bluuebunny/crossref_metadata_2025 huggingface dataset:
Infection by a eukaryotic gut parasite in wild Daphnia sp. associates with a distinct bacterial community
Authors: Rajarajan Amruta , Wolinska Justyna , Walser Jean-Claude , Mäder Minea , Spaak Piet
Published: August 2022

Host-associated bacterial communities play an important role in host fitness and resistance to diseases. Yet, few studies have investigated tripartite interaction between a host, parasite and host-associated bacterial communities in natural settings. Here, we use 16S rRNA gene amplicon sequencing to compare gut- and body- bacterial communities of wild water fleas belonging to the Daphnia longispina complex, between uninfected hosts and those infected with the common and virulent eukaryotic gut parasite Caullerya mesnili (Family: Ichthyosporea). We report community-level changes in host-associated bacteria with the presence of the parasite infection; namely decreased alpha diversity and increased beta diversity at the site of infection, i.e. host gut (but not host body). We also report decreased abundance of bacterial taxa proposed elsewhere to be beneficial for the host, and an appearance of taxa specifically associated with infected hosts. Our study highlights the host-microbiota-infection link in a natural system and raises questions about the role of host-associated microbiota in natural disease epidemics as well as the functional roles of bacteria specifically associated with infected hosts.
Intensification of Implementation Strategies: Developing a Model of Foundational and Enhanced Implementation Approaches to Support National Adoption and Scale-up
Authors: Hughes Jaime M , Zullig Leah L , Choate Ashley L , Decosimo Kasey P , Wang Virginia , Van Houtven Courtney H , Allen Kelli D , Nicole Hastings S
Published: August 2022

Implementation strategies are activities to support integration of evidence-based programs (EBPs) into routine care. Comprised of 170+ facilities, the Veterans Affairs Healthcare System is conducive to evaluating feasibility and scalability of implementation strategies on a national level. In previous work evaluating implementation of three EBPs for older Veterans (hospital-based walking, caregiver skills training, group physical therapy), we found facilities varied in their need for implementation support, with some needing minimal guidance and others requiring intensive support. Committed to national scalability, our team developed an implementation intensification model consisting of foundational (low-touch) and enhanced (high-touch) implementation support. This Forum article describes our multilevel and multistep process to develop and evaluate implementation intensification. Steps included (a) review completed trial data; (b) conduct listening sessions; (c) review literature; (d) draft foundational and enhanced implementation support packages; (e) iteratively refine packages; and (7) devise an evaluation plan. Our model of implementation intensification may be relevant to other health care systems seeking strategies that can adapt to diverse delivery settings, optimize resources, help build capacity, and ultimately enhance implementation outcomes. As more health care systems focus on spread of EBPs into routine care, identifying scalable and effective implementation strategies will be critical.
Quantitative trait locus (xQTL) approaches identify risk genes and drug targets from human non-coding genomes
Authors: Bykova Marina , Hou Yuan , Eng Charis , Cheng Feixiong
Published: August 2022

Advances and reduction of costs in various sequencing technologies allow for a closer look at variations present in the non-coding regions of the human genome. Correlating non-coding variants with large-scale multi-omic data holds the promise not only of a better understanding of likely causal connections between non-coding DNA and expression of traits but also identifying potential disease-modifying medicines. Genome–phenome association studies have created large datasets of DNA variants that are associated with multiple traits or diseases, such as Alzheimer’s disease; yet, the functional consequences of variants, in particular of non-coding variants, remain largely unknown. Recent advances in functional genomics and computational approaches have led to the identification of potential roles of DNA variants, such as various quantitative trait locus (xQTL) techniques. Multi-omic assays and analytic approaches toward xQTL have identified links between genetic loci and human transcriptomic, epigenomic, proteomic and metabolomic data. In this review, we first discuss the recent development of xQTL from multi-omic findings. We then highlight multimodal analysis of xQTL and genetic data for identification of risk genes and drug targets using Alzheimer’s disease as an example. We finally discuss challenges and future research directions (e.g. artificial intelligence) for annotation of non-coding variants in complex diseases.
Dominantly acting KIF5B variants with pleiotropic cellular consequences cause variable clinical phenotypes
Authors: Flex Elisabetta , Albadri Shahad , Radio Francesca Clementina , Cecchetti Serena , Lauri Antonella , Priolo Manuela , Kissopoulos Marta , Carpentieri Giovanna , Fasano Giulia , Venditti Martina , Magliocca Valentina , Bellacchio Emanuele , Welch Carrie L , Colombo Paolo C , Kochav Stephanie M , Chang Richard , Barrick Rebekah , Trivisano Marina , Micalizzi Alessia , Borghi Rossella , Messina Elena , Mancini Cecilia , Pizzi Simone , De Santis Flavia , Rosello Marion , Specchio Nicola , Compagnucci Claudia , McWalter Kirsty , Chung Wendy K , Del Bene Filippo , Tartaglia Marco
Published: August 2022

