bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroplast Methyltransferase Homolog RMT2 is Involved in Photosystem I Biogenesis
Authors: Kim Rick G. , Huang Weichao , Findinier Justin , Bunbury Freddy , Redekop Petra , Shrestha Ruben , Grismer TaraBryn S , Vilarrasa-Blasi Josep , Jinkerson Robert E. , Fakhimi Neda , Fauser Friedrich , Jonikas Martin C. , Onishi Masayuki , Xu Shou-Ling , Grossman Arthur R. 
Published: December 2023

AbstractOxygen (O2), a dominant element in the atmosphere and essential for most life on Earth, is produced by the photosynthetic oxidation of water. However, metabolic activity can cause accumulation of reactive O2species (ROS) and severe cell damage. To identify and characterize mechanisms enabling cells to cope with ROS, we performed a high-throughput O2sensitivity screen on a genome-wide insertional mutant library of the unicellular algaChlamydomonas reinhardtii. This screen led to identification of a gene encoding a protein designated Rubisco methyltransferase 2 (RMT2). Although homologous to methyltransferases, RMT2 has not been experimentally demonstrated to have methyltransferase activity. Furthermore, thermt2mutant was not compromised for Rubisco (first enzyme of Calvin-Benson Cycle) levels but did exhibit a marked decrease in accumulation/activity of photosystem I (PSI), which causes light sensitivity, with much less of an impact on other photosynthetic complexes. This mutant also shows increased accumulation of Ycf3 and Ycf4, proteins critical for PSI assembly. Rescue of the mutant phenotype with a wild-type (WT) copy of RMT2 fused to the mNeonGreen fluorophore indicates that the protein localizes to the chloroplast and appears to be enriched in/around the pyrenoid, an intrachloroplast compartment present in many algae that is packed with Rubisco and potentially hypoxic. These results indicate that RMT2 serves an important role in PSI biogenesis which, although still speculative, may be enriched around or within the pyrenoid.Significance StatementA high-throughput genetic screen was used to identify O2sensitive mutants ofChlamydomonas reinhardtii(Chlamydomonas throughout) that experience elevated oxidative stress in the light relative to WT cells. Identification of genes altered in these mutants offers opportunities to discover activities thata) protect photosynthetic cells from oxidative damage,b) participate in rapid assembly of photosynthetic complexes, which would limit accessibility of intermediates to O2, and/orc) facilitate repair of damaged cellular complexes. A mutant from this screen disrupted forRMT2, originally described as encoding a Rubisco methyltransferase, was defective for PSI biogenesis. Additionally, RMT2 appears to be enriched in/around the pyrenoid, a chloroplast localized compartment harboring much of the Chlamydomonas Rubisco, raising the possibility that this compartment plays a role in PSI biogenesis.
Usingfanyito reduce language barriers, promote information absorption, and communication
Authors: Wang Difei , Chen Guannan , Luo Xiao , Zhan Li , Xu Shuangbin , Wang Qianwen , Li Junrui , Wang Rui , Wen Shaodi , Yu Guangchuang 
Published: December 2023

AbstractUnderstanding the latest research advancements and sharing one’s own achievements is extremely important for young researchers. However, language barriers restrict the absorption of knowledge and career development. To address these issues, we have developed the fanyi package, which utilizes AI-driven online translation services to accurately translate between multiple languages. This helps researchers rapidly capture information, promotes the preservation of a multilingual environment, and ultimately fosters innovation in the academic community. Interpreting genes of interest (such as mutant genes) contributes to proposing molecular mechanisms, but accessing such information typically requires tedious manual retrieval. The fanyi package also provides tools for retrieving gene information from NCBI, enhancing the accessibility of gene information. Being able to quickly and efficiently obtain these pieces of information, coupled with translation capabilities, can help researchers better understand the information. The fanyi package is freely available viahttps://github.com/YuLab-SMU/fanyi. The translation functions are not limited to biomedicine research, they can be applied to any other domain as well.
Characterizing uncertainty in predictions of genomic sequence-to-activity models
Authors: Bajwa Ayesha , Rastogi Ruchir , Kathail Pooja , Shuai Richard W. , Ioannidis Nilah M. 
Published: December 2023

