bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamified intervention to educate healthcare professionals on rational use of antimicrobials
Authors: Neelambike Sumana M , Shettar Supreeta R , Maheshwarappa Yogeesh , Megha G K
Published: April 2024

Background

Antimicrobial resistance [AMR] is a global problem. It’s important to train health care professionals on rational use of antimicrobials to curb AMR.

Methods

This is a prospective interventional study conducted for the clinical practitioners, Undergraduates [MBBS/Interns], Post graduates and Pharmacy Students. A total of 50 participants were included in the study. The innovative games were administered for management of infections of all the different systems of the body in accordance with the ICMR treatment guidelines 2022 and latest IDSA guidelines involving different components. Pre-test and Post-test questionnaires were administered and evaluated.

Results

After the intervention, the knowledge on differentiating between bacterial and viral symptoms in respiratory tract infections and gastroenteritis improved from 48% to 94%. The practice of using right empirical choice of antimicrobials in the right dose for the right duration, based on the severity of the infection improved from 34 % to 82 %. The awareness/practice of using the right and rational combination of antibiotics improved from 44% to 84%. The knowledge on suspecting multi-drug resistant gram negative infections and other priority pathogens such as Methicillin-resistantStaphylococcus aureus[MRSA] andCandidainfection improved from 32% to 78%. The practice of using certain antibiotics in specific infection sites based on their pharmacodynamics and pharmacokinetics improved from 20% to 76%. The knowledge on intrinsic resistance of certain microorganisms to specific antimicrobial agents improved from 15 % to 80%.

Conclusion

The gamified intervention successfully improved participants’ knowledge and awareness on rational antimicrobial use. The substantial improvements in all the aforementioned components highlight the positive impact of the intervention in promoting optimal antimicrobial use and curbing AMR. Innovative gamified interventions create better and long-lasting awareness ensuring the appropriate use of antimicrobials.
Shared pathway-specific network mechanisms of dopamine and deep brain stimulation for the treatment of Parkinson's disease
Authors: Binns Thomas S. , Köhler Richard M. , Vanhoecke Jojo , Chikermane Meera , Gerster Moritz , Merk Timon , Pellegrini Franziska , Busch Johannes L. , Habets Jeroen G.V. , Cavallo Allesia , Beyer Jean-Christin , Al-Fatly Bassam , Li Ningfei , Horn Andreas , Krause Patricia , Faust Katharina , Schneider Gerd-Helge , Haufe Stefan , Kühn Andrea A. , Neumann Wolf-Julian
Published: April 2024

Deep brain stimulation is a brain circuit intervention that can modulate distinct neural pathways for the alleviation of neurological symptoms in patients with brain disorders. In Parkinson's disease, subthalamic deep brain stimulation clinically mimics the effect of dopaminergic drug treatment, but the shared pathway mechanisms on cortex - basal ganglia networks are unknown. To address this critical knowledge gap, we combined fully invasive neural multisite recordings in patients undergoing deep brain stimulation surgery with normative MRI-based whole-brain connectomics. Our findings demonstrate that dopamine and stimulation exert distinct mesoscale effects through modulation of local neural population activity. In contrast, at the macroscale, stimulation mimics dopamine in its suppression of excessive interregional network synchrony associated with indirect and hyperdirect cortex - basal ganglia pathways. Our results provide a better understanding of the circuit mechanisms of dopamine and deep brain stimulation, laying the foundation for advanced closed-loop neurostimulation therapies.
Longitudinal Exposomics in a Multiomic Wellness Cohort Reveals Distinctive and Dynamic Environmental Chemical Mixtures in Blood
Authors: Sdougkou Kalliroi , Papazian Stefano , Bonnefille Bénilde , Xie Hongyu , Edfors Fredrik , Fagerberg Linn , Uhlén Mathias , Bergström Göran , Martin Leah JM , Martin Jonathan W.
Published: April 2024

Chemical exposomes can now be comprehensively measured in human blood, but robust application of chemical exposomics in cohort studies requires knowledge of the longitudinal stability and interindividual variability of exogenous molecular profiles. Here we applied chemical exposomics to plasma of 46 adults, each sampled six times over two years in a multiomic wellness cohort. New chemicals were discovered, distinctive co-exposure patterns were observed, and intra-class correlation coefficients (ICC) for 519 confidently annotated substances are reported to support study design. Longitudinal stability of the chemical exposome (mean ICC 0.30) was significantly lower than the proteome, metabolome, lipidome or microbiome, and must be measured more frequently than other molecular profiles in health studies. Mixed-effects models nevertheless revealed significant associations between testosterone and perfluoroalkyl substances, and significant time-trends for low and high stability exposures alike. Complex exposome data structures were visualized and explored, demonstrating great potential for longitudinal exposomics in precision health research.

