bluuebunny/crossref_metadata_2025_split huggingface dataset:
Divergent epigenetic profiles from two differentially impacted wild populations of estuarine cordgrass (Sporobolus alterniflorus)
Authors: DeCarlo L. , Meckler F. , Hans M. , Kelemen S. , Magun H. , Noah M. , Pappajohn L. , Anderson N. , Berger R. , Berkel J. , Brooke N. , Chen L. , Chijioke O. , Dewees N. , Falkner P. , Frank J. , Holzman W. , Marino V. , Ravaschiere A. , Wang Y. , Williams A. , Williams Z. , Gentile D. , Cox R.L. 
Published: March 2021

AbstractThe effects of urbanization on watershed ecosystems present critical challenges to modern survival. Organisms in urbanized areas experience high rates of evolutionary change, but genetic adaptation alone cannot mitigate the rapid and severe effects of urbanization on biodiversity. Highly resilient, foundation species are key to maintaining an ecosystem’s integrity in the face of urban stressors. However, the rapid collapse and disappearance of watershed ecosystems calls into question the extent to which we can rely on such species for their services. Our research investigates the molecular mechanisms by which the foundation ecosystems provider,Sporobolus alterniflorus, adapts to life in an urbanized environment. To elucidate these mechanisms, we quantified changes in global DNA methylation (% 5-mC) as a result of acute heat stress. Specimens from two differentially impacted populations across an urban to suburban geographical transect formed the basis of this study. These two populations ofSporobolus alternifloraexhibit inverse global DNA methylation patterns when exposed to the same acute heat stress. Our findings suggest that epigenetic mechanisms, such as DNA methylation, control rapid and transient adaptation, in the form of differential stress responses, to distinct environment challenges.Highlights for manuscript submission▪estuarine grasses native to the Bronx River, NY face stresses associated with low dissolved oxygen and urbanization▪differentially impacted populations of estuarine grasses exhibit inverse global DNA methylation profiles in response to acute heat stress▪DNA methylation may represent a mechanism by which plants transiently respond to environmental stressors, and this may represent a form of rapid adaptive evolution▪stress priming by transgenerational epigenetic modification may enhance fitness in grasses native to the heavily impacted Bronx River estuary
Dispersal across habitat boundaries: uncovering the demographic fates of populations in unsuitable habitat
Authors: Szojka Megan C. , Germain Rachel M. 
Published: March 2021

AbstractPatchy landscapes are characterized by abrupt transitions among distinct habitat types, forcing species to cross habitat boundaries in order to spread. Since seed dispersal is a probabilistic process, with a kernel that decays with distance, most individuals will fail to reach new, suitable habitat. Although failed dispersers are presumed dead in population models, their demographic fates may not be so simple. If transient survival is possible within unsuitable habitat, then through time, individuals may be able to reach distant, suitable habitat, forming new populations and buffering species from extinction. In a fragmented Californian grassland, we explored the fates of individuals that crossed habitat boundaries, and if those fates differed among specialists dispersing from two habitat types: serpentine habitat patches and the invaded non-serpentine matrix. We surveyed the diversity of seedbank and adult life stages along transects that crossed boundaries between patches and the matrix. First, we considered how patch specialists might transiently survive in the matrix via seed dormancy or stepping-stone populations. Second, we investigated the dispersal of an invasive matrix specialist (Avena fatua) into patches, to assess if sink populations existed across the habitat boundary. We found that dormancy maintained populations of patch specialists deep into the matrix, as abundances of seedbanks and of adult plant communities differed with distance into the matrix. We found evidence that these dormant seeds disperse secondarily with vectors of material flows in the landscape, suggesting that they could eventually reach suitable patches even if they first land in the matrix. We found thatA. fatuawere largely absent deep in patches, where reproductive outputs plummeted and there was no evidence of a dormant seedbank. Our results not only reveal the demographic fates of individuals that land in unsuitable habitat, but that their ecological consequences differ depending on the direction by which the boundary is crossed (patch → matrix ≠ matrix → patch). Dormancy is often understood as a mechanism for persisting in face of temporal variability, but it may serve as a means of traversing unsuitable habitat in patchy systems, warranting its consideration in estimates of habitat connectivity.
Pseudomonas aeruginosareaches collective decisions via transient segregation of quorum sensing activities across cells
Authors: Jayakumar Priyanikha , Thomas Stephen A. , Brown Sam P. , Kümmerli Rolf 
Published: March 2021

