bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the forecast quality of near-term climate projections by constraining internal variability based on decadal predictions and observations
Authors: Donat Markus G , Mahmood Rashed , Cos Pep , Ortega Pablo , Doblas-Reyes Francisco
Published: June 2024

Projections of near-term climate change in the next few decades are subject to substantial uncertainty from internal climate variability. Approaches to reduce this uncertainty by constraining the phasing of climate variability based on large ensembles of climate simulations have recently been developed. These approaches select those ensemble members that are in closer agreement with sea surface temperature patterns from either observations or initialized decadal predictions. Previous studies demonstrated the benefits of these constraints for projections up to 20 years into the future, but these studies applied the constraints to different ensembles of climate simulations, which prevents a consistent comparison of methods or identification of specific advantages of one method over another. Here we apply several methods to constrain internal variability phases, using either observations or decadal predictions as constraining reference, to an identical multi-model ensemble consisting of 311 simulations from 37 models from the Coupled Model Intercomparison Project phase 6 (CMIP6), and compare their forecast qualities. We show that constraining based on both observations and decadal predictions significantly enhances the skill of 10 and 20-year projections for near-surface temperatures in some regions, and that constraining based on decadal predictions leads to the largest added value in terms of probabilistic skill. We further explore the sensitivity to different implementations of the constraint that focus on the patterns of either internal variability alone or a combination of internal variability and long-term changes in response to forcing. Looking into the near-term future, all variations of the constraints suggest an accelerated warming of large parts of the Northern Hemisphere for the period 2020–2039, in comparison to the unconstrained CMIP6 ensemble.
Signaling without Saying
Authors: Henderson Robert , McCready Elin
Published: June 2024

Signaling without Saying develops game-theoretic approaches to social meaning to model the phenomenon of dogwhistles. Dogwhistles, known primarily from political speech, involve language that sends one message to an out-group while at the same time sending a second (often taboo, controversial, or inflammatory) message to an in-group. We argue that dogwhistles should be treated as primarily bearing social meaning, as understood by modern variationist sociolinguistic theories. We show that dogwhistle communication can be modeled in Bayesian signaling games where speakers are attempting to signal their sociolinguistic persona to listeners who are attempting to detect the persona of their interlocuter. Dogwhistles are useful precisely when optimal play for a speaker involves hiding the sociolinguistic persona being sent to one subaudience from another subaudience. With this basic formal account in hand, this work explores dogwhistles in depth, but also a variety of related phenomena. We identify for the first time two different kinds of dogwhistle meaning, and model them. We show how novel implicatures in the social meaning domain can arise when a listener detects a dogwhistle, and connect them to implicatures familiar in the truth-conditional domain. We show how social meaning can be added to theories of trust in testimonial evidence, and explain why dogwhistles can help establish trust with an audience, even when expressing false propositions. Finally, we look at connections between dogwhistles, as we model them, and other issues important in epistemology and philosophy of language which might involve social meaning, like standpoint theory.
Stoic Tolerance?
Authors: Atkins Jed W
Published: June 2024

Chapter 2 examines Stoic treatments of endurance, focusing on the writings of Seneca and Marcus Aurelius. Stoicism provides an alternate ancient tradition against which to assess the contours and distinctiveness of the North African Christian tradition. The Stoic concept of endurance reveals different theological, cosmological, political, and psychological commitments than those within the North African Christian tradition. For the Stoics judgment involves recognizing that the only actions that are truly good or evil are those within one’s own power. This conception of judgment dissociates endurance from political judgment in the sense of a judgment about the common good. Stoic endurance becomes strangely apolitical and unstable: if there are no external evils to forbear, tolerance, which requires objection, disappears. Stoicism becomes simultaneously too politically quietist and too personally rigorous—a morally demanding philosophy that nevertheless leaves society largely unchanged.
Augustine on Political Judgment and Tolerance
Authors: Atkins Jed W
Published: June 2024

Chapter 8 examines how Augustine applies his account of judgment and patience to the controversy with the Donatists. I argue that Augustine’s so-called anti-Donatist writings deepen and extend, rather than undermine, the tradition of thinking about tolerance he inherited from Tertullian, Cyprian, and Lactantius. Augustine’s account confronts a common objection to the notion of tolerance as forbearing what one finds objectionable: doesn’t such forbearance in the face of injustice make one complicit in the resulting wrong? Augustine’s theory answers this objection by linking judgment and tolerance. One must consider one’s obligation to judge before one can tolerate. Augustine’s particular account of judgment and tolerance presupposes that human beings are social and temporal creatures. Tolerance depends on a judgment that acknowledges the realities of space and time. Conversely, to judge without properly acknowledging space and time distorts judgment and underwrites a simple dualism in the present that makes tolerance impossible.
Issues of science, history, and language
Authors: Kragh Helge
Published: June 2024