Teaser

The first cohort-level application of longitudinal exposomics revealed novel and dynamic co-exposures in blood of relevance to precision health.
Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice
Authors: Leidmaa Este , Zimmer Andreas , Stein Valentin , Gellner Anne-Kathrin
Published: April 2024

Background

The blood-brain barrier (BBB) maintains brain homeostasis by protecting the brain from pathological stimuli and controlling the entry of physiological substances from the periphery. Consequently, alterations in BBB permeability may pose a threat to brain health. Long-term consumption of a high-fat high-sugar/Western diet (HFD) is known to induce BBB dysfunction. However, nothing is known about the immediate effects of acute HFD consumption on the BBB.

Methods

After consumption of either HFD or standard chow, mice were injected into the tail vein with fluorescent tracers of different sizes, including the drug doxorubicin. Individual brain regions were homogenized and analyzed for tracer extravasation using spectrophotometry. Localized tracer leakage over time in the somatosensory cortex was studied using high-resolution in vivo 2-photon microscopy.

Results

We demonstrate region-specific BBB leakage already after 1 hour of HFD for low- and high-molecular-weight tracers. Acute HFD also significantly increased BBB permeability to the anticancer drug doxorubicin.

Conclusion

These previously unknown effects of acute HFD may have direct and drastic implications for the clinical use of drugs depending on the dietary habits of the patient.
Optimizing Variable Selection in Phylogenetic Eigenvector Regression for Trait Correlation Analysis
Authors: Chen Zheng-Lin , Niu Deng-Ke
Published: April 2024

Phylogenetic autocorrelation refers to the similarity in traits among closely related species due to shared evolutionary history, violating the assumption of independence in conventional statistical analyses. Phylogenetic eigenvector regression (PVR) addresses this issue by incorporating phylogenetic eigenvectors derived from phylogenetic trees to control for shared ancestry and isolate trait correlations. In this study, we investigated how different selections of dependent and independent variables affect eigenvector identification and trait correlation results. We used simulated data to analyze both fixed-balanced and random phylogenetic trees, which allowed us to record internal node data. This enabled us to determine the true correlation between traits using traditional Pearson and Spearman rank correlations, providing a gold standard for comparison. We found that the eigenvectors selected differed significantly when switching between dependent variables (X1andX2), which led to inconsistent PVR correlation results. We assessed three criteria—R2, Pagel’s λ, and AIC—to determine which dependent variable produced more accurate results. Our results indicate that, under scenarios with significant phylogenetic autocorrelation and larger sample sizes (128 and 1024 species), the criterion of maximizingR2consistently provided the more accurate model. This was true across multiple evolutionary models, tree structures, and regression estimators, including L2 (OLS), MM, and L1. However, in smaller samples (16 species), Pagel’s λ was more effective as a selection criterion. These findings emphasize the importance of using appropriate criteria, such asR2or λ, for selecting dependent variables to enhance the accuracy and consistency of evolutionary inferences. Additionally, our preliminary findings suggest that similar issues of variable selection may affect other spatial statistical tools, such as spatial eigenvector mapping, conditional autoregressive models, simultaneous autoregressive models, and generalized additive models. These insights extend beyond phylogenetic analyses to other contexts where spatial autocorrelation exists or coexists with phylogenetic autocorrelation. Future work is needed to address how to appropriately select dependent and independent variables in these contexts, which remains a key challenge for understanding evolutionary and ecological relationships.
Chromosome-level baobab (Adansonia digitata) genome illuminates its evolutionary insights
Authors: Kitony Justine K. , Colt Kelly , Abramson Bradley W. , Hartwick Nolan T. , Petrus Semar , Konozy Emadeldin H. E. , Karimi Nisa , Yant Levi , Michael Todd P.
Published: April 2024