AbstractGenomic sequence-to-activity models are increasingly utilized to understand gene regulatory syntax and probe the functional consequences of regulatory variation. Current models make accurate predictions of relative activity levels across the human reference genome, but their performance is more limited for predicting the effects of genetic variants, such as explaining gene expression variation across individuals. To better understand the causes of these shortcomings, we examine the uncertainty in predictions of genomic sequence-to-activity models using an ensemble of Basenji2 model replicates. We characterize prediction consistency on four types of sequences: reference genome sequences, reference genome sequences perturbed with TF motifs, eQTLs, and personal genome sequences. We observe that models tend to make high-confidence predictions on reference sequences, even when incorrect, and low-confidence predictions on sequences with variants. For eQTLs and personal genome sequences, we find that model replicates make inconsistent predictions in >50% of cases. Our findings suggest strategies to improve performance of these models.
FlowAtlas.jl: an interactive tool bridging FlowJo with computational tools in Julia
Authors: Coppard Valerie , Szep Grisha , Georgieva Zoya , Howlett Sarah K. , Jarvis Lorna B. , Rainbow Daniel B. , Suchanek Ondrej , Needham Edward J. , Mousa Hani S. , Menon David K. , Feyertag Felix , Mahbubani Krishna T. , Saeb-Parsy Kourosh , Jones Joanne L. 
Published: December 2023

AbstractAs the dimensionality, throughput, and complexity of cytometry data increases, so does the demand for user-friendly, interactive analysis tools that leverage high-performance machine learning frameworks. Here we introduce FlowAtlas.jl: an interactive web application that bridges the user-friendly environment of FlowJo and computational tools in Julia developed by the scientific machine learning community. We demonstrate the capabilities of FlowAtlas using a novel human multi-tissue, multi-donor immune cell dataset, highlighting key immunological findings.
Transcriptional and Cellular Response of hiPSC-derived Microglia-Neural Progenitor Co-Cultures Exposed to IL-6
Authors: Couch Amalie C. M. , Brown Amelia M. , Raimundo Catarina , Solomon Shiden , Taylor Morgan , Sichlinger Laura , Matuleviciute Rugile , Srivastava Deepak P. , Vernon Anthony C. 
Published: December 2023

AbstractElevated interleukin (IL-)6 levels during prenatal development have been linked to increased risk for neurodevelopmental disorders (NDD) in the offspring, but the mechanism remains unclear. Human-induced pluripotent stem cell (hiPSC) models offer a valuable tool to study the effects of IL-6 on features relevant for human neurodevelopmentin vitro. We previously reported that hiPSC-derived microglia-like cells (MGLs) respond to IL-6, but neural progenitor cells (NPCs) in monoculture do not. Therefore, we investigated whether co-culturing hiPSC-derived MGLs with NPCs would trigger a cellular response to IL-6 stimulation via secreted factors from the MGLs. Using N=4 donor lines without psychiatric diagnosis, we first confirmed that NPCs can respond to IL-6 through trans-signalling when recombinant IL-6Ra is present, and that this response is dose-dependent. MGLs secreted soluble IL-6R, but at lower levels than foundin vivoand below that needed to activate trans-signalling in NPCs. Whilst transcriptomic and secretome analysis confirmed that MGLs undergo substantial transcriptomic changes after IL-6 exposure and subsequently secrete a cytokine milieu, NPCs in co-culture with MGLs exhibited a minimal transcriptional response. Furthermore, there were no significant cell fate-acquisition changes when differentiated into post-mitotic cultures, nor alterations in synaptic densities in mature neurons. These findings highlight the need to investigate if trans-IL-6 signalling to NPCs is a relevant disease mechanism linking prenatal IL-6 exposure to increased risk for psychiatric disorders. Moreover, our findings underscore the importance of establishing more complexin vitrohuman models with diverse cell types, which may show cell-specific responses to microglia-released cytokines to fully understand how IL-6 exposure may influence human neurodevelopment.
Development of a non-invasive novel individual marmoset holder for evaluation by awake functional magnetic resonance brain imaging
Authors: Seki Fumiko , Yurimoto Terumi , Kamioka Michiko , Inoue Takashi , Komaki Yuji , Iriki Atsushi , Sasaki Erika , Yamazaki Yumiko 
Published: December 2023

