bluuebunny/crossref_metadata_2025_split huggingface dataset:
scParadise: Tunable highly accurate multi-task cell type annotation and surface protein abundance prediction
Authors: Chechekhina Elizaveta , Tkachuk Vsevolod , Chechekhin Vadim 
Published: September 2024

AbstractscRNA-seq is revolutionizing biomedical research by revealing tissue architecture, cellular composition, and functional interactions. However, accurate cell type annotation remains a challenge, particularly for rare cell types, with existing automated methods often falling short. Multimodal data, combining mRNA expression and protein markers, improves deep cellular analysis and make functional characterization of complex tissues more accurate. However, it is costly and complex to obtain. We presentscParadise, a cutting-edge Python framework featuring three tools:scAdamfor multi-level cell annotation,scEvefor surface protein prediction, andscNoahfor benchmarking. scAdam surpasses current methods in annotating rare cell types and ensures consistent results across diverse datasets, while scEve enhances clustering and cell type separation. With scNoah’s advanced metrics, scParadise offers a powerful, fast, and reliable solution for single-cell analysis, setting a new standard in scRNA-seq data processing.
Ancient polyploidy and low rate of chromosome loss explain the high chromosome numbers of homosporous ferns
Authors: Li Zheng , Kinosian Sylvia P. , Zhan Shing H. , Barker M. S. 
Published: September 2024

AbstractA longstanding question in plant evolution is why ferns have many more chromosomes than angiosperms. The leading hypothesis proposes that ferns have ancient polyploidy without chromosome loss or gene deletion to explain the high chromosome numbers of ferns. Here, we test this hypothesis by estimating ancient polyploidy frequency, chromosome evolution, protein evolution in meiosis genes, and patterns of gene retention in ferns. We found similar rates of paleopolyploidy in ferns and angiosperms from independent phylogenomic and chromosome number evolution analyses, but lower rates of chromosome loss in ferns. We found elevated evolutionary rates in meiosis genes in angiosperms, but not in ferns. Finally, we found some evidence of parallel and biased gene retention in ferns, but this was comparatively weak to patterns in angiosperms. This work provides genomic evidence supporting a decades-old hypothesis on fern genome evolution and provides a foundation for future work on plant genome structure.
in vitroanalysis of a competitive inhibition model for T7 RNA polymerase biosensors
Authors: Delaney Ryan , Lamb Katherine A. , Irvin Olivia M. , Baumer Zachary T. , Whitehead Timothy A. 
Published: September 2024

AbstractT7 RNA polymerase (T7 RNAP) biosensors, in which T7 RNAP transcribes some reporter gene or signal in response to external stimuli, have wide applications in synthetic biology and metabolic engineering. We adapted a biochemical reaction network model and used anin vitrotranscription assay to determine network parameters for different T7 RNAP constructs. Under conditions where template DNA is limiting, the EC50values of native and engineered T7 RNAPs ranged from 33 nM (29 -37 95% c.i.) to 570 nM (258 -714 95% c.i.) (wild-type T7 RNAP). The measured EC50values were largely insensitive to free magnesium, pH, or other buffer conditions. Many biosensor configurations use a split RNAP construct, where the C-terminal (CT7) and N-terminal T7 (NT7) are fused to proximity induced dimerization modules. We used proteolysis and ion exchange chromatography to prepare a CT7 (80 kDa) product. The impact of free CT7 on T7 RNAP transcriptional activity was well described by a competitive inhibition model, with an inhibitory constant KI= 24 nM (22-26 95% c.i.) of the sensor. These model parameters will be useful for forward modeling and design of T7 RNAP-based genetic circuits.HighlightsEC50values for natural and engineered T7 RNAPs measured in vitroC-terminal T7 RNAP is a competitive inhibitor of full-length T7 RNAPThe inhibition constant of C-terminal T7 RNAP is lower than the EC50of T7 RNAP
Structural basis for the access and binding of resolvin D1 (RvD1) to formyl peptide receptor 2 (FPR2/ALX), a class A GPCR
Authors: Mun Brian , Obi Peter , Szlenk Christopher T. , Natesan Senthil 
Published: September 2024

