bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Primitives for Cost-Benefit Decision-Making
Authors: Rakocevic Lara I. , Davila Luis D. , Heaton Cory N. , Beck Dirk W. , Ibanez-Alcala Raquel J. , Hossain Safa B. , Reyes Neftali F. , Macias Andrea Y. , Salcido Alexis A. , Tyulmankov Danil , Batson Serina A. , Drammis Sabrina M. , Negishi Kenichiro , Vara Paulina , Giri Atanu , Gutierrez Sofia M. , Moschak Travis M. , Goosens Ki A. , Friedman Alexander 
Published: January 2025

SummaryCost-benefit decision-making is a critical process performed by all organisms, including humans. Various factors, including risk1,2, uncertainty3, age4, sex5, and neuropsychiatric disorders6, can alter decision-making. To explore cost-benefit decision-making in humans, we developed a comprehensive task and analysis framework that presents participants with a series of approach-avoid trade-offs across a variety of contexts. With this system, we found that cost-benefit decisions in humans are made using a set of computational strategies that may be used for integrating costs and rewards, which we term ‘decision-making primitives’. We further show that these decision-making primitives are used by rodents performing a similar decision-making task7. We find that utilization of these primitives in both rodents and humans shifts based on factors like hunger and sex, and that individuals use primitives differently. We additionally demonstrate that using a naturally-inspired neural network architecture generates output that overlaps with human and rodent performance over a non-constrained neural network. This novel conceptual framework, by isolating discrete ‘decision-making primitives’, has potential to help us identify how different brain regions give rise to decision-making behavior, as well as to facilitate better diagnosis of neuropsychiatric disorders and development of naturally-inspired artificial intelligence systems of decision-making.
Improvement of D-lactic acid production from methanol by metabolically engineeredKomagataella phaffiivia ultra-violet mutagenesis
Authors: Inoue Yoshifumi , Nakamura Kaito , Yamada Ryosuke , Matsumoto Takuya , Ogino Hiroyasu 
Published: January 2025

AbstractMethanol has attracted attention as an alternative carbon source to petroleum.Komagataella phaffii, a methanol-assimilating yeast, is a useful host for the chemical production from methanol. A previous study successfully constructed a metabolically engineeredK. phaffiiGS115/S8/Z3 strain capable of producing D-lactic acid from methanol. In this study, we aimed to develop a strain with improved D-lactic acid production by applying ultra-violet mutagenesis to the D-lactic acid-producing strain, GS115/S8/Z3. The resulting mutant strain DLac_Mut2_221 produced 5.38 g/L of D-lactic acid from methanol, a 1.52-fold increase compared to the parent strain GS115/S8/Z3. Transcriptome analysis revealed 167 differentially expressed genes in DLac_Mut2_221, comprising 104 upregulated and 63 downregulated genes. These results suggest that the improvement in D-lactic acid production from methanol in the mutant strain involves three important mechanisms: (1) avoiding excessive formaldehyde accumulation, (2) activating the glyoxylate pathway, and (3) reducing the expression ofO-glycosylated proteins required for cell wall stability. Metabolic engineering strategies forK. phaffiibased on the knowledge gained from this study will contribute to improving the productivity of various useful chemicals from methanol.
A simple neural circuit model explains diverse types of integration kernels in perceptual decision-making
Authors: Shen Xuewen , Li Fangting , Min Bin 
Published: January 2025