Abstract

Baobab,Adansonia digitata, is a long-lived tree endemic to Africa that holds great economic, ecological, and cultural value. However, our knowledge of its genomic features, evolutionary history, and diversity is limited, rendering it orphaned scientifically. We generated a haploid chromosome-level reference genome anchored into 42 chromosomes forA. digitata, as well as draft assemblies for a sibling tree, two trees from distinct locations in Africa, and a related species,A. zafrom Madagascar. Unlike any other plant to date, DNA transposable elements (TEs) make up 33% of theA. digitatagenome compared to only 10% long terminal repeat retrotransposons (LTR-RTs), which are usually predominant in plant genomes. Baobab has undergone a whole genome duplication (WGD) shared with the Malvoideae ∼30 million years ago (MYA), as well as a confirmed autotetraplody event 3-4 million MYA that coincides with the most recent burst of TE insertions. Resequencing 25A. digitatatrees from Africa revealed three subpopulations that suggest gene flow through most of West Africa but separated from East Africa. Gene enrichment analysis for baobab-specific and high fixation index (Fst) suggested baobab may have retained multiple copies of circadian, light and growth genes to coordinate genome protection for longevity through theUV RESISTANCE LOCUS 8(UVR8) and synchronizing flower development with pollinators. This study lays the groundwork for the creation of breeding resources and the conservation of baobab biodiversity.
Three-Dimensional Molecular Atlas of Octopus Arm Neuroanatomy Highlights Spatial and Functional Complexity
Authors: Winters-Bostwick Gabrielle C. , Giancola-Detmering Sarah E. , Bostwick Caleb J. , Crook Robyn J.
Published: April 2024

Octopus arms, notable for their complex anatomy and remarkable flexibility, have sparked significant interest within the neuroscience community. However, there remains a dearth of knowledge about the molecular and functional identities of various cell types in the arm’s nervous system. To address this gap, we used hybridization chain reaction (HCR) to identify distinct neuronal types in the arms of the pygmy octopus,Octopus bocki, including putative dopaminergic, octopaminergic, serotonergic, GABAergic, glutamatergic, cholinergic, and peptidergic neurons. We obtained high-resolution multiplexed fluorescent images at 0.28x0.28x1.0 μM voxel size from 10 arm base and arm tip cross sections (each 50 μM thick) and created three-dimensional reconstructions of the axial ganglia, illustrating the spatial distribution of multiple neuronal populations. Our analysis unveiled anatomically distinct and molecularly diverse scattered neurons, while also highlighting multiple populations of dense small excitatory neurons that appear uniformly distributed throughout the cortical layer. Our data provide new insights into how different types of neurons may contribute to the ability of an octopus to interact with its environment and execute complex tasks. In addition, our findings establish a benchmark for future studies, allowing pioneering exploration of octopus arm molecular neuroanatomy, and offering exciting new avenues in invertebrate neuroscience research.
Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity
Authors: Wu Yifan , Song Yang , Soto Jennifer , Hoffman Tyler , Zhang Aaron , Han Xiao , Fang Zhiwei , Eoh Joon , Gu Luo , Gu Zhen , Li Song
Published: April 2024

Living tissue and extracellular matrices possess viscoelastic properties, but understanding how viscoelastic matrix regulates chromatin and the epigenome is limited. Here, we find that the regulation of the epigenetic state by the viscoelastic matrix is more pronounced on softer matrices. Cells on viscoelastic matrices exhibit larger nuclei, increased nuclear lamina ruffling, loosely organized chromatin, and faster chromatin dynamics, compared to those on elastic matrices. These changes are accompanied by a global increase in euchromatic marks and a local increase in chromatin accessibility at thecis-regulatory elements associated with neuronal and pluripotent genes. Consequently, viscoelastic matrices enhanced the efficiency of reprogramming fibroblasts into neurons and induced pluripotent stem cells, respectively. Together, our findings demonstrate the key roles of matrix viscoelasticity in the regulation of epigenetic state, and uncover a new mechanism of biophysical regulation of chromatin and cell reprogramming, with implications for the design of smart materials to engineer cell fate.
A new leaf sensing organ in a predatory insect group, the praying mantises
Authors: Brannoch Sydney K. , Katzke Julian , Taylor Danielle S. , Economo Evan , Ogawa Yuri , Narendra Ajay , Svenson Gavin J. , Martin Joshua
Published: April 2024

