bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating a biomedical knowledge base by addressing GPT inaccurate responses and benchmarking context
Authors: Darnell S. Solomon , Overall Rupert W. , Guarracino Andrea , Colonna Vicenza , Villani Flavia , Garrison Erik , Isaac Arun , Muli Priscilla , Muriithi Frederick Muriuki , Kabui Alexander , Kilyungi Munyoki , Lisso Felix , Kibet Adrian , Muhia Brian , Nijveen Harm , Yousefi Siamak , Ashbrook David , Huang Pengzhi , Suh G. Edward , Umar Muhammad , Batten Christopher , Chen Hao , Sen Śaunak , Williams Robert W. , Prins Pjotr
Published: October 2024

We created GNQA, a generative pre-trained transformer (GPT) knowledge base driven by a performant retrieval augmented generation (RAG) with a focus on aging, dementia, Alzheimer’s and diabetes. We uploaded a corpus of three thousand peer reviewed publications on these topics into the RAG. To address concerns about inaccurate responses and GPT ‘hallucinations’, we implemented a context provenance tracking mechanism that enables researchers to validate responses against the original material and to get references to the original papers. To assess the effectiveness of contextual information we collected evaluations and feedback from both domain expert users and ‘citizen scientists’ on the relevance of GPT responses.

A key innovation of our study is automated evaluation by way of a RAG assessment system (RAGAS). RAGAS combines human expert assessment with AI-driven evaluation to measure the effectiveness of RAG systems. When evaluating the responses to their questions, human respondents give a “thumbs-up” 76% of the time. Meanwhile, RAGAS scores 90% on answer relevance on questions posed by experts. And when GPT-generates questions, RAGAS scores 74% on answer relevance. With RAGAS we created a benchmark that can be used to continuously assess the performance of our knowledge base.

Full GNQA functionality is embedded in the freeGeneNetwork.orgweb service, an open-source system containing over 25 years of experimental data on model organisms and human. The code developed for this study is published under a free and open-source software license athttps://git.genenetwork.org/gn-ai/tree/README.md.
Genetic diversity and fine-scale structure of two populations of a subterranean rodent,Ellobius talpinus
Authors: Rudyk Anna I. , Kuprina Kristina V. , Bergaliev Arman M. , Galkina Svetlana A. , Romanovich Anna E. , Novikov Eugene A. , Volodina Elena V. , Smorkatcheva Antonina V.
Published: October 2024

Subterranean rodents represent an interesting model system for molecular ecologists. Their lifestyle is associated with fragmented environments, limited dispersal ability, and low fecundity. These characteristics all are expected to increase inter- and intrapopulation differentiation and reduce intra- population genetic diversity, yet the published empirical data revealed the lack of generality of this pattern. This emphasizes the importance of accumulating more data on individual species to understand what factors shape the genetic dynamics of populations. This study represents the first characterization of the population genetic diversity and fine-scale genetic structure of a highly specialized subterranean vole,Ellobius talpinus. We used nine microsatellite loci and a fragment of the mitochondrial D-loop to investigate genetic patterns of two distant populations: the Novosibirsk population at the extreme northeastern edge of the species range, and the sub-peripheral Saratov population. As a result, the two populations exhibit distinct patterns of genetic structure. The Novosibirsk population showed a low nuclear diversity with an observed heterozygosity (Ho) of 0.34 and an unbiased expected heterozygosity (uHe) of 0.55. Mitochondrial D-loop was nearly monomorphic with over 90% of the observed haplotypes being identical, resulting in a haplotype diversity (Hd) of 0.14 and nucleotide diversity (π) of 0.0004. In contrast, the Saratov population displayed moderate nuclear (Ho= 0.64;uHe= 0.76) and high mitochondrial variation (Hd= 0.83;π= 0.034), compared to the surface-dwelling voles. Nine haplotypes representing four well-differentiated mitochondrial clades were found in the Saratov population. In a heterogeneous landscape, significant genetic differentiation was revealed at both intermediate (dozens of kilometers) and fine (several kilometers) scales. However, within the continuous suitable habitat, no fine-scale spatial structure was observed apart from that caused by kin clustering. The spatial genetic patterns revealed inE. talpinusappear to reflect a combination of effects of strong social structure, local natural and anthropogenic barriers limiting dispersal opportunities, and occasional long-distance dispersal.
Identification and Expression of the peach TNLRMiagenes for the Resistance to the Root-knot NematodeMeloidogyne incognita
Authors: Duval Henri , Heurtevin Laure , Dlalah Naïma , Caravel Claire , Callot Caroline , Van Ghelder Cyril
Published: October 2024

Root-Knot Nematodes (RKN) are major pests for world agriculture. As RKN are polyphagous endoparasites, present in various climates and able to multiply rapidly, the quest to discover new natural resistances in plants is essential. InPrunusspecies, several major resistance genes to RKN that belong to the NLR family, have been detected in recent years. In Peach, the RMia gene, which confers resistance to the RKNMeloidogyne incognita, M. arenaria, andM. ethiopica, was localized on the chromosome 2. In this study, we used short-and long-read sequencing technologies to identify the RMia gene in two independent RKN-resistant peach varieties. We characterized three candidate genes and studied their expression profile upon RKN infection. Our study identified and characterized these candidates that are most likely involved in the RKN resistance. Ultimately, we developed new molecular markers associated to this resistance that can be used in breeding programs.
Decoding m6Am by simultaneous transcription-start mapping and methylation quantification
Authors: Liu Jianheng Fox , Hawley Ben R. , Nicholson Luke S. , Jaffrey Samie R.
Published: October 2024