AbstractThe ability to accumulate evidence over time for deliberate decision is essential for both humans and animals. Decades of decision-making research have documented various types of integration kernels that characterize how evidence is temporally weighted. While numerous normative models have been proposed to explain these kernels, there remains a gap in circuit models that account for the complexity and heterogeneity of single neuron activities. In this study, we sought to address this gap by using low-rank neural network modeling in the context of a perceptual decision-making task. Firstly, we demonstrated that even a simple rank-one neural network model yields diverse types of integration kernels observed in human data—including primacy, recency, and non-monotonic kernels—with a performance comparable to state-of-the-art normative models such as the drift diffusion model and the divisive normalization model. Moreover, going beyond the previous normative models, this model enabled us to gain insights at two levels. At the collective level, we derived a novel explicit mechanistic expression that explains how these kernels emerge from a neural circuit. At the single neuron level, this model exhibited heterogenous single neuron response kernels, resembling the diversity observed in neurophysiological recordings. In sum, we present a simple rank-one neural circuit that reproduces diverse types of integration kernels at the collective level while simultaneously capturing complexity of single neuron responses observed experimentally.Author SummaryThis study introduces a simple rank-one neural network model that replicates diverse integration kernels—such as primacy and recency—observed in human decision-making tasks. The model performs comparably to normative models like the drift diffusion model but offers novel insights by linking neural circuit dynamics to these kernels. Additionally, it captures the heterogeneity of single neuron responses, resembling diversity observed in experimental data. This work bridges the gap between decision-making models and the complexity of neural activity, offering a new perspective on how evidence is integrated in the brain.
Use of Antibody Structural Information in Disease Prediction Models Reveals Antigen Specific B Cell Receptor Sequences in Bulk Repertoire Data
Authors: Nwogu Onyekachi , Gill Kirandeep K. , Moore Carolina , Kroner John W. , Chang Wan-Chi , Burkle Jeffrey , Stevens Mariana L. , Baatyrbek kyzy Asel , Miraldi Emily R. , Biagini Jocelyn M. , Devonshire Ashley L. , Kottyan Leah , Schwartz Justin T. , Assa’ad Amal H. , Martin Lisa J. , Andorf Sandra , Khurana Hershey Gurjit K. , Roskin Krishna M. 
Published: January 2025

AbstractConvergent antibodies are highly similar antibodies elicited in multiple individuals in response to the same antigen. Convergent antibodies provide insight into shared immunological responses and show great promise as diagnostic biomarkers. They have typically been identified using methods that consider the amino acid sequence of the third complementarity-determining region (CDR3) of immunoglobulin heavy chain (IgH). In this study, we extend the definition of convergent antibodies to use structural information about the three IgH CDR regions (CDR1-3). We benchmark the performance of both definitions of convergence by their ability to predict disease status from bulk IgH sequencing data for two different diseases (HIV infection and food sensitization). We show that using predicted structural information outperforms prior approaches for the prediction of food sensitization status and performs on par for HIV infection status. Additionally, the structurally convergent antibody groups driving HIV prediction are from known HIV binders. Thus, the use of structural information allows for the identification of antigen specific antibody groups from bulk IgH sequencing data.
Cervical transcutaneous vagus nerve stimulation enhances speech recognition in noise: A crossover, placebo-controlled study
Authors: Jigo Michael , Carmel Jason B. , Wang Qi , Rodenkirch Charles 
Published: January 2025

AbstractUnderstanding speech in noisy environments is a widespread challenge, even for people with clinically normal hearing and users of hearing aids and cochlear implants. While these devices improve speech audibility, they do not optimize the brain’s ability to isolate relevant speech from background noise. Tonic vagus nerve stimulation (VNS) has been shown to rapidly improve sensory processing in the brain and enhance auditory perception in humans. Here, we investigated whether tonic cervical transcutaneous VNS (ctVNS) can enhance speech-in-noise recognition. Two cohorts of older human adults (60-84 years) completed audiological speech-in-noise assessments, QuickSIN (n=16) or AzBio (n=14), while receiving tonic ctVNS or placebo stimulation to the neck-shoulder junction in a counterbalanced, crossover fashion. Participants repeated sentences spoken amid various levels of background babble. Relative to placebo stimulation, tonic ctVNS improved the signal-to-noise ratio for reliable speech perception (SNR-50) by an average of 0.72 dB in QuickSIN (p=0.033) and 0.38 dB in AzBio (p=0.045), and enhanced word recognition accuracy by 4% (QuickSIN: p=0.0066, AzBio: p=0.000025). Notably, ctVNS benefits exceeded minimum clinically important differences in 39% of participants on average. Improvements by tonic ctVNS were most pronounced in individuals with speech-in-noise deficits (p=0.0089), peaked at noise levels typical of real-world environments (p=0.029), and did not depend on hearing loss severity (p=0.97) or age (p=0.88). Our findings demonstrate that tonic ctVNS delivers immediate, clinically meaningful improvements in speech-in-noise recognition, highlighting its potential to complement traditional assistive hearing technologies and inform novel therapies for sensory processing disorders.
DominantRDH12-retinitis pigmentosa impairs photoreceptor development and cone function in retinal organoids
Authors: Méjécase Cécile , Zhou Ya , Owen Nicholas , Soro-Barrio Pablo , Cheloni Riccardo , Nair Neelima , Sarkar Hajrah , Toualbi Lyes , Moosajee Mariya 
Published: January 2025