AbstractBacteria engage in a cell-to-cell communication process called quorum sensing (QS) to coordinate expression of cooperative exoproducts at the group level. While population-level QS-responses are well studied, we know little about commitments of single cells to QS. Here, we use flow cytometry to track the investment ofPseudomonas aeruginosaindividuals into their intertwined Las and Rhl QS-systems. Using fluorescent reporters, we show that QS gene expression (signal synthase, receptor and exoproduct) was heterogenous and followed a gradual instead of a sharp temporal induction pattern. The simultaneous monitoring of two QS genes revealed that cells transiently segregate into low receptor (lasR) expressers that fully commit to QS, and high receptor expressers that delay QS commitment. Our mathematical model shows that such gene expression segregation could mechanistically be spurred by transcription factor limitation. In evolutionary terms, temporal segregation could serve as a QS-brake to allow for a bet-hedging strategy in unpredictable environments.
Alternative dimerization is required for activity and inhibition of the HEPN ribonuclease RnlA
Authors: Garcia-Rodriguez Gabriela , Charlier Daniel , Wilmaerts Dorien , Michiels Jan , Loris Remy 
Published: March 2021

ABSTRACTThernlABtoxin-antitoxin operon fromEscherichia colifunctions as an anti-phage defense system. RnlA was recently identified as a member of the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding domain) superfamily of ribonucleases. The activity of the toxin RnlA requires tight regulation by the antitoxin RnlB, the mechanism of which remains unknown. Here we show that RnlA exists in an equilibrium between two different homodimer states: an inactive resting state and an active canonical HEPN dimer. Mutants interfering with the transition between states show that canonical HEPN dimerization via the highly conserved RX4-6H motif is required for activity. The antitoxin RnlB binds the canonical HEPN dimer conformation, inhibiting RnlA by blocking access to its active site. Single-alanine substitutions mutants of the highly conserved R255, E258, R318 and H323 show that these residues are involved in catalysis and substrate binding and locate the catalytic site near the dimer interface of the canonical HEPN dimer rather than in a groove located between the HEPN domain and the preceding TBP-like domain. Overall, these findings elucidate the structural basis of the activity and inhibition of RnlA and highlight the crucial role of conformational heterogeneity in protein function.
Early life stress is associated with earlier emergence of permanent molars
Authors: McDermott Cassidy L. , Hilton Katherine , Park Anne T. , Tooley Ursula A. , Boroshok Austin L. , Mupparapu Muralidhar , Scott JoAnna M. , Bumann Erin E. , Mackey Allyson P. 
Published: March 2021

AbstractExposure to adversity can accelerate biological aging. However, existing biomarkers of early aging are either difficult to detect in individuals at scale, like epigenetic signatures, or cannot be detected until late childhood, like pubertal onset. We evaluated the hypothesis that early adversity is associated with earlier molar eruption, an easily assessed measure that has been used to track the length of childhood across primates. In a pre-registered analysis (N= 117, ages 4-7), we demonstrate that lower family income and exposure to adverse childhood experiences (ACEs) are significantly associated with earlier eruption of the first permanent molars, as rated in T2-weighted magnetic resonance images (MRI). We replicate relationships between income and molar eruption in a population-representative dataset (NHANES;N= 1,973). These findings suggest that the impact of stress on the pace of biological development is evident in early childhood, and detectable in the timing of molar eruption.
RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues
Authors: Li Manci , Schwabenlander Marc D. , Rowden Gage R. , Schefers Jeremy M. , Seelig Davis , Larsen Peter A. 
Published: March 2021

