bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the need for temporary fishing closures to support sustainability for a small-scale octopus fishery
Authors: Wulfing Sophie , Kadba Ahilya Sudarshan , Baker-Médard Mez , White Easton R. 
Published: April 2023

1ABSTRACTThe blue octopus (Octopus cyanea) fishery off the southwest coast of Madagascar is important for coastal communities. This fishery is a key economic resource for the local community as blue octopus catch is sold by local fishers to international and local export markets. Thus, it is important to monitor and evaluate the status of octopus to ensure its sustainability. One common octopus management approach is through the use of temporary spatial closures. Models can be a useful support tool to evaluate the status of a population and assess different possible management strategies. To better understand the biology and assess the sustainability of blue octopus, we parameterize a Levkovitch population matrix model using existing catch data. We found that the octopus population was experiencing a 1.8% decline per month at the time of data collection in 2006. However, since 2006, a number of management practices, including temporary closures lasting several weeks to several months have been implemented successfully. In line with these efforts, our model indicates that the fishery has likely been sustained since 2006 due to these annual closures. Our model provides support to the idea that temporary closures have restored this population and that temporary closures provide flexibility in management strategies that local communities can tailor to their economic and social needs. In addition, we were able to estimate several important life history metrics, such as time in each stage, stable stage distribution, reproductive value, and per stage survivability, that can be used in future work. Collectively, our study provides insight into the biology of blue octopus as well as demonstrate how temporary closures can be an effective conservation strategy due to the wide range of implementation options.
CTNSmRNA as a potential treatment for nephropathic cystinosis
Authors: Bondue Tjessa , Berlingerio Sante P. , Siegerist Florian , Sendino-Garví Elena , Schindler Maximilian , Cairoli Sara , Goffredo Bianca M. , Arcolino Fanny O. , Dieker Jürgen , Janssen Manoe , Endlich Nicole , Brock Roland , Gijsbers Rik , Heuvel Lambertus van den , Levtchenko Elena 
Published: April 2023

AbstractMessenger RNA (mRNA) therapies are emerging in different disease areas, but have not yet reached the kidney field. Our aim was to study the feasibility to correct the genetic defect in nephropathic cystinosis using synthetic mRNA. Cystinosis is a prototype disorder of proximal tubular dysfunction caused by mutations in theCTNSgene, encoding the lysosomal cystine-H+symporter cystinosin, and leading to cystine accumulation in all cells of the body. The kidneys are the first and most severely affected organs, presenting glomerular and proximal tubular dysfunction. Cysteamine is the current therapeutic standard that reduces cellular cystine levels, but has many side effects and does not restore kidney function. Here, we show that synthetic mRNA is safe and effective to reintroduce functional cystinosin using lipofection inCTNS-/-kidney cells and following direct injection inctns-/-zebrafish larvae.CTNSmRNA therapy results in prompt lysosomal expression of the functional protein and decreases cellular cystine accumulation for up to 14 days. In thectns-/-zebrafish,CTNSmRNA therapy improves proximal tubular reabsorption, reduces proteinuria, and restores brush border expression of the multi-ligand receptor megalin. We propose that mRNA-based therapy, if sufficient kidney targeting can be achieved, may be a new approach to treat cystinosis.Translational statementCystinosis is a systemic lysosomal storage disease caused by mutations in theCTNS(cystinosin) gene. It initially affects the kidneys and leads to kidney failure, if left untreated. The current standard therapy, cysteamine, is not curative and has many side-effects. Here we demonstrate the potential of mRNA-based therapy to swiftly restore cystinosin function and ameliorate the kidney phenotype. Future research will focus on mRNA delivery methods and targeting kidney cells in cystinosis rodent models.
Designing host-associated microbiomes using the consumer/resource model
Authors: Plata Germán , Srinivasan Karthik , Krishnamurthy Madan , Herron Lukas , Dixit Purushottam 
Published: April 2023