AbstractRetinal dehydrogenase 12 (RDH12) is a photoreceptor NADPH-dependent retinal reductase enzyme, converting all-trans-retinal to all-trans-retinol. Heterozygous variants inRDH12cause a rare autosomal dominant (AD) retinitis pigmentosa. As no disease models exist, we generated human induced pluripotent stem cell derived retinal organoids (RO) from aRDH12-AD patient (with pathogenic c.759del p.(Phe254Leufs*24) variant), alongside a healthy control (WT).RDH12-AD RO exhibited correct localisation of RDH12 to the photoreceptor inner segments up to week 44; transmission electron microscopy at week 37 showed photoreceptors were less abundant and shorter in length compared to WT. Visual cone function, retinol biosynthesis and the vitamin A pathway were also highly disrupted at week 44. Our study is the first to describe aRDH12-AD disease model with pathology at later stages of photoreceptor differentiation, in keeping with the milder disease course seen in humans. It provides insights into the aetiology and possible targets for future therapeutic development.
Evidence for reduced choroid plexus volume in the aged brain
Authors: Youh R , Perera C , Harrison IF , Lythgoe MF , Wright DK , Nizari S , Wells JA 
Published: January 2025

AbstractBackgroundThe choroid plexus plays an important role in brain homeostasis, including the active secretion of cerebrospinal fluid. Its function and structure have been reported to be affected by normal ageing. However, existing measures of choroid plexus volume may be complicated by partial volume (in vivoMRI) and tissue fixation artefacts (histology). In this study, we investigate possible changes in choroid plexus volume within the lateral ventricles of aged mice utilising two structural MRI protocols explicitly designed for time-efficient, high-resolutionin vivoimaging of the choroid plexus.MethodsTwo MRI sequences were utilised to examinein vivochoroid plexus volume in the lateral ventricles of young (∼6 months) and aged (∼24 months) mouse brains: 1) an ultra-long echo-time T2 weighted fast-spin-echo and 2) a multi-TE T2* mapping protocol. A test-retest study was performed on a subset of the data to examine the reproducibility of choroid plexus volume estimation. A two-way ANOVA test was performed to determine possible differences in choroid plexus volume in young and aged mouse groups across the two distinct MRI protocols.ResultsReproducibility tests showed a low test-retest variability of the manual segmentation pipeline for both MRI protocols. A statistically significant reduction ofin vivochoroid plexus volume was found in the aged mouse brain. This finding is concordant with previous histology studies that have observed a reduction in epithelial cell height with ageing across a wide range of species.ConclusionsWe present anin vivoinvestigation of changes to lateral ventricle choroid plexus volume in the mouse brain utilising a manual segmentation approach based on two bespoke MRI protocols designed for time-efficient high resolution imaging of the choroid plexus. Furthermore, based on these protocols, we provide evidence for a reduction in choroid plexus volume in the aged brain. This research provides insight for studies utilising MRI measurements of choroid plexus volume as a biomarker of age-related neurologic conditions as it indicates that the ageing process itself does not result in hypertrophy of the choroid plexus, but a decrease in tissue volume.
NLRP11 is required for canonical NLRP3 and non-canonical inflammasome activation during human macrophage infection with mycobacteria
Authors: Szczerba Mateusz , Ganesh Akshaya , Gil-Marqués María Luisa , Briken Volker , Goldberg Marcia B. 
Published: January 2025