AbstractChronic wasting disease (CWD) is a prion disease circulating in wild and farmed cervid populations throughout North America (United States and Canada), Europe (Finland, Norway, Sweden), and South Korea. CWD is an immediate threat to cervid heritage and the disease is causing substantial economic losses across multiple sectors. In North America, hunting and farming industries focused on the processing and consumption of white-tailed deer (WTD) venison are particularly vulnerable to CWD, as millions of WTD are consumed annually. Real-time quaking-induced conversion (RT-QuIC) is a highly sensitive assay amplifying misfolded CWD prionsin vitroand has facilitated CWD prion detection in a variety of tissues and excreta. To date, no study has comprehensively examined CWD prion content across bulk skeletal muscle tissues harvested from individual CWD infected WTD. Here, we use RT-QuIC to quantify prion-seeding activity in a variety of skeletal muscles from both wild and farmed CWD-positive WTD. We successfully detected CWD prions in muscles commonly used for consumption (e.g., backstrap, tenderloin, etc.) as well as within tongue and neck samples of WTD. Our results help to establish the utility of RT-QuIC for monitoring CWD prions in venison and suggest that the method is useful for preventing CWD prions from entering animal and human food chains. Moreover, our work indicates that CWD prions are more widely distributed across skeletal muscles of infected WTD than previously reported.
Symptomatic and Neurotrophic Effects of GABAA Receptor Positive Allosteric Modulation in a Mouse Model of Chronic Stress
Authors: Bernardo Ashley , Lee Philip , Marcotte Michael , Mian Md Yeunus , Rezvanian Sepideh , Sharmin Dishary , Kovačević Aleksandra , Savić Miroslav , Cook James M. , Sibille Etienne , Prevot Thomas D. 
Published: March 2021

AbstractChronic stress is a risk factor for Major depressive disorder (MDD), and in rodents, it recapitulates human behavioral, cellular and molecular changes. In MDD and after chronic stress, neuronal dysfunctions and deficits in GABAergic signaling are observed and responsible for symptom severity. GABA signals predominantly through GABAA receptors (GABAA-R) composed of various subunit types that relate to downstream outcomes. Activity at α2-GABAA-Rs contributes to anxiolytic properties, α5-GABAA-Rs to cognitive functions, and α1-GABAA-Rs to sedation. Therefore, a therapy aiming at increasing α2- and α5-GABAA-Rs activity, but devoid of α1-GABAA-R activity, has potential to address several symptomologies of depression while avoiding side effects. This study investigated the activity profiles and behavioral efficacy of two molecules enantiomers of each other (GL-II-73 and GL-I-54), separately and as a racemic mixture (GL-RM), and potential disease-modifying effects on neuronal morphology. Results confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the α2-, α3-, α5-GABAA-Rs and α5-containing GABAA-Rs, respectively, and have anti-depressant and pro-cognitive effects independently. Using unpredictable chronic mild stress (UCMS) in male and female mice (n=12/group), we show that acute and chronic administration of GL-RM combined the anti-depressant and pro-cognitive effects of each enantiomer, although at lower doses avoiding sedation. Morphology studies showed reversal of spine density loss caused by UCMS after chronic GL-RM treatment at apical and basal dendrites of the PFC and CA1. Together, these results support using a racemic mixture with combined α2-, α3-, α5-GABAA-R profile to reverse chronic stress-induced mood symptoms, cognitive deficits, and with anti-stress neurotrophic effects.
Genes identified in rodent studies of alcohol intake are enriched for heritability of human substance use
Authors: Huggett Spencer B. , Johnson Emma C. , Hatoum Alexander S. , Lai Dongbing , Bubier Jason A. , Chesler Elissa J. , Agrawal Arpana , Palmer Abraham A. , Edenberg Howard J , Palmer Rohan H.C. 
Published: March 2021

