bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping neurotransmitter systems to the structural and functional organization of the human neocortex
Authors: Hansen Justine Y. , Shafiei Golia , Markello Ross D. , Smart Kelly , Cox Sylvia M. L. , Nørgaard Martin , Beliveau Vincent , Wu Yanjun , Gallezot Jean-Dominique , Aumont Étienne , Servaes Stijn , Scala Stephanie G. , DuBois Jonathan M. , Wainstein Gabriel , Bezgin Gleb , Funck Thomas , Schmitz Taylor W. , Spreng R. Nathan , Galovic Marian , Koepp Matthias J. , Duncan John S. , Coles Jonathan P. , Fryer Tim D. , Aigbirhio Franklin I. , McGinnity Colm J. , Hammers Alexander , Soucy Jean-Paul , Baillet Sylvain , Guimond Synthia , Hietala Jarmo , Bédard Marc-André , Leyton Marco , Kobayashi Eliane , Rosa-Neto Pedro , Ganz Melanie , Knudsen Gitte M. , Palomero-Gallagher Nicola , Shine James M. , Carson Richard E. , Tuominen Lauri , Dagher Alain , Misic Bratislav 
Published: October 2021

AbstractNeurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macroscale neuroanatomy and how they shape emergent function remains poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from >1 200 healthy individuals to construct a whole-brain 3-D normative atlas of 19 receptors and transporters across 9 different neurotransmitter systems. We find that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncover a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we find both expected and novel associations between receptor distributions and cortical thinning patterns across 13 disorders. We replicate all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization.
inPOSE: a flexible toolbox for chromosomal cloning and amplification of bacterial transgenes
Authors: Shukla Ranti Dev , Zvara Ágnes , Avramucz Ákos , Biketova Alona Yu. , Nyerges Akos , Puskás László G. , Fehér Tamás 
Published: October 2021

AbstractCloning genes and operons encoding heterologous functions in bacterial hosts is almost exclusively carried out today using plasmid vectors. This has multiple drawbacks, including the need for constant selection and the variation in copy numbers. Chromosomal integration of transgenes has always offered a viable alternative, however, to date it has been of limited use due to its tedious nature and to being limited often to a single copy. We introduce here a strategy that uses bacterial insertion sequences, the simplest autonomous transposable elements to insert and amplify genetic cargo into a bacterial chromosome. Transgene insertion can take place either as transposition or homologous recombination, and copy-number amplification is achieved using controlled copy-paste transposition. We display successful use of IS1 and IS3 for this purpose in Escherichia coli cells, using various selection markers. We demonstrate the insertion of selectable genes, an unselectable gene, and a five-gene operon in up to two copies in a single step. We continue with the amplification of the inserted cassette to double-digit copy numbers within two rounds of transposase induction and selection. Finally, we analyze the stability of the cloned genetic constructs in the lack of selection and find it to be superior to all investigated plasmid-based systems. Due to the ubiquitous nature of transposable elements, we believe that with proper design, this strategy can be adapted to numerous further bacterial species.
Impact of antibiotic perturbation on intestinal viral communities in mice
Authors: Anderson Jacqueline Moltzau , Lachnit Tim , Lipinski Simone , Falk-Paulsen Maren , Rosenstiel Philip 
Published: October 2021

AbstractViruses and bacteriophages have a strong impact on intestinal barrier function and the composition and functional properties of commensal bacterial communities. To improve our understanding of the role of the enteric intestinal virome, we longitudinally characterized the virome in fecal samples from wild-type (WT) C57BL/6J and knock-out (KO) NOD2 mice in response to an antibiotic perturbation. Sequencing of viral-like-particles (VLPs) demonstrated both a high diversity and high inter-individual variation of the murine gut virome composed of eukaryotic viruses and bacteriophages. Antibiotics also had a significant impact on the gut murine virome causing a delayed resilience independent of genotype. However, compositional shifts in the virome and bacteriome were highly correlated, suggesting that the loss of specific phages may contribute to a dysregulation of the bacterial community composition. Bacteriophage species may be playing an important role in either upregulating or downregulating the bacterial community, and restoring a healthy virome may therefore be a central goal of microbiota-targeted therapies.
Response of total (DNA) and metabolically active (RNA) microbial communities in Miscanthus × giganteus cultivated soil to different nitrogen fertilization rates
Authors: Yang Jihoon , Lee Jaejin , Choi Jinlyung , Ma Lanying , Heaton Emily , Howe Adina 
Published: October 2021