The language of science differs in a number of ways from ordinary language, and the relation between the two has been discussed for centuries. Eponyms and metaphors are common to the two versions, and yet they function differently. Words constantly change in meaning, such as illustrated by the words ‘atom’, ‘molecule’, and ‘scientist’, the latter a neologism coined in 1834. As discussed in one of the sections, what counts as a science has also changed over time. There are several ‘lost sciences’ no longer recognized as proper sciences. The last section deals in some detail with the history of words entering geology, a science which was only named so in the mid-seventeenth century.
Heavenly sciences
Authors: Kragh Helge
Published: June 2024

Surprisingly many of our common words are derived from the astronomical sciences. The planets and other celestial bodies have particular names that reflect their histories and attempts to categorize them. For example, the term ‘asteroid’ was proposed by William Herschel because he thought they looked somewhat like stars. One of the sections deals with the vocabulary associated with the belief in extraterrestrial life, including a ‘cosmic language’ with which all advanced beings in the universe can communicate. The chapter also looks at words such as nebula, galaxy, and Milky Way, and how these have been conceived in the past. The final section is devoted to names of twentieth-century cosmology of which ‘Big Bang’ coined in 1949 is probably the most successful and best known.
Development of pENTR-NeCo-lacZα vectors for the preparation of negative control constructs in Gateway cloning
Authors: Kuzuhara Taiki , Monden Kota , Hachiya Takushi , Nakagawa Tsuyoshi
Published: June 2024

Gateway cloning is a useful technology for the simple and reliable preparation of various construct in many organisms. However, there is a problem regarding the negative control construct in the Gateway cloning system. In this study, we developed the pENTR-NeCo-lacZα vector system to create an empty vector that can be used as a negative control construct in Gateway cloning.
Effects of inbreeding and elevated rearing temperatures on strategic sperm investment
Authors: Chung Meng-Han Joseph , Mahmud-Al-Hasan Md , Jennions Michael D , Head Megan L
Published: June 2024

Males often strategically adjust the number of available sperm based on the social context (i.e. sperm priming response), but it remains unclear how environmental and genetic factors shape this adjustment. In freshwater ecosystems, high ambient temperatures often lead to isolated pools of hotter water in which inbreeding occurs. Higher water temperatures and inbreeding can impair fish development, potentially disrupting sperm production. We used guppies (Poecilia reticulata) to investigate how developmental temperature (26 °C, 30 °C) and male inbreeding status (inbred, outbred) influence their sperm priming response. We also tested if sperm priming was affected by whether the female was a relative (sister) and whether she was inbred or outbred. There was no effect of rearing temperature; male inbreeding status alone determined the number of available sperm in response to female presence, her inbreeding status, and her relatedness. Inbred males produced significantly more sperm in the presence of an unrelated, outbred female than when no female was present. Conversely, outbred males did not alter the number of sperm available in response to female presence or relatedness. Moreover, inbred males produced marginally more sperm when exposed to an unrelated female that was outbred rather than inbred, but there was no difference when exposed to an inbred female that was unrelated versus related. Together, a sperm priming response was only observed in inbred males when exposed to an outbred female. Outbred females in our study were larger than inbred females, suggesting that inbred males strategically allocated ejaculate resources toward females in better condition.
Hapsolutely: a user-friendly tool integrating haplotype phasing, network construction, and haploweb calculation
Authors: Vences Miguel , Patmanidis Stefanos , Schmidt Jan-Christopher , Matschiner Michael , Miralles Aurélien , Renner Susanne S
Published: June 2024

Motivation

Haplotype networks are a routine approach to visualize relationships among alleles. Such visual analysis of single-locus data is still of importance, especially in species diagnosis and delimitation, where a limited amount of sequence data usually are available and sufficient, along with other datasets in the framework of integrative taxonomy. In diploid organisms, this often requires separating (phasing) sequences with heterozygotic positions, and typically separate programs are required for phasing, reformatting of input files, and haplotype network construction. We therefore developed Hapsolutely, a user-friendly program with an ergonomic graphical user interface that integrates haplotype phasing from single-locus sequences with five approaches for network/genealogy reconstruction.

Results

Among the novel options implemented, Hapsolutely integrates phasing and graphical reconstruction steps of haplotype networks, supports input of species partition data in the common SPART and SPART-XML formats, and calculates and visualizes haplowebs and fields for recombination, thus allowing graphical comparison of allele distribution and allele sharing among subsets for the purpose of species delimitation. The new tool has been specifically developed with a focus on the workflow in alpha-taxonomy, where exploring fields for recombination across alternative species partitions may help species delimitation.

