bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome Assembly and Population Sequencing Reveal Three Populations and Signatures of Insecticide Resistance ofTuta absolutain Latin America
Authors: Lewald Kyle M , Tabuloc Christine A , Godfrey Kristine E , Arnó Judit , Perini Clérison R , Guedes Jerson C , Chiu Joanna C
Published: April 2023

Tuta absoluta is one of the largest threats to tomato agriculture worldwide. Native to South America, it has rapidly spread throughout Europe, Africa, and Asia over the past two decades. To understand how T. absoluta has been so successful and to improve containment strategies, high-quality genomic resources and an understanding of population history are critical. Here, we describe a highly contiguous annotated genome assembly, as well as a genome-wide population analysis of samples collected across Latin America. The new genome assembly has an L50 of 17 with only 132 contigs. Based on hundreds of thousands of single nucleotide polymorphisms, we detect three major population clusters in Latin America with some evidence of admixture along the Andes Mountain range. Based on coalescent simulations, we find these clusters diverged from each other tens of thousands of generations ago prior to domestication of tomatoes. We further identify several genomic loci with patterns consistent with positive selection and that are related to insecticide resistance, immunity, and metabolism. This data will further future research toward genetic control strategies and inform future containment policies.
Correlated stabilizing selection shapes the topology of gene regulatory networks
Authors: Petit Apolline J R , Guez Jeremy , Le Rouzic Arnaud
Published: April 2023

The evolution of gene expression is constrained by the topology of gene regulatory networks, as co-expressed genes are likely to have their expressions affected together by mutations. Conversely, co-expression can also be an advantage when genes are under joint selection. Here, we assessed theoretically whether correlated selection (selection for a combination of traits) was able to affect the pattern of correlated gene expressions and the underlying gene regulatory networks. We ran individual-based simulations, applying a stabilizing correlated fitness function to three genetic architectures: a quantitative genetics (multilinear) model featuring epistasis and pleiotropy, a quantitative genetics model where each genes has an independent mutational structure, and a gene regulatory network model, mimicking the mechanisms of gene expression regulation. Simulations showed that correlated mutational effects evolved in the three genetic architectures as a response to correlated selection, but the response in gene networks was specific. The intensity of gene co-expression was mostly explained by the regulatory distance between genes (largest correlations being associated to genes directly interacting with each other), and the sign of co-expression was associated with the nature of the regulation (transcription activation or inhibition). These results concur to the idea that gene network topologies could partly reflect past selection patterns on gene expression.
International Standards for Dementia Workforce Education and Training: A Scoping Review
Authors: Pit Sabrina Winona , Horstmanshof Louise , Moehead Anne , Hayes Oliver , Schache Valerie , Parkinson Lynne
Published: April 2023

Background and Objectives

The increasing number of people with dementia requires transparency and quality dementia education, training, and care. This scoping review aimed to determine the key elements of national or state-wide standards on dementia education and training that could underpin the development of international standards for dementia workforce training and education.

Research Design and Methods

The English-language peer-reviewed and gray literature were searched (2010–20). Key search domains were training, workforce, standards/frameworks, and dementia.

Results

Thirteen standards were identified from the United Kingdom (n = 5), the United States (n = 4), Australia (n = 3), and Ireland (n = 1). Most standards focused on training health care professionals with some including people in customer-centric settings, people living with dementia, and informal carers or the general community. Seventeen training topics were identified in 10 or more of the 13 standards. Cultural safety, rural issues, health care professional self-care, digital literacy, and health promotion topics were less commonly reported. The barriers to standards implementation were lack of organizational support, lack of access to relevant training, low staff literacy, lack of funding, high staff turnover, ineffective past program cycles, and inconsistent service delivery. Enablers included a strong implementation plan, funding, strength of partnerships, and building on previous work.

Discussion and Implications

The U.K. Dementia Skills and Core Training Standard, the Irish Department of Health Dementia Together, and the National Health Services Scotland Standard are the recommended strongest standards for underpinning the development of international standards. It is essential that training standards are tailored to the needs of the consumer, worker, and regions.
Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice
Authors: Hua Juan , Xu Bo , Liu Wenjing , Shi JingTian , Jiang Hui , Zha XiaoJun , Zhang Xiansheng , Wan Yangyang
Published: April 2023

