bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract

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

Abstract
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

ABSTRACT
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

ABSTRACT
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

Abstract
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.
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

AbstractHydrogels 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

AbstractAnopheles 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.
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

SUMMARYThe 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 summaryHuman 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

ABSTRACTSingle-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

SummaryEpithelial 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.