bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Intracerebroventricular Fibroblast Growth Factor 23 on gene expression in the Rats’ Hypothalamus
Authors: Ursem Stan R , Diepenbroek Charlene , Kool Tess , Eggels Leslie , Heijboer Annemieke C , la Fleur Susanne E 
Published: November 2022

AbstractFibroblast growth factor 23 (FGF23) is a key regulator of systemic phosphate homeostasis, but also an interplay with glucose metabolism has been suggested. Several studies implicate a function of FGF23 in the brain, and indeed we have recently identified FGF23 protein in several brain areas in rats, such as the hypothalamus, third ventricle and choroid plexus. In the current study, we aimed to determine the effect of an intracerebroventricular (icv) injection of FGF23 in the third ventricle of rats on hypothalamic genes involved in glucose regulation. In addition, we assessed whether glycerol can be used safely for icv injections as glycerol is used as a stabilizing compound for FGF23 protein.Adult Wistar rats received an icv injection of recombinant rat FGF23 or vehicle. Dose dependent behavioral changes, suggestive of stress, were observed directly after infusion of FGF23. After 60 min animals were sacrificed and the arcuate nucleus, lateral hypothalamus and choroid plexus were isolated. In these brain regions gene expression was determined of the FGF23 receptor complex (FGFR1, αKlotho), NPY, POMC, phosphate transporters (SLC20 and SLC34 families) and markers of cellular ER stress (ATF4 and the ratio of spliced/unspliced XBP1).We showed that glycerol is well tolerated as stabilizer for icv injections. In FGF23-treated animals, cellular ER stress markers were increased in the arcuate nucleus. FGF23 injection did not affect expression of its receptor complex, NPY, POMC, or phosphate transporters. Future studies are warranted to investigate the effect of FGF23 in the brain on the protein level and on neuronal activation.
Polystyrene-colonizing bacteria are enriched for long-chain alkane degradation pathways
Authors: Hsueh Shu Wei , Jian You-Hua , Fugmann Sebastian D. , Yang Shu Yuan 
Published: November 2022

AbstractOne of the most promising strategies for the management of plastic waste is microbial biodegradation, but efficient degraders for many types of plastics are still lacking, including for polystyrene (PS). Genomics has emerged as a powerful tool for mining environmental microbes that may have the ability to degrade different types of plastics. In this study, we use 16S sequencing to analyze the microbiomes for multiple PS samples collected from sites with different vegetation in Taiwan to reveal potential common properties between species that have exhibit growth advantages on PS surfaces. Phylum enrichment analysis identified Cyanobacteria and Deinococcus-Thermus as being the most over-represented groups on PS, and both phyla include species known to reside in extreme environments and could encode unique enzymes that grant them properties suitable for colonization on PS surfaces. Investigation of functional enrichment in PS-enriched species highlighted carbon metabolic pathways, especially those related to hydrocarbon degradation. This is corroborated by the finding that genes encoding long-chain alkane hydroxylases such as AlmA are more prevalent in the genomes of PS-associated bacteria. Our analyses illustrate how plastic in the environment support the colonization of different microbes compared to surrounding soil. In addition, our results point to the possibility that alkane hydroxylases could confer growth advantages of microbes on PS.
Reference genome sequences of the oriental armyworm,Mythimna separata(Lepidoptera: Noctuidae)
Authors: Yokoi Kakeru , Furukawa Seiichi , Zhou Rui , Jouraku Akiya , Bono Hidemasa 
Published: November 2022

