bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective and non-selective evolutionary signatures found in the simplest replicative biological entities
Authors: Jacquat Andrés Gustavo , Theumer Martín Gustavo , Dambolena José Sebastián
Published: June 2024

Mitoviruses, which are considered evolutionary relics of extinct alpha-proteobacteria RNA phages, represent one of the simplest self-replicating biological systems. This study aims to quantitatively describe genomes and identify potential genomic signatures that support the protein phylogenetic-based classification criterion. Genomic variables, such as mononucleotide and dinucleotide composition, codon usage bias, and minimal free energy derived from optimized predicted RNA secondary structure, were analyzed. From the values obtained, the main evolutionary pressures were discussed, indicating that natural selection plays a significant role in shaping mitovirus genomes. However, neutral evolution also makes a significant contribution. This study reveals a significant discovery of structural divergence in Kvaramitovirus. The energy minimization approach employed to study 2D folding in this study reveals a distinct spatial organization of their genomes, providing evidence for the hypothesis of a single evolutionary event of circularization in the most recent common ancestor of the lineage. This hypothesis was discussed in light of recent discoveries by other researchers that partially support the existence of mitoviruses with circular genomes. Finally, this study represents a significant advancement in the understanding of mitoviruses, as it quantitatively describes the nucleotide sequence at the family and genus taxonomic levels. Additionally, we provide hypotheses that can be experimentally validated to inspire new research and address the gaps in knowledge of this fascinating, basally divergent RNA virus lineage.
The origin of large emission line widths in massive galaxies at redshifts z ∼ 3–4
Authors: Martínez-Marín M , Glazebrook K , Nanayakkara T , Jacobs C , Labbé I , Kacprzak G G , Papovich C , Schreiber C
Published: June 2024

We present a sample of 22 massive galaxies with stellar masses >1010 M⊙ at 3 < z < 4 with deep H and K-band high resolution spectra (R = 3500–3000) from Keck/MOSFIRE and VLT/KMOS near-infrared spectrographs. We find a large fraction have strong [O iii] 5007 and Hβ emission lines with large line widths (σ 100–450 km s−1). We measure the sizes of our galaxies from Hubble Space Telescope images and consider the potential kinematic scaling relations of our sample, and rule out an explanation for these broad lines in terms of galaxy-wide kinematics. Based on consideration of the [O iii] 5007/Hβ flux ratios, their location in the mass–excitation diagram, and the derived bolometric luminosities, we conclude that active galactic nuclei (AGN) and their narrow-line regions most likely give rise to this emission. At redshifts 3 < z < 4, we find significantly high AGN fractions in massive galaxies, ranging from 60–70 per cent for the mass range 10 < log (M⋆/M⊙) < 11, with a lower limit 30 per cent for all galaxies within that redshift range when we apply our most stringent AGN criteria. We also find a considerably lower AGN fraction in massive quiescent galaxies, ranging from 20–30 per cent. These fractions of AGN point to the period between 3 < z < 4 being a time of heightened activity for the development of supermassive black holes in the massive end of the galaxy population and provide evidence for their role in the emergence of the first massive quenched galaxies at this epoch.
Bayesian inference methodology to characterize the dust emissivity at far-infrared and submillimeter frequencies
Authors: Adak Debabrata , Shaikh Shabbir , Sinha Srijita , Ghosh Tuhin , Boulanger Francois , Lagache Guilaine , Souradeep Tarun , Miville-Deschênes Marc-Antoine
Published: June 2024

We present a Bayesian inference method to characterize the dust emission properties using the well-known dust-${\rm H\,{\small I}}$ correlation in the diffuse interstellar medium at Planck frequencies $\nu \ge 217$ GHz. We use the Galactic ${\rm H\,{\small I}}$ map from the Galactic All-Sky Survey (GASS) as a template to trace the Galactic dust emission. We jointly infer the pixel-dependent dust emissivity and the zero level present in the Planck intensity maps. We use the Hamiltonian Monte Carlo technique to sample the high-dimensional parameter space ($D \sim 10^3$). We demonstrate that the methodology leads to unbiased recovery of dust emissivity per pixel and the zero level when applied to realistic Planck sky simulations over a 6300 $\rm {deg}^2$ area around the Southern Galactic pole. As an application on data, we analyse the Planck intensity map at 353 GHz to jointly infer the pixel-dependent dust emissivity at $N_{\rm side}=32$ resolution (1.8° pixel size) and the global offset. We find that the spatially varying dust emissivity has a mean of 0.031 MJy sr$^{-1}$$(10^{20} \, \mathrm{cm^{-2}})^{-1}$ and $1\sigma$ standard deviation of 0.007 MJy sr$^{-1}$$(10^{20} \, \mathrm{cm^{-2}})^{-1}$. The mean dust emissivity increases monotonically with increasing mean ${\rm H\,{\small I}}$ column density. We find that the inferred global offset is consistent with the expected level of cosmic infrared background (CIB) monopole added to the Planck data at 353 GHz. This method is useful in studying the line-of-sight variations of dust spectral energy distribution in the multiphase interstellar medium.
Measuring the dust attenuation law of galaxies using photometric data
Authors: Meldorf C , Palmese A , Salim S
Published: June 2024

