bluuebunny/crossref_metadata_2025_split huggingface dataset:
The abundances and occurrences of foliar microbes are poorly predicted by variation in plant traits and abiotic conditions
Authors: Harrison Joshua G. , Buerkle C. Alex 
Published: May 2022

AbstractMuch effort has been made to understand why foliar microbes live where they do. However, whether foliar microbiome composition can be predicted is unknown. Here, we determine the limits of prediction using metabarcoding data of both fungal and bacterial assemblages that occur within (endophytes) and without (epiphytes) leaves from 59 plant taxa. We built random forest models for prevalent taxa and quantified the combined predictive power of 24 plant traits, 12 abiotic conditions and 7 additional features. As response variables, we considered microbial relative and absolute abundances, and occurrences. Most microbial taxa were too rare to effectively model, but model performance was generally poor even for the most prevalent and abundant taxa (modelR2was typically <0.1). Fungi were more tractable for modeling than bacteria. Models of Shannon’s diversity were moderately successful but those for richness were not. Taxa responded idiosyncratically and non-linearly to variation in the foliar habitat. When prevalent microbes were included as features in models, performance improved. Our results suggest that easily measurable aspects of the phyllosphere habitat are poor predictors of microbiome composition. These results pose a challenge for the study of microbial biogeography and we discuss possible ways forward.
Cytoplasmic TDP-43 accumulation drives changes in C-bouton number and size in a mouse model of sporadic Amyotrophic Lateral Sclerosis
Authors: Bak Anna Normann , Djukic Svetlana , Kadlecova Marion , Braunstein Thomas Hartig , Jensen Dennis Bo , Meehan Claire Francesca 
Published: May 2022

AbstractAn altered neuronal excitability of spinal motoneurones has consistently been implicated in Amyotrophic Lateral Sclerosis (ALS) leading to several investigations of synaptic input to these motoneurones. One such input that has repeatedly been shown to be affected is a population of large cholinergic synapses terminating mainly on the soma of the motoneurones referred to as C-boutons. Most research on these synapses during disease progression has used transgenic Superoxide Dismutase 1 (SOD1) mouse models of the disease which have not only produced conflicting findings, but also fail to recapitulate the key pathological feature seen in ALS; cytoplasmic accumulations of TAR DNA-binding protein 43 (TDP-43). Additionally, they fail to distinguish between slow and fast motoneurones, the latter of which have more C-boutons but are lost earlier in the disease.To circumvent these issues, we quantified the frequency and volume of C-boutons on traced soleus and gastrocnemius motoneurones, representing predominantly slow and fast motor pools respectively. Experiments were performed using the TDP-43ΔNLS mouse model that carries a transgenic construct of TDP-43 devoid of its nuclear localization signal, preventing its nuclear import. This results in the emergence of pathological TDP-43 inclusions in the cytoplasm, modelling the main pathology seen in this disorder, accompanied by a severe and lethal ALS phenotype.Our results confirmed changes in both the number and volume of C-boutons with a decrease in number on the more vulnerable, predominantly fast gastrocnemius motoneurones and an increase in number on the less vulnerable, predominantly slow soleus motoneurones. Importantly, these changes were only found in male mice. However, both sexes and motor pools showed a decrease in C-bouton volume. Our experiments confirm that cytoplasmic TDP-43 accumulation is sufficient to drive C-bouton changes.
Environmental DNA reveals invasive crayfish microbial associates and ecosystem-wide biodiversity before and after eradication
Authors: Ballare Kimberly M. , Worth Anna , Goodearly Tyler , Ruiz-Ramos Dannise V. , Beraut Eric , Nava Hailey , Fairbairn Colin , Wayne Robert K. , Shapiro Beth , Short Ginny , Meyer Rachel S. 
Published: May 2022