Animals’ sensory systems enable them to navigate and interact with their environments. Adaptive specializations of these systems can generate novel structures or organs that support highly unique niche adaptations. We report the discovery of a novel sensory organ in a group of praying mantises (Insecta, Mantodea, Nanomantoidea), which have an unusual “leaf-planking” ecomorphic life strategy, laying against the undersides of broadleaf vegetation. Histology, scanning electron microscopy, and x-ray computed tomography all support the novelty of this distinct morphology while electrophysiology reveals that the sensory organ, herein designated the gustifolium organ, detects plant volatiles. The location of the gustifolium organon the ventral thoracic surface of these mantises appears to facilitate the chemical detection of the leaves on which it resides. The gustifolium is a novel plant volatile-detecting sensory structure in an obligate predatory insect, directly linked to a newly-identified, highly-adapted life strategy.
The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer
Authors: Torrens Laura , Moody Sarah , de Carvalho Ana Carolina , Kazachkova Mariya , Abedi-Ardekani Behnoush , Cheema Saamin , Senkin Sergey , Cattiaux Thomas , Cortez Cardoso Penha Ricardo , Atkins Joshua R , Gaborieau Valérie , Chopard Priscilia , Carreira Christine , Abbasi Ammal , Bergstrom Erik N , Vangara Raviteja , Wang Jingwei , Fitzgerald Stephen , Latimer Calli , Diaz-Gay Marcos , Jones David , Teague Jon , Ribeiro Pinto Felipe , Kowalski Luiz Paulo , Polesel Jerry , Giudici Fabiola , de Oliveira José Carlos , Lagiou Pagona , Lagiou Areti , Vilensky Marta , Mates Dana , Mates Ioan N , Arantes Lidia MRB , Reis Rui , Podesta Jose Roberto V , von Zeidler Sandra V , Holcatova Ivana , Curado Maria Paula , Canova Cristina , Fabianova Elenora , Rodríguez-Urrego Paula A , Humphreys Laura , Alexandrov Ludmil B , Brennan Paul , Stratton Michael R , Perdomo Sandra
Published: April 2024

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.
Mucin-7 as a Potential Candidate Risk Allele for Cleft Lip and/or Palate
Authors: Montel Rachel A. , Rengifo Tatiana P. , Chang Sulie L.
Published: April 2024

Cleft lip and/or palate (CL/P) occur in approximately 1 in 700 live births in the United States. High hereditary rates (50-80%) of CL/P indicate a strong genetic cause. The concept of strong genetic causes has been well-demonstrated in previous studies such as GWAS studies that identifiedIRF6for Van der Woode syndrome. Since the risk for genetic factors is strongly associated with CL/P, we hypothesized that RNA sequencing (RNA-seq) from CL/P patients may reveal enriched genes. Differential expression analysis examined changes in gene expression in CL/P patients compared to healthy controls, and gene-enrichment in relevant pathways. To explore the relationship between variants driving the observed changes in gene expression, we performed variant analysis and reported all CL/P-specific single nucleotide polymorphisms (SNPs). Our findings demonstrate that the normally upregulatedMUC7gene is significantly downregulated in CL/P patients. Using our list of prioritized differentially expressed genes (DEGs), we observed significantly enriched pathways for biological processes related to cornification, skin and epidermis development, and keratinocyte and epidermal cell differentiation. By performing variant analyses, a single nucleotide polymorphism (SNP) inMUC7, and 47 SNPs in 20 additional genes (CLCA4,ETNK2,ERLNC1,HAL,HOPX,IVL,KLK11,LIPK,LY6D,MUC21,NCCRP1,NEBL,PHYH,SERPINB11,SERPINB4,SORD,SPINK5,SULT2B1,TMEM154,TMPRSS11A) were revealed. To our knowledge, this is the first report on the potential role ofMUC7in contributing to CL/P. Together, these findings provide further insight into the genetic causes of CL/P.
Mathematical assessment of wastewater-based epidemiology to predict SARS-CoV-2 cases and hospitalizations in Miami-Dade County
Authors: Pant Binod , Safdar Salman , Ngonghala Calistus N. , Gumel Abba B.
Published: April 2024