AbstractMiscanthus x giganteus is a promising high-yielding perennial plant to meet growing bioenergy demands but the degree to which the soil microbiome affects its nitrogen cycling and subsequently, biomass yield remains unclear. In this study, we hypothesize that contributions of metabolically active soil microbial membership may be underestimated with DNA-based approaches. We assessed the response of the soil microbiome to nitrogen availability in terms of both DNA and RNA soil microbial communities from the Long-term Assessment of Miscanthus Productivity and Sustainability (LAMPS) field trial. DNA and RNA were extracted from 271 samples, and 16S SSU rRNA amplicon sequencing was performed to characterize microbial community structure. Significant differences were observed in the resulting soil microbiomes and were best explained by the sequencing library of origin, either DNA and RNA. Similar numbers of taxa were detected in DNA and RNA microbial communities, with more than 90% of taxa shared. However, the profile of dominant taxa within DNA and RNA differed, with varying proportions of Actinobacteria and Proteobacteria and Firmicutes and Proteobacteria. Only RNA microbial communities showed seasonal responses to nitrogen fertilization, and these differences were associated with nitrogen-cycling bacteria. The relative abundance of bacteria associated with nitrogen cycling was 7-folds higher in RNA than in DNA, and genes associated with denitrifying bacteria were significantly enriched in RNA, suggesting that these bacteria may be underestimated with DNA-only approaches. Our findings indicate that RNA-based SSU characterization can be a significant and complementing resource for understanding the role of soil microbiomes in bioenergy crop production.ImportanceMiscanthus x giganteus is becoming a cornerstone of bioeconomy cropping systems, but it remains unclear how the soil microbiome supplies nitrogen to this low-input crop. DNA-based techniques are used to provide community characterization but may miss important metabolically active taxa. By analyzing both DNA- and actively transcribed RNA-based microbial communities, we found that nitrogen cycling taxa in the soil microbiome may be underestimated using only DNA-based approaches. Accurately understanding the role of microbes and how they cycle nutrients is important for the development of sustainable bioenergy crops, and RNA-based approaches are recommended as a complement to DNA approaches to better understand the microbial, plant, and management interactions.
Circular RNA detection identifiescircPSEN1alterations in brain specific to Autosomal Dominant Alzheimer Disease
Authors: Chen Hsiang-Han , Eteleeb Abdallah , Wang Ciyang , Fernandez Maria Victoria , Budde John P. , Bergmann Kristy , Norton Joanne , Wang Fengxian , Ebl Curtis , Morris John C. , Perrin Richard J. , Bateman Randall J. , McDade Eric , Xiong Chengjie , Goate Alison , Farlow Martin , Chhatwal Jasmeer , Schofield Peter R , Chui Helena , Harari Oscar , Cruchaga Carlos , Ibanez Laura ,   Dominantly Inherited Alzheimer Network
Published: October 2021

AbstractBackgroundAutosomal-dominant Alzheimer’s disease (ADAD) is caused by pathogenic mutations inAPP, PSEN1, andPSEN2, which usually lead to an early age at onset (<65). Circular RNAs are a family of non-coding RNAs highly expressed in the nervous system and especially in synapses. We aimed to investigate differences in brain gene expression of linear and circular transcripts from the three ADAD genes in controls, sporadic AD, and ADAD.MethodsWe obtained and sequenced RNA from brain cortex using standard protocols. Linear counts were obtained using the TOPMed pipeline; circular counts, using python package DCC. After stringent quality control (QC), we obtained the counts forPSEN1, PSEN2and APP genes. Only circPSEN1passed QC. We used DESeq2 to compare the counts across groups, correcting for biological and technical variables. Finally, we performedin-silicofunctional analyses using the Circular RNA interactome website and DIANA mirPath software.ResultsOur results show significant differences in gene counts of circPSEN1in ADAD individuals, when compared to sporadic AD and controls (ADAD=22, AD=274, Controls=25 – ADADvsCO: log2FC=0.786, p=9.08×10-05, ADADvsAD: log2FC=0.576, p=2.00×10-03). The high gene counts are contributed by two circPSEN1species (hsa_circ_0008521 and hsa_circ_0003848). No significant differences were observed in linearPSEN1gene expression between cases and controls, indicating that this finding is specific to the circular forms. In addition, the high circPSEN1levels do not seem to be specific toPSEN1mutation carriers; the counts are also elevated in APP andPSEN2mutation carriers.In-silicofunctional analyses suggest that circPSEN1is involved in several pathways such as axon guidance (p=3.39×10−07), hippo signaling pathway (p=7.38×10−07), lysine degradation (p=2.48×10−05) or Wnt signaling pathway (p=5.58×10−04) among other KEGG pathways. Additionally, circPSEN1counts were able to discriminate ADAD from sporadic AD and controls with an AUC above 0.70.ConclusionsOur findings show the differential expression of circPSEN1is increased in ADAD. Given the biological function previously ascribed to circular RNAs and the results of ourin-silicoanalyses, we hypothesize that this finding might be related to neuroinflammatory events that lead or that are caused by the accumulation of amyloid-beta.
Contributions of occupation characteristics and educational attainment to racial/ethnic inequities in COVID-19 mortality
Authors: Matthay Ellicott C. , Duchowny Kate A. , Riley Alicia R. , Thomas Marilyn , Chen Yea-Hung , Bibbins-Domingo Kirsten , Glymour M. Maria 
Published: October 2021

