bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parallel genetic adaptation amidst a background of changing effective population sizes in divergent yellow perch (Perca flavescens) populations
Authors: Yin Xiaoshen , Schraidt Claire E. , Sparks Morgan M. , Euclide Peter T. , Hoyt Tyler J. , Ruetz Carl R. , Höök Tomas O. , Christie Mark R. 
Published: April 2024

AbstractAquatic ecosystems are highly dynamic environments vulnerable to natural and anthropogenic disturbances. High-economic value fisheries are one of many ecosystem services affected by these disturbances and it is critical to accurately characterize the genetic diversity and effective population sizes of valuable fish stocks through time. We used genome-wide data to reconstruct the demographic histories of economically important yellow perch (Perca flavescens) populations. In two isolated and genetically divergent populations, we provide independent evidence for simultaneous increases in effective population sizes over both historic and contemporary time scales including negative genome-wide estimates of Tajima’s D, 3.1 times more SNPs than adjacent populations, and contemporary effective population sizes that have increased 10- and 47-fold from their minimum, respectively. The excess of segregating sites and negative Tajima’s D values likely arose from mutations accompanying historic population expansions with insufficient time for purifying selection, whereas linkage disequilibrium-based estimates ofNealso suggest contemporary increases that may have been driven by reduced fishing pressure or environmental remediation. We also identified parallel, genetic adaptation to reduced visual clarity in the same two habitats. These results suggest that the synchrony of key ecological and evolutionary processes can drive parallel demographic and evolutionary trajectories across independent populations.
Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation
Authors: Arya Subhash B. , Collie Samuel P. , Xu Yang , Fernandez Martin , Sexton Jonathan Z. , Mosalaganti Shyamal , Coulombe Pierre A. , Parent Carole A. 
Published: April 2024

SUMMARYAcute inflammation, characterized by a rapid influx of neutrophils, is a protective response that can lead to chronic inflammatory diseases when left unresolved. Secretion of LTB4-containing exosomes is required for effective neutrophil infiltration during inflammation. In this study, we show that neutrophils release nuclear DNA in a non-lytic, rapid, and repetitive manner, via a mechanism distinct from suicidal NET release and cell death. The packaging of nuclear DNA occurs in the lumen of nuclear envelope (NE)-derived multivesicular bodies (MVBs) that harbor the LTB4synthesizing machinery and is mediated by the lamin B receptor (LBR) and chromatin decondensation. Disruption of secreted exosome-associated DNA (SEAD) in a model of sterile inflammation in mouse skin amplifies and prolongs the presence of neutrophils, impeding the onset of resolution. Together, these findings advance our understanding of neutrophil functions during inflammation and the physiological significance of NETs, with implications for novel treatments for inflammatory disorders.
Tumor suppressor p73 transcriptionally regulatesc-FLIPto impede its priming of extrinsic apoptosis while a “switcher compound” degrades c-FLIP protein
Authors: Zhang Shengliang , Zhou Lanlan , El-Deiry Wafik S. 
Published: April 2024

AbstractThe tumor suppressor p73 is a member of the p53 family, and transcriptionally activates multiple p53-targets involved in cell cycle regulation and apoptosis. In addition to pro-apoptotic signaling, outcomes of p73 activation include cell survival signals. Thus, p73 activity and targets may provide insight in cell fate outcomes between cell survival and apoptosis following cellular stress. We report thatcellular FLICE inhibitory protein(c-FLIP), a master antiapoptotic factor, is a transcriptional target of p73. The activation of p73 (α and β isoforms) transcriptionally upregulatesc-FLIP-L/Sexpression in cancer cells. The cell fate decision following p73 activation is determined by the adjustment of the balance of outcomes of p73 activation between p73-induced pro-apoptotic signaling andc-FLIP-L/Sexpression in cancer cells. p73 primes extrinsic apoptosis via an autocrine death ligand-DR5 axis, and the priming appears to be titrated at the level of c-FLIP-L/S. The p73-upregulation ofc-FLIP-L/Sincreases the threshold of extrinsic apoptosis. Cells with poor priming levels convert to cell cycle arrest and survival. Depletion ofc-FLIP-L/Sincreases the p73-priming levels towards extrinsic apoptosis and sensitizes cancer cells to p73-primed extrinsic apoptosis. We further identified a small-molecule CB-7587351 (“switcher compound”) that alters p73 activation outcomes through c-FLIP-L/S protein degradation. Therapeutic activation of p73 can restore p53-signaling in mutant p53-expressing cancer cells effectively bypassing the p53 deficiency in cancer cells. Our discovery of p73 transcriptional upregulation of c-FLIP provides a promising strategy for depleting c-FLIP to improve antitumor efficacy of p73-targeting cancer therapy for p53-mutant tumors.
Anemonefish use sialic acid metabolism as Trojan horse to avoid giant sea anemone stinging
Authors: Roux Natacha , Delannoy Clément , Yu Shin-Yi , Miura Saori , Carlu Lilian , Besseau Laurence , Nakagawa Takahiro , Sato Chihiro , Kitajima Ken , Guerardel Yann , Laudet Vincent 
Published: April 2024