Several different mutations in the proteome of centriole 1 centriolar protein B (POC1B) have been linked to cone dystrophy or cone-rod dystrophy (CORD). However, mutations in POC1B that are associated with both CORD and oligoasthenoteratozoospermia (OAT) have not been reported previously. Here, whole-exome sequencing was performed to identify a homozygous frameshift variant (c.151delG) in POC1B in the two brothers who had been diagnosed with both CORD and OAT from a consanguineous family. Transcript and protein analyses of biological samples from the two patients carrying the variant showed that POC1B protein is lost in sperm cells. The system CRISPR/Cas9 was utilized to create poc1bc.151delG/c.151delG knock-in (KI) mice. Notably, poc1bc.151delG/c.151delG KI male mice presented with OAT phenotype. Additionally, testicular histology and transmission electron microscopy analysis of the testes and sperm indicated that Poc1b mutation results in abnormal formation of acrosomes and flagella. Collectively, according to our experimental data on human volunteers and animal models, biallelic mutations in POC1B can cause OAT and CORD in mice and humans.
Drought stress triggers alterations of adaxial and abaxial stomatal development in basil leaves increasing water-use efficiency
Authors: Driesen Elisa , De Proft Maurice , Saeys Wouter
Published: April 2023

The physiological control of stomatal opening by which plants adjust for water availability has been extensively researched. However, the impact of water availability on stomatal development has not received as much attention, especially for amphistomatic plants. Therefore, the acclimation of stomatal development in basil (Ocimum basilicum L.) leaves was investigated. Our results show that leaves developed under water-deficit conditions possess higher stomatal densities and decreased stomatal length for both the adaxial and abaxial leaf sides. Although the stomatal developmental reaction to water deficit was similar for the two leaf surfaces, it was proven that adaxial stomata are more sensitive to water stress than abaxial stomata, with more closed adaxial stomata under water-deficit conditions. Furthermore, plants with leaves containing smaller stomata at higher densities possessed a higher water use efficiency. Our findings highlight the importance of stomatal development as a tool for long-term acclimation to limit water loss, with minimal reduction in biomass production. This highlights the central role that stomata play in both the short (opening) and long-term (development) reaction of plants to water availability, making them key tools for efficient resource use and anticipation of future environmental changes.
Association of gallstone disease with risk of colorectal cancer: a systematic review and meta-analysis of observational studies
Authors: Polychronidis Georgios , Siddiqi Haziq , Ali Ahmed Fasih , Papatheodorou Stefania , Giovannucci Edward L , Song Mingyang
Published: April 2023

Background

Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed.

Objective

To systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex.

Methods

PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs.

Results

The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies [RR = 1.61 (1.29; 2.01)], whereas a more modest association was found in population-based case-control and cohort studies [RR = 1.10 (1.02; 1.19)]. Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women [RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44)]. When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer [RR = 1.16 (1.07; 1.26)] but not distal colon cancer [RR = 0.99 (0.96; 1.03)] or rectal cancer [RR = 0.94 (0.89; 1.00)].

Conclusions

Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.
The Effect of Pollen Diet Composition and Quantity on Diapause Survival and Performance in an Annual Pollinator (Bombus Impatiens)
Authors: Treanore E D , Ramos-Medero A V , Garcia J , Amsalem E
Published: April 2023

Synopsis

Most pollination services are provided by annual bees that go through a winter diapause, during which they are exposed to extreme temperatures, pathogens, and starvation. The ability of bees to successfully face these stressors during diapause and subsequently initiate a nest depends on their overall nutritional state and an adequate preparatory diet.

Here, we used queens of the common eastern bumble bee, Bombus impatiens, to examine how pollen diets varying in their protein to lipid ratio and total nutrient amounts affected queen performance during and after diapause. We compared diapause survival and reproductive performance post-diapause across different diets and found that queen survival was highest when pollen had a nutritional ratio of approximately 5:1 (protein to lipid). This diet is significantly enriched in proteins compared to the pollen fed to bumble bees in the lab (1:1) or commonly available in agricultural landscapes. Altering the quantity of macronutrients within this ratio did not improve survival or performance. Our results emphasize the importance of adequate nutrition for diapause performance in bees with annual life cycles and the importance of providing annual bees with floral provisioning based on their individual nutritional targets.
Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients
Authors: An Guohua , Creech C Buddy , Wu Nan , Nation Roger L , Gu Kenan , Nalbant Demet , Jimenez-Truque Natalia , Fissell William , Patel Pratish C , Fishbane Nicholas , Watanabe Amy , Rolsma Stephanie , Kirkpatrick Carl M J , Landersdorfer Cornelia B , Winokur Patricia
Published: April 2023

Objectives

We aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients by utilizing population pharmacokinetics and target attainment analysis.

Patients and methods

A prospective and opportunistic pharmacokinetic (PK) study was conducted in 130 critically ill patients in two ICU sites. The plasma concentrations of cefepime were determined using a validated LC-MS/MS method. All cefepime PK data were analysed simultaneously using the non-linear mixed-effects modelling approach. Monte Carlo simulations were performed to evaluate the PTA of cefepime at different MIC values following different dose regimens in subjects with different renal functions.

