bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural insights into the orthosteric inhibition of P2X receptors by non-ATP-analog antagonists
Authors: Sheng Danqi , Yue Chenxi , Jin Fei , Wang Yao , Ichikawa Muneyoshi , Yu Ye , Guo Chang-Run , Hattori Motoyuki
Published: September 2023

P2X receptors are extracellular ATP-gated ion channels that form homo-or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery.

Here, we determined the cryo-EM structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5’-phosphate derivatives, PPNDS and PPADS, at 3.3 and 3.6 Å resolution, respectively, and performed structure-based mutational analysis by patch-clamp recording as well as MD simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo-and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes. Overall, our work provides structural insights into the orthosteric inhibition and subtype specificity of P2X receptors by the classical P2X antagonists, pyridoxal-5’-phosphate derivatives, thereby facilitating the rational design of novel competitive antagonists for P2X receptors.
Unsupervised Alignment in Neuroscience: Introducing a Toolbox for Gromov-Wasserstein Optimal Transport
Authors: Sasaki Masaru , Takeda Ken , Abe Kota , Oizumi Masafumi
Published: September 2023

Background

Understanding how sensory stimuli are represented across different brains, species, and artificial neural networks is a critical topic in neuroscience. Traditional methods for comparing these representations typically rely on supervised alignment, which assumes direct correspondence between stimuli representations across brains or models. However, it has limitations when this assumption is not valid, or when validating the assumption itself is the goal of the research.

New method

To address the limitations of supervised alignment, we propose an unsupervised alignment method based on Gromov-Wasserstein optimal transport (GWOT). GWOT optimally identifies correspondences between representations by leveraging internal relationships without external labels, revealing intricate structural correspondences such as one-to-one, group-to-group, and shifted mappings.

Results

We provide a comprehensive methodological guide and introduce a toolbox called GWTune for using GWOT in neuroscience. Our results show that GWOT can reveal detailed structural distinctions that supervised methods may overlook. We also demonstrate successful unsupervised alignment in key data domains, including behavioral data, neural activity recordings, and artificial neural network models, demonstrating its flexibility and broad applicability.

Comparison with existing methods

Unlike traditional supervised alignment methods such as Representational Similarity Analysis, which assume direct correspondence between stimuli, GWOT provides a nuanced approach that can handle different types of structural correspondence, including fine-grained and coarse correspondences. Our method would provide richer insights into the similarity or difference of representations by revealing finer structural differences.

Conclusion

We anticipate that our work will significantly broaden the accessibility and application of unsupervised alignment in neuroscience, offering novel perspectives on complex representational structures. By providing a user-friendly toolbox and a detailed tutorial, we aim to facilitate the adoption of unsupervised alignment techniques, enabling researchers to achieve a deeper understanding of cross-brain and cross-species representation analysis.
Insights into Biomarker Correlations in Relation to Stress: A Preliminary Analysis
Authors: Lundström Annika , Mandalios Caterina
Published: September 2023

The objective of this study was to analyze specific biomarkers of interest and find correlations between them using hormonal and cardiovascular measurements. The aim was to explore these physiological patterns during a typical weekday. While this research provides valuable insights into physiological patterns and their potential impact on mental performance, it’s essential to note that the study did not aim to diagnose, treat, or propose specific medical interventions based on the findings. Instead, the focus was solely on observational data collection and analysis for the purpose of exploring correlations and understanding daily physiological fluctuations in the context of stress and cognitive performance. Furthermore, the team observed how a low-level stress-triggered cognitive task could alter, and possibly impair, mental performance due to fluctuations in these selected data points. Five (5) adult, healthy participants (aged between 20 and 35 years) volunteered for the small-scaled study (two male and three female).

In the current study, participants with larger hormonal and cardiovascular fluctuations during a 5-minute stress-induced task did not achieve as well as those with more stable physiological measurements. Interestingly, a significant peak in cortisol levels was detected during the mental task, likely due to the stress-induced environment.

The current, and vastly limited methods used for at-home, hormonal measurements, as well as the slightly unreliable sensor technology used in general pulse oximeters measuring blood oxygen saturation in this trial, indicate the great need to develop new solutions. This includes innovations that would make health monitoring more convenient, while at the same time emphasizing improved mental well-being in daily situations, all without having to continuously wear a gadget to obtain precise insights about multiple health metrics.
An optogenetic method for the controlled release of single molecules
Authors: Kashyap Purba , Bertelli Sara , Cao Fakun , Kostritskaia Yulia , Blank Fenja , Srikanth Niranjan , Saleppico Roberto , Bierhuizen Dolf , Lu Xiaocen , Nickel Walter , Campbell Robert E. , Plested Andrew , Stauber Tobias , Taylor Marcus J. , Ewers Helge
Published: September 2023