AbstractBackgroundRacial/ethnic inequities in COVID-19 mortality are hypothesized to be driven by education and occupation, but limited empirical evidence has assessed these mechanisms.ObjectiveTo quantify the extent to which educational attainment and occupation explain racial/ethnic inequities in COVID-19 mortality.DesignObservational cohort.SettingCalifornia.ParticipantsCalifornians aged 18-65 years.MeasurementsWe linked all COVID-19-confirmed deaths in California through February 12, 2021 (N=14,783), to population estimates within strata defined by race/ethnicity, sex, age, USA nativity, region of residence, education, and occupation. We characterized occupations using measures related to COVID-19 exposure including essential sector, telework-ability, and wages. Using sex-stratified regressions, we predicted COVID-19 mortality by race/ethnicity if all races/ethnicities had the same education and occupation distribution as White people and if all people held the safest educational/occupational positions.ResultsCOVID-19 mortality per 100,000 ranged from 15 for White and Asian females to 139 for Latinx males. Accounting for differences in age, nativity, and region, if all races/ethnicities had the education and occupation distribution of Whites, COVID-19 mortality would be reduced for Latinx males (−22%) and females (−23%), and Black males (−1%) and females (−8%), but increased for Asian males (+22%) and females (+23%). Additionally, if all individuals had the COVID-19 mortality associated with the safest educational and occupational position (Bachelor’s degree, non-essential, telework, highest wage quintile), there would have been 57% fewer COVID-19 deaths.ConclusionEducational and occupational disadvantage are important risk factors for COVID-19 mortality across all racial/ethnic groups, especially Latinx individuals. Eliminating avoidable excess risk associated with low-education, essential, on-site, and low-wage jobs may reduce COVID-19 mortality and inequities, but is unlikely to be sufficient to achieve equity.
Characterizing Sleep Disorders in an Autism-Specific Collection of Electronic Health Records
Authors: Singer EV , Niarchou M , Maxwell-Horn A , Hucks D , Johnston R , Sutcliffe J , Davis LK , Malow BA 
Published: October 2021

AbstractBackgroundSleep problems are common in individuals with autism spectrum disorder (ASD). This study reviews one detailed approach to querying the electronic health record (EHR).MethodsWe developed methods for identifying individuals with ASD and defined their sleep problems using International Classification of Diseases (ICD) codes or key words. We examined treatment responses to melatonin.ResultsSleep problems were documented in 86% of patients and using specific keywords yielded more sleep diagnoses than ICD codes alone. About two-thirds of patients benefitted from melatonin.ConclusionsOur study provides a framework for using deidentified medical records to characterize sleep, a common co-occurring condition, in ASD. Using specific keywords could be helpful in future work that queries the EHR.
Ruxolitinib As a Salvage Therapy for Acute and Chronic Graft-versus-Host Disease in Children and Young Adults: a single institution experience
Authors: Mavers Melissa , Klinger Edna , Shyr David C , Shah Ami J , Bertaina Alice , Soni Sandeep 
Published: October 2021

ABSTRACTBackgroundRuxolitinib, a Janus kinase (JAK)-1/JAK-2 inhibitor that reduces T-cell activation and proliferation leading to a potent anti-inflammatory effect, was recently approved to treat steroid-refractory acute graft-versus-host disease (aGvHD) and is under study for chronic GvHD (cGvHD). However, there are few reports on its use in pediatric and young adult patients with GvHD.MethodsWe retrospectively report our single center experience with ruxolitinib in 15 patients aged 11-29 years: 5 patients with steroid refractory/steroid dependent aGvHD and 10 patients with cGvHD who had failed at least one systemic therapy.ResultsIn the aGvHD group, ruxolitinib led to an overall response rate (ORR) of 40% at day 28 and 80% with longer follow-up (complete response, CR 60%), with a median of 21 days (5-74) to achieve a response. In the cGvHD group (9 evaluable patients), we observed an ORR of 67% and a CR of 22%, with a median of 78 days (35-180) to achieve a response. Adverse events included cytopenias, gastrointestinal symptoms, infections, and an allergic reaction attributable to ruxolitinib.ConclusionsOverall, our results show that ruxolitinib is an effective salvage therapy for severe GvHD in pediatric and young adult patients. The toxicities noted warrant adequate antimicrobial prophylaxis and close monitoring of blood counts.
Pneumococcal Vaccination Coverage and Uptake Among Adults in Switzerland: A Nationwide Cross-Sectional Study of Vaccination Records
Authors: Zens Kyra D. , Baroutsou Vasiliki , Fehr Jan S. , Lang Phung 
Published: October 2021