Results

The PK of cefepime in critically ill patients was best characterized by a two-compartment model with zero-order input and first-order elimination. Creatinine clearance and body weight were identified to be significant covariates. Our simulation results showed that prolonged 3 h infusion does not provide significant improvement on target attainment compared with the traditional intermittent 0.5 h infusion. In contrast, for a given daily dose continuous infusion provided much higher breakpoint coverage than either 0.5 h or 3 h intermittent infusions. To balance the target attainment and potential neurotoxicity, cefepime 3 g/day continuous infusion appears to be a better dosing regimen than 6 g/day continuous infusion.

Conclusions

Continuous infusion may represent a promising strategy for cefepime treatment in critically ill patients. With the availability of institution- and/or unit-specific cefepime susceptibility patterns as well as individual patients’ renal function, our PTA results may represent useful references for physicians to make dosing decisions.
Selective extinction at the end-Cretaceous and appearance of the modern Decapoda
Authors: Schweitzer Carrie E , Feldmann Rodney M
Published: April 2023

Extinction and origination of genera and families of marine Decapoda at the end of the Cretaceous established the modern fauna. Podotrematous crabs suffered high extinction levels, whereas heterotrematous crabs experienced both extinction and radiation. Anomuran decapods exhibited high extinction levels at the generic but not family level. In general, family extinctions predominantly occurred among podotrematous and heterotrematous crabs, which also exhibit overall shorter family ranges. Possible refugia promoted survival of genera and families into the Paleocene, whereas habitation of the Western Interior Seaway ensured high levels of extinction. Areas proximal to the Chicxulub impact site experienced moderate levels of extinction. Habitat specialists preferentially survived the end-Cretaceous extinction in some clades. Heterotrematous crabs recovered rapidly in the Paleocene, especially in the siliciclastic environments of the Americas. Because decapod crustaceans are highly variable in morphology, habitat, and ecology, no one pattern of extinction and recovery can explain the end-Cretaceous decapod extinction event. Rather, a mosaic of responses in various decapod groups led to their differential survival.
Consumer-Driven Memorialization
Authors: Anderson Stephanie , Hamilton Kathy
Published: April 2023

Consumer research has focused on market-mediated efforts to memorialize the past, but this overshadows the issues that arise when consumers, as nonprofessionals, make the past consumable. Consumer-driven memorialization is defined as consumer engagement with traces of the past in memoryscapes of low market-mediation that creates a complex interplay of remembering and forgetting. Based on an ethnographic study of urban exploration, we theorize that consumer-driven memorialization comprises two practices of tracing and trace-making. Tracing involves consumer attempts to recover traces of the past, while trace-making involves consumer attempts to create traces for the future. Consumers enact multiple roles during consumer-driven memorialization: explorers experience the past, archaeologists materialize the past, artists aestheticize the past, and historians narrate the past. The theorization of consumer-driven memorialization offers three contributions. First, the dimensions of consumer-driven memorialization broaden understanding of what constitutes a consumable past in contexts of low market-mediation. Second, we explain how the ideological and material challenges that emerge in consumer-driven memorialization generate a complex interplay between remembering and forgetting. Third, we shed light on how consumer-driven memorialization is inscribed in space.
Jamestown Canyon virus (Bunyavirales: Peribunyaviridae) vector ecology in a focus of human transmission in New Hampshire, USA
Authors: Poggi Joseph D , Conery Colin , Mathewson Abigail , Bolton Denise , Lovell Rebecca , Harrington Laura C , Notarangelo Marco
Published: April 2023

Jamestown Canyon virus disease (JCVD) is a potentially neuroinvasive condition caused by the arbovirus Jamestown Canyon virus (JCV). Human cases of JCVD have increased in New Hampshire (NH) over the past decade, but vector surveillance is limited by funding and person power. We conducted mosquito surveillance with a focus on human JCVD cases south central NH during 2021. Routine surveillance with CDC miniature traps baited with CO2 (lights removed) was supplemented by a paired trapping design to test the collection efficiency of octenol, and New Jersey light traps. We performed virus testing, blood meal analysis, and compared morphological identification with DNA barcoding. Over 50,000 mosquitoes were collected representing 28 species. Twelve JCV-positive pools were derived from 6 species of more than 1,600 pools tested. Of those, Aedes excrucians/stimulans (MLE 4.95, Diptera: Culicidae, Walker, 1856, 1848), and Aedes sticticus (MLE 2.02, Meigen, 1838) had the highest JCV infection rates, and Aedes canadensis (MLE 0.13, Theobold, 1901) and Coquillettidia perturbans (0.10, Diptera: Culicidae, Walker, 1856) had the lowest infection rates. One hundred and fifty-one blood meals were matched to a vertebrate host. All putative vectors fed on the amplifying host of JCV, white-tailed deer (36–100% of bloodmeals). Putative vectors that fed on human hosts included Aedes excrucians (8%), Anopheles punctipennis (25%, Diptera: Culicidae, Say, 1823), and Coquillettidia perturbans (51%). CDC traps baited with CO2 were effective for collecting putative vectors. DNA barcoding enhanced morphological identifications of damaged specimens. We present the first ecological overview of JCV vectors in NH.
Gray-Level Co-occurrence Matrix Analysis of Nuclear Textural Patterns in Laryngeal Squamous Cell Carcinoma: Focus on Artificial Intelligence Methods
Authors: Valjarevic Svetlana , Jovanovic Milan B , Miladinovic Nenad , Cumic Jelena , Dugalic Stefan , Corridon Peter R , Pantic Igor
Published: April 2023

