bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutritional value of extracted soybean, full fat soya and maize gluten meal proteins in comparison to a fish meal based reference diet for fingerling tilapia (Oreochromis mossambicus)
Authors: Bell M. E. , Davies S. J. 
Published: November 2023

AbstractA two-month investigation evaluated potential selected plant protein sources compared to fish meal protein in scientifically formulated diets for fingerling tilapia (Oreochromis mossambicus). Six nutritionally balanced diets: one reference (control) diet (fish-meal-based diet), three selected plant proteins (solvent extracted soybean, full fat soybean, and maize gluten) were substituted in the LT (Low Temperature dried) fish-meal-based control diet protein at 50% respectively, and the remaining diets were replaced with 75% inclusion of solvent extracted soybean and maize gluten meals. Results showed that SESB50, FFSB50 and MG50 fed tilapia did not appreciably differ in their growthperformance (final mean weights of 12.07, 10.75 and 9.18% respectively) with a final mean weight of 14.95g being significantly superior for the fish meal control (CO) group. Substitution of fish meal diet with solvent-extracted soybean and maize gluten at levels of 75% gave the poorest growth performance and Feed Efficiency (FE) (7.01g final weight, 51% FE). However, the MG50 diet also showed some inferior feed utilisation performance. However, tilapia fed on a full fat soybean diet (FFSB50) did not vary significantly from the control (CON) diet in terms of Apparent Net Protein Utilisation (ANPU) at 34.20 and 37.53% respectively. Whilst this preliminary study concluded that limitations on the use of the selected plant proteins in diets for tilapia are apparent, several approaches that could result in the future improvement of the nutritional value of soybean and maize gluten products for use in fish diets are also stated.HighlightsA scientifically formulated reference diet using a Low Temperature dried (LT) fish meal produced superior growth performance for fingerling tilapia compared to selected oilseed (soybean) and grain (maize gluten) derived protein concentrates.Soybean and full fat soybean meals were effective in contributing to 50% inclusion in experimental diets, but 75% of soybean and maize gluten meal was not able to support similar growth of tilapia over eight weeks.Feed utilisation parameters such as Protein Efficiency Ratio (PER), Apparent Net Protein Utilisation (ANPU), Net Energy Utilisation (NEU) and Feed Efficiency (FE) gave supporting evidence and conclusions for optimal threshold inclusions of the test plant ingredients for tilapia.
A note on predator-prey dynamics in radiocarbon datasets
Authors: Marom Nimrod , Wolkowski Uri 
Published: November 2023

AbstractPredator-prey interactions have been a central theme in population ecology for the past century, but real-world data sets only exist for recent, relatively short (<100 years) time spans. This limits our ability to study centennial/millennial-scale predator-prey dynamics. We propose that regional radiocarbon databases can be used to reconstruct a signal of predator-prey population dynamics in deep time, overcoming this limitation. We support our argument with examples from Pleistocene Beringia and the Holocene Judean Desert.
A transcriptomic dataset for investigating the Arabidopsis Unfolded Protein Response under chronic, proteotoxic endoplasmic reticulum stress
Authors: Ducloy Amélie , Azzopardi Marianne , Ivsic Caroline , Cueff Gwendal , Sourdeval Delphine , Charif Delphine , Cacas Jean-Luc 
Published: November 2023

AbstractThe Unfolded Protein Response (UPR) is a retrograde, ER-to-nucleus, signalling pathway which is conserved across kingdoms. In plants, it contributes to development, reproduction, immunity and tolerance to abiotic stress. This RNA sequencing dataset was produced from 14-day-oldArabidopsis thalianaseedlings challenged by tunicamycin (Tm), an antibiotic inhibiting Asn-linked glycosylation in the endoplasmic reticulum (ER), causing an ER stress and eventually activating the UPR. Wild-type (WT) and a double mutant deficient for two main actors of the UPR (INOSITOL-REQUIRING ENZYME 1AandINOSITOL-REQUIRING ENZYME 1B) were used as genetic backgrounds in our experimental setup, allowing to distinguish among differentially-expressed genes (DEGs) which ones are dependent on or independent on IRE1s. Also, shoots and roots were harvested separately to determine organ-specific transcriptomic responses to Tm. Library and sequencing were performed using DNBseq™ technology by the Beijing Genomics Institute. Reads were mapped and quantified against the Arabidopsis genome. Differentially-expressed genes were identified using Rflomics upon filtering and normalization by the Trimmed Mean of M-value (TMM) method. While the genotype effect was weak under mock conditions (with a total of 182 DEGs in shoots and 195 DEGs in roots), the tunicamycin effect on each genotype was characterized by several hundred of DEGs in both shoots and roots. Among these genes, 872 and 563 genes were statistically up- and down-regulated in the shoot tissues of the double mutant when compared to those of WT, respectively. In roots of Tm-challenged seedlings, 425 and 439 genes were significantly up- and down-regulated in mutants with respect to WT. We believe that our dataset could be reused for investigating any biological questions linked to ER homeostasis and its role in plant physiology.SPECIFICATIONS TABLE
Single cell RNA-sequencing suggests a novel lipid associated mast cell population following weight cycling
Authors: Caslin Heather L. , Cottam Matthew A. , Betjemann Alexa M. , Mashayekhi Mona , Silver Heidi J , Hasty Alyssa H. 
Published: November 2023

