bluuebunny/crossref_metadata_2025 huggingface dataset:
Russian Disjunction To li To li and Obligatory Ignorance
Authors: Ivlieva Natalia
Published: September 2024

In this paper, we explore the behavior of one complex disjunction in Russian that has some special properties that set it apart from other simple and complex disjunctions: it never gives rise to free choice inferences in environments in which other disjunctions do and under universal quantifiers it behaves different from other disjunctions. We show that the data resist an analysis in terms of wide scope disjunction and propose that those special properties are due to obligatory ignorance inferences associated with this disjunction. The paper provides one more argument for a grammatical theory of ignorance along the lines of ( 7).
Assembly of the intracluster light in the Horizon-AGN simulation
Authors: Brown Harley J , Martin Garreth , Pearce Frazer R , Hatch Nina A , Bahé Yannick M , Dubois Yohan
Published: September 2024

The diffuse stellar component of galaxy clusters made up of intergalactic stars is termed the intracluster light (ICL). Although there is a developing understanding of the mechanisms by which the ICL is formed, no strong consensus has yet been reached on which objects the stars of the ICL are primarily sourced from. We investigate the assembly of the ICL starting approximately 10 Gyr before $z=0$ in 11 galaxy clusters (halo masses between $\sim 1\times 10^{14}$ and $\sim 7\times 10^{14}$ M$_{\odot }$ at $z\approx 0$) in the Horizon-AGN simulation. By tracking the stars of galaxies that fall into these clusters past cluster infall, we are able to link almost all of the $z\approx 0$ ICL back to progenitor objects. Satellite stripping, mergers, and pre-processing are all found to make significant contributions to the ICL, but any contribution from in situ star formation directly into the ICL appears negligible. Even after compensating for resolution effects, we find that approximately 90 per cent of the stacked ICL of the 11 clusters that is not pre-processed should come from galaxies infalling with stellar masses above $10^{9}$ M$_{\odot }$, with roughly half coming from infalling galaxies with stellar masses within half a dex of $10^{11}$ M$_{\odot }$. The fact that the ICL appears largely sourced from such massive objects suggests that the ICL assembly of any individual cluster may be principally stochastic.
An explanation for the slow-rise phase of solar eruptions
Authors: Xing Yaoyu , Duan Aiying , Jiang Chaowei
Published: September 2024

Solar eruptions are sudden release of the magnetic free energy accumulated within a quasi-static evolutionary process of the corona. Interestingly, many solar eruptions are preceded by a short-term slow-rise phase, during which the pre-eruption structure rises at a speed significantly larger than that of the quasi-static evolution. Here we suggest an explanation for the slow-rise phase based on a recent high-accuracy magnetohydrodynamic simulation for initiation of solar eruption. The simulation shows that by continuously shearing a bipolar magnetic arcade, an internal current sheet forms gradually, and an eruption begins once magnetic reconnection is triggered at the current sheet. We find in the simulation that the overlying field presents a slow-rise phase before the reconnection sets in. In addition, the rising speed is significantly larger than that of the core field during this phase. This slow rise is a manifestation of the growing expansion of the arcade in the process of approaching a fully open field state, which is inherent to the formation of a current sheet before the eruption. We also show three flare events with slow-rise phases that are highly consistent with these key characteristics in the simulation: an expansion of the overlying coronal loops with speeds much larger than the quasi-static evolution speed, and for those events with filament eruption, the slow rise of filament is much smaller than that of the overlying loops. In this type of events, the eruption might be initiated through the mechanism as shown in the simulation, and the expansion of overlying coronal loops is a better indicator of the slow-rise phase.
The symbiotic recurrent nova V745 Sco at radio wavelengths
Authors: Molina Isabella , Chomiuk Laura , Linford Justin D , Aydi Elias , Mioduszewski Amy J , Mukai Koji , Sokolovsky Kirill V , Strader Jay , Craig Peter , Dong Dillon , Harris Chelsea E , Nyamai Miriam M , Rupen Michael P , Sokoloski Jennifer L , Walter Frederick M , Weston Jennifer H S , Williams Montana N
Published: September 2024

V745 Sco is a Galactic symbiotic recurrent nova with nova eruptions in 1937, 1989, and 2014. We study the behaviour of V745 Sco at radio wavelengths (0.6–37 GHz), covering both its 1989 and 2014 eruptions and informed by optical, X-ray, and $\gamma$-ray data. The radio light curves are synchrotron-dominated. Surprisingly, compared to expectations for synchrotron emission from explosive transients such as radio supernovae, the light curves spanning 0.6–37 GHz all peak around the same time ($\sim$18–26 d after eruption) and with similar flux densities (5–9 mJy). We model the synchrotron light curves as interaction of the nova ejecta with the red giant wind, but find that simple spherically symmetric models with wind-like circumstellar material (CSM) cannot explain the radio light curve. Instead, we conclude that the shock suddenly breaks out of a dense CSM absorbing screen around 20 d after eruption, and then expands into a relatively low-density wind ($\dot{M}_{out} \approx 10^{-9}\!-\!10^{-8}$ M$_{\odot }$ yr$^{-1}$ for $v_w = 10$ km s$^{-1}$) out to $\sim$1 yr post-eruption. The dense, close-in CSM may be an equatorial density enhancement or a more spherical red giant wind with $\dot{M}_{in} \approx [5\!-\!10] \times 10^{-7}$ M$_{\odot }$ yr$^{-1}$, truncated beyond several $\times 10^{14}$ cm. The outer lower-density CSM would not be visible in typical radio observations of Type Ia supernovae: V745 Sco cannot be ruled out as a Type Ia progenitor based on CSM constraints alone. Complementary constraints from the free–free radio optical depth and the synchrotron luminosity imply the shock is efficient at accelerating relativistic electrons and amplifying magnetic fields, with $\epsilon _e$ and $\epsilon _B \approx 0.01\!-\!0.1$.
Molecular clouds as hubs in spiral galaxies: gas inflow and evolutionary sequence
Authors: Zhou J W , Dib Sami , Davis Timothy A
Published: September 2024

