bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hsa-miR-31-5p controls a metabolic switch in psoriatic keratinocytes that identifies therapeutic intervention
Authors: Wang Mao-Jie , Xu Yong-Yue , Vos HarmJan , Gulersonmez Can , Stigter Edwin , Gerritsen Johan , Gallego Marc Pages , van Es Robert , Li Li , Deng Hao , Han Ling , Huang Run-Yue , Lu Chuan-Jian , Burgering Boudewijn MT 
Published: January 2022

AbstractPsoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Immune cell activation requires increased glucose consumption, consequently limiting glucose availability for other cell types like keratinocytes. In psoriasis Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes. Here we show that miR-31 expression in keratinocytes is induced by limited glucose availability and increases survival under limiting glucose conditions, by increasing glutamine metabolism. In addition, miR-31 induced glutamine metabolism results in secretion of specific metabolites (aspartate and glutamate) but also immuno-modulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibition of glutaminase (GLS) using CB-839 impedes miR31-induced metabolic rewiring and secretion of immuno-modulatory factors. Concordantly, pharmacological targeting of GLS alleviated psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.
Reproductive outcomes in sport horse commercial French breeding farms: clinical relevance of mares’ age, parity and lactating status
Authors: Derisoud Emilie , Grimard Bénédicte , Gourtay Clothilde , Auclair-Ronzaud Juliette , Chavatte-Palmer Pascale 
Published: January 2022

AbstractBackgroundFor a long time, important and progressive fertility decline is observed with mare age. Parity and yearly breeding, however, are controversial factors impacting fertility. Most of these studies were performed on race horses and before 2010, on data accumulated before. The cumulative effects of age and nulliparity/nursing with improved reproductive technologies and practices, often observed in sport horses, has not been investigated yet.ObjectivesTo investigate the effect of age, parity and nursing, as well as reproductive management, on post-insemination inflammation and fertility in sports mares.Study designAge, parity, nursing status, follicular size before ovulation, estrus and/or ovulation induction, artificial insemination (AI) protocol, post-breeding inflammation and treatment, Day 14 pregnancies rates (PR) and number of embryos, as well as subsequent foaling the next year were recorded for 277 mares (506 cycles) over one breeding season in two French commercial studs.MethodsMultivariate logistic regression models were used.ResultsPR was 41.9% per cycle and 76.5% at the end of the season. Post-insemination fluid accumulation risk was increased in >10-year-old, barren or July or August inseminated mares (p<0.0001, OR=3.29, 5.389 and 3.329, respectively). PR were reduced in mares >10-year-old vs younger or inseminated with frozen vs fresh or refrigerated semen (p<0.05, OR=0.622 and 0.582, respectively). More pregnancy on Day 14 were observed in mares with multiple ovulations compared to mono- ovulation (p<0.05, OR=1.791). Regardless the age, PR only tended to be improved in multiparous (p=0.07, OR=1.434 in parous vs nulliparous) but in >10-year-old mares, multiparity greatly increased PR (44.09% in parous vs 30.89% in nulliparous, p<0.05).Main limitationsLimited number of mares.ConclusionIn sport horse, maternal age was more important than parity and lactating status for reproductive success but cumulative effects of nulliparity and aging was deleterious on PR, demonstrating their importance in the management of sport mares.
On the hormonal control of posterior regeneration in the annelid Platynereis dumerilii
Authors: Álvarez-Campos Patricia , Planques Anabelle , Bideau Loïc , Vervoort Michel , Gazave Eve 
Published: January 2022