N6,2’-O-dimethyladenosine (m6Am) is a modified nucleotide located at the first transcribed position in mRNA and snRNA that is essential for diverse physiological processes. m6Am mapping methods assume each gene uses a single start nucleotide. However, gene transcription usually involves multiple start sites, generating numerous 5’ isoforms. Thus, gene levels annotations cannot capture the diversity of m6Am modification in the transcriptome. Here we describe CROWN-seq, which simultaneously identifies transcription-start nucleotides and quantifies m6Am stoichiometry for each 5’ isoform that initiates with adenosine. Using CROWN-seq, we map the m6Am landscape in nine human cell lines. Our findings reveal that m6Am is nearly always a high stoichiometry modification, with only a small subset of cellular mRNAs showing lower m6Am stoichiometry. We find that m6Am is associated with increased transcript expression and provide evidence that m6Am may be linked to transcription initiation associated with specific promoter sequences and initiation mechanisms. These data suggest a potential new function for m6Am in influencing transcription.
Tracing the taxonomic distribution of plant cell wall degrading enzymes across the tree of life using feature architecture aware orthology assignments
Authors: Tran Vinh , Langschied Felix , Muelbaier Hannah , Dosch Julian , Arthen Freya , Balint Miklos , Ebersberger Ingo
Published: October 2024

The decomposition of plant material is a key driver of the global carbon cycle, traditionally attributed to fungi and bacteria. However, some invertebrates also possess orthologs to bacterial or fungal cellulolytic enzymes, likely acquired via horizontal gene transfer. This reticulated mode of evolution necessitates ortholog searches in large taxon sets to comprehensively map the repertoire of plant cell wall degrading enzymes (PCDs) across the tree of life, a task surpassing capacities of current software. Here, we use fDOG, a novel profile-based ortholog search tool to trace 235 potential PCDs across more than 18,000 taxa. fDOG allows to start the ortholog search from a single protein sequence as a seed, it performs on par with state-of-the-art software that require the comparison of entire proteomes, and it is unique in routinely scoring protein feature architecture differences between the seed protein and its orthologs. Visualizing the presence-absence patterns of PCD orthologs using a UMAP highlights taxa where recent changes in the enzyme repertoire indicate a change in lifestyle. Three invertebrates have a particularly rich set of PCD orthologs encoded in their genome. Only few of the orthologs show differing protein feature architectures relative to the seed that suggest functional modifications. Thus, the corresponding species represent lineages within the invertebrates that may contribute to the global carbon cycle. This study shows how fDOG can be used to create a multi-scale view on the taxonomic distribution of a metabolic capacity that ranges from tree of life-wide surveys to individual feature architecture changes within a species.
Deoxysphingolipids activate cGAS-STING in colon cancer cells and enhance tumor immunity
Authors: Saha Suchandrima , Valezquez Fabiola N. , Dehpanah Fatemeh , Mao Cungui , Montrose David C.
Published: October 2024

Bioactive sphingolipids (SLs) play critical roles in cellular function, including modifying the oncogenic potential of cancer cells. Depletion of the non-essential amino acid serine induces an intracellular shift from the generation of canonical SLs to non-canonical SLs known as deoxySLs, which can exert antitumor effects. Recent evidence has shown that restricting endogenous and exogenous sources of serine from cancer cells promotes antitumor immunity by activating the cyclic GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) pathway. However, it is not known whether deoxySLs play a role in mediating this antitumor immune response. In this study, we demonstrated that depleting both externally supplied and internally synthesized serine from CT26 colon cancer cells maximally increased the levels of deoxySLs compared to removing either source alone. The ability of serine restriction to induce cytosolic accumulation of mitochondrial DNA (mtDNA) and subsequent activation of cGAS-STING components, including downstream Type I interferons (IFNs) was prevented by blocking deoxySL generation with the serine-palmitoyl transferase (SPT) inhibitor, myriocin. Direct administration of deoxysphinganine to cells induced mitochondrial dysfunction, in association with accumulation of cytosolic mtDNA, and increased expression of cGAS-STING components and Type I IFNs. A similar increase in IFNs was observed following mutation of SPT or supplementation of WT cells with alanine. Increasing deoxySLs in tumors through SPT mutation or feeding an alanine-enriched diet suppressed tumor growth in mice, while combining SPT mutation with a high alanine diet accentuated the antitumor effects. The observed tumor growth suppression was associated with increased infiltration of activated dendritic and cytotoxic T cells. Collectively, these findings reveal a novel role for deoxySLs in mediating antitumor immunity and provide support for the potential of using diet modification as an anticancer approach.
A human brain network linked to restoration of consciousness after deep brain stimulation
Authors: Warren Aaron E.L , Raguž Marina , Friedrich Helen , Schaper Frederic L.W.V.J. , Tasserie Jordy , Snider Samuel B. , Li Jian , Chua Melissa M.J. , Butenko Konstantin , Friedrich Maximilian U. , Jha Rohan , Iglesias Juan E. , Carney Patrick W. , Fischer David , Fox Michael D. , Boes Aaron D. , Edlow Brian L. , Horn Andreas , Chudy Darko , Rolston John D.
Published: October 2024

Disorders of consciousness (DoC) are states of impaired arousal or awareness. Deep brain stimulation (DBS) is a potential treatment, but outcomes vary, possibly due to differences in patient characteristics, electrode placement, or stimulation of specific brain networks. We studied 40 patients with DoC who underwent DBS targeting the thalamic centromedian-parafascicular complex. Better-preserved gray matter, especially in the striatum, correlated with consciousness improvement.

