bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft genome sequences of strains CBS6241 and CBS6242 of the basidiomycetous yeastFilobasidium floriforme
Authors: Guerreiro Marco Alexandre , Ahrendt Steven , Pangilinan Jasmyn , Chen Cindy , Yan Mi , Lipzen Anna , Barry Kerrie , Grigoriev Igor V , Begerow Dominik , Nowrousian Minou 
Published: November 2021

AbstractThe Tremellomycetes are a species-rich group within the basidiomycete fungi; however, most analyses of this group to date have focused on pathogenic Cryptococcus species within the order Tremellales. Recent genome-assisted studies of other Tremellomycetes have identified interesting features with respect to biotechnological applications as well as the evolution of genes involved in mating and sexual development. Here, we report genome sequences of two strains of Filobasidium floriforme, a species from the order Filobasidiales, which branches basally to the Tremellales, Trichosporonales, and Holtermanniales. The assembled genomes of strains CBS6241 and CBS6242 are 27.4 Mb and 26.4 Mb in size, respectively, with 8314 and 7695 predicted protein-coding genes. Overall sequence identity at nucleic acid level between the strains is 97%. Among the predicted genes are pheromone precursor and pheromone receptor genes as well as two genes encoding homedomain (HD) transcription factors, which are predicted to be part of the mating type (MAT) locus. Sequence analysis indicates that CBS6241 and CBS6242 carry different alleles for both the pheromone/receptor genes as well as the HD transcription factors. Orthology inference identified 1482 orthogroups exclusively found in F. floriforme, some of which were involved in carbohydrate transport and metabolism. Subsequent CAZyme repertoire characterization identified 267 and 247 enzymes for CBS6241 and CBS6242, respectively, the second highest number of CAZymes among the analyzed Tremellomycete species. In addition, F. floriforme contains five CAZymes absent in other species and several plant-cell-wall degrading CAZymes with the highest copy number in Tremellomycota, indicating the biotechnological potential of this species.
Genomic characterization of a wild diploid isolate of Saccharomyces cerevisiae reveals an extensive and dynamic landscape of structural variation
Authors: Heasley Lydia R , Argueso Juan Lucas 
Published: November 2021

Abstract
The budding yeast Saccharomyces cerevisiae has been extensively characterized for many decades and is a crucial resource for the study of numerous facets of eukaryotic biology. Recent whole genome sequence analysis of over 1000 natural isolates of S. cerevisiae has provided critical insights into the evolutionary landscape of this species by revealing a population structure comprised of numerous genomically diverse lineages. These survey-level analyses have been largely devoid of structural genomic information, mainly because short-read sequencing is not suitable for detailed characterization of genomic architecture. Consequently, we still lack a complete perspective of the genomic variation that exists within this species. Single molecule long-read sequencing technologies, such as Oxford Nanopore and PacBio, provide sequencing-based approaches with which to rigorously define the structure of a genome, and have empowered yeast geneticists to explore this poorly described realm of eukaryotic genomics. Here, we present the comprehensive genomic structural analysis of a wild diploid isolate of S. cerevisiae, YJM311. We used long-read sequence analysis to construct a haplotype-phased, telomere-to-telomere length assembly of the YJM311 genome and characterized the structural variations (SVs) therein. We discovered that the genome of YJM311 contains significant intragenomic structural variation, some of which imparts notable consequences to the genomic stability and developmental biology of the strain. Collectively, we outline a new methodology for creating accurate haplotype-phased genome assemblies and highlight how such genomic analyses can be used to define the structural architectures of natural S. cerevisiae isolates. It is our hope that continued structural characterization of S. cerevisiae genomes, such as we have reported here for YJM311, will comprehensively advance our understanding of eukaryotic genome structure-function relationships, structural genomic diversity, and evolution.
Single nucleotide substitutions effectively block Cas9 and allow for scarless genome editing inCaenorhabditis elegans
Authors: Medley Jeffrey C , Hebbar Shilpa , Sydzyik Joel T , Zinovyeva Anna Y 
Published: November 2021