We decomposed the molecular gas in the spiral galaxy NGC 628 (M74) into multiscale hub-filament structures using the CO (2$-$1) line by the dendrogram algorithm. All leaf structures as potential hubs were classified into three categories, i.e. leaf-HFs-A, leaf-HFs-B and leaf-HFs-C. Leaf-HFs-A exhibit the best hub-filament morphology, which also have the highest density contrast, the largest mass and the lowest virial ratio. We employed the filfinder algorithm to identify and characterize filaments within 185 leaf-HFs-A structures, and fitted the velocity gradients around the intensity peaks. Measurements of velocity gradients provide evidence for gas inflow within these structures, which can serve as a kinematic evidence that these structures are hub-filament structures. The numbers of the associated 21 μm and H α structures and the peak intensities of 7.7 μm, 21 μm, and H α emissions decrease from leaf-HFs-A to leaf-HFs-C. The spatial separations between the intensity peaks of CO and 21 μm structures of leaf-HFs-A are larger than those of leaf-HFs-C. These evidence indicate that leaf-HFs-A are more evolved than leaf-HFs-C. There may be an evolutionary sequence from leaf-HFs-C to leaf-HFs-A. Currently, leaf-HFs-C lack a distinct gravitational collapse process that would result in a significant density contrast. The density contrast can effectively measure the extent of the gravitational collapse and the depth of the gravitational potential of the structure which, in turn, shapes the hub-filament morphology. Combined with the kinematic analysis presented in previous studies, a picture emerges that molecular gas in spiral galaxies is organized into network structures through the gravitational coupling of multiscale hub-filament structures. Molecular clouds, acting as knots within these networks, serve as hubs, which are local gravitational centres and the main sites of star formation.
E-Cigarette Brand Use by Race/Ethnicity in a US Sample of Adolescent and Young Adult E-Cigarette Users, 2022–2023
Authors: Kreslake Jennifer M , Bertrand Adrian , Minter Tyler , Schillo Barbara A
Published: September 2024

Introduction

To determine whether e-cigarette brand use varies according to race/ethnicity among adolescent and young adult e-cigarette users.

Aims and Methods

Data are from a cross-sectional online survey of respondents aged 15–24 years (January 2022–June 2023; 300 unique respondents/week). The analytic sample was restricted to current e-cigarette users (n = 6387). Respondents selected their usual brand and reported frequency of past 30-day e-cigarette use (in days). ANOVAs measured differences in frequency of use by usual brand, stratified by race/ethnicity. Linear regression identified changes in usual brand over time by race/ethnicity, controlling for age and use of other tobacco/nicotine products.

Results

One-quarter (25.6%) of Black and 22.2% of Hispanic e-cigarette users reported JUUL as their usual brand, compared to those who are White (15.7%) or another race (16.5%). Puff Bar was the second-most reported brand among Black (15.1%) or Hispanic (16.6%) e-cigarette users, to a greater extent than White (7.8%) e-cigarette users. Frequency of use varied significantly according to respondents’ usual brand when stratified by race/ethnicity (p < .001).

Conclusions

Across all racial and ethnic categories, frequency of use was greater for brands marketed with more flavor options and containing nicotine (EB Design, SMOK, Hyde, and Vuse). Despite declines in popularity, Black or Hispanic respondents report using JUUL and Puff Bar to a greater extent than other respondents, and vape less frequently than White non-Hispanic respondents regardless of brand. As e-cigarette brands continue to proliferate, monitoring e-cigarette brand selection by race/ethnicity can inform studies of nicotine exposure, polyuse, and health disparities.

Implications

Our study demonstrates the importance of research methods to detect rapidly changing patterns of e-cigarette use by race/ethnicity and age. The inclusion of measures capturing brand use can detect evidence of product features and targeted marketing that may have consequences for patterns of tobacco use and nicotine exposure among these groups.
An unusual case of incidental pancreatic neuroendocrine tumor presenting with main pancreatic duct cystic dilatation
Authors: Essoun Samuel , Adu-Aryee Nii A , Obaka Henry E , Seshie Bernard , Dey Dzifa , Naporo Simon
Published: September 2024