We developed a system for optogenetic release of single molecules in live cells. We confined soluble and transmembrane proteins to the Golgi apparatus via a photocleavable protein and released them by short pulses of light. Our method allows for the controlled delivery of functional proteins to cytosol and plasma membrane in amounts compatible with single molecule imaging, greatly simplifying access to single molecule microscopy of any protein in live cells. Furthermore, we could reconstitute cellular functions such as ion conductance by delivering BK and VRAC ion channels to the plasma membrane. Finally, we could induce NF-kB signaling in T-Lymphoblasts stimulated by IL-1 by controlled release of a signaling protein that had been knocked-out in the same cells. We observed light induced formation of functional inflammatory signaling complexes that could trigger IKK phosphorylation in single cells. We thus developed an optogenetic method for the reconstitution and investigation of cellular function at the single molecule level.
A Neural Speech Decoding Framework Leveraging Deep Learning and Speech Synthesis
Authors: Chen Xupeng , Wang Ran , Khalilian-Gourtani Amirhossein , Yu Leyao , Dugan Patricia , Friedman Daniel , Doyle Werner , Devinsky Orrin , Wang Yao , Flinker Adeen
Published: September 2023

Decoding human speech from neural signals is essential for brain-computer interface (BCI) technologies restoring speech function in populations with neurological deficits. However, it remains a highly challenging task, compounded by the scarce availability of neural signals with corresponding speech, data complexity, and high dimensionality, and the limited publicly available source code. Here, we present a novel deep learning-based neural speech decoding framework that includes an ECoG Decoder that translates electrocorticographic (ECoG) signals from the cortex into interpretable speech parameters and a novel differentiable Speech Synthesizer that maps speech parameters to spectrograms. We develop a companion audio-to-audio auto-encoder consisting of a Speech Encoder and the same Speech Synthesizer to generate reference speech parameters to facilitate the ECoG Decoder training. This framework generates natural-sounding speech and is highly reproducible across a cohort of 48 participants. Among three neural network architectures for the ECoG Decoder, the 3D ResNet model has the best decoding performance (PCC=0.804) in predicting the original speech spectrogram, closely followed by the SWIN model (PCC=0.796). Our experimental results show that our models can decode speech with high correlation even when limited to only causal operations, which is necessary for adoption by real-time neural prostheses. We successfully decode speech in participants with either left or right hemisphere coverage, which could lead to speech prostheses in patients with speech deficits resulting from left hemisphere damage. Further, we use an occlusion analysis to identify cortical regions contributing to speech decoding across our models. Finally, we provide open-source code for our two-stage training pipeline along with associated preprocessing and visualization tools to enable reproducible research and drive research across the speech science and prostheses communities.
Long-term three-dimensional high-resolution imaging of live unlabeled small intestinal organoids using low-coherence holotomography
Authors: Lee Mahn Jae , Lee Jaehyeok , Ha Jeongmin , Kim Geon , Kim Hye-Jin , Lee Sumin , Koo Bon-Kyoung , Park YongKeun
Published: September 2023

The prevailing challenges in live unlabeled high-resolution imaging of native organoids stem from technical issues like complex sample handling and optical scattering in three-dimensional architectures. In this study, we introduce low-coherence holotomography as an advanced, label-free, quantitative imaging modality, designed to overcome related technical obstacles for long-term live imaging of 3D organoids. We successfully captured high-resolution morphological intricacies and dynamic events within mouse small intestinal organoids at a subcellular resolution. Furthermore, this method provides a unique advantage in differentiating between viable and non-viable organoids, thereby expanding its potential applications in organoid-based research.
U6 snRNA m6A modification is required for accurate and efficient cis- and trans-splicing ofC. elegansmRNAs
Authors: Shen Aykut , Hencel Katarzyna , Parker Matthew T. , Scott Robyn , Skukan Roberta , Adesina Aduragbemi S. , Metheringham Carey L. , Miska Eric A. , Nam Yunsun , Haerty Wilfried , Simpson Gordon G. , Akay Alper
Published: September 2023

pre-mRNA splicing is a critical feature of eukaryotic gene expression. Many eukaryotes use cis-splicing to remove intronic sequences from pre-mRNAs. In addition to cis-splicing, many organisms use trans-splicing to replace the 5′ ends of mRNAs with a non-coding spliced-leader RNA. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that m6A modification of U6 snRNA A43 by the RNA methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing ofC. eleganspre-mRNAs. The absence of U6 snRNA m6A modification primarily leads to alternative splicing at 5′ splice sites. Furthermore, weaker 5′ splice site recognition by the unmodified U6 snRNA A43 affects splicing at 3′ splice sites. U6 snRNA m6A43 and the splicing factor SNRNP27K function to recognise an overlapping set of 5′ splice sites with an adenosine at +4 position. Finally, we show that U6 snRNA m6A43 is required for efficient SL trans-splicing at weak 3′ trans-splice sites. We conclude that the U6 snRNA m6A modification is important for accurate and efficient cis- and trans-splicing inC. elegans.
MERRA-based trend analysis identifies complex, multidecadal patterns of changing climatic suitability for Cassin’s Sparrow (Peucaea cassinii)
Authors: Schnase John L. , Carroll Mark L. , Montesano Paul M. , Seamster Virginia A.
Published: September 2023