Fitting model spectral energy distributions (SEDs) to galaxy photometric data is a widely used method to recover galaxy parameters from galaxy surveys. However, the parameter space used to describe galaxies is wide and interdependent, and distinctions between real and spurious correlations that are found between these parameters can be difficult to discern. In this work, we use the SED fitting code bagpipes (Bayesian Analysis of Galaxies for Physical Inference and Parameter EStimation) to investigate degeneracies between galaxy parameters and the effect of the choice of different sets of photometric bands. In particular, we focus on optical to infrared wavelength coverage, and on two parameters describing the galaxies’ dust attenuation law: AV and δ, which characterize dust column density and the slope of a flexible dust attenuation law, respectively. We demonstrate that (1) a degeneracy between the residual (the difference between truth and recovered values) AV and star formation rate exists, but this is lifted when Wide-Field Infrared Survey Explorer bands are included, and (2) bagpipes is able to accurately recover the input AV and δ distributions and relations (differences in slope of less than 1.7σ for a flat relation and less than 1.2σ for an observationally motivated relation) and is not introducing spurious correlations between these parameters. Our findings suggest that the information needed to constrain AV and δ well enough individually exists in the data, especially when infrared is added. This indicates that recent works finding a correlation between AV and δ are not being misled by fitting degeneracies from their SED fitting code.
Size–mass relation of the brightest cluster galaxies at z ∼ 1
Authors: Yang Lilan , Silverman John , Oguri Masamune , Ding Xuheng , Toba Yoshiki , Huang Song , Kawinwanichakij Lalitwadee
Published: June 2024

We present the size–mass relation of the brightest cluster galaxies (BCGs) at 0.1 < z < 1.4 using the imaging data obtained by the Hyper Suprime-Cam Subaru Strategic Program. Our sample consists of 471 photometrically selected BCGs with stellar mass logM*/M⊙ = 11–12. We measure the size of the BCGs using i-band imaging and model fits based on a single Sérsic light profile. Stellar masses are determined through spectral energy distribution fitting using Sérsic-modelled photometry data across five optical bands (grizy). The size–mass scaling relation of BCGs is $r_\mathrm{ e}\propto M_*^{0.73-1.00}$ at z < 1, with a slope that does not evolve significantly. The slope of the size–mass relation for BCGs is steeper than other non-BCG galaxies, which implies that BCGs are a special galaxy population. The size of BCGs at a given stellar mass evolves rapidly as ∝ (1 + z)−1.58 ± 0.13 and increases with redshift by a factor of 2.5 from z ∼ 1.2 to z ∼ 0.2. The rapid size growth is in agreement with semi-analytical model results, indicating that the BCG growth is dominated by frequent minor mergers. Furthermore, we explore the size–mass relationship of BCGs with respect to the halo mass of the cluster and find there is no significant correlation, which might imply that a dependence on the environment predominantly affects the outer envelope of the BCGs.
ARTEMIS emulator: exploring the effect of cosmology and galaxy formation physics on Milky Way-mass haloes and their satellites
Authors: Brown Shaun T , Fattahi Azadeh , McCarthy Ian G , Font Andreea S , Oman Kyle A , Riley Alexander H
Published: June 2024

We present the new ARTEMIS emulator suite of high-resolution (baryon mass of 2.23 × 104h−1 M⊙) zoom-in simulations of Milky Way-mass systems. Here, three haloes from the original ARTEMIS sample have been rerun multiple times, systematically varying parameters for the stellar feedback model, the density threshold for star formation, the reionization redshift, and the assumed warm dark matter (WDM) particle mass (assuming a thermal relic). From these simulations, emulators are trained for a wide range of statistics that allow for fast predictions at combinations of parameters not originally sampled, running in ∼1 ms (a factor of ∼1011 faster than the simulations). In this paper, we explore the dependence of the central haloes’ stellar mass on the varied parameters, finding the stellar feedback parameters to be the most important. When constraining the parameters to match the present-day stellar mass halo mass relation inferred from abundance matching we find that there is a strong degeneracy in the stellar feedback parameters, corresponding to a freedom in formation time of the stellar component for a fixed halo assembly history. We additionally explore the dependence of the satellite stellar mass function, where it is found that variations in stellar feedback, the reionization redshift, and the WDM mass all have a significant effect. The presented emulators are a powerful tool which allows for fundamentally new ways of analysing and interpreting cosmological hydrodynamic simulations. Crucially, allowing their free (subgrid) parameters to be varied and marginalized, leading to more robust constraints and predictions.
Corporate Purpose Swings as a Social, Atheoretical Process: Will the Pendulum Break?
Authors: Galanis Michael
Published: June 2024