AbstractBiodiversity monitoring in conservation projects is essential to understand environmental status and recovery. However, traditional field surveys can be expensive, time-consuming, biased towards visual detection, and focused on measuring a limited set of taxa. Environmental DNA (eDNA) methods provide a new approach to biodiversity monitoring that has the potential to sample a taxonomically broader set of organisms with similar effort, but many of these approaches are still in the early stages of development and testing. Here, we use multilocus eDNA metabarcoding to understand how the removal of invasive red swamp crayfish impacts local biodiversity of a desert oasis ecosystem, as well as to detect crayfish both directly and indirectly. We tracked crayfish DNA signatures, microbial DNA associated with crayfish, and biodiversity of plant, fungal, animal, and bacterial communities through time. We were unsuccessful in detecting crayfish directly in either control tanks or oases using targeted metabarcoding primers for invertebrates and eukaryotes, similar to previous studies which have shown variable levels of success in detecting crayfish from environmental samples. However, we were successful in discerning a suite of 90 crayfish-associated taxa to serve as candidate bioindicators of invasive presence using 16S and Fungal ITS2 metabarcoding. Ranking these 90 taxa by their geographic distribution in eDNA surveys and by evidence of crayfish-associations in the literature, we support 9 taxa to be high-ranking, and suggest they be prioritized in future biomonitoring. Biodiversity analyses from five metabarcode loci including plants, animals, and both prokaryotic and eukaryotic microbes showed that communities differed but that species richness remained relatively similar between oases through time. Our results reveal that, while there are limitations of eDNA approaches to detect crayfish and other invasive species, microbial bioindicators offer a largely untapped biomonitoring opportunity for invasive species management, adding a valuable resource to a conservation manager’s toolkit.
Metabolic shift toward ketosis in asocial cavefish increases social-like affinity
Authors: Iwashita Motoko , Tran Amity , Garcia Marianne , Cashon Jia , Burbano Devanne , Salgado Vanessa , Hasegawa Malia , Balmilero-Unciano Rhoada , Politan Kaylah , Wong Miki , Lee Ryan W.Y. , Yoshizawa Masato 
Published: May 2022

AbstractSocial affinity and collective behavior are nearly ubiquitous in the animal kingdom, but many lineages feature evolutionarily asocial species. These solitary species may have evolved to conserve energy in food-sparse environments. However, the mechanism by which metabolic shifts regulate social affinity is not well investigated. In this study, we used the Mexican tetra (Astyanax mexicanus), which features riverine sighted surface (surface fish) and cave-dwelling populations (cavefish), to address the impact of metabolic shifts on asociality and other cave-associated behaviors in cavefish, including repetitive turning, sleeplessness, swimming longer distances, and enhanced foraging behavior. After one month of ketosis-inducing ketogenic diet feeding, asocial cavefish exhibited significantly higher social affinity, whereas social affinity regressed in cavefish fed the standard diet. The ketogenic diet also reduced repetitive turning and swimming in cavefish. No major behavioral shifts were found regarding sleeplessness and foraging behavior, suggesting that other evolved behaviors are not largely regulated by ketosis. We further examined the effects of the ketogenic diet via supplementation with extragenic ketone bodies, revealing that ketone bodies are pivotal molecules positively associated with social affinity. Our study indicated that fish that evolved to be asocial remain capable of exhibiting social affinity under ketosis, possibly linking the seasonal food availability and sociality.
Butyrate differentiates permissiveness to Clostridioides difficile infection and influences growth of diverse C. difficile isolates
Authors: Pensinger Daniel A. , Fisher Andrea T. , Dobrila Horia A. , Van Treuren William , Gardner Jackson O. , Higginbottom Steven K. , Carter Matthew M. , Schumann Benjamin , Bertozzi Carolyn R. , Anikst Victoria , Martin Cody , Robilotti Elizabeth V. , Chow JoMay , Buck Rachael H. , Tompkins Lucy S. , Sonnenburg Justin L. , Hryckowian Andrew J. 
Published: May 2022