This study presents a wastewater-based mathematical model for assessing the transmission dynamics of the SARS-CoV-2 pandemic in Miami-Dade County, Florida. The model, which takes the form of a deterministic system of nonlinear differential equations, monitors the temporal dynamics of the disease, as well as changes in viral RNA concentration in the county’s wastewater system (which consists of three sewage treatment plants). The model was calibrated using the wastewater data during the third wave of the SARS-CoV-2 pandemic in Miami-Dade (specifically, the time period from July 3, 2021 to October 9, 2021). The calibrated model was used to predict SARS-CoV-2 case and hospitalization trends in the county during the aforementioned time period, showing a strong correlation (with a correlation coefficientr= 0.99) between the observed (detected) weekly case data and the corresponding weekly data predicted by the calibrated model. The model’s prediction of the week when maximum number of SARS-CoV-2 cases will be recorded in the county during the simulation period precisely matches the time when the maximum observed/reported cases were recorded (which was August 14, 2021). Furthermore, the model’s projection of the maximum number of cases for the week of August 14, 2021 is about 15 times higher than the maximum observed weekly case count for the county on that day (i.e., the maximum case count estimated by the model was 15 times higher than the actual/observed count for confirmed cases). This result is consistent with the result of numerous SARS-CoV-2 modeling studies (including other wastewater-based modeling, as well as statistical models) in the literature. Furthermore, the model accurately predicts a one-week lag between the peak in weekly COVID-19 case and hospitalization data during the time period of the study in Miami-Dade, with the model-predicted hospitalizations peaking on August 21, 2021. Detailed time-varying global sensitivity analysis was carried out to determine the parameters (wastewater-based, epidemiological and biological) that have the most influence on the chosen response function - the cumulative viral load in the wastewater. This analysis revealed that the transmission rate of infectious individuals, shedding rate of infectious individuals, recovery rate of infectious individuals, average fecal loadperpersonperunit time and the proportion of shed viral RNA that is not lost in sewage before measurement at the wastewater treatment plant were most influential to the response function during the entire time period of the study. This study shows, conclusively, that wastewater surveillance data can be a very powerful indicator for measuring (i.e., providing early-warning signal and current burden) and predicting the future trajectory and burden (e.g., number of cases and hospitalizations) of emerging and re-emerging infectious diseases, such as SARS-CoV-2, in a community.
Recent Advancements in Machine Learning-Based Bloodstream Infection Prediction: A Systematic Review and Meta-analysis of Diagnostic Test Accuracy
Authors: Bopche Rajeev , Damås Jan Kristian
Published: April 2024

Abstract. Purpose: Bloodstream infections (BSIs) present significant public health challenges. With the advent of machine learning (ML), promising predictive models have been developed. This study evaluates their performance through a systematic review and meta-analysis. Methods: We performed a comprehensive systematic review across multiple databases, including PubMed, IEEE Xplore, ScienceDirect, ACM Digital Library, SpringerLink, Web of Science, Scopus, and Google Scholar. Eligible studies focused on BSIs within any hospital setting, employing ML models as the diagnostic test. We evaluated the risk of bias with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist and assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Models reporting the area under the receiver operating characteristic curve (AUROC) were included in the meta-analysis to identify key performance drivers. Results: After screening, a total of 30 studies were eligible for synthesis, from which 41 models and 8 data types were extracted. Most of the studies were carried out in the inpatient settings (n=17; 56%), followed by the emergency department (ED) settings (n=7; 23%), and followed by the ICU settings (n=6; 20%). The reported AUROCs in the hospital inpatients settings, ranged from 0.51-0.866, in the ICU settings AUROCs ranged from 0.668-0.970, and in the emergency department (ED) settings the AUROCs of the models ranged from 0.728-0.844. One study reported prospective cohort study, while two prospectively validated their models. In the meta-analysis, laboratory tests, Complete Blood Count/Differential Count (CBC/DC), and ML model type contributed the most to model performance. Conclusion: This systematic review and meta-analysis show that on retrospective data, individual ML models can accurately predict BSIs at different stages of patient trajectory. Although they enable early prediction of BSI, a comprehensive approach to integrate data types and models is necessary. Systematic reporting, externally validated, and clinical implementation studies are needed to establish clinical confidence.
Five-layered robot (F-robot) based on functionally graded multilayer foam antiviral low-carbon (F-MAX) system for Pathogenic Microorganism Elimination
Authors: Fan Haotian , Gu Wangcheng , Zhou Dongrui , Ge Song , Xiao Pengfeng , Fei Zhongjie
Published: April 2024

