bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and quantification of transposable element transcripts using Long-Read RNA-seq inDrosophilagermline tissues
Authors: Rebollo Rita , Gerenton Pierre , Cumunel Eric , Mary Arnaud , Sabot François , Burlet Nelly , Gillet Benjamin , Hughes Sandrine , Oliveira Daniel S. , Goubert Clément , Fablet Marie , Vieira Cristina , Lacroix Vincent 
Published: May 2023

AbstractTransposable elements (TEs) are repeated DNA sequences potentially able to move throughout the genome. In addition to their inherent mutagenic effects, TEs can disrupt nearby genes by donating their intrinsic regulatory sequences, for instance, promoting the ectopic expression of a cellular gene. TE transcription is therefore not only necessary for TE transpositionper sebut can also be associated with TE-gene fusion transcripts, and in some cases, be the product of pervasive transcription. Hence, correctly determining the transcription state of a TE copy is essential to apprehend the impact of the TE in the host genome. Methods to identify and quantify TE transcription have mostly relied on short RNA-seq reads to estimate TE expression at the family level while using specific algorithms to discriminate copy-specific transcription. However, assigning short reads to their correct genomic location, and genomic feature is not trivial. Here we retrieved full-length cDNA (TeloPrime, Lexogen) ofDrosophila melanogastergonads and sequenced them using Oxford Nanopore Technologies. We show that long-read RNA-seq can be used to identify and quantify transcribed TEs at the copy level. In particular, TE insertions overlapping annotated genes are better estimated using long reads than short reads. Nevertheless, long TE transcripts (> 4.5 kb) are not well captured. Most expressed TE insertions correspond to copies that have lost their ability to transpose, and within a family, only a few copies are indeed expressed. Long-read sequencing also allowed the identification of spliced transcripts for around 107 TE copies. Overall, this first comparison of TEs between testes and ovaries uncovers differences in their transcriptional landscape, at the subclass and insertion level.
Chemogenetic approaches reveal dual functions of microglia in epilepsy
Authors: Dheer Aastha , Bosco Dale B. , Zheng Jiaying , Wang Lingxiao , Zhao Shunyi , Haruwaka Koichiro , Yi Min-Hee , Barath Abhijeet , Tian Dai-Shi , Wu Long-Jun 
Published: May 2023

AbstractMicroglia are key players in maintaining brain homeostasis and exhibit phenotypic alterations in response to epileptic stimuli. However, it is still relatively unknown if these alterations are pro- or anti-epileptic. To unravel this dilemma, we employed chemogenetic manipulation of microglia via of the artificial Gi-Dreadd receptor within a kainic acid (KA) induced murine seizure model. Our results indicate that Gi-Dreadd activation can reduce seizure severity. Additionally, we observed increased interaction between microglia and neuronal soma, which correlated with reduced neuronal hyperactivity. Interestingly, prolonged activation of microglial Gi-Dreadds by repeated doses over 3 days, arrested microglia in a less active, homeostatic-like state, which associated with increased neuronal loss after KA induced seizures. RNAseq analysis revealed that prolonged activation of Gi-Dreadd interferes with interferon β signaling and microglia proliferation. Thus, our findings highlight the importance of microglial activation not only duringstatus epilepticus(SE) but also within later seizure induced pathology.
Are fungi capacitors?
Authors: Szaciłowski Konrad , Beasley Alexander E. , Mech Krzysztof , Adamatzky Andrew 
Published: May 2023

AbstractThe emerging field of living technologies aims to create new functional hybrid materials in which living systems interface and interact with inanimate ones. Combining research into living technologies with emerging developments in computing architecture has enabled the generation of organic electronics from plants and slime mould. Here, we expand on this work by studying capacitive properties of a substrate colonised by mycelium of grey oyster fungi,Pleurotus ostreatus. Capacitors play a fundamental role in traditional analogue and digital electronic systems and have a range of uses including sensing, energy storage and filter circuits. Mycelium has the potential to be used as an organic replacement for traditional capacitor technology. Here, were show that the capacitance of mycelium is in the order of hundreds of picofarads and at the same time a voltage-dependent pseudocapacitance of the order of hundreds of microfarads. We also demonstrate that the charge density of the mycelium ‘dielectric’ decays rapidly with increasing distance from the source probes. This is important as it indicates that small cells of mycelium could be used as a charge carrier or storage medium, when employed as part of an array with reasonable density.
Dynamics of Gut Metabolome and Microbiome Maturation during Early Life
Authors: Aatsinki Anna-Katariina , Lamichhane Santosh , Isokääntä Heidi , Sen Partho , Kråkström Matilda , Alves Marina Amaral , Keskitalo Anniina , Munukka Eveliina , Karlsson Hasse , Perasto Laura , Lukkarinen Minna , Oresic Matej , Kailanto Henna-Maria , Karlsson Linnea , Lahti Leo , Dickens Alex M 
Published: May 2023