ABSTRACTA disrupted “dysbiotic” gut microbiome engenders susceptibility to the diarrheal pathogen Clostridioides difficile by impacting the metabolic milieu of the gut. Diet, in particular the microbiota accessible carbohydrates (MACs) found in dietary fiber, is one of the most powerful ways to affect the composition and metabolic output of the gut microbiome. As such, diet is a powerful tool for understanding the biology of C. difficile and for developing alternative approaches for coping with this pathogen. One prominent class of metabolites produced by the gut microbiome are short chain fatty acids (SCFAs), the major metabolic end products of MAC metabolism. SCFAs are known decrease the fitness of C. difficile in vitro and that high intestinal SCFA concentrations are associated with reduced fitness of C. difficile in animal models of C. difficile infection (CDI). Here, we use controlled dietary conditions (8 diets that differ only by MAC composition) to show that C. difficile fitness is most consistently impacted by butyrate, rather than the other two prominent SCFAs (acetate and propionate), during murine model CDI. We similarly show that butyrate concentrations are lower in fecal samples from humans with CDI relative to healthy controls. Finally, we demonstrate that butyrate impacts growth in diverse C. difficile isolates. These findings provide a foundation for future work which will dissect how butyrate directly impacts C. difficile fitness and will lead to the development of diverse approaches distinct from antibiotics or fecal transplant, such as dietary interventions, for mitigating CDI in at-risk human populations.IMPORTANCEClostridioides difficile is a leading cause of infectious diarrhea in humans and it imposes a tremendous burden on the healthcare system. Current treatments for C. difficile infection (CDI) include antibiotics and fecal microbiota transplant, which contribute to recurrent CDIs and face major regulatory hurdles, respectively. Therefore, there is an ongoing need to develop new ways to cope with CDI. Notably, a disrupted “dysbiotic” gut microbiota is the primary risk factor for CDI but we incompletely understand how a healthy microbiota resists CDI. Here, we show that a specific molecule produced by the gut microbiota, butyrate, is negatively associated with C. difficile burdens in humans and in a mouse model of CDI and that butyrate impedes the growth of diverse C. difficile strains in pure culture. These findings help to build a foundation for designing alternative, possibly diet-based, strategies for mitigating CDI in humans.
Purified cytosolic crystals from Bacillus thuringiensis as a novel active pharmaceutical ingredient (API)
Authors: Chicca Jeffrey , Cazeault Nicholas R. , Rus Florentina , Abraham Ambily , Garceau Carli , Li Hanchen , Atwa Samar M. , Flanagan Kelly , Soto Ernesto R. , Morrison Mary S. , Gazzola David , Hu Yan , Liu David R. , Nielsen Martin K. , Urban Joseph F. , Ostroff Gary R. , Aroian Raffi V. 
Published: May 2022

ABSTRACTBacillus thuringiensis or Bt is a Gram-positive soil bacterium, widely and safely applied in the environment as an insecticide for combatting insect pests that damage crops and vector diseases. Dominant active ingredients made by Bt are insect-killing crystal (Cry) proteins released as crystalline inclusions upon bacterial sporulation. Some Bt Cry proteins, e.g., Cry5B, target nematodes (roundworms) and show exceptional promise as anthelmintics (cures for parasitic nematode diseases). We have recently described IBaCC (for Inactivated Bacteria with Cytosolic Crystal(s)) in which bioactive Bt Cry crystals (containing Cry5B) are fully contained within the cytosol of dead bacterial ghosts. Here we demonstrate that these IBaCC-trapped Cry5B crystals can be liberated and purified away from cellular constituents yielding Purified Cytosolic Crystals (PCC). Cry5B PCC contains ∼95% Cry5B protein out of the total protein content. Cry5B PCC is highly bioactive against parasitic nematode larvae and adults in vitro. Cry5B PCC is also highly active in vivo against experimental human hookworm and Ascaris infections in rodents. The process was scaled up to the 100 liter scale to produce PCC for a pilot study to treat two foals infected with the Ascarid, Parascaris spp. Single dose Cry5B PCC brought the fecal egg counts of both foals to zero. These studies describe the process for the scalable production of purified Bt crystals and define a new active pharmaceutical ingredient form of Bt Cry proteins.NON-TECHNICAL IMPORTANCE PARAGRAPHBacillus thuringiensis crystal proteins are widely and safely used as insecticides. Recent studies show they also can cure gastrointestinal parasitic worm (nematode) infections when ingested. However, reproducible, scalable, and practical techniques for purifying these proteins have been lacking. Here, we address this severe limitation and present scalable and practical methods for large-scale purification of potently bioactive B. thuringiensis crystals and crystal proteins. The resultant product, called Purified Cytosolic Crystals (PCC), is highly compatible with ingestible drug delivery and formulation. Furthermore, there are growing applications in agriculture and insect control where access to large quantities of purified crystal proteins are desirable and where these methods will find great utility.
Machine Learning for Identifying Data-Driven Subphenotypes of Incident Post-Acute SARS-CoV-2 Infection Conditions with Large Scale Electronic Health Records: Findings from the RECOVER Initiative
Authors: Zhang Hao , Zang Chengxi , Xu Zhenxing , Zhang Yongkang , Xu Jie , Bian Jiang , Morozyuk Dmitry , Khullar Dhruv , Zhang Yiye , Nordvig Anna S. , Schenck Edward J. , Shenkman Elizabeth A. , Rothman Russel L. , Block Jason P. , Lyman Kristin , Weiner Mark G. , Carton Thomas W. , Wang Fei , Kaushal Rainu 
Published: May 2022