Gray-level co-occurrence matrix (GLCM) and discrete wavelet transform (DWT) analyses are two contemporary computational methods that can identify discrete changes in cell and tissue textural features. Previous research has indicated that these methods may be applicable in the pathology for identification and classification of various types of cancers. In this study, we present findings that squamous epithelial cells in laryngeal carcinoma, which appear morphologically intact during conventional pathohistological evaluation, have distinct nuclear GLCM and DWT features. The average values of nuclear GLCM indicators of these cells, such as angular second moment, inverse difference moment, and textural contrast, substantially differ when compared to those in noncancerous tissue. In this work, we also propose machine learning models based on random forests and support vector machine that can be successfully trained to separate the cells using GLCM and DWT quantifiers as input data. We show that, based on a limited cell sample, these models have relatively good classification accuracy and discriminatory power, which makes them suitable candidates for future development of AI-based sensors potentially applicable in laryngeal carcinoma diagnostic protocols.
Defining the relationship between phylogeny, clinical manifestation, and phenotype for Trichophyton mentagrophytes/interdigitale complex; a literature review and taxonomic recommendations
Authors: Švarcová Michaela , Větrovský Tomáš , Kolařík Miroslav , Hubka Vit
Published: April 2023

This study looked for correlations between molecular identification, clinical manifestation, and morphology for Trichophyton interdigitale and Trichophyton mentagrophytes. For this purpose, a total of 110 isolates were obtained from Czech patients with various clinical manifestations of dermatophytosis. Phenotypic characters were analyzed, and the strains were characterized using multilocus sequence typing. Among the 12 measured/scored phenotypic features, statistically significant differences were found only in growth rates at 37 °C and in the production of spiral hyphae, but none of these features is diagnostic. Correlations were found between T. interdigitale and higher age of patients and between clinical manifestations such as tinea pedis or onychomychosis. The MLST approach showed that internal transcribed spacer (ITS) genotyping of T. mentagrophytes isolates has limited practical benefits because of extensive gene flow between sublineages. Based on our results and previous studies, there are few taxonomic arguments for preserving both species names. The species show a lack of monophyly and unique morphology. On the other hand, some genotypes are associated with predominant clinical manifestations and sources of infections, which keep those names alive. This practice is questionable because the use of both names confuses identification, leading to difficulty in comparing epidemiological studies. The current identification method using ITS genotyping is ambiguous for some isolates and is not user-friendly. Additionally, identification tools such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry fail to distinguish these species. To avoid further confusion and to simplify identification in practice, we recommend using the name T. mentagrophytes for the entire complex. When clear differentiation of populations corresponding to T. interdigitale and Trichophyton indotineae is possible based on molecular data, we recommend optionally using a variety rank: T. mentagrophytes var. interdigitale and T. mentagrophytes var. indotineae.
Carbon monoxide emission lines reveal an inverted atmosphere in the ultra hot Jupiter WASP-33 b consistent with an eastward hot spot
Authors: van Sluijs Lennart , Birkby Jayne L , Lothringer Joshua , Lee Elspeth K H , Crossfield Ian J M , Parmentier Vivien , Brogi Matteo , Kulesa Craig , McCarthy Don , Charbonneau David
Published: April 2023

We report the first detection of CO emission at high spectral resolution in the day-side infrared thermal spectrum of an exoplanet. These emission lines, found in the atmosphere of the transiting ultra hot Jupiter (UHJ) WASP-33 b, provide unambiguous evidence of its thermal inversion. Using spectra from the MMT Exoplanet Atmosphere Survey (MEASURE, R ∼ 15 000), covering pre- and post-eclipse phases, we cross-correlate with 1D PHOENIX spectral templates to detect CO at S/N = 7.9 ($v_{\rm {sys}}=0.15^{+0.64}_{-0.65}$ km s−1, $K_{\rm {p}}=229.5^{+1.1}_{-1.0}$ km s−1). Moreover, using cross-correlation-to-log-likelihood mapping, we find that the scaling parameter which controls the spectral line contrast changes with phase. We thus use the general circulation model SPARC/MITgcm post-processed by the 3D gCMCRT radiative transfer code to interpret this variation, finding it consistent with an eastward-shifted hot spot. Pre-eclipse, when the hot spot faces Earth, the thermal profiles are shallower leading to smaller line contrast despite greater overall flux. Post-eclipse, the western part of the day-side faces Earth and has much steeper thermal profiles, leading to larger line contrast despite less overall flux. This demonstrates that within the log-likelihood framework, even relatively moderate resolution spectra can be used to understand the 3D nature of close-in exoplanets, and that resolution can be traded for photon-collecting power when the induced Doppler-shift is sufficiently large. We highlight CO as a good probe of UHJ thermal structure and dynamics that does not suffer from stellar activity, unlike species that are also present in the host star e.g. iron lines.
A novel role of TRIM28 B box domain in L1 retrotransposition and ORF2p-mediated cDNA synthesis
Authors: Du Qianhui , Stow Emily C , LaCoste Dawn , Freeman Benjamin , Baddoo Melody , Shareef Afzaal M , Miller Kyle M , Belancio Victoria P
Published: April 2023