Kinesins are motor proteins involved in microtubule (MT)-mediated intracellular transport. They contribute to key cellular processes, including intracellular trafficking, organelle dynamics and cell division. Pathogenic variants in kinesin-encoding genes underlie several human diseases characterized by an extremely variable clinical phenotype, ranging from isolated neurodevelopmental/neurodegenerative disorders to syndromic phenotypes belonging to a family of conditions collectively termed as ‘ciliopathies.’ Among kinesins, kinesin-1 is the most abundant MT motor for transport of cargoes towards the plus end of MTs. Three kinesin-1 heavy chain isoforms exist in mammals. Different from KIF5A and KIF5C, which are specifically expressed in neurons and established to cause neurological diseases when mutated, KIF5B is an ubiquitous protein. Three de novo missense KIF5B variants were recently described in four subjects with a syndromic skeletal disorder characterized by kyphomelic dysplasia, hypotonia and DD/ID. Here, we report three dominantly acting KIF5B variants (p.Asn255del, p.Leu498Pro and p.Leu537Pro) resulting in a clinically wide phenotypic spectrum, ranging from dilated cardiomyopathy with adult-onset ophthalmoplegia and progressive skeletal myopathy to a neurodevelopmental condition characterized by severe hypotonia with or without seizures. In vitro and in vivo analyses provide evidence that the identified disease-associated KIF5B variants disrupt lysosomal, autophagosome and mitochondrial organization, and impact cilium biogenesis. All variants, and one of the previously reported missense changes, were shown to affect multiple developmental processes in zebrafish. These findings document pleiotropic consequences of aberrant KIF5B function on development and cell homeostasis, and expand the phenotypic spectrum resulting from altered kinesin-mediated processes.
Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men
Authors: Wang Anqi , Xu Yili , Yu Yao , Nead Kevin T , Kim TaeBeom , Xu Keren , Dadaev Tokhir , Saunders Ed , Sheng Xin , Wan Peggy , Pooler Loreall , Xia Lucy Y , Chanock Stephen , Berndt Sonja I , Gapstur Susan M , Stevens Victoria , Albanes Demetrius , Weinstein Stephanie J , Gnanapragasam Vincent , Giles Graham G , Nguyen-Dumont Tu , Milne Roger L , Pomerantz Mark M , Schmidt Julie A , Stopsack Konrad H , Mucci Lorelei A , Catalona William J , Hetrick Kurt N , Doheny Kimberly F , MacInnis Robert J , Southey Melissa C , Eeles Rosalind A , Wiklund Fredrik , Kote-Jarai Zsofia , de Smith Adam J , Conti David V , Huff Chad , Haiman Christopher A , Darst Burcu F
Published: August 2022

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.93, 95% CI = 0.76–1.13, P = 0.46) or aggressive (aggregate OR = 1.14, 95% CI = 0.92–1.41, P = 0.22) prostate cancer risk. CHIP was weakly associated with genetic risk of overall prostate cancer, measured using a polygenic risk score (OR = 1.05 per unit increase, 95% CI = 1.01–1.10, P = 0.01). CHIP was not significantly associated with carrying pathogenic/likely pathogenic/deleterious variants in DNA repair genes, which have previously been found to be associated with aggressive prostate cancer. While findings from this study suggest that CHIP is likely not a risk factor for prostate cancer, it will be important to investigate other types of CH in association with prostate cancer risk.
Aeroallergen-related Diseases Predate the Diagnosis of Inflammatory Bowel Disease
Authors: Alenezy Namarik , Nugent Zoann , Herman Sari , Zaborniak Karver , Ramsey Clare D , Bernstein Charles N
Published: August 2022

Objective

This study aimed to determine whether having a diagnosis of asthma or allergic rhinitis (AR) increased the risk of being diagnosed with inflammatory bowel disease (IBD) and whether there was increased incidence of these diseases after a diagnosis of IBD.

Design

This is a retrospective, historical cohort–based study. We used the administrative data of Manitoba Health and the population-based University of Manitoba IBD Epidemiology Database. We used numbers of prescriptions for drugs used to treat asthma and to treat AR to identify diagnoses of asthma and AR, respectively.

We calculated relative risks (RRs) to assess incidence of IBD compared with matched controls after diagnoses of asthma and AR and hazard ratios to determine the incidence of asthma and AR after IBD diagnosis.

Results

Compared with controls, a diagnosis of asthma or AR preceding a diagnosis of IBD was increased in cases (RR, 1.62; 95% confidence interval [CI], 1.50-1.75; and RR, 2.10; 95% CI, 1.97-2.24) with a similar outcome by subtype of IBD (Crohn’s disease vs ulcerative colitis) and by sex. On sensitivity analysis, diagnoses of asthma or AR were comparable when considering at least 5, 10, 15 or 20 drug prescriptions. Persons with IBD were more likely to develop asthma or AR than controls after being diagnosed with IBD (hazard ratio for asthma, 1.31, 95% CI, 1.18-1.45; and hazard ratio for AR, 2.62, 95% CI, 2.45-2.80).

Conclusions

The association between asthma, AR, and IBD suggest the possibility that whatever triggers the onset of these atopic diseases may trigger the onset of IBD as well, and aeroallergens are plausible culprits.
The Dialectic of the International: Elaborating the Historical Materialism of the Gay Liberationists
Authors: Stoffel Alexander
Published: August 2022