AbstractThe post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum of symptoms and signs that are persistent, exacerbated, or newly incident in the post-acute SARS-CoV-2 infection period of COVID-19 patients. Most studies have examined these conditions individually without providing concluding evidence on co-occurring conditions. To answer this question, this study leveraged electronic health records (EHRs) from two large clinical research networks from the national Patient-Centered Clinical Research Network (PCORnet) and investigated patients’ newly incident diagnoses that appeared within 30 to 180 days after a documented SARS-CoV-2 infection. Through machine learning, we identified four reproducible subphenotypes of PASC dominated by blood and circulatory system, respiratory, musculoskeletal and nervous system, and digestive system problems, respectively. We also demonstrated that these subphenotypes were associated with distinct patterns of patient demographics, underlying conditions present prior to SARS-CoV-2 infection, acute infection phase severity, and use of new medications in the post-acute period. Our study provides novel insights into the heterogeneity of PASC and can inform stratified decision-making in the treatment of COVID-19 patients with PASC conditions.
Understanding Post-Acute Sequelae of SARS-CoV-2 Infection through Data-Driven Analysis with Longitudinal Electronic Health Records: Findings from the RECOVER Initiative
Authors: Zang Chengxi , Zhang Yongkang , Xu Jie , Bian Jiang , Morozyuk Dmitry , Schenck Edward J. , Khullar Dhruv , Nordvig Anna S. , Shenkman Elizabeth A. , Rothman Russel L. , Block Jason P. , Lyman Kristin , Weiner Mark , Carton Thomas W. , Wang Fei , Kaushal Rainu 
Published: May 2022

AbstractRecent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with small sample sizes1 or specific patient populations2,3 limiting generalizability. This study aims to characterize PASC using the EHR data warehouses from two large national patient-centered clinical research networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) and 16.8 million patients in Florida respectively. With a high-throughput causal inference pipeline using high-dimensional inverse propensity score adjustment, we identified a broad list of diagnoses and medications with significantly higher incidence 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We found more PASC diagnoses and a higher risk of PASC in NYC than in Florida, which highlights the heterogeneity of PASC in different populations.
Neuroanatomical and Functional Consequences of Oxytocin Treatment at Birth
Authors: Kenkel William M. , Ortiz Richard J. , Yee Jason R. , Perkeybile Allison M. , Kulkarni Praveen , Carter C. Sue , Cushing Bruce S. , Ferris Craig F. 
Published: May 2022

ABSTRACTBirth is a critical period for the developing brain, a time when surging hormone levels help prepare the fetal brain for the tremendous physiological changes it must accomplish upon entry into the ‘extrauterine world’. A number of obstetrical conditions warrant manipulations of these hormones at the time of birth, but we know little of their possible consequences on the developing brain. One of the most notable birth signaling hormones is oxytocin, which is administered to roughly 50% of laboring women in the United States prior to / during delivery. Previously, we found evidence for behavioral, epigenetic, and neuroendocrine consequences in adult prairie vole offspring following maternal oxytocin treatment immediately prior to birth. Here, we examined the neurodevelopmental consequences in adult prairie vole offspring following maternal oxytocin treatment immediately. Control prairie voles and those exposed to 0.25 mg/kg oxytocin were scanned as adults using anatomical and functional MRI, with neuroanatomy and brain function analyzed as voxel-based morphometry and resting state functional connectivity, respectively. Overall, anatomical differences brought on by oxytocin treatment, while widespread, were generally small, while differences in functional connectivity, particularly among oxytocin-exposed males, were larger. Analyses of functional connectivity based in graph theory revealed that oxytocin-exposed males in particular showed markedly increased connectivity throughout the brain and across several parameters, including closeness and degree. These results are interpreted in the context of the organizational effects of oxytocin exposure in early life and these findings add to a growing literature on how the perinatal brain is sensitive to hormonal manipulations at birth.
Ecological Dynamics Imposes Fundamental Challenges in Microbial Source Tracking
Authors: Wang Xu-Wen , Wu Lu , Dai Lei , Yin Xiaole , Zhang Tong , Weiss Scott T. , Liu Yang-Yu 
Published: May 2022

