bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecosystem engineering alters density-dependent feedbacks in an aquatic insect population
Authors: Phillips Joseph S. , McCormick Amanda R. , Botsch Jamieson C. , Ives Anthony R. 
Published: January 2021

AbstractEcosystem engineers have large impacts on the communities in which they live, and these impacts may feed back to populations of engineers themselves. In this study, we assessed the effect of ecosystem engineering on density-dependent feedbacks for midges in Lake Mývatn, Iceland. The midge larvae reside in the sediment and build silk tubes that provide a substrate for algal growth, thereby elevating benthic primary production. Benthic algae are in turn the primary food source for the midge larvae, setting the stage for the effects of engineering to feed back to the midges themselves. Using a field mesocosm experiment manipulating larval midge densities, we found a generally positive but nonlinear relationship between density and benthic production. Furthermore, adult emergence increased with the primary production per midge larva. By combining these two relationships in a simple model, we found that the positive effect of midges on benthic production weakened the negative density dependence at low to intermediate larval densities. However, this benefit disappeared at high densities when midge consumption of primary producers exceeded their positive effects on primary production through ecosystem engineering. Our results illustrate how ecosystem engineering can alter density-dependent feedbacks for engineer populations.
The contribution of astrocyte and neuronal Panx1 to seizures is model and brain region dependent
Authors: Obot Price , Velíšek Libor , Velíšková Jana , Scemes Eliana 
Published: January 2021

AbstractPannexin1 (Panx1) is an ATP release channel expressed in neurons and astrocytes that plays important roles in CNS physiology and pathology. Evidence for the involvement of Panx1 in seizures includes the reduction of epileptiform activity and ictal discharges following Panx1 channel blockade or deletion. However, very little is known about the relative contribution of astrocyte and neuronal Panx1 channels to hyperexcitability. To this end, mice with global and cell type specific deletion of Panx1 were used in onein vivoand twoin vitroseizure models. In the low-Mg2+in vitromodel, global deletion but not cell-type specific deletion of Panx1 reduced the frequency of epileptiform discharges. This reduced frequency of discharges did not impact the overall power spectra obtained from local field potentials. In thein vitroKA model, in contrast, global or cell type specific deletion of Panx1 did not affect the frequency of discharges, but reduced the overall power spectra. EEG recordings following KA-injectionin vivorevealed that although global deletion of Panx1 did not affect the onset of status epilepticus (SE), SE onset was delayed in mice lacking neuronal Panx1 and accelerated in mice lacking astrocyte Panx1. EEG power spectral analysis disclosed a Panx1-dependent cortical region effect; while in the occipital region, overall spectral power was reduced in all three Panx1 genotypes; in the frontal cortex, the overall power was not affected by deletion of Panx1. Together, our results show that the contribution of Panx1 to ictal activity is model, cell-type and brain region dependent.
Excision of mutagenic replication-blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice
Authors: Kay Jennifer E. , Corrigan Joshua J. , Armijo Amanda L. , Nazari Ilana S. , Kohale Ishwar N. , Torous Dorothea K. , Avlasevich Svetlana L. , Croy Robert G. , Wadduwage Dushan N. , Carrasco Sebastian E. , Dertinger Stephen D. , White Forest M. , Essigmann John M. , Samson Leona D. , Engelward Bevin P. 
Published: January 2021

SummaryN-nitrosodimethylamine (NDMA) is a DNA methylating agent that has been discovered to contaminate water, food and drugs. The alkyladenine glycosylase (AAG) removes methylated bases to initiate the base excision repair (BER) pathway. To understand how gene-environment interactions impact disease susceptibility, we studiedAag−/−andAag-overexpressing mice that harbor increased levels of either replication-blocking lesions (3-methyladenine, or 3MeA) or strand breaks (BER intermediates), respectively. Remarkably, the disease outcome switched from cancer to lethality simply by changing AAG levels. To understand the underlying basis for this observation, we integrated a suite of molecular, cellular and physiological analyses. We found that unrepaired 3MeA is somewhat toxic but highly mutagenic (promoting cancer), whereas excess strand breaks are poorly mutagenic and highly toxic (suppressing cancer and promoting lethality). We demonstrate that the levels of a single DNA repair protein tips the balance between blocks and breaks, and thus dictates the disease consequences of DNA damage.
TCF11 Has a Potent Tumor-Repressing Effect than Its Prototypic Nrf1α by Definition of both Similar yet Different Regulatory Profiles, with a Striking Disparity from Nrf2
Authors: Wang Meng , Ren Yonggang , Hu Shaofan , Liu Keli , Qiu Lu , Zhang Yiguo 
Published: January 2021