What is the relation between sexuality and the international? The literature on sexuality within international studies demonstrates that a full appreciation of contemporary transformations of sexuality across the globe requires an interrogation of the divisions—West/non-West, North/South, or core/periphery—that characterize our view of the international. While many have studied how the transnational circulation of sexual discourses troubles such divisions, fewer have asked how they came about in the first place. Historical materialism is uniquely instructive in this regard. This methodology expounds the division of the international into distinct spheres as historically constituted and founded on capitalist social relations. Such a methodology can be found within the intellectual writings of the gay liberation movement. Through their fraught relationship with the Cuban government, which represented them as a cultural imperialist offensive against the newly formed Communist state, the gay liberationists developed a dialectical conception of the international that acknowledged the differential constitution of sexual life within specific contexts, yet sought to reveal the international systems of power that produce and regulate those seemingly distinct sexual formations across international divides. Gay liberationism, this article argues, offers us a rich tradition for developing accounts of sexuality within a stratified capitalist world order.
Pyrethroid Susceptibility in Field Populations of Picture-Winged Flies (Diptera: Ulidiidae) Infesting Fresh Market Sweet Corn in Florida
Authors: Schwan Resende Eric , Beuzelin Julien M , Dunkley Victoria E , Paula-Moraes Silvana V , Seal Dakshina R , Nuessly Gregg S
Published: August 2022

Picture-winged flies (Diptera: Ulidiidae) are the most damaging insect pests of sweet corn (Zea mays L.) produced in Florida for the fresh market. Management of these pests, referred to as corn silk flies, relies on frequent pyrethroid applications targeting adults. In response to the need for an insecticide resistance management (IRM) program for corn silk flies in this highly intensive crop system, glass vial bioassays were conducted to determine the susceptibility of 12 corn silk fly populations to the pyrethroid beta-cyfluthrin. Two Euxesta eluta Loew and nine Euxesta stigmatias Loew populations were obtained by collecting infested ears in commercial and experimental fields in 2020 and 2021. One E. eluta laboratory colony was used as a susceptible reference population. The E. eluta reference colony was the most susceptible population, with an LC50 value of 0.01 µg/vial. The E. stigmatias field populations were generally less susceptible to beta-cyfluthrin than the E. eluta field populations, with the highest LC50 values attaining 3.51 µg/vial and 0.19 µg/vial, respectively. In addition, the five E. stigmatias populations from commercial sweet corn fields were as much as 17.6 times less susceptible than the four E. stigmatias populations from nontreated fields. Results suggest that E. stigmatias is less susceptible to pyrethroids than E. eluta. Results also suggest that corn silk flies in commercial sweet corn fields are selected for reduced pyrethroid susceptibility throughout the growing season. This study successfully used the glass vial bioassay method for corn silk flies, providing a new tool to initiate an IRM program.
Observing EAGLE galaxies with JWST: predictions for Milky Way progenitors and their building blocks
Authors: Evans Tilly A , Fattahi Azadeh , Deason Alis J , Frenk Carlos S
Published: August 2022

We present predictions, derived from the EAGLE ΛCDM cosmological hydrodynamical simulations, for the abundance and properties of galaxies expected to be detected at high redshift by the James Webb Space Telescope (JWST). We consider the galaxy population as a whole and focus on the sub-population of progenitors of Milky Way (MW) analogues, defined to be galaxies with accretion histories similar to the MW’s, that is, galaxies that underwent a merger resembling the Gaia-Enceladus-Sausage (GES) event and that contain an analogue of the Large Magellanic Cloud (LMC) satellite today. We derive the luminosity function of all EAGLE galaxies in JWST/NIRCam passbands, in the redshift range z = 2 − 8, taking into account dust obscuration and different exposure times. For an exposure time of T = 105s, average MW progenitors are observable as far back as z ∼ 6 in most bands, and this changes to z ∼ 5 and z ∼ 4 for the GES and LMC progenitors, respectively. The progenitors of GES and LMC analogues are, on average, ∼2 and ∼1 mag fainter than the MW progenitors at most redshifts. They lie, on average, within ∼60 and 30 arcsec, respectively, of their future MW host at all times, and thus will appear within the field of view of JWST/NIRCam. We conclude that galaxies resembling the main progenitor of the MW and its major accreted components should be observable with JWST beyond redshift 2, providing a new and unique window in studying the formation history of our own galaxy.
SOFIA/HAWC+ observations of the Crab Nebula: dust properties from polarized emission
Authors: Chastenet Jérémy , De Looze Ilse , Hensley Brandon S , Vandenbroucke Bert , Barlow Mike J , Rho Jeonghee , Ravi Aravind P , Gomez Haley L , Kirchschlager Florian , Macías-Pérez Juan , Matsuura Mikako , Pattle Kate , Ponthieu Nicolas , Priestley Felix D , Relaño Monica , Ritacco Alessia , Wesson Roger
Published: August 2022

Supernova remnants (SNRs) are well-recognized dust producers, but their net dust production rate remains elusive due to uncertainties in grain properties that propagate into observed dust mass uncertainties, and determine how efficiently these grains are processed by reverse shocks. In this paper, we present a detection of polarized dust emission in the Crab pulsar wind nebula, the second SNR with confirmed polarized dust emission after Cassiopeia A. We constrain the bulk composition of the dust with new SOFIA/HAWC+ polarimetric data in band C 89 μm and band D 154 μm. After correcting for synchrotron polarization, we report dust polarization fractions ranging between 3.7–9.6 per cent and 2.7–7.6 per cent in three individual dusty filaments at 89 and 154 μm, respectively. The detected polarized signal suggests the presence of large (≳0.05–0.1 μm) grains in the Crab Nebula. With the observed polarization, and polarized and total fluxes, we constrain the temperatures and masses of carbonaceous and silicate grains. We find that the carbon-rich grain mass fraction varies between 12 and 70 per cent, demonstrating that carbonaceous and silicate grains co-exist in this SNR. Temperatures range from ∼40 to ∼70 K and from ∼30 to ∼50 K for carbonaceous and silicate grains, respectively. Dust masses range from ∼10−4 to ∼10−2 M⊙ for carbonaceous grains and to ∼10−1 M⊙ for silicate grains, in three individual regions.
Still at odds with conventional galaxy evolution: the star formation history of ultradiffuse galaxy Dragonfly 44
Authors: Webb Kristi A , Villaume Alexa , Laine Seppo , Romanowsky Aaron J , Balogh Michael , van Dokkum Pieter , Forbes Duncan A , Brodie Jean , Martin Christopher , Matuszewski Matt
Published: August 2022