AbstractRegeneration is the process by which many animals are able to restore lost or injured body parts. After amputation of the posterior part of its body, the annelid Platynereis dumerilii is able to regenerate the pygidium, the posteriormost part of its body that bears the anus, and a subterminal growth zone containing stem cells that allows the subsequent addition of new segments. The ability to regenerate their posterior part (posterior regeneration) is promoted in juvenile worms by a hormone produced by the brain and is lost when this hormonal activity becomes low at the time the worms undergo their sexual maturation. By characterizing posterior regeneration at the morphological and molecular levels in worms that have been decapitated, we show that the presence of the head is essential for multiple aspects of posterior regeneration, as well as for the subsequent production of new segments. We also show that methylfarnesoate, the molecule proposed to be the brain hormone, can partially rescue the posterior regeneration defects observed in decapitated worms. Our results are therefore consistent with a key role of brain hormonal activity in the control of regeneration and growth in P. dumerilii, and support the hypothesis of the involvement of methylfarnesoate in this control.
Tropical Origin, Global Diversification and Dispersal in the Pond Damselflies (Coenagrionoidea) Revealed by a New Molecular Phylogeny
Authors: Willink B. , Ware J. , Svensson E. I. 
Published: January 2022

AbstractThe processes responsible for the formation of Earth’s most conspicuous diversity pattern, the latitudinal diversity gradient (LDG), remain unexplored for many clades in the Tree of Life. Here, we present a densely-sampled and dated molecular phylogeny for the most speciose clade of damselflies worldwide (Odonata: Coenagrionoidea), and investigate the role of time, macroevolutionary processes and biome-shift dynamics in shaping the LDG in this ancient insect superfamily. We used process-based biogeographic models to jointly infer ancestral ranges and speciation times, and to characterise within-biome dispersal and biome-shift dynamics across the cosmopolitan distribution of Coenagrionoidea. We also investigated temporal and biome-dependent variation in diversification rates. Our results uncover a tropical origin of pond damselflies and featherlegs ∼ 105 Ma, while highligthing uncertainty of ancestral ranges within the tropics in deep time. Even though diversification rates have declined since the origin of this clade, global climate change and biome-shifts have slowly increased diversity in warm- and cold-temperate areas, where lineage turnover rates have been relatively higher. This study underscores the importance of biogeographic origin and time to diversify as important drivers of the LDG in pond damselflies and their relatives, while diversification dynamics have instead resulted in the formation of ephemeral species in temperate regions. Biome-shifts, although limited by tropical niche conservatism, have been the main factor reducing the steepness of the LDG in the last 30 Myr. With ongoing climate change and increasing northward range expansions of many damselfly taxa, the LDG may become less pronounced. Our results support recent calls to unify biogeographic and macroevolutionary approaches to increase our understanding of how latitudinal diversity gradients are formed and why they vary across time and among taxa.
Delimiting the cryptic diversity and host preferences of Sycophila parasitoid wasps associated with oak galls using phylogenomic data
Authors: Zhang Y. Miles , Sheikh Sofia I. , Ward Anna K.G. , Forbes Andrew A. , Prior Kirsten M. , Stone Graham N. , Gates Michael W. , Egan Scott P. , Zhang Linyi , Davis Charles , Weinersmith Kelly L. , Melika George , Lucky Andrea 
Published: January 2022

AbstractCryptic species diversity is a major challenge for the species-rich community of parasitoids attacking oak gall wasps due to a high degree of sexual dimorphism, morphological plasticity, small size, and poorly known biology. As such, we know very little about the number of species present, nor the evolutionary forces responsible for generating this diversity. One hypothesis is that trait diversity in the gall wasps, including the morphology of the galls they induce, has evolved in response to selection imposed by the parasitoid community, with reciprocal selection driving diversification of the parasitoids. Using a rare, continental-scale data set of Sycophila parasitoid wasps reared from 44 species of cynipid galls from 18 species of oak across the US, we combined mitochondrial DNA barcodes, Ultraconserved Elements (UCEs), morphological, and natural history data to delimit putative species. Using these results, we generate the first large-scale assessment of ecological specialization and host association in this species-rich group, with implications for evolutionary ecology and biocontrol. We find most Sycophila target specific subsets of available cynipid host galls with similar morphologies, and generally attack larger galls. Our results suggest that parasitoid wasps such as Sycophila have adaptations allowing them to exploit particular host trait combinations, while hosts with contrasting traits are resistant to attack. These findings support the tritrophic niche concept for the structuring of plant-herbivore-parasitoid communities.
NELL-1 regulates the matrisome to alter osteosarcoma disease progression
Authors: Qin Qizhi , Gomez-Salazar Mario , Tower Robert J. , Chang Leslie , Morris Carol D. , McCarthy Edward F. , Ting Kang , Zhang Xinli , James Aaron W. 
Published: January 2022

