bluuebunny/crossref_metadata_2025_split huggingface dataset:
Greater reliance on model-free learning in adolescent anorexia nervosa: An examination of dual-system reinforcement learning
Authors: Brown Carina S. , Devine Sean , Otto A. Ross , Bischoff-Grethe Amanda , Wierenga Christina E. 
Published: February 2024

AbstractAlterations in learning and decision-making systems are thought to contribute to core features of anorexia nervosa (AN), a psychiatric disorder characterized by persistent dietary restriction and weight loss. Instrumental learning theory identifies a dual-system of habit and goal-directed decision-making, linked to model-free and model-based reinforcement learning algorithms. Difficulty arbitrating between these systems, resulting in an over-reliance on one strategy over the other, has been implicated in compulsivity and extreme goal pursuit, both of which are observed in AN. Characterizing alterations in model-free and model-based systems, and their neural correlates, in AN may clarify mechanisms contributing to symptom heterogeneity (e.g., binge/purge symptoms). This study tested whether adolescents with restricting AN (AN-R;n= 36) and binge/purge AN (AN-BP;n= 20) differentially utilized model-based and model-free learning systems compared to a healthy control group (HC;n= 28) during a Markov two-step decision-making task under conditions of reward and punishment. Associations between model-free and model-based learning and resting-state functional connectivity between neural regions of interest, including orbitofrontal cortex (OFC), nucleus accumbens (NAcc), putamen, and sensory motor cortex (SMC) were examined. AN-R showed higher utilization of model-free learning compared to HC for reward, but attenuated model-free and model-based learning for punishment. In AN-R only, higher model-based learning was associated with stronger OFC-to-left NAcc functional connectivity, regions linked to goal-directed behavior. Greater utilization of model-free learning for reward in AN-R may differentiate this group, particularly during adolescence, and facilitate dietary restriction by prioritizing habitual control in rewarding contexts.
Organellomics: AI-driven deep organellar phenotyping reveals novel ALS mechanisms in human neurons
Authors: Krispin Sagy , van Zuiden Welmoed , Danino Yehuda M. , Molitor Lena , Rudberg Noam , Bar Chen , Coyne Alyssa , Meimoun Thea , Waldron Fergal M , Gregory Jenna M , Fisher Tal , Nachshon Aharon , Stern-Ginossar Noam , Yacovzada Nancy , Hornstein Eran 
Published: February 2024

AbstractSystematic assessment of organelle architectures, termed the organellome, offers valuable insights into cellular states and pathomechanisms, but remains largely uncharted. Here, we present a pipeline for deep phenotypic learning using vision transformers, resulting in the Neuronal Organellomics Vision Atlas (NOVA) model that studies 3 million confocal images of 25 distinct membrane-bound and membraneless organelles in human neurons. Our organellomics approach evaluates cellular phenotypes by quantifying changes in the localization and morphology of multiple organelles, and by consolidating information across organelles it yields an integrated depiction of cellular state. We reveal significant interactions between cytoplasmic mislocalized TDP-43 — a hallmark of ALS — and processing bodies (P-bodies), membraneless organelles that regulate mRNA stability, which is confirmed through patient-derived neurons and human neuropathology. Furthermore, organellomics delineates phenotypic changes in neurons carrying ALS-associated mutations and demonstrates diagnostic potential for patient-derived neurons. Together, organellomics offer a novel approach to studying the neuro-cellular biology of diseases.
The proteostasis interactomes of trafficking-deficient KV11.1 variants associated with Long QT Syndrome and pharmacological chaperone rescue
Authors: Egly Christian L. , Barny Lea , Do Tri , McDonald Eli F. , Plate Lars , Knollmann Bjorn C. 
Published: February 2024