AbstractA key step towards rational microbiome engineering isin silicosampling of realistic microbial communities that correspond to desired host phenotypes, and vice versa. This remains challenging due to a lack of generative models that simultaneously capture compositions of host-associated microbiomes and host phenotypes. To that end, we present a generative model based on the mechanistic consumer/resource (C/R) framework. In the model, variation in microbial ecosystem composition arises due to differences in the availability ofeffective resources(inferred latent variables) while species’ resource preferences remain conserved. The same latent variables are used to model phenotypic states of hosts.In silicomicrobiomes generated by our model accurately reproduce universal and dataset-specific statistics of bacterial communities. The model allows us to address three salient questions in host-associated microbial ecologies: (1) which host phenotypes maximally constrain the composition of the host-associated microbiomes? (2) how context-specific are phenotype/microbiome associations, and (3) what are plausible microbiome compositions that correspond to desired host phenotypes? Our approach aids the analysis and design of microbial communities associated with host phenotypes of interest.
Thermoprotection by a cell membrane-localized metacaspase in a green alga
Authors: Zou Yong , Sabljić Igor , Horbach Natalia , Dauphinee Adrian N. , Åsman Anna , Temino Lucia Sancho , Drag Marcin , Stael Simon , Poreba Marcin , Ståhlberg Jerry , Bozhkov Peter V. 
Published: April 2023

AbstractCaspases are restricted to animals, while other organisms, including plants possess metacaspases (MCAs), a more ancient and broader class of structurally-related yet biochemically distinct proteases. Our current understanding of plant MCAs is derived from studies in streptophytes, and mostly in Arabidopsis expressing nine MCAs with partly redundant activities. In contrast to streptophytes, most chlorophytes contain only one or two hitherto uncharacterized MCAs, providing an excellent platform for MCA research. Here we investigate CrMCA-II, a single type II MCA from a model chlorophyteChlamydomonas reinhardtii. Surprisingly, unlike other studied MCAs and similar to caspases, CrMCA-II dimerizes bothin vitroandin vivo. Furthermore, activation of CrMCA-IIin vivocorrelates with the dimerization. Most of CrMCA-II in the cell is present as a zymogen attached to the plasma membrane (PM). Deletion ofCrMCA-IIby CRISPR/Cas9 compromises thermotolerance leading to increased cell death under heat stress. Adding back either wild-type or catalytically dead CrMCA-II restores thermoprotection, suggesting that its proteolytic activity is dispensable for this effect. Finally, we link the non-proteolytic role of CrMCA-II in thermotolerance to the ability to modulate PM fluidity. Our study reveals an ancient, MCA-dependent thermotolerance mechanism retained by Chlamydomonas and probably lost during the evolution of multicellularity.
The Shank/ProSAP N-terminal (SPN) domain of Shank3 regulates targeting to postsynaptic sites and postsynaptic signalling
Authors: Woike Daniel , Tibbe Debora , Nia Fatemeh Hassani , Martens Victoria , Wang Emily , Barsukov Igor , Kreienkamp Hans-Jürgen 
Published: April 2023

AbstractMembers of the Shank family of postsynaptic scaffold proteins (Shank1-3) link neurotransmitter receptors to the actin cytoskeleton in dendritic spines through establishing numerous interactions within the postsynaptic density (PSD) of excitatory synapses. Large Shank isoforms carry at their N-termini a highly conserved domain termed the Shank/ProSAP N-terminal (SPN) domain, followed by a set of ankyrin repeats. Both domains are involved in an intramolecular interaction which is believed to regulate accessibility for additional interaction partners, such as Ras family G-proteins, αCaMKII and cytoskeletal proteins. Here we analyse the functional relevance of the SPN-Ank module; we show that binding of active Ras or Rap1a to the SPN domain can differentially regulate the localization of Shank3 in dendrites. In Shank1 and Shank3, the linker between the SPN and Ank domains binds to inactive αCaMKII. Due to this interaction, both Shank1 and Shank3 exert a negative effect on αCaMKII activity at postsynaptic sites in micein vivo. The relevance of the SPN-Ank intramolecular interaction was further analysed in primary cultured neurons; here we observed that in the context of full-length Shank3, a closed conformation of the SPN-Ank tandem is necessary for proper clustering of Shank3 on the head of dendritic spines. Shank3 variants carrying Ank repeats which are not associated with the SPN domain lead to the atypical formation of postsynaptic clusters on dendritic shafts, at the expense of dendritic spines. Our data show that the SPN-Ank tandem motif contributes to the regulation of postsynaptic signalling, and is also necessary for proper targeting of Shank3 to postsynaptic sites. Our data also suggest how missense variants found in autistic patients which alter SPN and Ank domains affect the synaptic function of Shank3.
Neoepitope-specific vaccination of a patient with diffuse midline glioma targeting H3K27M induces polyclonal B and T cell responses across diverse HLA alleles
Authors: Boschert Tamara , Kromer Kristina , Lerner Taga , Lindner Katharina , Haltenhof Gordon , Tan Chin Leng , Jähne Kristine , Poschke Isabel , Bunse Lukas , Grassl Niklas , Mildenberger Iris , Sahm Katharina , Platten Michael , Lindner John M , Green Edward W 
Published: April 2023