ABSTRACTQuantifying the contributions of possible environmental sources (“sources”) to a specific microbial community (“sink”) is a classical problem in microbiology known as microbial source tracking (MST). Solving the MST problem will not only help us understand how microbial communities were formed, but also have far-reaching applications in pollution control, public health, and forensics. Numerous computational methods, referred to as MST solvers hereafter, have been developed in the past and applied to various real datasets to demonstrate their utility across different contexts. Yet, those MST solvers do not consider microbial interactions and priority effects in microbial communities. Here, we revisit the performance of several representative MST solvers. We show compelling evidence that solving the MST problem using existing MST solvers is impractical when ecological dynamics plays a role in community assembly. In particular, we clearly demonstrate that the presence of either microbial interactions or priority effects will render the MST problem mathematically unsolvable for any MST solver. We further analyze data from fecal microbiota transplantation studies, finding that the state-of-the-art MST solvers fail to identify donors for most of the recipients. Finally, we perform community coalescence experiments to demonstrate that the state-of-the-art MST solvers fail to identify the sources for most of the sinks. Our findings suggest that ecological dynamics imposes fundamental challenges in solving the MST problem using computational approaches.
Two therapeutic CRISPR/Cas9 gene editing approaches revert FTD/ALS cellular pathology caused by aC9orf72repeat expansion mutation in patient derived cells
Authors: Sckaff M , Gill K , Sachdev A , Birk AM , Aladesuyi Arogundade O , Watry HL , Keough KC , Tsai Y-C , Ziegle J , Conklin BR , Clelland CD 
Published: May 2022

AbstractCRISPR gene editing holds promise to cure or arrest genetic disease, if we can find and implement curative edits reliably, safely and effectively. Expansion of a hexanucleotide repeat inC9orf72is the leading known genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated three approaches to editing the mutantC9orf72gene for their ability to correct pathology in neurons derived from patient iPSCs: excision of the repeat region, excision of the mutant allele, and excision of regulatory region exon 1A. All three approaches normalized RNA abnormalities and TDP-43 pathology, but only repeat excision and mutant allele excision completely eliminated pathologic dipeptide repeats. Our work sheds light on the complex regulation of theC9orf72gene and suggests that because of sense and anti-sense transcription, silencing a single regulatory region may not reverse all pathology. Our work also provides a roadmap for evaluating CRISPR gene correction using patient iPSCs.
Transcriptional signature pattern in black, blue and purple wheat and impact on seed pigmentation and other associated features: Comparative transcriptomics, genomics and metabolite profiling
Authors: Sharma Saloni , Kumar Ashish , Singh Dalwinder , Kumari Anita , Kapoor Payal , Kaur Satveer , Sheoran Bhawna , Garg Monika 
Published: May 2022

AbstractAnthocyanin biosynthesis in plants is complex, especially in a polyploid monocot wheat plant. Using whole-genome sequencing, transcriptomics, and LC-MS/MS, we investigated anthocyanin production in pigmented (black, blue, and purple) wheat seeds. According to differential gene expression profiling, 2AS-MYC, 7DL-MYB, WD40 regulatory genes controls purple pericarp coloration, 4DL-MYC, 2AS-MYC, 7DL-MYB, WD40 controls blue aleurone coloration, and 4DL-MYC, 7DL-MYB, WD40 controls black aleurone colour. We believe that at least one MYC and MYB isoform is sufficient to regulate the anthocyanin synthesis in pericarp or aleurone. Based upon the reduced expressions of the genes belonging to the 4D, SSR molecular marker mapping, variant calling using genome sequencing and IGV browser gene structure visualization, it was inferred that the advanced black and blue wheat lines were substitution lines (4E{4D}), with very small recombinations. Pericarp anthocyanin profiling is controlled by a mutation in chromosome 2AS of purple wheat, and environmental variations more influence pigmented pericarp trait. The expression patterns of anthocyanin structural and other genes varied in different colored wheat, corroborating differences in agronomical metrics.