Cassin’s Sparrow (Peucaea cassinii) is a grassland resident of the American Southwest. Despite decades of study, there remains uncertainty regarding the conservation status of the species. The species’ past response to a changing climate may help explain this uncertainty, especially if patterns vary across the species’ range. In this study, we combine data from NASA’s Modern-Era Reanalysis for Research and Applications, Version 2 (MERRA-2; M2) with field observations spanning the past 40 years to examine historical changes in climatic suitability for Cassin’s Sparrow across its full annual range within the continental United States. We examine two time- and variable-specific time series using MaxEnt. The M2 times series uses a mix of 30 microclimatic variables and ecosystem functional attributes related to energy and water fluxes for predictors; the MERRAclim (MC) time series uses 19 MERRA-2-derived bioclimatic variables for predictors. Trend analysis reveals complex patterns of slowly increasing climatic suitability over 69.5% of the study area in the MC time series accompanied by decreases over 24.4% of the area. Shifts in the study area-wide, weighted centroid for climatic suitability show a northwesterly, 40-year displacement of 1.85 km/yr. The M2 time series points to a less favorable history with increasing and decreasing trends over 54.9% and 40.1% of the study area, respectively, and a westerly weighted centroid shift of 2.60 km/yr. A clear subset of seven M2 and MC variables emerged as the most important determinants of suitability over the past 40 years. These variables also demonstrated complex patterns of non-constant trends across the study area. Suitability trends in both time series appear to have little in common with current, state-level, abundance-derived conservation status assessments. Increasing winds, drying land surface conditions, and variability in North American Monsoon rainfall appear to be dominating, climate-related influences on the species. We thus see complex patterns of historical change in climatic suitability depending on whether time series models are driven by bioclimatic variables alone or by variables more aligned with ecological function. This leads us to conclude that modeled estimates of climatic suitability for Cassin’s Sparrow can vary widely depending on the temporal frame, spatial extent, and environmental drivers considered, and that this variability mirrors the uncertainty in the literature regarding the species’ conservation status. Furthermore, these factors should be taken into account in future conservation assessments for the species, and retrospective ecological niche modeling, as applied here, offers a promising approach to addressing these issues.
Biological motion perception in the theoretical framework of perceptual decision-making: An event-related potential study
Authors: Oğuz Osman Çağrı , Aydın Berfin , Urgen Burcu A.
Published: September 2023

Biological motion perception plays a critical role in various decisions in daily life for humans. Failure to decide accordingly in such a perceptual task could have life-threatening consequences. Neurophysiological studies on non-human primates and computational modeling studies suggest two processes that mediate perceptual decision-making. One of these signals is associated with the accumulation of sensory evidence and the other with response selection. Recent EEG studies with human participants have introduced an event-related potential called Centroparietal Positive Potential (CPP) as a neural marker aligned with the sensory evidence accumulation while effectively distinguishing it from motor-related event-related potential, namely lateralized readiness potential (LRP). The present study aims to investigate the neural mechanisms of biological motion perception in the theoretical framework of perceptual decision-making, which has been overlooked before. More specifically, we examine whether CPP would track the coherence of the biological motion stimuli and could be distinguished from the LRP signal. We recorded EEG from human participants while they were engaged in a direction discrimination task of a point-light walker whose coherence was manipulated by embedding it in various levels of noise. Our behavioral findings revealed shorter reaction times and reduced miss rates as the coherence of the target stimuli increased. In addition, CPP tracked the coherence of the biological motion stimuli with a tendency to reach a common level during the response, albeit with a later onset than the previously reported results in random-dot motion paradigms. Furthermore, CPP was distinguished from the LRP signal based on its temporal profile. Overall, our results suggest that the mechanisms underlying perceptual decision-making generalize to more complex and socially significant stimuli like biological motion. We discuss the implications of these findings for advancing computational models of biological motion perception and perceptual decision-making.
Regularized partial correlation provides reliable functional connectivity estimates while correcting for widespread confounding
Authors: Peterson Kirsten L. , Sanchez-Romero Ruben , Mill Ravi D. , Cole Michael W.
Published: September 2023

