bluuebunny/crossref_metadata_2025 huggingface dataset:
The concreteness effect from memory illusions’ perspective: the DIM-HA effect
Authors: Marín-Gutiérrez Alejandro , Díez Villoria Emiliano , González Ana María
Published: July 2023

A vast body of evidence has shown that concrete nouns are processed faster and more accurately than abstract nouns in a variety of cognitive tasks. This phenomenon is widely known as the concreteness effect and explanations for its occurrence seem to reflect differences in processing and organization between both type of concepts. While there is considerable evidence to support this concrete effect, the nature of these differences is still controversial. In developing this explanation, we have proposed a relatively different approach from a false memory perspective using the DRM paradigm. Three different experiments were created to address the importance of association in creating concrete and abstract false memories. Results showed that false recognition rates differed significantly between concrete and abstract critical words when they were associated strongly with their respective lists, which led to a higher proportion of abstract false alarms both in behavioral and electrophysiological experiments. The principal outcomes were discussed in terms of theories of associative activation and qualitatively different representation.
Dietary pattern and diversity analysis using ‘DietR’ package in R
Authors: Sadohara Rie , Jacobs David , Pereira Mark A. , Johnson Abigail J.
Published: July 2023

There are scarce resources available for analyzing 24-hour dietary records. Here we introduce DietR, a set of functions written in R for the analysis of 24-hour dietary recall or records data, collected with either the Automated Self-Administered 24-hour (ASA24) dietary assessment tool or two-day data from the National Health and Nutrition Examination Survey (NHANES). The R functions are intended for food and nutrition researchers who are not computational experts. DietR provides users with functions to (1) clean dietary data; (2) analyze 24-hour dietary intakes in relation to other study-specific metadata variables; (3) visualize percentages of calorie intake from macronutrients; (4) perform principal component analysis (PCA) ork-means to group participants by similar dietary patterns; (5) generate foodtrees based on the hierarchical information of food items consumed; (6) perform principal coordinate analysis (PCoA) taking food classification information into account; (7) and calculate diversity metrics for overall diet and specific food groups. DietR includes a set of tutorials available on a website (https://computational-nutrition-lab.github.io/DietR/), which are designed to be self-paced study materials. DietR enables users to visualize dietary data and conduct data-driven dietary pattern analyses using R to answer research questions regarding diet. As a demonstration of DietR, we applied DietR to a set of created 24-hour dietary records data to demonstrate the basic functions of the package. We also applied DietR to a subset of 24-hour recall data from NHANES to demonstrate analyses using dietary diversity metrics. We present the results of this example NHANES analysis comparing legume diversity with waist circumference.
The dopamine inhibitor GBR12909 improves attention and compulsive behaviour in female rats
Authors: Abdulkader Sara , Gigg John
Published: July 2023

Background

Stimulants such as methylphenidate are the first-line treatment for attention deficit hyperactivity disorder (ADHD). A principal mechanism of action for these drugs is to reduce dopamine reuptake in the striatum. However, the ensuing risk of abuse with such stimulants means there is an urgent need for new, low-risk therapeutic agents. GBR12909 is a highly selective dopamine reuptake inhibitor, making it an important experimental tool. Indeed, this drug completed Phase II clinical trials for treatment of cocaine abuse. Understanding such drugs has the potential to expand our understanding of the striatal dopamine contribution to impulsivity, attention and compulsive behaviour and will help the development of novel targeted treatments for ADHD without an abuse risk.

Aims

The aim of this work was to examine the role of low doses of GBR12909 on attention, impulsivity and compulsive behaviour as measured by 5C-CPT. Oldham’s methods was used to determine the presence of a rate-dependent effect.

Methods

Female Lister hooded rats were trained to criterion in the 5C-CPT (>70% accuracy, < 30% omission and < 40% false alarms). Effects of GBR12909 (0.25-1 mg/kg) were investigated on attention, impulsivity and compulsive behaviour under challenging task conditions.

Results

The two lowest doses of GBR12909 improved selective attention in a rate-dependent manner while the highest dose of GBR 12909 showed a tendency toward improving compulsive behaviour in a baseline-dependent manner. However, GBR 12909 impaired waiting impulsivity in a baseline-dependent manner.

Conclusions

GBR12909 has a clearly beneficial effect on attention and compulsive behaviour in the female rat. These findings support further clinical investigation of GBR-type dopamine uptake blockers or GBR analogues to facilitate the discovery of medications for inattentive ADHD, stimulant abuse, compulsive drug seeking behaviour and obsessive-compulsive disorder.
Genetic Variations and Altered Blood mRNA Level of Circadian Genes and BDNF as Risk Factors of Post-Stroke Cognitive Impairment among Eastern Indians
Authors: Sadhukhan Dipanwita , Biswas Arindam , Mishra Smriti , Maji Daytee , Mitra Parama , Mukherjee Priyanka , Podder Gargi , Ray Biman Kanti , Biswas Atanu , Banerjee Tapas Kumar , Hui Subhra Prakash , Deb Ishani
Published: July 2023

Background

Post-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It regulates and being regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI is limited.

Aim

We aim here to determine a) genetic risk variants in circadian clock genes,BDNFand b) dysregulation in expression level ofCLOCK, BMAL1 andBDNF, that may be associated with PSCI.