AbstractH3K27M, a driver mutation with T- and B-cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient who was treated with an H3K27M peptide vaccine and subsequently entered complete remission. The vaccine robustly expanded class II HLA-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive T cell receptors and identified critical, conserved motifs in their CDR3 regions. Using detailed HLA mapping, we further demonstrate that diverse HLA-DQ, and -DR alleles present immunogenic H3K27M epitopes. Furthermore, we identified and profiled H3K27M-reactive B cell receptors from activated B cells in the cerebrospinal fluid. Our results uncover the breadth of the adaptive immune response against a shared clonal neoantigen across multiple HLA allelotypes and support the use of class II-restricted peptide vaccines to stimulate tumor-specific T and B cells harboring receptors with therapeutic potential.
Temperature and day length drive local adaptation in the Patagonian foundation tree speciesNothofagus pumilio
Authors: Sekely Jill , Marchelli Paula , Arana Verónica , Dauphin Benjamin , Mattera María Gabriela , Pastorino Mario , Scotti Ivan , Soliani Carolina , Heer Katrin , Opgenoorth Lars 
Published: April 2023

SummaryClimate change alters relationships among environmental conditions and thus has the potential to change the selection pressures acting on adaptive gene variants. Using a landscape genomic approach, we show that the southern beech speciesNothofagus pumiliohas notable genetic adaptations to climate along its 2000-kilometer-long range in the Andes. We screened 47,336 SNP loci in 1,632 contigs and found that high-latitude sampling sites have lower genetic diversity, likely due to greater impact of glacial oscillations at high latitudes. Using four genome scan methods, we identified 457 outlier SNPs that are either strongly differentiated among subpopulations or associated with environmental covariates related to temperature, day length, and precipitation. Temperature and day length parameters were associated with notably more outliers than precipitation (n = 133, 113, and 61 outliers, respectively), and almost half of all annotated outliers were related to stress response (n=38, 21%) or catabolism-metabolism (n=43, 24%). Our findings suggest thatNothofagus pumiliois an ideal Andean model of genetic adaptation to climate change because it is locally adapted to extant climate conditions, and shifting patterns among environmental parameters may be detrimental to its future survival and adaptation potential.
Identification of transcription factor co-binding patterns with non-negative matrix factorization
Authors: Rauluseviciute Ieva , Launay Timothée , Barzaghi Guido , Nikumbh Sarvesh , Lenhard Boris , Krebs Arnaud Regis , Castro-Mondragon Jaime A. , Mathelier Anthony 
Published: April 2023