AbstractEarly-life gut microbiome-metabolome crosstalk has a pivotal role in the maintenance of host physiology. However, our understanding on early-life gut microbiome-metabolome maturation trajectories in humans remains limited. This study aims to explore the longitudinal patterns of gut metabolites during early life, and how they are related to gut microbiota composition in birth cohort samples of n = 670 children collected at 2.5 (n=272), 6 (n=232), 14 (n=289), and 30 months (n=157) of age.Factor analysis showed that breastfeeding has an effect on several metabolites including secondary bile acids. We found that the prevalent gut microbial abundances were associated with metabolite levels, especially in the 2.5 months-olds. We also demonstrated that the prevalent early colonizersBacteroides, EscherichiaandBifidobacteriumabundances associated with microbial metabolites bile acids especially in the breastfed infants.Taken together, our results suggests that as the microbiome matures during the early-life there is an association with the metabolome composition in an analogous fashion to how the genome information mature during early life.
Snow flies self-amputate freezing limbs to sustain behavior at sub-zero temperatures
Authors: Golding Dominic , Rupp Katie , Sustar Anne , Pratt Brandon , Tuthill John C. 
Published: May 2023

AbstractAll living things are profoundly affected by temperature. In spite of the thermodynamic constraints on biology, some animals have evolved to live and move in extremely cold environments. Here, we investigate behavioral mechanisms of cold tolerance in the snow fly (Chioneaspp.), a flightless crane fly that is active throughout the winter in boreal and alpine environments of the northern hemisphere. Using thermal imaging, we show that adult snow flies maintain the ability to walk down to an average body temperature of -7 °C. At this supercooling limit, ice crystallization occurs within the snow fly’s hemolymph and rapidly spreads throughout the body, resulting in death. However, we discovered that snow flies frequently survive freezing by rapidly amputating legs before ice crystallization can spread to their vital organs. Self-amputation of freezing limbs is a last-ditch tactic to prolong survival in frigid conditions that few animals can endure. Understanding the extreme physiology and behavior of snow insects is urgently important, as the alpine ecosystems they inhabit are being disproportionately altered by anthropogenic climate change.
A zebrafish xenotransplant model of anaplastic thyroid cancer to study the tumor microenvironment and innate immune cell interactionsin vivo
Authors: Michael Cassia , Di Cristofano Antonio , de Oliveira Sofia 
Published: May 2023

AbstractAnaplastic thyroid cancer (ATC) is a rare malignant subtype of thyroid cancer. While ATC is rare it accounts for a disproportionately high number of thyroid cancer-related deaths. Here we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643) derived fluorescently labeled ATC cell lines we show these cell lines display different engraftment rates, mass volume, proliferation, and angiogenic potential. Next, using a PIP-FUCCI reporter to track proliferationin-vivowe observed cells in each phase of the cell cycle. Additionally, we performed long-term non-invasive intravital microscopy over 48 hours to understand cellular dynamics in the tumor microenvironment at the single cell level. Lastly, we tested a well-known mTOR inhibitor to show our model could be used as an effective screening platform for new therapeutic compounds. Altogether, we show that zebrafish xenotransplants make a great model to study thyroid carcinogenesis and the tumor microenvironment, while also being a suitable model to test new therapeuticsin vivo.SUMMARY STATEMENTAnaplastic thyroid cancer xenotransplant model in zebrafish larvae to study thyroid cancer tumorigenesis and tumor microenvironment. Using confocal microscopy to understand cell cycle progression, interactions with the innate immune system, and test therapeutic compounds in vivo.
Gene expression QTL mapping in stimulated iPSC-derived macrophages provides insights into common complex diseases
Authors: Panousis Nikolaos I , Garwany Omar El , Knights Andrew , Rop Jesse Cheruiyot , Kumasaka Natsuhiko , Imaz Maria , Vilarino Lorena Boquete , Tsingene Anthi , Barnett Alice , Gomez Celine , Anderson Carl A. , Gaffney Daniel J. 
Published: May 2023