This article argues that conceptualising corporate purpose as a normative question which can be examined in isolation from its socio-historical context is inappropriate and ultimately futile. Corporate purpose is examined here as historically determined, a social fact, independently from whichever theoretical position might prevail in scholarly debates. Interestingly, corporate law doctrine pertinent to corporate purpose has remained mostly static but fairly open-ended. This has allowed purpose itself to oscillate between shareholder primacy and the balancing of stakeholder interests rather seamlessly as a socio-historical phenomenon. However, the article finds that, where it is used by private business organisation, corporate law has a limited capacity to accommodate purpose oscillations. Those are limited to merely one-dimensional movements representing corporate income distribution choices considered as socially legitimate each time. Using concepts such as Polanyi’s ‘double-movement’ and Gramsci’s ‘passive revolution’, the article argues that, for as long as social dynamics focused on wealth distribution, private corporate purpose had little difficulty in absorbing social critique and in finding a legitimacy basis for the private business corporation. However, more recently, critique has been shifting away from merely distributional trepidations and towards other non-economic concerns caused by economic growth per se. These concerns add new dimensions for corporate purpose oscillations, which cannot be accommodated irrespective of how open-ended corporate law doctrine on purpose might be. The article concludes with an analysis of what this might entail for corporate law as a socially legitimate structure for private business.
Optimizing Promoters and Subcellular Localization for Constitutive Transgene Expression in Marchantia polymorpha
Authors: Tse Sze Wai , Annese Davide , Romani Facundo , Guzman-Chavez Fernando , Bonter Ignacy , Forestier Edith , Frangedakis Eftychios , Haseloff Jim
Published: June 2024

Marchantia polymorpha has become an important model system for comparative studies and synthetic biology. The systematic characterization of genetic elements would make heterologous gene expression more predictable in this test bed for gene circuit assembly and bioproduction. Yet, the toolbox of genetic parts for Marchantia includes only a few constitutive promoters that need benchmarking to assess their utility. We compared the expression patterns of previously characterized and new constitutive promoters. We found that driving expression with the double enhancer version of the cauliflower mosaic virus 35S promoter (pro35S × 2) provided the highest yield of proteins, although it also inhibits the growth of transformants. In contrast, promoters derived from the Marchantia genes for ETHYLENE RESPONSE FACTOR 1 and the CLASS II HOMEODOMAIN-LEUCINE ZIPPER protein drove expression to higher levels across all tissues without a growth penalty and can provide intermediate levels of gene expression. In addition, we showed that the cytosol is the best subcellular compartment to target heterologous proteins for higher levels of expression without a significant growth burden. To demonstrate the potential of these promoters in Marchantia, we expressed RUBY, a polycistronic betalain synthesis cassette linked by P2A sequences, to demonstrate coordinated expression of metabolic enzymes. A heat-shock-inducible promoter was used to further mitigate growth burdens associated with high amounts of betalain accumulation. We have expanded the existing tool kit for gene expression in Marchantia and provided new resources for the Marchantia research community.
Faith, Feminism and Politics: The Inter-war Campaigning Strategies of St Joan’s Social and Political Alliance
Authors: Mangion Carmen M
Published: June 2024

Knitting together faith, feminism, and politics, this article examines St Joan’s Social and Political Alliance as a significant contributor to the interwar feminist movement locating them within the public, political sphere. It contends that religious identities, in this study, a Catholic identity, can help to deepen and complicate our understanding of feminism. Members of St Joan’s Alliance walked a tightrope, navigating their feminist and Catholic ideals. The article begins by explaining their ‘equalitarian’ feminism and how they married this to their Catholicism. Then, two means of promoting and furthering their public presence as interwar feminists are identified. First, the Alliance encouraged Catholic women’s involvement in the democratic process. As public speakers and political actors, they educated and politicized new citizens. Secondly, the periodical press, a key strategic tool, was used to amplify the political campaigns of the Alliance to its Catholic readers, and to participate in public conversations amongst the wider community of feminist and women’s activists. The Alliance articulated their feminist programme cogently to their co-religionists, sometimes having to justify its feminism, some of which was deemed contrary to the ideal of Catholic womanhood. St Joan’s Alliance was not a peripheral feminist organization; it operated on the national and global stage alongside other similar organizations.
An insight into the gut microbiota after Schistosoma japonicum eggs immunization in an experimental ulcerative colitis model
Authors: Wu Peng , Li Wenhao , Xie Yiting , Guan Wei , Yang Shuguo , Li Jian , Zhao Yanqing
Published: June 2024

Schistosome infection and schistosome‐derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS‐induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS‐induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.
Application of Human Acellular Dermal Matrix with Skin Graft for Lacunar Soft-Tissue Defect of Lateral Heel after Calcaneal Fracture
Authors: Song Xiaoliang , Zhao Shuo , Wang Fengyu , Liu Yuan , Wang Li , Xu Yali , Lv Li , Duan Wenxu , Zhang Hongjuan , Bai Runze , Sun Hejun , Shao Xinzhong
Published: June 2024

OBJECTIVE

To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture.

METHODS

From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up.

RESULTS

Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days).