Functional connectivity (FC) has been invaluable for understanding the brain’s communication network, with strong potential for enhanced FC approaches to yield additional insights. Unlike with the fMRI field-standard method of pairwise correlation, theory suggests that partial correlation can estimate FC without confounded and indirect connections. However, partial correlation FC can also display low repeat reliability, impairing the accuracy of individual estimates. We hypothesized that reliability would be increased by adding regularization, which can reduce overfitting to noise in regression-based approaches like partial correlation. We therefore tested several regularized alternatives – graphical lasso, graphical ridge, and principal component regression – against unregularized partial and pairwise correlation, applying them to empirical resting-state fMRI and simulated data. As hypothesized, regularization vastly improved reliability, quantified using between-session similarity and intraclass correlation. This enhanced reliability then granted substantially more accurate individual FC estimates when validated against structural connectivity (empirical data) and ground truth networks (simulations). Graphical lasso showed especially high accuracy among regularized approaches, seemingly by maintaining more valid underlying network structures. We additionally found graphical lasso to be robust to noise levels, data quantity, and subject motion – common fMRI error sources. Lastly, we demonstrated that resting-state graphical lasso FC can effectively predict fMRI task activations and individual differences in behavior, further establishing its reliability, external validity, and ability to characterize task-related functionality. We recommend graphical lasso or similar regularized methods for calculating FC, as they can yield more valid estimates of unconfounded connectivity than field-standard pairwise correlation, while overcoming the poor reliability of unregularized partial correlation.
SECRET AGENT O-GlcNAcylates hundreds of proteins involved in diverse cellular processes in Arabidopsis
Authors: Shrestha Ruben , Karunadasa Sumudu , Grismer Tara , Reyes Andres , Xu Shou-Ling
Published: September 2023

O-GlcNAcylation is a critical post-translational modification of proteins observed in both plants and animals and plays a key role in growth and development. While considerable knowledge exists about over 3000 substrates in animals, our understanding of this modification in plants remains limited. Unlike animals, plants possess two putative homologs: SECRET AGENT (SEC) and SPINDLY (SPY), with SPY also exhibiting O-fucosylation activity. To investigate SEC’s role as a major O-GlcNAc transferase in plants, we utilized LWAC enrichment and SILIA labeling, quantifying at both MS1 and MS2 levels. Our findings reveal a significant reduction in O-GlcNAc levels in thesecmutant, indicating SEC’s critical role in mediating O-GlcNAcylation. Through a comprehensive approach, combining HCD and EThcD fragmentation with substantial fractionations, we expanded our GlcNAc profiling, identifying 436 O-GlcNAc targets, including 227 new targets. The targets span diverse cellular processes, suggesting broad regulatory functions of O-GlcNAcylation. The expanded targets also enabled exploration of crosstalk between O-GlcNAcylation and O-fucosylation. We also examined EThcD fragmentation for site assignment. This report advances our understanding of O-GlcNAcylation in plants, facilitating further research in this field.
A modular circuit architecture coordinates the diversification of courtship strategies inDrosophila
Authors: Coleman Rory T. , Morantte Ianessa , Koreman Gabriel T. , Cheng Megan L. , Ding Yun , Ruta Vanessa
Published: September 2023

Identifying a mate is a central imperative for males of most species but poses the challenge of distinguishing a suitable partner from an array of potential male competitors or females of related species. Mate recognition systems are thus subject to strong selective pressures, driving the rapid coevolution of female sensory cues and male sensory preferences. Here we leverage the rapid evolution of female pheromones across theDrosophilagenus to gain insight into how males coordinately adapt their detection and interpretation of these chemical cues to hone their mating strategies. While in someDrosophilaspecies females produce unique pheromones that act to attract and arouse their conspecific males, the pheromones of most species are sexually monomorphic such that females possess no distinguishing chemosensory signatures that males can use for mate recognition. By comparing several close and distantly-relatedDrosophilaspecies, we reveal thatD. yakubamales have evolved the distinct ability to use a sexually-monomorphic pheromone, 7-tricosene (7-T), as an excitatory cue to promote courtship, a sensory innovation that enablesD. yakubamales to court in the dark thereby expanding their reproductive opportunities. To gain insight into the neural adaptations that enable 7-T to act as an excitatory cue, we compared the functional properties of two key nodes within the pheromone circuits ofD. yakubaand a subset of its closest relatives. We show that the instructive role of 7-T inD. yakubaarises from concurrent peripheral and central circuit changes: a distinct subpopulation of sensory neurons has acquired sensitivity to 7-T which in turn selectively signals to a distinct subset of P1 neurons in the central brain that trigger courtship behaviors. Such a modular circuit organization, in which different sensory inputs can independently couple to multiple parallel courtship control nodes, may facilitate the evolution of mate recognition systems by allowing males to take advantage of novel sensory modalities to become aroused. Together, our findings suggest how peripheral and central circuit adaptations can be flexibly linked to underlie the rapid evolution of mate recognition and courtship strategies across species.
Multiplexed CRISPR gene editing in primary human islet cells with Cas9 ribonucleoprotein
Authors: Bevacqua Romina J. , Zhao Weichen , Merheb Emilio , Kim Seung Hyun , Marson Alexander , Gloyn Anna L. , Kim Seung K.
Published: September 2023

