bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecosystem Links: Macrophytes, Snail Preferences, and Trematode Transmission in Man-Made Water Bodies
Authors: Mudavanhu Aspire , Goossens Emilie , Schols Ruben , Manyangadze Tawanda , Nhiwatiwa Tamuka , Huyse Tine , Brendonck Luc 
Published: March 2024

AbstractFreshwater snails act as obligate intermediate hosts for trematode parasites that cause trematodiases threatening public and veterinary health, and biodiversity conservation. Therefore, interest has re-emerged in snails as a target for disease control, yet their ecology is poorly understood. We studied the relationship between physical and chemical water parameters, macroinvertebrates, macrophytes, land use, and snail abundance, diversity, and infection rate in man-made reservoirs in eastern Zimbabwe. We observed no significant relationship between water quality parameters or macroinvertebrates and snail communities, but a significant association existed between specific macrophytes and snail species. Schistosome-competent snails (i.e.,Biomphalaria pfeifferiand bulinids) were most associated with emergentCladium mariscus,whereasPhysella acutawas associated with submerged oxygen weed,Lagarosiphon major. This offers a possibility to incorporate the management of macrophytes in integrated snail control schemes. Diversity of freshwater snail species significantly varied across land use types with the lowest observed diversity in the commercial tobacco farm section, dominated by invasive exoticP. acutaandPseudosuccinea columella, as compared to the less impacted conserved area, reflecting the adverse effects of agriculture on biodiversity. Out of the 547 schistosome host snails, 88 were shedding cercariae (16.1%) of various types, including schistosomes and amphistomes. We did not find any significant associations between macroinvertebrate or macrophyte diversity and snails and their infection rate.
Rice OsPLATZ3 controls ROS homeostasis by inhibiting ROS-Scavenging Activity during Tapetum Degeneration
Authors: Li Yuanya , Wang Jing , Tang Fengxian , Li Lin , Cheng Xingyu , Sun Xialing , Yu Shuangshuang , Xia Pan , Wang Yuxiang , Tong Mingyang , Cheng Lizhong 
Published: March 2024

AbstractOsPLATZ3, a transcription factor of rice (Oryza sativa) belonging to the PLATZ family, is involved in the repression of transcriptional activity.PLATZ3exhibits preferential expression in the tapetal cells during anthers development, regulating tapetum degeneration by controlling the dynamics of reactive oxygen species (ROS) in rice male reproductive processes. TheOsplatz3exhibits enlarged tapetum with delayed degeneration, significantly lower ROS levels from S5 to S12 in anthers compared to the wild-type, resulting in complete male sterility. In the anthers ofOsplatz3, there are significant changes in the regulators of programmed cell death (PCD)-induced tapetal degradation, such asTDR,EAT1, and their effectorsOsCP1,OsC6,OsAP25, andOsAP37. These findings indicate thatOsPLATZ3is a new addition to the tapetum PCD regulatory network. In the late stages of anthers development,Osplatz3exhibits phenotypes associated with oxidative stress. Transcriptome analysis revealed significant differential expression in 229 genes associated with maintaining ROS homeostasis. Furthermore, Electrophoretic Mobility Shift Assay (EMSA) demonstrate that OsPLATZ3 can bind to the promoter region ofOsAPX9, a gene encoding a plant ascorbate peroxidase domain protein with putative ROS scavenging capabilities. These findings suggest that OsPLATZ3 serves as a crucial regulatory factor in tapetum PCD by suppressing ROS scavenging activity.
Towards Efficientk-Mer Set Operations via Function-Assigned Masked Superstrings
Authors: Sladký Ondřej , Veselý Pavel , Břinda Karel 
Published: March 2024