CONCLUSIONS

The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.
Lived Experiences of Patients After Colorectal Cancer and Permanent Colostomy: A Parallel-Design Mixed-Methods Study
Authors: Duluklu Burcu , Çelik Sevilay Şenol
Published: June 2024

OBJECTIVE

To identify the lived experiences, quality of life (QoL), and level of ostomy adjustment (OA) in patients after colorectal cancer with a permanent colostomy (PC).

METHODS

In this parallel-design mixed-methods study, the researchers interviewed 14 patients after colorectal cancer whose PC was created more than 1 year prior. Qualitative data were interpreted using hermeneutic interpretive phenomenological design. Quantitative data were collected with the Stoma QoL Scale and OA Inventory-23.

RESULTS

The mean age of the participants was 61.5 (SD, 10.0) years, and the mean PC duration was 7.7 (SD, 5.0) years. Mean QoL and OA scores were just above the median. Three superordinate themes consisting of nine themes emerged from the analysis: (1) early experiences (acceptance, medical problems, and emotional changes); (2) long-term experiences (physiologic experiences, psychosocial experiences, economic experiences, and coping strategies); (3) feelings and expectations about the future (worries and expectations).

CONCLUSIONS

Even individuals who have been living with a PC for a long time may not be fully adapted to the process and may not have internalized lifestyle changes. Nurses should provide support to individuals with a PC through routine follow-ups, social support, and facilitative healthcare strategies regardless of the length of time since PC creation.
Factors Influencing Readiness for Hospital Discharge among Patients Undergoing Enterostomy: A Descriptive, Cross-sectional Study
Authors: Li Siqing , Luo Cuilian , Xie Minyi , Lai Jinman , Qiu Hong , Xu Lihong , Chen Jianchang , Mo Linjie , Guan Xiaofang , Tang Feng , Zhang Yan , Huang Qiaona , Liu Yuxia , Luo Wenxin , Chen Jianmin
Published: June 2024

Objective

To examine the factors influencing hospital discharge readiness among Chinese patients who have undergone enterostomy.

Methods

In this descriptive, cross-sectional study, researchers recruited patients with colorectal cancer who underwent enterostomy at a tertiary hospital in Guangdong Province, China, via convenience sampling between January 2021 and January 2023. Participants completed the Readiness for Hospital Discharge Scale, Ostomy Self-care Ability Scale, and Stoma-Quality of Life-Chinese Questionnaire (Chinese version) at the time of hospital discharge. Univariate, correlation, and multiple linear regression analyses were performed to explore the impact of self-care ability, quality of life, and other clinicodemographic characteristics on patients’ readiness for hospital discharge.

Results

Of the 200 questionnaires distributed, 177 (88.5%) were completed and included in the final analysis. The median scores for the factors considered in this study were as follows: Readiness for Hospital Discharge Scale was 148.00 (interquartile range [IQR], 117.50, 164.00), self-care intention of the Ostomy Self-care Ability Scale was 36.00 (IQR, 34.00, 40.00), self-care knowledge of the Ostomy Self-care Ability Scale was 17.00 (IQR, 15.00, 19.00), self-care skill of the Ostomy Self-care Ability Scale was 5.00 (IQR, 3.00, 6.00), and the total score for quality of life was 60.00 (IQR, 49.00, 69.00). Multiple linear regression analysis identified several key factors explaining 48.2% of the variance in global readiness for hospital discharge: global quality of life (β= .347,P< .001), self-care knowledge (β= .259,P< .001), leakage during hospitalization (β= −0.241,P< .001), monthly family income (β= .148,P= .008), stoma siting before surgery (β= .130,P= .020), and self-care intention (β= .127,P= .035).

Conclusions

The readiness for hospital discharge among patients undergoing enterostomy in this study was high. Factors such as quality of life, self-care knowledge, leakage during hospitalization, monthly family income, stoma siting before surgery, and self-care intention after undergoing enterostomy influenced the patients’ readiness for hospital discharge. Therefore, future studies should focus on developing interventions to enhance patients’ readiness for hospital discharge.
In Silico Identification of Potential Inhibitors of Mycobacterium tuberculosis DNA Gyrase from Phytoconstituents of Indian Medicinal Plants
Authors: Rout Janmejaya , Das Sayani , Kaledhonkar Sandip
Published: June 2024

