bluuebunny/crossref_metadata_2025 huggingface dataset:
LGBTQ+ IDENTITY SOCIAL SUPPORT AND CARE MECHANISMS AMONG LGBTQ+ MCI/ADRD CAREGIVERS
Authors: Lampe Nik , Akre Ellesse-Roselee , Barbee Harry , McKay Tara
Published: January 2025

LGBTQ+ caregivers for individuals living with mild cognitive impairment or Alzheimer’s disease and related dementias (MCI/ADRD) experience disparities in discrimination, social isolation, healthcare, and financial strain, compared to their heterosexual and cisgender counterparts. In this study, we examine the relationship between the roles of being an LGBTQ+ MCI/ADRD caregiver has on levels of LGBTQ+-identity social support and care outcomes among LGBTQ+ older adults. Using Wave 3 data (N=1,038) of The LGBTQ+ Social Networks, Aging, and Policy Study (QSNAPS), we use descriptive analyses to estimate sample characteristics and Chi-square tests and logistic regressions to test the associations between MCI/ADRD caregiver status and outcomes concerning LGBTQ+-identity social support from family, friends, coworkers, and neighbors as well as various LGBTQ+-affirming care practices. Eighty-three respondents (8.3%) in the QSNAPS Wave 3 sample identified as caregivers for individuals with neurocognitive disorders. Compared to LGBTQ+ non-MCI/ADRD caregivers, LGBTQ+ MCI/ADRD caregivers were: 51.7% less likely to have family support (p<.01) and 49.1% less likely to have neighbor support (p<.05). Compared to LGBTQ+ non-MCI/ADRD caregivers, LGBTQ+ MCI/ADRD caregivers were more likely to receive practical help from others (p< 0.1); and less likely to report their providers’ offices displaying LGBTQ-affirming materials (p< 0.1) and providers using gender-inclusive language (p< 0.1). No significant associations were found between MCI/ADRD caregiver status and other LGBTQ+-affirming care outcomes. Understanding LGBTQ+-identity social support and care mechanisms can inform targeted interventions to reduce health disparities among LGBTQ+ MCI/ADRD caregivers.
VETERAN AND FAMILY PERSPECTIVES OF THE VA NURSING HOME TO HOME PROGRAM
Authors: Haverhals Leah , Manheim Chelsea , Fix Rachel
Published: January 2025

Veterans meeting United States (US) Veterans Health Administration (VA) service-connected disability requirements are eligible for VA provided nursing home (NH) care, resulting in high utilization. In 2023, the VA launched the Nursing Home to Home (NHTH) pilot program at three VA Medical Centers. NHTH’s objective is to identify Veterans residing in VA-contracted NHs interested in returning to live in the community. Through assessments by an interdisciplinary team, care coordination, and follow-up services, efforts are initiated to support appropriate, safe, and successful discharges. From March-July 2024, we conducted N=11 interviews with 13 Veterans and family members to describe their experiences with NHTH. Veterans felt more comfortable at home, had adequate caregiving and home health support, and said their healthcare needs were met. Several shared they were confident in bathing and dressing independently and expressed increased self-determination in improving their mobility. Families and Veterans noted the time from program referral to NH discharge ranged from three to six months, which they felt was appropriate. Families shared the NHTH team was available to answer questions, provide education, and offer help navigating the VA, including identifying services Veterans may be eligible for that families had not been aware of previously. One family member shared the NH had not provided adequate care to the Veteran and was glad the Veteran returned home, and many Veterans noted they would recommend the program to other Veterans. After one year, feedback shared about NHTH has been largely positive, highlighting several benefits and showing potential for expansion.
DECOLONIZING GERONTOLOGY BY REPATRIATING EXPERTISE: THEORY, RESEARCH DESIGN, AND A RESEARCH STUDY EXAMPLE
Authors: Crampton Alexandra
Published: January 2025