AbstractThe design of efficient dynamic data structures for largek-mer sets belongs to central challenges of sequence bioinformatics. Recent advances in compactk-mer set representations via simplitigs/Spectrum-Preserving String Sets, culminating with the masked superstring framework, have provided data structures of remarkable space efficiency for wide ranges ofk-mer sets. However, the possibility to perform set operations remained limited due to the static nature of the underlying compact representations. Here, we developf-masked superstrings, a concept combining masked superstrings with custom demasking functionsfto enablek-mer set operations based on index merging. Combined with the FMSI index for masked superstrings, we obtain a memory-efficientk-mer membership index and compressed dictionary supporting set operations via Burrows-Wheeler Transform merging. The framework provides a promising theoretical solution to a pressing bioinformatics problem and highlights the potential off-masked superstrings to become an elementary data type fork-mer sets.2012 ACM Subject ClassificationApplied computing→Bioinformatics; Theory of computation→Pattern matchingFundingOndřej Sladký: Supported by GA ČR project 22-22997S and ERC-CZ project LL2406 of the Ministry of Education of Czech Republic.Pavel Veselý: Supported by GA ČR project 22-22997S, ERC-CZ project LL2406 of the Ministry of Education of Czech Republic, and Center for Foundations of Modern Computer Science (Charles Univ. project UNCE 24/SCI/008).Karel Břinda: Supported by French National Research Agency (ANR) under Grant ANR-24-CE451226 for the REALL project.
ADrosophilamodel to screen Alport syndromeCOL4A5variants for their functional pathogenicity
Authors: Duan Jianli , Wen Pei , Zhao Yunpo , van de Leemput Joyce , Yee Jennifer Lai , Fermin Damian , Warady Bradley A , Furth Susan L , Ng Derek K , Sampson Matthew G , Han Zhe 
Published: March 2024

ABSTRACTAlport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes (COL4A3/4/5) with most localized inCOL4A5. Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed. We usedDrosophila, an established model for kidney disease, and identifyCol4a1as the functional homolog of humanCOL4A5in the fly nephrocyte (equivalent of human podocyte). Fly nephrocytes deficient forCol4a1showed an irregular and thickened basement membrane and significantly reduced nephrocyte filtration function. This phenotype was restored by expressing human reference (wildtype)COL4A5, but not byCOL4A5carrying any of three established pathogenic patient-derived variants. We then screened seven additional patientCOL4A5variants; their ClinVar classification was either likely pathogenic or of uncertain significance. The findings support pathogenicity for four of these variants; the three others were found benign. Thus, demonstrating the effectiveness of thisDrosophilain vivo kidney platform in providing the urgently needed variant-level functional validation.SUMMARY STATEMENTDrosophila, an established model of kidney disease, was used to develop an in vivo functional screen to determine causation forCOL4A5genetic variants linked to Alport syndrome, a progressive nephropathy.
FGF21 deletion mildly exacerbates hepatic dysfunction in MASH diet and alcohol fed rats
Authors: Aldiss Peter , Nielsen Malte Hasle , Burm Hayley , Oró Denise , Hansen Henrik H. , Feigh Michael , Gillum Matthew P 
Published: March 2024

AbstractObjectiveFibroblast growth factor 21 (FGF21) is a hepatokine that improves dyslipidemia, steatosis, inflammation, and fibrosis. FGF21 analogues are in clinical development as treatments for metabolic and alcohol-associated liver disease, creating a need for new models to help understand FGF21 physiology and drug mechanisms of action. The aim of this study was to create and initially characterize the first FGF21 knockout (KO) rat line to validate its utility as a translational animal model that recapitulates human MASH and ALD, and to provide a resource for examining FGF21-related phenotypes that are more appropriate for the rat.MethodsWe generated an FGF21 KO rat model using CRISPR/Cas9 to insert an artificial STOP codon in exon 1 and exposed 6-month-old WT and KO rats to either chow (n=8 per genotype) or the GAN (Gubra Amylin NASH) diet (n=16 per genotype) for 12 weeks. We further evaluated alcohol drinking behavior and biochemistry in FGF21 KO and WT rats. In the diet model, we further analysed liver and blood biochemistry in addition to histopathological scoring of NAFLD activity score (NAS), fibrosis stage and the liver transcriptome for in-depth characterization of the model.ResultsLack of endogenous FGF21 increased plasma transaminases, liver weight, and total levels of liver TG in GAN-fed FGF21 KO rats. FGF21 deletion also increased ALT in alcohol-fed FGF21 KO rats. However, in the GAN diet model, FGF21 KO had no impact on body weight, fat mass, glycaemic traits, MASH histological endpoints including hepatic steatosis, NAS score, lobular inflammation, ballooning degeneration or fibrosis stage after 12 weeks. Similarly, there was no effect of the loss of endogenous FGF21 on the liver transcriptome in response to GAN diet feeding. Finally, we demonstrate that endogenous FGF21 does not regulate drinking behaviour in rats.ConclusionFGF21 deficiency accelerates hepatic dysfunction in diet and alcohol-induced liver disease models in rats, providing support from a new species that FGF21 might be a hepatoprotective factor.
Adaptive trade-offs between vertebrate defense and insect predation drive ant venom evolution
Authors: Touchard Axel , Robinson Samuel D. , Lalagüe Hadrien , Ascoët Steven , Billet Arnaud , Dejean Alain , Téné Nathan J. , Petitclerc Frédéric , Troispoux Valérie , Treilhou Michel , Bonnafé Elsa , Vetter Irina , Vizueta Joel , Moreau Corrie S. , Orivel Jérôme , Tysklind Niklas 
Published: March 2024