AbstractLepidopteran insects are an important group of animals, among which some are used as biochemical and physiological model species in the insect and silk industries, whereas others are major agricultural pests. Therefore, genome sequences of several lepidopteran insects have been reported thus far. The oriental armyworm,Mythimna separata, is an agricultural pest commonly used to study insect immune reactions and interactions with parasitoid wasps as hosts. To improve our understanding of these research topics, reference genome sequences were constructed in the present study. Using long-read and short-read sequence data,de novoassembly and polishing were performed, and haplotigs were purged. Subsequently, gene predictions and functional annotations were performed. To search for orthologs of the Toll and immune deficiency (IMD) pathways and C-type lectins, annotation data analysis, BLASTp, and Hummer scans were performed. TheM. separatagenome is 682 Mbp; its contig N50 was 2.7 Mbp with 21,970 genes and 24,452 coding sites predicted. All orthologs of the core components of the Toll and IMD pathways and 105 C-type lectins were identified. These results suggest that the genome data were of sufficient quality as reference genome data and could contribute to promotingM. separataand lepidopteran research at the molecular and genome levels.Simple SummaryThe oriental armyworm,Mythimna separata, an agricultural pest, is commonly used to study insect immune reactions and interactions with parasitoid wasps. To promote such studies, a reference genome was constructed. TheM. separatagenome is 682Mbp long—a size comparable to that of other lepidopteran insects. The contig N50 value of the genome is 2.7 Mb, which indicates sufficient quality to be used as reference genome data. Gene set data were constructed using genome and RNA-sequencing data; a total of 21,970 genes and 24,452 coding sites were predicted. Functional gene annotation was performed using the predicted amino acid sequences and reference gene set data of the model organism and other insect species as well as Unigene and Pfam datasets. Consequently, 45–80% of the amino acid sequences were annotated using these data sets. Using these data, most of the orthologs of core components in the Toll and immune deficiency (IMD) pathways were identified, suggesting the presence of these two pathways inM. separata. Additionally, 105 C-type lectins were identified in theM. separatagenome, which were more numerous than those in other insect species, suggesting that these genes may be duplicated.
Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis
Authors: Mota-Gómez Irene , Rodríguez Juan Antonio , Dupont Shannon , Lao Oscar , Jedamzick Johanna , Kuhn Ralf , Lacadie Scott , García-Moreno Sara Alexandra , Hurtado Alicia , Acemel Rafael D. , Capel Blanche , Marti-Renom Marc A. , Lupiáñez Darío G. 
Published: November 2022

ABSTRACTMammalian sex is determined by opposing networks of ovarian and testicular genes that are well characterized. However, its epigenetic regulation is still largely unknown, thus limiting our understanding of a fundamental process for species propagation. Here we explore the 3D chromatin landscape of sex determinationin vivo, by profiling FACS-sorted embryonic mouse gonadal populations, prior and after sex determination, in both sexes. We integrate Hi-C with ChIP-seq experiments usingMETALoci, a novel genome spatial auto-correlation analysis that identifies 3D enhancer hubs across the genome. We uncover a prominent rewiring of chromatin interactions during sex determination, affecting the enhancer hubs of hundreds of genes that display temporal- and sex-specific expression. Moreover, the identification of the 3D enhancer hubs allows the reconstruction of regulatory networks, revealing key transcription factors involved in sex determination. By combining predictive approaches and validations in transgenic mice we identify a novelFgf9regulatory hub, deletion of which results in male-to-female sex reversal with the upregulation of ovarian-specific markers and the initiation of meiosis. Thus, spatial auto-correlation analysis is an effective strategy to identify regulatory networks associated to biological processes and to further characterize the functional role of the 3D genome.
Modulation of TRPV4 Protects against Degeneration Induced by Sustained Loading and Promotes Matrix Synthesis in the Intervertebral Disc
Authors: Easson Garrett W.D. , Savadipour Alireza , Anandarajah Akila , Iannucci Leanne E. , Lake Spencer P. , Guilak Farshid , Tang Simon Y. 
Published: November 2022