Stimulation was most effective when electric fields extended into parafascicular and subparafascicular nuclei—ventral to the centromedian nucleus, near the midbrain— and when it engaged projection pathways of the ascending arousal network, including the hypothalamus, brainstem, and frontal lobe. Moreover, effective DBS sites were connected to networks similar to those underlying impaired consciousness due to generalized absence seizures and acquired lesions. These findings support the therapeutic potential of DBS for DoC, emphasizing the importance of precise targeting and revealing a broader link between effective DoC treatment and mechanisms underlying other conscciousness-impairing conditions.
A new AI-assisted data standard accelerates interoperability in biomedical research
Authors: Long Rodney Alan , Ballard Shannon , Shah Syed , Bianchi Owen , Jones Lietsel , Koretsky Mathew J. , Kuznetsov Nicole , Marsan Elise , Jen Bryant , Chiang Philip , Mukherjee Abhradeep , Blauwendraat Cornelis , Leonard Hampton , Vitale Dan , Levine Kristin , Bandres-Ciga Sara , Jarreau Paige , Brannelly Patrick , Pantazis Caroline , Screven Laurel , Andersh Kate , Kapasi Alifiya , Crary John F. , Gutman David , Dugger Brittany N. , Biber Sarah , Hohman Timothy , Faghri Faraz , Griswold Michael , Sargent Lana , van Keuren-Jensen Kendall , Singleton Andrew B. , Fann Yang , Nalls Mike A. , Iwaki Hirotaka
Published: October 2024

In this paper, we leveraged Large Language Models(LLMs) to accelerate data wrangling and automate labor-intensive aspects of data discovery and harmonization. This work promotes interoperability standards and enhances data discovery, facilitating AI-readiness in biomedical science with the generation of Common Data Elements (CDEs) as key to harmonizing multiple datasets. Thirty-one studies, various ontologies, and medical coding systems served as source material to create CDEs from which available metadata and context was sent as an API request to 4th-generation OpenAI GPT models to populate each metadata field. A human-in-the-loop (HITL) approach was used to assess quality and accuracy of the generated CDEs. To regulate CDE generation, we employed ElasticSearch and HITL to avoid duplicate CDEs and instead, added them as potential aliases for existing CDEs. The generated CDEs are foundational to assess the interoperability potential of datasets by determining how many data set column headers can be correctly mapped to CDEs as well as quantifying compliance with permissible values and data types. Subject matter experts reviewed generated CDEs and determined that 94.0% of generated metadata fields did not require manual revisions. Data tables from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Global Parkinson’s Genetic Program (GP2) were used as test cases for interoperability assessments. Column headers from all test cases were successfully mapped to generated CDEs at a rate of 32.4% via elastic search.The interoperability score, a metric for dataset compatibility to CDEs and other connected datasets, based on relevant criteria such as data field completeness and compliance with common harmonization standards averaged 53.8 out of 100 for test cases. With this project, we aim to automate the most tedious aspects of data harmonization, enhancing efficiency and scalability in biomedical research while decreasing activation energy for federated research.
Immune response induced by the Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV) in persons living with HIV (PLWH)
Authors: Cahn P. , Barreto L. , Figueroa M.I. , Fink V. , Rolón M.J. , Lopardo G. , Casetti I. , Ceschel M. , Patterson P. , Gambardella L. , Miernes G. , Nava A. , Gou J. , Wang R. , Zhu T. , Halperin S.A.
Published: October 2024

Background

Despite higher risk of poorer outcomes and potential sub-optimal vaccine effectiveness, people living with HIV (PLWH) are underrepresented in SARS-CoV-2 vaccine trials. We evaluated the safety and immunogenicity of the Ad5-nCoV vaccine (CanSino Biologics Inc./The Beijing Institute of Biotechnology) in PLWH.

Methods

In this single arm, open-label Phase 2b trial, PLWH were enrolled in Argentina. Participants received two doses of Ad5-nCoV vaccine (intramuscular, dosage 5×1010viral particles) at days 0 and 56. The primary outcomes were safety as serious adverse events [SAE], solicited and unsolicited local and systemic adverse events, impact on HIV viral load and CD4 counts and immunogenicity measured by S-RBD IgG and pseudo-virus neutralizing antibodies (nAbs) up to 52 weeks (ClinicalTrials.gov:NCT05005156).