In this study, a revolutionary air filtration technology, the F-MAX multilayer composite plate, is introduced, offering high efficiency and environmental sustainability. This innovative system is designed to capture a wide range of pollutants, including harmful viruses and bacteria, enhancing air quality significantly. The F-MAX combines multiple layers, each tailored to target specific particles, with features like an electrostatically charged melt-blown fabric and eco-friendly materials like lithium brine by-product magnesia. Its durability, antiviral, and antibacterial properties make it a sustainable choice for air purification, suitable for both commercial and residential use. This system represents healthier living environments, effectively removing airborne contaminants, and demonstrating a commitment to a sustainable future. Additionally, the study introduces the F-robot specifically designed for laboratory environments to ensure pristine air quality.

One-Sentence Summary

T-robot air filter, which use F-MAX, a multilayer composite consisted of self-healing cellular coating, Desert Rose (DR) coating, melt-blown cloth, and BMSC with high-efficiency, environmentally sustainable filtration, and antiviral properties, suitable for diverse environments.
Reanalysis of sequences of alleged Javan tiger highlights the difficulties in studying big cats and the need for high throughput sequencing
Authors: Khan Anubhab , Yulianto Yulianto , Aninta Sabhrina Gita , Wirdateti Wirdateti
Published: April 2024

Big cats are of conservation concern throughout their range. Genetic tools are often employed to study them for various purposes. However, there are several difficulties in using genetic tools for big cat conservation which may be resolved by modern methods of DNA sequencing. Recent reports of discovery of Javan tigers in West Java, Indonesia highlights few of the difficulties in big cat genetics. We reanalysed the data of the original reports and found that the results were unreliable. However, resequencing of the DNA extracts confirm that the sighting could have been that of a tiger, but the subspecies cannot be confirmed. The work highlights the urgency for development of high throughput sequencing infrastructure in the tropics and the need for reliable databases for studies of big cats.
Spatial mRNA expression patterns of orexin receptors in the dorsal hippocampus
Authors: Krause Gina Marie , Chirich Barreira Lara Mariel , Albrecht Anne
Published: April 2024

Orexins are wake-promoting neuropeptides that originate from hypothalamic neurons projecting to widespread brain areas throughout the central nervous system. They modulate various physiological functions via their orexin 1 (OXR1) and 2 (OXR2) receptors, including sleep-wake rhythm but also cognitive functions such as memory formation.

Here, we provide a detailed analysis of OXR1 and OXR2 mRNA expression profiles in the dorsal hippocampus as a key region for memory formation, using RNAscope® multiplexin situhybridization. Interconnected subareas relevant for cognition and memory such as the medial prefrontal cortex and the nucleus reuniens of the thalamus were assessed as well. Both receptor types display distinct profiles, with the highest percentage of OXR1 mRNA-positive cells in the hilus of the dentate gyrus. Here, the content of OXR1 mRNA per cell was slightly modulated at selected time points over a 12h light/ 12 dark light phase. Using RNAScope® and quantitative polymerase chain reaction approaches, we began to address a cell-type specific expression of OXR1 in hilar GABAergic interneurons.

The distinct expression profiles of both receptor subtypes within hippocampal subareas and circuits provide an interesting basis for future interventional studies on orexin receptor function in spatial and contextual memory.
Parallel comparison reveals conservation and re-wiring of abiotic stress response networks across three plant species
Authors: Lee Jia Min , Goh Jong Ching , Mutwil-Anderwald Daniela , Mutwil Marek
Published: April 2024

Abiotic stresses trigger significant alterations in plant morphology, yield, and nutrient composition. To counter these stresses, plants have developed strategies involving gene expression adjustments, impacting their growth and development to ensure survival and reproduction. Although transcriptomic studies have extensively examined stress responses, our understanding of their conservation remains limited. We conducted a comprehensive study on the effects of 24 different environmental and nutrient conditions on the growth yield of three hydroponically grown leafy crops (cai xin, lettuce, and spinach). This research identified optimal conditions for maximizing yield and vitamin content and pinpointed conditions that induce abiotic stress. Our findings highlight the substantial impact of stress on various plant functions, with photosynthesis playing a pivotal role in vitamin content regulation. A detailed comparative analysis of gene expression across these crops revealed conserved gene sets potentially crucial for abiotic stress response. Furthermore, we introduced a novel method that merges regression and genomics to construct reliable gene regulatory networks for stress response. Despite significant conservation of these networks among the studied crops, their key transcription factors showed limited similarity to those inArabidopsis thaliana, suggesting notable functional divergence. To give easy access to the data and comparative transcriptomic tools, we established StressPlantTools, an public online database (https://stress.sbs.ntu.edu.sg/), facilitating further research into stress-responsive genes.
Wax “tails” enable planthopper nymphs to self-right midair and land on their feet
Authors: McDonald Christina L. , Alcalde Gerwin T. , Jones Thomas C. , Laude Ruby Ana P. , Yap Sheryl A. , Bhamla M. Saad
Published: April 2024