The long interspersed element 1 (LINE-1 or L1) integration is affected by many cellular factors through various mechanisms. Some of these factors are required for L1 amplification, while others either suppress or enhance specific steps during L1 propagation. Previously, TRIM28 has been identified to suppress transposable elements, including L1 expression via its canonical role in chromatin remodeling. Here, we report that TRIM28 through its B box domain increases L1 retrotransposition and facilitates shorter cDNA and L1 insert generation in cultured cells. Consistent with the latter, we observe that tumor specific L1 inserts are shorter in endometrial, ovarian, and prostate tumors with higher TRIM28 mRNA expression than in those with lower TRIM28 expression. We determine that three amino acids in the B box domain that are involved in TRIM28 multimerization are critical for its effect on both L1 retrotransposition and cDNA synthesis. We provide evidence that B boxes from the other two members in the Class VI TRIM proteins, TRIM24 and TRIM33, also increase L1 retrotransposition. Our findings could lead to a better understanding of the host/L1 evolutionary arms race in the germline and their interplay during tumorigenesis.
RecA and SSB genome-wide distribution in ssDNA gaps and ends in Escherichia coli
Authors: Pham Phuong , Wood Elizabeth A , Cox Michael M , Goodman Myron F
Published: April 2023

Single-stranded DNA (ssDNA) gapped regions are common intermediates in DNA transactions. Using a new non-denaturing bisulfite treatment combined with ChIP-seq, abbreviated ‘ssGap-seq’, we explore RecA and SSB binding to ssDNA on a genomic scale in E. coli in a wide range of genetic backgrounds. Some results are expected. During log phase growth, RecA and SSB assembly profiles coincide globally, concentrated on the lagging strand and enhanced after UV irradiation. Unexpected results also abound. Near the terminus, RecA binding is favored over SSB, binding patterns change in the absence of RecG, and the absence of XerD results in massive RecA assembly. RecA may substitute for the absence of XerCD to resolve chromosome dimers. A RecA loading pathway may exist that is independent of RecBCD and RecFOR. Two prominent and focused peaks of RecA binding revealed a pair of 222 bp and GC-rich repeats, equidistant from dif and flanking the Ter domain. The repeats, here named RRS for replication risk sequence, trigger a genomically programmed generation of post-replication gaps that may play a special role in relieving topological stress during replication termination and chromosome segregation. As demonstrated here, ssGap-seq provides a new window on previously inaccessible aspects of ssDNA metabolism.
PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription
Authors: Mayayo-Peralta Isabel , Gregoricchio Sebastian , Schuurman Karianne , Yavuz Selçuk , Zaalberg Anniek , Kojic Aleksandar , Abbott Nina , Geverts Bart , Beerthuijzen Suzanne , Siefert Joseph , Severson Tesa M , van Baalen Martijn , Hoekman Liesbeth , Lieftink Cor , Altelaar Maarten , Beijersbergen Roderick L , Houtsmuller Adriaan B , Prekovic Stefan , Zwart Wilbert
Published: April 2023

How steroid hormone receptors (SHRs) regulate transcriptional activity remains partly understood. Upon activation, SHRs bind the genome together with a co-regulator repertoire, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited co-regulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we functionally dissected the Glucocorticoid Receptor (GR) complex. We describe a functional cross-talk between PAXIP1 and the cohesin subunit STAG2, critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on chromatin, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. In lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.
Selective translational control of cellular and viral mRNAs by RPS3 mRNA binding
Authors: Havkin-Solomon Tal , Itzhaki Elad , Joffe Nir , Reuven Nina , Shaul Yosef , Dikstein Rivka
Published: April 2023