AbstractStinging ants have diversified into various ecological niches, and several evolutionary drivers may have contributed to shape the composition of their venom. To comprehend the drivers underlying venom variation in ants, we selected 15 Neotropical species and recorded a range of traits, including ecology, morphology, and venom bioactivity. Principal component analysis of both morphological and venom bioactivity traits revealed that stinging ants display two functional strategies. Additionally, phylogenetic comparative analysis indicated that venom function (predatory, defensive, or both) and mandible morphology significantly correlate with venom bioactivity and amount, while pain-inducing activity trades off with insect paralysis. Further analysis of the venom biochemistry of the 15 species revealed switches between cytotoxic and neurotoxic venom compositions in some species. This study highlights the fact that ant venoms are not homogenous, and for some species, there are major shifts in venom composition associated with the diversification of venom ecological functions.SignificanceVenoms are under severe evolutionary pressures, exerted either on the innovation of toxins or the reduction of the metabolic cost of production (1). To reduce the metabolic costs associated with venom secretion, some venomous animals can regulate venom expenditure by metering the amount of venom injected and by switching between offensive and defensive compositions (2–2). Many ants use venom for subduing a wide range of arthropod prey, as well as for defensive purposes against invertebrates and vertebrates, but are unable to adapt venom composition to stimuli (5, 6). Consequently, the expression of venom genes directly affects the ability of ants to interact with the biotic environment, and the venom composition may be fine-tuned to the ecology of each species. A previous study showed that defensive traits in ants exhibit an evolutionary trade-off in which the presence of a sting is negatively correlated with several other defensive traits, further supporting that trade-offs in defensive traits significantly constrain trait evolution and influence species diversification in ants (7). However, the sting is not used for the same purpose depending on the ant species. Our study supports an evolutionary trade-off between the ability of venom to deter vertebrates and to paralyze insects which are correlated with different life history strategies among Formicidae.
A change incis-regulatory logic underlying obligate versus facultative muscle multinucleation in chordates
Authors: Johnson Christopher J. , Zhang Zheng , Zhang Haifeng , Shang Renjie , Piekarz Katarzyna M. , Bi Pengpeng , Stolfi Alberto 
Published: March 2024