AbstractMany disease-associated variants are thought to be regulatory but are not present in existing catalogues of expression quantitative trait loci (eQTL). We hypothesise that these variants may regulate expression in specific biological contexts, such as stimulated immune cells. Here, we used human iPSC-derived macrophages to map eQTLs across 24 cellular conditions. We found that 76% of eQTLs detected in at least one stimulated condition were also found in naive cells. The percentage of response eQTLs (reQTLs) varied widely across conditions (3.7% - 28.4%), with reQTLs specific to a single condition being rare (1.11%). Despite their relative rarity, reQTLs were overrepresented among disease-colocalizing eQTLs. We nominated an additional 21.7% of disease effector genes at GWAS loci via colocalization of reQTLs, with 38.6% of these not found in the Genotype–Tissue Expression (GTEx) catalogue. Our study highlights the diversity of genetic effects on expression and demonstrates how condition-specific regulatory variation can enhance our understanding of common disease risk alleles.
Genetic identification of novel medullary neurons underlying congenital central hypoventilation syndrome
Authors: Cui Ke , Xia Yiling , Patnaik Abhisarika , Lowenstein Elijah D. , Isik Eser Göksu , Knorz Adrian L. , Airaghi Laura , Crotti Michela , Studer Michèle , Rijli Filippo M. , Nothwang Hans G. , Hernandez-Miranda Luis R. 
Published: May 2023

AbstractCongenital Central Hypoventilation Syndrome (CCHS) is a rare, but life-threatening, respiratory disorder that is classically diagnosed in children. This disease is characterized by pronounced alveolar hypoventilation and diminished chemoreflexes, particularly to abnormally high levels of arterial pCO2. Mutations in the transcription factorsPHOX2BandLBX1have been identified in CCHS patients, but the dysfunctional circuit responsible for this disease remains unknown. Here, we show that distinct sets of medullary neurons co-expressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in CCHS. By combining murine intersectional chemogenetics, intersectional labeling, and the selective targeting of the CCHS disease-causingLbx1FSmutation to specific subgroups of dB2 neurons, we uncovered novel sets of these cells key for i) respiratory tidal volumes and the hypercarbic reflex, ii) neonatal respiratory stability and iii) neonatal survival. These data provide functional evidence for the essential role of dB2 neurons in neonatal respiratory physiology and will be instrumental for the development of therapeutic strategies for the management of CCHS. In summary, our work uncovers new neural components of the central circuit regulating breathing and establishes dB2 neuron dysfunction to be causative of CCHS.
Rescaling protein-protein interactions improves Martini 3 for flexible proteins in solution
Authors: Thomasen F. Emil , Skaalum Tórur , Kumar Ashutosh , Srinivasan Sriraksha , Vanni Stefano , Lindorff-Larsen Kresten 
Published: May 2023

AbstractMultidomain proteins with flexible linkers and disordered regions play important roles in many cellular processes, but characterizing their conformational ensembles is diffcult. We have previously shown that the coarse-grained model, Martini 3, produces too compact ensembles in solution, that may in part be remedied by strengthening protein–water interactions. Here, we show that decreasing the strength of protein–protein interactions leads to improved agreement with experimental data on a wide set of systems. We show that the ‘symmetry’ between rescaling protein–water and protein–protein interactions breaks down when studying interactions with or within membranes; rescaling protein-protein interactions better preserves the binding specificity of proteins with lipid membranes, whereas rescaling protein-water interactions preserves oligomerization of transmembrane helices. We conclude that decreasing the strength of protein–protein interactions improves the accuracy of Martini 3 for IDPs and multidomain proteins, both in solution and in the presence of a lipid membrane.
Chronic high-sugar diet in adulthood protectsCaenorhabditis elegansfrom 6-OHDA induced dopaminergic neurodegeneration
Authors: Morton Katherine S. , Hartman Jessica H. , Heffernan Nathan , Ryde Ian T. , Kenny-Ganzert Isabel W. , Meng Lingfeng , Sherwood David R. , Meyer Joel N. 
Published: May 2023