AbstractSarcomas produce abnormal extracellular matrix (ECM) which in turn provides instructive cues for cell growth and invasion. Neural EGF Like-Like molecule 1 (NELL1) is a secreted glycoprotein characterized by its non-neoplastic osteoinductive effects, yet highly expressed in skeletal sarcomas. Here, NELL1 gene deletion markedly reduced invasive behavior across human osteosarcoma (OS) cell lines. This resulted in reduced OS disease progression, inhibited metastatic potential and improved survival in a xenograft model. These observations were recapitulated with Nell1 conditional knockout in mouse models of p53/Rb driven sarcomagenesis, including reduced tumor frequency, and extended tumor free survival.Transcriptomic and phospho-proteomic analysis demonstrated that NELL1 loss skews the expression of matricellular proteins associated with reduced FAK signaling. Culture on OS enriched matricellular proteins reversed phenotypic and signaling changes among NELL1 knockout sarcoma cells. These findings in mouse and human models suggest that NELL1 expression alters the sarcoma matrix, thereby modulating cellular invasive potential and prognosis. Disruption of NELL1 signaling may represent a novel therapeutic approach to short circuit sarcoma disease progression.
A Cyclisation and Docking Protocol for Cyclic Peptide-Protein Modelling using HADDOCK2.4
Authors: Charitou Vicky , van Keulen Siri C. , Bonvin Alexandre M.J.J. 
Published: January 2022

AbstractAn emerging class of therapeutic molecules are cyclic peptides with over 40 cyclic peptide drugs currently in clinical use. Their mode of action is, however, not fully understood, impeding rational drug design. Computational techniques could positively impact their design but modeling them and their interactions remains challenging due to their cyclic nature and their flexibility. This study presents a step-by-step protocol for generating cyclic peptide conformations and docking them to their protein target using HADDOCK2.4. A dataset of 30 cyclic peptide-protein complexes was used to optimize both cyclisation and docking protocols. It supports peptides cyclized via an N- and C-terminus peptide bond and/or a disulfide bond. An ensemble of cyclic peptide conformations is then used in HADDOCK to dock them onto their target protein using knowledge of the binding site on the protein side to drive the modeling. The presented protocol predicts at least one acceptable model according to CAPRI criteria (Critical Assessment of Prediction of Interaction) for each complex of the dataset when the top 10 HADDOCK-ranked single structures are considered (100% success rate top10) both in the bound and unbound docking scenario. Moreover, its performance in both bound and fully unbound docking, is similar to the state-of-the-art software in the field, Autodock CrankPep. The presented cyclisation and docking protocol should make HADDOCK a valuable tool for rational cyclic peptide-based drug design and high-throughput screening.
EFA6R suppresses ovarian cancer cell migration and invasion
Authors: Tamaddon-Jahromi Salman , Murphy Kate , Walker William , Kanamarlapudi Venkateswarlu 
Published: January 2022