Introduction: Pancreatic lesions have varied morphology and presentation making their diagnosis challenging. The lesions may be asymptomatic incidentalomas on abdominal imaging for other conditions, symptomatic producing specific hormone effects or causing local effects. Case: We report a 35-year-old woman with recurrent abdominal pain confirmed gastroesophageal reflux disease. Initial CT imaging reported findings of a pancreatic pseudocysts. A careful review of the imaging showed cystic dilatation of the main pancreatic duct mimicking a main pancreatic duct intra-ductal papillary mucinous neoplasm. At surgery, a small nodule palpated in the pancreatic head with sacculation in the body and tail. A histopathological review showed a pancreatic neuroendocrine tumour blocking the main pancreatic duct at the neck causing downstream dilatation and sacculation. This case highlights the difficulty of diagnosing small asymptomatic pancreatic tumours especially with limited range of imaging modalities while increasing awareness of these conditions to improve our ability to manage them effectively.
Transcription factors WRKY2 and WRKY34 control LATERAL ORGAN BOUNDARIES DOMAIN10 expression in pollen vegetative cell nuclei
Authors: Nguyen Thu-Hien , Kim Min Jung , Kim Jungmook
Published: September 2024

The intricate regulation of gene expression determining cell fate during male gametogenesis involves a complex interplay of multiple transcriptional regulators. In Arabidopsis (Arabidopsis thaliana), the LATERAL ORGAN BOUNDARIES DOMAIN 10 (LBD10) transcription factor is prominent in early microspores and both the germ and vegetative cells of bicellular pollen, playing an important role in pollen development. However, in mature pollen, LBD10 exclusively localizes in the vegetative cell nucleus (VCN). Here, we identify cis-acting elements and trans-acting factors responsible for the specific expression of LBD10 in the VCN during pollen maturation. Using a series of LBD10 promoter deletion constructs fused with GUS or GFP reporters, we pinpoint two crucial core promoter sequences. These sequences are situated within two 200 bp regions upstream of the start codon and independently govern LBD10 expression in the VCN. We demonstrate that a W-box motif (AGTCAC) at −770 bp is essential for activating the expression of LBD10 in vegetative cells during pollen maturation. Our transient gene expression assays using Arabidopsis protoplasts and chromatin immunoprecipitation assays show that the transcription factors WRKY2 and WRKY34 recognize the LBD10 promoter region containing W-box motifs. Collectively, our findings suggest that WRKY2 and WRKY34 binding to the W-box motifs plays a role in the VCN-specific expression of LBD10 in pollen. This interaction may contribute to male gametophyte development, shedding light on the intricate regulatory network governing this critical biological process.
Bestrophin-like protein 4 is involved in photosynthetic acclimation to light fluctuations in Chlamydomonas
Authors: Adler Liat , Lau Chun Sing , Shaikh Kashif M , van Maldegem Kim A , Payne-Dwyer Alex L , Lefoulon Cecile , Girr Philipp , Atkinson Nicky , Barrett James , Emrich-Mills Tom Z , Dukic Emilija , Blatt Michael R , Leake Mark C , Peltier Gilles , Spetea Cornelia , Burlacot Adrien , McCormick Alistair J , Mackinder Luke C M , Walker Charlotte E
Published: September 2024

In many eukaryotic algae, CO2 fixation by Rubisco is enhanced by a CO2-concentrating mechanism, which utilizes a Rubisco-rich organelle called the pyrenoid. The pyrenoid is traversed by a network of thylakoid membranes called pyrenoid tubules, which are proposed to deliver CO2. In the model alga Chlamydomonas (Chlamydomonas reinhardtii), the pyrenoid tubules have been proposed to be tethered to the Rubisco matrix by a bestrophin-like transmembrane protein, BST4. Here, we show that BST4 forms a complex that localizes to the pyrenoid tubules. A Chlamydomonas mutant impaired in the accumulation of BST4 (bst4) formed normal pyrenoid tubules, and heterologous expression of BST4 in Arabidopsis (Arabidopsis thaliana) did not lead to the incorporation of thylakoids into a reconstituted Rubisco condensate. Chlamydomonas bst4 mutants did not show impaired growth under continuous light at air level CO2 but were impaired in their growth under fluctuating light. By quantifying the non-photochemical quenching (NPQ) of chlorophyll fluorescence, we propose that bst4 has a transiently lower thylakoid lumenal pH during dark-to-light transition compared to control strains. We conclude that BST4 is not a tethering protein but is most likely a pyrenoid tubule ion channel involved in the ion homeostasis of the lumen with particular importance during light fluctuations.
Exploring police employees’ attitudes and behaviours as a bystander towards police sexual misconduct
Authors: Bubbear Rogers Ellie , Sweeting Fay
Published: September 2024

Police sexual misconduct (PSM) can have a severe impact on the police workforce, affecting all police personnel, not just officers, but it has received little academic attention. Such misconduct often goes unreported, despite many instances having bystanders present. This research explored police employees’ attitudes and behaviours as a bystander towards PSM. Four focus groups involving 25 police personnel were conducted across three forces in the East of England, and the data were analysed using thematic analysis. The findings revealed that participants’ attitudes towards sexual misconduct varied based on their perception of the misconduct and that barriers deterred them from reporting or challenging such behaviours. Nevertheless, participants felt accountable to act as bystanders while also holding other personnel responsible.
Neurostructural changes in schizophrenia and treatment-resistance: a narrative review
Authors: Paul Tanya , See Jia Whei , Vijayakumar Vetrivel , Njideaka-Kevin Temiloluwa , Loh Hanyou , Lee Vivian Jia Qi , Dogrul Bekir Nihat
Published: September 2024