AbstractIn Caenorhabditis elegans, germline injection of Cas9 complexes is reliably used to achieve genome editing through homology-directed repair of Cas9-generated DNA breaks. To prevent Cas9 from targeting repaired DNA, additional blocking mutations are often incorporated into homologous repair templates. Cas9 can be blocked either by mutating the PAM sequence that is essential for Cas9 activity or by mutating the guide sequence that targets Cas9 to a specific genomic location. However, it is unclear how many nucleotides within the guide sequence should be mutated, since Cas9 can recognize “off-target” sequences that are imperfectly paired to its guide. In this study, we examined whether single-nucleotide substitutions within the guide sequence are sufficient to block Cas9 and allow for efficient genome editing. We show that a single mismatch within the guide sequence effectively blocks Cas9 and allows for recovery of edited animals. Surprisingly, we found that a low rate of edited animals can be recovered without introducing any blocking mutations, suggesting a temporal block to Cas9 activity in C. elegans. Furthermore, we show that the maternal genome of hermaphrodite animals is preferentially edited over the paternal genome. We demonstrate that maternally provided haplotypes can be selected using balancer chromosomes and propose a method of mutant isolation that greatly reduces screening efforts postinjection. Collectively, our findings expand the repertoire of genome editing strategies in C. elegans and demonstrate that extraneous blocking mutations are not required to recover edited animals when the desired mutation is located within the guide sequence.
phiC31 integrase for recombination-mediated single-copy insertion and genome manipulation in Caenorhabditis elegans
Authors: Yang Fang-Jung , Chen Chiao-Nung , Chang Tiffany , Cheng Ting-Wei , Chang Ni-Chen , Kao Chia-Yi , Lee Chih-Chi , Huang Yu-Ching , Hsu Jung-Chen , Li Jengyi , Lu Meiyeh J , Chan Shih-Peng , Wang John 
Published: November 2021

Abstract
Caenorhabditis elegans benefits from a large set of tools for genome manipulation. Yet, the precise single-copy insertion of very large DNA constructs (&gt;10 kb) and the generation of inversions are still challenging. Here, we adapted the phiC31 integrase system for C. elegans. We generated an integrated phiC31 integrase expressing strain flanked by attP sites that serves as a landing pad for integration of transgenes by recombination-mediated cassette exchange (RCME). This strain is unc-119(−) so RMCE integrants can be produced simply by injection of a plasmid carrying attB sites flanking unc-119(+) and the gene(s) of interest. Additionally, phiC31 integrase is removed concomitantly with integration, eliminating the need to outcross away the integrase. Integrations were obtained for insert sizes up to ∼33.4 kb. Taking advantage of this integration method we establish a dual-color fluorescent operon reporter system able to study post-transcriptional regulation of mRNA. Last, we show that large chromosomal segments can be inverted using phiC31 integrase. Thus, the phiC31 integrase system should be a useful addition to the C. elegans toolkit.
Population biology of accessory gland-expressed de novo genes in Drosophila melanogaster
Authors: Cridland Julie M , Majane Alex C , Zhao Li , Begun David J 
Published: November 2021

Abstract
Early work on de novo gene discovery in Drosophila was consistent with the idea that many such genes have male-biased patterns of expression, including a large number expressed in the testis. However, there has been little formal analysis of variation in the abundance and properties of de novo genes expressed in different tissues. Here, we investigate the population biology of recently evolved de novo genes expressed in the Drosophila melanogaster accessory gland, a somatic male tissue that plays an important role in male and female fertility and the post mating response of females, using the same collection of inbred lines used previously to identify testis-expressed de novo genes, thus allowing for direct cross tissue comparisons of these genes in two tissues of male reproduction. Using RNA-seq data, we identify candidate de novo genes located in annotated intergenic and intronic sequence and determine the properties of these genes including chromosomal location, expression, abundance, and coding capacity. Generally, we find major differences between the tissues in terms of gene abundance and expression, though other properties such as transcript length and chromosomal distribution are more similar. We also explore differences between regulatory mechanisms of de novo genes in the two tissues and how such differences may interact with selection to produce differences in D. melanogaster de novo genes expressed in the two tissues.
Eight-Year Changes in Multimorbidity and Frailty in Adults With Type 2 Diabetes Mellitus: Associations With Cognitive and Physical Function and Mortality
Authors: Espeland Mark A , Justice Jamie Nicole , Bahnson Judy , Evans Joni K , Munshi Medha , Hayden Kathleen M , Simpson Felicia R , Johnson Karen C , Johnston Craig , Kritchevsky Stephen R 
Published: November 2021