AbstractExchange factor for ADP-ribosylation factor (Arf)6 (EFA6)R expression loss in ovarian cancer has shown to decrease patient survival. EFA6R contains the catalytic Sec7, pleckstrin homology (PH), and coiled-coil (CC) domains. To gain further insight into the role of EFA6R, this study further investigated EFA6R expression in OC and its putative role as a metastatic suppressor. EFA6R mRNA expression, assessed by RT-qPCR, was significantly downregulated in OC tissues and cell lines. OC tissue microarray staining with EFA6R antibody showed that loss of protein expression correlated with increased cancer grade. Furthermore, EFA6R protein levels, assessed by immunoblotting, were significantly reduced in OC tissues and cell lines. Treatment of SKOV-3 cells with 5-aza-2’deoxycytidine, an epigenetic regulator, restored EFA6R expression and attenuated functional cell migration and invasion, which was reversed by siRNA-mediated knockdown of EFA6R expression. This study also revelated that exogenously expressed EFA6R localises to the plasma membrane, through its PH domain, and thereby inhibits cell migration and invasion in the CC domain-dependent and an Arf6-independent manner. EFA6R loss-of-function involves epigenetic mechanisms in which downregulation increases OC tumour cell migration and invasion.Summary statementEFA6R expression is epigenetically regulated in ovarian cancer cells and loss of expression correlates with increased tumour grade and enhanced tumour cell migration. EFA6R appears to mediate these effects independently of Arf6.
Within and among population differences in cuticular hydrocarbons in the seabird tick Ixodes uriae
Authors: Dupraz Marlène , Leroy Chloe , Thórarinsson Thorkell Lindberg , d’Ettorre Patrizia , McCoy Karen D. 
Published: January 2022

AbstractThe hydrophobic layer of the arthropod cuticle acts to maintain water balance, but can also serve to transmit chemical signals via cuticular hydrocarbons (CHC), essential mediators of arthropod behavior. CHC signatures typically vary qualitatively among species, but also quantitatively among populations within a species, and have been used as taxonomic tools to differentiate species or populations in a variety of taxa. Most work in this area to date has focused on insects, with little known for other arthropod groups such as ticks. The worldwide distribution and extensive host-range of the seabird tick Ixodes uriae make it a good model to study the factors influencing CHC composition. Genetically differentiated host-races of I. uriae have evolved across the distribution of this species but the factors promoting sympatric population divergence are still unknown. To test for a potential role of host-associated CHC in population isolation, we collected I. uriae specimens from two of its seabird hosts, the Atlantic puffin (Fratercula arctica) and the common guillemot (Uria aalge) in different colonies in Iceland. Using gas-chromatography and mass-spectrometry, we detected a complex cuticular mixture of 22 hydrocarbons, including n-alkanes, methyl-alkanes and alkenes ranging from 17 to 33 carbons in length. We found that each population had a distinct CHC profile. The host group explained the greatest amount of population divergence, with long-chain hydrocarbons being more abundant in puffin tick populations compared to guillemot tick populations. Future work will now be required to test whether the different CHC signals reinforce assortative mating, thereby playing a role in generating I. uriae population divergence patterns, and to evaluate diverse hypotheses on the origin of distinct population signatures.
The role of rice SOG1 and SOG1-like in DNA damage response
Authors: Nishizawa-Yokoi Ayako , Motoyama Ritsuko , Tanaka Tsuyoshi , Mori Akiko , Iida Keiko , Toki Seiichi 
Published: January 2022

AbstractHigher plants are constantly exposed to environmental stresses, and therefore complicated defense systems, including DNA damage response (DDR) and DNA repair systems, have developed to protect plant cells. InArabidopsis, the transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1) has been reported to play a key role in DDR. Here, we focus on DDR in rice—thought to be a simpler system compared withArabidopsisdue to lack of induction of endocycle even under DNA damage stress. Rice SOG1 (OsSOG1) and SOG1-like (OsSGL) were identified as putative AtSOG1 orthologs with complete or partial conservation of the serine-glutamine (SQ) motifs involved in activation via phosphorylation. In addition to OsSOG1- or OsSGL-knockout mutants, OsSOG1 non-phosphorylatable mutants (OsSOG1-7A) were generated by homologous recombination-mediated gene targeting. Based on DNA damage susceptibility and transcriptome analysis using these mutants, we demonstrated that OsSOG1, but not OsSGL, plays a central role in the DDR and DNA repair. OsSOG1 regulated target genes via CTT (N)7AAG motifs reported previously as AtSOG1 recognition sites. The loss of transcription activities and DNA damage tolerance of OsSOG1-7A was not complete compared with OsSOG1-knockout mutants, raising the possibility that another phosphorylation site might be involved in the activation of OsSOG1. Furthermore, our findings have highlighted differences in SOG1-mediated DDR between rice andArabidopsis, especially regarding induction of cell-cycle arrest and endocycle arrest, revealing rice-specific DDR mechanisms.One sentence summaryRice transcription factor SUPPRESSOR OF GAMMA RESPONSE 1 controls DNA damage response and DNA repair through activation via phosphorylation and the direct regulation of expression of numerous genes.
New insights into tomato CLE peptide repertoire and perception mechanisms
Authors: Carbonnel Samy , Falquet Laurent , Hazak Ora 
Published: January 2022