AbstractIntroductionThe voltage gated potassium ion channel KV11.1 plays a critical role in cardiac repolarization. Genetic variants that render Kv11.1 dysfunctional cause Long QT Syndrome (LQTS), which is associated with fatal arrhythmias. Approximately 90% of LQTS-associated variants cause intracellular protein transport (trafficking) dysfunction, which can be rescued by pharmacological chaperones like E-4031. Protein folding and trafficking decisions are regulated by chaperones, protein quality control factors, and trafficking machinery, comprising the cellular proteostasis network. Here, we test whether trafficking dysfunction is associated with alterations in the proteostasis network of pathogenic Kv11.1 variants, and whether pharmacological chaperones can normalize the proteostasis network of responsive variants.MethodsWe used affinity-purification coupled with tandem mass tag-based quantitative mass spectrometry to assess protein interaction changes in human embryonic kidney (HEK293) cells expressing wild-type (WT) KV11.1 or trafficking-deficient channel variants in the presence or absence of E-4031.ResultsaWe identified 573 core KV11.1 protein interactors. Both variants KV11.1-G601S and KV11.1-G601S-G965* had significantly increased interactions with proteins responsible for folding, trafficking, and degradation compared to WT. We found that proteasomal degradation is a key component for KV11.1 degradation and that the KV11.1-G601S-G965* variant was more responsive to E-4031 treatment. This suggests a role in the C-terminal domain and the ER retention motif of KV11.1 in regulating trafficking.ConclusionOur report characterizes the proteostasis network of KV11.1, two trafficking deficient KV11.1 variants, and variants treated with a pharmacological chaperone. The identified protein interactions could be targeted therapeutically to improve KV11.1 trafficking and treat Long QT Syndrome.
Quencher-free fluorescence monitoring of G-quadruplex folding
Authors: Parada Zach , Hoog Tanner G. , Adamala Katarzyna P. , Engelhart Aaron E 
Published: February 2024

AbstractGuanine-rich sequences exhibit a high degree of polymorphism and can form single-stranded, Watson-Crick duplex, and four-stranded G-quadruplex structures. These sequences have found a wide range of uses in synthetic biology applications, arising in part from their structural plasticity. High-throughput, low-cost tools for monitoring the folding and unfolding transitions of G-rich sequences would provide an enabling technology for accelerating prototyping of synthetic biological systems and for accelerating design-build-test cycles. Here, we show that unfolding transitions of a range of G-quadruplex-forming DNA sequences can be monitored in a FRET-like format using DNA sequences that possess only a single dye label, with no quencher. These quencher-free assays can be performed at low cost, with both cost and lead times ca. 1 order of magnitude lower than FRET-labeled strands. Thus, quencher-free secondary structure monitoring promises to be a valuable tool for testing and development of synthetic biology systems employing G-quadruplexes.
Shared neural computations for syntactic and morphological structures: evidence from Mandarin Chinese
Authors: Yu Xinchi , Mancha Sebastián , Tian Xing , Lau Ellen 
Published: February 2024

AbstractAlthough psycho-/neuro-linguistics has assumed a distinction between morphological and syntactic structure building as in traditional theoretical linguistics, this distinction has been increasingly challenged by theoretical linguists in recent years. Opposing a sharp, lexicalist distinction between morphology and syntax, non-lexicalist theories propose common morpho-syntactic structure building operations that cut across the realms of “morphology” and “syntax”, which are considered distinct territories in lexicalist theories. Taking advantage of two pairs of contrasts in Mandarin Chinese with desirable linguistic properties, namely compound vs. simplex nouns (the “morphology” contrast, differing in morphological structure complexity per lexicalist theories) and separable vs. inseparable verbs (the “syntax” contrast, differing in syntactic structure complexity per lexicalist theories), we report one of the first pieces of evidence for shared neural responses for morphological and syntactic structure complexity in language comprehension, supporting a non-lexicalist view where shared neural computations are employed across morpho-syntactic structure building. Specifically, we observed that the two contrasts both modulated neural responses in left anterior and centro-parietal electrodes in an a priori 275:400 ms time window, corroborated by topographical similarity analyses. These results serve as preliminary yetprima facieevidence towards shared neural computations across morphological and syntactic structure building in language comprehension.
foxe1mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations
Authors: Raterman Sophie T , Wagener Frank A D T G , Zethof Jan , Cuijpers Vincent , Klaren Peter H M , Metz Juriaan R , Von den Hoff Johannes W. 
Published: February 2024