ABSTRACTInflammation is essential to the body’s defense against tissue injury and microbial invasion. However, uncontrolled inflammation is highly detrimental and can result in chronic inflammatory diseases such as asthma, cancer, obesity, and diabetes. An increasing body of evidence suggests that specialized pro-resolving lipid mediators (SPMs), such as resolvins, are actively involved in critical cellular events that drive the resolution of inflammation and a return to homeostasis. An imbalance caused by insufficient SPMs can result in the unsuccessful resolution of inflammation. The D-series resolvins (metabolites of docosahexaenoic acid), such as resolvin D1 (RvD1) and resolvin D2 (RvD2), carry out their pro-resolving functions by directly binding to class A G protein-coupled receptors FPR2/ALXR and GPR32, and GPR18, respectively. We recently demonstrated that RvD1 and RvD2 preferentially partition and accumulate at the polar headgroup regions of the membrane. However, the mechanistic detail of how RvD1 gains access to the FPR2 binding site from a surrounding membrane environment remains unknown. In this study, we used classical MD and well-tempered metadynamics simulations to examine the structural basis for the access and binding of RvD1 to its target receptor from aqueous and membrane environments. The results offer valuable insights into the access path, potential binding pose, and key residue interactions essential for the access and binding of RvD1 to FPR2/ALXR and may help in identifying small molecule therapeutics as a possible treatment for inflammatory disorders.
The ECOLOPES PLANT MODEL : a high-resolution model to simulate plant community dynamics in cities and other human-dominated and managed environments
Authors: Joschinski Jens , Boulangeat Isabelle , Calbi Mariasole , Hauck Thomas E. , Vogler Verena , Mimet Anne 
Published: September 2024

AbstractCities and urbanized areas have become an important habitat for organisms. Although nature can provide multiple ecosystem services to humans, urban planning and architecture often do not adequately consider the ecological needs of species. In ECOLOPES we envision buildings, and in particular building envelopes, to be a joint habitat for humans, plants, animals and microbiota as equally relevant stakeholders. A centerpiece of the planning and design tools that ECOLOPES provides is a joint soil-plant-animal community model. We present the first prototype of the ECOLOPES PLANT (community) MODEL that responds to 3-dimensional (building) geometry and management, show potential applications as a stand-alone model, and discuss its technical and conceptual limitations that are yet to be overcome.
SeaMoon: Prediction of molecular motions based on language models
Authors: Lombard Valentin , Timsit Dan , Grudinin Sergei , Laine Elodie 
Published: September 2024

AbstractHow protein move and deform determines their interactions with the environment and is thus of utmost importance for cellular functioning. Following the revolution in single protein 3D structure prediction, researchers have focused on repurposing or developing deep learning models for sampling alternative protein conformations. In this work, we explored whether continuous compact representations of protein motions could be predicted directly from protein sequences, without exploiting nor sampling protein structures. Our approach, called SeaMoon, leverages protein Language Model (pLM) embeddings as input to a lightweight (∼1M trainable parameters) convolutional neural network. SeaMoon achieves a success rate of up to 40% when assessed against∼1 000 collections of experimental conformations exhibiting a wide range of motions. SeaMoon capture motions not accessible to the normal mode analysis, an unsupervised physics-based method relying solely on a protein structure’s 3D geometry, and generalises to proteins that do not have any detectable sequence similarity to the training set. SeaMoon is easily retrainable with novel or updated pLMs.
Evolving properties of biological materials captured via needle-based cavity expansion method
Authors: Varner Hannah M. , Naghibzadeh S. Kiana , Spaeth Katie C. , Klein Abigail , Cohen Tal 
Published: September 2024