RPS3, a universal core component of the 40S ribosomal subunit, interacts with mRNA at the entry channel. Whether RPS3 mRNA-binding contributes to specific mRNA translation and ribosome specialization in mammalian cells is unknown. Here we mutated RPS3 mRNA-contacting residues R116, R146 and K148 and report their impact on cellular and viral translation. R116D weakened cap-proximal initiation and promoted leaky scanning, while R146D had the opposite effect. Additionally, R146D and K148D displayed contrasting effects on start-codon fidelity. Translatome analysis uncovered common differentially translated genes of which the downregulated set bears long 5’UTR and weak AUG context, suggesting a stabilizing role during scanning and AUG selection. We identified an RPS3-dependent regulatory sequence (RPS3RS) in the sub-genomic 5’UTR of SARS-CoV-2 consisting of a CUG initiation codon and a downstream element that is also the viral transcription regulatory sequence (TRS). Furthermore, RPS3 mRNA-binding residues are essential for SARS-CoV-2 NSP1-mediated inhibition of host translation and for its ribosomal binding. Intriguingly, NSP1-induced mRNA degradation was also reduced in R116D cells, indicating that mRNA decay occurs in the ribosome context. Thus, RPS3 mRNA-binding residues have multiple translation regulatory functions and are exploited by SARS-CoV-2 in various ways to influence host and viral mRNA translation and stability.
Saccharomyces cerevisiae DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination
Authors: Cerqueira Paula G , Meyer Damon , Zhang Lilin , Mallory Benjamin , Liu Jie , Hua Fu Becky Xu , Zhang Xiaoping , Heyer Wolf-Dietrich
Published: April 2023

Saccharomyces cerevisiae DNA polymerase IV (Pol4) like its homolog, human DNA polymerase lambda (Polλ), is involved in Non-Homologous End-Joining and Microhomology-Mediated Repair. Using genetic analysis, we identified an additional role of Pol4 also in homology-directed DNA repair, specifically in Rad52-dependent/Rad51-independent direct-repeat recombination. Our results reveal that the requirement for Pol4 in repeat recombination was suppressed by the absence of Rad51, suggesting that Pol4 counteracts the Rad51 inhibition of Rad52-mediated repeat recombination events. Using purified proteins and model substrates, we reconstituted in vitro reactions emulating DNA synthesis during direct-repeat recombination and show that Rad51 directly inhibits Polδ DNA synthesis. Interestingly, although Pol4 was not capable of performing extensive DNA synthesis by itself, it aided Polδ in overcoming the DNA synthesis inhibition by Rad51. In addition, Pol4 dependency and stimulation of Polδ DNA synthesis in the presence of Rad51 occurred in reactions containing Rad52 and RPA where DNA strand-annealing was necessary. Mechanistically, yeast Pol4 displaces Rad51 from ssDNA independent of DNA synthesis. Together our in vitro and in vivo data suggest that Rad51 suppresses Rad52-dependent/Rad51-independent direct-repeat recombination by binding to the primer-template and that Rad51 removal by Pol4 is critical for strand-annealing dependent DNA synthesis.
GeoBind: segmentation of nucleic acid binding interface on protein surface with geometric deep learning
Authors: Li Pengpai , Liu Zhi-Ping
Published: April 2023

Unveiling the nucleic acid binding sites of a protein helps reveal its regulatory functions in vivo. Current methods encode protein sites from the handcrafted features of their local neighbors and recognize them via a classification, which are limited in expressive ability. Here, we present GeoBind, a geometric deep learning method for predicting nucleic binding sites on protein surface in a segmentation manner. GeoBind takes the whole point clouds of protein surface as input and learns the high-level representation based on the aggregation of their neighbors in local reference frames. Testing GeoBind on benchmark datasets, we demonstrate GeoBind is superior to state-of-the-art predictors. Specific case studies are performed to show the powerful ability of GeoBind to explore molecular surfaces when deciphering proteins with multimer formation. To show the versatility of GeoBind, we further extend GeoBind to five other types of ligand binding sites prediction tasks and achieve competitive performances.
The Dictyostelium discoideum genome lacks significant DNA methylation and uncovers palindromic sequences as a source of false positives in bisulfite sequencing
Authors: Drewell Robert A , Cormier Tayla C , Steenwyk Jacob L , Denis James St , Tabima Javier F , Dresch Jacqueline M , Larochelle Denis A
Published: April 2023

DNA methylation, the addition of a methyl (CH3) group to a cytosine residue, is an evolutionarily conserved epigenetic mark involved in a number of different biological functions in eukaryotes, including transcriptional regulation, chromatin structural organization, cellular differentiation and development. In the social amoeba Dictyostelium, previous studies have shown the existence of a DNA methyltransferase (DNMA) belonging to the DNMT2 family, but the extent and function of 5-methylcytosine in the genome are unclear. Here, we present the whole genome DNA methylation profile of Dictyostelium discoideum using deep coverage replicate sequencing of bisulfite-converted gDNA extracted from post-starvation cells. We find an overall very low number of sites with any detectable level of DNA methylation, occurring at significant levels in only 303–3432 cytosines out of the ∼7.5 million total cytosines in the genome depending on the replicate. Furthermore, a knockout of the DNMA enzyme leads to no overall decrease in DNA methylation. Of the identified sites, significant methylation is only detected at 11 sites in all four of the methylomes analyzed. Targeted bisulfite PCR sequencing and computational analysis demonstrate that the methylation profile does not change during development and that these 11 cytosines are most likely false positives generated by protection from bisulfite conversion due to their location in hairpin-forming palindromic DNA sequences. Our data therefore provide evidence that there is no significant DNA methylation in Dictyostelium before fruiting body formation and identify a reproducible experimental artifact from bisulfite sequencing.
Paying forward to future generations: how infrastructure can do more
Authors: Bowditch Garry
Published: April 2023