AbstractFOXE1 mutations in humans are associated with Bamforth-Lazarus syndrome, characterized by cleft palate and hypothyroidism. Moreover, polymorphisms of FOXE1 are implicated in non-syndromic cleft palate. Much uncertainty still exists about the function of transcription factor FOXE1 in development. To address this, we have previously developed afoxe1mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we further investigate the thyroid status and skeletal phenotype of adultfoxe1mutants. Compared to wild type controls, mutant fish have increased expression of hypothalamictshβ, and hepaticdio1anddio2. In plasma we found higher circulating Mg levels; together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales, likely due to enhanced osteoclast activity as measured by increased expression levels of the markerstracp, ctskandrankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations infoxe1mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). Taken together, this study shows that thefoxe1mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clearfoxe1-ethanol interaction.
Identification of genes involved in Kranz anatomy evolution of non-model grasses using unsupervised machine learning
Authors: Prochetto Santiago , Stegmayer Georgina , Studer Anthony J. , Reinheimer Renata 
Published: February 2024

AbstractKranz syndrome is a set of leaf anatomical and functional characteristics of species using C4photosynthesis. The current model for the evolution of C4photosynthesis from a C3ancestor proposes a series of gradual anatomical changes followed by a biochemical adaptation of the C4cycle enzymatic machinery. In this work, leaf anatomical traits from closely related C3, C4and intermediate species (Proto-Kranz, PK) were analyzed together with gene expression data to discover potential drivers for the establishment of Kranz anatomy using unsupervised machine learning. Species-specific Self-Organizing Maps (SOM) were developed to group features (genes and phenotypic traits) into clusters (neurons) according to their expression along the leaf developmental gradient. The analysis with SOM allowed us to identify candidate genes as enablers of key anatomical traits differentiation related to the area of mesophyll (M) and bundle sheath (BS) cells, vein density, and the interface between M and BS cells. At the same time, we identified a small subset of genes that displaced together with the change in the area of the BS cell along evolution suggesting a salient role in the origin of Kranz anatomy in grasses.HighlightKranz syndrome is a set of leaf anatomical and functional characteristics of species using C4photosynthesis. We discovered, with a novel machine learning methodology, some key genes for Kranz differentiation.
Cycling reduces the entropy of neuronal activity in the human adult cortex
Authors: Silva Ferré Iara Beatriz , Corso Gilberto , Santos Lima Gustavo Zampier dos , Lopes Sergio Roberto , Leocadio-Miguel Mario André , França Lucas G S , de Lima Prado Thiago , Araújo John 
Published: February 2024

AbstractElectroencephalogram (EEG) data is often analyzed from a Brain Complexity (BC) perspective, having successfully been applied to study the brain in both health and disease. In this study, we employed recurrence entropy to quantify BC associated with the neurophysiology of movement by comparing BC in both resting state and cycling movement. We measured EEG in 24 healthy adults, and placed the electrodes on occipital, parietal, temporal and frontal sites, on both the right and left sides. EEG measurements were performed for cycling and resting states and for eyes closed and open. We then computed recurrence entropy for the acquired EEG series. Our results show that open eyes show larger entropy compared to closed eyes; the entropy is also larger for resting state, compared to cycling state for all analyzed brain regions. The decrease in neuronal complexity measured by the recurrence entropy could explain the neural mechanisms involved in how the cycling movements suppress the freezing of gate in patients with Parkinson’s disease due to the constant sensory feedback caused by cycling that is associated with entropy reduction.
Mutations inHUA2restore flowering in the Arabidopsistrehalose 6-phosphate synthase1(tps1) mutant
Authors: Zeng Liping , Zacharaki Vasiliki , Wang Yanwei , Schmid Markus 
Published: February 2024