AbstractAnemonefish association with giant sea anemone is an iconic example of mutualistic symbiosis. Living inside the sea anemone without triggering the firing of highly toxic nematocysts present at the surface of sea anemone tentacles provides a unique shelter to the fish, which in return, by its territorial aggressiveness, protects the sea anemone from predators. The mechanisms by which the fish avoids triggering nematocysts discharge remain elusive. One hypothesis proposes that absence of sialic acids might disable nematocysts discharge. Here, we verified four predictions about the role of sialic acids in anemonefish protection: (i) sialic acid levels are lower in anemonefish mucus than in non-symbiotic and sensitive damselfish mucus; (ii) this decrease is specific to mucus and not observed in other organs; (iii) during post-embryonic development the levels of sialic acids are inversely correlated with the level of protection; (iv) the levels of sialic acids are minimal in sea anemone mucus. Taken together, our results allow us to propose a general model, in which anemonefish specifically regulates the level of sialic acids in their mucus to avoid nematocysts discharge. Our analysis also highlights several genes implicated in sialic acid removal as potential targets for allowing protection. Interestingly, our results also suggest that unrelated juveniles of damselfish (Dascyllus trimaculatus) capable to live in proximity with giant sea anemone may use the same mechanisms. Altogether, our data suggest that clownfish use sialic acids as a Trojan horse system to downplay the defenses of the sea anemones and illustrate the convergent tinkering used by fish to allow a mutualistic association with their hosts.Significance statementThe mutualistic relationship between anemonefish and giant sea anemones, where the fish shelter among the anemone’s tentacles while defending it from predators, is a classic example of symbiosis. However, how the fish avoids triggering the anemone’s venomous nematocysts has remained a mystery. This study reveals that the fish decrease the levels of sialic acids in their mucus, potentially preventing nematocyst discharge. This finding shed light on the mechanisms underlying this symbiotic relationship. Moreover, the discovery that unrelated damselfish may employ similar strategies underscores the broader significance of convergent adaptations in facilitating similar mutualistic associations in marine fishes.
Molecular and physiological characterization of brassinosteroid receptor BRI1 mutants inSorghum bicolor
Authors: Rico-Medina Andrés , Blasco-Escámez David , Fontanet-Manzaneque Juan B. , Laibach Natalie , Lozano-Elena Fidel , Martignago Damiano , Caño-Delgado Ana I. 
Published: April 2024

SUMMARYThe high sequence and structural similarities between BRI1 brassinosteroid receptors of Arabidopsis (AtBRI1) and sorghum (SbBRI1) prompted us to study the functionally conserved roles of BRI in both organisms.Introducing sorghum SbBRI1 in Arabidopsisbri1mutants restores defective growth and developmental phenotypes to WT levels.Sorghum mutants for SbBRI1 receptors show defective BR sensitivity and impaired growth and development throughout the entire sorghum life cycle. Embryonic analysis of sorghum primary roots permit to trace back root growth and development to early stages, revealing the functionally conserved roles of SbBRI1 receptor in BR perception during meristem development. RNA-seq analysis uncovers the downstream regulation of the SbBRI1 pathway in cell wall biogenesis during cell growth.Together, these results uncover that sorghum SbBRI1 receptor protein play functionally conserved roles in plant growth and development, while encourage the study of BR pathways in sorghum and its implications for improving resilience in cereal crops.
Specific oncogene activation of the cell of origin in mucosal melanoma
Authors: Babu Swathy , Chen Jiajia , Robitschek Emily , Baron Chloé S. , McConnell Alicia , Wu Constance , Dedeilia Aikaterini , Sade-Feldman Moshe , Modhurima Rodsy , Manos Michael P. , Chen Kevin Y. , Cox Anna M. , Ludwig Calvin G. , Yang Jiekun , Kellis Manolis , Buchbinder Elizabeth I. , Hacohen Nir , Boland Genevieve M. , Abraham Brian J. , Liu David , Zon Leonard I. , Insco Megan L. 
Published: April 2024

AbstractMucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we developed a zebrafish model in which all melanocytes experienced CCND1 expression and loss of PTEN and TP53. Surprisingly, melanoma only developed from melanocytes lining internal organs, analogous to the location of patient MM. We found that zebrafish MMs had a unique chromatin landscape from cutaneous melanoma. Internal melanocytes could be labeled using a MM-specific transcriptional enhancer. Normal zebrafish internal melanocytes shared a gene expression signature with MMs. Patient and zebrafish MMs have increased migratory neural crest gene and decreased antigen presentation gene expression, consistent with the increased metastatic behavior and decreased immunotherapy sensitivity of MM. Our work suggests the cell state of the originating melanocyte influences the behavior of derived melanomas. Our animal model phenotypically and transcriptionally mimics patient tumors, allowing this model to be used for MM therapeutic discovery.
Effects of diet particle size on growth performance of the edible cricket,Teleogryllus occipitalis(Orthoptera: Gryllidae)
Authors: Murata Kohyoh , Suzuki Takeshi 
Published: April 2024

AbstractFarming edible crickets has environmental and nutritional benefits, as well as social benefits such as livelihood diversification. Commercial feeds for poultry and fish farming are often used to feed crickets, and in recent years, crop and food-processing by-products have also been used to improve sustainability. However, the design of feed for crickets has not been standardized. Here, we investigated growth and development of the Asian field cricket,Teleogryllus occipitalis(Audinet-Serville) (Orthoptera: Gryllidae), fed on different forms of the same diet. Body weights and the rate of development were significantly greater in crickets fed on millimetre-order granules than in crickets fed on micrometre-order powder. The result suggests that the granular form is easier forT. occipitalisto grasp and ingest than the powdery form, or that greater hydrophobicity of the powdery form inhibits digestion. Simply feeding millimetre-order granules may contribute to the development of feed design for farming edible crickets.
PACS-1 variant protein is aberrantly localized inC. elegansmodel of PACS1/PACS2 syndromes
Authors: Byrd Dana T. , Han Ziyuan Christina , Piggott Christopher A. , Jin Yishi 
Published: April 2024

AbstractPACS (Phosphofurin Acidic Cluster Sorting Protein) proteins are known for their roles in sorting cargo proteins to organelles and can physically interact with WD40 repeat-containing protein WDR37. PACS1, PACS2, and WDR37 variants are associated with multisystemic syndromes and neurodevelopmental disorders characterized by intellectual disability, seizures, developmental delays, craniofacial abnormalities, and autism spectrum disorder. However, the effects of syndromic variants on functionin vivoremains unknown. Here, we report the expression pattern ofC. elegansorthologs of PACS and WDR37 and their interaction. We show that cePACS-1 and ceWDR-37 co-localize to somatic cytoplasm of many types of cells, and are mutually required for expression, supporting a conclusion that the intermolecular dependence of PACS1/PACS2/PACS-1 and WDR37/WDR-37 is evolutionarily conserved. We further show that editing in PACS1 and PACS2 variants in cePACS-1 changes protein localization in multiple cell types, including neurons. Moreover, expression of human PACS1 can functionally complementC. elegansPACS-1 in neurons, demonstrating conserved functions of the PACS-WDR37 axis in an invertebrate model system. Our findings reveal effects of human variants and suggest potential strategies to identify regulatory network components that may contribute to understanding molecular underpinnings of PACS/WDR37 syndromes.
Octopus Hypnosis: Non-Chemical Sedation in Studying Arm-Sucker Coordination
Authors: Gribkova Ekaterina D. , Cui Jilai , Gillette Rhanor 
Published: April 2024