Successful genome editing in primary human islets could reveal features of the genetic regulatory landscape underlying β cell function and diabetes risk. Here, we describe a CRISPR-based strategy to interrogate functions of predicted regulatory DNA elements using electroporation of a complex of Cas9 ribonucleoprotein (Cas9 RNP) and guide RNAs into primary human islet cells. We successfully targeted coding regions including thePDX1exon 1, and non-coding DNA linked to diabetes susceptibility. CRISPR/Cas9 RNP approaches revealed genetic targets of regulation by DNA elements containing candidate diabetes risk SNPs, including anin vivoenhancer of theMPHOSPH9gene. CRISPR/Cas9 RNP multiplexed targeting of twocis-regulatory elements linked to diabetes risk inPCSK1, which encodes an endoprotease crucial for insulin processing, also demonstrated efficient simultaneous editing ofPCSK1regulatory elements, resulting in impaired β cellPCSK1regulation and insulin secretion. Multiplex CRISPR/Cas9 RNP provides powerful approaches to investigate and elucidate human islet cell gene regulation in health and diabetes.
Using theE. coliAlleleome in Strain Design
Authors: Phaneuf Patrick , Jarczynska Zofia D. , Kandasamy Vijayalakshmi , Chauhan Siddharth , Feist AM , Palsson Bernhard O.
Published: September 2023

Leveraging observed variants in strain design is a promising technique for creating strains with specific properties. Adaptive laboratory evolution (ALE) experiments generate variants that enhance fitness under specific conditions and can contribute to application-specific strain designs. Further, the wild-type (WT) coding alleleome of an organism, the complete set of its genes’ WT alleles, can provide an additional amount and diversity of variants not yet accessible from the aggregation of ALE experiment results. This study used both an ALE mutation database (3093 genomes) and a large set of WT genomes (12,661 genomes) to explore the sequence solution space of genes involved in tolerance to 10 conditions of industrial importance. To accomplish this, ALE variants for 22 genes previously identified as potentially important for industrial chemical tolerance were collected and supplemented with all available variants from the WT coding alleleome. A total of 4879 variants were reintroduced and used in 10 selection experiments. Both ALE and WT contributed highly enriched variants, where the enrichment and benefits depended on the conditions, genes, and gene product regions. The results also revealed that variants not originating from the initial experiment could potentially confer substantially greater benefits. Additionally, ALE and WT variants rarely overlapped on AA positions, but their clustering did coincide with where highly enriched variants were ultimately located. For genes primarily hosting potential gain-of-function variations, substitutions predicted to have a conservative impact frequently outperformed more radical substitutions. Case studies demonstrated that maximizing the amount of variants enabled easier identification of variant trends, which in turn can be used to better understand areas and characteristics of genes that can be feasibly varied, representing what could be thought of as a genome design variable. The combination of ALE and WT variants is a promising approach for use in future projects to better constrain and ultimately achieve practical coverage in the exploration of feasible sequence solution space.

Visual Abstract
Young Eurasian Scops Owls produce individually distinctive vocalizations
Authors: Grieco Fabrizio
Published: September 2023

Vocal distinctiveness is expected to occur more often in colonial-breeding species as the parents need to recognize their offspring in a large group of conspecifics. In this study, I examined the food-begging calls of the young of a territorial nocturnal raptor, the Scops Owl, shortly before and after fledging. The calls showed complex spectral structure not described in previous studies. I found a high degree of repeatability in many acoustic features, particularly call duration, spectral centre of gravity, and spectral skewness. Discriminant analysis assigned 52.7% of the calls to the correct individual, and 69.1% when restricting analysis within broods. The calculated information capacity HSwas 4.69 bits. Differences in acoustic features between siblings appeared before fledging and could be detected over up to ten days despite temporal variation. The results suggest that the vocalizations of young Scops Owls could potentially act as identity signals. However, the functional significance of acoustic signatures remains unclear. A few hypotheses are discussed. Call distinctiveness could simply reflect the development of vocal individuality typical of the adults; it could help parents recognize their offspring preventing misdirected parental care when breeding density is high; it could mediate preferential feeding; or it could be used by siblings communicating between each other. Further studies are needed to determine whether parents and offspring assess identity signals in vocalizations.
Description of a new genus of thePectobacteriaceaefamily isolated from lake water in France;Prodigiosinella aquatilisgen. nov. sp. nov. includes two subspeciesProdigiosinella aquatilissubsp.aquatilisssp. nov. andProdigiosinella aquatilissubsp.natabilisssp. nov
Authors: Hugouvieux-Cotte-Pattat Nicole , Flandrois Jean-Pierre , Briolay Jérôme , Reverchon Sylvie , Brochier-Armanet Céline
Published: September 2023