Availability and implementation

Hapsolutely is written in Python, and integrates code from Phase, SeqPHASE, and PopART in C++ and Haxe. Compiled stand-alone executables for MS Windows and Mac OS along with a detailed manual can be downloaded from https://www.itaxotools.org; the source code is openly available on GitHub (https://github.com/iTaxoTools/Hapsolutely).
Combined with the semantic features of CT and selected clinical variables, a machine learning model for accurately predicting the prognosis of Omicron was established
Authors: Jin Di , Li Zicong , Deng Zhikang , Nan Jiayu , Huang Pei , Zeng Bingliang , Fan Bing
Published: June 2024

Objectives

To efficiently use medical resources and offer optimal personalized treatment for individuals with Omicron infection, it is vital to predict the disease’s outcome early on. This research developed three machine learning models to foresee the results for Omicron-infected patients.

Methods

Data from 253 Omicron-infected patients, including their CT scans, clinical details, and relevant laboratory values, were studied. The patients were categorized into two groups based on their disease progression: favourable prognosis and unfavourable prognosis. Patients manifesting respiratory failure, acute liver or kidney impairment, or fatalities were placed in the “poor” group. Those lacking such symptoms were allocated to the “good” group. The participants were randomly split into training set (202) and validation set (51) with an 8:2 ratio. Radiomics features were produced using image processing, focused segmentation, feature extraction, and selection, leading to the establishment of a radiomics model. A univariate logistic regression method identified potential clinical factors contributing to a clinical model’s development. Eventually, the fused feature set, integrating radiomics features and clinical indicators, was used for the combined model. The model’s prediction performance was assessed using the area under the receiver operating characteristic curve (AUC). The model’s clinical usefulness was evaluated by generating calibration and decision curves.

Results

Compared to other classification models, the combined model showcased the best classification performance. It achieved an AUC of 0.848 and accuracy of 0.763 in the training set, and 0.797 and 0.750 in the validation set, respectively.

Conclusions

This study employed machine learning model to accurately predict the prognosis of Omicron-infected patients.

Advances in knowledge

(1) Topic innovation: At present, there is a lack of research on the use of CT images to construct machine learning models to predict the prognosis of patients with Omicron infection. This study intends to establish clinical, radiomics, and combined models to provide more possibilities for the identification of the two. (2) Platform innovation: The feature extraction and screening and the establishment of omics model in this study will be completed in the intelligent scientific research platform, which can reduce the error caused by human error, simplify the operation steps, and save the time of data processing time.
Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection
Authors: Wu Yan , Zhang Jin , Lin Anqi , Zhang Tinglin , Liu Yong , Zhang Chunlei , Yin Yongkui , Guo Ran , Gao Jie , Li Yulin , Chu Yanhui
Published: June 2024

Background

Given the significant impact on human health, it is imperative to develop novel treatment approaches for diabetic wounds, which are prevalent and serious complications of diabetes. The diabetic wound microenvironment has a high level of reactive oxygen species (ROS) and an imbalance between proinflammatory and anti-inflammatory cells/factors, which hamper the healing of chronic wounds. This study aimed to develop poly(L-lactic acid) (PLLA) nanofibrous membranes incorporating curcumin and silver nanoparticles (AgNPs), defined as PLLA/C/Ag, for diabetic wound healing.

Methods

PLLA/C/Ag were fabricated via an air-jet spinning approach. The membranes underwent preparation and characterization through various techniques including Fourier-transform infrared spectroscopy, measurement of water contact angle, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy, assessment of in vitro release of curcumin and Ag+, testing of mechanical strength, flexibility, water absorption and biodegradability. In addition, the antioxidant, antibacterial and anti-inflammatory properties of the membranes were evaluated in vitro, and the ability of the membranes to heal wounds was tested in vivo using diabetic mice.

Results

Loose hydrophilic nanofibrous membranes with uniform fibre sizes were prepared through air-jet spinning. The membranes enabled the efficient and sustained release of curcumin. More importantly, antibacterial AgNPs were successfully reduced in situ from AgNO3. The incorporation of AgNPs endowed the membrane with superior antibacterial activity, and the bioactivities of curcumin and the AgNPs gave the membrane efficient ROS scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further results from animal studies indicated that the PLLA/C/Ag membranes had the most efficient wound healing properties, which were achieved by stimulating angiogenesis and collagen deposition and inhibiting inflammation.