This presentation provides a rationale, a research design, and a research example of decolonizing gerontology through integration of Indigenous philosophy and practices. Colonization in gerontology is identified on three levels; reducing complexity of aging into problems for outside experts to solve; associating aging with loss that negates (and potentially threatens) modern values of youth, independence, and productivity; and limiting the research role of older adults to that of consenting research subjects. Decolonization in gerontology explores complexity of lived experience, and expands the research role of older adults to actively challenge, deepen, and redirect the research. My research design incorporates Shawn Wilson’s decolonization work and lessons from the successful repatriation of Ahayu: da by Zuni negotiators. My research example is from a study conducted between July 2021 and July 2024 in a Midwestern retirement community where the average age is 86. Covid restrictions persisted through May, 2023. My research goal was to repatriate gerontological constructs, such as “successful aging” and “older adulthood” through community-engaged research. Data were collected using ethnographic methods of participant observation, in-depth interviews, archival document collection, and frequent consultation with research participants. Although “successful aging” and “older adulthood” were recognized by research participants, these constructs were rejected as non-informative by those confronting major disruption to roles, status, and/or functioning. Construct repatriation included reformulating aging as reckoning with loss of capacities, relationships, and other sources of meaning that had been integral to a sense of self and means of flourishing. Research presentations became a means of shared reckoning.
Global Rumours: The Press, Telegraphy and the Boxer War in China, Summer 1900
Authors: Klein Thoralf
Published: January 2025

In the summer of 1900, at the height of the Boxer War, the European and North American press began to spread the story that all the Western foreigners in Beijing had been massacred. Bringing together the histories of rumour, media and imperialism, as well as global history, this article traces the trajectory of how this press rumour emerged as a result of the interplay between news production, media technology and imperialist discourse. It shows how rumours emerge in response to a lack of reliable information, despite attempts by newsmakers to cling to established standards of objectivity. As the backbone of the transnational media network, telegraphy globalized rumours that would otherwise have remained local. However, the incompleteness of telegraphic information, as well as the spatial layout of the newspaper page, allowed editors to print different, and often downright contradictory, versions of the same story. This endowed press rumours with an unusual complexity. Finally, the rumour of the wholesale killing of Westerners in the Chinese capital owed much to imperialist ‘horizons of expectation’, which shifted the discussion to how the besieged Westerners had died. Even after the truth gradually filtered through, it was some time before the global rumour mill finally ground to a halt.
Learning Biomolecular Models using Signal Temporal Logic
Authors: Krasowski Hanna , Palanques-Tost Eric , Belta Calin , Arcak Murat
Published: January 2025

Modeling dynamical biological systems is key for understanding, predicting, and controlling complex biological behaviors. Traditional methods for identifying governing equations, such as ordinary differential equations (ODEs), typically require extensive quantitative data, which is often scarce in biological systems due to experimental limitations. To address this challenge, we introduce an approach that determines biomolecular models from qualitative system behaviors expressed as Signal Temporal Logic (STL) statements, which are naturally suited to translate expert knowledge into computationally tractable specifications. Our method represents the biological network as a graph, where edges represent interactions between species, and uses a genetic algorithm to identify the graph. To infer the parameters of the ODEs modeling the interactions, we propose a gradient-based algorithm. On a numerical example, we evaluate two loss functions using STL robustness and analyze different initialization techniques to improve the convergence of the approach.
Cortically-mediated muscle responses to balance perturbations increase with perturbation magnitude in older adults with and without Parkinson’s disease
Authors: Boebinger Scott E. , Payne Aiden M. , Xiao Jifei , Martino Giovanni , Borich Michael , McKay J. Lucas , Ting Lena H.
Published: January 2025

We lack a clear understanding of how cortical contributions to balance are altered in aging and Parkinson’s disease (PD), which limits development of rehabilitation strategies. Processes like balance control are typically mediated through brainstem circuits, with higher-order circuits becoming engaged as needed. Using reactive balance recovery, we investigated how hierarchical neural mechanisms shape balance- correcting muscle activity across task difficulty in older adults (OAs) with and without PD. We hypothesize that feedback loops involving brainstem and cortical circuits contribute to balance control, and cortical engagement increases with challenge, aging, and PD. We decomposed perturbation-evoked agonist and antagonist muscle activity into hierarchical components based on latency using neuromechanical models consisting of two feedback loops with different delays to reflect different neural conduction and processing times. Agonist muscle activity was decomposed into two components that both increased with balance challenge in both groups. The first component occurred ∼120ms and the second occurred ∼210ms, consistent with the latencies of brainstem and transcortical circuits, respectively. Exploratory comparisons to young adults revealed larger transcortical components in OA and PD groups at lower balance challenge levels, consistent with increased cortical involvement with aging. Antagonist muscle activity included destabilizing and stabilizing components, with the destabilizing component correlating to balance ability in OAs but not in PD. These findings demonstrate that neuromechanical models can identify changes in the hierarchical control of balance without direct brain measurements. Identifying cortical contributions during balance control may complement clinical measures of balance ability to inform balance rehabilitation and assistive devices.