ThePectobacteriaceaefamily comprises plant pathogens able to provoke diverse diseases, including plant maceration due to the production of pectinases disrupting the plant cell wall. To better understand their natural diversity, a survey of pectinolytic bacteria was performed in lakes of the French region La Camargue near the Mediterranean Sea. Sixteen atypical pectinolytic isolates were obtained from brackish water of three lakes. The genome of six isolates was sequenced; their size is around 4.8 to 5.0 Mb, including a plasmid of 59 to 61 kb; their G+C values range from 49.1 to 49.3 mol%. Phylogenetic analyses indicated that the novel strains formed a new clade ofPectobacteriaceae, separate from previously described genera of this family. These analyses suggested also thatAcerihabitansdoes not belong toPectobacteriaceaeand should be reclassified in theBruguierivoracaceaefamily, whileSymbiopectobacteriumcould be a truePectobacteriaceaemember. Based on phenotypic, genomic and phylogenetic characteristics, we propose the creation of a new genus with the nameProdigiosinellagen. nov. Both the phenotypic and phylogenetic analyses separated the strains into two distinct subgroups. However, the DNA–DNA relatedness values revealed a close relationship between the two groups, supporting their appurtenance to the same species. Thus, it is proposed to classify them as two subspecies ofProdigiosinella aquatilissp. nov., for which we propose the nameProdigiosinella aquatilissubsp.aquatilisssp. nov. (LS101T= CFBP 8826T= LMG 32072T) andProdigiosinella aquatilissubsp.natabilisssp. nov. (CE70T= CFBP 9054T= LMG 32867T).
Corticotropin releasing factor alters the functional diversity of accumbal cholinergic interneurons
Authors: Ingebretson Anna E. , Alonso-Caraballo Yanaira , Razidlo John A. , Lemos Julia C.
Published: September 2023

Cholinergic interneurons (ChIs) provide the main source of acetylcholine in the striatum and have emerged as a critical modulator of behavioral flexibility, motivation, and associative learning. In the dorsal striatum, ChIs display heterogeneous firing patterns. Here, we investigated the spontaneous firing patterns of ChIs in the nucleus accumbens (NAc) shell, a region of the ventral striatum. We identified four distinct ChI firing signatures: regular single-spiking, irregular single-spiking, rhythmic bursting, and a mixed-mode pattern composed of bursting activity and regular single spiking. ChIs from females had lower firing rates compared to males and had both a higher proportion of mixed-mode firing patterns and a lower proportion of regular single-spiking neurons compared to males. We further observed that across the estrous cycle, the diestrus phase was characterized by higher proportions of irregular ChI firing patterns compared to other phases. Using pooled data from males and females, we examined how the stress-associated neuropeptide corticotropin releasing factor (CRF) impacts these firing patterns. ChI firing patterns showed differential sensitivity to CRF. This translated into differential ChI sensitivity to CRF across the estrous cycle. Furthermore, CRF shifted the proportion of ChI firing patterns toward more regular spiking activity over bursting patterns. Finally, we found that repeated stressor exposure altered ChI firing patterns and sensitivity to CRF in the NAc core, but not the NAc shell. These findings highlight the heterogeneous nature of ChI firing patterns, which may have implications for accumbal-dependent motivated behaviors.

New and Noteworthy

ChIs within the dorsal and ventral striatum can exert a huge influence on network output and motivated behaviors. However, the firing patterns and neuromodulation of ChIs within the ventral striatum, specifically the NAc shell, are understudied. Here we report that NAc shell ChIs have heterogenous ChI firing patterns that are labile and can be modulated by the stress-linked neuropeptide CRF and by the estrous cycle.
Neurological Imprints of Boys’ Love Culture: Shaping Sexual Orientation Identity in the Digital Age’s Young females
Authors: Ao Na , Jiang Xiaowei , Chen Yanan , Chen Yingying , Niu Huihui , Hu Shuoyan
Published: September 2023

With the omnipresence of social media, Boys’ Love (BL) culture has found a burgeoning audience among young females. While this cultural phenomenon offers a platform for self-expression to some, its potential implications remain underexplored. This study investigates whether immersion in BL culture impacts the process of young females forming self-recognition and identification of sexual orientation. Employing an fNIRS-based experiment focusing on the prefrontal cortex, we compared the neurological responses of young females within and outside the BL media cocoon when exposed to sexuality-related stimuli. Our findings revealed significant neural differences in the experimental group viewing BL images compared to the control group. These results provide fresh insights into how BL content may shape our cognition and attitudes, emphasizing the need for guidance in content consumption among young females.
Simple ways to avoid collecting highly137Cs-contaminatedAralia elatabuds
Authors: Sakai Masaru , Watanabe Mirai , Koshikawa Masami Kanao , Tanaka Asuka , Takahashi Akiko , Takechi Seiichi , Takagi Mai , Tsuji Takashi , Tsuji Hideki , Takeda Toshimasa , Jo Jaeick , Tamaoki Masanori , Hayashi Seiji
Published: September 2023