ABSTRACTTranscription factor (TF) binding to DNA is critical to transcription regulation. Although the binding properties of numerous individual TFs are well-documented, a more detailed comprehension of how TFs interact cooperatively with DNA, forming either complex or co-binding to the same region, is required. Indeed, the combinatorial binding of TFs is essential to cell differentiation, development, and response to external stimuli. We present COBIND, a novel method based on non-negative matrix factorization (NMF) to identify TF co-binding patterns automatically. COBIND applies NMF to one-hot encoded regions flanking known TF binding sites (TFBSs) to pinpoint enriched DNA patterns at fixed distances. We applied COBIND to 8,293 TFBS datasets from UniBind for 404 TFs in seven species. The method uncovered already established co-binding patterns (e.g.,between POU5F1 and SOX2 or SOX17) and new co-binding configurations not yet reported in the literature and inferred through motif similarity and protein-protein interaction knowledge. Our extensive analyses across species revealed that 84% of the studied TFs share a co-binding motif with other TFs from the same structural family. The co-binding patterns captured by COBIND are likely functionally relevant as they harbor higher evolutionarily conservation than isolated TFBSs. Open chromatin data from matching human cell lines further supported the co-binding predictions. Finally, we used single-molecule footprinting data from mouse embryonic stem cells to confirm that the co-binding events captured by COBIND were likely occurring on the same DNA molecules.
Self-supervision advances morphological profiling by unlocking powerful image representations
Authors: Kim Vladislav , Adaloglou Nikolaos , Osterland Marc , Morelli Flavio M. , Halawa Marah , König Tim , Gnutt David , Zapata Paula A. Marin 
Published: April 2023

AbstractCell Painting is an image-based assay that offers valuable insights into drug mechanisms of action and off-target effects. However, traditional feature extraction tools such as CellProfiler are computationally intensive and require frequent parameter adjustments. Inspired by recent advances in AI, we trained self-supervised learning (SSL) models DINO, MAE, and SimCLR on subsets of the JUMP-CP dataset to obtain powerful image representations for Cell Painting. We assessed the reproducibility and biological relevance of SSL features and uncovered the critical factors influencing model performance, such as training set composition and domain-specific normalization techniques. Our best model (DINO) surpassed CellProfiler in drug target and gene family classification, significantly reducing computational time and costs. All SSL models showed remarkable generalizability without fine-tuning, outperforming CellProfiler on an unseen dataset of genetic perturbations. Our study demonstrates the effectiveness of SSL methods for morphological profiling, suggesting promising research directions for improving the analysis of related image modalities.
Non-destructive spatial mapping of vegetation plots: a re-introduction of the pantograph
Authors: Martyn Trace E. , Mayfield Margaret M. 
Published: April 2023

SummaryNon-destructive spatial mapping of herbaceous plants is often not possible with many modern imaging techniques, especially in systems with highly structured, dense herbaceous canopies. For this purpose we suggest using a modern version of the classic pantograph, a simple instrument that allows precisely scaled drawings. The pantograph version we describe here was specifically designed for small-scale herbaceous vegetation mapping.Specifically, our pantograph design is useful for rapidly collecting accurate, spatially explicit data at the scale of 0.1-2 m2and includes a paired drawing board for easy use in field conditions.We tested the design and technique on 100 annual plant plots that ranged in total density and in plant stature. Based on this mapping trial, we present guidelines for effective manual mapping and map digitization.A pantograph is a useful and inexpensive to make tool for non-destructively spatially mapping individual herbaceous plants in the field. Here, we present instructions for the design and fabrication of our modern pantograph, board, and pencil attachment designed specifically for researchers wanting to include small-scale spatial context in their research.
AbNatiV: VQ-VAE-based assessment of antibody and nanobody nativeness for hit selection, humanisation, and engineering
Authors: Ramon Aubin , Ali Montader , Atkinson Misha , Saturnino Alessio , Didi Kieran , Visentin Cristina , Ricagno Stefano , Xu Xing , Greenig Matthew , Sormanni Pietro 
Published: April 2023