AbstractVertebrates and tunicates are sister groups that share a common fusogenic factor, Myomaker (Mymk), that drives myoblast fusion and muscle multinucleation. Yet they are divergent in when and where they express Mymk. In vertebrates, all developing skeletal muscles express Mymk and are obligately multinucleated. In tunicates, Mymk is only expressed in post-metamorphic multinucleated muscles, but is absent from mononucleated larval muscles. In this study, we demonstrate thatcis-regulatory sequence differences in the promoter region ofMymkunderlie the different spatiotemporal patterns of its transcriptional activation in tunicates and vertebrates. While in vertebrates Myogenic Regulatory Factors (MRFs) like MyoD1 alone are required and sufficient forMymktranscription in all skeletal muscles, we show that transcription ofMymkin post-metamorphic muscles of the tunicateCionarequires the combinatorial activity of MRF/MyoD and Early B-Cell Factor (Ebf). This macroevolutionary difference appears to be encoded incis,likely due to the presence of a putative Ebf binding site adjacent to predicted MRF binding sites in theCiona Mymkpromoter. We further discuss howMymkand myoblast fusion might have been regulated in the last common ancestor of tunicates and vertebrates, for which we propose two models.
NEK1haploinsufficiency worsens DNA damage but not defective ciliogenesis inC9ORF72patient-derived iPSC-motoneurons
Authors: Santangelo Serena , Invernizzi Sabrina , Sorce Marta Nice , Casiraghi Valeria , Peverelli Silvia , Brusati Alberto , Colombrita Claudia , Ticozzi Nicola , Silani Vincenzo , Bossolasco Patrizia , Ratti Antonia 
Published: March 2024

AbstractA hexanucleotide G4C2repeat expansion (HRE) inC9ORF72gene is the major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to both loss- and gain-of-function pathomechanisms. The wide clinical heterogeneity amongC9ORF72patients suggests potential modifying genetic factors. Notably,C9ORF72mutations often co-occur with other variants in ALS/FTD-associated genes, such asNEK1, which encodes for a kinase involved in multiple pathways including DNA damage response and ciliogenesis. In this study, we generated induced pluripotent stem cells (iPSCs) and differentiated motoneurons (iPSC-MNs) derived from an ALS patient carrying bothC9ORF72HRE and aNEK1loss-of-function mutation to study the effect of theNEK1haploinsufficiency onC9ORF72pathology. Double mutantC9ORF72/NEK1cells showed increased pathologicalC9ORF72RNA foci in iPSCs and higher DNA damage levels in iPSC-MNs compared to single mutantC9ORF72cells. In contrast, ciliogenesis was similarly impaired in bothC9ORF72andC9ORF72/NEK1iPSC-MNs showing shorter cilia. Altogether, our study supports the use of patient-derived iPSCs to functionally explore the contribution of genetic modifiers inC9ORF72-associated pathology.
De novo assembly and characterization of a highly degenerated ZW sex chromosome in the fish Megaleporinus macrocephalus
Authors: Borges Carolina Heloisa de Souza , Utsunomia Ricardo , Varani Alessandro , Uliano-Silva Marcela , Lira Lieschen Valeria G. , Butzge Arno J. , Agudelo John F. Gomez , Manso Shisley , Freitas Milena V. , Ariede Raquel B. , Mastrochirico-Filho Vito A. , Penaloza Carolina , Barria Agustín , Porto-Foresti Fábio , Foresti Fausto , Hattori Ricardo , Guiguen Yann , Houston Ross D. , Hashimoto Diogo Teruo 
Published: March 2024

AbstractBackgroundMegaleporinus macrocephalus(piauçu) is a Neotropical fish within Characoidei that presents a well-established heteromorphic ZZ/ZW sex-determination system and thus, constitutes a good model for studying W and Z chromosomes in fishes. We used PacBio reads and Hi-C to assemble a chromosome-level reference genome forM. macrocephalus. We generated family segregation information to construct a genetic map, pool-seq of males and females to characterize its sex system, and RNA-seq to highlight candidate genes ofM. macrocephalussex determination.ResultsM. macrocephalusreference genome is 1,282,030,339 bp in length and has a contig and scaffold N50 of 5.0 Mb and 45.03 Mb, respectively. Based on patterns of recombination suppression, coverage, Fst,and sex-specific SNPs, three major regions were distinguished in the sex chromosome: W-specific (highly differentiated), Z-specific (in degeneration), and PAR. The sex chromosome gene repertoire was composed of genes from the TGF-β family(amhr2,bmp7) and Wnt/β-catenin pathway (wnt4,wnt7a), and some of them were differentially expressed.ConclusionsThe chromosome-level genome of piauçu exhibits high quality, establishing a valuable resource for advancing research within the group. Our discoveries offer insights into the evolutionary dynamics of Z and W sex chromosomes in fish, emphasizing ongoing degenerative processes and indicating complex interactions between Z and W sequences in specific genomic regions. Notably,amhr2andbmp7are potential candidate genes for sex determination inM. macrocephalus.
Inhibition of NFAT promotes loss of tissue resident uterine natural killer cells and attendant pregnancy complications in humans
Authors: Asiimwe Rebecca , Knott Brittney , Greene Morgan E. , Wright Emma , Bell Markayla , Epstein Daniel , Yates Stefani D. , Gonzalez Michael V. , Fry Samantha , Boydston Emily , Clevenger Stephanie , Locke Jayme E. , Brocato Brian E. , Burgan Constantine M. , Burney Richard , Arora Nitin , Duncan Virginia E. , Richter Holly E. , Gunn Deidre , Freud Aharon G. , Little Shawn C. , Porrett Paige M. 
Published: March 2024