AbstractBackgroundThe mechanical properties of biological tissues change over time and with disease progression. Quantifying these mechanical properties can thus be instrumental for medical diagnosis and for evaluation of tissue viability for transplant. However, soft and biological materials are exceptionally challenging to mechanically characterize using conventional testing methods, which are hindered by limitations of sample size, fixturing capabilities, and sample preparation.ObjectiveWe hypothesize that Volume Controlled Cavity Expansion (VCCE) is well-suited to capture subtle mechanical differences in biological tissue. The objective of this work is therefore twofold: first, we seek to quantify how stiffness of liver and gelatin evolve with age. In achieving this understanding, we aim to demonstrate the precision of VCCE in measuring subtle changes in the mechanical properties of biological tissues.MethodsPerforming VCCE tests over 15 days in samples of gelatin and liver (porcine and bovine), we track the evolving pressure-volume response and deformation limits of the materials.ResultsIn both materials, we observed time-dependent variation of the stiffness and fracture thresholds. In gelatin VCCE repeatably captured stiffening over time, which was correlated with a higher fracture stress. This was in contrast to observations in bovine liver, where stiffening corresponded to a lower fracture stress. Porcine liver initially stiffened, then reversed this trend and relaxed.ConclusionThrough this work we show that liver and gelatin stiffen with age, and that this trend is measurable via VCCE. These results highlight the utility of VCCE and call attention to the need for a new class of mechanism based constitutive models that are capable of capturing variations in material over time with a minimal number of parameters.
Robust and highly efficient transformation method for a minimal Mycoplasma cell
Authors: Mizutani Masaki , Glass John I , Fukatsu Takema , Suzuki Yo , Kakizawa Shigeyuki 
Published: September 2024

ABSTRACTMycoplasmas have been widely investigated for their pathogenicity, as well as for genomics and synthetic biology. Conventionally, transformation of mycoplasmas was not highly efficient, and due to the low transformation efficiency, large amounts of DNA and recipient cells were required for that purpose. Here we report a robust and highly efficient transformation method for the minimal cell JCVI-syn3B, which was created through streamlining of the genome ofMycoplasma mycoides. When the growth states of JCVI-syn3B were examined in detail by focusing on such factors as pH, color, absorbance, CFU, and transformation efficiency, we found that the growth phase after the lag phase can be divided into three distinct phases, of which the highest transformation efficiency was observed during the early-exponential growth phase. Notably, we attained the transformation efficiency up to 4.4 × 10-2transformants per cell per μg plasmid DNA. We developed a method to obtain several hundred to several thousand transformants with less than 0.2 mL of cultured cells and 10 ng of plasmid DNA. Moreover, we established a transformation method using frozen stock of transformation-ready cells. These procedures and information could simplify and enhance the transformation process of minimal cells, facilitating advanced genetic engineering and biological research using minimal cells.IMPORTANCEMycoplasmas are parasitic and pathogenic bacteria for many animals. They are also useful bacteria to understand cellular process of life and for bioengineering because of their simple metabolism, small genomes and cultivability. Genetic manipulation is crucial for these purposes, but transformation efficiency in mycoplasmas is typically quite low. Here we report a highly efficient transformation method for the minimal genome mycoplasma JCVI-syn3B. Using this method, transformants can be obtainable only 10 nanograms of plasmid DNA, which is around one-thousandth amount required for traditional mycoplasma transformations. Moreover, we established a convenient method using frozen stocks of transformation-ready cells. These improved methods play a crucial role in further studies using minimal cells.
Opioids Diminish the Placebo Antidepressant Response: A Post Hoc Analysis of a Randomized Controlled Ketamine Trial
Authors: Lii Theresa R. , Flohr Josephine R. , Okada Robin L. , Cianfichi Lisa J. , Hack Laura M. , Schatzberg Alan F. , Heifets Boris D. 
Published: September 2024