AbstractMonoclonal antibodies have emerged as key therapeutics, and nanobodies are rapidly gaining momentum following the approval of the first nanobody drug in 2019. Nonetheless, the development of these biologics as therapeutics remains a challenge. Despite the availability of established in vitro directed evolution technologies that are relatively fast and cheap to deploy, the gold standard for generating therapeutic antibodies remains discovery from animal immunization or patients. Immune-system derived antibodies tend to have favourable properties in vivo, including long half-life, low reactivity with self-antigens, and low toxicity. Here, we present AbNatiV, a deep-learning tool for assessing the nativeness of antibodies and nanobodies, i.e., their likelihood of belonging to the distribution of immune-system derived human antibodies or camelid nanobodies. AbNatiV is a multi-purpose tool that accurately predicts the nativeness of Fv sequences from any source, including synthetic libraries and computational design. It provides an interpretable score that predicts the likelihood of immunogenicity, and a residue-level profile that can guide the engineering of antibodies and nanobodies indistinguishable from immune-system-derived ones. We further introduce an automated humanisation pipeline, which we applied to two nanobodies. Wet-lab experiments show that AbNatiV-humanized nanobodies retain binding and stability at par or better than their wild type, unlike nanobodies humanised relying on conventional structural and residue-frequency analysis. We make AbNatiV available as downloadable software and as a webserver.
Microbes as part of ancestral neuronal circuits: Bacterial produced signals affect neurons controlling eating behavior inHydra
Authors: Giez Christoph , Pinkle Denis , Giencke Yan , Wittlieb Jörg , Herbst Eva , Spratte Tobias , Lachnit Tim , Klimovich Alexander , Selhuber-Unkel Christine , Bosch Thomas 
Published: April 2023

SummaryAlthough recent studies indicate the impact of microbes on the central nervous systems and behavior, it remains unclear how the relationship between the functionality of the nervous system, behavior and the microbiota arise. We studied the eating behavior of Hydra, a host that has a simple nervous system and a low-complexity microbiota. To identify the neuronal subpopulations involved, we used a subpopulation specific cell ablation system and calcium imaging. The role of the microbiota was uncovered by reducing the diversity of the natural microbiota. Here, we demonstrate that different neuronal subpopulations are functioning together to control the eating behavior. The microbiota participates in control of the eating behavior since germ-free or mono-colonized animals have drastic difficulties in mouth opening. This was restored by adding a full complement of the microbiota. In summary, we provide a mechanistic explanation of how the eating behavior is controlled inHydraand how microbes can affect the neuronal circuit.Highlights-Multiple neuronal modules and their networks control complex behavior in an animal lacking a central nervous system.-Its associated microbes participate in these neuronal circuits and influence the eating behavior.-Disorganization of the microbiota negatively impacts this eating behavior.-Glutamate participates in an evolutionary ancient interkingdom language.
Suppression of autoimmune arthritis and neuroinflammation via an amino acid-conjugated butyrate prodrug with enhanced oral bioavailability
Authors: Cao Shijie , Budina Erica , Raczy Michal M. , Solanki Ani , Nguyen Mindy , Beckman Taryn N. , Reda Joseph W. , Hultgren Kevin , Ang Phillip , Slezak Anna J. , Hesser Lauren A. , Alpar Aaron T. , Refvik Kirsten C. , Shores Lucas S. , Pillai Ishita , Wallace Rachel P. , Dhar Arjun , Watkins Elyse A. , Hubbell Jeffrey A. 
Published: April 2023

AbstractButyrate, a metabolite produced by commensal bacteria, has been intensively studied for its immunomodulatory effects on various immune cells, including T regulatory cells, macrophages, and dendritic cells. Butyrate’s development as a drug has been limited by its poor oral bioavailability due to its rapid metabolism in the gut, its low potency and thus high dosing, and its foul smell and taste. By simply esterifying butyrate to serine (O-butyryl-L-serine, SerBut), a design based on the concept of utilizing amino acid transporters to escape the gut and enhance systemic uptake thus increasing bioavailability, we developed an odorless and tasteless compound for oral administration. In the collagen antibody-induced arthritis (CAIA) and experimental autoimmune encephalomyelitis (EAE) murine models of rheumatoid arthritis and multiple sclerosis, we demonstrated that SerBut significantly ameliorated disease severity, modulated key immune cell populations both systemically and in disease-associated tissues, and reduced inflammatory responses without compromising global immune response to vaccination. Our findings highlight SerBut as a promising next-generation therapeutic agent for autoimmune and inflammatory diseases.