DNA gyrase, the sole type-II topoisomerase inMycobacterium tuberculosis, plays a significant role in the bacteria’s survival by catalyzing the DNA topology change and is considered a crucial drug target. The emergence of drug resistance inMycobacterium tuberculosisspecifically against the second line of drugs; fluoroquinolones, targeting DNA gyrase, demands new potential compounds that would efficiently interact with it. To find a common suitable inhibitor for the apo and mutated forms of DNA gyrase, in this study, the compounds from an Indian medicinal plant database were screened for selecting potential drug-like molecules and two compounds IM5 and IM7 were selected after successful virtual screening and hit optimization with ADMET predictions, and chosen for MD simulation. The MMPBSA analysis of binding free energy validates the docking results of the two molecules. The principal component analysis also supported the stability of the complexes and thus, these two molecules have turned out to be promising candidates againstMycobacterium tuberculosis. Overall, this work sheds light on the potential of DNA gyrase inhibitors as therapeutic agents forMycobacterium tuberculosistreatment, and IM5 and IM7 showed promise as future research compounds.
LRRK2G2019S variant is associated with transcriptional changes in Parkinson’s disease human myeloid cells under proinflammatory environment
Authors: Navarro Elisa , Efthymiou Anastasia G. , Parks Madison , Riboldi Giulietta M , Vialle Ricardo A. , Udine Evan , Muller Benjamin Z. , Humphrey Jack , Allan Amanda , Argyrou Charlie Charalambos , Lopes Katia de Paiva , Münch Alexandra , Raymond Deborah , Sachdev Rivka , Shanker Vicki L. , Miravite Joan , Katsnelson Viktoryia , Leaver Katherine , Frucht Steve , Bressman Susan B , Marcora Edoardo , Saunders-Pullman Rachel , Goate Alison , Raj Towfique
Published: June 2024

The G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is a major risk factor for the development of Parkinson’s disease (PD). LRRK2, although ubiquitously expressed, is highly abundant in cells of the innate immune system. Given the importance of central and peripheral immune cells in the development of PD, we sought to investigate the consequences of the G2019S mutation on microglial and monocyte transcriptome and function. We have generated large-scale transcriptomic profiles of isogenic human induced microglial cells (iMGLs) and patient derived monocytes carrying the G2019S mutation under baseline culture conditions and following exposure to the proinflammatory factors IFNγ and LPS. We demonstrate that the G2019S mutation exerts a profound impact on the transcriptomic profile of these myeloid cells, and describe corresponding functional differences in iMGLs. The G2019S mutation led to an upregulation in lipid metabolism and phagolysosomal pathway genes in untreated and LPS/IFNγ stimulated iMGLs, which was accompanied by an increased phagocytic capacity of myelin debris. We also identified dysregulation of cell cycle genes, with a downregulation of the E2F4 regulon. Transcriptomic characterization of human-derived monocytes carrying the G2019S mutation confirmed alteration in lipid metabolism associated genes. Altogether, these findings reveal the influence of G2019S on the dysregulation of the myeloid cell transcriptome under proinflammatory conditions.
Evidence for domain-general arousal from semantic and neuroimaging meta-analyses reconciles opposing views on arousal
Authors: Sabat Magdalena , de Dampierre Charles , Tallon-Baudry Catherine
Published: June 2024

The term arousal is very often used, but classical textbooks from different domains of neuroscience and psychology offer surprisingly different views on what arousal is. The huge number of scientific articles with the term arousal (∼50.000) highlights the importance of the concept but also explains why such a vast literature has never been systematically reviewed so far. Here, we leverage the tools of natural language processing to probe the nature of arousal in a data-driven, comprehensive manner. We show that arousal comes in seven varieties: cognitive, emotional, physiological, sexual, related to stress disorders, to sleep, or to sleep disorders. We then ask whether domain-general arousal exists, and run meta-analyses of the brain imaging literature to reveal that all varieties of arousal, except arousal in sleep disorders for lack of data, converge onto a cortical arousal network composed of the pre-supplementary motor area and the left and right dorsal anterior insula. More precisely, we find that activity in dysgranular insular area 7, the region with the highest convergence across varieties of arousal is also specific to arousal. Our results show that arousal corresponds to a construct at least partially shared across different domains of neuroscience and identify the domain-general cortical arousal network. Novel taxonomies of arousal reconciling seemingly opposing views on what arousal is should thus include domain-general arousal as a central component.

Significance statement

The term arousal has been used in almost 50.000 scientific papers, but it is only loosely defined. The few attempts at defining arousal in neuroscience and psychology resulted in divergent views: arousal as a multi-dimensional construct or arousal as a global state. Is arousal an abstraction of the scientists’ mind reflecting a myriad of distinct processes, or is there some common neuronal feature? We used large-scale semi-automatic text mining methods and neuroimaging meta-analyses to review this vast and heterogeneous literature. Our results reveal the existence of domain-general arousal, a process shared by situations as different as a cognitive task, an emotional context, and the transition to wakefulness or sexual behavior. Domain-general arousal reconciles the concepts of general and multi-dimensional arousal.
RTM-align: an improved RNA alignment tool with enhanced short sequence performance via post-standardization and fragment alignment
Authors: Qiu Zijie , Xu Sheng , Wei Junkang , Shen Tao , Sun Siqi
Published: June 2024