The striking appearance of wax ‘tails’ — posterior wax projections on planthopper nymphs — has captivated entomologists and naturalists alike. Despite their intriguing presence, the functional roles of these structures remain largely unexplored. This study leverages high-speed imaging to uncover the biomechanical implications of these wax formations in the aerial dynamics of planthopper nymphs (Ricania sp.). We quantitatively demonstrate that removing wax tails significantly increases body rotations during jumps. Specifically, nymphs without wax projections undergo continuous rotations, averaging 4.3±1.9 per jump, in contrast to wax-intact nymphs, who narrowly complete a full rotation, averaging only 0.7±0.2 per jump. This suggests that wax structures effectively counteract rotation through aerodynamic drag forces. These stark differences in body rotation correlate with landing success: nymphs with wax intact achieve a near perfect landing rate of 98.5%, while those without wax manage only a 35.5% success rate. Jump trajectory analysis reveals transitions from parabolic to Tartaglia shapes at higher take-off velocities for wax-intact nymphs, illustrating how wax structures assist nymphs in achieving stable, controlled descents. Our findings confirm the aerodynamic self-righting functionality of wax tails in stabilizing planthopper landings, advancing our understanding of the complex interplay between wax morphology and aerial maneuverability, with broader implications for the evolution of flight in wingless insects and bioinspired robotics.
Virophage replication mode determines ecological and evolutionary changes in a host-virus-virophage system
Authors: del Arco Ana , Becks Lutz
Published: April 2024

Giant viruses can control their eukaryotic host populations, shaping the ecology and evolution of aquatic microbial communities. Understanding the impact of the viruses’ own parasites, the virophages, on their control of microbial communities remains a challenge. Most virophages have two modes of host infection and replication. They can exist as free particles that co-infect a host cell with the virus and replicate but inhibit viral replication. Virophages can also integrate into the host genome and remain dormant until the host is infected with a virus, leading to virophage reactivation and replication that does not immediately inhibit viral replication. Both replication modes are present within host-virus-virophage communities, and their relative contributions are expected to be context dependent and dynamic over time. The consequences of this dynamic regime for ecological and evolutionary dynamics remain unexplored. Here, we test whether and how the relative contribution of virophage replication modes influences the ecological dynamics of an experimental host-virus-virophage system and the evolutionary responses of the virophage. To do this, we indirectly manipulated the level of virophage (Mavirus) integration into the host (Cafeteria burkhardae) in the presence of the giant Cafeteria roenbergensis virus (CroV) (later identified asCafeteria burkhardae, Schoenle et al. 2020). Our results show that higher virophage integration is positively correlated with host survival, but negatively correlated with virophage reactivation. In addition, communities with higher virophage integration were characterised by lower population densities and reduced fluctuations in both host and viral populations, whereas virophage fluctuations were increased. This study reveals the complex interplay between virophages, viruses and hosts, in which the virophage dual replication mode is a dynamic and reactive mechanism contributing to persistence of the microbial community.
Sex-specific recombination landscape in a species with holocentric chromosomes
Authors: Chmielewski Sebastian , Konczal Mateusz , Parrett Jonathan M. , Rombauts Stephane , Dudek Katarzyna , Radwan Jacek , Babik Wiesław
Published: April 2024