Findings

Between June 2021-January 2022, 140 PLWH received at least one dose of Ad5-nCoV vaccine. At baseline, the majority were on antiretroviral therapy (99.3%), virologically suppressed (93.6%), with a median (IQR) CD4-cell count:736 (531-946) cells/ul. At baseline, 38 (27%) participants were seropositive for S-RBD antibodies, and 40 (28%) for nAbs. There were no SAEs related to the vaccine. Solicited AE within 7 days after first and second dose occurred in 93 (69%) and 75 (60%) participants, mostly grade 1, included pain, drowsiness and headache. The incidence of unsolicited AE within 28 days of vaccination was 10.7%. There were no significant changes in plasma viral load, CD4, CD4/CD8 ratio and no new AIDS-defining illnesses were reported. There were significant increases in the geometric mean titers (GMT) of S-RBD and nAbs between baseline to week 52. Seroconversion rates 28 days after the first and second doses (day 84) were 80% and 94% for S-RBD, and 35% and 78% for nAbs.

Interpretation

Two doses of the Ad5-nCoV vaccine were safe and induced an adequate immune response in virologically suppressed PLWH, maintaining high antibody titers at least during the first year post-vaccination.

Funding

CanSino Biologics Inc, Tianjin, China
Temporal and Thematic Analysis of Promotional Waterpipe-Related Posts on Twitter/X in the US
Authors: Ye Puhua , Wu Mengwei , Han Yiwei , Shimazaki Yuka , Cornacchione Ross Jennifer , Sutfin Erin L. , Li Dongmei , Xie Zidian
Published: October 2024

Introduction

Waterpipe tobacco smoking (WTS), also known as hookah, shisha, or narghile, is particularly popular among young people in the United States (US). WTS poses serious health risks similar to those of cigarette smoking.

Methods

Using the Twitter/X streaming API (Application Programming Interface), we collected 4,853,562 tweets between March 9, 2021, and March 14, 2023, using waterpipe-related keywords, such as “hookah” and “waterpipe”. After geographical filtering to identify tweets from the US and keyword filtering for the promotional content, we identified 23,803 promotional waterpipe-related tweets. We examined trends in the posting time of these promotional waterpipe-related tweets and identified prevalent topics from these tweets using the BERTopic (Bidirectional Encoder Representations from Transformers) modeling.

Results

The number of promotional waterpipe-related tweets showed an overall decreasing trend during the study period. The posting of promotional waterpipe-related tweets was more active later in the day. Major topics in the promotional tweets included “Promotion from hookah lounges and online hookah business" (63.97%, 15,227/23,803), "promoting hookah parties and events" (32.26%, 7,679/23,803), and "promoting engineered and durable hookah products" (3.77%, 897/23,803). Twitter/X accounts posting waterpipe-related promotional content have substantial variations in the number of relevant tweets (mean = 2.28, SD = 12.22) and followers (mean = 5,937, SD = 76,770).

Conclusions

This study demonstrates a significant social media activity in promoting waterpipe tobacco smoking. Our findings underscore the urgent need to regulate the promotional content of WTS on social media and promote public health education messages on social media to counteract the promotion of WTS.
Mediation analyses link cardiometabolic factors and liver fat with white matter hyperintensities and cognitive performance: A UK Biobank study
Authors: Askeland-Gjerde Daniel E. , Westlye Lars T. , Andersson Patrik , Korbmacher Max , de Lange Ann-Marie , van der Meer Dennis , Smeland Olav B. , Halvorsen Sigrun , Andreassen Ole A. , Gurholt Tiril P.
Published: October 2024

Background

Liver fat is associated with cardiometabolic disease, cerebrovascular disease, and dementia. Cerebrovascular disease, most frequently cerebral small vessel disease, identified by MRI as white matter hyperintensities (WMH), often contributes to dementia. However, liver fat’s role in the relationship between cardiometabolic risk, WMH, and cognitive performance is unclear.

Methods

In the UK Biobank cohort (n=32,628; 52.6% female; mean age 64.2±7.7 years; n=23,467 cognitive performance subsample), we used linear regression to investigate associations between cardiometabolic factors measured at baseline and liver fat, WMH, and cognitive performance measured at follow-up, on average, 9.3±2.0 years later. We used structural equation modeling to investigate whether liver fat mediates associations between cardiometabolic factors and WMH and whether WMH mediates associations between liver fat and cognitive performance.

Results

Nearly all cardiometabolic factors were significantly associated with liver fat (|r| in [0.03,0.41], p in [1.4x10-8,0〉) and WMH (|r| in [0.05,0.14], p in [1.5x10-13,2.7x10-148]) in regression models. Liver fat was associated with WMH (r=0.09,p=3x10-64) and cognitive performance (r=-0.03,p=1.5x10-7). Liver fat mediated the associations between cardiometabolic factors and WMH (|βmediation| in [0.01,0.03], pmediation in [5.7x10-9,0〉) and WMH mediated the associations between liver fat and cognitive performance (βmediation=-0.01,pmediation≍0).

Conclusions

Our findings indicate that liver fat mediates associations between cardiometabolic factors and WMH and that WMH mediates the association between liver fat and cognitive performance. This suggests that liver fat might be important for understanding the effects of cardiometabolic factors on cerebrovascular disease and cognitive function. Experimental studies are warranted to determine relevant targets for preventing vascular-driven cognitive impairment.
What role do adolescents’ independent food purchasing choices play in their dietary quality?
Authors: Shaw Sarah , Crozier Sarah , Cooper Cyrus , Smith Dianna , Barker Mary , Vogel Christina
Published: October 2024

During adolescence, many young people start to make more independent food purchases. Subsequently, these independent food choices will increasingly contribute to their overall diet quality; little is known, however, about this relationship. This study aimed to examine the role adolescents’ independent food purchases play in their diet quality and assess if these relationships vary according to socio-economic status.