AbstractBackgroundThe endogenous opioid system is thought to play a role in the placebo antidepressant response. A recent trial comparing the rapid antidepressant effects of ketamine versus placebo in surgical patients, some of whom were on chronic opioid therapy, revealed a substantial placebo effect. This finding provided an opportunity to test the hypothesis that opioid agonist exposure interacts with placebo antidepressant responses.MethodsThispost hocanalysis utilized data from a previously reported randomized, anesthesia-blinded, placebo-controlled trial of intravenous ketamine in depressed patients undergoing routine surgery. Mixed-effects models were used to determine whether baseline opioid use influenced antidepressant responses to the trial interventions, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) over 1 to 14 days post-treatment.ResultsIn the placebo arm, baseline opioid use was associated with a 10-point increase (95% CI: 0.81–19.4) in MADRS scores across all post-treatment time points, indicating worse depression in this subgroup. In an alternative model using percent change in MADRS scores, the difference between opioid users and non-users was 38.4% (95% CI: 8.59–68.2), with opioid users experiencing less improvement. For ketamine-treated participants, baseline opioid use did not significantly impact MADRS scores or the percent change in MADRS scores. Pain intensity was not a significant predictor of MADRS outcomes, and the correlation between post-treatment MADRS scores and pain intensity was negligible (R=0.12).LimitationsThis analysis was unregistered and conducted on a small sample; the findings need to be confirmed by prospective controlled studies.ConclusionsOpioid use at baseline attenuated the placebo antidepressant response independently of pain in depressed patients who received the study treatment under general anesthesia for routine surgery. The antidepressant response was preserved in opioid users who received intravenous ketamine.
Non-invasive epidermal proteome assessment-based diagnosis and molecular subclassification of psoriasis and eczematous dermatitis
Authors: Murphy Michael J. , Chen Gloria , Edemobi Princess , Junejo Muhammad H. , Wride A. Mitchel , Spaulding Sarah L. , Wang Yiwei , Cohen Jeffrey M. , Damsky William 
Published: September 2024

AbstractBackgroundImmunologic heterogeneity is known to exist within both eczematous dermatitis and psoriasis; however, selection of molecularly targeted therapies for individual patients generally does assess for or incorporate such information about patient-specific immune changes.ObjectiveWe sought to develop a rapid, non-invasive method for obtaining and analyzing epidermal protein biomarkers from skin and utilize this methodology to dissect immunologic heterogeneity in both psoriasis and eczematous dermatitis.MethodsWe optimize and evaluate detergent-based immune profiling system (DIPS) which utilizes a combination of two detergents to solubilize full-thickness epidermis when applied to the skin with an applicator. Downstream proteomic profiling of this material allows high-throughput immunologic characterization of immune biomarkers.ResultsDIPS was performed on 43 patients with psoriasis and 27 patients with eczematous dermatitis. This approach was found to be painless, nonscarring, and enabled rapid turnaround from sample collection to data output. We used this approach to accurately differentiate psoriasis and eczema using a limited set of proteins and to identify cases of eczema/psoriasis overlap with non-canonical molecular profiles. Additionally, we measured patient-specific cytokine profiles in eczema that correlated with response to IL-4Rα blockade.ConclusionDIPS is a promising new non-invasive cutaneous immune profiling approach that can deconvolute immune heterogeneity amongst patients with both psoriasis and eczematous dermatitis.Clinical ImplicationDIPS has potential applications in both research and day-to-day dermatologic practice and may help personalize diagnosis and medication selection in patients with inflammatory skin diseases.Capsule summaryDetergent-based immune profiling system (DIPS), a novel non-invasive approach for molecular evaluation of skin disease, is described and evaluated in psoriasis and eczematous dermatitis
Unmasking Neuroendocrine Prostate Cancer with a Machine Learning-Driven 7-Gene Stemness Signature that Predicts Progression
Authors: Sabater Agustina , Sanchis Pablo , Seniuk Rocio , Pascual Gaston , Anselmino Nicolas , Alonso Daniel , Cayol Federico , Vazquez Elba , Marti Marcelo , Cotignola Javier , Toro Ayelen , Labanca Estefania , Bizzotto Juan , Gueron Geraldine 
Published: September 2024

ABSTRACTProstate cancer (PCa) poses a significant global health challenge, particularly due to its progression into aggressive forms like neuroendocrine prostate cancer (NEPC). This study developed and validated a stemness-associated gene signature using advanced machine learning techniques, including Random Forest and Lasso regression, applied to large-scale transcriptomic datasets. The resulting 7-gene signature (KMT5C, MEN1, TYMS, IRF5, DNMT3B, CDC25B and DPP4) was validated across independent cohorts and patient-derived xenograft (PDX) models. The signature demonstrated strong prognostic value for progression-free, disease-free, relapse-free, metastasis-free, and overall survival. Importantly, the signature not only identified specific NEPC subtypes, such as large-cell neuroendocrine carcinoma, which is associated with very poor outcomes, but also predicted a poor prognosis for PCa cases that exhibit this molecular signature, even when they were not histopathologically classified as NEPC. This dual prognostic and classifier capability makes the 7-gene signature a robust tool for personalized medicine, providing a valuable resource for predicting disease progression and guiding treatment strategies in PCa management.
Evolutionary uniqueN-glycan-dependent protein quality control system plays pivotal roles in cellular fitness and extracellular vesicle transport inCryptococcus neoformans
Authors: Mota Catia , Kim Kiseung , Son Ye Ji , Thak Eun Jung , Lee Su-Bin , Kim Ju-El , Yoon Jeong-Kee , Kang Min-Ho , Hwang Heeyoun , Bahn Yong-Sun , Alspaugh J. Andrew , Kang Hyun Ah 
Published: September 2024