Methods

BDNF (rs6265G/A, rs56164415C/T), CLOCK (rs1801260T/C, rs4580704G/C) and CRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analysed their gene expression in PBMC from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA.

Results

Among the studied variants, only rs4580704/CLOCKshowed an overall association with PSCI (P = 0.001) and lower BMSE score. Its ‘C’ allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNFwhile the ‘CC’ genotype of rs2292912/CRY2negatively influenced language and executive function. A significant decrease in gene expression forCLOCKandBDNFin PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. Unlike, Pro-BDNF, plasma level mBDNF was also lower in them.

Conclusions

Our results suggest that the circadian genes andBDNFplay a role in PSCI on both genetic and transcript level.
Identification of Spinster Homolog 3 as a novel putative LL-37 receptor
Authors: Corrêa Alana Bazán , de Lima Thais Martins , Ariga Suely Kubo , Pinheiro da Silva Fabiano
Published: July 2023

Background

Antimicrobial Peptides are primitive components of the innate immune response. LL-37, a human antimicrobial peptide, has been researched for its therapeutic potential in immune-inflammatory diseases. This study aimed to identify novel LL-37 receptors.

Methods and Results

Using the phage display technique, the sequence GNWSFV was selected and found to bind to LL-37. BLAST analysis revealed that this sequence has a high degree of similarity to a portion of human transmembrane protein Spinster Homolog 3.

Conclusion

Our study suggests that Spinster Homolog 3 may be a potential therapeutic target for LL-37-related diseases.
Prevalence and Associated Risk Factors of Scabies and Impetigo: A Cross-Sectional Study in the Nata Catchment Areas of Tutume District, Botswana
Authors: Nthibo Leungo Audrey , Molefi Tuduetso Leka , Kololo Sidney Otladisa , Leeme Tshepo Botho , Selemogo Mpho , Molefi Mooketsi
Published: July 2023

Background

Scabies is a poorly understood disease in the developing world, particularly in regions with high disease burden. Lack of epidemiological data, especially in sub-Saharan Africa, hampers our understanding of the disease’s occurrence and impact. This study aimed to estimate the prevalence and associated risk factors of scabies and impetigo in the Nata catchment areas of Tutume district.

Methodology

A cross-sectional study was conducted in the Nata catchment area, targeting the settlements of Manxhotae, Malelejwe, Ndutshaa, and Tshwaane. Participants were randomly selected from randomly selected households. Data were collected using questionnaires, and scabies was confirmed by skin examination using the International Alliance for the Control of Scabies (IACS) consensus criteria. Statistical significance was set at p<0.05, with a 95% confidence interval for precision.

Results

A total of 429 participants were enrolled across the four settlements. The highest prevalence of scabies was in Manxhotae at 27.1% (21.2-34.0) and Ndutshaa at 23.4% (13.4-37.3). Malelejwe and Tshwaane had lower prevalence of 10.4% (6.2-16.8) and 3.4% (0.8-12.7), respectively. Only five(5) cases of impetigo were identified. Multivariable logistic regression analysis using the IACS criteria revealed that younger age and a household member with an itch were strongly associated with scabies, with adjusted odds ratios (AOR) of 5.69 [3.16-10.26] and 5.31 [2.76-10.21], respectively, however, a less sensitive criterion also included less frequent bathing as a significant exposure, AOR of 3.3 [1.9-5.8]

Conclusion

The prevalence of scabies in the Nata catchment area was unexpectedly high. The risk factors included younger age, a household member with an itch, and less frequent bathing. Prospective studies are needed to explore household disease transmission dynamics and risk factors specific to the youth.

Author Summary

This study was carried out in the Nata catchment area in Tutume district, Botswana. It aimed to assess the burden, risk factors informing effective disease control programs. The survey involved interviews and skin examination by a health worker. Findings revealed a higher incidence of scabies cases, while impetigo cases were less prevalent. These results highlight the need for community-wide interventions to mitigate the disease’s impact. Identified risk factors include younger age, residing with an individual experiencing itchiness, and infrequent bathing. Overall, this study supports advocating for scabies as a neglected tropical disease.
Multigenerational effects of tire wear particle leachate through trophic transfer from producer to primary consumer
Authors: Chai Yanchao , Wang Haiqing , Yang Jiaxin
Published: July 2023

Tire wear particle (TWP) and their leachate have been known toxic for aquatic organism due to additives released from the rubber matrix. However, it is not clear whether the ecotoxicity of TWP leachate could be transferred through algae-zooplankton food chain especially after multi generations. In this work, the effect of different concentrations TWP leachate on growth of microalgae,Chlorella pyrenoidesa, was studied. Subsequently, those algae were fed to zooplankton rotifer,Brachionus calyciflorus, which continuously lasted for ten generations to explore multigenerational accumulation of TWP leachate ecotoxicity through food-chain transfer. The results showed that the TWP leachate displayed growth inhibition for algae with evident concentration effect. For rotifer fed with those contaminated microalgae, though the first two generations showed hormesis, the ecotoxicity exhibited after 2 generations, characterized by reduction of lifespan and offspring number. The ecological effects of TWP leachate were transferred from algae to rotifer. In addition, the ecotoxicity gradually aggravated along with generation passage and exposure concentration of algae. What was even more, population passage of rotifer collapsed totally with no offspring after 5-generations feed by algae exposed to high concentration TWP leachate. Based on those, it is summarized that the ecological effects of TWP leachate indeed can be transferred from low to high trophic level in food chain, and accumulate across generations passage. The indirect non-contact exposure through food chain should be considered at the risk assessment of TWP. Single generation exposure will underestimate their ecological risk from long term.
Analysis of RNA translation with a deep learning architecture provides new insight into translation control
Authors: Fan Xiaojuan , Chang Tiangen , Chen Chuyun , Hafner Markus , Wang Zefeng
Published: July 2023