A convenience sample of adolescents aged 11-18 years and attending secondary school or college in Hampshire, England, were recruited to participate in a one-week cross-sectional observational study. A validated 20-item Food Frequency Questionnaire assessed diet quality. Participants used an ecological momentary assessment mobile phone app to record food purchases.

Over seven days, 552 food/drink items were purchased on 253 food purchasing occasions by 80 participants. The majority of purchases (n=329, 60%) were coded as ‘not adhering’ to the UK Eatwell Guide, 32% were coded as ‘adhering’ and 9% fell between these two categories. Healthier food purchasing was associated with better diet quality (β 0.48, (95%CI 0.01, 0.96) p=0.05); results attenuated after adjustment for confounders (β 0.36, (95%CI −0.15, 0.87) p=0.16). Interaction models showed purchasing healthfulness was more strongly associated with diet quality among young people of lower SES (p=0.01). The majority of adolescents’ independent food purchases did not adhere to healthy eating guidelines. For adolescents experiencing socioeconomic disadvantage, these food choices had a more detrimental impact on their overall diet quality than they did for more advantaged adolescents. Future research should focus on identifying ways to support more healthful independent food choices by adolescents to reduce dietary inequalities and improve health and well-being among the next generation of adults.
Effects of the COVID-19 pandemic on TB outcomes in the United States: a Bayesian analysis
Authors: Swartwood Nicole A. , Cohen Ted , Marks Suzanne M. , Hill Andrew N. , Asay Garrett R. Beeler , Self Julie , Feng Pei-Jean I. , Robert Horsburgh C. , Salomon Joshua A. , Menzies Nicolas A.
Published: October 2024

Background

Tuberculosis (TB) cases and deaths in the United States fluctuated substantially during the COVID-19 pandemic. We analyzed multiple data sources to understand the factors contributing to these changes and estimated future TB trends.

Methods

We identified four mechanisms potentially contributing to observed TB trends during 2020– 2023: immigration, respiratory contact rates, rates of accurate diagnosis and treatment initiation, and mortality rates for persons with TB disease. We employed a Bayesian approach to synthesize evidence on how these mechanisms changed during the pandemic and how they might have combined to produce observed 2020–2023 TB data, using a transmission-dynamic model to link mechanisms to TB outcomes. We also simulated a no-pandemic counterfactual scenario that assumed mechanisms followed pre-pandemic trends. We estimated TB outcomes associated with the pandemic until 2035 to capture lagged effects. We evaluated additional scenarios to estimate the individual effect of each mechanism.

Results

Over the 2020–2035 study period, we estimate an additional 2,784 (95% uncertainty interval: 2,164–3,461) TB cases and 1,138 (1,076–1,201) TB deaths in the United States associated with changes occurring during the COVID-19 pandemic. The four mechanisms had offsetting effects – decreases in TB diagnosis rates and increases in TB mortality rates led to more TB deaths, while reductions in contact rates reduced TB deaths. Immigration changes initially reduced TB deaths, but increased deaths over time.

Discussion

While the direct impacts of the COVID-19 pandemic occurred between 2020–2023, these changes may continue to influence TB incidence and mortality in future years.

The COVID-19 pandemic disrupted steady declines in U.S. tuberculosis rates. Despite sharp decreases in TB cases over 2020–2021, we projected there would be 2,784 additional TB cases and 1,138 additional TB deaths during 2020–2035 associated with pandemic-related changes.
Predicting the natural yeast phenotypic landscape with machine learning
Authors: Khaiwal Sakshi , Chiara Matteo De , Barré Benjamin P , Barrio-Hernandez Inigo , Stenberg Simon , Beltrao Pedro , Warringer Jonas , Liti Gianni
Published: October 2024

Most organisms’ traits result from the complex interplay of many genetic and environmental factors, making their prediction from genotypes difficult. Here, we used machine learning models to explore genotype-phenotype connections for 223 life history traits measured across 1011 genome-sequencedSaccharomyces cerevisiaestrains. Firstly, we used genome-wide association studies to connect genetic variants with the phenotypes. Next, we benchmarked an automated machine learning pipeline that includes preprocessing, feature selection, and hyperparameters optimization in combination with multiple linear and complex machine learning methods. We determined gradient boosting machines as best performing in 65% of predictions and pangenome as best predictor, suggesting a considerable contribution of the accessory genome in controlling phenotypes. The accuracy broadly varied among the phenotypes (r = 0.2-0.9), consistent with varying levels of complexity, with stress resistance being easier to predict compared to growth across carbon and nitrogen nutrients. While no specific genomic features could be linked to the predictions for most phenotypes, machine learning identifies high-impact variants with established relationships to phenotypes despite being rare in the population. Near-perfect accuracies (r>0.95) were achieved when other phenomics data were used to aid predictions, suggesting shared useful information can be conveyed across phenotypes. Overall, our study underscores the power of machine learning to interpret the functional outcome of genetic variants.
Imputing not available values in single-cell DNA methylation data using the median is straightforward and effective
Authors: Tang Songming , Li Siyu , Chen Shengquan
Published: October 2024