ABSTRACTBackgroundRodent paradigms and human genome-wide association studies (GWASs) on drug use have the potential to provide biological insight into the pathophysiology of addiction.MethodsUsing GeneWeaver, we created rodent alcohol and nicotine gene-sets derived from 19 gene expression studies on alcohol and nicotine outcomes. We partitioned the SNP-heritability of these gene-sets using four large human GWASs: 1) alcoholic drinks per week, 2) problematic alcohol use, 3) cigarettes per day and 4) smoking cessation. We benchmarked our findings with curated human alcoholism and nicotine addiction gene-sets and performed specificity analyses using other rodent gene-sets (e.g., locomotor behavior) and other human GWASs (e.g., height).ResultsThe rodent alcohol gene-set was enriched for heritability of drinks per week, cigarettes per day, and smoking cessation, but not problematic alcohol use. However, the rodent nicotine gene-set was not significantly associated with any of these traits. Both rodent gene-sets showed enrichment for several non-substance use GWASs, and the extent of this relationship tended to increase as a function of trait heritability. In general, larger gene-sets demonstrated more significant enrichment. Finally, when evaluating human traits with similar heritabilities, both rodent gene-sets showed greater enrichment for substance use traits.ConclusionOur results suggest that rodent gene expression studies can help to identify genes that capture heritability of substance use traits in humans, yet the specificity to human substance use was less than expected due to various factors such as the genetic architecture of a trait. We outline various limitations, interpretations and considerations for future research.
Adult neurogenesis mediates forgetting of multiple types of memory in the rat
Authors: Scott Gavin A. , Terstege Dylan J. , Roebuck Andrew J. , Gorzo Kelsea A. , Vu Alex P. , Howland John G. , Epp Jonathan R. 
Published: March 2021

AbstractThe formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampal dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.Significance StatementRecent evidence indicates that hippocampal neurogenesis mediates forgetting of older memories and enhances encoding of new memories free of proactive interference. This evidence comes from multiple rodent species, behavioral tasks, and methods of increasing neurogenesis. However, a recent paper by (Kodali et al. 2016) found that voluntary exercise-induced neurogenesis did not cause forgetting in the Morris Water Task in rats. The results call into question whether the phenomenon is a conserved function of neurogenesis across species. In the present study, we show that voluntary running causes robust forgetting in rats in a neurogenesis-dependent manner and that the effect is present across three different behavioral tasks, confirming the existence of the phenomenon in rats and adding to the growing evidence that forgetting is a conserved function of hippocampal neurogenesis.
Population-scale detection of non-reference sequence variants using colored de Bruijn Graphs
Authors: Krannich Thomas , White W. Timothy J. , Niehus Sebastian , Holley Guillaume , Halldórsson Bjarni V. , Kehr Birte 
Published: March 2021

AbstractMotivationWith the increasing throughput of sequencing technologies, structural variant (SV) detection has become possible across tens of thousands of genomes. Non-reference sequence (NRS) variants have drawn less attention compared to other types of SVs due to the computational complexity of detecting them. When using short-read data, the detection of NRS variants inevitably involves a de novo assembly which requires high-quality sequence data at high coverage. Previous studies have demonstrated how sequence data of multiple genomes can be combined for the reliable detection of NRS variants. However, the algorithms proposed in these studies have limited scalability to larger sets of genomes.ResultsWe introduce PopIns2, a tool to discover and characterize NRS variants in many genomes, which scales to considerably larger numbers of genomes than its predecessor PopIns. In this article, we briefly outline the PopIns2 workflow and highlight our novel algorithmic contributions. We developed an entirely new approach for merging contig assemblies of unaligned reads from many genomes into a single set of NRS using a colored de Bruijn graph. Our tests on simulated data indicate that the new merging algorithm ranks among the best approaches in terms of quality and reliability and that PopIns2 shows the best precision for a growing number of genomes processed. Results on the Polaris Diversity Cohort and a set of 1000 Icelandic human genomes demonstrate unmatched scalability for the application on population-scale datasets.AvailabilityThe source code of PopIns2 is available from https://github.com/kehrlab/PopIns2.Contactthomas.krannich@bihealth.de or birte.kehr@klinik.uni-regensburg.de
Characterization and functional interrogation of SARS-CoV-2 RNA interactome
Authors: Labeau Athéna , Lefevre-Utile Alain , Bonnet-Madin Lucie , Fery-Simonian Luc , Soumelis Vassili , Lotteau Vincent , Vidalain Pierre-Olivier , Amara Ali , Meertens Laurent 
Published: March 2021

SUMMARYSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19 pandemic, which has caused a devastating global health crisis. The emergence of highly transmissible novel viral strains that escape neutralizing responses emphasizes the urgent need to deepen our understanding of SARS-CoV-2 biology and to develop additional therapeutic strategies. Using a comprehensive identification of RNA binding proteins (RBP) by mass spectrometry (ChIRP-M/S) approach, we identified 142 high-confidence cellular factors that bind the SARS-CoV-2 viral genome during infection. By systematically knocking down their expression in a human lung epithelial cell line, we found that the majority of the RBPs identified in our study are proviral factors that regulate SARS-CoV-2 genome replication. We showed that some of these proteins represented drug targets of interest for inhibiting SARS-CoV-2 infection. In conclusion, this study provides a comprehensive view of the SARS-CoV-2 RNA interactome during infection and highlights candidates for host-centered antiviral therapies.
Ferroptotic stress promotes the accumulation of pro-inflammatory proximal tubular cells in maladaptive renal repair
Authors: Ide Shintaro , Kobayashi Yoshihiko , Ide Kana , Strausser Sarah A. , Herbek Savannah , O’Brien Lori L. , Crowley Steven D. , Barisoni Laura , Tata Aleksandra , Tata Purushothama Rao , Souma Tomokazu 
Published: March 2021

AbstractOverwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair in mice and humans. Using single-cell transcriptomic and mouse genetic approaches, we show that proximal tubular (PT) cells develop a molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT cells transiently appear after mild injury and return to their original state without inducing fibrosis, they accumulate and contribute to persistent inflammation after severe injury. This transient inflammatory PT state significantly downregulates glutathione metabolism genes, making them vulnerable to ferroptotic stress. Genetic induction of high ferroptotic stress in these cells after mild injury leads to the accumulation of the inflammatory PT cells, enhancing inflammation and fibrosis. Our study broadens the roles of ferroptotic stress from being a trigger of regulated cell death to include the promotion and accumulation of proinflammatory cells that underlie maladaptive repair.
Selecting Mutual Funds for Retirement Accounts (A)
Authors: Braun Phillip A. 
Published: March 2021

Alice Monroe, a 30-year-old married mother of two, was an admissions officer at the Kellogg School of Management at Northwestern University. She was just completing her first year of service at Northwestern and qualified for the university's 403(b) retirement plan. It was early October 2017, and she had until the end of the month to decide if and to what extent she would participate in Northwestern's retirement plan–that is, how much of her salary should she put into the retirement plan, and into which mutual fund or funds should she allocate her savings?
The case includes background on defined contribution and benefit plans as well as mutual funds. It goes into detail about Northwestern's retirement plan, including data on the performance of 15 of the plan's core mutual funds. The case also provides each fund's strategy, Morningstar Rating and Morningstar Category, expense ratio, assets under management, turnover rate, and historical performance for the last 10 years.
Using modern portfolio theory (diversification and risk-return trade-off) and with an understanding of mutual fund fees and the tax advantages of retirement savings, students will decide how much Alice should invest and in which mutual funds.