AbstractBackgroundAlthough functional MRI (fMRI) in awake marmosets (Callithrix jacchus) is fascinating for functional brain mapping and evaluation of brain disease models, it is difficult to launch awake fMRI on scanners with less than 15 cm of bore size. A universal marmoset holder for the small-bore size MRI was designed, and evaluated whether this holder could conduct auditory stimulation fMRI in the awake state.New MethodThe marmoset holder was designed with an outer diameter of 71.9 mm. A holder was designed to allow adjustment according to the individual head shape, enabling to use the holder universally. An awake fMRI study of auditory response was conducted to evaluate the practicality of the new holder. Whole-brain activation was investigated when marmosets heard the marmoset social communication “phee call,” an artificial tone sound, music (bossa nova), and reversed of those.ResultsThe prefrontal cortex was significantly activated in response to phee calls, whereas only the auditory cortex was activated in response to pure tones. In response to bossa nova, the marmoset’s visual and auditory cortices were activated. In contrast, the auditory response was decreased when marmosets heard phee calls and bossa nova music played backward. Their stimulus-specific responses indicated they perceived and differentiated sound characteristics in the fMRI environment.Comparison with Existing MethodsA holder does not require surgical intervention or custom-made helmet to minimize head movement in small space.ConclusionOur newly developed holder made it possible to perform longitudinal fMRI experiments on multiple marmosets in a less invasive manner.HighlightWe designed a universal marmoset holder for the optimization of small-bore size MRI. We aimed to evaluate whether the data acquired by fMRI with this holder indicated that awake marmosets were likely to recognize sounds during fMRI and whether the brain activity shown as fMRI signals reflected the characteristics of each sound.After the acclimatization of the marmosets to the holder, an awake fMRI study was conducted to evaluate the practicality of the new holder and successfully acquired the auditory responses to the set of sound stimuli.Our newly developed holder does not require surgical intervention to minimize head movement, which allows for less invasive fMRI experiments and makes it easier to conduct longitudinal fMRI for multiple marmosets.
Trophic microRNA: Precursor and mature microRNA ingestion downregulates the target transcripts and hampers larval development inPlutella xylostella
Authors: Bardapurkar Rutwik , Pandit Sagar 
Published: December 2023

AbstractMicroRNAs (miRNAs) are post-transcriptional gene regulators. In the miRNA pathway’s cytoplasmic part, the miRNA is processed from a hairpin-structured precursor (pre-miRNA) to a double-stranded (ds) mature RNA and ultimately to a single-stranded mature miRNA. In insects, ingesting these two ds forms can regulate the target gene expression; this inspired the trophic miRNA’s use as a functional genomics and pest management tool. However, systematic studies enabling comparisons of pre- and mature forms, dosages, administration times, and instar-wise effects on target transcripts and phenotypes, which can help develop a miRNA administration method, are unavailable due to the different focuses of the previous investigations. We investigated the impact of trophically deliveredPx-let-7 miRNA on the Brassicaceae pest,Plutella xylostella, to compare the efficacies of its pre- and ds-mature forms. Continuous feeding on the miRNA-supplemented diet suppressed expressions ofFTZ-F1andE74, the target ecdysone pathway genes. Both the pre-let-7 and mature let-7 miRNA forms similarly downregulated the target transcripts in all four larval instars. Pre-let-7 and let-7 ingestions decreasedP. xylostella’s larval mass and instar duration and increased mortality in all instars, exhibiting adverse effects on larval growth and development. Pre-miRNA processingDicer-1was upregulated upon pre-let-7 ingestion, indicating the miRNA uptake by the midgut cells. The scrambled sequence controls did not affect the target transcripts, suggesting the sequence-specific targeting by the mature miRNA and hairpin cassette’s non-involvement in the target downregulation. This work provides a framework for miRNA and target gene function analyses and potentiates the trophic miRNA’s utility in pest management.
KNL1 and NDC80 represent new universal markers for the detection of functional centromeres in plants
Authors: Oliveira Ludmila , Neumann Pavel , Mata-Sucre Yennifer , Kuo Yi-Tzu , Marques André , Schubert Veit , Macas Jiří 
Published: December 2023