When infrastructure is done well, it forms the fabric beneath us that enables individuals, businesses and communities to experience more prosperous and inclusive living for current and future generations. In this brief commentary paper, I offer arguments and case examples from my recent book BIG FIXES: Building Bridges to an Inclusive Future. Unfortunately, as an infrastructure practitioner for over 30 years, I have observed a global shift among policymakers to exaggerate the benefits of investing in infrastructure without accountability and a framework for governance to assure positive long-term outcomes. In essence, infrastructure has fallen victim to short-termism. The central thesis of my book for readers and future contributors of Oxford Open Infrastructure and Health (OOIH) aligns well with the journal’s mission for infrastructure and health scholarship that fosters ‘Big Connections’. My argument is as follows. Is your vision of infrastructure about physical assets like roads, bridges, tunnels, power lines, water pipes, schools and hospitals? If so, then it is too narrow. There is an urgent need for policymakers, investors and scholars to widen their perspective to consider infrastructure as a gift that current generations pay forward to future generations. The infrastructure decisions of our forebearers act like ripples on a lake, radiating out in time and space. These ripples can amplify benefits into the future, like favorable tailwinds. But equally, where short-sightedness has taken root in the past, the consequences of earlier infrastructure decisions (or none at all) can saddle future generations with the burden of headwinds—slowing, dragging upon efforts to improve. When a society invests in infrastructure, they express hope and optimism for the future. However, that aspiration implies a big bundle of expectations, including health and economic well-being and sustaining and building trust between people and the institutions created to serve them. Moreover, as environmental and social issues grow in importance, society has less room to be complacent with nonresponsive infrastructure blocking adaptation and innovation to support new growth. These are examples of the lens to view ‘Big Connections’ referred to by OOIH.
Update: on selected ROP cell polarity mechanisms in plant cell morphogenesis
Authors: Müller Sabine
Published: April 2023

The unequal (asymmetric) distribution of cell structures and proteins within a cell is designated as cell polarity. Cell polarity is a crucial prerequisite for morphogenetic processes such as oriented cell division and directed cell expansion. Rho-related GTPase from plants (ROPs) are required for cellular morphogenesis through the reorganization of the cytoskeleton and vesicle transport in various tissues. Here, I review recent advances in ROP-dependent tip growth, vesicle transport, and tip architecture. I report on the regulatory mechanisms of ROP upstream regulators found in different cell types. It appears that these regulators assemble in nanodomains with specific lipid compositions and recruit ROPs for activation in a stimulus-dependent manner. Current models link mechanosensing/mechanotransduction to ROP polarity signaling involved in feedback mechanisms via the cytoskeleton. Finally, I discuss ROP signaling components that are upregulated by tissue-specific transcription factors and exhibit specific localization patterns during cell division, clearly suggesting ROP signaling in division plane alignment.
Visual policy narrative messaging improves COVID-19 vaccine uptake
Authors: Shanahan Elizabeth A , DeLeo Rob A , Albright Elizabeth A , Li Meng , Koebele Elizabeth A , Taylor Kristin , Crow Deserai Anderson , Dickinson Katherine L , Minkowitz Honey , Birkland Thomas A , Zhang Manli
Published: April 2023

In the face of vaccine hesitancy, public health officials are seeking more effective risk communication approaches to increase vaccination rates. We test the influence of visual policy narratives on COVID-19 vaccination behavior through a panel survey experiment conducted in early 2021 (n = 3,900) and then 8 weeks later (n = 2,268). We examine the effects of three visual policy narrative messages that test the narrative mechanism of character selection (yourself, your circle, and your community) and a nonnarrative control on COVID-19 vaccine behavior. Visual risk messages that use narratives positively influence COVID-19 vaccination through serial mediation of affective response to the messages and motivation to get the COVID-19 vaccination. Additionally, character selection matters, as messages focusing on protecting others (i.e. your circle and your community) perform stronger than those of yourself. Political ideology moderated some of the effects, with conservative respondents in the nonnarrative control condition having a higher probability of vaccination in comparison to the protect yourself condition. Taken together, these results suggest that public health officials should use narrative-based visual communication messages that emphasize communal benefits of vaccinations.
Dimension matters when modeling network communities in hyperbolic spaces
Authors: Désy Béatrice , Desrosiers Patrick , Allard Antoine
Published: April 2023