ABSTRACTThe NLRP11 protein is only expressed in primates and participates in the activation of the canonical NLRP3 and non-canonical NLRP3 inflammasome activation after infection with gram-negative bacteria. Here, we generated a series of defined NLRP11 deletion mutants to further analyze the role of NLRP11 in NLRP3 inflammasome activation. Like the complete NLRP11 deletion mutant (NLRP11-/-), the NLRP11 mutant lacking the NACHT and LRR domains (NLRP11ΔN_LRR) showed reduced activation of the canonical NLRP3 inflammasome, whereas a pyrin domain mutant (NLRP11ΔPYD) had no effect on NLRP3 activation. TheNLRP11-/-andNLRP11ΔN_LRRmutants but not theNLRP11ΔPYDmutant also displayed reduced activation of caspase-4 during infection with the intracytosolic, gram-negative pathogenShigella flexneri. We found that the human adapted, gram-positive pathogenMycobacterium tuberculosisand the opportunistic pathogenM. kansasiiboth activate the non-canonical NLRP11 inflammasome in a caspase-4/5-dependent pathway. In conclusion, we show that NLRP11 functions in the non-canonical caspase-4/5 inflammasome activation pathway and the canonical NRLP3 inflammasome pathway, and that NLRP11 is required for full recognition of mycobacteria by each of these pathways. Our work extends the spectrum of bacterial pathogen recognition by the non-canonical NLRP11-caspase4/5 pathway beyond gram-negative bacteria.IMPORTANCEThe activation of inflammasome complexes plays a crucial role in intracellular pathogen detection. NLRP11 and caspase-4 are essential for recognizing lipopolysaccharide (LPS), a molecule found in gram-negative bacteria such as the human pathogensShigellaspp., which activate both canonical NLRP3 and non-canonical inflammasome pathways. Through a series of deletion mutants, we demonstrate that the NACHT and LRR domains of NLPR11, but not its pyrin domain, are critical for detection ofS. flexneri. Notably, our research reveals that the gram-positive bacteriumM. tuberculosisis also detected by NLPR11 and caspase-4, despite not producing LPS. These findings significantly expand the range of pathogens recognized by NLRP11 and caspase-4 to now include gram-positive bacteria and underscore the versatility of these innate immune components in pathogen detection.
Cortical state change by auditory deviants: a mismatch response generation mechanism in unconsciousness
Authors: Hockley Adam , Bohórquez Laura H , Malmierca Manuel S 
Published: January 2025

ABSTRACTMismatch negativity is an auditory-evoked biomarker for an array of neuropsychological disorders that occurs irrespective of consciousness, yet the generation mechanisms are still debated. Cortical slow oscillations occur during sleep or anesthesia and consist of reliable changes between “Up” and “Down” phases, characterised by high and low neural activity, respectively. Here we measure electrocorticography responses in the urethane-anesthetised rat and we demonstrate that during an auditory “oddball” paradigm, deviants trigger cortical Up phase initiations. Triggering of Up phases creates a mismatch response across the cortex, and when deviants fail to trigger Up phases, no mismatch response is present. We therefore propose triggering of cortical Up phases as a mechanism for mismatch negativity generation in unconscious states.
Food quality andvgll3genotype influence reproductive traits in female Atlantic salmon
Authors: Maamela Katja Susanna , Åsheim Eirik Ryvoll , O’Sullivan Ronan James , Debes Paul Vincent , House Andrew Herbert , Liljeström Petra , Prokkola Jenni Maria , Niemelä Petri Toivo , Erkinaro Jaakko , Mobley Kenyon Brice , Primmer Craig Robert 
Published: January 2025