NEW & NOTEWORTHY

A neuromechanical model can decompose perturbation evoked muscle activity into components attributed to brainstem and higher-order sensorimotor feedback based on latency. In older adults with and without PD contributions from higher-order neural circuits increase with balance challenge and are related to clinical measures of balance ability. Interpreting the neural substrates of motor output for balance may reveal individual differences in the hierarchical control of balance, that could inform rehabilitation.
Robust measurement of microbial reduction of graphene oxide nanoparticles using image analysis
Authors: Bennett Danielle T. , Meyer Anne S.
Published: January 2025

Shewanella oneidensis(S. oneidensis) has the capacity to reduce electron acceptors within a medium and is thus used frequently in microbial fuel generation, pollutant breakdown, and nanoparticle fabrication. Microbial fuel setups, however, often require costly or labour-intensive components, thus making optimization of their performance onerous. For rapid optimization of setup conditions, a model reduction assay can be employed to allow simultaneous, large-scale experiments at lower cost and effort. SinceS. oneidensisuses different extracellular electron transfer pathways depending on the electron acceptor, it is essential to use a reduction assay that mirrors the pathways employed in the microbial fuel system. For microbial fuel setups that use nanoparticles to stimulate electron transfer, reduction of graphene oxide provides a more accurate model than other commonly used assays as it is a bulk material that forms flocculates in solutions with a large ionic component. However, graphene oxide flocculates can interfere with traditional absorbance-based measurement techniques. This study introduces a novel image analysis method for quantifying graphene oxide reduction, showing improved performance and statistical accuracy over traditional methods. A comparative analysis shows that the image analysis method produces smaller errors between replicates and reveals more statistically significant differences between samples than traditional plate reader measurements under conditions causing graphene oxide flocculation. Image analysis can also detect reduction activity at earlier time points due to its utilization of larger solution volumes, enhancing color detection. These improvements in accuracy make image analysis a promising method for optimizing microbial fuel cells that use nanoparticles or bulk substrates.

IMPORTANCE

Shewanella oneidensis(S. oneidensis) is widely used in reduction processes such as microbial fuel generation due to its capacity to reduce electron acceptors. Often, these setups are labor intensive to operate and require days to produce results, so use of a model assay would reduce the time and expense needed for optimization. Our research developed a novel digital analysis method for analysis of graphene oxide flocculates that may be utilized as a model assay for reduction platforms featuring nanoparticles. Use of this model reduction assay will enable rapid optimization and drive improvements in the microbial fuel generation sector.
Stimulation of the Medial SNr Promotes Sustained Motor Recovery and Counteracts Parkinsonian Pathophysiology in Dopamine Depleted Mice
Authors: Aristieta Asier , Parker John E. , Cundiff Mary D. , Fuchs Thomas , Lim Byung Kook , Rubin Jonathan E. , Gittis Aryn H.
Published: January 2025

Dopamine loss alters the activity of neural circuits in the basal ganglia, contributing to motor symptoms of Parkinson’s disease and catalepsy. Treatments that reduce basal ganglia pathophysiology alleviate motor symptoms but require maintenance. Cell-type specific interventions can reduce pathophysiology and provide sustained therapeutic benefits, but a lack of understanding of pathways involved limits translation. Here, we establish patterns of neuromodulation and electrophysiological biomarkers at the level of basal ganglia output that predict the duration of therapeutic effects. Focal activation of neurons in the ventromedial substantia nigra reticulata (SNr) engaged a gradual recovery of movement that persisted for hours after treatment, accompanied by a persistent reduction in parkinsonian pathophysiology. Global SNr inhibition, as prescribed by the classic rate model, provided only transient effects on movement and did not reverse network pathophysiology. These findings represent important steps towards developing therapeutic strategies that aim to repair, rather than simply mask, circuit dysfunction in disease.
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

Cost-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

Methanol 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

The 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 Summary

This 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

Convergent 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

Understanding 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

Retinal 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

Background

The 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.

Methods

Two 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.

Results

Reproducibility 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.

Conclusions

We 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

The 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.