Collection and cooking of wild vegetables have provided seasonal enjoyments for Japanese local people as provisioning and cultural ecosystem services. However, the Fukushima Daiichi Nuclear Power Plant accident in March 2011 caused extensive radiocesium contamination of wild vegetables. Restrictions on commercial shipments of wild vegetables have been in place for the last 10 years. Some species, including buds ofAralia elata, are currently showing radiocesium concentrations both above and below the Japanese reference level for food (100 Bq/kg), suggesting that there are factors decreasing and increasing the137Cs concentration. Here, we evaluated easy-to-measure environmental variables (dose rate at the soil surface, organic soil layer thickness, slope steepness, and presence/absence of decontamination practices) and the137Cs concentrations of 40A. elatabuds at 38 locations in Fukushima Prefecture to provide helpful information on avoiding collecting highly contaminated buds. The137Cs concentrations inA. elatabuds increased significantly with increases in the dose rate at the soil surface. Meanwhile, the137Cs concentration inA. elatabuds were not reduced by decontamination practices. These findings suggest that measuring the latest dose rate at the soil surface at the base ofA. elataplants is a helpful way to avoid collecting buds with higher137Cs concentrations and aid in the management of species in polluted regions.
Gaze-contingent processing improves mobility performance and visual orientation in simulated head-steered prosthetic vision
Authors: de Ruyter van Steveninck Jaap , Nipshagen Mo , van Gerven Marcel , Güçlü Umut , Güçlüturk Yağmur , van Wezel Richard
Published: September 2023

The enabling technology of visual prosthetics for the blind is making rapid progress. However, there are still uncertainties regarding the functional outcomes, which can depend on many design choices in the development. In visual prostheses with a head-mounted camera, a particularly challenging question is how to deal with the gaze-locked visual percept associated with spatial updating conflicts in the brain. A recently proposed compensation strategy is gaze-contingent image processing with eyetracking, which enables natural visual scanning and reestablished spatial updating based on eye movements. The current study evaluates the benefits of gaze-contingent processing versus gaze-locked and gaze-ignored simulations in the context of mobility and orientation, using a simulated prosthetic vision paradigm with sighted subjects. Compared to gaze-locked vision, gaze-contingent processing was found to improve the speed in all experimental tasks, as well as the subjective quality of vision. Similar or further improvements were found in a control condition that ignores gaze-depended effects, a simulation that is unattainable in the clinical reality. Our results suggest that gaze-locked vision and spatial updating conflicts can be debilitating for complex visually-guided activities of daily living such as mobility and orientation. Therefore, for prospective users of head-steered prostheses with an unimpaired oculomotor system, the inclusion of a compensatory eye-tracking system is strongly endorsed.
The discovery of an evolutionarily conserved enhancer within the MYEOV locus suggests an unexpected role for this non-coding region in cancer
Authors: Davidson Brigid SA , Arcila-Galvis Juliana Estefania , Trevisan-Herraz Marco , Mikulasova Aneta , Brackley Chris A , Russell Lisa J , Rico Daniel
Published: September 2023

Themyeloma overexpressedgene (MYEOV) has been proposed to be a proto-oncogene due to high RNA transcript levels found in multiple cancers, including myeloma, breast, lung, pancreas and esophageal cancer. The presence of an open reading frame (ORF) in humans and other primates suggests protein-coding potential. Yet, we still lack evidence of a functional MYEOV protein. It remains undetermined howMYEOVoverexpression affects cancerous tissues. In this work, we show thatMYEOVhas originated and may still function as an enhancer, possibly regulatingCCND1. Firstly,MYEOV3’ end enhancer activity was confirmed in humans using publicly available ATAC-STARR-seq data, performed on B-cell-derived GM12878 cells. We detected enhancer histone marks H3K4me1 and H3K27ac overlappingMYEOVin multiple healthy human tissues, which include B cells, liver and lung tissue. The analysis of 3D genome datasets revealed chromatin interactions between theMYEOV-3’-enhancer and the proto-oncogeneCCND1. BLAST searches and multi-sequence alignments results showed that this human enhancer element is conserved from the amphibians/amniotes divergence, with a 273 bp conserved region also found in all mammals, and even in chickens, and it consistently located near the correspondingCCND1orthologues. Furthermore, we observed conservation of active enhancer state in theMYEOVorthologues of four non-human primates, dog, rat and mouse. When studying this homologous region in mice, where the ORF ofMYEOVis absent, we not only observed an enhancer chromatin state but also found interactions between the mouse enhancer homolog andCcnd1using 3D-genome interaction data. This is similar to the interaction observed in humans and, interestingly, coincides with CTCF binding sites in both species. Taken together, this suggests thatMYEOVis a primate-specific gene with ade novoORF that originated at an evolutionarily older enhancer region. This deeply conserved enhancer element is possibly regulatingCCND1in both humans and mice, opening the possibility of studyingMYEOVregulatory functions in cancer using non-primate animal models.
One-carbon metabolism nutrients impact the interplay between DNA methylation and gene expression in liver, enhancing protein synthesis in Atlantic Salmon
Authors: Saito Takaya , Espe Marit , Vikeså Vibeke , Bock Christoph , Thomsen Tårn H. , Adam Anne-Catrin , Fernandes Jorge M.O. , Skjaerven Kaja H.
Published: September 2023

Supplementation of one-carbon (1C) metabolism micronutrients, which include B-vitamins and methionine, is essential for the healthy growth and development of Atlantic salmon (Salmo salar). However, the recent shift towards non-fish meal diets in salmon aquaculture has led to the need for reassessments of recommended micronutrient levels. Despite the importance of 1C metabolism in growth performance and various cellular regulations, the molecular mechanisms affected by these dietary alterations are less understood.