Over the last decade, random hyperbolic graphs have proved successful in providing geometric explanations for many key properties of real-world networks, including strong clustering, high navigability, and heterogeneous degree distributions. These properties are ubiquitous in systems as varied as the internet, transportation, brain or epidemic networks, which are thus unified under the hyperbolic network interpretation on a surface of constant negative curvature. Although a few studies have shown that hyperbolic models can generate community structures, another salient feature observed in real networks, we argue that the current models are overlooking the choice of the latent space dimensionality that is required to adequately represent clustered networked data. We show that there is an important qualitative difference between the lowest-dimensional model and its higher-dimensional counterparts with respect to how similarity between nodes restricts connection probabilities. Since more dimensions also increase the number of nearest neighbors for angular clusters representing communities, considering only one more dimension allows us to generate more realistic and diverse community structures.
A simple, dual direct expression plasmid system in prokaryotic and mammalian cells
Authors: Murakami Manabu , Murakami Agnieszka M , Yonekura Manabu , Miyoshi Ichiro , Itagaki Shirou , Niwa Yasutaka
Published: April 2023

We introduce a simple, dual direct cloning plasmid system (pgMAX-II) for gene expression analysis in both prokaryotic (Escherichia coli) and mammalian cells. This system, which uses a prokaryotic expression unit adapted from the pgMAX system and a mammalian promoter, is effective for subcloning using the DNA topoisomerase II toxin CcdB. Given that molecular biological cloning systems broadly rely on E. coli for rapid growth, the proposed concept may have wide applicability beyond mammalian cells.
Aircraft and satellite observations reveal historical gap between top–down and bottom–up CO2 emissions from Canadian oil sands
Authors: Wren Sumi N , McLinden Chris A , Griffin Debora , Li Shao-Meng , Cober Stewart G , Darlington Andrea , Hayden Katherine , Mihele Cristian , Mittermeier Richard L , Wheeler Michael J , Wolde Mengistu , Liggio John
Published: April 2023

Measurement-based estimates of greenhouse gas (GHG) emissions from complex industrial operations are challenging to obtain, but serve as an important, independent check on inventory-reported emissions. Such top–down estimates, while important for oil and gas (O&G) emissions globally, are particularly relevant for Canadian oil sands (OS) operations, which represent the largest O&G contributor to national GHG emissions. We present a multifaceted top–down approach for estimating CO2 emissions that combines aircraft-measured CO2/NOx emission ratios (ERs) with inventory and satellite-derived NOx emissions from Ozone Monitoring Instrument (OMI) and TROPOspheric Ozone Monitoring Instrument (TROPOMI) and apply it to the Athabasca Oil Sands Region (AOSR) in Alberta, Canada. Historical CO2 emissions were reconstructed for the surface mining region, and average top–down estimates were found to be >65% higher than facility-reported, bottom–up estimates from 2005 to 2020. Higher top–down vs. bottom–up emissions estimates were also consistently obtained for individual surface mining and in situ extraction facilities, which represent a growing category of energy-intensive OS operations. Although the magnitudes of the measured discrepancies vary between facilities, they combine such that the observed reporting gap for total AOSR emissions is ≥(31 ± 8) Mt for each of the last 3 years (2018–2020). This potential underestimation is large and broadly highlights the importance of continued review and refinement of bottom–up estimation methodologies and inventories. The ER method herein offers a powerful approach for upscaling measured facility-level or regional fossil fuel CO2 emissions by taking advantage of satellite remote sensing observations.
Nonuse and hypocritical use of strategic narratives in Megaprojects: the case of the Florence high-speed railway
Authors: Coticchia Fabrizio , Di Giulio Marco
Published: April 2023

Since megaprojects are costly, impactful, and often contentious policymaking processes, scholars have started to look at policy narratives as instruments that actors use strategically to justify their preferences and achieve their goals. But is this really the case? Do actors always adopt a narrative to support their goals? Do they develop arguments that are consistent with their official goals and in a timely manner? This paper suggests that, when megaprojects are not salient, narratives are likely to be strategically nonused or used in a hypocritical way, as such strategies better fit the process-related goals of significant actors. Such a claim is illustrated by a case study on the construction of a new high-speed railway line and station in the city of Florence (Italy). Relying on content and discourse analysis of official documents, and experts’ interviews, the paper shows that, despite favorable premises for the emergence of a battle of narratives, this never took place, as some of the proponents choose to nonuse a strategic narrative, while others occasionally publicly used arguments to jeopardize the whole project. In turn, opponents effectively developed a strategic narrative that, differently from other similar cases, mostly relied on technical arguments and emplotment. Hence, the case study generates hypotheses that could be tested in further studies on the conditions under which a coalitional dynamic emerges and the role played by policy narratives in the process.