Schizophrenia is a complex disorder characterized by multiple neurochemical abnormalities and structural changes in the brain. These abnormalities may begin before recognizable clinical symptoms appear and continue as a dynamic process throughout the illness. Recent advances in imaging techniques have significantly enriched our comprehension of these structural alterations, particularly focusing on gray and white matter irregularities and prefrontal, temporal, and cingulate cortex alterations. Some of the changes suggest treatment resistance to antipsychotic medications, while treatment nonadherence and relapses may further exacerbate structural abnormalities. This narrative review aims to discuss the literature about alterations and deficits within the brain, which could improve the understanding of schizophrenia and how to interpret neurostructural changes.
Designing, delivering and evaluating a specialty specific quality improvement course for the rheumatology multidisciplinary team
Authors: Benson Rosalind M , Sharp Charlotte A , MacPhie Elizabeth M , Baird Hannah S
Published: September 2024

Objectives

Quality improvement (QI) methodology aims to drive improvement in healthcare using a systematic approach. QI is an integral part of healthcare professional training curricula. However, many members of the rheumatology community have not accessed formal QI methodology training, including those expected to supervise QI activity. The BSR QI practical methodology workshop was created to address this knowledge gap in a specialty-specific course designed and delivered by, and for, the multidisciplinary team.

Methods

Course design centred on the Institute for Healthcare Improvement approach, ‘Model for improvement’, adapting materials from the well-established Trainees Improving Patient Safety through QI (TIPSQI) initiative. The course was delivered online (2021) and face-to-face (2022). Kolbs’ four stage experiential learning cycle informed course design utilising rheumatology-specific cases and facilitated breakout rooms to teach QI tools.

Kirkpatrick’s four-stage model was used to design the course evaluation. Data from surveys completed before, immediately after, and six months’ following the courses were used to evaluate the course.

Results

Baseline knowledge of specific QI tools was limited. Post course evaluation demonstrated increased confidence to use and teach tools. Sustained confidence to contribute to and lead QI activity was reported. Course satisfaction was high; 100% of delegates would recommend the course to colleagues.

Conclusion

This successful, rheumatology specific QI course led to improved delegate knowledge of QI methodology and confidence in leading and teaching QI initiatives. It has contributed to building momentum in a growing rheumatology QI community of practice and to embedding a sustainable culture of improvement across the rheumatology community.
Radiological impact assessment of natural radioactivity in soil and water in Cape Coast North, Central Region of Ghana
Authors: Annan Ruth Araba Tawiah , Eghan Moses Jojo , Amoako Joseph Kwabena , Otoo Francis , Adotey Dennis Kpakpo , Opoku-Ntim Irene , Kansaana Charles , Adeti Prince James
Published: September 2024

The objective of the study is to evaluate natural radioactivity and its radiological impact on the health of the populace within Cape Coast North. Soil and water samples were taken and analysed using a high purity germanium (HPGe) detector. Results for the average activity concentrations of 226Ra, 232Th, and 40K in soil samples range from 15.0 to 60.8 Bq/kg with a mean of 20.9 ± 7.2 Bq/kg, 16.3 to 97.2 Bq/kg with a mean of 43.8 ± 2.4 Bq/kg, and 4.7 to 411.4 Bq/kg with an average of 140.6 ± 4.2 Bq/kg, respectively. The absorbed dose rate in air and outdoor annual effective dose to the public were estimated to be 46.6 nGyh−1 and 0.1 mSv, respectively, which fell below the recommended average. The average activity concentrations of 226Ra, 232Th, and 40K in water samples were 1.4, 0.4, and 1.2 Bq/L, respectively. The annual effective dose is 0.4 mSv, which is greater than the WHO recommended level of 0.1 mSv/y.
Trajectories of Public Islam: Public Religious Expressions among American Muslim Advocates
Authors: Cantori Valentina
Published: September 2024

In American mainstream cultural discourse, Islam is often constructed as undemocratic, violent, and un-American. How do American Muslim advocates react to these tarnished representations of their religion? This paper examines the ways in which Muslim advocates construct public discourse around Islam by exploring the possibilities for and recognizing the constraints on their public religious expressions in U.S. civic life as advocates navigate cultural templates infused with de-sacralized Christian meanings. Based on participant observation in two Muslim advocacy organizations, the article demonstrates that advocates map Islam differently, depending on whether the imagined audience of their public discourse is other Muslims or non-Muslims. When advocates imagine addressing non-Muslims, the public discourse of both groups similarly emphasizes Islamic compatibility of Muslim with American values. Among both groups, there is a process of filtering certain religious expressions for more expansive social maps that uncovers the unequal power dynamics shaping trajectories of public religion in civic life for one of the most stigmatized ethno-religious groups in the United States today. This paper contributes to expanding our understanding of how civic culture enables and constrains historically marginalized groups’ attempts at redefining belonging.
After Restructuring: Understanding Religion, Nonreligion, and Spirituality in the Twenty-First Century
Authors: Edgell Penny
Published: September 2024

The Restructuring of American Religion (1988) provided a still-influential framework for the study of American religion that centered the emergence, after World War II, of a left–right religio-political divide driving mobilization around conflicts understood as moral. But in the last 30 years, the landscape of American religion has been transformed by decline in commitment to mainstream religious institutions, especially white Christian ones, and by the emergence of large groups of Americans who are religiously indifferent or who embrace spirituality or nonreligion. A new framework is needed to account for this transformed landscape. This framework must avoid problems characteristic of earlier approaches by conceiving of morals and interests as mutually constitutive, centering whiteness, racialization, and the defense of heteropatriarchy in explaining religio-political conflict, integrating the study of nonreligion and spirituality and religion, and analyzing not only decline in religious commitment but the changing meaning of religious identity in a transformed landscape.
A new dentition-based phylogeny of Litopterna (Mammalia: Placentalia) and ‘archaic’ South American ungulates
Authors: Püschel Hans P , Shelley Sarah L , Williamson Thomas E , Perini Fernando A , Wible John R , Brusatte Stephen L
Published: September 2024