Recent advances in single-cell DNA methylation have provided unprecedented opportunities to explore cellular epigenetic differences with maximal resolution. Due to the number of methylation sites exceeding the computational limits of current analytical methods, a common workflow for single-cell DNA methylation analysis is binning the genome into multiple regions and computing the average methylation level within each region. In this process, imputing not available (NA) values which are caused by the limited number of captured methylation sites is a necessary preprocessing step for downstream analyses. Existing studies have employed several simple imputation methods (such as zero imputation or mean imputation); however, there is a lack of theoretical studies or benchmark tests evaluating these approaches. Through both experiments and theoretical analysis, we found that using the median to impute missing data can effectively and simply reflect the methylation state of the NA values, providing an accurate foundation for downstream analyses.
Failure to reproduce the effect of procedural memory interference on wakeful consolidation of episodic memory in younger and older adults
Authors: Kamal Lara , Celik Busra , Alpert Griffin , Gonzalez Samantha , Nguyen Vian , Freedberg Michael
Published: October 2024

Brown and Robertson (2007) revealed that skill learning interferes with the wakeful consolidation of episodic memories in young adults. This finding is commonly used as evidence that episodic and procedural memories should not be learned in close temporal proximity but has not been reproduced by an independent laboratory. Additionally, older adults experience episodic memory deficits, but it is unknown whether this group is also vulnerable to this type of interference. We aimed to reproduce Brown and Robertson’s (2007) finding in younger adults, while also comparing the magnitude of interference between younger and older adults. Forty younger (18-40 years; n =20) and older adults (≥55 years; n = 20) visited the laboratory in the morning and acquired episodic memories (a list of words) immediately before a procedural finger-tapping (procedural) task. Half of all participants were exposed to a learnable sequential structure. In the afternoon of the same day, participants were asked to recall the episodic memories from the morning session. We found weak evidence of interference for both age groups and no statistical difference in interference between groups. Our results suggest that the interfering effects of these memory types may be negligible or overestimated, and that these memory types can be acquired together without interference.
Uncovering locomotor learning dynamics in people with Parkinson’s disease
Authors: Kim Aram , Schweighofer Nicolas , Petzinger Giselle M. , Finley James M.
Published: October 2024

Locomotor learning is important for improving gait and balance impairments in people with Parkinson’s disease (PD). While PD disrupts neural networks involved in motor learning, there is a limited understanding of how PD influences the time course of locomotor learning and retention. Here, we used a virtual obstacle negotiation task to investigate whether the early stages of PD affect the acquisition and retention of locomotor skills. On Day 1, 15 participants with PD and 20 age-matched controls were instructed to achieve a specified level of foot clearance while repeatedly stepping over two different virtual obstacles on a treadmill. We assessed online performance improvement on Day 1 and overnight retention after at least 24 hours on Day 2. We used a hierarchical Bayesian state-space model to estimate the learning rate and the degree of interference between the two obstacles. There was a 93% probability that people with PD learned the locomotor skill faster than controls, but there was limited evidence of group differences in interference between the two heights of obstacles. Both groups improved their performance to a similar magnitude during skill acquisition and performed similarly during retention on Day 2. Notably, a slower learning rate was associated with greater online performance improvement, while lower interference was linked to better overnight retention, and this effect was strongest for the control group. These results highlight that people with early-stage PD retain the ability to use multisensory information to acquire and retain locomotor skills. In particular, our finding that people with early-stage PD learned faster than age-matched controls may reflect the emergence of compensatory motor learning strategies used to offset early motor impairments in people with PD.
Phosphorylation Toggles the SARS-CoV-2 Nucleocapsid Protein Between Two Membrane-Associated Condensate States
Authors: Favetta Bruna , Wang Huan , Cubuk Jasmine , Barai Mayur , Ramirez Cesar , Gormley Adam J. , Murthy Sanjeeva , Soranno Andrea , Shi Zheng , Schuster Benjamin S.
Published: October 2024

The SARS-CoV-2 Nucleocapsid protein (N) performs several functions during the viral lifecycle, including transcription regulation and viral genome encapsulation. We hypothesized that N toggles between these functions via phosphorylation-induced conformational change, thereby altering N interactions with membranes and RNA. We found that phosphorylation changes how biomolecular condensates composed of N and RNA interact with membranes: phosphorylated N (pN) condensates form thin films, while condensates with unmodified N are engulfed. This partly results from changes in material properties, with pN forming less viscous and elastic condensates. The weakening of protein-RNA interaction in condensates upon phosphorylation is driven by a decrease in binding between pN and unstructured RNA. We show that phosphorylation induces a conformational change in the serine/arginine-rich region of N that increases interaction between pN monomers and decreases nonspecific interaction with RNA. These findings connect the conformation, material properties, and membrane-associated states of N, with potential implications for COVID-19 treatment.
Parasitic-plant parasite utilizes flowering pathways at unconventional stages to form stem-derived galls
Authors: Udandarao Naga Jyothi , Yamashita Yuki , Ushima Ryo , Tsuchida Tsutomu , Bessho-Uehara Kanako
Published: October 2024