AbstractBackgroundIndices of multimorbidity and deficit accumulation (ie, frailty indices) have been proposed as markers of biological aging. If true, changes in these indices over time should predict downstream changes in cognition and physical function, and mortality.MethodsWe examined associations that 8-year changes in (i) a multimorbidity index comprised of 9 chronic diseases and (ii) a frailty index (FI) based on deficit accumulation in functional, behavioral, and clinical characteristics had with subsequent measures of cognitive and physical function over 10 years. We drew data from 3 842 participants in the Action for Health in Diabetes clinical trial. They were aged 45–76 years at baseline and at risk for accelerated biological aging due to overweight/obesity and type 2 diabetes mellitus.ResultsA total of 1 501 (39%) of the cohort had 8-year increases of 1 among the 9 diseases tracked in the multimorbidity index and 868 (23%) had increases of ≥2. Those with greatest increases in multimorbidity tended to be older individuals, males, and non-Hispanic Whites. Greater FI increases tended to occur among individuals who were older, non-Hispanic White, heavier, and who had more baseline morbidities. Changes in multimorbidity and FI were moderately correlated (r = 0.26; p &lt; .001). Increases in both multimorbidity and FI were associated with subsequently poorer composite cognitive function and 400-m walk speed and increased risk for death (all p &lt; .001).ConclusionsAccelerated biological aging, as captured by multimorbidity and frailty indices, predicts subsequent reduced function and mortality. Whether intensive lifestyle interventions generally targeting multimorbidity and FI reduce risks for downstream outcomes remains to be seen.Clinical Trials Registration Number: NCT00017953
Is Wrist Accelerometry Suitable for Threshold Scoring? A Comparison of Hip-Worn and Wrist-Worn ActiGraph Data in Low-Active Older Adults With Obesity
Authors: Fanning Jason , Miller Michael E , Chen Shyh-Huei , Davids Carlo , Kershner Kyle , Rejeski W Jack 
Published: November 2021

AbstractBackgroundHip- and wrist-worn ActiGraph accelerometers are widely used in research on physical activity as they offer an objective assessment of movement intensity across the day. Herein we characterize and contrast key structured physical activities and common activities of daily living via accelerometry data collected at the hip and wrist from a sample of community-dwelling older adults.MethodsLow-active, older adults with obesity (age 60+ years) were fit with an ActiGraph GT3X+ accelerometer on their nondominant wrist and hip before completing a series of tasks in a randomized order, including sitting/standing, sweeping, folding laundry, stair climbing, ambulation at different intensities, and cycling at different intensities. Participants returned a week later and completed the tasks once again. Vector magnitude counts/second were time-matched during each task and then summarized into counts/minute (CPM).ResultsMonitors at both wear locations similarly characterized standing, sitting, and ambulatory tasks. A key finding was that light home chores (sweeping, folding laundry) produced higher and more variable CPM values than fast walking via wrist ActiGraph. Regression analyses revealed wrist CPM values were poor predictors of hip CPM values, with devices aligning best during fast walking (R2 = 0.25) and stair climbing (R2 = 0.35).ConclusionsAs older adults spend a considerable portion of their day in nonexercise activities of daily living, researchers should be cautious in the use of simply acceleration thresholds for scoring wrist-worn accelerometer data. Methods for better classifying wrist-worn activity monitor data in older adults are needed.
How Do Individuals in a Radical Echo Chamber React to Opposing Views? Evidence from a Content Analysis of Stormfront
Authors: Bright Jonathan , Marchal Nahema , Ganesh Bharath , Rudinac Stevan 
Published: November 2021

AbstractCalls to “break up” radical echo chambers by injecting them with alternative viewpoints are common. Yet, thus far there is little evidence about the impact of such counter-messaging. To what extent and how do individuals who inhabit a radical echo chamber engage with messages that challenge their core beliefs? Drawing on data from the radical right forum Stormfront we address this question with a large-scale content and longitudinal analysis of users’ posting behavior, which analyses more than 35,000 English language contributions to the forum spanning 2011 through 2013. Our findings show that engaging with oppositional views is actually a core practice among Stromfront users which invites active participation and encourages engagement. Indeed, many “echoes” in the echo chamber we studied were not core beliefs being restated, but the sound of opposing viewpoints being undermined and marginalized. These findings underscore the limited potential for counter-messages to undermine radical echo chambers.
Current Trends in IBD—Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System
Authors: Yau Yunki Y , Wasinger Valerie C , Hirten Robert P , Chuang Emil , Huntsman Merodean , Stylli Jack , Shimizu Jeff , Yajnik Vijay , Smith Jeffrey , Lee Shaoying N , Singh Sharat , Wahl Christopher , Leong Rupert W , Sands Bruce E 
Published: November 2021