Ever since the discovery of Macrauchenia patachonica by Charles Darwin in 1834, the affinities of litopterns—a group of extinct South American Native Ungulates (SANUs)—have been elusive. In particular, the interfamilial relationships and timing of the familial diversification within the order Litopterna have not been addressed with adequate taxon and character sampling, and modern phylogenetic methods. We address these issues using a new morphological matrix of 703 dental and mandibular characters, scored for the earliest litopterns alongside early SANUs of other orders (Astrapotheria, Notoungulata, Pyrotheria, and Xenungulata). We also included members of families that have been often included within Litopterna, such as Didolodontidae, Protolipternidae, Indaleciidae, and Notonychopidae, the last two sometimes grouped in the order Notopterna. We conducted maximum parsimony and undated and tip-dated Bayesian phylogenetic analyses. Our results indicate that (1) didolodontids, protolipternids, and kollpaniines should be considered early SANUs, but not particularly closely related to any order, (2) Indaleciidae and Notonychopidae usually form a monophyletic group (Notopterna), and (3) Litopterna is a monophyletic unit composed of four families [Adianthidae, Anisolambdidae (subfamilies Anisolambdinae and Sparnotheriodontinae), Macraucheniidae, Proterotheriidae], and tentatively the notoptern families Indaleciidae and Notonychopidae with a probable origin ~64.0 Mya in the Early Palaeocene.
Smoking and Type 1 Versus Type 2 Myocardial Infarction Among People With HIV in the United States: Results from the Center for AIDS Research Network Integrated Clinical Systems Cohort
Authors: Crane Heidi M. , Nance Robin M. , Ruderman Stephanie A. , Drumright Lydia N. , Mixson L. Sarah , Heckbert Susan R. , Feinstein Matthew J. , Budoff Matthew J. , Bamford Laura , Cachay Edward , Napravnik Sonia , Moore Richard D. , Keruly Jeanne , Willig Amanda L. , Burkholder Greer A. , Hahn Andrew , Ma Jimmy , Fredericksen Rob , Saag Michael S. , Chander Geetanjali , Kitahata Mari M. , Crothers Kristina , Mayer Kenneth H. , O'Cleirigh Conall , Cropsey Karen , Whitney Bridget M. , Delaney Joseph A. C.
Published: September 2024

Smoking is a myocardial infarction (MI) risk factor among people with HIV (PWH). Questions persist regarding the role of smoking behaviors and measurements (e.g., intensity, duration) on MI risk. We used Cox proportional hazards regression to compare the association of smoking parameterization with incidents of type 1 and type 2 MI and whether smoking intensity or duration improves MI risk prediction among PWH. Among 11,637 PWH, 37% reported currently smoking, and there were 346 MIs. Current smoking was associated with type 1 (84% increased risk) but not type 2 MI in adjusted analyses. The type 1 MI model with pack years had the best goodness of fit compared with other smoking parameterizations. Ever or never parameterization and smoking diagnosis data had significantly poorer model fit. These results highlight the importance of differentiating MI types and performing patient-based smoking assessments to improve HIV care and research rather than relying on smoking status from diagnoses.
Post-transcriptional regulation by TIA1 and TIAL1 controls the transcriptional program enforcing T cell quiescence
Authors: Osma-Garcia Ines C. , Maloudi Orlane , Mouysset Mailys , Capitan-Sobrino Dunja , Nguyen Trang-My M. , Aubert Yann , Diaz-Muñoz Manuel D.
Published: September 2024

Immune protection against new and recurrent infections relies on long-term maintenance of a highly diversified T-cell repertoire. Transcription factors cooperate to enforce T-cell metabolic quiescence and maintenance. However, less is known about the post-transcriptional networks that preserve peripheral naïve T cells. Here we describe the RNA binding proteins TIA1 and TIAL1 as key promoters of CD4 and CD8 T cell quiescence. T cells deficient in TIA1 and TIAL1 undergo uncontrolled cell proliferation in the absence of cognate antigens, leading this to a premature T-cell activation, exhaustion and death. Mechanistically, TIA1 and TIAL1 control the expression of master regulatory transcription factors, FOXP1, LEF1 and TCF1, that restrain homeostatic T-cell proliferation. In summary, our study highlights a previously unrecognised dependency on post-transcriptional gene regulation by TIA1 and TIAL1 for implementing the quiescent transcriptional programs for long survival of T cells.
Foliar application of nano urea results in higher biomass, chlorophyll, and nitrogen content than equimolar bulk urea through differential gene regulation inArabidopsis thaliana
Authors: Dey Arpan , Jangir Neelam , Verma Devanshu , Shekhawat Rajveer Singh , Yadav Pankaj , Sadhukhan Ayan
Published: September 2024