Galls induced by various organisms exhibit diverse morphological and physiological characteristics, involving complex plant-insect interactions. Most transcriptome analyses to date have focused on leaf-derived galls. To better understand gall formation mechanisms, we investigated stem-derived galls induced by the weevilSmicronyx madaranuson the parasitic plantCuscuta campestrisat gene expression, cellular, and physiological levels. RNA-seq across four developmental stages identified differentially expressed genes and associated gene ontology terms. Consistent with histological observations, genes related to cell division and the cell cycle were upregulated early but decreased as the gall matured. Similar to leaf-derived galls, we found high expression ofPLETHORAand meristem-related homeobox genes in early gall development, suggesting that stem cell induction and maintenance are involved in various gall types. Like leaf- derived galls, the expression of genes related to floral organ development increased through the gall development. However, their expression patterns were dramatically different: downstream genes in the flowering pathway were highly expressed at the initial gall stage, whereas upstream genes were highly expressed later. This suggests that the weevil might activate the flowering pathway at unconventional stages, potentially rerouting the typical flowering cascade to influence gall development. Unlike the decrease in photosynthesis-related genes in leaf-derived galls, we observed an increase in these genes in galls formed on the stem of the holoparasitic plant. Shading experiments confirmed that photosynthesis is crucial for both gall growth and the weevil. This study highlights how gall-inducers can co-opt host resources and genetic pathways, offering new insights into the complexity of plant-insect interactions.
Spatial and seasonal biodiversity variation in a large Mediterranean lagoon using environmental DNA metabarcoding through sponge tissue collection
Authors: Corral-Lou Andrea , Ramón-Laca Ana , Alcaraz Lourdes , Cassidy Robert , Taboada Sergi , Mariani Stefano , Mercado Borja , Vicente Martin , Pérez-Ruzafa Ángel , Gallego Ramón , Riesgo Ana
Published: October 2024

Ecosystem monitoring is a fundamental tool to avert biodiversity loss, gathering valuable information that can be used to develop conservation policies, evaluating management outcomes, and guiding science-based decision-making. The Mar Menor costal lagoon (South-East of Spain) has experienced episodes of eutrophication due to intensive agriculture and other human activities, causing mass mortalities of marine fauna. In this scenario, biodiversity monitoring is crucial to evaluate the status of fauna and flora and take appropriate measures. Here, our main objective was to assess faunal composition and its spatial and temporal structure associated with the pillars used to support the built recreational well-being facilities along the Mar Menor. We capitalised on the many sea sponges that settle on these structures by collecting tissue samples for subsequent extraction of filtered environmental DNA (i.e. ‘natural sampler DNA’, nsDNA) in northern and southern areas of the lagoon, both in spring and summer. We metabarcoded all samples at the cytochrome oxidase subunit I gene (COI), and reliably identified 76 taxa belonging to nine different phyla, with annelids, poriferans, molluscs and cnidarians being the richest groups. We detected emblematic species of threatened status, such as pipefishes (genusSyngnathus) and the piddock clam,Pholas dactylus, and others known to become invasive, such as the ascidiansStyela canopusandBotrylloides niger, the barnacleAmphibalanus amphitrite, and the polychaetesBranchiomma bairdiandBranchiomma boholense. The use of common and widely distributed sponges as natural eDNA samplers allowed us to characterise both spatial and temporal diversity, further emphasizing the importance of this low-cost approach to monitoring biological communities in shallow coastal ecosystems.
Small molecule-directed differentiation of submerged-cultured human nasal airway epithelia for respiratory disease modelling
Authors: Dreyer Henriette H.M. , Ithakisiou Georgia-Nefeli , Spelier Sacha , Iwanski Malina K. , Katrukha Eugene , Terstappen Jonne , Rodenburg Lisa W. , den Hertog-Oosterhoff Loes A. , Smits Shannon M.A. , van der Windt Isabelle S. , Azink Lotte T. , Bijlard Linda H.M. , Passier Koen , van Beuningen Sam F.B. , Lebbink Robert Jan , Haarman Eric G. , van der Ent Cornelis K. , Kapitein Lukas C. , Bont Louis J. , Beekman Jeffrey M. , Amatngalim Gimano D.
Published: October 2024

Submerged cultures of undifferentiated or transformed epithelial cells are widely used in respiratory research due to their ease of use and scalability. However, these systems fail to capture the cellular diversity of the human airway epithelium. In this study, we developed anin vitromodel where cryopreserved human nasal epithelial cells, collected by brushings, are differentiated under submerged conditions on standard plastic cultureware. By applying small-molecule inhibitors targeting Notch and BMP signaling, we achieved efficient differentiation of cultures containing basal, secretory, and ciliated cells. This approach supports scalable culturing of both 2D epithelial monolayers and 3D organoids, validated as (personalized) disease models for primary ciliary dyskinesia, cystic fibrosis, and respiratory syncytial virus infection. This model offers a cost-effective, scalable platform that combines the simplicity of traditional cultures with the cellular complexity of the human airway epithelium, providing a valuable tool for respiratory disease research.
Charting the landscape of cytoskeletal diversity in microbial eukaryotes
Authors: Mikus Felix , Ramos Armando Rubio , Shah Hiral , Olivetta Marine , Borgers Susanne , Hellgoth Jonas , Saint-Donat Clémence , Araújo Margarida , Bhickta Chandni , Cherek Paulina , Bilbao Jone , Txurruka Estibalitz , Leisch Nikolaus , Schwab Yannick , Husnik Filip , Seoane Sergio , Probert Ian , Guichard Paul , Hamel Virginie , Dey Gautam , Dudin Omaya
Published: October 2024