Accurate annotation of coding regions in RNAs is essential for understanding gene translation. We developed a deep neural network to directly predict and analyze translation initiation and termination sites from RNA sequences. Trained with human transcripts, our model learned hidden rules of translation control and achieved a near perfect prediction of canonical translation sites across entire human transcriptome. Surprisingly, this model revealed a new role of codon usage in regulating translation termination, which was experimentally validated. We also identified thousands of new open reading frames in mRNAs or lncRNAs, some of which were confirmed experimentally. The model trained with human mRNAs achieved high prediction accuracy of canonical translation sites in all eukaryotes and good prediction in polycistronic transcripts from prokaryotes or RNA viruses, suggesting a high degree of conservation in translation control. Collectively, we present a general and efficient deep learning model for RNA translation, generating new insights into the complexity of translation regulation.
Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal new properties of the cardiac voltage-gated sodium channel
Authors: Minard Annabel Y , Clark Colin J , Ahern Christopher A , Piper Robert C
Published: July 2023

Voltage-gated sodium (NaV) channels drive the upstroke of the action potential and are comprised of a pore-forming α-subunit and regulatory β-subunits. The β-subunits modulate the gating, trafficking, and pharmacology of the α-subunit. These functions are routinely assessed by ectopic expression in heterologous cells. However, currently available expression systems may not capture the full range of these effects since they contain endogenous β-subunits. To better reveal β-subunit functions, we engineered a human cell line devoid of endogenous NaVβ-subunits and their immediate phylogenetic relatives. This new cell line, β-subunit-eliminated eHAP expression cells (BeHAPe), were derived from haploid eHAP cells by engineering inactivating mutations in SCN1B, SCN2B, SCN3B, SCN4B, MPZL1, MPZL2, MPZL3, MPZ and JAML. In diploid BeHAPe cells, the cardiac NaVα-subunit, NaV1.5, was highly sensitive to β-subunit modulation and revealed that each β-subunit and even MPZ imparted unique gating properties. Furthermore, combining β1 and β2 with NaV1.5 generated a sodium channel with hybrid properties, distinct from the effects of the individual subunits. Thus, this approach revealed an expanded ability of β-subunits to regulate NaV1.5 activity and can be used to improve the characterization of other α/β NaVcomplexes.
TheSORL1p.Y1816C variant causes impaired endosomal dimerization and autosomal dominant Alzheimer’s disease
Authors: Jensen Anne Mette G. , Raska Jan , Fojtik Petr , Monti Giulia , Lunding Melanie , Vochyanova Simona , Pospisilova Veronika , van der Lee Sven J. , Dongen Jasper Van , Bossaerts Liene , Broeckhoven Christine Van , Dols Oriol , Lléo Alberto , Benussi Luisa , Ghidoni Roberta , Hulsman Marc , Sleegers Kristel , Bohaciakova Dasa , Holstege Henne , Andersen Olav M.
Published: July 2023

Truncating genetic variants ofSORL1, encoding the endosome recycling receptor SORLA, have been accepted as causal of Alzheimer’s disease (AD). However, most genetic variants observed inSORL1are missense variants, for which it is complicated to determine the pathogenicity level because carriers come from pedigrees too small to be informative for penetrance estimations. Here, we describe three unrelated families in which theSORL1coding missense variant rs772677709, that leads to a p.Y1816C substitution, segregates with Alzheimer’s disease. Further, we investigate the effect of SORLA p.Y1816C on receptor maturation, cellular localization and trafficking in cell-based assays. Under physiological circumstances, SORLA dimerizes within the endosome, allowing retromer-dependent trafficking from the endosome to the cell surface, where the luminal part is shed into the extracellular space (sSORLA). Our results showed that the p.Y1816C mutant impairs SORLA dimerization in the endosome leading to a strong decrease in trafficking to the cell surface, resulting in decreased sSORLA shedding. Furthermore, we find that iPSC-derived neurons with engineered p.Y1816C mutation have enlarged endosomes, a defining cytopathology of AD.

Our studies provide genetic as well as functional evidence that theSORL1p.Y1816C variant is causal for AD. The high penetrance of the mutation suggests this mutation should be considered in clinical genetic screening of multiplex early-onset AD families.
Estimating the instantaneous reproduction number (Rt)by using particle filter
Authors: Won Yong Sul , Son Woo-Sik , Choi Sunhwa , Kim Jong-Hoon
Published: July 2023

Background

Monitoring the transmission of coronavirus disease 2019 (COVID-19) requires accurate estimation of the effective reproduction number (Rt). However, existing methods for calculatingRtmay yield biased estimates if important real-world factors, such as delays in confirmation, pre-symptomatic transmissions, or imperfect data observation, are not considered.