IMPORTANCE

The 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

Mismatch 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

Age 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

Gene 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

The 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 Summary

Adaptive 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.
The diffusion of cooperative and solo bubble net feeding in Canadian Pacific humpback whales
Authors: Wray Janie , O'Mahony Eadin N , Baer Grace , Robinson Nicole , Dundas Archie , Gaggiotti Oscar E , Rendell Luke , Keen Eric
Published: January 2025

Cooperative foraging, a mutualistic resource acquisition behaviour observed across diverse taxa, can drive social network structure, as it typically involves high rates of interactions between individuals. Understanding the mechanisms and distribution of such behaviours is important to elucidate the drivers of social organisation. Bubble net feeding ('bubble netting') is a specialised foraging technique practised by certain humpback whale (Megaptera novaeangliae) populations globally. Over 20 years of study in the northern Canadian Pacific, we observed the diffusion of two morphs of this behaviour: social cooperative and independent, or 'solo', bubble netting. Network-based diffusion analyses - a tool developed to test for social learning - find strong evidence for the social learning of bubble netting when a static social network is used, even after accounting for individual-level traits such as site fidelity and sex (10.6 x10^3 to 35.4x10^3 times more support for social versus asocial learning; p < 0.0001). However, we could not completely exclude homophily due to the inherent sociality of this cooperative foraging behaviour. Nonetheless, it is clear that the rapid diffusion of bubble netting throughout this population has significant consequences for its social structure, which should be information considered by those planning the conservation of this threatened population.
The scaffold protein CasL regulates T cell migration by restricting membrane blebbing
Authors: Kurtz Liz A , Shearer Hope E , Trevail Rosanne , Symeonides Menelaos , Karimi Mobin , Roy Nathan H
Published: January 2025

T cell migration into inflamed tissue is a key control point in the inflammatory response and relies on integrin interactions with their endothelial ligands. Here, we identify the signaling scaffold CasL (Hef1, NEDD9) as a central regulator of integrin-dependent migration in primary T cells. We found CasL is specifically needed for efficient migration on ICAM-1, but not VCAM-1 coated surfaces. While WT T cells migrating on ICAM-1 form an actin-rich cell front and move smoothly, T cells lacking CasL instead form numerous, aberrant membrane blebs. The abnormal blebbing observed in CasL KO T cells likely stems from diminished F-actin in the cell front coupled with increased contractile forces behind the nucleus, suggesting CasL regulates the cytoskeletal architecture in migrating T cells. Importantly, using anin vivoallogeneic hematopoietic transplant model we found that CasL promotes T cell migration into inflamed peripheral tissue, but was dispensable for trafficking to secondary lymphoid organs. Together, these results indicate CasL functions to control the balance of cytoskeletal components during integrin-dependent migration and highlight the importance of integrin signaling for proper migration into inflamed tissue.
Preclinical Proof of Concept for SNAPTM-TIL: a personalized, next-generation tumor-infiltrating lymphocyte therapy platform
Authors: Halder Tithi Ghosh , Kelley Erin , Soria-Bustos Jorge , Thode Trason , Ng Serina , Bargenquast Taylor , Weston Alexis , Rodriguez del Villar Ryan , Kaadige Mohan , Borazanci Erkut , Gordon Michael , Moser Justin , Tsai Frank , Priceman Saul J. , Forman Stephen J. , Xing Yan , Altin John A. , Soldi Raffaella , Sharma Sunil
Published: January 2025

Tumor-infiltrating lymphocyte (TIL) therapy, which involves extracting, expanding, and reinfusing immune cells to target cancer cells, has shown promise in melanoma treatment, but requires optimization for broader efficacy. The success of TIL therapy depends on the recognition of tumor-associated antigens, but neoantigen-reactive T-cells are often rare and exhausted in less immunogenic malignancies. Isolating T cells enriched in neoantigen reactivity prior toin vitroexpansion and reinfusion may improve the response rates. To this end, our proprietary Specific Neo-Antigen Peptides (SNAP™) technology platform improves the accuracy of neoantigen prediction and validation by combining advanced computational modeling and PepSeq, a high-throughput screen for the physical credentialing of putative neoantigens based on their affinity to bind patient-specific HLA class II proteins. This approach allows for the education and enrichment of TILs (SNAP-TILs) with personalized, predefined, highly immunogenic neoantigens prior to expansion. Using the SNAP platform, we consistently achieved, on average, an SNAP-TIL product comprising 96% CD3+ cells, with a mixture of 75% effector and 23% central memory cells. SNAP-TILs exhibited greater efficacy and selectivity in immune infiltration than TIL, which was expanded by the rapid expansion protocol alone usingex vivomodels. SNAP-TIL was also reactive in highly and poorly immunogenic tumors, with 70% and 50% tumor growth inhibition in melanoma and pancreatic patient-derived xenograft models, respectively. This study demonstrates the novel benefit of our Personalized Neoantigen Pipeline approach, potentially providing a durable antitumor immune response for a larger proportion of cancer patients.
Intraflagellar Transport Selectivity Occurs with the Proximal Portion of the Trypanosome Flagellum
Authors: Alves Aline Araujo , Jung Jamin , Moneron Gaël , Vaucelle Humbeline , Fort Cécile , Buisson Johanna , Schietroma Cataldo , Bastin Philippe
Published: January 2025