Understanding the three-dimensional structure of RNA is crucial for studying various biological processes. Accurate alignment and comparison of RNA structures are essential for illustrating RNA functionality and evolution. The existing RNA alignment tools suffer from limitations such as size-dependency of scoring functions and inadequate handling of short RNA fragments, leading to the conflicting interpretation of structural and functional relationships among RNA molecules. Hence, we introduce RTM-align, a novel RNA structural alignment tool enhanced for short RNAs. RTM-align employs the RTM-score, which integrates post-standardization to ensure size-independence and utilizes a fragment alignment strategy that improves alignment accuracy by concentrating on structural motifs and local structural elements. Benchmarking results demonstrate that RTM-align outperforms existing tools in RNA structure comparison, offering a universal scoring scale regardless of RNA length. The improvement is particularly evident in evaluating predicted structures for CASP15 RNA targets, with significant enhancements observed for the short RNA target R1117. RTM-align is expected to significantly improve the accuracy and reliability of RNA structure alignment and comparison, thereby aiding in the deeper understanding and discovery of novel RNA functions and their interactions in biological systems. RTM-align is now available athttps://github.com/BEAM-Labs/RTM-align.
Development and assessment of a new multichannel electrocutaneous device for non-invasive somatosensory stimulation for magnetic resonance applications
Authors: Travassos Carolina , Sayal Alexandre , Fonte Paulo , Carolino Nuno , Direito Bruno , Lopes Luis , Afonso Sonia , Lopes Tania , Sousa Teresa , Castelo-Branco Miguel
Published: June 2024

Electrocutaneous stimulation (ES) relies on the application of an electrical current flowing through the surface of the skin, eliciting a tactile percept. It can be applied for somatosensory mapping approaches at functional magnetic resonance imaging (fMRI) to obtain somatotopic maps illustrating the spatial patterns reflecting the functional organization of the primary somatosensory cortex (S1). However, its accessibility remains constrained, particularly in applications requiring multiple stimulation channels. Furthermore, the magnetic resonance (MR) environment poses several limitations in this regard. This study presents a prototype of a multichannel electrocutaneous stimulation device designed for somatosensory stimulation of the upper limbs of human participants in an MR environment in an inexpensive, safe, customizable, controlled, reproducible, and automated way. Our current-controlled, voltage-limited, stimulation device comprises 20 stimulation channels that can be individually configured to deliver various non-simultaneous combinations of personalized electrical pulses, depending on the subject, stimulation site, and stimulation paradigm. It can deliver a predefined electrical stimulus during fMRI acquisition, synchronized with the stimulation task design and triggered upon initiation of the acquisition sequence. Regarding device assessment, we conducted tests using an electrical circuit equivalent to the impedance of the human body and the electrode-skin interface to validate its feasibility. Then, we evaluated user acceptability by testing the device in human participants. Considering the stringent conditions of the MR environment, we performed a comprehensive set of safety and compatibility evaluations using a phantom. Lastly, we acquired structural and functional MR data from a participant during a somatosensory stimulation experiment to validate brain activity elicited by electric stimulation with our device. These assessments confirmed the device’s safety in fMRI studies and its ability to elicit brain activity in the expected brain areas. The scope of application of our device includes fMRI studies focused on somatosensory mapping and brain-computer interfaces related to somatosensory feedback.
Vascular regional analysis unveils differential responses to anti-angiogenic therapy in pancreatic xenografts through macroscopic photoacoustic imaging
Authors: Sweeney Allison , Xavierselvan Marvin , Langley Andrew , Solomon Patrick , Arora Aayush , Mallidi Srivalleesha
Published: June 2024

Pancreatic cancer (PC) is a highly lethal malignancy and the third leading cause of cancer deaths in the U.S. Despite major innovations in imaging technologies, there are limited surrogate radiographic indicators to aid in therapy planning and monitoring. Amongst the various imaging techniques Ultrasound-guided photoacoustic imaging (US-PAI) is a promising modality based on endogenous blood (hemoglobin) and blood oxygen saturation (StO2) contrast to monitor response to anti-angiogenic therapies. Adaptation of US-PAI to the clinical realm requires macroscopic configurations for adequate depth visualization, illuminating the need for surrogate radiographic markers, including the tumoral microvessel density (MVD). In this work, subcutaneous xenografts with PC cell lines AsPC-1 and MIA-PaCa-2 were used to investigate the effects of receptor tyrosine kinase inhibitor (sunitinib) treatment on MVD and StO2. Through histological correlation, we have shown that regions of high and low vascular density (HVD and LVD) can be identified through frequency domain filtering of macroscopic PA images which could not be garnered from purely global analysis. We utilized vascular regional analysis (VRA) of treatment-induced StO2and total hemoglobin (HbT) changes. VRA as a tool to monitor treatment response allowed us to identify potential timepoints of vascular remodeling, highlighting its ability to provide insights into the TME not only for sunitinib treatment but also other anti-angiogenic therapies.
Multi-omics profiling of mouse polycystic kidney disease progression at a single cell resolution
Authors: Muto Yoshiharu , Yoshimura Yasuhiro , Wu Haojia , Chang-Panesso Monica , Ledru Nicolas , Woodward Owen M. , Outeda Patricia , Cheng Tao , Mahjoub Moe R. , Watnick Terry J. , Humphreys Benjamin D.
Published: June 2024