Method

To include real-world factors, we expanded the susceptible-exposed-infectious-recovered (SEIR) model by incorporating pre-symptomatic (P) and asymptomatic (A) states, creating the SEPIAR model. By utilizing both stochastic and deterministic versions of the model, and incorporating predetermined time series ofRt, we generated simulated datasets that simulate real-world challenges in estimatingRt. We then compared the performance of our proposed particle filtering method for estimatingRtwith the existing EpiEstim approach based on renewal equations.

Results

The particle filtering method accurately estimatedRteven in the presence of data with delays, pre-symptomatic transmission, and imperfect observation. When evaluating via the root mean square error (RMSE) metric, the performance of the particle filtering method was better in general and was comparable to the EpiEstim approach if perfectly deconvolved infection time series were provided, and substantially better whenRtexhibited short-term fluctuations and the data was right truncated.

Conclusions

The SEPIAR model, in conjunction with the particle filtering method, offers a reliable tool for predicting the transmission trend of COVID-19 and assessing the impact of intervention strategies. This approach enables enhanced monitoring of COVID-19 transmission and can inform public health policies aimed at controlling the spread of the disease.
A machine-learning evaluation of biomarkers designed for the future of precision medicine
Authors: Climer Sharlee
Published: July 2023

Precision medicine is cognizant of the impact of genetics and environments on subtypes of heterogeneous diseases and aims to identify, diagnose, and treat each subtype appropriately. Real-valued biomarkers, such as protein levels in plasma, are key for practical subtype diagnoses and hold potential to elucidate subtypes and illuminate promising drug targets. Biomarkers that are common across all subtypes have been discovered using fold change (FC) and the area under the receiver operating characteristic curve (AUC). However, FC and AUC fail to identify biomarkers for subtypes when they comprise less than half of the disease group. We present here a machine-learning biomarker evaluation method based on clustering of the data points, referred to as Difference in Bicluster Distances (DBD). We contribute efficient, yet optimal, software coupled with rigorous validation techniques, and demonstrate our approach on a late-onset Alzheimer disease (AD) gene expression dataset. Our trials produced four significant genes and appropriate thresholds for biomarker diagnostics. While none of these genes were identified as significant by either FC or AUC for the given dataset, the genes have been independently associated with AD or neurological disorders by other groups using completely independent means. In summary, DBD provides a unique and effective method for screening real-valued data to identify biomarkers associated with subtypes of heterogeneous diseases.
Systems biology and machine learning approaches identify metabolites that influence dietary lifespan and healthspan responses across flies and humans
Authors: Hilsabeck Tyler A.U. , Narayan Vikram P. , Wilson Kenneth A. , Carrera Enrique , Raftery Daniel , Promislow Daniel , Brem Rachel B. , Campisi Judith , Kapahi Pankaj
Published: July 2023

Dietary restriction (DR) is a potent method to enhance lifespan and healthspan, but individual responses are influenced by genetic variations. Understanding how metabolism-related genetic differences impact longevity and healthspan are unclear. To investigate this, we used metabolites as markers to reveal how different genotypes respond to diet to influence longevity and healthspan traits. We analyzed data fromDrosophilaGenetic Reference Panel strains raised under AL and DR conditions, combining metabolomic, phenotypic, and genome-wide information. Employing two computational methods across species—random forest modeling within the DGRP and Mendelian randomization in the UK Biobank—we pinpointed key traits with cross-species relevance that influence lifespan and healthspan. Notably, orotate was linked to parental age at death in humans and counteracted DR effects in flies, while threonine extended lifespan, in a strain- and sex-specific manner. Thus, utilizing natural genetic variation data from flies and humans, we employed a systems biology approach to elucidate potential therapeutic pathways and metabolomic targets for diet-dependent changes in lifespan and healthspan.
Learning and memory deficits produced by aspartame are heritable via the paternal lineage
Authors: Jones Sara K. , McCarthy Deirdre M. , Stanwood Gregg D. , Schatschneider Chris , Bhide Pradeep G.
Published: July 2023

Environmental exposures produce heritable traits that can linger in the population for one or two generations. Millions of individuals consume substances such as artificial sweeteners daily that are declared safe by regulatory agencies without evaluation of their potential heritable effects. We show that consumption of aspartame, an FDA-approved artificial sweetener, daily for up to 16-weeks at doses equivalent to only 7-15% of the FDA recommended maximum daily intake value (equivalent to 2-4 small, 8 oz diet soda drinks per day) produces significant spatial learning and memory deficits in mice. Moreover, the cognitive deficits are transmitted to male and female descendants along the paternal lineage suggesting that aspartame’s adverse cognitive effects are heritable, and that they are more pervasive than current estimates, which consider effects in the directly exposed individuals only. Traditionally, deleterious environmental exposures of pregnant and nursing women are viewed as risk factors for the health of future generations. Environmental exposures of men are not considered to pose similar risks. Our findings suggest that environmental exposures of men can produce adverse impact on mental health of future generations and demonstrate the need for considering heritable effects via the paternal lineage as part of the regulatory evaluations of artificial sweeteners.
Multi-organ Metabolic Model ofZea maysConnects Temperature Stress with Thermodynamics-Reducing Power-Energy Generation Axis
Authors: Chowdhury Niaz Bahar , Decouard Berengere , Quillere Isabelle , Rigault Martine , Sajeevan Karuna Anna , Acharya Bibek , Chowdhury Ratul , Hirel Bertrand , Dellagi Alia , Maranas Costas , Saha Rajib
Published: July 2023