We study the star formation history (SFH) of the ultradiffuse galaxy (UDG) Dragonfly 44 (DF44) based on the simultaneous fit to near-ultraviolet to near-infrared photometry and high signal-to-noise optical spectroscopy. In fitting the observations, we adopt an advanced physical model with a flexible SFH and discuss the results in the context of the degeneracies between stellar population parameters. Through reconstructing the mass-assembly history with a prior for extended star formation (SF) (akin to methods in the literature), we find that DF44 formed 90 per cent of its stellar mass by z ∼ 0.9 (∼7.2 Gyr ago). In comparison, using a prior that prefers concentrated SF (as informed by previous studies of DF44’s stellar populations) suggests that DF44 formed as early as z ∼ 8 (∼12.9 Gyr ago). Regardless of whether DF44 is old or very old, the SFHs imply early SF and rapid quenching. This result, together with DF44’s large size and evidence that it is on its first infall into the Coma cluster, challenges UDG formation scenarios from simulations that treat all UDGs as contiguous with the canonical dwarf population. While our results cannot confirm any particular formation scenario, we can conclude from this that DF44 experienced a rare quenching event.
The SAMI Galaxy Survey: Using concentrated star formation and stellar population ages to understand environmental quenching
Authors: Wang(王迪) Di , Croom Scott M , Bryant Julia J , Vaughan Sam P , Schaefer Adam L , D’Eugenio Francesco , Barsanti Stefania , Brough Sarah , Lagos Claudia del P , Medling Anne M , Oh Sree , van de Sande Jesse , Santucci Giulia , Bland-Hawthorn Joss , Goodwin Michael , Groves Brent , Lawrence Jon , Owers Matt S , Richards Samuel
Published: August 2022

We study environmental quenching using the spatial distribution of current star formation and stellar population ages with the full SAMI Galaxy Survey. By using a star formation concentration index [C-index, defined as log10(r50, H α/r50, cont)], we separate our sample into regular galaxies (C-index ≥−0.2) and galaxies with centrally concentrated star formation (SF-concentrated; C-index <−0.2). Concentrated star formation is a potential indicator of galaxies currently undergoing ‘outside-in’ quenching. Our environments cover ungrouped galaxies, low-mass groups (M200 ≤ 1012.5M⊙), high-mass groups (M200 in the range 1012.5–14 M⊙) and clusters (M200 > 1014M⊙). We find the fraction of SF-concentrated galaxies increases as halo mass increases by 9 ± 2 per cent, 8 ± 3 per cent, 19 ± 4 per cent, and 29 ± 4 per cent for ungrouped galaxies, low-mass groups, high-mass groups, and clusters, respectively. We interpret these results as evidence for ‘outside-in’ quenching in groups and clusters. To investigate the quenching time-scale in SF-concentrated galaxies, we calculate light-weighted age (AgeL) and mass-weighted age (AgeM) using full spectral fitting, as well as the Dn4000 and HδA indices. We assume that the average galaxy age radial profile before entering a group or cluster is similar to ungrouped regular galaxies. At large radius (1–2 Re), SF-concentrated galaxies in high-mass groups have older ages than ungrouped regular galaxies with an age difference of 1.83 ± 0.38 Gyr for AgeL and 1.34 ± 0.56 Gyr for AgeM. This suggests that while ‘outside-in’ quenching can be effective in groups, the process will not quickly quench the entire galaxy. In contrast, the ages at 1–2 Re of cluster SF-concentrated galaxies and ungrouped regular galaxies are consistent (difference of 0.19 ± 0.21 Gyr for AgeL, 0.40 ± 0.61 Gyr for AgeM), suggesting the quenching process must be rapid.
Simulations of astrometric planet detection in Alpha Centauri by intensity interferometry
Authors: Rai Km Nitu , Sarangi Subrata , Saha Prasenjit , Basak Soumen
Published: August 2022

Recent dynamical studies indicate that the possibility of an Earth-like planet around α Cen A or B should be taken seriously. Such a planet, if it exists, would perturb the orbital astrometry by $\lt {10}\, {\mu {\rm as}}$, which is 10−6 of the separation between the two stars. We assess the feasibility of detecting such perturbations using ground-based intensity interferometry. We simulate a dedicated set-up consisting of four 40-cm telescopes equipped with photon counters and correlators with a time resolution of $0.1\, \rm ns$, and a sort of matched filter implemented through an aperture mask. The astrometric error from one night of observing α Cen AB is $\approx 0.5\, \rm mas$. The error decreases if longer observing times and multiple spectral channels are used, as (channels × nights)−1/2.
The Genomic Basis of Evolutionary Novelties in a Leafhopper
Authors: Li Zheng , Li Yiyuan , Xue Allen Z , Dang Vy , Holmes V Renee , Johnston J Spencer , Barrick Jeffrey E , Moran Nancy A
Published: August 2022