AbstractAge at maturity is an important factor contributing to life-history diversity. In Atlantic salmon, this trait often shows sex-specific variation, but female salmon are seldom included in experimental studies of maturation. As a result, there is a gap in our knowledge of how different genetic and environmental factors affect female maturation. Using a 4-year common-garden experiment, we assessed the influence of diet (low-fat vs. control) andvgll3(a candidate gene in a genomic region known to influence age at maturity in Atlantic salmon) on maturation and related phenotypic traits of female Atlantic salmon from two 2nd-generation hatchery populations. We found the early-maturation-associatedvgll3*E allele to be associated with higher probability of maturation. Heritability of maturation was estimated to be 0.295 withvgll3’s contribution to phenotypic variance being ∼2%. In addition, both body size and body condition measured in the spring prior to spawning influenced maturation. Body condition, in turn, was influenced by population and diet. The northern Oulu population and the low-fat diet were associated with lower body condition compared to the southern Neva population and the control diet. Moreover, there was an interaction between population and diet on body condition, suggesting that populations may respond differently to nutrient availability. These results broaden our understanding of the processes underlying maturation and demonstrate that genes and environment interact to shape age at maturity in female Atlantic salmon.
Augmenting the human interactome for disease prediction through gene networks inferred from human cell atlas
Authors: Sung Euijeong , Cha Junha , Baek Seungbyn , Lee Insuk 
Published: January 2025

AbstractGene co-expression network inference from bulk tissue samples often misses cell-type-specific interactions, which can be detected through single-cell gene expression data. However, the noise and sparsity of single-cell data challenge the inference of these networks. We developed scNET, a framework for integrative cell-type-specific co-expression network inference from single-cell transcriptome data, demonstrating its utility in augmenting the human interactome for more accurate disease gene prediction. We address the limitations inde novonetwork inference from single-cell expression data through dropout imputation, metacells formation, and data transformation. Employing this data preprocessing pipeline, we inferred cell-type-specific co-expression links from single-cell atlas data, covering various cell types and tissues, and integrated over 850K of these inferred links into a preexisting human interactome, HumanNet, resulting in HumanNet-plus. This integration notably enhanced accuracy of network-based disease gene prediction. These findings suggest that with proper data preprocessing, network inference from single-cell gene expression data can be highly effective, potentially enriching the human interactome and advancing the field of network medicine.
Structural rearrangements and selection promote phenotypic evolution inAnolislizards
Authors: Araya-Donoso Raúl , Baty Sarah M. , Johnson Jaime E. , Lasku Eris , Taft Jody M. , Fisher Rebecca E. , Losos Jonathan , Dolby Greer A. , Kusumi Kenro , Geneva Anthony J. 
Published: January 2025

AbstractThe genomic characteristics of adaptively radiated groups could contribute to their high species number and ecological disparity, by increasing their evolutionary potential. Here, we explored the genomic features ofAnolislizards, focusing on three species with unique phenotypes:A. auratus, one of the species with the longest tail;A. frenatus, one of the largest species; andA. carolinensis, one of the species that inhabits the coldest environments. We assembled and annotated two new chromosome-level reference genomes forA. auratusandA. frenatus, and compared them with the available genomes ofA. carolinensisandA. sagrei. We evaluated the presence of structural rearrangements, quantified the density of repeat elements, and identified signatures of positive selection in coding and regulatory regions. We detected substantial rearrangements in scaffolds 1, 2 and 3 ofA. frenatusdifferent from the other species, in which the rearrangement breakpoints corresponded to hotspots of developmental genes. Further, we detected an accumulation of repeats around key developmental genes in anoles and phrynosomatid outgroups. Finally, we detected signatures of positive selection on coding sequences and regulatory regions of genes relevant to development and physiology that could affect the unique phenotypes of the analyzed species. Our results suggest that anoles have genomic features associated with genes that affect organismal morphology and physiology. This could provide a genomic substrate that promoted phenotypic disparity in anoles, and contributed to their ability to adaptively radiate.Author SummaryAdaptive radiations are often characterized by high species richness and phenotypic differentiation. Besides the ecological context, the genetic features of organisms could also contribute to their ability to diversify.Anolislizards are an adaptively radiated group that shows high phenotypic disparity in morphology and physiology. In this study, we explored the genome of four species within theAnolisradiation with distinctive phenotypes. We generated a high-quality chromosome-level reference genome forA. auratusandA. frenatus, and compared them withA. carolinensisandA. sagrei. We detected major structural rearrangements inA. frenatus, a high density of repeat elements around key developmental genes, and signatures of natural selection associated with genes functionally relevant for the analyzed species. Hence, the genomic characteristics of anoles were associated with their unique phenotypic diversity. We highlight the potential relevance of genomic features to influence the ability of groups of organisms to radiate adaptively.