AbstractOur recent study showed weight cycled mice have increased adipose mast cells compared to obese mice by single cell RNA-sequencing. Here, we aimed to confirm and elucidate these changes. Further analysis of our dataset showed that our initial mast cell cluster could subcluster into two unique populations: one with very high expression of classical mast cell markers and another with elevated lipid handling and antigen presentation genes. This new mast cell cluster accounted for most of the mast cells in the weight cycled group although it was not possible to detect the different populations by new studies with flow cytometry or Toluidine blue staining in mice, possibly due to a downregulation in classical mast cell genes. Interestingly, a pilot study in humans did suggest the existence of two mast cell populations in subcutaneous adipose tissue from obese women that appear similar to the murine populations detected by sequencing; one of which was significantly correlated with weight variance. Together, these data suggest that weight cycling may induce a unique population of mast cells similar to lipid associated macrophages. Future studies will focus on isolation of these cells to better determine their lineage, differentiation, and functional roles.
Sclerostin modulates the degree of mineralization and the stiffness profile of the fibrocartilaginous enthesis for mechanical tissue integrity
Authors: Yambe Shinsei , Yoshimoto Yuki , Ikeda Kazutaka , Maki Koichiro , Takimoto Aki , Higuchi Shinnosuke , Yu Xinyi , Uchibe Kenta , Miura Shigenori , Watanabe Hitomi , Sakuma Tetsushi , Yamamoto Takashi , Tanimoto Kotaro , Kondoh Gen , Docheva Denitsa , Adachi Taiji , Shukunami Chisa 
Published: November 2023

ABSTRACTFibrocartilaginous entheses consist of four graded tissue layers including tendon, the unmineralized and mineralized fibrocartilage, and subchondral bone with varying degrees of stiffness. Here we examined the functional role of sclerostin that is expressed in mature mineralized fibrochondrocytes. Following rapid mineralization of the unmineralized fibrocartilage and parallel replacement of epiphyseal hyaline cartilage by bone, the unmineralized fibrocartilage re-expanded after a decline in alkaline phosphatase activity at the mineralization front. Sclerostin was co-expressed with osteocalcin in the bottom of the mineralized fibrocartilage adjacent to subchondral bone. InScxdeficient mice with less mechanical loading due to defects of the Achilles tendon, the number of sclerostin+fibrochondrocytes was significantly reduced in the defective enthesis where chondrocyte maturation was markedly impaired in both fibrocartilage and hyaline cartilage. Loss of theSostgene, coding for sclerostin, caused increased mineral density in the mineralized zones of the fibrocartilaginous enthesis. Atomic force microscopy analysis revealed the higher stiffness of fibrocartilage. These lines of evidence suggest that sclerostin in mature mineralized fibrochondrocytes acts as a modulator for mechanical tissue integrity of the fibrocartilaginous enthesis.
cellstruct: Metrics scores to quantify the biological preservation between two embeddings
Authors: Loh Jui Wan , Ouyang John F. 
Published: November 2023