AbstractNrf1 and Nrf2, as two principal CNC-bZIP transcription factors, regulate similar but different targets involved in a variety of biological functions for maintaining cell homeostasis and organ integrity. Of note, the unique topobiological behavior of Nrf1 makes its functions more complicated than Nrf2, because it is allowed for alternatively transcribing and selectively splicing to yield multiple isoforms (e.g., TCF11, Nrf1α). In order to gain a better understanding of their similarities and differences in distinct regulatory profiles, all four distinct cell models for stably expressingTCF11,TCF11ΔN,Nrf1αorNrf2have been herein established by an Flp-In™ T-REx™-293 system and then identified by transcriptomic sequencing. Further analysis revealed that Nrf1α and TCF11 have similar yet different regulatory profiles, although both contribute basically to positive regulation of their co-targets, which are disparate from those regulated by Nrf2. Such disparity in those gene regulation by Nrf1 and Nrf2 was further corroborated by scrutinizing comprehensive functional annotation of their specific and/or common target genes. Conversely, the mutant TCF11ΔN, resulting from a deletion of the N-terminal amino acids 2-156 from TCF11, resembles Nrf2 with the largely consistent structure and function. Interestingly, our further experimental evidence demonstrates that TCF11 acts as a potent tumor-repressor relative to Nrf1α, albeit both isoforms possess a congruous capability to prevent malignant growth of tumor and upregulate those genes critical for improving the survival of patients with hepatocellular carcinoma.
Comparing utility functions between risky and riskless choice in rhesus monkeys
Authors: Bujold Philipe M. , Ferrari-Toniolo Simone , Seak Leo Chi U , Schultz Wolfram 
Published: January 2021

AbstractDecisions can be risky or riskless, depending on the outcomes of the choice. Expected Utility Theory describes risky choices as a utility maximization process: we choose the option with the highest subjective value (utility), which we compute considering both the option’s value and its associated risk. According to the random utility maximization framework, riskless choices could also be based on a utility measure. Neuronal mechanisms of utility-based choice may thus be common to both risky and riskless choices. This assumption would require the existence of a utility function that accounts for both risky and riskless decisions. Here, we investigated whether the choice behavior of macaque monkeys in riskless and risky decisions could be described by a common underlying utility function. We found that the utility functions elicited in the two choice scenarios were different from each other, even after taking into account the contribution of subjective probability weighting. Our results suggest that distinct utility representations exist for riskless and risky choices, which could reflect distinct neuronal representations of the utility quantities, or distinct brain mechanisms for risky and riskless choices. The different utility functions should be taken into account in neuronal investigations of utility-based choice.
Apolipoprotein M attenuates anthracycline cardiotoxicity and lysosomal injury
Authors: Guo Zhen , Ripoll Carla Valenzuela , Picataggi Antonino , Rawnsley David R. , Ozcan Mualla , Chirinos Julio A. , Chendamarai Ezhilarasi , Girardi Amanda , Riehl Terrence , Evie Hosannah , Diab Ahmed , Kovacs Attila , Hyrc Krzysztof , Ma Xiucui , Asnani Aarti , Shewale Swapnil V. , Scherrer-Crosbie Marielle , Cowart Lauren Ashley , Parks John S. , Zhao Lei , Gordon David , Ramirez-Valle Francisco , Margulies Kenneth B. , Cappola Thomas P. , Desai Ankit A. , Pederson Lauren N. , Bergom Carmen , Stitziel Nathan O. , Rettig Michael P. , DiPersio John F. , Hajny Stefan , Christoffersen Christina , Diwan Abhinav , Javaheri Ali 
Published: January 2021