AbstractPrecision in sensing the environmental cues and adjusting the growth and the physiology of the root system are necessary for plant robustness. Plants achieve their phenotypic plasticity by tightly controlling and buffering developmental decisions. In addition to the classical plant hormones that mediate plant development and stress responses, the CLE peptides constitute an additional crucial level of regulation. While the CLV3-CLV1 module appears to be highly conserved to control the proliferation of the shoot apical meristem stem cells, we do not yet fully understand the function of the additionalCLEgenes and whether they act in a similar way across the plant species, including tomato. Due to the small gene size and high sequence variability, it is extremely difficult to precisely annotateCLEgenes in plant genomes. Here we present our analysis of theCLEfamily in tomato, based on a combination of iterative tBLASTn and Hidden-Markov-Model (HMM), which allowed us to identify thirty-seven newSlCLEs in addition to the fifteen reported previously. We could confirm the biological activities of selected SlCLEs in suppressing root meristematic cell divisions. We show that root response is mediated bySlCLAVATA2, indicating the conservation of CLE perception mechanism.One-sentence summaryUsing a combination of iterative tBLASTn and Hidden-Markov-Model approaches, we uncovered 37 new tomatoCLEgenes predominantly expressed in roots, and we showed a conserved effect on root meristem arrest, that wasSlCLAVATA2-dependent.HighlightsWe applied a combined approach of iterative tBLASTn and Hidden-Markov-Model to identify fifty-two tomatoSlCLEgenes, including thirty-seven new genesAll identified genes encode for pre-propeptides with a single CLE-domain containing conserved residues similar to ArabidopsisAnalyzing the publicly available RNAseq datasets, we could confirm the expression ofSlCLEgenes that was often associated specifically with root or shoot, a certain developmental stage of the fruit, or with drought stress conditionsRemarkably, the majority ofSlCLEgenes are predominantly expressed in the root tissuesWe showed the conserved inhibitory effect on the root meristem and columella cells division for the selected SlCLE peptides that wereSlCLAVATA2-dependent.
Crosstalk of Histone Modifications in the Healthy Human Immune System
Authors: Dermadi Denis , Kalesinskas Laurynas , Ganesan Ananthakrishnan , Kuo Alex , Cheung Peggie , Cheng Sarah , Dvorak Mei , Scriba Thomas J. , Habtezion Aida , Donato Michele , Utz Paul J. , Khatri Purvesh 
Published: January 2022

ABSTRACTChromatin remodeling through post-translational modifications of histone tails (HPTM) is fundamental for regulation and maintenance of DNA-centered processes. Systems level understanding of coordination and interactions between HPTMs and their impact on the functional state of the immune cells remain unexplored due to the technical reasons. We leveraged large biologically heterogeneous data (>27 million cells), comprising of primary human immune cells profiled for 33 HPTMs and 4 histone variants at the single-cell level using high-dimensional mass cytometry (EpiTOF), to discover and map relations between HPTMs at the systems level. Briefly, we elucidated a comprehensive epigenetic network of HPTM interactions, discovered a novel subset of hematopoietic progenitors with distinct epigenetic profile, and revealed hitherto undescribed associations between a decrease in global methylations, modulation of one-carbon metabolism, and immune cell life span. Ultimately our work lays a foundation for future studies aimed at understanding complexity of HPTM interactions in immune response in infectious or autoimmune diseases, cancers, and vaccination.