AbstractSingle-cell transcriptomics (scRNA-seq) is extensively applied in uncovering biological heterogeneity. There are different dimensionality reduction techniques, but it is unclear which method works best in preserving biological information when creating a two-dimensional embedding. Therefore, we implemented cellstruct, which calculates three metrics scores to quantify the global or local biological similarity between a two-dimensional and its corresponding higher-dimensional PCA embeddings at either single-cell or cluster level. These scores pinpoint cell populations with low biological information preservation, in addition to visualizing the cell-cell or cluster-cluster relationships in the PCA embedding. Two study cases illustrate the usefulness of cellstruct in exploratory data analysis.
Cyld aborts hyperactivation of synovial fibroblasts in inflammatory arthritis by regulating the TAK1/IKK2 signaling axis
Authors: Rinotas Vagelis , Iliaki Kalliopi , Pavlidi Lydia , Meletakos Theodore , Mosialos George , Armaka Marietta 
Published: November 2023

AbstractTNF is a potent cytokine known for its involvement in physiology and pathology. In Rheumatoid Arthritis (RA), persistent TNF signals cause aberrant activation of synovial fibroblasts (SFs), the resident cells crucially involved in the inflammatory and destructive responses of the affected synovial membrane. However, the molecular switches that control the pathogenic activation of SFs remain poorly defined. Cyld is a major component of deubiquitination (DUB) machinery regulating the signaling responses towards survival/inflammation and programmed necrosis that induced by cytokines, growth factors and microbial products. Here we follow functional genetic approaches to understand how Cyld affects arthritogenic TNF signaling in SFs. We demonstrate that in spontaneous and induced RA models, SF-Cyld DUB deficiency deteriorates arthritic phenotypes due to increased levels of chemokines, adhesion receptors and bone-degrading enzymes generated by mutant SFs. Mechanistically, Cyld serves to restrict the TNF-induced hyperactivation of SFs by limiting Tak1-mediated signaling, and, therefore, leading to supervised NFkB and JNK activity. However, Cyld is not critically involved in the regulation of TNF-induced death of SFs. Our results identify SF-Cyld as a regulator of TNF-mediated arthritis and inform the signaling landscape underpinning the SF responses.
The helminth TGF-β mimic TGM4 is a modular ligand that binds CD44, CD49d and TGF-β receptors to preferentially target myeloid cells
Authors: Singh Shashi P. , Smyth Danielle J. , Cunningham Kyle , Mukundan Ananya , Byeon Chang-Hyeock , Hinck Cynthia S. , White Madeleine P. J. , Ciancia Claire , Wosowska Nątalia , Sanders Anna , Jin Regina , Lilla Sergio , Zanivan Sara , Schoenherr Christina , Inman Gareth , van Dinther Maarten , ten Dijke Peter , Hinck Andrew P. , Maizels Rick M. 
Published: November 2023

AbstractThe murine helminth parasiteHeligmosomoides polygyrusexpresses a family of modular proteins which, replicating the functional activity of the immunomodulatory cytokine TGF-β, have been named TGM (TGF-β Μimic). Multiple domains bind to different receptors, including TGF-β receptors TβRI (ALK5) and TβRII through domains 1-3, and prototypic family member TGM1 binds the cell surface co-receptor CD44 through domains 4-5. This allows TGM1 to induce T lymphocyte Foxp3 expression, characteristic of regulatory (Treg) cells, and to activate a range of TGF-β-responsive cell types. In contrast, a related protein, TGM4, targets a much more restricted cell repertoire, primarily acting on myeloid cells, with less potent effects on T cells and lacking activity on other TGF-β-responsive cell types. TGM4 binds avidly to myeloid cells by flow cytometry, and can outcompete TGM1 for cell binding. Analysis of receptor binding in comparison to TGM1 reveals a 10-fold higher affinity than TGM1 for TGFβR-I (TβRI), but a 100-fold lower affinity for TβRII through Domain 3. Consequently, TGM4 is more dependent on co-receptor binding; in addition to CD44, TGM4 also engages CD49d (Itga4) through Domains 1-3, as well as CD206 and Neuropilin-1 through Domains 4 and 5. TGM4 was found to effectively modulate macrophage populations, inhibiting lipopolysaccharide-driven inflammatory cytokine production and boosting interleukin (IL)-4-stimulated responses such as Arginase-1in vitroandin vivo. These results reveal that the modular nature of TGMs has allowed the fine tuning of the binding affinities of the TβR- and co-receptor binding domains to establish cell specificity for TGF-β signalling in a manner that cannot be attained by the mammalian cytokine.
Enhancing CAR-T Cell Metabolism to Overcome Hypoxic Conditions in the Brain Tumor Microenvironment
Authors: Hatae Ryusuke , Kyewalabye Keith , Yamamichi Akane , Chen Tiffany , Phyu Su , Chuntova Pavlina , Nejo Takahide , Levine Lauren S. , Spitzer Matthew H. , Okada Hideho 
Published: November 2023