AbstractObjectivesDetermine the role of apolipoprotein M (ApoM) in anthracycline (Dox) cardiotoxicity.BackgroundApoM binds the cardioprotective sphingolipid sphingosine-1-phosphate (S1P). Circulating ApoM is inversely associated with mortality in human heart failure (HF).MethodsIn the Penn HF Study (PHFS), we tested the relationship between ApoM and mortality in a subset with anthracycline-induced cardiomyopathy. We measured ApoM in humans and mice treated with Dox and utilized hepatic ApoM transgenic (ApomTG), ApoM knockout (ApomKO), ApoM knock-in mice with impaired S1P binding, and S1P receptor 3 (S1PR3) knockout mice in Dox cardiotoxicity. We assayed autophagy in left ventricular tissue from anthracycline-induced HF patients versus donor controls.ResultsApoM was inversely associated with mortality in PHFS, and Dox reduced circulating ApoM in mice and breast cancer patients.ApomTGmice were protected from Dox-induced cardiac dysfunction and loss of left ventricular mass.ApomTGattenuated Dox-induced impairment in autophagic flux in vivo and accumulation of insoluble p62, which was also observed in the myocardium of patients with anthracycline-induced HF. In vehicle-treated mice, ApoM negatively regulated transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis. The effect of ApoM on TFEB required both S1P binding and S1PR3. In the presence of Dox, ApoM preserved TFEB and cardiomyocyte lysosomal abundance assessed as lysosomal associated membrane protein 1 positive structures in vivo, while S1P mimetic pretreatment of cardiomyocytes prevented Dox-induced changes in lysosomal pH.ConclusionsApoM attenuates Dox cardiotoxicity via the autophagy-lysosome pathway. The association between ApoM and reduced mortality may be explained by its role in sustaining autophagy.HighlightsCirculating ApoM is inversely associated with survival in human anthracycline-induced cardiomyopathyAnthracycline treatment reduces circulating ApoM in humans and miceIncreasing ApoM attenuates doxorubicin cardiotoxicity, lysosomal injury and preserves myocardial autophagic flux, but does not impact doxorubicin anti-neoplastic efficacyAutophagic impairment is characteristic of human anthracycline cardiomyopathy
Quantifying community responses to environmental variation from replicate time series
Authors: Phillips Joseph S. , Nell Lucas A. , Botsch Jamieson C. 
Published: January 2021

AbstractTime-series data for ecological communities are increasingly available from long-term studies designed to track species responses to environmental change. However, classical multivariate methods for analyzing community composition have limited applicability for time series, as they do not account for temporal autocorrelation in community-member abundances. Furthermore, traditional approaches often obscure the connections between responses at the community level and those for individual taxa, limiting their capacity to infer mechanisms of community change. We show how linear mixed models that account for group-specific temporal autocorrelation and observation error can be used to infer both taxon- and community-level responses to environmental predictors from replicated time-series data. Variation in taxon-specific responses to predictors is modeled using random effects, which can be used to characterize variation in community composition. Moreover, the degree of autocorrelation is estimated separately for each taxon, since this is likely to vary due to differences in their underlying population dynamics. We illustrate the utility of the approach by analyzing the response of a predatory arthropod community to spatiotemporal variation in allochthonous resources in a subarctic landscape. Our results show how mixed models with temporal autocorrelation provide a unified approach to characterizing taxon- and community-level responses to environmental variation through time.
Decoding shared versus divergent transcriptomic signatures across cortico-amygdala circuitry in PTSD and depressive disorders
Authors: Jaffe Andrew E. , Tao Ran , Tran Matthew N. , Page Stephanie C. , Maynard Kristen R. , Pattie Elizabeth A. , Nguyen Claudia V. , Deep-Soboslay Amy , Bharadwaj Rahul , Young Keith A. , Friedman Matthew J. , Williamson Douglas E. ,   Traumatic Stress Brain Research Group, Shin Joo Heon , Hyde Thomas M. , Martinowich Keri , Kleinman Joel E. 
Published: January 2021

