bluuebunny/crossref_metadata_2025 huggingface dataset:
A review on plasma-based CO2 utilization: process considerations in the development of sustainable chemical production
Authors: LI Sirui , FELICE Giulia De , EICHKORN Simona , SHAO Tao , GALLUCCI Fausto
Published: May 2024

Plasma-based processes, particularly in carbon capture and utilization, hold great potential for addressing environmental challenges and advancing a circular carbon economy. While significant progress has been made in understanding plasma-induced reactions, plasma-catalyst interactions, and reactor development to enhance energy efficiency and conversion, there remains a notable gap in research concerning overall process development. This review emphasizes the critical need for considerations at the process level, including integration and intensification, to facilitate the industrialization of plasma technology for chemical production. Discussions centered on the development of plasma-based processes are made with a primary focus on CO2 conversion, offering insights to guide future work for the transition of the technology from laboratory scale to industrial applications. Identification of current research gaps, especially in upscaling and integrating plasma reactors with other process units, is the key to addressing critical issues. The review further delves into relevant research in process evaluation and assessment, providing methodological insights and highlighting key factors for comprehensive economic and sustainability analyses. Additionally, recent advancements in novel plasma systems are reviewed, presenting unique advantages and innovative concepts that could reshape the future of process development. This review provides essential information for navigating the path forward, ensuring a comprehensive understanding of challenges and opportunities in the development of plasma-based CCU process.
‘For the Benefit of the Afflicted’
Authors: L. Knoppers Laura
Published: May 2024

This chapter offers new insight into Puritan emotions and lived doctrine by focusing on the largely overlooked language of comfort that permeates Mary Rowlandson’s captivity narrative, The Sovereignty and Goodness of God (1682). Rowlandson’s harrowing account of her eleven-week captivity with the Algonquian peoples in wartime New England incorporates scripture verses, both remembered and read, that promise comfort. Yet the narrative tensions between rhetoric and traumatic experience, biblical citation and eye-witness accounting, providence and self-survival, along with the lack of closure after Rowlandson has been ransomed, have been seen as doctrinal failure and a turn towards the secular. Resituating Rowlandson in transatlantic Puritanism, we can see that the biblical language of comfort is inherently dual, pointing towards heavenly comfort that unsettles rather than valorizes the earthly. As such, the captivity narrative interacts closely with the sermon, the spiritual autobiography, and conversion narrative, showing how Rowlandson comes to understand her place as a pilgrim in this world.
Richard Baxter’s ‘Life’
Authors: Charlton Tom
Published: May 2024

This chapter explores how the nonconformist divine Richard Baxter chose to narrativize his experience as a Puritan during the civil wars, Interregnum, and the Restoration. It builds on the textual scholarship of the recent Oxford University Press edition of the Reliquiæ Baxterianæ to show how Baxter, and his posthumous editor Matthew Sylvester, revised and edited his principal autobiographical manuscript to present Baxter as the epitome of moderate Puritanism. Through his insistence that he was a moderate, Baxter’s self-conscious utilization of contemporary understandings of Puritanism for rhetorical and polemical effect both exploited and created shared textual habits in the representation of the Puritan experience to place himself at the centre of an evolving tradition. Baxter and ‘Puritanism’ became mutually reinforcing classifications; this chapter reveals the care and deliberation undertaken by Baxter and his editors to enable the definition of the former to buttress the latter and vice versa.
Conclusion
Authors: Constantine Mary-Ann
Published: May 2024

The conclusion returns the reader to Llanberis Lakes, and draws again on the work of Catherine Hutton to reflect on the reiterative nature of tour writing and its value as literature and as historical witness. It argues that because the form is so responsive to the immediate stimulus of the local and the specific, topographical writing is peculiarly resistant to linear narrative and argument: by being continually interrupted, its perspectives and chronologies perpetually shift. Tours thus reflect the messiness of history as it is always lived—contingent, accidental, and experienced at both micro and macro scales. The conclusion reasserts the importance of such texts in mapping the beginnings of our own unprecedented era of environmental degradation.
Pleistocene climate oscillations have shaped the expansion and contraction speciation model of the globose Eriosyce sect. Neoporteria cacti in Central Chile
Authors: Meriño Beatriz M , Villalobos-Barrantes Heidy M , Guerrero Pablo C
Published: May 2024

Background and Aims

Pleistocene climatic oscillations, characterized by arid (interglacial) and pluvial (glacial) phases, have profoundly impacted the floras of Mediterranean climates. Our study investigates the hypothesis that these climatic extremes have promoted phases of range expansion and contraction in the Eriosyce sect. Neoporteria, resulting in pronounced genetic structuring and restricted gene flow.

Methods

Using nuclear microsatellite markers, we genotyped 251 individuals across 18 populations, encompassing all 14 species and one subspecies within the Eriosyce sect. Neoporteria. Additionally, species distribution models were used to reconstruct past (Last Interglacial, Last Glacial Maximum and Mid-Holocene) and current potential distribution patterns, aiming to delineate the climatic influences on species range dynamics.