Global climate change has severely impacted maize productivity. A holistic understanding of metabolic crosstalk among its organs is essential to address this issue. Thus, we reconstructed the first multi-organ maize genome-scale metabolic model,iZMA6517, and contextualized it with heat and cold stress-related transcriptomics data using the novelEXpression disTributedREAction fluxMeasurement (EXTREAM) algorithm. Furthermore, implementing metabolic bottleneck analysis on contextualized models revealed fundamental differences between these stresses. While both stresses had reducing power bottlenecks, heat stress had additional energy generation bottlenecks. To tie these signatures, we performed thermodynamic driving force analysis, revealing thermodynamics-reducing power-energy generation axis dictating the nature of temperature stress responses. Thus, for global food security, a temperature-tolerant maize ideotype can be engineered by leveraging the proposed thermodynamics-reducing power-energy generation axis. We experimentally inoculated maize root with a beneficial mycorrhizal fungus,Rhizophagus irregularis, and as a proof of concept demonstrated its potential to alleviate temperature stress. In summary, this study will guide the engineering effort of temperature stress-tolerant maize ideotypes.
DISCOVERY AND VALIDATION OF GENES DRIVING DRUG-INTAKE AND RELATED BEHAVIORAL TRAITS IN MICE
Authors: Roy Tyler A. , Bubier Jason A. , Dickson Price E. , Wilcox Troy D. , Ndukum Juliet , Clark James W. , Sukoff Rizzo Stacey J. , Crabbe John C. , Denegre James M. , Svenson Karen L. , Braun Robert E. , Kumar Vivek , Murray Stephen A. , White Jacqueline K. , Philip Vivek M. , Chesler Elissa J.
Published: July 2023

Substance use disorders (SUDs) are heritable disorders characterized by compulsive drug use, but the biological mechanisms driving addiction remain largely unknown. Genetic correlations reveal that predisposing drug-naïve phenotypes, including anxiety, depression, novelty preference, and sensation seeking, are predictive of drug-use phenotypes, implicating shared genetic mechanisms. Because of this relationship, high-throughput behavioral screening of predictive phenotypes in knockout (KO) mice allows efficient discovery of genes likely to be involved in drug use. We used this strategy in two rounds of screening in which we identified 33 drug-use candidate genes and ultimately validated the perturbation of 22 of these genes as causal drivers of substance intake. In our initial round of screening, we employed the two-bottle-choice paradigms to assess alcohol, methamphetamine, and nicotine intake. We identified 19 KO strains that were extreme responders on at least one predictive phenotype. Thirteen of the 19 gene deletions (68%) significantly affected alcohol use three methamphetamine use, and two both. In the second round of screening, we employed a multivariate approach to identify outliers and performed validation using methamphetamine two-bottle choice and ethanol drinking-in-the-dark protocols. We identified 15 KO strains that were extreme responders across the predisposing drug-naïve phenotypes. Eight of the 15 gene deletions (53%) significantly affected intake or preference for three alcohol, eight methamphetamine or three both (3). We observed multiple relations between predisposing behaviors and drug intake, revealing many distinct biobehavioral processes underlying these relationships. The set of mouse models identified in this study can be used to characterize these addiction-related processes further.
ENTRAIN: integrating trajectory inference and gene regulatory networks with spatial data to co-localize the receptor-ligand interactions that specify cell fate
Authors: Kyaw Wunna , Chai Ryan C. , Khoo Weng Hua , Goldstein Leonard D. , Croucher Peter I. , Murray John M. , Phan Tri Giang
Published: July 2023

Cell fate is commonly studied by profiling the gene expression of single cells to infer developmental trajectories based on expression similarity, RNA velocity, or statistical mechanical properties. However, current approaches do not recover microenvironmental signals from the cellular niche that drive a differentiation trajectory. We resolve this with environment-aware trajectory inference (ENTRAIN), a computational method that integrates trajectory inference methods with ligand-receptor pair gene regulatory networks to identify extracellular signals and evaluate their relative contribution towards a differentiation trajectory. The output from ENTRAIN can be superimposed on spatial data to co-localize cells and molecules in space and time to map cell fate potentials to cell-cell interactions. We validate and benchmark our approach on single-cell bone marrow and spatially resolved embryonic neurogenesis datasets to identify known and novel environmental drivers of cellular differentiation. ENTRAIN is available as a public package athttps://github.com/theimagelab/entrainand can be used on both single-cell and spatially resolved datasets.
Methylotrophy in the Mire: direct and indirect routes for methane production in thawing permafrost
Authors: Ellenbogen Jared B. , Borton Mikayla A. , McGivern Bridget B. , Cronin Dylan R. , Hoyt David W. , Freire-Zapata Viviana , McCalley Carmody K. , Varner Ruth K. , Crill Patrick M. , Wehr Richard A. , Chanton Jeffrey P. , Woodcroft Ben J. , Tfaily Malak M. , Tyson Gene W. , Rich Virginia I. , Wrighton Kelly C.
Published: July 2023