Evolutionary innovations generate phenotypic and species diversity. Elucidating the genomic processes underlying such innovations is central to understanding biodiversity. In this study, we addressed the genomic basis of evolutionary novelties in the glassy-winged sharpshooter (Homalodisca vitripennis, GWSS), an agricultural pest. Prominent evolutionary innovations in leafhoppers include brochosomes, proteinaceous structures that are excreted and used to coat the body, and obligate symbiotic associations with two bacterial types that reside within cytoplasm of distinctive cell types. Using PacBio long-read sequencing and Dovetail Omni-C technology, we generated a chromosome-level genome assembly for the GWSS and then validated the assembly using flow cytometry and karyotyping. Additional transcriptomic and proteomic data were used to identify novel genes that underlie brochosome production. We found that brochosome-associated genes include novel gene families that have diversified through tandem duplications. We also identified the locations of genes involved in interactions with bacterial symbionts. Ancestors of the GWSS acquired bacterial genes through horizontal gene transfer (HGT), and these genes appear to contribute to symbiont support. Using a phylogenomics approach, we inferred HGT sources and timing. We found that some HGT events date to the common ancestor of the hemipteran suborder Auchenorrhyncha, representing some of the oldest known examples of HGT in animals. Overall, we show that evolutionary novelties in leafhoppers are generated by the combination of acquiring novel genes, produced both de novo and through tandem duplication, acquiring new symbiotic associations that enable use of novel diets and niches, and recruiting foreign genes to support symbionts and enhance herbivory.
Safety and efficacy of switching immunosuppressive drugs for maintenance treatment in patients with systemic lupus erythematosus: A retrospective cohort study
Authors: Ayano Masahiro , Kimoto Yasutaka , Mitoma Hiroki , Akahoshi Mitsuteru , Ono Nobuyuki , Arinobu Yojiro , Akashi Koichi , Horiuchi Takahiko , Niiro Hiroaki
Published: August 2022

Objectives

We aim to clarify the efficacy and safety of switching immunosuppressive drugs and to identify the predictive factors for treatment failure after switching in patients with systemic lupus erythematosus (SLE).

Methods

We retrospectively evaluated patients with SLE who switched immunosuppressive drugs for any reason in our hospital between 2015 and 2020. The efficacy endpoints were the change in SLE Disease Activity Index 2000 score, prednisolone dose, and disease status over 12 months, as well as treatment continuation rates. The safety endpoint was the frequency of adverse events over 1 year before and after switching. Cox hazard regression analyses were used to identify the predictive factors for treatment failure.

Results

Thirty-nine patients (age, 41.5 ± 12.6 years; 35 women and 4 men) were analysed. The SLE Disease Activity Index score and prednisolone dose were significantly reduced after switching, with few disease exacerbations over 12 months. The 1- and 2-year continuation rates were 71.4% and 62.3%, respectively. The frequency of adverse events was similar in the year before and after switching the drug. Drug switching due to inadequate efficacy was a predictive factor of less likely treatment failure.

Conclusions

Immunosuppressive drug switching led to reduced disease activity and decreased glucocorticoid dose without disease exacerbations and severe adverse events.
PRIESSTESS: interpretable, high-performing models of the sequence and structure preferences of RNA-binding proteins
Authors: Laverty Kaitlin U , Jolma Arttu , Pour Sara E , Zheng Hong , Ray Debashish , Morris Quaid , Hughes Timothy R
Published: August 2022

Modelling both primary sequence and secondary structure preferences for RNA binding proteins (RBPs) remains an ongoing challenge. Current models use varied RNA structure representations and can be difficult to interpret and evaluate. To address these issues, we present a universal RNA motif-finding/scanning strategy, termed PRIESSTESS (Predictive RBP-RNA InterpretablE Sequence-Structure moTif regrESSion), that can be applied to diverse RNA binding datasets. PRIESSTESS identifies dozens of enriched RNA sequence and/or structure motifs that are subsequently reduced to a set of core motifs by logistic regression with LASSO regularization. Importantly, these core motifs are easily visualized and interpreted, and provide a measure of RBP secondary structure specificity. We used PRIESSTESS to interrogate new HTR-SELEX data for 23 RBPs with diverse RNA binding modes and captured known primary sequence and secondary structure preferences for each. Moreover, when applying PRIESSTESS to 144 RBPs across 202 RNA binding datasets, 75% showed an RNA secondary structure preference but only 10% had a preference besides unpaired bases, suggesting that most RBPs simply recognize the accessibility of primary sequences.
Painters in chromatin: a unified quantitative framework to systematically characterize epigenome regulation and memory
Authors: Abdulla Amith Z , Vaillant Cédric , Jost Daniel
Published: August 2022