Key Results

The gene flow analysis disclosed disparate levels of genetic interchange among species, with marked restrictions observed between entities that are geographically or ecologically separated. Notably, Eriosyce subgibbosa from Hualpen emerged as genetically distinct, warranting its exclusion for clearer genetic clustering into north, central and south clusters. The species distribution models corroborated these findings, showing marked range expansions during warmer periods and contractions during colder times, indicating significant shifts in distribution patterns in response to climatic changes.

Conclusions

Our findings emphasize the critical role of Pleistocene climatic fluctuations in driving the dynamic patterns of range expansions and contractions that have led to geographical isolation and speciation within the Eriosyce sect. Neoporteria. Even in the face of ongoing gene flow, these climate-driven processes have played a pivotal role in sculpting the genetic architecture and diversity of species. This study elucidates the complex interplay between climatic variability and evolutionary dynamics among mediterranean cacti in central Chile, highlighting the necessity of considering historical climatic millennial oscillations in conservation and evolutionary biology studies.
Multi-modal domain adaptation for revealing spatial functional landscape from spatially resolved transcriptomics
Authors: Wang Lequn , Hu Yaofeng , Xiao Kai , Zhang Chuanchao , Shi Qianqian , Chen Luonan
Published: May 2024

Spatially resolved transcriptomics (SRT) has emerged as a powerful tool for investigating gene expression in spatial contexts, providing insights into the molecular mechanisms underlying organ development and disease pathology. However, the expression sparsity poses a computational challenge to integrate other modalities (e.g. histological images and spatial locations) that are simultaneously captured in SRT datasets for spatial clustering and variation analyses. In this study, to meet such a challenge, we propose multi-modal domain adaption for spatial transcriptomics (stMDA), a novel multi-modal unsupervised domain adaptation method, which integrates gene expression and other modalities to reveal the spatial functional landscape. Specifically, stMDA first learns the modality-specific representations from spatial multi-modal data using multiple neural network architectures and then aligns the spatial distributions across modal representations to integrate these multi-modal representations, thus facilitating the integration of global and spatially local information and improving the consistency of clustering assignments. Our results demonstrate that stMDA outperforms existing methods in identifying spatial domains across diverse platforms and species. Furthermore, stMDA excels in identifying spatially variable genes with high prognostic potential in cancer tissues. In conclusion, stMDA as a new tool of multi-modal data integration provides a powerful and flexible framework for analyzing SRT datasets, thereby advancing our understanding of intricate biological systems.
Histone deacetylase inhibition mitigates fibrosis-driven disease progression in recessive dystrophic epidermolysis bullosa
Authors: Primerano Alessia , De Domenico Emanuela , Cianfarani Francesca , De Luca Naomi , Floriddia Giovanna , Teson Massimo , Cristofoletti Cristina , Cardarelli Silvia , Scaglione Giovanni Luca , Baldini Enke , Cangelosi Davide , Uva Paolo , Reinoso Sánchez Jonathan Fernando , Roubaty Carole , Dengjel Jörn , Nyström Alexander , Mastroeni Simona , Ulisse Salvatore , Castiglia Daniele , Odorisio Teresa
Published: May 2024

Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering disease caused by mutations in the gene encoding type VII collagen (C7). RDEB is associated with fibrosis, which is responsible for severe complications. The phenotypic variability observed in siblings with RDEB suggests that epigenetic modifications contribute to disease severity. Identifying epigenetic changes may help to uncover molecular mechanisms underlying RDEB pathogenesis and new therapeutic targets.

Objectives

To investigate histone acetylation in RDEB skin and to explore histone deacetylase inhibitors (HDACi) as therapeutic molecules capable of counteracting fibrosis and disease progression in RDEB mice.

Methods

Acetylated histone levels were detected in human skin by immunofluorescence and in RDEB fibroblasts by enzyme-linked immunosorbent assay (ELISA). The effects of givinostat and valproic acid (VPA) on RDEB fibroblast fibrotic behaviour were assessed by a collagen–gel contraction assay, Western blot and immunocytofluorescence for α-smooth muscle actin, and ELISA for released transforming growth factor (TGF)-β1. RNA sequencing was performed in HDACi- and vehicle-treated RDEB fibroblasts. VPA was systemically administered to RDEB mice and effects on overt phenotype were monitored. Fibrosis was investigated in the skin using histological and immunofluorescence analyses. Eye and tongue defects were examined microscopically. Mass spectrometry proteomics was performed on skin protein extracts from VPA-treated RDEB and control mice.

Results

Histone acetylation decreases in RDEB skin and primary fibroblasts. RDEB fibroblasts treated with HDACi lowered fibrotic traits, including contractility, TGF-β1 release and proliferation. VPA administration to RDEB mice mitigated severe manifestations affecting the eyes and paws. These effects were associated with fibrosis inhibition. Proteomic analysis of mouse skin revealed that VPA almost normalized protein sets involved in protein synthesis and immune response, processes linked to the increased susceptibility to cancer and bacterial infections seen in people with RDEB.