AbstractWhile it is well-known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short-(hours) and long-term (days) and evaluated IVDs’ response. Activating TRPV4 with the agonist GSK101 resulted in a Ca2+flux propagating across the cells within the IVD. NF-κB signaling in the IVD peaked at 6 hours following TRPV4 activation that subsequently resulted in higher IL-6 production at 7 days. These cellular responses were concomitant with the accumulation of glycosaminoglycans and increased hydration in the nucleus pulposus that culminated in higher stiffness of the IVD. Sustained compressive loading of the IVD resulted in elevated NF-κB activity, IL-6 and VEGF-A production, and degenerative changes to the ECM. TRPV4 inhibition using GSK205 during loading mitigated the changes in inflammatory cytokines, protected against IVD degeneration, and but could not prevent ECM disorganization due to mechanical damage in the annulus fibrosus. These results indicate TRPV4 plays an important role in both short-and long-term adaptations of the IVD to mechanical loading. The modulation of TRPV4 may be a possible therapeutic for preventing load-induced IVD degeneration.
Subcellular proteome of radial glia reveals non-muscle myosins control basal endfeet to mediate interneuron organization
Authors: D’Arcy Brooke R , Lennox Ashley L , Musso Camila Manso , Bracher Annalise , Escobar-Tomlienovich Carla , Perez-Sanchez Stephany , Silver Debra L 
Published: November 2022

AbstractRadial glial cells (RGCs) are essential for the generation and organization of neurons in the cerebral cortex. RGCs have an elongated bipolar morphology with basal and apical endfeet which reside in distinct niches. Yet, how this subcellular compartmentalization of RGCs controls cortical development is largely unknown. Here, we employin vivoproximity labeling using unfused BirA to generate the first subcellular proteome of RGCs and uncover new principles governing local control of cortical development. We discover a cohort of proteins that are significantly enriched in RGC basal endfeet, with MYH9 and MYH10 among the most abundant.Myh9andMyh10transcripts also localize to endfeet with distinct temporal dynamics. Although they each encode isoforms of non-muscle myosin II heavy chain,Myh9andMyh10have drastically different requirements for RGC integrity.Myh9loss from RGCs decreases branching complexity and causes endfoot protrusion through the basement membrane. In contrast,Myh10controls endfoot adhesion, as mutants have unattached apical and basal endfeet. Finally, we show thatMyh9- andMyh10-mediated regulation of RGC complexity and endfoot position non-cell autonomously controls interneuron number and organization in the marginal zone. Our study demonstrates the utility ofin vivoproximity labeling for dissecting local control of complex systems, and reveals new mechanisms for dictating RGC integrity and cortical architecture.
Inter-species stimulus enhancement: Herring gulls (Larus argentatus) read human behaviour during foraging
Authors: Feist Franziska , Smith Kiera , Graham Paul 
Published: November 2022

AbstractHerring gulls are one of the few species that thrive in anthropogenic landscapes and their familiarity with people makes them an excellent target for studies of inter-species social cognition. Urban gulls pay attention to human behaviour in food-related contexts and we set out to investigate whether such cues can be used to redirect a gull’s attention to potential food items in their environment. Herring gulls were given free choice of two differently coloured anthropogenic food items in the presence of a demonstrator, who was either sitting still or pretending to eat food from an item that matched one of the secondary food items. We found that a demonstrator mimicking eating significantly increased the likelihood of an approach or peck. Furthermore, 95% of pecks were directed towards the secondary food item which colour-matched the demonstrator’s food item. The results show situation-dependent attentional modulation in gulls, whereby gulls are able to use human cues for stimulus enhancement and foraging decisions. Given the relatively recent history of urbanisation in herring gulls, this cross-species social information transfer is likely to be a by-product of the cognitive flexibility inherent in kleptoparasitic species.
Phencyclidine disrupts neural coordination and cognitive control by dysregulating translation
Authors: Park Eun Hye , Kao Hsin-Yi , Jourdi Hussam , van Dijk Milenna , Carrillo-Segura Simón , Tunnell Kayla W. , Gutierrez Jeffrey , Wallace Emma J. , Troy-Regier Matthew , Radwan Basma , Lesburguères Edith , Alarcon Juan Marcos , Fenton André A 
Published: November 2022