Microbial eukaryotes are small and often resistant to standard labelling and imaging techniques, and therefore remain understudied – despite their critical ecological importance - with the exception of a few established models. Here, we use Ultrastructure Expansion Microscopy (U-ExM) to carry out high-resolution volumetric imaging of over 200 cultured planktonic eukaryotes across major lineages. By combining U-ExM with pan- and specific immuno-labelling, we reveal novel microtubule and centrin-containing elements and assign molecular identities to enigmatic cytoskeletal structures observed previously only by electron microscopy. Our investigation represents the first systematic survey of the extensive cytoskeletal diversity on display across the eukaryotic tree, including the major species groups of dinoflagellates, haptophytes, ciliates, euglenids, cryptomonads, and green algae. Our U-ExM approach extends to mixed environmental samples, paving the way for environmental cell biology at ultrastructural resolution and unprecedented scale, a crucial step towards understanding and protecting complex ecosystems in the face of biodiversity loss.
Engineering Rydberg-pair interactions in divalent atoms with hyperfine-split ionization thresholds
Authors: Hummel Frederic , Weber Sebastian , Mögerle Johannes , Menke Henri , King Jonathan , Bloom Benjamin , Hofferberth Sebastian , Li Ming
Published: October 2024

Quantum information processing with neutral atoms relies on Rydberg excitation for entanglement generation. While the use of heavy divalent or open-shell elements, such as strontium or ytterbium, has benefits due to their optically active core and a variety of possible qubit encodings, their Rydberg structure is generally complex. For some isotopes in particular, hyperfine interactions are relevant even for highly excited electronic states. We employ multichannel quantum defect theory to infer the Rydberg structure of isotopes with nonzero nuclear spin and perform nonperturbative Rydberg-pair interaction calculations. We find that due to the high level density and sensitivities to external fields, experimental parameters must be precisely controlled. Specifically in Sr87, we study an intrinsic Förster resonance, unique to divalent atoms with hyperfine-split thresholds, which simultaneously provides line stability with respect to external field fluctuations and enhanced long-range interactions. Additionally, we provide parameters for pair states that can be effectively described by single-channel Rydberg series. The explored pair states provide exciting opportunities for applications in the blockade regime, as well as for more exotic long-range interactions such as largely flat, distance-independent potentials.

Published by the American Physical Society
2024
Stakeholder influence, local revenue mobilisation and service delivery in district local governments: evidence from districts in Northern Uganda
Authors: Acak Pasquine , Nalukenge Irene , Nyamuyonjo David , Kyejjusa Sarah
Published: October 2024

Purpose

This study examines the contribution of stakeholder influence and local revenue mobilisation to service delivery in district local governments in Northern Uganda.

Design/methodology/approach

This was a cross-sectional and correlational study. Data were collected from the district Local Governments in Northern Uganda using a questionnaire. The unit of analysis was a district. The district’s Chief Finance Officer (CFO), Clerk-to-Council, and Community Development Officer were units of enquiry in this study. The data were analysed using correlation coefficients and linear regression using partial least squares structural equation modelling (PLS-SEM).

Findings

The results suggest that stakeholder influence and local revenue mobilisation predict service delivery. The results further indicate that local revenue mobilisation contributes more to service delivery than stakeholder influence.

Originality/value

This study provides empirical evidence on the contribution of stakeholder influence and revenue mobilisation to service delivery using evidence from districts in Northern Uganda adding to the scanty literature in developing countries.
Acceptance of insects as food in Germany: risk–benefit perceptions and the role of risk preferences
Authors: Kirsten Lea , Garvert Rebecca , Teuber Ramona
Published: October 2024

Purpose

With a growing world population and climate crises, edible insects are a promising alternative to conventional livestock. However, Western consumers are largely opposed to eating insects. The aim of this study is to investigate the acceptance of insects in a German sample with a specific focus on risk–benefit perceptions and risk preferences.

Design/methodology/approach

Data were collected via an online survey (N = 569). Established scales for food neophobia (FN), risk perception, risk preference and acceptance were used. The statistical analyses included mean comparisons regarding acceptance and risk–benefit perceptions of unprocessed and processed insects. We further examined the role of perceived benefits and risks as well as risk preferences as determinants of acceptance via hierarchical multiple regressions.

Findings

Respondents indicated lower perceived risks, and higher perceived benefits and thus higher acceptance for processed insect products as compared to whole insects. Risk perception was the strongest predictor of acceptance of unprocessed as well as processed insect food. Respondents who reported to have already eaten insects before exhibited higher risk preferences than those who had not.

Originality/value

This study specifically considered the role of risk preferences, which has been so far largely overlooked in consumer research on insect foods. The findings indicate that acceptance of insect food is mainly driven by risk perception rather than individual risk preferences. However, risk preferences should not be totally overlooked as they seem to play a role especially for unprocessed insects and the decision to try insects for the first time.