Intraflagellar transport (IFT) trains move bidirectionally along the doublet microtubules (DMTs) of the axoneme within the flagellum. InTrypanosoma brucei, IFT trains predominantly associate with four of the nine DMTs. Using high-resolution microscopy, we reveal how this selective association is put in place. IFT proteins form a ring surrounding the 9 DMTs on top of the transition fibres. Volume electron microscopy revealed densities along all DMTs in the proximal portion of the flagellum, exhibiting thinner, shorter profiles with branches absent in mature IFT trains. As the axoneme extends within the flagellar pocket, IFT trains are detected but are often positioned outside DMTs 3-4/7-8. After the axoneme exits the flagellar pocket, IFT trains localise exclusively to DMTs 3-4 and 7-8. Super-resolution and expansion microscopy demonstrated that IFT proteins follow the same distribution as the IFT-like densities. This suggests they represent IFT trains undergoing assembly and/or disassembly and reveals their unexpected ability to shift from one DMT to another.

InTrypanosoma brucei, intraflagellar transport (IFT) trains selectively associate with specific axonemal microtubules. Using advanced microscopy, this study reveals how this restriction occurs at the proximal portion of the flagellum during the assembly and/or disassembly of IFT trains.
ggrain - a ggplot2 extension for raincloud plots
Authors: Judd Nicholas , van Langen Jordy , Poggiali Davide , Whitaker Kirstie , Rhys Marshall Tom , Allen Micah , Kievit Rogier
Published: January 2025

Clear data visualization isessentialto effectively communicate empirical findings across various research fields. Raincloud plots fill this need by offering a transparent and statistically robust approach to data visualization. This is achieved by combining three plots in an aesthetically pleasing fashion. First, a dot plot displays raw data with minimal distortion, allowing a fast glance at the sample size and outlier identification. Next, a box plot displays key distributional summary statistics such as the median and interquartile range. Lastly, a violin plot transparently displays the underlying distribution of the data. Despite the widespread use of raincloud plots, an R-package in alignment with the‘grammar of graphics’was lacking. ‘ggrain’ fills this need by offering one easy-to-use function (‘geom_rain’) allowing the quick and seamless plotting of rainclouds in the R ecosystem. Further, it enables more complex plotting features such as factorial grouping, mapping with a secondary (continuous) covariate, and connecting observations longitudinally across multiple waves.
Tracing of the developmental origin of the caudal fin muscle in zebrafish
Authors: Ota Kinya G , Abe Gembu
Published: January 2025

Teleost species possess complex caudal musculoskeletal systems. While mid-trunk muscles exhibit simple segmental patterns, several caudal skeletal muscles display intricate orientations in their muscle fibers. Due to this distinctive morphology, both early and recent researchers have studied the structure and development of the caudal musculoskeletal system. However, the early developmental origin of the cell populations within the caudal muscle system remains largely unknown. In this study, we performed lineage tracing of caudal muscle primordia in zebrafish using a transgenic line expressing EGFP in somite derivatives following tamoxifen induction. This approach allowed us to observe the specific cell populations that contribute to caudal muscle tissue formation at the early larval stage. By monitoring the growth of these labeled cells from the early larval stage, we identified the origins of muscle fibers in caudal fin muscles unique to teleosts, such as the adductor caudalis and flexor caudalis. Our findings provide descriptions that aid in understanding how fish-specialized caudal muscle structures were formed through the modification of developmental processes during evolution.