ABSTRACTEffective methods of anesthesia for octopuses are important for physiological studies as well as for their welfare in scientific research. Neurophysiological studies of octopus usually use general anesthesia for invasive procedures like electrode implantation. However, commonly used forms of general anesthesia using ethanol, magnesium chloride, and similar agents have certain drawbacks in levels of stress, recovery, and tissue viability in octopuses much as in humans. We explore an old, rarely used method of octopus “hypnosis”, in which a still reaction is induced where communication between central and peripheral nervous systems is seemingly decreased. We modify the procedure for better handling, continuous respiration, and isolation of peripheral nervous system of the arm cords from the central nervous system (CNS), providing alternative to general anesthesia. Illustrative small studies of arm-sucker coordination and electrode placements are presented. The modified procedure limits negative side-effects, markedly reduces animals’ stress levels, and offers new avenues for octopus neurobehavioral research.
Association of Genetically Predicted Levels of Circulating Blood Lipids with Coronary Artery Disease Incidence
Authors: Manikpurage Hasanga D. , Ricard Jasmin , Houessou Ursula , Bourgault Jérôme , Gagnon Eloi , Gobeil Emilie , Girard Arnaud , Li Zhonglin , Eslami Aida , Mathieu Patrick , Bossé Yohan , Arsenault Benoit J. , Thériault Sébastien 
Published: April 2024

AbstractBackgroundEstimating the genetic risk of coronary artery disease (CAD) is now possible by aggregating data from genome-wide association studies (GWAS) into polygenic risk scores (PRS). Combining multiple PRS for specific circulating blood lipids could improve risk prediction. Here, we sought to evaluate the performance of PRS derived from CAD and blood lipids GWAS to predict the incidence of CAD.MethodsThis study included individuals aged between 40 and 69 recruited in UK Biobank (UKB). We conducted GWAS for blood lipids measured by nuclear magnetic resonance in individuals without lipid-lowering treatments (n=73,915). Summary statistics were used to derive and calculate PRS in the remaining participants (n=318,051). A PRSCADwas also derived using the CARDIoGRAMplusC4D GWAS. Hazard ratios (HR) for CAD (9,017 / 301,576; median follow-up time: 12.6 years) were calculated per standard deviation increase in each PRS. Discrimination capacity and goodness of fit of the models were evaluated.ResultsOut of 30 PRS, 28 were significantly associated with the incidence of CAD (P<0.05). The optimal combination of PRS included PRS for CAD, VLDL-C, total cholesterol and triglycerides. Discriminative capacities were significantly increased in the model including PRSCADand clinical risk factors (CRF) (C-statistic=0.778 [0.773-0.782]) compared to the model with CRF only (C-statistic=0.755 [0.751-0.760]). Although the C-statistic remained similar when independent lipids PRS were added to the model with PRSCADand CRF (C-statistic=0.778 [0.773-0.783]), the goodness of fit was significantly increased (chi-square test statistic=20.18,P=1.56e-04).ConclusionsAlthough independently associated with CAD incidence, blood lipids PRS provide modest improvement in the predictive performance when added to PRSCAD.HighlightsGenome-wide association studies were conducted on 29 selected lipid traits measured by nuclear magnetic resonance spectroscopy in 73,915 participants from UK Biobank who were not taking lipid-lowering treatment.Polygenic risk scores for 27 out of 29 of these traits were associated with the incidence of coronary artery disease (CAD) in 9,017 cases out of 301,576 individuals followed for a median of 12.6 years.When combined to a PRS for coronary artery disease, there was a significant but modest improvement in the discrimination capacity for incident CAD.PRS for certain lipid traits might help to stratify the risk of CAD.Graphical Abstract
Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity
Authors: Schwartz Irene , Budroni Valentina , Meyenberg Mathilde , Hornegger Harald , Hacker Kathrin , Schwartz Siegfried , Hodakova Zuzana , Grabarczyk Daniel B. , Ehrmann Julian F. , Scinicariello Sara , Haselbach David , Menche Jörg , Clausen Tim , Karagöz G. Elif , Versteeg Gijs A. 
Published: April 2024