AbstractA conservedN-glycan-dependent endoplasmic reticulum protein quality control (ERQC) system has evolved in eukaryotes to ensure accuracy during glycoprotein folding. The human pathogenCryptococcus neoformanspossesses a uniqueN-glycosylation pathway that lacks the glucose addition step to the coreN-glycan precursors in the ER but includes additional basidiomycetes-specific mannosidases. To investigate the molecular features and functions of the ERQC system inC. neoformans,we characterized a set of mutants with deletion of genes coding for the ERQC sensor UDP-glucose:glycoprotein glucosyltransferase (UGG1) and putative α1,2-mannose trimming enzymes (MNS1,MNS101,MNL1, andMNL2). Theugg1Δ,mns1Δ,mns101Δ, andmns1Δ101Δ mutants showed alterations inN-glycan profiles, defective cell surface organization, decreased survival in host cells, and varying degrees of reducedin vivovirulence. Theugg1Δ strain exhibited severely impaired extracellular secretion of capsular polysaccharides and virulence-related enzymes. Comparative transcriptome analysis showed the upregulation of protein folding, proteolysis, and cell wall remodeling genes, which is indicative of induced ER stress inugg1Δ. However, no apparent changes were observed in the expression of genes involved in protein secretion or capsule biosynthesis. Additionally, extracellular vesicle (EV) analysis combined with proteomic analysis showed significant alterations in the number, size distribution, and cargo composition of EVs inugg1Δ. These findings highlight the essential role of the functional ERQC system for cellular fitness under adverse conditions and proper EV-mediated transport of virulence bags, which are crucial for the full fungal pathogenicity ofC. neoformans.
Adaptation to high pressure; insights from the genome of an evolvedEscherichia colistrain with increased piezotolerance
Authors: Allemann Marco N. , Ma Stacey , Sztain Terra , Bartholow Thomas G. , Marshall Ian P.G. , McCammon J. Andrew , Burkart Michael , Allen Eric E. , Bartlett Douglas H. , Marietou Angeliki 
Published: September 2024

AbstractPressure is a key environmental parameter that influences the activity and distribution of microbial life on our planet. Despite its key role there is still not a definitive list of essential genes for microbial adaptation to life under increasing pressure. In this study we used a previously characterizedEscherichia colistrain (AN62) evolved to grow at pressure (60 MPa) non-permissive to the parental strain and performed comparative genomics in order to identify the genome-level adaptations that might allowed the observed pressure-adapted phenotype. We identified 18 mutations in total of which 3 mutations were present in both the parental and evolved strain, 3 mutations were only present in the parental strain, and 12 mutations were observed only in the evolved AN62 strain. Among the characterized mutations we observed a point mutation in the acyl carrier protein (acpPV43G). Complementation experiments revealed that the observed V43G mutation in AcpP is responsible for increased levels of cis-vaccenic acid but is not alone responsible for the pressure adapted phenotype. Further molecular dynamics and docking simulations suggested that the V43G mutation promoted stronger binding of the AcpP protein to partner enzymes of the fatty acid biosynthesis pathway involved in fatty acid unsaturation.Data SummaryEscherichiacoli reads from the parental and evolved strain have been deposited in the Sequence Read Archive (SRA) under accession number RJNA600359. All software used in the bioinformatic analysis is publicly available.Impact StatementPressure is a key environmental parameter. Two-thirds of our planet is covered by oceans with an average depth of 3800m, which means that the majority of the marine life experiences deep sea conditions. Our results offer a list of gene mutations that could contribute to an improved pressure growth phenotype inEscherichia coli, offering a unique insight on the genome level adaptations that might contribute to high pressure adaptation.