To investigate the molecular effect of 1C nutrients, we analysed gene expression and DNA methylation using two types of omics data: RNA sequencing (RNA-seq) and reduced-representation bisulfite sequencing (RRBS). We collected liver samples at the end of a feeding trial that lasted 220 days through the smoltification stage, where fish were fed three different levels of four key 1C nutrients: methionine, vitamin B6, B9, and B12.

Our results indicate that the dosage of 1C nutrients significantly impacts genetic and epigenetic regulations in the liver of Atlantic salmon, particularly in biological pathways related to protein synthesis. The interplay between DNA methylation and gene expression in these pathways may play an important role in the mechanisms underlying growth performance affected by 1C metabolism.

Author Summary

Atlantic salmon rely on one-carbon (1C) metabolism micronutrients like B-vitamins and methionine, which they acquire through their diets. Small pelagic fish are the primary source in the wild, but finding sustainable alternatives such as plants, insects, and algae is challenging as salmon aquaculture expands. Adjusting nutrient levels when changing base ingredients further complicates the task. Understanding the molecular mechanisms affected by these micronutrients is crucial for aquaculture sustainability.

In this study, we investigated the molecular effects of 1C metabolism micronutrients on Atlantic salmon. Liver samples from salmon fed varying levels of key 1C nutrients over a 220-day trial were analysed using RNA sequencing (RNA-seq) and reduced-representation bisulfite sequencing (RRBS) to assess gene expression and DNA methylation, respectively.

Our results revealed significant impacts of 1C nutrient dosage on genetic and epigenetic regulations in the salmon liver, particularly in protein synthesis pathways. The interplay between DNA methylation and gene expression in these pathways influences growth performance under 1C metabolism.

Uncovering molecular changes resulting from dietary alterations provides valuable insights to optimize nutritional requirements in salmon aquaculture, supporting sustainable production and welfare of this important species.
Neuroectoderm phenotypes in a human stem cell model of O-GlcNAc transferase intellectual disability
Authors: Murray Marta , Davidson Lindsay , Ferenbach Andrew T. , Lefeber Dirk , van Aalten Daan M. F.
Published: September 2023

Most intellectual disabilities are caused by monogenic variation. Mutations in the O-GlcNAc transferase (OGT) gene have recently been linked to a novel congenital disorder of glycosylation (OGT-CDG), involving symptoms of possible neuroectodermal origin. To test the hypothesis that pathology is linked to defects in differentiation during early embryogenesis, we developed an OGT-CDG induced pluripotent stem cell lines together with isogenic controls generated by CRISPR/Cas9 gene-editing. Although the OGT-CDG variant leads to a significant decrease in OGT and O-GlcNAcase protein levels, there were no changes in differentiation potential or stemness. However, differentiation into ectoderm resulted in significant differences in O-GlcNAc homeostasis. Further differentiation to neuronal stem cells revealed differences in morphology between patient and control lines, accompanied by disruption of the O-GlcNAc pathway. This suggests a critical role for O-GlcNAcylation in early neuroectoderm architecture, with robust compensatory mechanisms in the earliest stages of stem cell differentiation.
Transfer of cyclobutane pyrimidine dimer photolyase to chloroplasts forPoaceaesurvival under ultraviolet-B radiation
Authors: Otake Momo , Teranishi Mika , Komatsu Chiharu , Hara Mamoru , Yoshiyama Kaoru Okamoto , Hidema Jun
Published: September 2023

Cyclobutane pyrimidine dimer (CPD) photolyase (PHR), the primary enzyme for repairing the CPD induced by ultraviolet B (UV-B) radiation, is essential for plants living under sunlight. Rice CPD photolyase (OsPHR), is such a unique triple-targeting protein. The signal sequences required for its translocation to the nucleus or mitochondria are located in the C-terminal region but were yet to be identified for chloroplasts. Here, we identified sequences located in the N-terminal region, including the serine-phosphorylation site at position 7 of OsPHR, and found that OsPHR is transported/localized to chloroplasts via a vesicle transport system under the control of serine phosphorylation. However, the sequence identified in this study is only conserved in somePoaceaespecies and in many other plants, PHR does not localize to chloroplasts Therefore, we reasoned thatPoaceaespecies need the ability to repair CPD in the chloroplast genome to survive under sunlight and have acquired this new mechanism for chloroplast translocation.