In eukaryotes, many stable and heritable phenotypes arise from the same DNA sequence, owing to epigenetic regulatory mechanisms relying on the molecular cooperativity of ‘reader–writer’ enzymes. In this work, we focus on the fundamental, generic mechanisms behind the epigenome memory encoded by post-translational modifications of histone tails. Based on experimental knowledge, we introduce a unified modeling framework, the painter model, describing the mechanistic interplay between sequence-specific recruitment of chromatin regulators, chromatin-state-specific reader–writer processes and long-range spreading mechanisms. A systematic analysis of the model building blocks highlights the crucial impact of tridimensional chromatin organization and state-specific recruitment of enzymes on the stability of epigenomic domains and on gene expression. In particular, we show that enhanced 3D compaction of the genome and enzyme limitation facilitate the formation of ultra-stable, confined chromatin domains. The model also captures how chromatin state dynamics impact the intrinsic transcriptional properties of the region, slower kinetics leading to noisier expression. We finally apply our framework to analyze experimental data, from the propagation of γH2AX around DNA breaks in human cells to the maintenance of heterochromatin in fission yeast, illustrating how the painter model can be used to extract quantitative information on epigenomic molecular processes.
Domain specific mutations in dyskerin disrupt 3′ end processing of scaRNA13
Authors: Nagpal Neha , Tai Albert K , Nandakumar Jayakrishnan , Agarwal Suneet
Published: August 2022

Mutations in DKC1 (encoding dyskerin) cause telomere diseases including dyskeratosis congenita (DC) by decreasing steady-state levels of TERC, the non-coding RNA component of telomerase. How DKC1 mutations variably impact numerous other snoRNAs remains unclear, which is a barrier to understanding disease mechanisms in DC beyond impaired telomere maintenance. Here, using DC patient iPSCs, we show that mutations in the dyskerin N-terminal extension domain (NTE) dysregulate scaRNA13. In iPSCs carrying the del37L NTE mutation or engineered to carry NTE mutations via CRISPR/Cas9, but not in those with C-terminal mutations, we found scaRNA13 transcripts with aberrant 3′ extensions, as seen when the exoribonuclease PARN is mutated in DC. Biogenesis of scaRNA13 was rescued by repair of the del37L DKC1 mutation by genome-editing, or genetic or pharmacological inactivation of the polymerase PAPD5, which counteracts PARN. Inspection of the human telomerase cryo-EM structure revealed that in addition to mediating intermolecular dyskerin interactions, the NTE interacts with terminal residues of the associated snoRNA, indicating a role for this domain in 3′ end definition. Our results provide mechanistic insights into the interplay of dyskerin and the PARN/PAPD5 axis in the biogenesis and accumulation of snoRNAs beyond TERC, broadening our understanding of ncRNA dysregulation in human diseases.
DNAffinity: a machine-learning approach to predict DNA binding affinities of transcription factors
Authors: Barissi Sandro , Sala Alba , Wieczór Miłosz , Battistini Federica , Orozco Modesto
Published: August 2022

We present a physics-based machine learning approach to predict in vitro transcription factor binding affinities from structural and mechanical DNA properties directly derived from atomistic molecular dynamics simulations. The method is able to predict affinities obtained with techniques as different as uPBM, gcPBM and HT-SELEX with an excellent performance, much better than existing algorithms. Due to its nature, the method can be extended to epigenetic variants, mismatches, mutations, or any non-coding nucleobases. When complemented with chromatin structure information, our in vitro trained method provides also good estimates of in vivo binding sites in yeast.
ADP-ribosylation of RNA in mammalian cells is mediated by TRPT1 and multiple PARPs
Authors: Weixler Lisa , Feijs Karla L H , Zaja Roko
Published: August 2022

RNA function relies heavily on posttranscriptional modifications. Recently, it was shown that certain PARPs and TRPT1 can ADP-ribosylate RNA in vitro. Traditionally, intracellular ADP-ribosylation has been considered mainly as a protein posttranslational modification. To date, it is not clear whether RNA ADP-ribosylation occurs in cells. Here we present evidence that different RNA species are ADP-ribosylated in human cells. The modification of cellular RNA is mediated by several transferases such as TRPT1, PARP10, PARP11, PARP12 and PARP15 and is counteracted by different hydrolases including TARG1, PARG and ARH3. In addition, diverse cellular stressors can modulate the content of ADP-ribosylated RNA in cells. We next investigated potential consequences of ADP-ribosylation for RNA and found that ADPr-capped mRNA is protected against XRN1 mediated degradation but is not translated. T4 RNA ligase 1 can ligate ADPr-RNA in absence of ATP, resulting in the incorporation of an abasic site. We thus provide the first evidence of RNA ADP-ribosylation in mammalian cells and postulate potential functions of this novel RNA modification.
Riboflavin intake and status and relationship to anemia
Authors: Aljaadi Abeer M , Devlin Angela M , Green Tim J
Published: August 2022

Riboflavin in its coenzyme forms, flavin mononucleotide and flavin adenine dinucleotide, is essential for multiple redox reactions necessary for energy production, antioxidant protection, and metabolism of other B vitamins, such as niacin, pyridoxine, and folate. Erythrocyte glutathione reductase activity coefficient (EGRac) is a biomarker of riboflavin status; ratios ≥1.40 are commonly interpreted as indicating biochemical deficiency. Most research on riboflavin status comes from low-income countries and rural settings, which reported high rates of riboflavin deficiency and inadequate intake. However, some studies suggest that riboflavin deficiency, based on the functional indicator EGRac, is also of concern in middle- and high-income countries. Biochemical riboflavin deficiency that does not cause clinical symptoms may contribute to anemia, particularly among women and children. Riboflavin enhances iron absorption, and riboflavin deficiency decreases iron mobilization from stores. The current knowledge on riboflavin’s role in metabolic processes and its biochemical status is summarized in this review, and the available evidence on the role of riboflavin in anemia among different populations is discussed.
Eastern Whip-poor-will abundance declines with urban land cover and increases with moth abundance in the American Midwest
Authors: Souza-Cole Ian , Ward Michael P , Mau Rebecca L , Foster Jeffrey T , Benson Thomas J
Published: August 2022

