Li Chiang-Shan R. 
Published: July 2022

AbstractReward and punishment motivate decision making and behavioral changes. Numerous studies have examined regional activities during anticipation and outcome of win and loss in the monetary incentive delay task (MIDT). However, the great majority of studies reported findings of anticipation or outcome and of win or loss alone. It remains unclear how the neural correlates share and differentiate amongst these processes. We conducted an Activation Likelihood Estimation meta-analysis of 77 studies of the MIDT (5,779 subjects), including 24 published since the most recent meta-analysis, to identify and, with conjunction and subtraction, contrast regional responses to win anticipation, loss anticipation, win outcome, and loss outcome. Win and loss anticipation engaged a shared network of bilateral anterior insula (AI), striatum, thalamus, supplementary motor area (SMA), and precentral gyrus. Win and loss outcomes did not share regional activities. Win and loss outcome each engaged higher activity in medial orbitofrontal cortex (mOFC) and dorsal anterior cingulate cortex. Bilateral striatum and right occipital cortex responded to both anticipation and outcome of win, and right AI to both phases of loss. Win anticipation vs. outcome engaged higher activity in bilateral AI, striatum, SMA and precentral gyrus and right thalamus, and lower activity in bilateral mOFC and posterior cingulate cortex as well as right inferior frontal and angular gyri. Loss anticipation relative to outcome involved higher activity in bilateral striatum and left AI. These findings collectively suggest shared and distinct regional responses during monetary wins and losses. Delineating the neural correlates of these component processes may facilitate empirical research of motivated behavior and dysfunctional approach and avoidance in psychopathology.HighlightsWin and loss anticipation both engaged the fronto-striatal-thalamic network.Win and loss outcomes shared no regional activities.The mOFC and dACC play distinct roles each in processing win and loss outcome.Win and loss anticipation engaged bilateral AI; loss outcome only the right AI.Win/loss anticipation vs. outcome engaged predominantly right/left AI.
Subcellular Redox Responses Reveal Different Cu-dependent Antioxidant Defenses between Mitochondria and Cytosol
Authors: Zhang Yuteng , Wen Meng-Hsuan , Qin Guoting , Cai Chengzhi , Chen Tai-Yen 
Published: July 2022

AbstractExcess intracellular Cu perturbs cellular redox balance and thus causes diseases. However, the relationship between cellular redox status and Cu homeostasis and how such an interplay is coordinated within cellular compartments has not yet been well established. Using combined approaches of organelle-specific redox sensor Grx1-roGFP2 and non-targeted proteomics, we investigate the real-time Cu-dependent antioxidant defenses of mitochondria and cytosol in live HEK293 cells. The Cu-dependent real-time imaging experiments show that CuCl2 treatment results in increased oxidative stress in both cytosol and mitochondria. In contrast, subsequent Cu depletion by BCS, a Cu chelating reagent, lowers oxidative stress in mitochondria but causes even higher oxidative stress in the cytosol. The proteomic data reveal that several mitochondrial proteins, but not cytosolic ones, undergo significant abundance change under Cu treatments. The proteomic analysis also shows that proteins with significant changes are related to mitochondrial oxidative phosphorylation and glutathione synthesis. The differences in redox behaviors and protein profiles in different cellular compartments reveal distinct mitochondrial and cytosolic response mechanisms upon Cu-induced oxidative stress. These findings provide insights into how redox and Cu homeostasis interplay by modulating specific protein expressions at the subcellular levels, shedding light on understanding the effects of Cu-induced redox misregulation on the diseases.Graphical abstract
Engineering Toxoplasma transgenic tissue cysts
Authors: Hong David D. , Brooks Krista , Goerner Amber L. , Vizcarra Edward A. , Loges Luiza N. , Wilson Emma H. , White Michael W. 
Published: July 2022

AbstractCurrent approaches to find therapeutic solutions to treat and prevent reactivation of toxoplasmosis have suffered from limited accessibility to the relevant Toxoplasma stages and a lack of accurate in vitro developmental models. The loss of developmental competency in vitro that is exacerbated during the generation of transgenic tachyzoites is also a major impediment to understanding the molecular basis of bradyzoite recrudescence, which is the central feature of reactivation. We have developed an innovative ex vivo model of bradyzoite recrudescence and applied this method to successfully modify Toxoplasma genes while avoiding the problems caused by continuous in vitro cell culture. We present four protocols required to engineer in vivo transgenic tissue cysts: 1) the reliable production of in vivo tissue cysts and excysted bradyzoites, 2) the use of fast-growing parasites from ex vivo bradyzoite infections to successfully generate transgenic tissue cysts in mice, 3) the cloning of transgenic bradyzoites via single cyst infections, and finally, 4) the long term cold storage and recovery of transgenic tissue cysts in brain tissue homogenates. We demonstrated these protocols by knocking out the Toxoplasma HXGPRT gene and the gene encoding the ApiAP2 transcription factor, AP2IX-9 in tissue cysts from mice. Unexpectedly, the knockout of the AP2IX-9 gene in the Type II ME49EW strain eliminated one of the three developmental pathways initiated by the bradyzoite; host-dependent bradyzoite to bradyzoite replication.