Conclusions

In this research, we successfully fabricated PLLA/C/Ag membranes that possess properties of antioxidants, antibacterial agents and anti-inflammatory agents, which can aid in the process of wound healing. Modulating wound inflammation, these new PLLA/C/Ag membranes serve as a novel dressing to enhance the healing of diabetic wounds.
Spatiotemporal dynamics of cortical somatosensory network in typically developing children
Authors: Song Yanlong , Shahdadian Sadra , Armstrong Eryn , Brock Emily , Conrad Shannon E , Acord Stephanie , Johnson Yvette R , Marks Warren , Papadelis Christos
Published: June 2024

Sense of touch is essential for our interactions with external objects and fine control of hand actions. Despite extensive research on human somatosensory processing, it is still elusive how involved brain regions interact as a dynamic network in processing tactile information. Few studies probed temporal dynamics of somatosensory information flow and reported inconsistent results. Here, we examined cortical somatosensory processing through magnetic source imaging and cortico–cortical coupling dynamics. We recorded magnetoencephalography signals from typically developing children during unilateral pneumatic stimulation. Neural activities underlying somatosensory evoked fields were mapped with dynamic statistical parametric mapping, assessed with spatiotemporal activation analysis, and modeled by Granger causality. Unilateral pneumatic stimulation evoked prominent and consistent activations in the contralateral primary and secondary somatosensory areas but weaker and less consistent activations in the ipsilateral primary and secondary somatosensory areas. Activations in the contralateral primary motor cortex and supramarginal gyrus were also consistently observed. Spatiotemporal activation and Granger causality analysis revealed initial serial information flow from contralateral primary to supramarginal gyrus, contralateral primary motor cortex, and contralateral secondary and later dynamic and parallel information flows between the consistently activated contralateral cortical areas. Our study reveals the spatiotemporal dynamics of cortical somatosensory processing in the normal developing brain.
The effects of electrical stimulation of ventromedial prefrontal cortex on skin sympathetic nerve activity
Authors: Patel Mariya , Braun Joe A , Henderson Luke A , Dawood Tye , Macefield Vaughan G
Published: June 2024

Skin sympathetic nerve activity (SSNA) is primarily involved in thermoregulation and emotional expression; however, the brain regions involved in the generation of SSNA are not completely understood. In recent years, our laboratory has shown that blood-oxygen-level-dependent signal intensity in the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are positively correlated with bursts of SSNA during emotional arousal and increases in signal intensity in the vmPFC occurring with increases in spontaneous bursts of SSNA even in the resting state. We have recently shown that unilateral transcranial alternating current stimulation (tACS) of the dlPFC causes modulation of SSNA but given that the current was delivered between electrodes over the dlPFC and the nasion, it is possible that the effects were due to current acting on the vmPFC. To test this, we delivered tACS to target the right vmPFC or dlPFC and nasion and recorded SSNA in 11 healthy participants by inserting a tungsten microelectrode into the right common peroneal nerve. The similarity in SSNA modulation between ipsilateral vmPFC and dlPFC suggests that the ipsilateral vmPFC, rather than the dlPFC, may be causing the modulation of SSNA during ipsilateral dlPFC stimulation.
MechanoProDB: a web-based database for exploring the mechanical properties of proteins
Authors: Mesbah Ismahene , Habermann Bianca , Rico Felix
Published: June 2024

The mechanical stability of proteins is crucial for biological processes. To understand the mechanical functions of proteins, it is important to know the protein structure and mechanical properties. Protein mechanics is usually investigated through force spectroscopy experiments and simulations that probe the forces required to unfold the protein of interest. While there is a wealth of data in the literature on force spectroscopy experiments and steered molecular dynamics simulations of forced protein unfolding, this information is spread and difficult to access by non-experts. Here, we introduce MechanoProDB, a novel web-based database resource for collecting and mining data obtained from experimental and computational works. MechanoProDB provides a curated repository for a wide range of proteins, including muscle proteins, adhesion molecules and membrane proteins. The database incorporates relevant parameters that provide insights into the mechanical stability of proteins and their conformational stability such as the unfolding forces, energy landscape parameters and contour lengths of unfolding steps. Additionally, it provides intuitive annotations of the unfolding pathways of each protein, allowing users to explore the individual steps during mechanical unfolding. The user-friendly interface of MechanoProDB allows researchers to efficiently navigate, search and download data pertaining to specific protein folds or experimental conditions. Users can visualize protein structures using interactive tools integrated within the database, such as Mol*, and plot available data through integrated plotting tools. To ensure data quality and reliability, we have carefully manually verified and curated the data currently available on MechanoProDB. Furthermore, the database also features an interface that enables users to contribute new data and annotations, promoting community-driven comprehensiveness. The freely available MechanoProDB aims to streamline and accelerate research in the field of mechanobiology and biophysics by offering a unique platform for data sharing and analysis. MechanoProDB is freely available at https://mechanoprodb.ibdm.univ-amu.fr.
Capabilities, sustainability, and innovation in mining value chains
Authors: Pietrobelli Carlo , Casaburi Gabriel , Iizuka Michiko
Published: June 2024