AbstractBackgroundDiets high in saturated fat and sugar, termed ‘western diets’, have been associated with several negative health outcomes, including increased risk for neurodegenerative disease. Parkinson’s Disease (PD) is the second most prevalent neurodegenerative disease and is characterized by the progressive death of dopaminergic neurons in the brain. We build upon previous work characterizing the impact of high sugar diets inCaenorhabditis elegansto mechanistically evaluate the relationship between high sugar diets and dopaminergic neurodegeneration.ResultsAdult high glucose and fructose diets, or exposure from day 1-5 of adulthood, led to increased lipid content and shorter lifespan and decreased reproduction. However, in contrast to previous reports, we found that adult chronic high-glucose and high-fructose diets did not induce dopaminergic neurodegeneration alone and were protective from 6-hydroxydopamine (6-OHDA) induced degeneration. Neither sugar altered baseline electron transport chain function, and both increased vulnerability to organism-wide ATP depletion when the electron transport chain was inhibited, arguing against energetic rescue as a basis for neuroprotection. The induction of oxidative stress by 6-OHDA is hypothesized to contribute to its pathology, and high sugar diets prevented this increase in the soma of the dopaminergic neurons. However, we did not find increased expression of antioxidant enzymes or glutathione levels. Instead, we found evidence suggesting downregulation of the dopamine reuptake transporterdat-1that could result in decreased 6-OHDA uptake.ConclusionOur work uncovers a neuroprotective role for high sugar diets, despite concomitant decreases in lifespan and reproduction. Our results support the broader finding that ATP depletion alone is insufficient to induce dopaminergic neurodegeneration, whereas increased neuronal oxidative stress may drive degeneration. Finally, our work highlights the importance of evaluating lifestyle by toxicant interactions.
Altered methionine metabolism impacts phenylpropanoid production and plant development inArabidopsis thaliana
Authors: Shin Doosan , Perez Veronica C. , Dickinson Gabriella K. , Zhao Haohao , Dai Ru , Tomiczek Breanna , Cho Keun Ho , Zhu Ning , Koh Jin , Grenning Alexander , Kim Jeongim 
Published: May 2023

AbstractPhenylpropanoids are specialized metabolites derived from phenylalanine. Glucosinolates are defense compounds derived mainly from methionine and tryptophan in Arabidopsis. It was previously shown that the phenylpropanoid pathway and glucosinolate production are metabolically linked. The accumulation of indole-3-acetaldoxime (IAOx), the precursor of tryptophan-derived glucosinolates, represses phenylpropanoid biosynthesis through accelerated degradation of phenylalanine-ammonia lyase (PAL). As PAL functions at the entry point of the phenylpropanoid pathway which produces indispensable specialized metabolites such as lignin, aldoxime-mediated phenylpropanoid repression is detrimental to plant survival. Although methionine-derived glucosinolates in Arabidopsis are abundant, any impact of aliphatic aldoximes (AAOx) derived from aliphatic amino acids such as methionine on phenylpropanoid production remains unclear.Here, we investigate the impact of AAOx accumulation on phenylpropanoid production using Arabidopsis aldoxime mutants,ref2andref5. REF2 and REF5 metabolize aldoximes to respective nitrile oxides redundantly, but with different substrate specificities.ref2andref5mutants have decreased phenylpropanoid contents due to the accumulation of aldoximes. As REF2 and REF5 have high substrate specificity toward AAOx and IAOx respectively, it was assumed thatref2accumulates AAOx, not IAOx. Our study indicates thatref2accumulates both AAOx and IAOx. Removing IAOx partially restored phenylpropanoid production inref2, but not to the wild-type level. However, when AAOx biosynthesis was silenced, phenylpropanoid production and PAL activity inref2were completely restored, suggesting an inhibitory effect of AAOx on phenylpropanoid production. Further feeding studies revealed that the abnormal growth phenotype commonly observed in Arabidopsis mutants lacking AAOx production is a consequence of methionine accumulation.Significance StatementAliphatic aldoximes are precursors of various specialized metabolites including defense compounds. This study reveals that aliphatic aldoximes repress phenylpropanoid production and that altered methionine metabolism affects plant growth and development. As phenylpropanoids include vital metabolites such as lignin, a major sink of fixed carbon, this metabolic link may contribute to available resource allocation during defense.
Neuroimaging Signatures of Metacognitive Improvement in Sensorimotor Timing
Authors: Bader Farah , Wiener Martin 
Published: May 2023