AbstractHighlightsRNA-free APOBEC3 (A3) can enter the nucleus, leading to genomic mutations.Three E3 ligases specifically bind the RNA-binding domain of nuclear A3s.Cancer-associated A3B and A3H-I are thereby targeted for proteasomal degradation.These E3 ligases thus act as genome guardians by limiting A3-mediated mutagenesis.APOBEC family members play crucial roles in antiviral restriction. However, certain APOBEC3 (A3) proteins drive harmful hypermutation in humans, contributing to cancer. The cancer-associated A3 proteins are capable of transiting from the cytosol to the nucleus, where they can cause genome mutations. Here, we uncover a specific set of cellular pathways that protect genomic DNA from the major cancer-associated A3 proteins. Through genetic and proteomic screening we identify UBR4, UBR5, and HUWE1 as key ubiquitin E3 ligases marking cancer-associated A3B and A3H-I for degradation, thereby limiting A3-driven hypermutation. Mechanistically, UBR5 and HUWE1 recognize unoccupied A3 RNA-binding domains, thus promoting proteasomal degradation of APOBEC3 protein that is not engaged in its antiviral cellular function. Depletion or mutation of the E3 ligases in cells and human cancer samples increases A3-driven genome mutagenesis. Our findings reveal that UBR4, UBR5, and HUWE1 are crucial factors in a ubiquitination cascade that maintains human genome stability.
Interpreting mammalian evolutionary constraint at synonymous sites in light of the unwanted transcript hypothesis
Authors: Christmas Matthew J. , Dong Michael , Meadows Jennifer R. S. , Kozyrev Sergey V. , Lindblad-Toh Kerstin 
Published: April 2024

AbstractThe unwanted transcript hypothesis presents a potential explanation for cryptic evolutionary constraint at synonymous sites in species with low effective population sizes, such as humans and other mammals. Selection for higher GC content and against mutations that alter splicing in native transcripts is predicted to shape synonymous site content and protect against unwanted transcripts. Here, we interpret mammalian synonymous site constraint in this context. Utilising the largest alignment of 240 placental mammal genomes and single-base resolution constraint scores, we show that 20.8% of four-fold degenerate sites are under significant constraint across mammals. There is a strong bias for guanine (G) and cytosine (C) at constrained sites, marked constraint near splice sites, and variation in human populations shows a bias against mutations that reduce synonymous site GC content. We find evidence for higher constraint on four-fold degenerate sites in species with small historic effective population sizes and high young transposable element genome content. Genes enriched for synonymous site constraint, including those forming CpG sites, are tightly regulated and integral to organismal viability through their involvement in embryo development and transcriptional regulation.
Synaptic architecture of a memory engram in the mouse hippocampus
Authors: Uytiepo Marco , Zhu Yongchuan , Bushong Eric , Polli Filip , Chou Katherine , Zhao Elise , Kim Christine , Luu Danielle , Chang Lyanne , Quach Tom , Haberl Matthias , Patapoutian Luca , Beutter Elizabeth , Zhang Weiheng , Dong Brian , McCue Elle , Ellisman Mark , Maximov Anton 
Published: April 2024

AbstractMemory engrams are formed through experience-dependent remodeling of neural circuits, but their detailed architectures have remained unresolved. Using 3D electron microscopy, we performed nanoscale reconstructions of the hippocampal CA3-CA1 pathway following chemogenetic labeling of cellular ensembles with a remote history of correlated excitation during associative learning. Projection neurons involved in memory acquisition expanded their connectomes via multi-synaptic boutons without altering the numbers and spatial arrangements of individual axonal terminals and dendritic spines. This expansion was driven by presynaptic activity elicited by specific negative valence stimuli, regardless of the co-activation state of postsynaptic partners. The rewiring of initial ensembles representing an engram coincided with local, input-specific changes in the shapes and organelle composition of glutamatergic synapses, reflecting their weights and potential for further modifications. Our findings challenge the view that the connectivity among neuronal substrates of memory traces is governed by Hebbian mechanisms, and offer a structural basis for representational drifts.