ABSTRACTBackgroundPhencyclidine (PCP) causes psychosis, is abused with increasing frequency, and was extensively used in antipsychotic drug discovery. PCP discoordinates hippocampal ensemble action potential discharge and impairs cognitive control in rats, but how this uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist impairs cognition remains unknown.MethodsThe effects of PCP were investigated i) on hippocampal CA1 ensemble action potential dischargein vivoin urethane-anesthetized rats and during awake behavior in mice; ii) on synaptic responses inex vivomouse hippocampus slices; iii) in mice on a hippocampus-dependent active place avoidance task that requires cognitive control; and iv) on activating the molecular machinery of translation in acute hippocampus slices. Mechanistic causality was assessed by comparing the PCP effects to the effects of inhibitors of protein synthesis, group-1-type metabotropic glutamate receptors (mGluR1/5), and subunit-selective NMDARs.ResultsConsistent with ionotropic actions, PCP discoordinated CA1 ensemble action potential discharge. PCP caused hyperactivity, and impaired active place avoidance, despite learning the task before PCP. Consistent with metabotropic actions, PCP exaggerated protein-synthesis dependent DHPG-induced mGluR1/5-stimulated long-term synaptic depression (LTD). Pretreatment with anisomycin or the mGluR1/5-antagonist MPEP, both of which repress translation, prevented the PCP-induced discoordination, and the cognitive and sensorimotor impairments. PCP as well as the NR2A-containing NMDAR-antagonist NVP-AAM077 unbalanced translation that engages the AKT, mTOR and 4EBP1 translation machinery and increased protein synthesis, whereas the NR2B-containing antagonist Ro25-6981 did not.ConclusionsPCP dysregulates translation, acting through NR2A-containing NMDAR subtypes, recruiting mGluR1/5 signaling pathways, leading to the neural discoordination that is central to the cognitive and sensorimotor impairments.
CSF1R inhibition by PLX5622 reduces pulmonary fungal infection by depleting MHCIIhiinterstitial lung macrophages
Authors: Mohamed Sally H. , Vanhoffelen Eliane , Fu Man Shun , Cosway Emilie , Anderson Graham , Velde Greetje Vande , Drummond Rebecca A. 
Published: November 2022

AbstractPLX5622 is a small molecular inhibitor of the CSF1 receptor (CSF1R) and is widely used to deplete macrophages within the central nervous system (CNS). However, recent reports have indicated that PLX5622 may affect myeloid cells in other organs including the bone marrow and spleen. We investigated the impact of PLX5622 treatment in wild-type C57BL/6 mice and discovered that one-week treatment with PLX5622 was sufficient to deplete interstitial macrophages in the lung and brain-infiltrating Ly6Clowpatrolling monocytes, in addition to CNS-resident macrophages. These cell types were previously indicated to act as infection reservoirs for the pathogenic fungusCryptococcus neoformans. We therefore took advantage of PLX5622-mediated depletion of these myeloid cell subsets to examine their functional role inC. neoformanslung infection and extrapulmonary dissemination. We found that PLX5622-treated mice had significantly reduced fungal lung infection and reduced extrapulmonary dissemination to the CNS but not to the spleen or liver. Fungal lung infection mapped to MHCIIhiinterstitial lung macrophages, which underwent significant expansion during infection following monocyte replenishment and not local division. Although PLX5622 depleted CNS infiltrating patrolling monocytes, these cells did not accumulate in the fungal-infected CNS following pulmonary infection. In addition, Nr4a1-deficient mice, which lack patrolling monocytes, had similar control and dissemination ofC. neoformansinfection to wild-type controls. Our data demonstrate that PLX5622 may have a beneficial effect in the control of intracellular replicating pathogenic fungi that utilise CSF1R-dependent myeloid cells as infection reservoirs.
Compensation and conversation in autism: atypical connectivity supports typical behavior
Authors: Jasmin Kyle , Martin Alex , Gotts Stephen J. 
Published: November 2022