The original research presented in this Special Section analyzes different aspects of the potential offered to mining firms in developing countries by new demands for solutions to face environmental, social and technological challenges. The evidence is drawn from extensive fieldworks and comparative econometric research on Latin America, and suggests that the existing opportunities will need to be pursued with firm-level efforts and active regulatory and innovation policies.
Optimal generation expansion planning model for solar PV generation on Run of River-based hydro-based power system using binary genetic algorithm
Authors: Pathak Kaushaki , Chaudhary Sandhya , Bhandari Murahari Prasad , Sharma Pragati , Poudel Nawaraj , Neupane Deependra
Published: June 2024

This paper presents a binary genetic algorithm approach developed to solve the optimal generation expansion planning problem for solar photo-voltaic (PV) based Run of River (ROR) hydro generation systems. The results show that the methodology effectively solves mixed-integer, constrained nonlinear generation expansion problems. The model is then used to optimize the generation expansion problem for the electricity grid in the eastern region of Nepal, considering the under construction and planned solar PV and ROR-based hydropower plants. The optimal problem is formulated to determine the optimal number, location and type of power plant to fulfill the demand for the electricity grid of the eastern zone grid of Nepal. Results show that the total generation from the optimal sites combining hydro and solar sites is found to be about 26% of that of total energy in the Nepalese grid. However, the total demand in the system under consideration for the year is about 1352 GWh. With eliminating line losses, a surplus generation of about 1377 GWh has been found. This surplus can be used as power pooling with neighboring countries. The system has a surplus during the wet season but needs to be improved during the dry season. Hence, appropriate policies can be formulated for power banking and pooling to balance the demand–supply in the system.
BioInstruct: instruction tuning of large language models for biomedical natural language processing
Authors: Tran Hieu , Yang Zhichao , Yao Zonghai , Yu Hong
Published: June 2024

Objectives

To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles.

Materials and Methods

We created the BioInstruct, comprising 25 005 instructions to instruction-tune LLMs (LLaMA 1 and 2, 7B and 13B version). The instructions were created by prompting the GPT-4 language model with 3-seed samples randomly drawn from an 80 human curated instructions. We employed Low-Rank Adaptation (LoRA) for parameter-efficient fine-tuning. We then evaluated these instruction-tuned LLMs on several BioNLP tasks, which can be grouped into 3 major categories: question answering (QA), information extraction (IE), and text generation (GEN). We also examined whether categories (eg, QA, IE, and generation) of instructions impact model performance.

Results and Discussion

Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA on average accuracy metric, 5.7% in IE on average F1 metric, and 96% in Generation tasks on average GPT-4 score metric. Our 7B-parameter instruction-tuned LLaMA 1 model was competitive or even surpassed other LLMs in the biomedical domain that were also fine-tuned from LLaMA 1 with vast domain-specific data or a variety of tasks. Our results also show that the performance gain is significantly higher when instruction fine-tuning is conducted with closely related tasks. Our findings align with the observations of multi-task learning, suggesting the synergies between 2 tasks.

Conclusion

The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.
Polychrome Bone Fluorescence: A Valuable Diagnostic Tool for Fourth-Degree Calvarial Burns. A Case Report
Authors: Malan Annemarie Martha , Öhlbauer Markus , Bader Rolf-Dieter , Wallner Britta
Published: June 2024

Fourth-degree calvarial burns are complex in management with regard to determining bone vitality and subsequent choice of defect coverage. Distinguishing viable and nonviable bone can be challenging. Tetracycline bone fluorescence is well described and in common use in maxillofacial patients with bisphosphonate osteonecrosis and has been reported in septic orthopedic surgery specifically periprosthetic joint infection. On the basis of viable bone fluoresces, the concept of polychrome fluorescence was extrapolated as a diagnostic tool for calvarial burns. Bone fluorescence presents an efficient, non-invasive, and cost-effective diagnostic tool delineating exact necrotic margins in fourth-degree burns ensuring targeted bone-sparing debridement. This report describes the use of polychrome bone fluorescence as an intraoperative tool including a single-center case report with fourth-degree calvarial burns.
The role of GDF5 in regulating enthesopathy development in the Hyp mouse model of XLH
Authors: Sorsby Melissa , Almardini Shaza , Alayyat Ahmad , Hughes Ashleigh , Venkat Shreya , Rahman Mansoor , Baker Jiana , Rana Rakshya , Rosen Vicki , Liu Eva S
Published: June 2024