AbstractPlant growth and development are regulated by many factors, including carbohydrate availability and signaling. Trehalose 6-phosphate (T6P), which is synthesized by TREHALOSE-6-PHOSPHATE SYNTHASE 1 (TPS1), is positively correlated with and functions as a signal that informs the cell about the carbohydrate status. Mutations inTPS1negatively affect the growth and development ofArabidopsis thalianaand complete loss-of-function alleles are embryo lethal, which can be overcome using inducible expression ofTPS1(GVG::TPS1) during embryogenesis. Using EMS mutagenesis in combination with genome re-sequencing we have identified several alleles in the floral regulatorHUA2that restore flowering and embryogenesis intps1-2 GVG::TPS1. Genetic analyses using aHUA2T-DNA insertion allele,hua2-4, confirmed this finding. RNA-seq analyses demonstrated thathua2-4has widespread effects on thetps1-2 GVG::TPS1transcriptome, including key genes and pathways involved in regulating flowering. Higher order mutants combiningtps1-2 GVG::TPS1andhua2-4with alleles in the key flowering time regulatorsFLOWERING LOCUS T(FT),SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1(SOC1), andFLOWERING LOCUS C(FLC) were constructed to analyze the role ofHUA2during floral transition intps1-2in more detail. Taken together, our findings demonstrate that loss ofHUA2can restore flowering and embryogenesis intps1-2 GVG::TPS1in part through activation ofFT, with contributions of the upstream regulatorsSOC1andFLC. Interestingly, we found that mutation ofFLCis sufficient to induce flowering intps1-2 GVG::TPS1. Furthermore, we observed that mutations inHUA2modulate carbohydrate signaling and that this regulation might contribute to flowering inhua2-4 tps1-2 GVG::TPS1.
Ensemble learning and ground-truth validation of synaptic connectivity inferred from spike trains
Authors: Donner Christian , Bartram Julian , Hornauer Philipp , Kim Taehoon , Roqueiro Damian , Hierlemann Andreas , Obozinski Guillaume , Schröter Manuel 
Published: February 2024

AbstractProbing the architecture of neuronal circuits and the principles that underlie their functional organization remains an important challenge of modern neurosciences. This holds true, in particular, for the inference of neuronal connectivity from large-scale extracellular recordings. Despite the popularity of this approach and a number of elaborate methods to reconstruct networks, the degree to which synaptic connections can be reconstructed from spike-train recordings alone remains controversial. Here, we provide a framework to probe and compare connectivity inference algorithms, using a combination of synthetic and empirical ground-truth data sets, obtained from simulations and parallel single-cell patch-clamp and high-density microelectrode array (HD-MEA) recordings in vitro. We find that reconstruction performance critically depends on the regularity of the recorded spontaneous activity, i.e., their dynamical regime, the type of connectivity, and the amount of available spike train data. We find gross differences between different algorithms, and many algorithms have difficulties in detecting inhibitory connections. We therefore introduce an ensemble artificial neural network (eANN) to improve connectivity inference. We train the eANN on the validated outputs of six established inference algorithms, and show how it improves network reconstruction accuracy and robustness. Overall, the eANN was robust across different dynamical regimes, with shorter recording time, and ameliorated the identification of synaptic connections, in particular inhibitory ones. Results indicated that the eANN also improved the topological characterization of neuronal networks. The presented methodology contributes to advancing the performance of inference algorithms and facilitates our understanding of how neuronal activity relates to synaptic connectivity.Author summaryThis study introduces an ensemble artificial neural network (eANN) to infer neuronal connectivity from multi-unit spike time recordings. We compare the eANN to previous algorithms and validate it using simulations and HD-MEA/patch-clamp datasets. The latter is obtained from three single-cell patch-clamp recordings and high-density microelectrode array (HD-MEA) measurements, in parallel. Our results demonstrate that the eANN outperforms all other algorithms across different dynamical regimes and provides a more accurate description of the underlying topological organization of the studied networks. We also provide a SHAP analysis of the trained eANN to understand which input features of the eANN contribute most to this superior performance. The eANN is a promising approach to improve connectivity inference from spike-train data.
What constitutes food system resilience? The importance of divergent framings between UK mainstream and local food system actors
Authors: Black Jasmine Elizabeth , Maye Damian , Krzywoszynska Anna , Jones Stephen 
Published: February 2024