Conclusions

Dysregulated histone acetylation contributes to RDEB pathogenesis by facilitating the progression of fibrosis. Repurposing of HDACi could be considered for disease-modifying treatments in RDEB.
Lytic and temperate phage naturally coexist in a dynamic population model
Authors: Kimchi Ofer , Meir Yigal , Wingreen Ned S
Published: May 2024

When phage infect their bacterial hosts, they may either lyse the cell and generate a burst of new phage, or lysogenize the bacterium, incorporating the phage genome into it. Phage lysis/lysogeny strategies are assumed to be highly optimized, with the optimal tradeoff depending on environmental conditions. However, in nature, phage of radically different lysis/lysogeny strategies coexist in the same environment, preying on the same bacteria. How can phage preying on the same bacteria coexist if one is more optimal than the other? Here, we address this conundrum within a modeling framework, simulating the population dynamics of communities of phage and their lysogens. We find that coexistence between phage of different lysis/lysogeny strategies is a natural outcome of chaotic population dynamics that arise within sufficiently diverse communities, which ensure no phage is able to absolutely dominate its competitors. Our results further suggest a bet-hedging mechanism at the level of the phage pan-genome, wherein obligate lytic (virulent) strains typically outcompete temperate strains, but also more readily fluctuate to extinction within a local community.
Flares in the Galactic centre – II. Polarization signatures of flares at mm-wavelengths
Authors: Najafi-Ziyazi Mahdi , Davelaar Jordy , Mizuno Yosuke , Porth Oliver
Published: May 2024

Recent polarimetric mm-observations of the galactic centre showed sinusoidal loops in the $\mathcal {Q{\small --}U}$ plane with a duration of one hour. The loops coincide with a quasi-simultaneous X-ray flare. A promising mechanism to explain the flaring events are magnetic flux eruptions in magnetically arrested accretion flows (MAD). In our previous work, we studied the accretion flow dynamics during flux eruptions. Here, we extend our previous study by investigating whether polarization loops can be a signature produced by magnetic flux eruptions. We find that loops in the $\mathcal {Q{\small --}U}$ plane are robustly produced in MAD models as they lead to enhanced emissivity of compressed disc material due to orbiting flux bundles. A timing analysis of the synthetic polarized light curves demonstrate a polarized excess variability at time-scales of $\simeq 1~\rm h$. The polarization loops are also clearly imprinted on the cross-correlation of the Stokes parameters which allows us to extract a typical periodicity of $30~\rm min$ to $1~\rm h$ with some evidence for a spin dependence. These results are intrinsic to the MAD state and should thus hold for a wide range of astrophysical objects. A subset of general relativistic magnetohydrodynamic simulations without saturated magnetic flux, namely, single temperature standard and normal evolution models, also produces $\mathcal {Q{\small --}U}$ loops. However, in disagreement with the observations, loops in these simulations are quasi-continuous with a low polarization excess.
Shallower radius valley around low-mass hosts: evidence for icy planets, collisions, or high-energy radiation scatter
Authors: Ho Cynthia S K , Rogers James G , Van Eylen Vincent , Owen James E , Schlichting Hilke E
Published: May 2024

The radius valley, i.e. a dearth of planets with radii between 1.5 and 2 Earth radii, provides insights into planetary formation and evolution. Using homogenously revised planetary parameters from Kepler 1-min short cadence light curves, we remodel transits of 72 small planets mostly orbiting low-mass stars, improving the precision and accuracy of planet parameters. By combining this sample with a similar sample of planets around higher mass stars, we determine the depth of the radius valley as a function of stellar mass. We find that the radius valley is shallower for low-mass stars compared to their higher mass counterparts. Upon comparison, we find that theoretical models of photoevaporation underpredict the number of planets observed inside the radius valley for low-mass stars: with decreasing stellar mass, the predicted fraction of planets inside the valley remains approximately constant whereas the observed fraction increases. We argue that this provides evidence for the presence of icy planets around low-mass stars. Alternatively, planets orbiting low-mass stars undergo more frequent collisions and scatter in the stars’ high-energy output may also cause planets to fill the valley. We predict that more precise mass measurements for planets orbiting low-mass stars would be able to distinguish between these scenarios.
Computational Photosynthesis (ComPhot): Simulation-Based Learning Platform to Study Photosynthesis
Authors: Philipps Sarah , Pfennig Tobias , Corvest Elouën , van Aalst Marvin , Fürtauer Lisa , Matuszyńska Anna
Published: May 2024

Studies show the advantage of active versus passive learning formats in delivering complicated concepts (Minocha and Clarke, 2009; Pluta et al., 2013). Hence, interactive teaching tools are not only more often positively evaluated by students but also contribute to better life-long teaching outcomes (Ang et al., 2021). Following this evidence, we created ComPhot, a stand-alone learning platform for motivated students and researchers. It guides the user in studying photosynthesis as a well-known biological process with the support of a computational model. ComPhot is a no-code, easy-to-use tool to lower the entry bar for starting the journey across computational biology and to provide insights into how photosynthesis and modeling photosynthesis work. This user-friendly interactive teaching platform can be used individually or to support teachers following a syllabus in biology, to include the concept of computational biology or mathematics, to show the possible field of application of mathematics to biology.