X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of growth/differentiation factor 5 (Gdf5) is enhanced in Hyp entheses at P14. Thus, to determine a role for GDF5 in enthesopathy development, Gdf5 was deleted globally in Hyp mice and conditionally in Scx + cells of Hyp mice. In both murine models, BMP/IHH signaling was similarly decreased in Hyp entheses, leading to decreased enthesopathy. BMP/IHH signaling remained unaffected in WT entheses with decreased Gdf5 expression. Moreover, deletion of Gdf5 in Hyp entheses starting at P30, after enthesopathy has developed, partially reversed enthesopathy. Taken together, these results demonstrate that while GDF5 is not essential for modulating BMP/IHH signaling in WT entheses, inappropriate GDF5 activity in Scx + cells contributes to XLH enthesopathy development. As such, inhibition of GDF5 signaling may be beneficial for the treatment of XLH enthesopathy.
The role of conflict in the formation and maintenance of variant sex chromosome systems in mammals
Authors: Hughes Jonathan J , Lagunas-Robles German , Campbell Polly
Published: June 2024

The XX/XY sex chromosome system is deeply conserved in therian mammals, as is the role of Sry in testis determination, giving the impression of stasis relative to other taxa. However, the long tradition of cytogenetic studies in mammals documents sex chromosome karyotypes that break this norm in myriad ways, ranging from fusions between sex chromosomes and autosomes to Y chromosome loss. Evolutionary conflict, in the form of sexual antagonism or meiotic drive, is the primary predicted driver of sex chromosome transformation and turnover. Yet conflict-based hypotheses are less considered in mammals, perhaps because of the perceived stability of the sex chromosome system. To address this gap, we catalog and characterize all described sex chromosome variants in mammals, test for family-specific rates of accumulation, and consider the role of conflict between the sexes or within the genome in the evolution of these systems. We identify 152 species with sex chromosomes that differ from the ancestral state and find evidence for different rates of ancestral to derived transitions among families. Sex chromosome-autosome fusions account for 79% of all variants whereas documented sex chromosome fissions are limited to three species. We propose that meiotic drive and drive suppression provide viable explanations for the evolution of many of these variant systems, particularly those involving autosomal fusions. We highlight taxa particularly worthy of further study and provide experimental predictions for testing the role of conflict and its alternatives in generating observed sex chromosome diversity.
Sorry you asked? Mayo, Myriad, and the battles over patent-eligibility
Authors: Cook-Deegan Robert , Geary Janis , Hapke Kara , Skvarkova Zuzana , Filipek Marina , Leaver Jillian
Published: June 2024

Genetic testing for inherited cancer risk changed dramatically when the US Supreme Court handed down unanimous rulings in Mayo v. Prometheus (2012) and Myriad v. Association for Molecular Pathology (2013). Those decisions struck down claims to methods based on ‘laws of nature’ (Mayo) and DNA molecules corresponding to sequences found in nature (Myriad). Senators Thom Tillis (R-NC) and Christopher Coons (D-DE) introduced legislation that would abrogate those decisions and specify narrow statutory exclusions to patent-eligibility in §101 of the US Patent Act. What would be the consequences of doing so? The Supreme Court decisions coincided with changes in how genetic tests were performed, reimbursed and regulated. Multi-gene sequencing supplanted oligo-gene testing as the cost of sequencing dropped 10,000-fold. Payers dramatically changed reimbursement practices. Food and Drug Administration regulation was proposed and remains in prospect. Databases for clinical interpretation made data freely available, augmenting a knowledge commons. The spectacular implosion of Theranos tempered investment in molecular diagnostics. These factors all complicate explanations of why venture capital funding for molecular diagnostics dropped relative to other sectors. Restoring patent-eligibility would put renewed pressure on other patent doctrines, such as obviousness, enablement and written description, that were not raised in the Supreme Court cases.
Please Mind the Gap: Indel-Aware Parsimony for Fast and Accurate Ancestral Sequence Reconstruction and Multiple Sequence Alignment Including Long Indels
Authors: Iglhaut Clara , Pečerska Jūlija , Gil Manuel , Anisimova Maria
Published: June 2024

Despite having important biological implications, insertion, and deletion (indel) events are often disregarded or mishandled during phylogenetic inference. In multiple sequence alignment, indels are represented as gaps and are estimated without considering the distinct evolutionary history of insertions and deletions. Consequently, indels are usually excluded from subsequent inference steps, such as ancestral sequence reconstruction and phylogenetic tree search. Here, we introduce indel-aware parsimony (indelMaP), a novel way to treat gaps under the parsimony criterion by considering insertions and deletions as separate evolutionary events and accounting for long indels. By identifying the precise location of an evolutionary event on the tree, we can separate overlapping indel events and use affine gap penalties for long indel modeling. Our indel-aware approach harnesses the phylogenetic signal from indels, including them into all inference stages. Validation and comparison to state-of-the-art inference tools on simulated data show that indelMaP is most suitable for densely sampled datasets with closely to moderately related sequences, where it can reach alignment quality comparable to probabilistic methods and accurately infer ancestral sequences, including indel patterns. Due to its remarkable speed, our method is well suited for epidemiological datasets, eliminating the need for downsampling and enabling the exploitation of the additional information provided by dense taxonomic sampling. Moreover, indelMaP offers new insights into the indel patterns of biologically significant sequences and advances our understanding of genetic variability by considering gaps as crucial evolutionary signals rather than mere artefacts.
Ethical Considerations in Co-Authoring Research with Music Therapy Stakeholders
Authors: Devlin Kerry , Meadows Anthony , Johnston Morgan , Johnston Cheryl
Published: June 2024