While wetlands are major sources of biogenic methane (CH4), our understanding of resident microbial metabolisms is incomplete, which compromises prediction of CH4emissions under ongoing climate change. Here, we employed genome-resolved multi-omics to expand our understanding of methanogenesis in the thawing permafrost peatland of Stordalen Mire, in arctic Sweden. In quadrupling the genomic representation of the site’s methanogens and examining their encoded metabolisms, we revealed that nearly 20% (72) of the metagenome-assembled genomes (MAGs) encoded potential for methylotrophic methanogenesis. Further, 27% of the transcriptionally active methanogens expressed methylotrophic genes; forMethanosarcinalesandMethanobacterialesMAGs, these data indicated use of methylated oxygen compounds (e.g., methanol), while forMethanomassiliicoccales, they primarily implicated methyl sulfides and methylamines. In addition to methanogenic methylotrophy, >1700 bacterial MAGs across 19 phyla encoded anaerobic methylotrophic potential, with expression across 12 phyla. Metabolomic analyses revealed the presence of diverse methylated compounds in the Mire, including some known methylotrophic substrates. Active methylotrophy was observed across all stages of a permafrost thaw gradient in Stordalen, with the most frozen non-methanogenic palsa found to host bacterial methylotrophy, and the partially thawed bog and fully thawed fen seen to house both methanogenic and bacterial methylotrophic activity. Methanogenesis across increasing permafrost thaw is thus revised from sole dominance of hydrogenotrophic production, and the appearance of acetoclastic at full thaw, to consider co-occurrence of methylotrophy throughout. Collectively, these findings indicate that methanogenic and bacterial methylotrophy may be an important and previously underappreciated component of carbon cycling and emissions in these rapidly changing wetland habitats.
Age-associated alterations in thalamocortical structural connectivity in psychosis-spectrum youths
Authors: Lewis Lydia , Corcoran Mary , Cho Kang Ik K. , Kwak YooBin , Hayes Rebecca , Jalbrzikowski Maria
Published: July 2023

Objective

Psychotic symptoms typically emerge in adolescence when connections between the thalamus and cortex are still maturing. The extent to which thalamocortical connectivity differences observed in psychosis occur as a function of age-associated alterations is not fully understood.

Methods

We analyzed diffusion-weighted imaging data from 1254 participants 8-23 years old (typically developing youth: N=626, psychosis-spectrum youth: N=329, other psychopathology: N=299) from the Philadelphia Neurodevelopmental Cohort. Using deterministic fiber tractography, we modeled eight tracts between the thalamus and cortical regions of interest. We extracted diffusion spectrum imaging (DSI) and conventional diffusion tensor imaging (DTI) measures. We used generalized additive models to determine group and age-associated differences in thalamocortical connectivity.

Results

Compared to typically developing youth and youth with other psychopathologies, psychosis-spectrum youth exhibited thalamocortical reductions in DSI global fractional anisotropy (p-values range=3.0×10−6-0.05) and DTI fractional anisotropy (p-values range=4.2×10−4-0.03). Compared to typically developing youth, psychosis-spectrum youth exhibited shallower thalamus-prefrontal age-associated increases in DSI global fractional anisotropy and DTI fractional anisotropy during middle childhood, and steeper thalamus-prefrontal age-associated increases in those measures during adolescence. Both typically developing youth and youth with other psychopathologies exhibited decreases in mean and radial diffusivity in thalamus-frontal tracts during adolescence; psychosis-spectrum youth failed to show these age-related decreases.

Conclusion

Our findings suggest group differences and altered age-related patterns of thalamocortical white matter connectivity in psychosis-spectrum youth. Consistent alterations present as early as middle childhood and altered age-associated patterns during adolescence and young adulthood may contribute to the disruptions in thalamocortical connectivity observed in adults with psychosis.
Comparison of blood and urine concentrations of equol by LC‒MS/MS method and factors associated with equol production in 466 Japanese men and women
Authors: Yoshikata Remi , Myint Khin Zay Yar , Taguchi Junichi
Published: July 2023