ComPhot introduces and explains the biochemical background of our simulated system and how to translate it into mathematical terms. We provide diverse teaching materials that include text, guiding questions, videos, and, most importantly, simulations. Within our simulators, users can perform computational photosynthesis modeling in their browser by simply setting and manipulating slider bars. Our comprehensive approach conveys fundamental insights into photosynthesis, photoprotection, and fluorescence measurements and empowers users to devise their own in silico experiments by varying light conditions or designing synthetic strains. This tool acts as a stepping stone, fostering engagement and understanding while propelling research and innovation in photosynthesis. Although this guide has been written in English, we are proud to release the tool in four of the developers’ languages to expand the audience: English, German, French, and Polish.
Diagnosis and Treatment of Varus Posteromedial Rotational Instability of the Elbow Joint in Children: Re-Understanding of the Injury Mechanism Associated With Coronoid Process Fractures
Authors: You Haifeng , Lyu Xuemin , Yang Zheng , Gong Maoqi , Jiang Xieyuan , Li Qiang
Published: May 2024

Purpose:

To investigate the injury mechanism, diagnosis, and treatment of varus-posteromedial rotational instability of the elbow joint in children.

Methods:

According to the diagnostic criteria of varus posteromedial rotational instability of elbow joint, 16 children with coronoid process fractures treated in our department from July 2013 to July 2017 were re-evaluated. There were 14 males and 2 females, aged 7 to 14 years, with an average age of 11.6 years. Eight cases on left and 8 cases on right side. An associated elbow dislocation occurred in 8 of 16 cases. Nine patients were treated with a lateral soft tissue repair only. In 7 other patients in addition to the lateral soft tissue repair, the coronoid process fractures were treated with open reduction and fixation. At the last clinical follow-up, each elbow joint range of motion was recorded, radiographs were obtained, and functional performance was evaluated by the Mayo elbow performance score (MEPS).

Results:

The average follow-up time was 81.9 months for the 9 patients treated with lateral elbow soft tissue repair. At the last follow-up, 2 of the patients had MEPS scores as excellent, 1 was good, and 6 were rated as moderate or poor. Four patients had a cubitus varus deformity. The average follow-up time was 30.3 months for the 7 patients treated with both soft tissue repair and coronoid fracture stabilization. The elbow joint MEPS scores for each of these 7 patients was excellent at the last follow-up, and no complications such as cubitus varus occurred.

Conclusion:

The results of the study suggest that children could also develop elbow varus-posterior medial rotational instability injuries under the same mechanism. Although the morbidity rate is low, due to insufficient understanding of the injury mechanism, it is prone to missed diagnosis, misdiagnosis, and delayed treatment, resulting in severe complications such as elbow instability, dislocation, traumatic arthritis, and elbow stiffness. On the contrary, according to the treatment principle of the posterior medial rotational instability of the elbow joint in adult, while the lateral repair is carried out, strong and effective reduction and fixation of the coronoid process fractures are adopted, it is expected that such children with rare elbow injuries can obtain excellent treatment outcomes.
Subcutaneous daratumumab in Chinese patients with relapsed or refractory multiple myeloma: an open-label, multicenter, phase 1 study (MMY1010)
Authors: An Gang , Ge Zheng , Jing Hongmei , Liu Jing , Yang Guoping , Feng Ru , Xu Zhongyuan , Qi Ming , Wang Jianping , Song Juanjuan , Zhou Wei , Sun Binbin , Zhu Dian , Chen Xi , Cui Canchan , Qiu Lugui
Published: May 2024

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) μg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.
MetALD: Does it require a different therapeutic option?
Authors: Marek George W. , Malhi Harmeet
Published: May 2024