While stakeholders provide invaluable perspectives about music therapy, particularly through the lens of their expertise as participants in music therapy encounters, their perspectives are rarely amplified in the context of full participation in research teams. In support of stakeholder participation in music therapy research, this article introduces and explores ethical considerations related to co-authorship. These ethical considerations are approached in three ways: (1) describing how co-authorship has been undertaken with music therapy stakeholders, specifically disabled children and adults, in a range of contexts, (2) Identifying ethical considerations related to our team’s own research project (Devlin, K., Johnston, M., & Johnston, C. [2024]. Making mistakes together: therapy participant, parent, and therapist perspectives on music therapy in two different settings. Music Therapy Perspectives) with two coauthors who are also stakeholders, and (3) providing guidelines for music therapists interested in coauthoring research with stakeholders. In doing so, the importance of co-authorship as an accessible, equitable research practice is emphasized.

Plain language abstract This article is about planning, doing, and writing research with people who are usually studied in music therapy research. We call this co-research. We talk about: •How to keep people safe •How to make decisions together •How to work and write as a team •If we should use our real names
Distinct SARS-CoV-2 populational immune backgrounds tolerate divergent RBD evolutionary preferences
Authors: Ma Wentai , Fu Haoyi , Jian Fanchong , Cao Yunlong , Li Mingkun
Published: June 2024

Immune evasion is a pivotal force shaping the evolution of viruses. Nonetheless, the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery. Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023, the Chinese population possessed a markedly distinct (less potent) immune background due to its low infection rate, compared to countries experiencing multiple infection waves, presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts. We compared the mutation spectrum and functional potential of the newly derived mutations that occurred in BA.5.2.48, BF.7.14 and BA.5.2.49—variants prevalent in China—with their counterparts in other countries. We found that the emerging mutations in the receptor-binding-domain region in these lineages were more widely dispersed and evenly distributed across different epitopes. These mutations led to a higher angiotensin-converting enzyme 2 (ACE2) binding affinity and reduced potential for immune evasion compared to their counterparts in other countries. These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population. Despite the emergence of numerous immune-evading variants in China, none of them outcompeted the original strain until the arrival of the XBB variant, which had stronger immune evasion and subsequently outcompeted all circulating variants. Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2. Thus, in addition to viral genome surveillance, immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.
Framework for standardizing digital health in resource-constrained settings: a case study of Uganda’s digital health communication infrastructure
Authors: Alunyu Egwar Andrew , Amiyo Mercy Rebekah , Nabukenya Josephine
Published: June 2024

Uganda has several digital health interventions, but most are not interoperable, failing the goal of digitizing the healthcare environment. One major reason for this failure is that the implementations are not based on a common set of standards formally agreed upon by the country’s health ministry. Therefore, Uganda and other countries that have fallen behind in standardizing their health systems need to implement and fast-track the formulation of contextual digital health standards. This study followed a design science approach to develop a framework for standardizing the digital health communication infrastructure. The design went through three cycles of design and improvement. Results show that 17 digital health stakeholders in Uganda who evaluated the framework agreed that they are suitable to guide standardization activities in Uganda. This study argues that other countries with digital health challenges similar to those in Uganda can adopt the framework.
The m6A reader ECT8 is an abiotic stress sensor that accelerates mRNA decay in Arabidopsis
Authors: Cai Zhihe , Tang Qian , Song Peizhe , Tian Enlin , Yang Junbo , Jia Guifang
Published: June 2024