AbstractStreptococcus pneumoniae, or pneumococcus, is a common, opportunistic pathogen which can cause severe disease, particularly in adults 65+. In Switzerland, vaccination is recommended for children under 5 and for adults with health predispositions; vaccination of healthy adults 65+ is not recommended. In 2020 we conducted a nationwide, cross-sectional survey of vaccination records to evaluate pneumococcal vaccination coverage and factors affecting uptake among adults 18-85. We found that nationwide coverage was 4.5% without significant regional differences. Coverage was comparable between men and women and between those aged 18-39 (3.0%) and 40-64 (3.2%). Coverage was significantly higher among those 65-85 (9.6%). While 2.7% of individuals reporting no health predisposition were vaccinated, 14.8% with asthma or chronic pulmonary disease, 27.1% with immunosuppression, 12.9% with diabetes, 11.6% with heart, liver, or kidney disease, and 25.9% with >1 health risk were vaccinated. Adjusted odds of vaccination for all health predispositions except heart, liver, or kidney disease were significantly increased. Among unvaccinated individuals “not enough information about the topic” and “not suggested by a doctor/healthcare provider” were the major reasons for abstaining from vaccination. Respondents reporting a health predisposition were significantly less likely to report “not at increased risk due to chronic health conditions or age” as a reason for not being vaccinated (3.7% versus 29.1%) and were more likely to report willingness to be vaccinated in the future compared to those not-at-risk (54.2% versus 39.9%). Our results indicate that pneumococcal vaccination coverage in Switzerland is low among both individuals 65-85 and among those with predisposing health risks. It appears that at-risk individuals are aware of their increased risk, but feel they do not have enough information on the topic to seek vaccination, or have not been recommended a vaccination by their physician.
R-loop mapping and characterization during Drosophila embryogenesis reveals developmental plasticity in R-loop signatures
Authors: Munden Alexander , Benton Mary Lauren , Capra John A. , Nordman Jared 
Published: October 2021

ABSTRACTR-loops are involved in transcriptional regulation, DNA and histone post-translational modifications, genome replication and genome stability. To what extent R-loop abundance and genome-wide localization is actively regulated during metazoan embryogenesis is unknown. Drosophila embryogenesis provides a powerful system to address these questions due to its well-characterized developmental program, the sudden onset of zygotic transcription and available genome-wide ChIP and transcription data sets. Here, we measure the overall abundance and genome localization of R-loops in early and late-stage embryos relative to Drosophila cultured cells. We demonstrate that absolute R-loop levels change during embryogenesis and that resolution of R-loops is critical for embryonic development. R-loop mapping by strand-specific DRIP-seq reveals that R-loop localization is plastic across development, both in the genes which form R-loops and where they localize relative to gene bodies. Importantly, these changes are not driven by changes in the transcriptional program. Negative GC skew and absolute changes in AT skew are associated with R-loop formation in Drosophila. Furthermore, we demonstrate that while some chromatin binding proteins and histone modification such as H3K27me3 are associated with R-loops throughout development, other chromatin factors associated with R-loops in a developmental specific manner. Our findings highlight the importance and developmental plasticity of R-loops during Drosophila embryogenesis.
Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes
Authors: Guthrie Leah , Spencer Sean Paul , Perelman Dalia , Van Treuren Will , Han Shuo , Yu Feiqiao Brian , Sonnenburg Erica D. , Fischbach Michael A. , Meyer Timothy W. , Sonnenburg Justin L. 
Published: October 2021

SummaryMetabolism of dietary compounds by the gut microbiota generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDMs generation; however, it is unclear if interindividual differences in diet or gut microbiome dominantly contribute to MDM variance. Here we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. Notably, the coefficient of variation in three uMDMs of interest, PAG, PCS, and IS (primary outcome), did not significantly decrease. The majority of circulating MDMs maintained variation despite identical diets. These results highlight the highly personalized profile of MDMs and limited contribution of short-term dietary heterogeneity, suggesting that dietary modification may need to be paired with microbial therapies to control MDM profiles.
A hold-and-feed mechanism drives directional DNA loop extrusion by condensin
Authors: Shaltiel Indra A. , Datta Sumanjit , Lecomte Léa , Hassler Markus , Kschonsak Marc , Bravo Sol , Stober Catherine , Eustermann Sebastian , Haering Christian H. 
Published: October 2021

AbstractSMC protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop in two separate chambers. Single-molecule and cryo-electron microscopy provide evidence for a power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon ATP binding, while the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of ‘motor’ and ‘anchor’ chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the course of the SMC reaction cycle determines the directionality of DNA loop extrusion.