AbstractThe efficacy of chimeric antigen receptor (CAR)-T therapy has been limited against brain tumors to date. CAR-T cells infiltrating syngeneic intracerebral SB28-EGFRvIII glioma revealed impaired mitochondrial ATP production and a markedly hypoxic status compared to ones migrating to subcutaneous tumors. Drug screenings to improve metabolic states of T cells under hypoxic conditions led us to evaluate the combination of AMPK activator Metformin and the mTOR inhibitor Rapamycin (Met+Rap). Met+Rap-pretreated mouse CAR-T cells showed activated PPAR-gamma coactivator 1α (PGC-1α) through mTOR inhibition and AMPK activation, and a higher level of mitochondrial spare respiratory capacity than those pretreated with individual drugs or without pretreatment. Moreover, Met+Rap-pretreated CAR-T cells demonstrated persistent and effective anti-glioma cytotoxic activities in the hypoxic condition. Furthermore, a single intravenous infusion of Met+Rap-pretreated CAR-T cells significantly extended the survival of mice bearing intracerebral SB28-EGFRvIII gliomas. Mass cytometric analyses highlighted increased glioma-infiltrating CAR-T cells in the Met+Rap group with fewer Ly6c+ CD11b+ monocytic myeloid-derived suppressor cells in the tumors. Finally, human CAR-T cells pretreated with Met+Rap recapitulated the observations with murine CAR-T cells, demonstrating improved functions in vitro hypoxic conditions. These findings advocate for translational and clinical exploration of Met+Rap-pretreated CAR-T cells in human trials.
Multi-genome comparisons reveal gain-and-loss evolution of theanti-Mullerian hormone receptor type 2gene, an old master sex determining gene, in Percidae
Authors: Kuhl Heiner , Euclide Peter T , Klopp Christophe , Cabau Cedric , Zahm Margot , Roques Céline , Iampietro Carole , Kuchly Claire , Donnadieu Cécile , Feron Romain , Parrinello Hugues , Poncet Charles , Jaffrelo Lydia , Confolent Carole , Wen Ming , Herpin Amaury , Jouanno Elodie , Bestin Anastasia , Haffray Pierrick , Morvezen Romain , de Almeida Taina Rocha , Lecocq Thomas , Schaerlinger Bérénice , Chardard Dominique , Żarski Daniel , Larson Wes , Postlethwait John H. , Timirkhanov Serik , Kloas Werner , Wuertz Sven , Stöck Matthias , Guiguen Yann 
Published: November 2023

ABSTRACTThe Percidae family comprises many fish species of major importance for aquaculture and fisheries. Based on three new chromosome-scale assemblies inPerca fluviatilis,Perca schrenkiiandSander vitreusalong with additional percid fish reference genomes, we provide an evolutionary and comparative genomic analysis of their sex-determination systems. We explored the fate of a duplicated anti-Mullerian hormone receptor type-2 gene (amhr2bY), previously suggested to be the master sex determining (MSD) gene inP. flavescens. Phylogenetically related and structurally similar amhr2duplications (amhr2b) were found inP. schrenkiiandSander lucioperca, potentially dating this duplication event to their last common ancestor around 19-27 Mya. InP. fluviatilisandS. vitreus, thisamhr2bduplicate has been lost while it was subject to amplification inS. lucioperca. Analyses of theamhr2blocus inP. schrenkiisuggest that this duplication could be also male-specific as it is inP. flavescens. InP. fluviatilis, a relatively small (100 kb) non-recombinant sex-determining region (SDR) was characterized on chromosome-18 using population-genomics approaches. This SDR is characterized by many male-specific single-nucleotide variants (SNVs) and no large duplication/insertion event, suggesting thatP. fluviatilishas a male heterogametic sex determination system (XX/XY), generated by allelic diversification. This SDR contains six annotated genes, including three (c18h1orf198,hsdl1,tbc1d32) with higher expression in testis than ovary. Together, our results provide a new example of the highly dynamic sex chromosome turnover in teleosts and provide new genomic resources for Percidae, including sex-genotyping tools for all three knownPercaspecies.
Discovering cryptic pocket opening and binding of a stimulant derivative in a vestibular site of the 5-HT3Areceptor
Authors: Haloi Nandan , Karlsson Emelia , Delarue Marc , Howard Rebecca J. , Lindahl Erik 
Published: November 2023