Indian Farmers Fertilizer Cooperative (IFFCO)’s liquid nano urea formulation (NUF) was applied to one-month-oldArabidopsis thalianaplants grown in vermiculite as a 0.4% foliar spray twice at an interval of 10 days and compared with sprays of equimolar bulk urea. NUF resulted in a 51 ± 14.9% increase in biomass, 29.5 ± 9.1% in chlorophyll, 8.4 ± 3.1% in nitrogen, and 4.5 ± 0.3% in amino acid content of the leaves, compared to bulk urea. NUF’s zeta potential of -54.7 mV and particle size of ≃27.7 nm, measured by dynamic light scattering and transmission electron microscopy, make it suitable for stomatal uptake. We conducted a differential gene expression analysis by mRNA sequencing to understand the molecular basis of the phenotypic gains under NUF rather than urea. NUF resulted in significantly higher expression levels of 211 genes (log2fold-change > 0.5,FDR< 0.05) involved in the biosynthesis of carbohydrates, amino acids, nucleotides, lipids, phytohormones, and secondary metabolites, cell wall biosynthesis and modification, growth and developmental processes, cell cycle, and stress response than bulk urea. On the other hand, 1,286 genes (log2fold-change < -0.5) involved in cell death, abscission, senescence, nitrogen transport and metabolism, and biotic stress response showed lower expression levels upon NUF application than bulk urea. Our results suggest that although NUF foliar spray suppresses nitrogen uptake genes, possibly due to nitrogen excess, it enhances growth by up-regulating the synthesis of essential biomolecules and growth-promoting genes, compared to bulk urea.
Enhanced Ultrasound Image Formation with Computationally Efficient Cross-Angular Delay Multiply and Sum Beamforming
Authors: Smith Cameron A. B. , Toulemonde Matthieu , Lerendegui Marcelo , Riemer Kai , Malounda Dina , Weinberg Peter D. , Shapiro Mikhail G. , Tang Meng-Xing
Published: September 2024

Ultrasound imaging is a valuable clinical tool. It is commonly achieved using the delay and sum beamformer algorithm, which takes the signals received by an array of sensors and generates an image estimating the spatial distribution of the signal sources. This algorithm, while computationally efficient, has limited resolution and suffers from high side lobes. Nonlinear processing has proven to be an effective way to enhance the image quality produced by beamforming in a computationally efficient manner. In this work, we describe a new beamforming algorithm called Cross-Angular Delay Multiply and Sum, which takes advantage of nonlinear compounding to enhance contrast and resolution. This is then implemented with a mathematical reformulation to produce images with tighter point spread functions and enhanced contrast at a low computational cost. We tested this new algorithm over a range ofin vitroandin vivoscenarios for both conventional B-Mode and amplitude modulation imaging, and for two types of ultrasound contrast agents, demonstrating its potential for clinical settings.
Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy
Authors: Bridge Jacob , Johnson Matthew J. , Kim Jihyun , Wenthe Sophia , Krueger Joshua , Wick Bryce , Kluesner Mitchell , Crane Andrew T. , Bell Jason , Skeate Joseph G. , Moriarity Branden S. , Webber Beau R.
Published: September 2024

Gamma delta (γδ) T cells are defined by their unique ability to recognize a limited repertoire of non-peptide, non-MHC-associated antigens on transformed and pathogen-infected cells. In addition to their lack of alloreactivity, γδ T cells exhibit properties distinct from other lymphocyte subsets, prompting significant interest in their development as an off-the-shelf cellular immunotherapeutic. However, their low abundance in circulation, heterogeneity, limited methods forex vivoexpansion, and under-developed methodologies for genetic modification have hindered basic study and clinical application of γδ T cells. Here, we implement a feeder-free, scalable approach forex vivomanufacture of polyclonal, non-virally modified, gene edited chimeric antigen receptor (CAR)-γδ T cells in support of therapeutic application. Engineered CAR-γδ T cells demonstrate high functionin vitroand andin vivo.Longitudinalin vivopharmacokinetic profiling of adoptively transferred polyclonal CAR-γδ T cells uncover subset-specific responses to IL-15 cytokine armoring and multiplex base editing. Our results present a robust platform for genetic modification of polyclonal CAR-γδ T cells and present unique opportunities to further define synergy and the contribution of discrete, engineered CAR-γδ T cell subsets to therapeutic efficacyin vivo.
Ecological and evolutionary impacts of urbanization: applying a causal modeling framework
Authors: Borden Jesse B. , Gibbs James P. , Vanek John P. , Cosentino Bradley J.
Published: September 2024

Urbanization, as the fastest growing land use type, shapes biodiversity through a suite of abiotic and biotic changes driven by the profound alteration of environmental conditions in built environments. Understanding the mechanisms behind biodiversity patterns in urban areas requires disentangling the direct and indirect pathways through which urbanization impacts ecological and evolutionary dynamics. We show how a structural causal modeling framework can be used to provide insight into processes generating biodiversity patterns in urban contexts by building structural equation models to disentangle direct and indirect pathways by which urbanization affects abundance and coat color variation in eastern gray squirrels (Sciurus carolinensis). Integrating camera traps and point count surveys across 49 sites, we observed pronounced urban-rural gradients in squirrel abundance and color variation. Human population density affected abundance of color morphs by mediating resource availability, predator activity, habitat amount, and fragmentation. But markedly different mechanisms drove abundance of color morphs across the landscape. Our findings reveal how explicit modeling of multiple pathways of environmental change can deepen our mechanistic understanding of how urbanization alters biodiversity patterns.
Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake
Authors: Sharpe Amanda L. , Liter Laci R. , Donohue Darius , Carter Kelsey A. , Vangeneugden Patricia , Weaver Sofia , Stout Michael B. , Beckstead Michael J.
Published: September 2024