N 6-methyladenosine (m6A) is the most abundant mRNA modification and plays diverse roles in eukaryotes, including plants. It regulates various processes, including plant growth, development, and responses to external or internal stress responses. However, the mechanisms underlying how m6A is related to environmental stresses in both mammals and plants remain elusive. Here, we identified EVOLUTIONARILY CONSERVED C-TERMINAL REGION 8 (ECT8) as an m6A reader protein and showed that its m6A-binding capability is required for salt stress responses in Arabidopsis (Arabidopsis thaliana). ECT8 accelerates the degradation of its target transcripts through direct interaction with the decapping protein DECAPPING 5 within processing bodies. We observed a significant increase in the ECT8 expression level under various environmental stresses. Using salt stress as a representative stressor, we found that the transcript and protein levels of ECT8 rise in response to salt stress. The increased abundance of ECT8 protein results in the enhanced binding capability to m6A-modified mRNAs, thereby accelerating their degradation, especially those of negative regulators of salt stress responses. Our results demonstrated that ECT8 acts as an abiotic stress sensor, facilitating mRNA decay, which is vital for maintaining transcriptome homeostasis and enhancing stress tolerance in plants. Our findings not only advance the understanding of epitranscriptomic gene regulation but also offer potential applications for breeding more resilient crops in the face of rapidly changing environmental conditions.
Partner-switching components PmgA and Ssr1600 regulate high-light acclimation in Synechocystis sp. PCC 6803
Authors: Nakamura Riku , Takahashi Yuji , Tachibana Shogo , Terada Arisa , Suzuki Kakeru , Kondo Kumika , Tozawa Yuzuru , Hihara Yukako
Published: June 2024

Photomixotrophic growth A (PmgA) is a pleiotropic regulator essential for growth under photomixotrophic and prolonged high-light (HL) conditions in the cyanobacterium Synechocystis sp. PCC 6803. The overall similarity with the antisigma factor of the bacterial partner-switching system indicates that PmgA exerts a regulatory function via phosphorylation of its target proteins. In this study, we performed an in vitro phosphorylation assay and protein–protein interaction analysis and found that PmgA interacts with 4 antisigma antagonist homologs, Ssr1600, Slr1856, Slr1859, and Slr1912, but specifically phosphorylates Ssr1600. Phenotypic analyses using the set of gene disruption and overexpression strains of pmgA and ssr1600 revealed that phosphorylation by PmgA is essential for the accumulation of Ssr1600 protein in vivo. The ssr1600-disrupted mutant showed similar phenotypes as those previously reported for the pmgA-disrupted mutant, namely, no obvious phenotype just after the shift to HL, but higher chlorophyll content, 5-aminolevulinic acid synthesis activity, and psaAB transcript levels than those in the wild type after 6 h. These findings indicate that the phosphorylated form of Ssr1600 works as the output of the partner-switching system to coordinately repress chlorophyll biosynthesis and accumulation of photosystem I during HL acclimation.
Nonnegligible cascading impacts of global urban expansion on net primary productivity
Authors: Liu Kangyao , Pei Fengsong , Liu Xiaoping , Zeng Zhenzhong , Zhu Peng , Fang Chuanglin , Xu Xiaocong , Wang Shaojian , Mao Jiafu , Chen Xiuzhi , Wu Changjiang , Cai Yiling , Zeng Li , Shi Qian , Li Xia
Published: June 2024

Accelerated global urban expansion not only directly occupies surrounding ecosystems, but also induces cascading losses of natural vegetation elsewhere through cropland displacement. Yet, how such effects alter the net primary productivity (NPP) worldwide remains unclear. Here, we quantified the direct and cascading impacts of global urban expansion on terrestrial NPP from 1992 to 2020 and projected the impacts under the shared socioeconomic pathways framework by 2100. We found that global urban expansion caused a cascading loss of 29.2 to 63.9 Tg C/year of terrestrial NPP in the historical period (1992–2020), accounting for 13–29% of the total direct NPP loss. Instead, our projections indicate that during 2020–2100, mainly due to the increased relocation of displaced croplands to low-productive ecosystems, the cascading impacts gradually change from negative to positive, leading to a net NPP increase. Such an increase may offset up to 7% of the total direct NPP loss, better balancing crop compensation with NPP maintenance. Our findings highlight the unexpected large cascading impacts of urban expansion on the carbon cycle and stress the importance of regulating land transitions to curtail land-use emissions.
Enhancing social cohesion with cooperative bots in societies of greedy, mobile individuals
Authors: Shi Lei , He Zhixue , Shen Chen , Tanimoto Jun
Published: June 2024

Addressing collective issues in social development requires a high level of social cohesion, characterized by cooperation and close social connections. However, social cohesion is challenged by selfish, greedy individuals. With the advancement of artificial intelligence (AI), the dynamics of human–machine hybrid interactions introduce new complexities in fostering social cohesion. This study explores the impact of simple bots on social cohesion from the perspective of human–machine hybrid populations within network. By investigating collective self-organizing movement during migration, results indicate that cooperative bots can promote cooperation, facilitate individual aggregation, and thereby enhance social cohesion. The random exploration movement of bots can break the frozen state of greedy population, help to separate defectors in cooperative clusters, and promote the establishment of cooperative clusters. However, the presence of defective bots can weaken social cohesion, underscoring the importance of carefully designing bot behavior. Our research reveals the potential of bots in guiding social self-organization and provides insights for enhancing social cohesion in the era of human–machine interaction within social networks.