AbstractUterine natural killer cells (uNKs) are a tissue resident lymphocyte population that are critical for pregnancy success. Although mouse models have demonstrated that NK deficiency results in abnormal placentation and poor pregnancy outcomes, the generalizability of this knowledge to humans remains unclear. Here we identify uterus transplant (UTx) recipients as a human population with reduced uNK cells and altered pregnancy phenotypes. We show that the NK reduction in UTx correlates with impaired transcriptional programming of NK tissue residency arising from the inhibition of NFAT-mediated signaling. Our observations suggest that NFAT-dependent genes modulate multiple molecular tissue residency programs in uNKs. These include early residency programs involving AP-1-family transcription factors and TGF-β-mediated upregulation of surface integrins. Collectively, our data identify a previously undescribed role for NFAT in uterine NK tissue residency and provide novel mechanistic insights into the biologic basis of pregnancy complications due to alteration of tissue resident NK subsets in humans.One Sentence SummaryRole of NFAT in uterine NK cell tissue residency
Post-Translational Modifications Control Phase Transitions of Tau
Authors: Powell Wyatt C. , Nahum McKinley , Pankratz Karl , Herlory Morgane , Greenwood James , Poliyenko Darya , Holland Patrick , Jing Ruiheng , Biggerstaff Luke , Stowell Michael H. B. , Walczak Maciej A. 
Published: March 2024

ABSTRACTThe self-assembly of Tau(297-391) into filaments, which mirror the structures observed in Alzheimer’s disease (AD) brains, raises questions about the role of AD-specific post-translational modifications (PTMs) in the formation of paired helical filaments (PHFs). To investigate this, we developed a synthetic approach to produce Tau(291-391) featuring N-acetyllysine, phosphoserine, phosphotyrosine, and N-glycosylation at positions commonly modified in post-mortem AD brains, thus facilitating the study of their roles in Tau pathology. Using transmission electron microscopy (TEM), cryo-electron microscopy (cryo-EM), and a range of optical microscopy techniques, we discovered that these modifications generally hinder thein vitroassembly of Tau into PHFs. Interestingly, while acetylation’s effect on Tau assembly displayed variability, either promoting or inhibiting phase transitions in the context of cofactor free aggregation, heparin-induced aggregation, and RNA-mediated liquid-liquid phase separation (LLPS), phosphorylation uniformly mitigated these processes. Our observations suggest that PTMs, particularly those situated outside the fibril’s rigid core are pivotal in the nucleation of PHFs. Moreover, in scenarios involving heparin-induced aggregation leading to the formation of heterogeneous aggregates, most AD-specific PTMs, except for K311, appeared to decelerate the aggregation process. The impact of acetylation on RNA-induced LLPS was notably site-dependent, exhibiting both facilitative and inhibitory effects, whereas phosphorylation consistently reduced LLPS across all proteoforms examined. These insights underscore the complex interplay between site-specific PTMs and environmental factors in modulating Tau aggregation kinetics, enhancing our understanding of the molecular underpinnings of Tau pathology in AD and highlighting the critical role of PTMs located outside the ordered filament core in driving the self-assembly of Tau into PHF structures.