Populations of avian aerial insectivores have declined across North America. A leading factor hypothesized to be driving these trends is a decline in prey populations, although a loss of suitable habitat on the landscape or other factors may also play a role. The Eastern Whip-poor-will (Antrostomus vociferus; hereafter: whip-poor-will) is an aerial insectivorous nightjar that has disappeared from many of its historic breeding locations. We investigated the role that food availability and land cover at multiple scales play in whip-poor-will distribution by estimating their abundance at 23 sites across central Illinois. To do this, we conducted nocturnal point counts to estimate whip-poor-will abundance and collected nocturnal insects using UV-light traps at these sites to quantify potential food abundance. Additionally, we described whip-poor-will diet using DNA metabarcoding of fecal samples. We found that the number of large moths at a site had a positive effect on the abundance of whip-poor-wills, aligning with our diet analysis which identified moths as the primary prey item for this species (present in 92% of samples). Whip-poor-wills also showed an affinity for forest edges, but only when edges were associated with high moth abundances. Conversely, developed land-cover in landscapes surrounding sites led to decreased whip-poor-will abundance. Given the continued expansion of developed areas, coupled with concerning trends in moth populations, declines in the abundance of this species may continue. Efforts should be made to protect and sustain moth populations and the impacts of development should be scrutinized in the pursuit of conserving whip-poor-wills.
Updating splits, lumps, and shuffles: Reconciling GenBank names with standardized avian taxonomies
Authors: Hosner Peter A , Zhao Min , Kimball Rebecca T , Braun Edward L , Burleigh J Gordon
Published: August 2022

Biodiversity research has advanced by testing expectations of ecological and evolutionary hypotheses through the linking of large-scale genetic, distributional, and trait datasets. The rise of molecular systematics over the past 30 years has resulted in a wealth of DNA sequences from around the globe. Yet, advances in molecular systematics also have created taxonomic instability, as new estimates of evolutionary relationships and interpretations of species limits have required widespread scientific name changes. Taxonomic instability, colloquially “splits, lumps, and shuffles,” presents logistical challenges to large-scale biodiversity research because (1) the same species or sets of populations may be listed under different names in different data sources, or (2) the same name may apply to different sets of populations representing different taxonomic concepts. Consequently, distributional and trait data are often difficult to link directly to primary DNA sequence data without extensive and time-consuming curation. Here, we present RANT: Reconciliation of Avian NCBI Taxonomy. RANT applies taxonomic reconciliation to standardize avian taxon names in use in NCBI GenBank, a primary source of genetic data, to a widely used and regularly updated avian taxonomy: eBird/Clements. Of 14,341 avian species/subspecies names in GenBank, 11,031 directly matched an eBird/Clements; these link to more than 6 million nucleotide sequences. For the remaining unmatched avian names in GenBank, we used Avibase’s system of taxonomic concepts, taxonomic descriptions in Cornell’s Birds of the World, and DNA sequence metadata to identify corresponding eBird/Clements names. Reconciled names linked to more than 600,000 nucleotide sequences, ~9% of all avian sequences on GenBank. Nearly 10% of eBird/Clements names had nucleotide sequences listed under 2 or more GenBank names. Our taxonomic reconciliation is a first step towards rigorous and open-source curation of avian GenBank sequences and is available at GitHub, where it can be updated to correspond to future annual eBird/Clements taxonomic updates.
Seven finance and trade lessons from Covid-19 for future pandemics
Authors: Agarwal Ruchir , Gopinath Gita
Published: August 2022

Pandemics and epidemics pose systemic risks to lives, societies, and to global economic security—and their frequency is expected to increase as rising trade and increased human interaction with animals leads to the emergence of new diseases. The Covid-19 pandemic teaches us that we can and must be better prepared, with scope for much greater global coordination to address the financing, supply-chain, and trade barriers that amplified the pandemic’s economic costs and contributed to the emergence of new variants. This paper draws seven early lessons from the Covid-19 pandemic that could inform future policy priorities and help shape a better global response to future crises.
From Evolution to Revolution: Accelerating Crop Domestication through Genome Editing
Authors: Kumar Kishor , Mandal Swarupa Nanda , Pradhan Bhubaneswar , Kaur Pavneet , Kaur Karminderbir , Neelam Kumari
Published: August 2022

Crop domestication has a tremendous impact on socioeconomic conditions and human civilization. Modern cultivars were domesticated from their wild progenitors thousands of years ago by the selection of natural variation by humans. New cultivars are being developed by crossing two or more compatible individuals. But the limited genetic diversity in the cultivars severely affects the yield and renders the crop susceptible to many biotic and abiotic stresses. Crop wild relatives (CWRs) are the rich reservoir for many valuable agronomic traits. The incorporation of useful genes from CWR is one of the sustainable approaches for enriching the gene pool of cultivated crops. However, CWRs are not suited for urban and intensive cultivation because of several undesirable traits. Researchers have begun to study the domestication traits in the CWRs and modify them using genome-editing tools to make them suitable for extensive cultivation. Growing evidence has shown that modification in these genes is not sufficient to bring the desired change in the neodomesticated crop. However, the other dynamic genetic factors such as microRNAs (miRNAs), transposable elements, cis-regulatory elements and epigenetic changes have reshaped the domesticated crops. The creation of allelic series for many valuable domestication traits through genome editing holds great potential for the accelerated development of neodomesticated crops. The present review describes the current understanding of the genetics of domestication traits that are responsible for the agricultural revolution. The targeted mutagenesis in these domestication genes via clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 could be used for the rapid domestication of CWRs.
The cutin polymer matrix undergoes a fine architectural tuning from early tomato fruit development to ripening
Authors: Reynoud Nicolas , Geneix Nathalie , Petit Johann , D’Orlando Angelina , Fanuel Mathieu , Marion Didier , Rothan Christophe , Lahaye Marc , Bakan Bénédicte
Published: August 2022