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to end-stage kidney disease. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single nucleus multimodal atlas of an orthologous mouse PKD model at early, mid and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes. We catalogue differentially expressed genes and activated epigenetic regions in each cell type during PKD progression, characterizing cell-type-specific responses toPkd1deletion. We describe heterogeneous, atypical collecting duct cells as well as proximal tubular cells that constitute cyst epithelia in PKD. The transcriptional regulation of the cyst lining cell marker GPRC5A is conserved between mouse and human PKD cystic epithelia, suggesting shared gene regulatory pathways. Our single nucleus multiomic analysis of mouse PKD provides a foundation to understand the earliest changes molecular deregulation in a mouse model of PKD at a single-cell resolution.
Structural determinants of protein kinase A essential for CFTR channel activation
Authors: Mihályi Csaba , Iordanov Iordan , Szöllősi András , Csanády László
Published: June 2024

CFTR, the anion channel mutated in cystic fibrosis (CF) patients, is activated by the catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both reversibly, through binding, and irreversibly, through phosphorylation of multiple serines in CFTR’s regulatory (R) domain. Here we identify key molecular determinants of the CFTR/PKA-C interaction essential for these processes. By comparing CFTR current activation in the presence of ATP or an ATP analog unsuitable for phosphotransfer, as well as pseudosubstrate peptides of various lengths, we identify two distinct specific regions of the PKA-C surface which interact with CFTR to cause reversible and irreversible CFTR stimulation, respectively. Whereas the “substrate site” mediates CFTR phosphorylation, a distinct hydrophobic patch (the “docking site”) is responsible for reversible CFTR activation, achieved by stabilizing the R domain in a “released” conformation permissive to channel gating. Furthermore, by comparing PKA-C variants with different posttranslational modification patterns we find that direct membrane tethering of the kinase through its N-terminal myristoyl group is an unappreciated fundamental requirement for CFTR activation: PKA-C demyristoylation abolishes reversible, and profoundly slows irreversible, CFTR stimulation. For the F508del CFTR mutant, present in ∼90% of CF patients, maximal activation by de-myristoylated PKA-C is reduced by ∼10-fold compared to that by myristoylated PKA-C. Finally, in bacterial genera that contain common CF pathogens we identify virulence factors that demyristoylate PKA-Cin vitro, raising the possibility that during recurrent bacterial infections in CF patients PKA-C demyristoylation may contribute to the exacerbation of lung disease.

Significance Statement

CFTR is an anion channel crucial for salt-water transport across epithelia, and is activated by the catalytic subunit of protein kinase A (PKA-C). Reduced activity of mutant CFTR causes cystic fibrosis and CFTR hyperstimulation by sustained PKA-C activity causes diarrhea. PKA-C activates CFTR reversibly through simple binding, and irreversibly by phosphorylating the channel. We uncover here important structural requirements for these two processes. First, two distinct PKA-C surface areas mediate reversible and irreversible CFTR activation. Second, membrane anchoring of PKA-C through a covalently linked fatty (myristic) acid is required for both effects. Finally, we identify bacterial enzymes that cleave the myristic acid from PKA-C, thereby reducing activation of mutant CFTR channels, present in cystic fibrosis patients, by up to tenfold.
Faster but not sweeter: A model of E. coli Re-level lipopolysaccharide for Martini 3 and a Martini 2 version with accelerated kinetics
Authors: Brandner Astrid , Prakaash Dheeraj , Gonzalez Alexandre Blanco , Waterhouse Fergus , Khalid Syma
Published: June 2024

Lipopolysaccharide (LPS) is a complex glycolipid molecule that is the main lipidic component of the outer leaflet of the outer membrane of Gram-negative bacteria. It has very limited lateral motion compared to phospholipids, which are more ubiquitous in biological membranes, including in the inner leaflet of the outer membrane of Gram-negative bacteria. The slow-moving nature of LPS can present a hurdle for molecular dynamics simulations given the (pragmatically) accessible timescales to simulations are currently limited to microseconds, during which LPS displays some conformational dynamics, but hardly any lateral diffusion. Thus, it is not feasible to observe phenomena such as insertion of molecules, including antibiotics/antimicrobials directly into the outer membrane from the extracellular side nor to observe LPS dissociating from proteins via molecular dynamics using currently available models at the atomistic and more coarse-grained levels of granularity. Here we present a model of deep rough LPS compatible with the Martini 2 coarse-grained force field with scaled down non-bonded interactions to enable faster diffusion. We show that the faster-diffusing LPS model is able to reproduce the salient biophysical properties of the standard models, but due to its faster lateral motion, molecules are able to penetrate deeper into membranes containing the faster model. We show that faster LPS model is able to reproduce experimentally determined patterns of interaction with outer membrane proteins, while also allowing for LPS to associate/dissociate with proteins within microsecond timescales. We also complete the Martini 3 LPS toolkit for E. coli by presenting a (standard) model of deep rough LPS for this forcefield.
Cognitive reserves hold back age-related upregulation of neural activities in speech-in-noise perception
Authors: Zhang Lei , Ross Bernhard , Du Yi , Alain Claude
Published: June 2024