Although opioid abuse is more prevalent in young individuals, opioid use, overdose, and use disorders continue to climb at a rapid rate among the elderly. Little is known about abuse potential in a healthy aged population, in part due to technical and logistical difficulties testing intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice. Male and female mice were grouped into young (mean: 19 weeks) and old (mean: 101 weeks), and were trained to self-administer intravenous fentanyl or remifentanil in daily sessions. In both old and young mice, acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve (remifentanil) and dose-escalation (fentanyl) were conducted. Surprisingly, old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. Baseline intake of remifentanil was also substantially greater in old mice compared to their young counterparts; however, we did not see increased intake of fentanyl with age at either dose tested. Further, compared to young mice, the old mice showed a greater incubation of responding for cues previously associated with remifentanil after a forced abstinence, but again this was not observed with fentanyl. Together these data suggest that an aged population may have an increased drug-abuse vulnerability for opioids compared to young counterparts and underscore the importance of future work on mechanisms responsible for this increased vulnerability.
Ciliary marginal zone of the developing human retina maintains retinal progenitor cells until late gestational stages
Authors: Eldred Kiara C. , Edgerton Sierra J. , Ortuño-Lizarán Isabel , Wohlschlegel Juliette , Sherman Stephanie M. , Petter Sidnee , Wyatt-Draher Gracious , Hoffer Dawn , Glass Ian , Torre Anna La , Reh Thomas A.
Published: September 2024

Non-mammalian vertebrates maintain a proliferative stem cell population at the far periphery of their retina called the ciliary marginal zone (CMZ), which gives rise to all retinal cell types and contributes to retinal regeneration upon injury. Humans do not maintain a proliferative CMZ into adulthood; however, it is not known how long in development this region continues to generate new neurons. Here, we identify a population of cells in the far peripheral retina of the fetal human that continues to proliferate long after the rest of the retina is quiescent. Single cell RNA-sequencing and EdU tracing at late time points in development reveal that this region has features of the non-mammalian CMZ, including the capacity to produce both early and late born cell types at late developmental stages, and a longer cell cycle than more centrally located retinal progenitor cells (RPCs). Moreover, while more central RPCs exit the cell cycle with the addition of a TGFβ-inhibitor, we show that early RPCs within the CMZ do not. These findings define the late stages of neurogenesis in human retinal development, and present a unique model system to study the fetal CMZ in humans.
Computational Study of the Excitation of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes
Authors: Shetty Roshni , Samurkashian Raffi , Tung Leslie
Published: September 2024

Human induced pluripotent stem-cell derived cardiomyocytes (hiPSC-CMs) have proven to be a revolutionary advance for tissue engineering, disease modeling, and drug testing and discovery. Computational modeling enables a detailed electrophysiological analysis that is otherwise difficult or impossible to achieve under strictly experimental settings. Action potential characteristics of hiPSC-CMs measured in our lab at four different pacing rates were used it to modify the computational Kernik-Clancy hiPSC-CM model. The modified model was used to compare the excitation of single hiPSC-CMs with that of single human ventricular cardiomyocytes (hV-CMs) under varying conditions, including at stimulation at different strengths, rates and pulse durations. The physiological stimulation of both hiPSC-CMs and hV-CMs embedded within a tissue strand involves a biphasic waveform during which time excitatory currents (particularlyINa, but alsoICaTandICaLfor hiPSC-CMs andINaLandICaLfor hV-CMs) are activated during both phases of the waveform.INain particular activated more slowly and with diminished amplitude under conditions of increasing pacing rate or increasing intracellular resistance. Lastly, histograms characterizing the relative amounts of excitatory currents in a population of hiPSC-CMs become broader with increasing levels ofINablock, withICaTandICaLworking in tandem to excite cells whereINahas failed to activate. In general, hiPSC-CMs were found to be more excitable from rest compared with hV-CMs owing to their more depolarized resting potential and intrinsic automaticity despite a lower sodium channel density. Such a mismatch should be taken into consideration for applications using these cells, particularly for cardiac repair.

Key Points

Cardiomyocytes (CMs) generated from human stem cells derived from blood or skin have great potential for cardiac repair, safety pharmacology and disease modeling, but understanding their excitability is crucial for their proper application.

Computational modeling reveals greater excitability of these cells in terms of various metrics compared with that of human adult ventricular CMs at multiple pacing rates.

The excitation of CMs within a strand differs substantially from that usually used to study single isolated CMs and is dissected in terms of the underlying ionic currents.

Computational modeling also predicts how a heterogeneous population of stem cell-derived CMs and their underlying ionic currents could respond to varying levels of reduced sodium current.