Equol is produced from daidzein by the action of gut bacteria on soy isoflavones. However, not all people can produce equol, and metabolism differs even among the producers. We aimed to examine the equol producer status in both men and women, and investigate the relationships among the serum and urinary isoflavones as well as to other biomedical parameters. In this study, we measured the equol and daidzein concentrations from the blood and urine of 292 men and 174 women aged between 22 and 88 years by liquid chromatography/tandem mass spectrometry (LC/MS/MS).We then analysed the cut-off value for equol producers in both sexes, the relationship of serum and urinary equol concentrations, and other parameters, such as sex, age, endocrine function, glucose metabolism, lipid metabolism, and renal function with regards to equol-producing ability, among the different age groups. Equol producers were defined as those whose log ratio of urinary equol and daidzein concentration or log (equol/daidzein) was -1.42 or higher. Among 466 participants, 195 were equol producers (42%). The proportion of equol producers was larger in women. The cut-off value for equol producers was consistent in both sexes. Positive relationships were noted between serum and urinary equol levels in equol producers of both sexes; however, such an association was not detected in nonproducers. PSA levels in men were significantly lower in equol producers (0.8 v.s. 1.0 ng/ml, p=0.004), especially in those in their 40 s (0.82 vs. 1.13 ng/ml, p<0.001) and 60 s (0.64 vs. 1.02 ng/ml, p<0.001).
Carbapenem-resistantAcinetobacter baumanniiat a hospital in Botswana: Detecting a protracted outbreak using whole genome sequencing
Authors: Strysko Jonathan , Thela Tefelo , Feder Andries , Thubuka Janet , Machiya Tichaona , Mkubwa Jack , Mochankana Kagiso , Tiroyakgosi Celda , Kgomanyane Kgomotso , Ntereke Tlhalefo Dudu , Zankere Tshiamo , Lechiile Kwana , Gatonye Teresia , Tembo Chimwemwe Viola , Vurayai Moses , Mannathoko Naledi , Mokomane Margaret , Moustafa Ahmed M , Goldfarb David M , Richard-Greenblatt Melissa , McGann Carolyn , Coffin Susan E , Cancedda Corrado , Lautenbach Ebbing , Bogoshi Dineo , Smith Anthony M , Planet Paul J
Published: July 2023

Carbapenem-resistantAcinetobacter baumannii(CRAb) has emerged as a major and often fatal cause of bloodstream infections among hospitalized patients in low- and middle-income countries (LMICs). CRAb outbreaks are hypothesized to arise from reservoirs in the hospital environment, but outbreak investigations in LMICs are seldom able to incorporate whole genome sequencing (WGS) due to resource limitations. We performed WGS at the National Institute for Communicable Diseases (Johannesburg, South Africa) on storedA. baumanniiisolates (n=43) collected during 2021–2022 from a 530-bed referral hospital in Gaborone, Botswana where CRAb infection incidence was noted to be rising. This included blood culture isolates from patients (aged 2 days – 69 years), and environmental isolates collected at the hospital’s 33-bed neonatal unit. Multilocus sequence typing (MLST), antimicrobial/biocide resistance gene identification, and phylogenetic analyses were performed using publicly accessible analysis pipelines. Single nucleotide polymorphism (SNP) matrices were used to assess clonal lineage. MLST revealed 79% of isolates were sequence type 1 (ST1), including all 19 healthcare-associated blood isolates and three out of five environmental isolates. Genes encoding for carbapenemases (blaNDM-1,blaOXA-23) and biocide resistance (qacE) were present in all 22 ST1 isolates. Phylogenetic analysis of the ST1 clade demonstrated spatial clustering by hospital unit. Nearly identical isolates spanned wide ranges in time (>1 year), suggesting ongoing transmission from environmental sources. One highly similar clade (average difference of 2.3 SNPs) contained all eight neonatal blood isolates and three environmental isolates from the neonatal unit. These results were critical in identifying environmental reservoirs (e.g. sinks) and developing remediation strategies. Using a phylogenetically informed approach, we also identified diagnostic genes useful for future tracking of outbreak clones without the need for WGS. This work highlights the power of South-South and South-North partnerships in building public health laboratory capacity in LMICs to detect and contain the spread of antimicrobial resistance.
Species distribution modeling for disease ecology: a multi-scale case study for schistosomiasis host snails in Brazil
Authors: Singleton Alyson L. , Glidden Caroline K. , Chamberlin Andrew J. , Tuan Roseli , Palasio Raquel G. S. , Pinter Adriano , Caldeira Roberta L. , Mendonça Cristiane L. F. , Carvalho Omar S. , Monteiro Miguel V. , Athni Tejas S. , Sokolow Susanne H. , Mordecai Erin A. , De Leo Guilio A.
Published: July 2023

Species distribution models (SDMs) are increasingly popular tools for profiling disease risk in ecology, particularly for infectious diseases of public health importance that include an obligate non-human host in their transmission cycle. SDMs can create high-resolution maps of host distribution across geographical scales, reflecting baseline risk of disease. However, as SDM computational methods have rapidly expanded, there are many outstanding methodological questions. Here we address key questions about SDM application, using schistosomiasis risk in Brazil as a case study. Schistosomiasis—a debilitating parasitic disease of poverty affecting over 200 million people across Africa, Asia, and South America—is transmitted to humans through contact with the free-living infectious stage ofSchistosomaspp. parasites released from freshwater snails, the parasite’s obligate intermediate hosts. In this study, we compared snail SDM performance across machine learning (ML) approaches (MaxEnt, Random Forest, and Boosted Regression Trees), geographic extents (national, regional, and state), types of presence data (expert-collected and publicly-available), and snail species (Biomphalaria glabrata,B. tenagophilaandB. straminea). We used high-resolution (1km) climate, hydrology, land-use/land-cover (LULC), and soil property data to describe the snails’ ecological niche and evaluated models on multiple criteria. Although all ML approaches produced comparable spatially cross-validated performance metrics, their suitability maps showed major qualitative differences that required validation based on local expert knowledge. Additionally, our findings revealed varying importance of LULC and bioclimatic variables for different snail species at different spatial scales. Finally, we found that models using publicly-available data predicted snail distribution with comparable AUC values to models using expert-collected data. This work serves as an instructional guide to SDM methods that can be applied to a range of vector-borne and zoonotic diseases. In addition, it advances our understanding of the relevant environment and bioclimatic determinants of schistosomiasis risk in Brazil.
Physiological costs of prospecting in a resident cooperative breeder, the Florida scrub-jay
Authors: Suh Young Ha , Taff Conor , Bowman Reed , Fitzpatrick John W
Published: July 2023