AbstractPost-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disease with a projected lifetime risk of 8.7%. PTSD is highly comorbid with depressive disorders including major depressive disorder (MDD) and bipolar disorder (BD). It is hypothesized that the overlap in symptoms stems from partially shared underlying neurobiological mechanisms. To better understand shared and unique transcriptional patterns of PTSD and MDD we performed RNA-sequencing in the postmortem brain of two prefrontal cortex (PFC) regions and two amygdala (AMY) regions, from neurotypical donors (N=109) as well as donors with diagnoses of PTSD (N=107) or MDD (N=109) across 1285 RNA-seq samples. We identified a small number of differentially expressed genes (DEGs) specific to PTSD, mostly in the cortex compared to amygdala. PTSD-specific DEGs were preferentially enriched in cortistatin-expressing cells, a subpopulation of somatostatin interneurons. These PTSD DEGs also showed strong enrichment for gene sets associated with immune-related pathways and microglia, largely driven by decreased expression of these genes in PTSD donors. While we identified a greater number of DEGs for MDD, there were only a few that were specific to MDD as they showed high overlap with PTSD DEGs. Finally, we used weighted gene co-expression network analysis (WGCNA) as an orthogonal approach to confirm the observed cellular and molecular associations. These findings highlight the sub-population of cortistatin-expressing interneurons as having potential functional significance in PTSD and provide supporting evidence for dysregulated neuroinflammation and immune signaling in MDD and PTSD pathophysiology.
Arsenic hexoxide has differential effects on cell proliferation and genome-wide gene expression in human primary mammary epithelial and MCF7 cells
Authors: Kim Donguk , Park Na Yeon , Kang Keunsoo , Calderwood Stuart K. , Cho Dong-Hyung , Bae Ill Ju , Bunch Heeyoun 
Published: January 2021

ABSTRACTArsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer effects in humans [1, 2]. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models [3, 4]. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA-sequencing and bioinformatics analyses, differentially expressed genes in significantly affected biological pathways in these cell types were validated by real-time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly differential effects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without affecting the growth of HUMEC in a dose-dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are significantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6-treated MCF7 cells. Together, we provide the first evidence of differential effects of AS6 on normal and cancerous breast epithelial cells, suggesting that AS6 at moderate concentrations induces cell cycle arrest and apoptosis through modulating genome-wide gene expression, leading to compromised DNA repair and increased genome instability selectively in human breast cancer cells.
Genes encoding teleost orthologs of human haplo-insufficient and monoallelic genes remain in duplicate more frequently than the whole genome
Authors: Picolo Floriane , Grandchamp Anna , Piégu Benoît , Veitia Reiner A. , Monget Philippe 
Published: January 2021

AbstractGene dosage is important is an important issue both in cell and evolutionary biology. Most genes are present in two copies in eukaryotic cells. The first outstanding exception is monoallelic gene expression (MA) that concerns genes localized on the X chromosome or in regions undergoing parental imprinting in eutherians, and many other genes scattered throughout the genome. The second exception concerns haploinsufficiency (HI), responsible for the fact that a single functional copy of a gene in a diploid organism is insufficient to ensure a normal biological function. One of the most important mechanisms ensuring functional innovation during evolution is Whole genome duplication (WGD). In addition to the two WGDs that have occurred in vertebrate genomes, the teleost genomes underwent an additional WGD, after their divergence from tetrapod. In the present work, we have studied on 57 teleost species whether the orthologs of human MA or HI genes remain more frequently in duplicates or returned more frequently in singleton than the rest of the genome. Our results show that the teleost orthologs of HI human genes remained more frequently in duplicate than the rest of the genome in all the teleost species studied. No signal was observed for the orthologs of genes localized on the human X chromosome or subjected to parental imprinting. Surprisingly, the teleost orthologs of the other human MA genes remained in duplicate more frequently than the rest of the genome for most teleost species. These results suggest that the teleost orthologs of MA and HI human genes also undergo selective pressures either related to absolute protein amounts and/or of dosage balance issues. However, these constraints seem to be different for MA genes in teleost in comparison with human genomes.
Comparative analysis of whole genome sequences ofLeptospiraspp. from RefSeq database provide interspecific divergence and repertoire of virulence factors
Authors: Abdullah Mohd , Kadivella Mohammad , Sharma Rolee , Baig Mirza. S. , Faisal Syed M. , Azam Sarwar 
Published: January 2021