New guidelines for the definitions of steatotic liver disease have named the entity of metabolic dysfunction and alcohol-associated liver disease (MetALD) as an overlap condition of metabolic dysfunction–associated steatotic liver disease (MASLD) and alcohol-associated liver disease. There is a broad range of therapeutics in all stages of development for MASLD, but these therapeutics, in general, have not been studied in patients with significant ongoing alcohol use. In this review, we discuss the current understanding of the endogenous and exogenous risks for MASLD and MetALD. Rational strategies for therapeutic intervention in MetALD include biopsychosocial interventions, alcohol use cessation strategies, including the use of medications for alcohol use disorder, and judicious use of therapeutics for steatotic liver disease. Therapeutics with promise for MetALD include incretin-based therapies, FGF21 agonists, thyroid hormone receptor beta agonists, sodium-glucose co-transporter 2 inhibitors, and agents to modify de novo lipogenesis. Currently, glucagon-like peptide 1 receptor agonists and peroxisome proliferator–activated receptor γ agonists have the largest body of literature supporting their use in MASLD, and there is a paucity of agents in trials for alcohol-associated liver disease. From existing studies, it is not clear if unique therapeutics or a combinatorial approach are needed for MetALD. Further elucidation of the safety and benefits of MASLD-related therapies is of paramount importance for advancing therapeutics for MetALD in carefully designed inclusive clinical trials.
Programmable soft DNA hydrogels stimulate cellular endocytic pathways and proliferation
Authors: Singh Ankur , Singh Nihal , Jinugu Manasi Esther , Thareja Prachi , Bhatia Dhiraj
Published: May 2024

Hydrogels are pivotal in tissue engineering, regenerative medicine, and drug delivery applications. DNA molecules stand out among various biomaterials due to their unparalleled precision, programmability, and customization. In this study, we introduce a palate of novel cellular scaffolding platforms made of pure DNA-based hydrogel systems while improving the shortcomings of the existing platforms. DNA strands can form complex supramolecular branched structures essential for designing novel functional materials by its precise sequence-based self-assembly. These unique geometric scaffolds offer a soft, cushiony platform, ideal for culturing cells to mimic the complex native in vivo environments better. Each hydrogel comprises repeating units of branched DNA supramolecular structures, each possessing a distinct number of branching arms. The epithelial cells grown over these hydrogels show dynamic changes at multiple levels, from morphology to protein expression patterns, enhanced membrane traffic, and proliferation. The DNA hydrogels explored here are mechanically weak and soft and thus appropriate for applications in cell biology. This research lays the groundwork for developing a DNA hydrogel system with a higher dynamic range of stiffness, which will open exciting avenues for tissue engineering and beyond.

Graphical abstract illustrating diverse branched DNA supramolecular architectures forming DNA hydrogels of various geometric profiles, each put to use in the cell culture applications.
Variation in spatial population structure in theAnopheles gambiaespecies complex
Authors: McCann Robert S. , Courneya Jean-Paul , Donnelly Martin J. , Laufer Miriam K. , Mzilahowa Themba , Stewart Kathleen , Agossa Fiacre , Tezzo Francis Wat’senga , Miles Alistair , Takala-Harrison Shannon , O’Connor Timothy D. ,   Ag1000G Consortium
Published: May 2024

Anopheles gambiae,Anopheles coluzzii, andAnopheles arabiensisare three of the most widespread vectors of malaria parasites, with geographical ranges stretching across wide swaths of Africa. Understanding the population structure of these closely related species, including the extent to which populations are connected by gene flow, is essential for understanding how vector control implemented in one location might indirectly affect vector populations in other locations. Here, we assessed the population structure of each species based on a combined data set of publicly available and newly processed whole-genome sequences. The data set included single nucleotide polymorphisms from whole genomes of 2,410 individual mosquitoes sampled from 128 locations across 19 African countries. We found thatA. gambiaesampled from several countries in West and Central Africa showed low genetic differentiation from each other according to principal components analysis (PCA) and ADMIXTURE modeling. Using Estimated Effective Migration Surfaces (EEMS), we showed that this low genetic differentiation indicates high effective migration rates forA. gambiaeacross this region. Outside of this region, we found eight groups of sampling locations from Central, East, and Southern Africa for whichA. gambiaeshowed higher genetic differentiation, and lower effective migration rates, between each other and the West/Central Africa group. These results indicate that the barriers to and corridors for migration between populations ofA. gambiaediffer across the geographical range of this malaria vector species. Using the same methods, we found higher genetic differentiation and lower migration rates between populations ofA. coluzziiin West and Central Africa than forA. gambiaein the same region. In contrast, we found lower genetic differentiation and higher migration rates between populations ofA. arabiensisin Tanzania, compared toA. gambiaein the same region. These differences betweenA. gambiae,A. coluzzii, andA. arabiensisindicate that migration barriers and corridors may vary, even between very closely related species. Overall, our results demonstrate that migration rates vary both within and between species ofAnophelesmosquitoes, presumably based on species-specific responses to the ecological or environmental conditions that may impede or facilitate migration, and the geographical patterns of these conditions across the landscape. Together with previous findings, this study provides robust evidence that migration rates between populations of malaria vectors depend on the ecological context, which should be considered when planning surveillance of vector populations, monitoring for insecticide resistance, and evaluating interventions.
Collective phases and long-term dynamics in a fish school model with burst-and-coast swimming
Authors: Wang Weijia , Escobedo Ramón , Sanchez Stéphane , Han Zhangang , Sire Clément , Theraulaz Guy
Published: May 2024