Abstract
Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease. The ability to characterize this interface may provide valuable information for both disease monitoring and identification of new treatment targets. Endoscopy remains the primary tool for disease monitoring, and mucosal healing is the primary therapeutic target in IBD treatment. However, establishing mucosal healing requires repetitive endoscopic procedures, and endoscopy is limited by factors such as invasiveness, cost, and risk of adverse events. Moreover, the use of a bowel preparation for colonoscopies alters the mucus layer and thus perturbs evaluation of the host-microbe interaction. Stool sampling may also be inaccurate because it reflects the end state of metabolites and proteins, failing to take into account the degradation or alteration of substrates of interest by bacterial proteases and other enzymes during passage through the colon.
A novel sampling capsule, called the Recoverable Sampling System (RSS), is being developed as a complementary tool to colonoscopy. The RSS is intended to be a platform for noninvasive autonomous sampling, preservation, handling, and storage of analytes of interest found in the gastrointestinal fluids. A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses.
Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets.
Colon Capsule Endoscopy in the Assessment of Mucosal Healing in Crohn’s Disease
Authors: Papalia Isabella , Tjandra Douglas , Quah Stephanie , Tan Christina , Gorelik Alexandra , Sivanesan Suresh , Macrae Finlay 
Published: November 2021

Abstract

Background
Patients with Crohn’s disease (CD) undergo frequent endoscopic procedures, with visualization of the gastrointestinal mucosa central to treatment decision-making. Subsequently, a noninvasive alternative to optical colonoscopy (OC) would be welcomed. One such technology is capsule endoscopy, including the PillCam COLON 2 (PCC2), though research validating its use in ileocolonic CD is limited. This study aims to compare PCC2 with ileocolonoscopy (OC) in assessing mucosal CD through use of a standardized scoring system.

Methods
At an Australian tertiary hospital, same-day PCC2 and ileocolonoscopy results of 47 CD patients, with known nonstricturing disease, were prospectively collected and analyzed for correlation and agreement. Deidentified recordings were reported by a single expert gastroenterologist. Mucosal disease was quantified using the Simple Endoscopic Score for Crohn’s Disease (SES-CD). The SES-CD results of paired endoscopic modalities were compared in total per bowel segment and per SES-CD variable.

Results
Of 47 PCC2 recordings, 68% were complete, fully assessing terminal ileum to rectum, and OC was complete in 89%. Correlation (r) between total SES-CD scores was strongest in the terminal ileum (r = 0.77, P &lt; .001), with the SES-CD variable of “ulcer detection” showing the strongest agreement. The PCC2 (vs OC) identified additional ulcers in the terminal ileum; ascending, transverse, and descending colon; and rectum; scores were 5 (1), 5 (3), 1 (1), 2 (1), and 2 (2), respectively.

Conclusions
The PCC2 shows promise in assessing ileocolonic mucosa, especially in proximal bowel segments, with greater reach of visualization in the small bowel. Given the resource and safety considerations raised by the Coronavirus disease 2019 pandemic, capsule endoscopy has particular significance.
This article aims to contribute to the limited body of research surrounding the validity of capsule endoscopy technology in assessing ileocolonic mucosa in Crohn’s Disease patients. In doing so, an alternative option for patients enduring frequent endoscopies is given potential.
Research-Based Product Innovation to Address Critical Unmet Needs of Patients with Inflammatory Bowel Diseases
Authors: Honig Gerard , Larkin Paul B , Heller Caren , Hurtado-Lorenzo Andrés 
Published: November 2021

Abstract
Despite progress in recent decades, patients with inflammatory bowel diseases face many critical unmet needs, demonstrating the limitations of available treatment options. Addressing these unmet needs will require interventions targeting multiple aspects of inflammatory bowel disease pathology, including disease drivers that are not targeted by available therapies. The vast majority of late-stage investigational therapies also focus primarily on a narrow range of fundamental mechanisms. Thus, there is a pressing need to advance to clinical stage differentiated investigational therapies directly targeting a broader range of key mechanistic drivers of inflammatory bowel diseases. In addition, innovations are critically needed to enable treatments to be tailored to the specific underlying abnormal biological pathways of patients; interventions with improved safety profiles; biomarkers to develop prognostic, predictive, and monitoring tests; novel devices for nonpharmacological approaches such as minimally invasive monitoring; and digital health technologies. To address these needs, the Crohn’s & Colitis Foundation launched IBD Ventures, a venture philanthropy–funding mechanism, and IBD Innovate®, an innovative, product-focused scientific conference. This special IBD Innovate® supplement is a collection of articles reflecting the diverse and exciting research and development that is currently ongoing in the inflammatory bowel disease field to deliver innovative and differentiated products addressing critical unmet needs of patients. Here, we highlight the pipeline of new product opportunities currently advancing at the preclinical and early clinical development stages. We categorize and describe novel and differentiated potential product opportunities based on their potential to address the following critical unmet patient needs: (1) biomarkers for prognosis of disease course and prediction/monitoring of treatment response; (2) restoration of eubiosis; (3) restoration of barrier function and mucosal healing; (4) more effective and safer anti-inflammatories; (5) neuromodulatory and behavioral therapies; (6) management of disease complications; and (7) targeted drug delivery.