AbstractLeptospirosis is an emerging zoonotic and neglected disease across the world causing huge loss of life and economy. The disease is caused byLeptospiraof which 605 sequenced genomes representing 72 species are available in RefSeq database. A comparative genomics approach based on Average Amino acid Identity (AAI), Average Nucleotide Identity (ANI), and Insilco DNA-DNA hybridization provide insight that taxonomic and evolutionary position of few genomes needs to be changed and reclassified. Clustering on the basis of AAI of core and pan-genome contradict clustering pattern on basis of ANI into 4 clusters. Amino acid identity based hierarchical clustering clearly established 3 clusters ofLeptospiracorrelating with level of virulence. Whole genome tree supported three cluster classifications and groupedLeptospirainto three clades termed as pathogenic, intermediate and saprophytic.Leptospiragenus consist of diverse species and exist in heterogeneous environment, it contains relatively large and closed core genome of 1038 genes. Analysis provided pan genome remains open with 20822 genes. COG analysis revealed that mobilome related genes were found mainly in pan-genome of pathogenic clade. Clade specific genes mined in the study can be used as marker for determining clade and associating level of virulence of any newLeptospiraspecies. Many knownLeptospiravirulent genes were absent in set of 78 virulent factors mined using Virulence Factor database. A deep search approach provided a repertoire of 496 virulent genes in pan-genome. Further validation of virulent genes will help in accurately targeting pathogenicLeptospiraand controlling leptospirosis.Graphical Abstract
Trans Fats Consumption and Body Mass Index in Cross Sectional Analysis
Authors: Golomb Beatrice A. , Pavlovsky Arthur , Koslik Hayley J. 
Published: January 2021

AbstractBackgroundTrans fats remain on the market in parts of the world. Emerging evidence suggests that factors beyond calorie balance may affect fat deposition and body mass index (BMI). Trans fats are prooxidant, proinflammatory, and have shown adverse metabolic effects and increased fat deposition in animals.ObjectiveTo assess the relation of dietary trans fatty acid consumption (dTFA) to BMI in humans.DesignCross-sectional analysis of baseline data from a broadly-sampling study.SettingCommunity-dwelling adults from Southern California.Participants1018 adult men and women aged 20-85 without known diabetes, CVD, or cancer, with screening LDL 115-190mg/dL. Women of procreative potential and children were excluded.MeasurementsHeight, weight, and waist circumference were measured, and BMI calculated (kg/m2). The Fred Hutchinson Food Frequency Questionnaire provided data on dTFA (grams/day) and calories consumed. Additional covariates included activity, chocolate consumption frequency, and mood. Regression assessed the relation of BMI (outcome) to dTFA, unadjusted and in models adjusting for age and sex, and adding calories and activity, chocolate consumption frequency, and mood.ResultsHigher dTFA was associated with higher BMI and waist circumference. The coefficient was strengthened, not attenuated, with adjustment for calories and activity, and other assessed covariates. In the fully adjusted model, each gram/day of dTFAs was associated with 0.44 higher BMI (SE=0.12;95%CI=0.21,0.67); P<0.001 and 1cm greater waist circumference (SE=0.35;95%CI=0.37,1.7); P=0.003.ConclusionFindings relating greater dTFA to higher BMI in humans comport with experimental data in animals, extend adverse metabolic associations of dTFA, and buttress evidence that foods’ composition, as well as caloric number, bears on BMI. Findings are cross-sectional but strength and consistency of association, biological gradient, and biological plausibility add “weight” to the prospect of a causal connection.Strengths and limitations of this studyFindings are cross-sectional and rely on dietary recall.Observational studies carry risks of bias and confounding; but randomized trials are problematic where products with potential for harm are under evaluation.Although some nations have implemented plans to remove or reduce dTFAs from the food supply, dTFA remain on the market in other nations, rendering findings of continued interest.The association of increased dTFA with increased BMI and waist circumference fits with other documented adverse metabolic associations of dTFA and is buttressed by experimental documentation that dTFA (without excess calories) increases visceral fat in animals, supporting prospects for causality in the observed association.