Intermittent and asynchronous burst-and-coast swimming is widely adopted by various species of fish as an energy-efficient locomotion mode. This swimming mode significantly influences the way in which fish integrate information and make decisions in a social context. Here, we introduce a simplified fish school model in which individuals have an asynchronous burst-and-coast swimming mode and selectively interact only with one or two neighbors that exert the largest influence on their behavior and over a limited spatial range. The interactions consist for a fish to be attracted and aligned with these neighbors. We show that, by adjusting the interactions between individuals above a sufficiently high level, depending on the relative strength of attraction and alignment, the model is able to produce a cohesive fish school that replicates the main collective phases observed in nature: schooling, milling and swarming when each individual interacts with only one neighbor, and schooling and swarming when each individual interacts with two neighbors. Moreover, the model shows that these patterns can be maintained over long simulations. However, with the exception of swarming, these patterns do not persist indefinitely in time and fish lose cohesion and progressively disperse. We further identify the mechanisms leading to the dispersion.
Functional conservation and divergence of Arabidopsis VENOSA4 and human SAMHD1 in DNA repair
Authors: Sarmiento-Mañús Raquel , Fontcuberta-Cervera Sara , Kawade Kensuke , Oikawa Akira , Tsukaya Hirokazu , Quesada Víctor , Micol José Luis , Ponce María Rosa
Published: May 2024

The human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probableArabidopsis thalianaortholog of SAMHD1, also functions in DSB repair by HR. Theven4loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation. Hydroxyurea, which blocks DNA replication and generates DSBs, inducedVEN4expression. Theven4mutants were hypersensitive to hydroxyurea, with decreased DSB repair by HR. Metabolomic analysis of the strongven4-0mutant revealed depletion of metabolites associated with DNA damage responses. In contrast to SAMHD1, VEN4 showed no evident involvement in preventing R-loop accumulation. Our study thus reveals functional conservation in DNA repair by VEN4 and SAMHD1.

One sentence summary

Human SAMHD1 is involved in dNTP metabolism and DNA repair; the latter function is conserved in VEN4, its likely Arabidopsis ortholog.
Dual nuclease single-cell lineage tracing by Cas9 and Cas12a
Authors: Chen Cheng , Liao Yuanxin , Zhu Miao , Wang Li , Yu Xinran , Li Meishi , Peng Guangdun
Published: May 2024

Single-cell lineage tracing based on CRISPR/Cas9 gene editing enables the simultaneous linkage of cell states and lineage history at a high resolution. Despite its immense potential in resolving the cell fate determination and genealogy within an organism, existing implementations of this technology suffer from limitations in recording capabilities and considerable barcode dropout. Here, we introduce DuTracer, a versatile tool, which utilizes two orthogonal gene editing systems to record deep cell lineage history at single-cell resolution in an inducible manner. DuTracer shows the ability of enhanced lineage recording with minimized target dropouts and deepened tree depth. Application of DuTracer in mouse embryoid bodies and neuromesodermal organoids illustrates the lineage relationship of different cell types and proposes potential lineage-biased molecular drivers. Moreover, we have developed an entropy-based approach to quantify the lineage recording ability of DuTracer in cell differentiation models. Together, DuTracer facilitates the precise and regulatory interrogation of cellular lineages of complex biological processes.
Structural Insights into Subunit-Dependent Functional Regulation in Epithelial Sodium Channels
Authors: Houser Alexandra , Baconguis Isabelle
Published: May 2024

Epithelial sodium channels (ENaC) play a crucial role in Na+reabsorption in mammals. To date, four subunits have been identified—α, β, γ, and δ—believed to form different heteromeric complexes. Currently, only the structure of the αβγ complex is known. To understand how these channels form with varying subunit compositions and define the contribution of each subunit to distinct properties, we co-expressed human δ, β, and γ. Using single-particle cryo-electron microscopy, we observed three distinct ENaC complexes. The structures unveil a pattern in which β and γ positions are conserved among the different complexes while the α position in αβγ trimer is occupied by either δ or another β. The presence of δ induces structural rearrangements in the γ subunit explaining the differences in channel activity observed between αβγ and δβγ channels. These structures define the mechanism by which ENaC subunit composition tunes ENaC function.
CLAVATA signalling shapes barley inflorescence architecture by controlling activity and determinacy of shoot apical and rachilla meristems
Authors: Vardanega Isaia , Maika Jan Eric , Demesa-Arevalo Edgar , Lan Tianyu , Kirschner Gwendolyn K. , Imani Jafargholi , Acosta Ivan F. , Makowska Katarzyna , Hensel Götz , Ranaweera Thilanka , Shiu Shin-Han , Schnurbusch Thorsten , von Korff Schmising Maria , Simon Rüdiger
Published: May 2024