Prospecting is an understudied yet pivotal information-gathering process often preceding natal dispersal. While prospecting may enable individuals to optimise dispersal outcomes and obtain high quality territories, it is also likely to incur costs stemming from energy expenditure and predation risks. This trade-off may drive individual differences in prospecting effort. We tested for evidence of costs of prospecting behaviour in a wild population of Florida scrub-jays,Aphelocoma coerulescens, which prospect as nonbreeding helpers. Using random sampling across all helpers, we compared prospecting effort—approximated by frequency, distance, and activity level—with body mass changes and oxidative stress levels. We tested if prospecting incurred costs and if early-life body condition predicted subsequent prospecting effort. Prospecting frequency was positively linked to oxidative damage but not to any loss in body mass during the breeding season, suggesting that extra-territorial movement costs manifest unevenly. Early-stage body condition did not affect subsequent prospecting effort across a large set of helpers, but early-stage body condition and morphometric measures did correlate with subsequent oxidative status of those sampled. Our results suggest that prospecting movement carries some physiological costs, perhaps contributing to individual differences in prospecting. This research highlights how body condition plays a role in trade-offs between information gathering movement and physiological costs of movement itself, ultimately providing insight on the evolution of prospecting in social species.

HIGHLIGHTS

Prospecting prior to breeding enables informed dispersal but incurs cost

We tested whether prospecting by nonbreeding Florida scrub-jays results in physiological costs or varies with initial condition

We measured oxidative status using assays testing antioxidant capacity and oxidative damage

Frequent prospecting was linked to subsequent oxidative damage

Early-stage body condition and wing length affected subsequent oxidative status
Investigating the effects of radiation, T cell depletion, and bone marrow transplantation on murine gut microbiota
Authors: Kreisinger Jakub , Dooley James , Singh Kailash , Čížková Dagmar , Schmiedová Lucie , Bendová Barbora , Liston Adrian , Moudra Alena
Published: July 2023

Microbiome research has gained much attention in recent years as the importance of gut microbiota in regulating host health becomes increasingly evident. However, the impact of radiation on the microbiota in the murine bone marrow transplantation model is still poorly understood. In this paper, we present the major conclusions of our investigation into the effects of radiation and subsequent bone marrow transplantation with or without T cell depletion of the donor bone-marrow on the microbiota of the ileum and cecum. Our findings show that radiation has different effects on the microbiota of the two intestinal regions, with the cecum showing increased interindividual variation, suggesting an impaired ability of the host to regulate microbial symbionts, consistent with the Anna Karenina principle. Additionally, we observed changes in the ileum composition, including an increase in bacterial taxa that are important modulators of host health, such asAkkermansiaandFaecalibaculum.

In contrast, radiation in the cecum was associated with an increased abundance of several common commensal taxa in the gut, includingLachnospiraceaeandBacteroides. Finally, we found that high doses of radiation had more substantial effects on the caecal microbiota of the T-cell-depleted group than that of the non-T-cell-depleted group. Overall, our results contribute to a better understanding of the complex relationship between radiation and the gut microbiota in the context of bone marrow transplantation and highlight the importance of considering different intestinal regions when studying microbiome responses to environmental stressors.
PyLabRobot: An Open-Source, Hardware Agnostic Interface for Liquid-Handling Robots and Accessories
Authors: Wierenga Rick P. , Golas Stefan , Ho Wilson , Coley Connor , Esvelt Kevin M.
Published: July 2023

Liquid handling robots are often limited by proprietary programming interfaces that are only compatible with a single type of robot and operating system, restricting method sharing and slowing development. Here we present PyLabRobot, an open-source, cross-platform Python interface capable of programming diverse liquid-handling robots, including Hamilton STARs, Tecan EVOs, and Opentron OT-2s. PyLabRobot provides a universal set of commands and representations for deck layout and labware, enabling the control of diverse accessory devices. The interface is extensible and can work with any robot that manipulates liquids within a Cartesian coordinate system. We validated the system through unit tests and several application demonstrations, including a browser-based simulator, a position calibration tool, and a path-teaching tool for complex movements. PyLabRobot provides a flexible, open, and collaborative programming environment for laboratory automation.

Figure Abstract

PyLabRobot overcomes the limitations of proprietary robotic systems.(a) Scientists with access to liquid-handling robots are currently limited by proprietary interfaces that require specialized knowledge, hinder cross-platform operability, and restrict sharing of methods among different robot types. For complex tasks, many researchers need assistance from a specialist familiar with their particular system, most notably when creating or editing protocols. (b) PyLabRobot (https://github.com/PyLabRobot/pylabrobot) offers a single interface that allows any person with basic Python skills to program diverse types of liquid-handling robots and share protocols freely, fostering a more collaborative and efficient research environment. The Python API makes it easy to interact with a large scientific computing ecosystem and allows users to leverage large language models for programming assistance.