AbstractCentromere is the chromosomal site of kinetochore assembly and microtubule attachment for chromosome segregation. Given its importance, markers that allow specific labeling of centromeric chromatin throughout the cell cycle and across all chromosome types are sought for facilitating various centromere studies. Antibodies against the N-terminal region of CENH3 are commonly used for this purpose, since CENH3 is the near-universal marker of functional centromeres. However, because the N-terminal region of CENH3 is highly variable among plant species, antibodies directed against this region usually function only in a small group of closely related species. As a more versatile alternative, we present here antibodies targeted to the conserved domains of two outer kinetochore proteins, KNL1 and NDC80. Sequence comparison of these domains across more than 350 plant species revealed a high degree of conservation, particularly within a six amino acid motif, FFGPVS in KNL1, suggesting that both antibodies would function in a wide range of plant species. This assumption was confirmed by immunolabeling experiments in angiosperm (monocot and dicot) and gymnosperm species, including those with mono-, holo-, and meta-polycentric chromosomes. In addition to centromere labeling on condensed chromosomes during cell division, both antibodies detected the corresponding regions in the interphase nuclei of most species tested. These results demonstrated that KNL1 and NDC80 are better suited for immunolabeling centromeres than CENH3, because antibodies against these proteins offer incomparably greater versatility across different plant species which is particularly convenient for studying the organization and function of the centromere in non-model species.
Metabolism of ʟ -arabinose converges with virulence regulation to promote enteric pathogen fitness
Authors: Cottam Curtis , White Rhys T , Beck Lauren C , Stewart Christopher J , Beatson Scott A , Lowe Elisabeth C , Grinter Rhys , Connolly James PR 
Published: December 2023

AbstractVirulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified a novel transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagicEscherichia coli(EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Accordingly, we discovered that ʟ-arabinose induces expression of the EHEC type 3 secretion system, enhancing its ability to attach to host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of ʟ-arabinose as a signal. Finally, using the murine pathogenCitrobacter rodentium,we show that ʟ-arabinose metabolism provides a fitness benefit during enteric infection via virulence factor regulation, as opposed to supporting pathogen growth. This study describes an intrinsic mechanism of integrating central sugar metabolism with virulence regulation and highlights the unexpected impact that nutrient utilisation can have in enteric pathogens.
Campycins are novel broad spectrum antibacterials killingCampylobacter jejuniby targeting the essential major outer membrane protein (MOMP)
Authors: Zampara Athina , Gencay Yilmaz Emre , Brøndsted Lone , Sørensen Martine Camilla Holst 
Published: December 2023

ABSTRACTPyocins are high molecular weight bacteriocins produced byPseudomonas aeruginosathat can be retargeted to new bacterial species by exchanging the pyocin tail fibers with bacteriophage receptor binding proteins (RBPs). Here, we develop retargeted pyocins called campycins as new antibacterials to specifically and effectively kill the major foodborne pathogenCampylobacter jejuni.We used two diverse RBPs (H-fibers) encoded by CJIE1 prophages found in the genomes ofC. jejunistrains CAMSA2147 and RM1221 to construct Campycin 1 and Campycin 2, respectively. Together Campycin 1 and 2 could target allC. jejunistrains tested due to complementary antibacterial spectrums. In addition, both campycins led to more than 3 log reductions inC. jejunicounts under microaerobic conditions at 42°C, whereas the killing efficiency was less efficient under anaerobic conditions at 5°C. We furthermore discovered that both H-fibers used to construct the campycins bind to the essential major outer membrane protein (MOMP) present in allC. jejuni,in a strain specific manner. Protein sequence alignment and structural modelling suggest that the highly variable extracellular loops of MOMP form the binding sites of the diverse H-fibers. Furtherin silicoanalyses of 5000 MOMP sequences suggest that the protein fall into three major clades predicted to be targeted by either Campycin 1 or Campycin 2. Thus, campycins are promising antibacterials againstC. jejuniexpected to broadly target numerous strains of this human pathogen found in nature and agriculture.IMPORTANCECampylobacter jejuniis the leading cause of bacterial foodborne gastroenteritis and responsible for more than 800 million cases globally each year posing a continuous risk to human health and a huge economic and societal burden. Here, we developed re-targeted R2 pyocins (campycins) as novel antibacterials againstC. jejuniby using the receptor binding proteins of CJIE1 prophages observed in manyC. jejunigenomes. Notably, campycins broadly target the highly variable yet essential major outer membrane protein (MOMP), and result in more than 3-log reductions inC. jejunicounts under conditions promoting bacterial growth. We therefore propose that campycins have the potential to lowerC. jejunicolonization levels in the chicken gut, the main reservoir and cause of human disease, representing a novel efficient antibacterial solution specifically developed to target this widespread foodborne pathogen.
Sequential Transitions of Male Sexual Behaviors Driven by Dual Acetylcholine-Dopamine Dynamics
Authors: Miyasaka Ai , Kanda Takeshi , Nonaka Naoki , Terakoshi Yuka , Cherasse Yoan , Ishikawa Yukiko , Li Yulong , Takizawa Hotaka , Seita Jun , Yanagisawa Masashi , Sakurai Takeshi , Sakurai Katsuyasu , Liu Qinghua 
Published: December 2023