AbstractBackgroundIt is well-established that individuals with autism show atypical functional brain connectivity. However, the role this plays in behavior, especially in naturalistic social settings, has remained unclear. Some atypical patterns may reflect core deficits, while others may instead compensate for deficits and promote adaptive behavior. Distinguishing these possibilities requires measuring the ‘typicality’ of spontaneous behavior and determining which connectivity patterns correlate with it.MethodsThirty-nine male participants (19 autism, 20 typically-developed) engaged in 115 spontaneous conversations with an experimenter during fMRI scanning (Jasmin, et al., 2019, Brain). A classifier algorithm was trained to distinguish participants by diagnosis based on 81 semantic, affective and linguistic dimensions derived from their use of language. The algorithm’s certainty that a participant was in either the autism or typical group was used as a measure of task performance and compared with functional connectivity levels.ResultsThe algorithm accurately classified participants (74%,P= .002), and its scores correlated with clinician-observed autism signs (ADOS) (rs= .56,P= .03). In support of a compensatory role, greater functional connectivity, most prominently between left-hemisphere social communication regions and right inferior frontal cortex, correlated with more typical language behaviour, only for the autism group (rs= .56,P= .01).ConclusionWe report a simple and highly generalizable method for quantifying behavioral performance and neural compensation during complex spontaneous social behavior, without the need for ana prioribenchmark. The findings suggest that functional connectivity increases in autism during communication reflect a neural compensation strategy.
Defense systems are pervasive across chromosomally integrated mobile genetic elements and are inversely correlated to virulence and antimicrobial resistance
Authors: Botelho João 
Published: November 2022

AbstractMobile genetic elements (MGEs) are key promoters of microbial evolution. These elements can be located extrachromosomally or integrated into the chromosome. Well-known examples of chromosomally integrated MGEs (ciMGEs) are integrative and conjugative/mobilizable elements (ICEs and IMEs), and most studies to date have focused on the biological mechanisms that shape their lifestyle. It is crucial to profile the diversity and understand their distribution across the microbial community, as the number of genome sequences increases exponentially. Herein, I scanned a collection of more than 20000 bacterial and archaeal non-redundant genomes and found over 13000 ciMGEs across multiple phyla, representing a massive increase in the number of ciMGEs available in public databases (<1000). Although ICEs are the most important ciMGEs for the accretion of defense systems, virulence, and antimicrobial resistance (AMR) genes, IMEs outnumbered ICEs. Moreover, defense systems, AMR, and virulence genes were negatively correlated in both ICEs and IMEs. Multiple ciMGEs form heterogeneous communities and challenge inter-phylum barriers. Finally, I observed that the functional landscape of ICEs was populated by uncharacterized proteins. Altogether, this study provides a comprehensive catalog of nucleotide sequences and associated metadata for ciMGEs from 34 phyla across the bacterial and archaeal domains.
Geometry of population activity in spiking networks with low-rank structure
Authors: Cimesa Ljubica , Ciric Lazar , Ostojic Srdjan 
Published: November 2022

AbstractRecurrent network models are instrumental in investigating how behaviorally-relevant computations emerge from collective neural dynamics. A recently developed class of models based on low-rank connectivity provides an analytically tractable framework for understanding of how connectivity structure determines the geometry of low-dimensional dynamics and the ensuing computations. Such models however lack some fundamental biological constraints, and in particular represent individual neurons in terms of abstract units that communicate through continuous firing rates rather than discrete action potentials. Here we examine how far the theoretical insights obtained from low-rank rate networks transfer to more biologically plausible networks of spiking neurons. Adding a low-rank structure on top of random excitatory-inhibitory connectivity, we systematically compare the geometry of activity in networks of integrate-and-fire neurons to rate networks with statistically equivalent low-rank connectivity. We show that the mean-field predictions of rate networks allow us to identify low-dimensional dynamics at constant population-average activity in spiking networks, as well as novel non-linear regimes of activity such as out-of-phase oscillations and slow manifolds. We finally exploit these results to directly build spiking networks that perform nonlinear computations.Author summaryBehaviorally relevant information processing is believed to emerge from interactions among neurons forming networks in the brain, and computational modeling is an important approach for understanding this process. Models of neuronal networks have been developed at different levels of detail, with typically a trade off between analytic tractability and biological realism. The relation between network connectivity, dynamics and computations is best understood in abstract models where individual neurons are represented as simplified units with continuous firing activity. Here we examine how far the results obtained in a specific, analytically-tractable class of rate models extend to more biologically realistic spiking networks where neurons interact through discrete action potentials. Our results show that abstract rate models provide accurate predictions for the collective dynamics and the resulting computations in more biologically faithful spiking networks.