During cognitive tasks, increased frontoparietal neural activity and functional connectivity are commonly observed in older adults. Cognitive reserves accrued from positive life choices can provide additional neural resources to cope with aging. However, how cognitive reserves interact with upregulated neural activity in older adults is poorly understood. We measured brain activity with fMRI during a speech-in-noise task and assessed whether cognitive reserve accumulated from long-term musical training bolsters or holds back age-related upregulated activity. Older musicians exhibited less upregulation of task-induced functional connectivity than older non-musicians in auditory dorsal regions, which predicted better behavioral performance in older musicians. These results suggest that cognitive reserve may hold back neural recruitment. Besides functional connectivity strength, we also found that older musicians showed more youth-like fine spatial patterns of functional connectivity than older non-musicians. Our findings enlightened the intricate interplay between cognitive reserve and age-related upregulated activity during speech in noise perception.

Significance Statement

Understanding the interplay between cognitive reserve and age-related neural changes is vital for developing strategies to mitigate cognitive decline in older adults. This study reveals that long-term musical training, which provides cognitive reserve for speech perception, helps older musicians preserve youth-like levels of functional connectivity and fine-scale activity patterns in the auditory dorsal stream during speech-in-noise perception. Unlike older non-musicians, who exhibit age-related neural upregulation, older musicians maintain youth-like connectivity patterns akin to those of younger adults, resulting in superior speech-in-noise perception. These findings support the “Hold-back upregulation” hypothesis and suggest that musical training counteracts age-related declines by preserving youthful brain function. The results offer valuable insights for designing interventions to enhance aging populations’ cognitive function and communication abilities.
The 11β-hydroxysteroid dehydrogenase type 1 inhibitor SPI-62 prevents morbidity in a mouse model of Cushing’s syndrome
Authors: Pan Xingyu , Hou Qiongqiong , Su Jing , Xu Jiahui , Li Min , Li Jiawen , Shi Xuerou , Schmicker Caleb , Magers Tobias , Bracken William M , Katz David A.
Published: June 2024

11β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitors represent a potential therapeutic approach for patients with Cushing’s syndrome, autonomous cortisol secretion (ACS), or iatrogenic glucocorticoid (GC) excess. We assessed whether the HSD-1 inhibitor SPI-62 prevents GC-associated morbidity in a mouse Cushing’s syndrome model. Corticosterone (CORT) was administered to mice for 5 weeks. Animals who received CORT were randomized between vehicle and 3 SPI-62 regimens. A control group received neither CORT nor SPI-62. Body weight was measured daily to enable weight-based SPI-62 administration. Food consumption by pair-housed animals was reported weekly. Insulin sensitivity was evaluated by fasting homeostatic model assessment of insulin resistance. Adiposity and skeletal myopathy were measured using magnetic resonance imaging and post-mortem weights of fat depots and skeletal muscles. Grip strength was measured with a digital meter. Ambulation behavior in an open field maze was assessed. Post-mortem dermal thickness was quantified. Skin structure was evaluated by histology. CORT was associated with decreased insulin sensitivity, increased adiposity, skeletal myoatrophy, reduced grip strength, decreased dermal thickness, and skin structural changes. A trend of increased food consumption and an unexpected biphasic weight change were observed with CORT. SPI-62 attenuated all observed adverse effects in a dose-dependent manner. In general, results for the high SPI-62 regimen were similar as those in animals who received no CORT, suggesting that full HSD-1 inhibition should be maintained throughout a dose interval to mitigate the effects of glucocorticoid excess.
Spontaneous symmetry breaking of cooperation between species
Authors: Hauert Christoph , Szabó György
Published: June 2024

In mutualistic associations two species cooperate by exchanging goods or services with members of another species for their mutual benefit. At the same time competition for reproduction primarily continues with members of their own species. Inintra-species interactions the prisoner’s dilemma is the leading mathematical metaphor to study the evolution of cooperation. Here we considerinter-species interactions in the spatial prisoner’s dilemma, where members of each species reside on one lattice layer. Cooperators provide benefits to neighbouring members of the other species at a cost to themselves. Hence, interactions occur across layers but competition remains within layers. We show that rich and complex dynamics unfold when varying the cost-to-benefit ratio of cooperation,r. Four distinct dynamical domains emerge that are separated by critical phase transitions, each characterized by diverging fluctuations in the frequency of cooperation:(i)for largercooperation is too costly and defection dominates;(ii)for lowerrcooperators survive at equal frequencies in both species;(iii)loweringrfurther results in an intriguing, spontaneous symmetry breaking of cooperation between species with increasing asymmetry for decreasingr;(iv)finally, for smallr, bursts of mutual defection appear that increase in size with decreasingrand eventually drive the populations into absorbing states. Typically one species is cooperating and the other defecting and hence establish perfect asymmetry. Intriguingly and despite the symmetrical model setup, natural selection can nevertheless favour the spontaneous emergence of asymmetric evolutionary outcomes where, on average, one species exploits the other in a dynamical equilibrium.