Grasses exhibit a large variety of diverse inflorescence architectures, from complex branched inflorescences inOryzeae(rice) to simple spike-type inflorescences inTriticeae(e.g. barley, wheat). Inflorescence architecture depends on shape, longevity and determinacy of meristems that direct growth of the main rachis and lateral branches, but how individual meristem activities are determined and integrated within complex inflorescences is not yet understood. We found that activity of distinct meristems in the barley inflorescence is coordinated by a signalling pathway comprising the receptor like kinaseHordeum vulgareCLAVATA1 (HvCLV1) and the secreted CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE)-family peptide FON2- LIKE CLE PROTEIN1 (HvFCP1). HvFCP1 interacts with HvCLV1 to promote spikelet formation but restricts inflorescence meristem and rachilla meristem proliferation.Hvfcp1orHvclv1mutants generate branched inflorescences with additional rows of spikelets and supernumerary florets. Transcriptome analysis reveals thatHvFCP1/HvCLV1signalling controls inflorescence branching through the regulation of trehalose-6-phosphate synthesis and sugar transport. Our discoveries reveal the potential to engineer barley inflorescence architecture by manipulating regulation of distinct meristem activities.
Genetic background affects the strength of crossover interference in house mice
Authors: Morgan Andrew P , Payseur Bret A
Published: May 2024

Meiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles fromM. m. musculustend to increase recombination rate, while inheriting aM. m. musculusX chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.
Direct lineage conversion of postnatal mouse cortical astrocytes to oligodendrocyte lineage cells
Authors: Bajohr Justine , Scott Erica Y. , Olfat Arman , Sadria Mehrshad , Lee Kevin , Fahim Maria , Taha Hiba T. , Lozano Casasbuenas Daniela , Derham Ann , Yuzwa Scott A. , Bader Gary D. , Faiz Maryam
Published: May 2024

Oligodendrocyte lineage cells (OLCs) are lost in many CNS diseases. Here, we investigate the generation of new OLCs via ectopic expression ofSox10,Olig2orNkx6.2in mouse postnatal astrocytes. Using stringent analyses including, Aldh1l1-astrocyte fate mapping and live cell imaging we confirm thatSox10andOlig2, but notNkx6.2, directly convert Aldh1l1posastrocytes to MBP+ and PDGFRα+ induced OLCs (iOLCs), respectively. With single cell RNA sequencing (scRNA-seq) we uncover the molecular signatures of iOLCs. Transcriptomic analysis ofSox10- and control cultures over time reveals a clear trajectory from astrocytes to iOLCs. Finally, perturbation models CellOracle and Fatecode support the idea thatSox10drives cells towards a terminal iOLC fate. Altogether, this multidimensional analysis shows bonafide conversion of astrocytes to iOLCs usingSox10orOlig2and provides a foundation for astrocyte DLR strategies to promote OLC repair.
Generative Artificial Intelligence Model for Simulating Brain Structural Changes in Schizophrenia
Authors: Yamaguchi Hiroyuki , Sugihara Genichi , Simizu Masaaki , Yamashita Yuichi
Published: May 2024

Background

Recent advancements in generative artificial intelligence (AI) for image generation have presented significant opportunities for medical imaging, offering a promising avenue for generating realistic virtual medical images while ensuring patient privacy. The generation of a large number of virtual medical images through AI has the potential to augment training datasets for discriminative AI models, particularly in fields with limited data availability, such as neuroimaging. Current studies on generative AI in neuroimaging have mainly focused on disease discrimination; however, its potential for simulating complex phenomena in psychiatric disorders remains unknown. In this study, as examples of a simulation, we aimed to present a novel generative AI model that transforms magnetic resonance imaging (MRI) images of healthy individuals into images that resemble those of patients with schizophrenia (SZ) and explore its application.

Methods

We used anonymized public datasets from the Center for Biomedical Research Excellence (SZ, 71 patients; healthy subjects [HSs], 71 patients) and the Autism Brain Imaging Data Exchange (autism spectrum disorder [ASD], 79 subjects; HSs, 105 subjects). We developed a model to transform MRI images of HSs into MRI images of SZ using cycle generative adversarial networks. The efficacy of the transformation was evaluated using voxel-based morphometry to assess the differences in brain region volume and the accuracy of age prediction pre- and post-transformation. In addition, the model was examined for its applicability in simulating disease comorbidities and disease progression.

Results

The model successfully transformed HS images into SZ images and identified brain volume changes consistent with existing case-control studies. We also applied this model to ASD MRI images, where simulations comparing SZ with and without ASD backgrounds highlighted the differences in brain structures due to comorbidities. Furthermore, simulation of disease progression while preserving individual characteristics showcased the model’s ability to reflect realistic disease trajectories.