The cuticle is a complex polymer matrix that protects all aerial organs of plants, fulfills multiple roles in plant–environment interactions, and is critical for plant development. These functions are associated with the structural features of cuticles, and the architectural modeling of cuticles during plant development is crucial for understanding their physical properties and biological functions. In this work, the in-depth architecture of the cutin polymer matrix during fruit development was investigated. Using cherry tomato fruit (Solanum lycopersicum) as a model from the beginning of the cell expansion phase to the red ripe stage, we designed an experimental scheme combining sample pretreatment, Raman mapping, multivariate data analyses, and biochemical analyses. These approaches revealed clear chemical areas with different contributions of cutin, polysaccharides, and phenolics within the cutin polymer matrix. Besides, we demonstrated that these areas are finely tuned during fruit development, including compositional and macromolecular rearrangements. The specific spatiotemporal accumulation of phenolic compounds (p-coumaric acid and flavonoids) suggests that they fulfill distinct functions during fruit development. In addition, we highlighted an unexpected dynamic remodeling of the cutin-embedded polysaccharides pectin, cellulose, and hemicellulose. Such structural tuning enables consistent adaption of the cutin-polysaccharide continuum and the functional performance of the fruit cuticle at the different developmental stages. This study provides insights into the plant cuticle architecture and in particular into the organization of the epidermal cell wall-cuticle.
Skeletal muscle releases extracellular vesicles with distinct protein and microRNA signatures that function in the muscle microenvironment
Authors: Watanabe Sho , Sudo Yuri , Makino Takumi , Kimura Satoshi , Tomita Kenji , Noguchi Makoto , Sakurai Hidetoshi , Shimizu Makoto , Takahashi Yu , Sato Ryuichiro , Yamauchi Yoshio
Published: August 2022

Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and are present in the blood, their identity is poorly characterized in vivo, limiting the identification of their origin in the blood. Since skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined markers that distinguish skeletal muscle-derived EVs (SkM-EVs) from others, whether skeletal muscle releases EVs in vivo and how much SkM-EVs account for plasma EVs remain poorly understood. In this work, we perform quantitative proteomic analyses on EVs released from C2C12 cells and human iPS cell-derived myocytes and identify potential marker proteins that mark SkM-EVs. These markers we identified apply to in vivo tracking of SkM-EVs. The results show that skeletal muscle makes only a subtle contribution to plasma EVs as their source in both control and exercise conditions in mice. On the other hand, we demonstrate that SkM-EVs are concentrated in the skeletal muscle interstitium. Furthermore, we show that interstitium EVs are highly enriched with the muscle-specific miRNAs and repress the expression of the paired box transcription factor Pax7, a master regulator for myogenesis. Taken together, our findings confirm previous studies showing that skeletal muscle cells release exosome-like EVs with specific protein and miRNA profiles in vivo and suggest that SkM-EVs mainly play a role within the muscle microenvironment where they accumulate.
Kaon–baryon coupling schemes and kaon condensation in hyperon-mixed matter
Authors: Muto Takumi , Maruyama Toshiki , Tatsumi Toshitaka
Published: August 2022

The possible coexistence of kaon condensation and hyperons in highly dense matter [the (Y + K) phase] is investigated on the basis of the relativistic mean-field theory combined with the effective chiral Lagrangian. Two coupling schemes for the s-wave kaon–baryon interaction are compared regarding the onset density of kaon condensation in hyperon-mixed matter and the equation of state for the developed (Y + K) phase. One is the contact interaction scheme related to the nonlinear effective chiral Lagrangian. The other is the meson exchange scheme, where the interaction vertices between the kaon field and baryons are described by an exchange of mesons (σ, σ* mesons for scalar coupling, and ω, ρ, ϕ mesons for vector coupling). It is shown that in the meson exchange scheme, the contribution from the nonlinear scalar self-interaction gives rise to a repulsive effect for the kaon effective energy, pushing up the onset density of kaon condensation as compared with the contact interaction scheme. In general, the difference in kaon–baryon dynamics between the contact interaction scheme and the meson exchange scheme relies on the specific forms of the nonlinear self-interacting meson terms. They generate many-baryon forces through the equations of motion for the meson mean fields. However, they should have a definite effect on the ground state properties of nuclear matter only around the saturation density. It is shown that the nonlinear self-interacting term is not relevant to repulsive energy leading to stiffening of the equation of state at high densities, and that it cannot be compensated with a large attractive energy due to the appearance of the (Y + K) phase in the case of the contact interaction scheme. We also discuss what effects are necessary in the contact interaction scheme to make the equation of state with (Y + K) phase stiff enough to be consistent with recent observations of massive neutron stars.