AbstractLigand-gated ion channels propagate electrochemical signals in the nervous system. A diverse set of modulators including stimulants, anesthetics, and lipids regulate their function; however, structures of ligand-bound complexes can be difficult to capture by experimental methods, particularly when binding is dynamic or transient. Here, we used computational methods and electrophysiology to identify a possible bound state of a modulatory stimulant derivative in a cryptic vestibular pocket, distinct from the orthosteric neurotransmitter binding site, of a mammalian serotonin-3A receptor. Starting from a closed-pocket experimental structure, we first applied a molecular dynamics simulations-based goal-oriented adaptive sampling method to identify possible open-pocket conformations. To find plausible ligand-binding poses, we performed Boltzmann docking, which combines traditional docking with Markov state modeling, of the newly sampled conformations. Clustering and analysis of stability and accessibility of docked poses supported a preferred binding site; we further validated this site by mutagenesis and electrophysiology, suggesting a mechanism of potentiation by stabilizing intersubunit contacts. Given the pharmaceutical relevance of serotonin-3 receptors in emesis, psychiatric and gastrointestinal diseases, characterizing relatively unexplored modulatory sites such as these could open valuable avenues to understanding conformational cycling and designing state-dependent drugs.Significance5-HT3Areceptors receive the chemical signals of excitatory neurotransmission across the synapse in the central and peripheral nervous systems, and are involved in conditions including emesis, pain, psychiatric disorders, drug abuse, and irritable bowel syndrome. Given their pharmaceutical importance, there is great interest in understanding how and where ligands interact with these receptors. A pocket facing the extracellular vestibule of this membrane protein has been proposed as a modulatory site, but it remains largely uncharacterized in the context of structural modeling or pharmacologically relevant ligands. Here, we are able to identify and investigate binding of a stimulant derivative, 4-bromoamphetamine, in this site by using an integrative computational and experimental approach that is able to account for conformational flexibility.
ROS-mediated TNFR Wengen activation in response to apoptosis
Authors: Esteban-Collado José , Fernàndez-Mañas Mar , Fernández-Moreno Manuel , Maeso Ignacio , Corominas Montserrat , Serras Florenci 
Published: November 2023

AbstractThe activation of tumor necrosis factor receptors (TNFR) controls pleiotropic pro-inflammatory functions ranging from apoptosis to survival. The ability to trigger a particular function will depend on the upstream activation, association with regulatory complexes and downstream pathways. InDrosophila,two TNFRs have been identified, Wengen (Wgn) and Grindelwald (Grnd). Although several reports associate these receptors with JNK-dependent apoptosis, it has recently been found that Wgn activates a variety of functions. We demonstrate that Wgn is required for survival by protecting cells from apoptosis. This is mediated by the signaling molecule dTRAF1 and results in the activation of the p38 MAP kinase signaling pathway. Remarkably, Wgn is required for apoptosis-induced regeneration and is activated by the reactive oxygen species (ROS) produced following apoptosis. This ROS activation is exclusive for Wgn, but not for Grnd, and occurs in the absence of the ligand Eiger/TNFα. Furthermore, based on protein sequence conservation, the extracellular Cys-rich domain of Grnd is much more divergent and phylogenetically restricted than that of Wgn, which is more similar to TNFR families from other animals, including those of human TNFRs. Taken together, our results show a novel function for a TNFR that responds to cellular damage by ensuring the cell survival required for the response to damage.
The yeast ribosomal protein Rpl1b is not required for respiration
Authors: Futcher B. 
Published: November 2023

AbstractPreviously, Segev and Gerst found that mutants in any of the four ribosomal protein genesrpl1b, rpl2b, rps11a, orrps26bhad a petite phenotype—i.e., the mutants were deficient in respiration. Strikingly, mutants of their paralogsrpl1a, rpl2a, rps11b, andrps26awere grande—i.e., competent for respiration. It is remarkable that these paralogs should have opposite phenotypes, because three of the paralog pairs (Rpl1a/Rpl1b, Rpl2a/Rpl2b, Rps11a/Rps11b) are 100% identical to each other in amino acid sequence, while Rps26a and Rps26b differ in 2 amino acids out of 119. However, while attempting to use this paralog-specific petite phenotype in an unrelated experiment, I found that therpl1b, rpl2b, rps11a, andrps26bdeletion mutants are competent for respiration, contrary to Segev and Gerst.