Discussion

The findings suggest that our generative AI model can capture subtle changes in brain structures associated with SZ and offers a novel tool for visualizing brain alterations across various conditions. The potential of this model extends beyond clinical diagnoses to advancements in the simulation of disease mechanisms, which may ultimately contribute to the refinement of therapeutic strategies.
Impact of Cerebrospinal Fluid Leukocyte Infiltration and Neuroimmmune Mediators on Survival with HIV-Associated Cryptococcal Meningitis
Authors: Okurut Samuel , Boulware David R. , Manabe Yukari C. , Tugume Lillian , Skipper Caleb P. , Ssebambulidde Kenneth , Rhein Joshua , Musubire Abdu K. , Akampurira Andrew , Okafor Elizabeth , Olobo Joseph O. , Janoff Edward N. , Meya David B. ,   ASTRO Trial Team
Published: May 2024

Introduction

Cryptococcal meningitis remains a prominent cause of death in persons with advanced HIV disease. CSF leukocyte infiltration predicts survival at 18 weeks; however, how CSF immune response relates to CSF leukocyte infiltration is unknown.

Methods

We enrolled 401 adults with HIV-associated cryptococcal meningitis in Uganda who received amphotericin and fluconazole induction therapy. We assessed the association of CSF leukocytes, chemokine, and cytokine responses with 18-week survival.

Results

Participants with CSF leukocytes ≥50/µL, had higher probability 68% (52/77) of 18-week survival compared with 52% (151/292) 18-week survival in those with ≤50 cells/µL (Hazard Ratio=1.63, 95% confidence intervals 1.14-2.23; p=0.008). Survival was also associated with higher expression of T helper (Th)-1, Th17 cytokines, and immune regulatory elements. CSF levels of Programmed Death-1 Ligand, CXCL10, and Interleukin (IL)-2 independently predicted survival. In multivariate analysis, CSF leukocytes were inversely associated with CSF fungal burden and positively associated with CSF protein, interferon-gamma (IFN-γ), IL-17A, tumor necrosis factor (TNF)-α, and peripheral blood CD4+and CD8+T cells expression.

Conclusion

18-week survival after diagnosis of cryptococcal meningitis was associated with higher CSF leukocytes at baseline with greater T helper 1 (IFN-γ, IL-2 and TNF-α cytokines), T helper 17 (IL-17A cytokine) and CXCR3+T cell (CXCL10 chemokine) responses. These results highlight the interdependent contribution of soluble and cellular immune responses in predicting survival with HIV-associated cryptococcal meningitis.
Sex and Marital-Status Differences in Delayed Initiation for Pharyngeal Cancer Treatment, Before and After Medicaid Expansion
Authors: Semprini Jason
Published: May 2024

Background

In the United States, pharyngeal cancer has become the most common type of head and neck cancer, with 80% of cases found in males. Although disparities in treatment delays have been observed in pharyngeal patients, less is known about how policies facilitate timely care. This study aimed to estimate the association between Medicaid expansion and delaying initiation of pharyngeal cancer treatment.

Methodology

We extracted Surveillance, Epidemiological, End Results (SEER) case data to analyze pharyngeal cancers diagnosed between 2000-2018. The outcome of interest was a binary variable indicating if the patient initiated treatment two or more months after diagnosis. We conducted subgroup analyses by sex, marital status, and type of treatment received (surgery, radiation, chemotherapy, post-operative radiation, systemic therapy). We implement the Matrix Completion algorithm to account for staggered rollout of Medicaid expansion within our difference-in-differences design.

Results

Our sample included 79,433 patients diagnosed with pharynx cancer. Delayed treatment was lowest among married females receiving systemic therapy (5%), and highest among married males and females not recommended to receive surgery (43%). Generally, there was no association between Medicaid expansion and changes in delayed treatment. Subgroup analyses show that Medicaid expansion was associated with reduced treatment delays in unmarried females receiving systemic therapy (-4.5%-points), and married males receiving chemotherapy (Est. = -2.6%-points), radiotherapy (Est. = -3.1%-points), and married males not recommended to receive surgery (Est. = -4.6%-points).

Conclusions

Given the importance of timely pharyngeal cancer treatment, health systems must identify and address the drivers of treatment delays to advance cancer equity.
What Factors are Important to the Success of Resubmitted Grant Applications in Health Research? A Retrospective Study of Over 20,000 Applications to the Canadian Institutes of Health Research
Authors: Wrightson J.G , Lasinsky A. , Snell R.R. , Hogel M. , Mota A. , Khan K.M. , Ardern C.L.
Published: May 2024

Background

In this retrospective study, we investigated the outcomes (funded/not funded) and factors related to the funding of resubmitted applications to the Canadian Institutes of Health Research (CIHR) Open Operating Grants Competition and Project Grant Competition between 2000 and 2022.

Method and Findings

The primary outcome was the proportion of resubmissions and new applications that were funded. Using a random forest model, we explored the importance of variables related to the success of resubmissions. A higher proportion of resubmissions (∼23%) were funded compared to new submissions (∼12%). The most important variables related to resubmission success were the rank (%) and score (/5) given to the preceding (initial) application and the number of the number of CIHR-funded grants where the PI was a named team member.

Conclusion

Resubmitting applications to the CIHR Project Grant Competition was beneficial, particularly for projects that were previously highly ranked and received high scores. These results may offer guidance for researchers who are deciding whether to resubmit rejected applications.