Our study presents a cautionary note for applications using these cells, particularly for cardiac repair.
Knocking out the carboxyltransferase interactor 1 (CTI1) in Chlamydomonas boosted oil content by fivefold without affecting cell growth
Authors: Li Zhongze , Kim Minjae , da Silva Nascimento Jose Roberto , Legeret Bertrand , Jorge Gabriel Lemes , Bertrand Marie , Beisson Fred , Thelen Jay J , Li-Beisson Yonghua
Published: September 2024

The first step in chloroplastde novofatty acid synthesis is catalyzed by acetyl-CoA carboxylase (ACCase). As the rate-limiting step for this pathway, ACCase is subject to both positive and negative regulation. In this study, we identify a Chlamydomonas homolog of the plant carboxyltransferase interactor 1 (CrCTI1) and show that this protein, interacts with the Chlamydomonas α-carboxyltransferase (Crα-CT) subunit of the ACCase by yeast two-hybrid protein-protein interaction assay. Three independent CRISPR-Cas9 mediated knock-out mutants for CrCTI1 each produced an “enhanced oil” phenotype, accumulating 25% more total fatty acids and storing up to five-fold more triacylglycerols (TAGs) in lipid droplets. The TAG phenotype of thecrcti1mutants was not influenced by light but was affected by trophic growth conditions. By growing cells under heterotrophic conditions, we observed a crucial function of CrCTI1 in balancing lipid accumulation and cell growth. Mutating a previously mappedin vivophosphorylation site (CrCTI1 Ser108 to either Ala or to Asp), did not affect the interaction with Crα-CT. However, mutating all six predicted phosphorylation sites within Crα-CT to create a phosphomimetic mutant reduced significantly this pairwise interaction. Comparative proteomic analyses of thecrcti1mutants and WT suggested a role for CrCTI1 in regulating carbon flux by coordinating carbon metabolism, antioxidant and fatty acid β-oxidation pathways, to enable cells adapt to carbon availability. Taken together, this study identifies CrCTI1 as a negative regulator of fatty acid synthesis in algae and provides a new molecular brick for genetic engineering of microalgae for biotechnology purposes.
Force Field Limitations of All-Atom Continuous Constant pH Molecular Dynamics
Authors: Peeples Craig , Liu Ruibin , Shen Jana
Published: September 2024

All-atom constant pH molecular dynamics simulations offer a powerful tool for understanding pH-mediated and proton-coupled biological processes. As the protonation equilibria of protein sidechains are shifted by electrostatic interactions and desolvation energies, pKa values calculated from the constant pH simulations may be sensitive to the underlying protein force field and water model. Here we investigated the force field dependence of the all-atom particle mesh Ewald (PME) continuous constant pH (PME-CpHMD) simulations of a mini-protein BBL. The replica-exchange titration simulations based on the Amber ff19SB and ff14SB force fields with the respective water models showed significantly overestimated pKa downshifts for a buried histidine (His166) and for two glutamic acids (Glu141 and Glu161) that are involved in salt-bridge interactions. These errors (due to undersolvation of neutral histidines and overstabilization of salt bridges) are consistent with the previously reported \pka's based on the CHARMM c22/CMAP force field, albeit in larger magnitudes. The pKa calculations also demonstrated that ff19SB with OPC water is significantly more accurate than ff14SB with TIP3P water, and the salt-bridge related pKa downshifts can be partially alleviated by the atom-pair specific Lennard-Jones corrections (NBFIX). Together, these data suggest that the accuracies of the protonation equilibria of proteins from constant pH simulations can significantly benefit from improvements of force fields.
Claudin-4 remodeling of nucleus-cell cycle crosstalk maintains ovarian tumor genome stability and drives resistance to genomic instability-inducing agents
Authors: Villagomez Fabian R. , Lang Julie , Nunez-Avellaneda Daniel , Behbakht Kian , Dimmick Hannah L. , Webb Patricia , Nephew Kenneth P. , Neville Margaret , Woodruff Elizabeth R. , Bitler Benjamin G.
Published: September 2024

During cancer development, the interplay between the nucleus and the cell cycle leads to a state of genomic instability, often accompanied by observable morphological aberrations. These aberrations can be controlled by tumor cells to evade cell death, either by preventing or eliminating genomic instability. In epithelial ovarian cancer (EOC), overexpression of the multifunctional protein claudin-4 is a key contributor to therapy resistance through mechanisms associated with genomic instability. However, the molecular mechanisms underlying claudin-4 overexpression in EOC remain poorly understood. Here, we altered claudin-4 expression and employed a unique claudin-4 targeting peptide (CMP) to manipulate the function of claudin-4. We found that claudin-4 facilitates genome maintenance by linking the nuclear envelope and cytoskeleton dynamics with cell cycle progression. Claudin-4 caused nuclei constriction by excluding lamin B1 and promoting perinuclear F-actin accumulation, associated with remodeling nuclear architecture, thus altering nuclear envelope dynamics. Consequently, cell cycle modifications due to claudin-4 overexpression resulted in fewer cells entering the S-phase and reduced genomic instability. Importantly, disrupting biological interactions of claudin-4 using CMP and forskolin altered oxidative stress cellular response and increased the efficacy of PARP inhibitor treatment. Our data indicate that claudin-4 protects tumor genome integrity by remodeling the crosstalk between the nuclei and the cell cycle, leading to resistance to genomic instability formation and the effects of genomic instability-inducing agents.

Abstract Figure

Graphical abstract

Claudin-4 plays a crucial role in remodeling the cytoskeleton, particularly influencing nuclear architecture. This remodeling appears to act as a regulatory mechanism, limiting the progression of ovarian cancer cells into the S-phase and correlating with reduced genomic instability in ovarian tumors. Moreover, since olaparib treatment triggered a cellular oxidative response, it is likely that this claudin-4-mediated remodeling contributes to resistance against the effects of the PARP inhibitor.