AbstractError monitoring is an essential human ability underlying learning and metacognition. In the time domain, humans possess a remarkable ability to learn and adapt to temporal intervals, yet the neural mechanisms underlying this are not well understood. Recently, we demonstrated that humans exhibit improvements in sensorimotor time estimates when given the chance to incorporate feedback from a previous trial (Bader and Wiener 2021), suggesting that humans are metacognitively aware of their own timing errors. To test the neural basis of this metacognitive ability, human participants of both sexes underwent fMRI while they performed a visual temporal reproduction task with randomized suprasecond intervals (1-6s). Crucially, each trial was repeated following feedback, allowing a “re-do” to learn from the successes or errors in the initial trial. Behaviorally, we replicated our previous finding that subjects improve their performance on re-do trials despite the feedback being temporally uninformative (i.e. early or late). For neuroimaging, we observed a dissociation between estimating and reproducing time intervals, with the former more likely to engage regions associated with the default mode network (DMN), including the superior frontal gyri, precuneus, and posterior cingulate, whereas the latter activated regions associated traditionally with the “Timing Network” (TN), including the supplementary motor area (SMA), precentral gyrus, and right supramarginal gyrus. Notably, greater DMN involvement was observed in Re-do trials. Further, the extent of the DMN was greater on re-do trials, whereas for the TN it was more constrained. Finally, Task-based connectivity between these networks demonstrated higher inter-network correlation on initial trials, but primarily when estimating trials, whereas on re-do trials communication was higher during reproduction. Overall, these results suggest the DMN and TN work in concert to mediate subjective awareness of one’s sense of time for the purpose of improving timing performance.Significance StatementA finely tuned sense of time perception is imperative for everyday motor actions (e.g., hitting a baseball). Timing self-regulation requires correct assessment and updating duration estimates if necessary. Using a modified version of a classical task of time measurement, we explored the neural regions involved in error detection, time awareness, and learning to time. Reinforcing the role of the SMA in measuring temporal information and providing evidence of co-activation with the DMN, this study demonstrates that the brain overlays sensorimotor timing with a metacognitive awareness of its passage.
An Open-Source Tool for Automated Human-Level Circling Behavior Detection
Authors: Stanley O.R. , Swaminathan A. , Wojahn E. , Ahmed Z. M. , Cullen K. E. 
Published: May 2023

ABSTRACTQuantifying behavior and relating it to underlying biological states is of paramount importance in many life science fields. Although barriers to recording postural data have been reduced by progress in deep-learning-based computer vision tools for keypoint tracking, extracting specific behaviors from this data remains challenging. Manual behavior coding, the present gold standard, is labor-intensive and subject to intra-and inter-observer variability. Automatic methods are stymied by the difficulty of explicitly defining complex behaviors, even ones which appear obvious to the human eye. Here, we demonstrate an effective technique for detecting one such behavior, a form of locomotion characterized by stereotyped spinning, termed ’circling’. Though circling has an extensive history as a behavioral marker, at present there exists no standard automated detection method. Accordingly, we developed a technique to identify instances of the behavior by applying simple postprocessing to markerless keypoint data from videos of freely-exploring (Cib2-/-;Cib3-/-) mutant mice, a strain we previously found to exhibit circling. Our technique agrees with human consensus at the same level as do individual observers, and it achieves >90% accuracy in discriminating videos of wild type mice from videos of mutants. As using this technique requires no experience writing or modifying code, it also provides a convenient, noninvasive, quantitative tool for analyzing circling mouse models. Additionally, as our approach was agnostic to the underlying behavior, these results support the feasibility of algorithmically detecting specific, research-relevant behaviors using readily-interpretable parameters tuned on the basis of human consensus.