PurposeThis paper examines how key actors in the UK food system (FS) understand the role of the local food sector in relation to FS resilience.Design/methodology/approachDiscourse analysis was used to assess and compare the framings of the UK FS in 36 publications released during Covid-19 from alternative food networks (AFNs) actors and from other more mainstream FS actors, including the UK government.FindingsThe analysis shows that AFNs actors perceive the UK FS as not resilient and identify local FSs as a route towards greater resilience (“systemic” framing). In contrast, other food actors perceive the UK FS as already resilient, with the role of local food limited to specific functions within the existing system (“add-on” framing). The two groups converge on the importance of dynamic public procurement and local abattoir provision, but this convergence does not undermine the fundamental divergence in the understanding of the role of “the local” in resilient UK FSs. The local food sector’s messages appear to have gone largely unheard in mainstream policy.Research limitations/implicationsThe paper presents an analysis of public sector reports focused on the UK FS released during the Covid-19 pandemic years 2020–2021. The corpus inclusion criteria mean that publications during this period which focus on other food sector issues, such social injustices, climate change and health, were not included in the analysis, although they may have touched upon local food issues. The authors further recognise that Covid-19 had a longer lasting effect on FSs than the years 2020–2021, and that many other publications on FSs have been published since. The time span chosen targets the time at which FSs were most disrupted and therefore aims to capture emerging issues and solutions for the UK FS. The authors’ insights should be further validated through a more complete review of both public reports and academic papers covering a wider base of food-related issues and sectors as well as a broader timespan.Originality/valueA comparison of how different FS actors understand the importance of local food, especially in relation to resilience, has not been undertaken to date. The findings raise important questions about the disconnect between AFN actors and other actors in the framing of resilience. Considering the need to ensure resilience of the UK FS, this study's findings raise important insights for UK food policy about the “local food blindspot” and for food movement actors wishing to progress their vision of transformative change.
Build trust, they will come: the case of casino high rollers!
Authors: Ji Chunli , Prentice Catherine , Sthapit Erose , Lei Inman 
Published: February 2024

Purpose
Using the analogy of “If you build it, they will come” from the movie Field of Dreams, this study aims to draw on relational signaling and commitment–trust theories to examine the role of different types of trust (cognitive, affective and relational) in the relationship between relational-encounter quality and customer loyalty to service employees and to the organization in the case of an integrated casino resort. The study confirms that building it (trust), they (customers) will come to the casino exhibited in their loyalty to casino hosts and their affiliated casinos.

Design/methodology/approach
The study was conducted with very important person (VIP) customers who have a designated VIP host to provide them with personal services at an integrated casino resort in Macau. The questionnaire was distributed to the respondents by VIP hosts using WeChat and Tencent QQ.

Findings
The study shows that different types of trust (cognitive, affective and relational) play a significant mediation role in the relationship between relational-encounter quality and the customers’ loyalty to the hosts and their affiliated casinos.

Originality/value
To the best of the authors’ knowledge, this study is the first to investigate the roles of different types of trust (cognitive, affective and relational) in the relational encounter between casino hosts and VIP customers and provides insights into the link between service employees and their firm through the nurturing of the service encounter with the firm’s key accounts.