SummaryThe neural mechanisms regulating sequential transitions of male sexual behaviors, such as mounting, intromission, and ejaculation, in the brain remain unclear. Here, we report that dopamine (DA) and acetylcholine (ACh) dynamics in the ventral shell of the nucleus accumbens (vsNAc) closely aligns with serial transitions of sexual behaviors in male mice. During intromission, the vsNAc exhibits dual ACh-DA rhythms generated by reciprocal regulation between ACh and DA signaling via nicotinic acetylcholine (nAChR) and dopamine D2 (D2R) receptors. Knockdown of choline acetyl transferase (ChAT) or D2R in the vsNAc diminished the likelihood of intromission and ejaculation. Optogenetic manipulations reveal that DA signaling sustains male sexual behaviors by suppressing activities of D2RvsNAcneurons. Moreover, ACh signaling promotes the initiation of mounting and intromission, but also induces the intromission-to-ejaculation transition by triggering a slowdown of DA rhythm. Therefore, dual ACh-DA dynamics harmonize in the vsNAc to drive sequential transitions of male mating behaviors.
Substantial decline of phasic dopamine signaling in senescent male rats does not impact dopamine-dependent Pavlovian conditioning
Authors: Sandberg Stefan G. , Sanford Christina A. , Phillips Paul E. M. 
Published: December 2023

AbstractNormal aging is associated with cognitive decline which impacts financial decision making. One of the underlying features of decision making is probability estimation, in which nucleus accumbens dopamine signaling has been implicated. Here we used fast-scan cyclic voltammetry to probe for age differences in dopamine signaling, and pharmacological manipulation to test for age differences in the dopamine dependence of Pavlovian conditioning. We found differences in phasic dopamine signaling to reward delivery, and unconditioned and conditioned stimuli, but no difference in conditioned approach between adult and senescent groups. In addition, we found that dopamine receptor antagonism with flupenthixol (225 μg/kg, i.p.) partially inhibited conditioned approach in the adult group, whereas it completely blocked conditioned approach in the senescent group. Further increase in concentration to 300 μg/kg, i.p. resulted in complete inhibition of conditioned approach behavior in both age groups. Therefore, while phasic dopamine signaling in the nucleus accumbens of senescent animals is greatly diminished in concentration, these animals maintain dopamine dependent Pavlovian conditioning.
Early Jurassic origin of avian endothermy and thermophysiological diversity in Dinosauria
Authors: Chiarenza Alfio Alessandro , Cantalapiedra Juan L. , Jones Lewis A. , Gamboa Sara , Galván Sofía , Farnsworth Alexander J. , Valdes Paul J. , Sotelo Graciela , Varela Sara 
Published: December 2023

AbstractA fundamental question in dinosaur evolution is how they adapted to substantial long-term shifts in Earth System during the Mesozoic and when they developed environmentally independent, avian-style acclimatization due to the evolution of an endothermic physiology. Combining fossil occurrences with macroevolutionary and paleoclimatic models, we unveil distinct evolutionary pathways in the main dinosaur lineages: ornithischians and theropods diversified across broader climatic landscapes, trending toward cooler niches. An Early Jurassic shift to colder climates in Theropoda suggests an early adoption of endothermic thermophysiology. Conversely, sauropodomorphs exhibited prolonged climatic conservatism associated with higher thermal conditions. Paleo-biome mapping emphasizes temperature, rather than plant productivity, as the primary driver of this pattern, suggesting poikilothermic physiology with a stronger dependence on higher temperatures in sauropods since the Early Jurassic.One-Sentence SummaryDinosaur climatic evolution reveals early endothermy emergence in theropods, ornithischians but heterotherm sauropodomorphs.