The rate and chromosomal positioning of meiotic recombination significantly affects the distribution of the genetic diversity in eukaryotic genomes. Many studies have revealed sex-specific recombination patterns, with male recombination typically biased toward chromosome ends, while female recombination is more evenly distributed along chromosomes, or concentrated near the chromosome center. It has been proposed that such pattern in females may counteract meiotic drive caused by selfish genetic elements near centromeres and should not occur in species devoid of clearly defined centromeres, but evidence for the latter is scarce. Here, we constructed a sex-specific genetic map of a species with holocentric chromosomes, the bulb mite (Rhizoglyphus robini), a sexual selection model with alternative male reproductive phenotypes. We found a similar recombination landscape in both males and females, with a consistent pattern of increased rates towards both chromosome ends, and higher recombination rate in females than in males. A region on chromosome 7, carrying a high density of markers associated with the expression of alternative male reproductive phenotypes, was among several regions with particularly low male recombination rate. We detected a positive correlation between the recombination rate and the repeat density (highest at chromosome ends), and negative correlation with the gene density (peaking at chromosome centers). Our results are consistent with the meiotic drive hypothesis and suggest that recombination evolution is closely linked to the chromosome features.
Protein codes promote selective subcellular compartmentalization
Authors: Kilgore Henry R. , Chinn Itamar , Mikhael Peter G. , Mitnikov Ilan , Van Dongen Catherine , Zylberberg Guy , Afeyan Lena , Banani Salman , Wilson-Hawken Susana , Lee Tong Ihn , Barzilay Regina , Young Richard A.
Published: April 2024

Cells have evolved mechanisms to distribute ∼10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must efficiently assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence codes that guide them to compartment destinations. A protein language model, ProtGPS, was developed that predicts with high performance the compartment localization of human proteins excluded from the training set. ProtGPS successfully guided generation of novel protein sequences that selectively assemble in targeted subcellular compartments. ProtGPS also identified pathological mutations that change this code and lead to altered subcellular localization of proteins. Our results indicate that protein sequences contain not only a folding code, but also a previously unrecognized code governing their distribution in specific cellular compartments.
Neural Dynamics During the Generation and Evaluation of Creative and Non-Creative Ideas
Authors: Kenett Yoed N. , Chrysikou Evangelia G. , Bassett Dani S. , Thompson-Schill Sharon L.
Published: April 2024

What are the neural dynamics that drive creative thinking? Recent studies have provided much insight into the neural mechanisms of creative thought. Specifically, the interaction between the executive control, default mode, and salience brain networks has been shown to be an important marker of individual differences in creative ability. However, how these different brain systems might be recruited dynamically during the two key components of the creative process— generation and evaluation of ideas—remains far from understood. In the current study we applied state-of-the-art network neuroscience methodologies to examine the neural dynamics related to the generation and evaluation of creative and non-creative ideas using a novel within-subjects design. Participants completed two functional magnetic resonance imaging sessions, taking place a week apart. In the first imaging session, participants generated either creative (alternative uses) or non-creative (common characteristics) responses to common objects. In the second imaging session, participants evaluated their own creative and non-creative responses to the same objects. Network neuroscience methods were applied to examine and directly compare reconfiguration, integration, and recruitment of brain networks during these four conditions. We found that generating creative ideas led to significantly higher network reconfiguration than generating non-creative ideas, whereas evaluating creative and non-creative ideas led to similar levels of network integration. Furthermore, we found that these differences were attributable to different dynamic patterns of neural activity across the executive control, default mode, and salience networks. This study is the first to show within-subject differences in neural dynamics related to generating and evaluating creative and non-creative ideas.
An optogenetic assay for the dauer decision in Caenorhabditis elegans
Authors: Parker Ariel , Mullins James , Corver Abel , Miller Anastasia , Mosley Iman , Gordus Andrew
Published: April 2024

The dauer decision inCaenorhabditis elegansis a critical developmental decision that ensures survival under harsh environmental conditions. Factors such as temperature, food availability, and pheromone strongly influence the decision to enter and exit dauer. Traditional assays that assess the dauer decision are often confounded by the influence of pheromones from the population, which are often dynamic and highly variable. To mitigate this issue, we developed a simple, single-housing assay for dauer quantification that is compatible with optogenetics. We show that insulin-like peptides (ILPs) from ASJ and other neurons strongly influence the decision to exit dauer, and that ASJ activity can be manipulated with optogenetics to influence the dauer decision in a temporally precise manner.
Paired transcriptomic analyses of atheromatous and control vessels reveal novel autophagy and immunoregulatory genes in peripheral artery disease
Authors: Machiraju Praveen , Srinivas Rajesh , Kannan Ramraj , George Robbie , Heymans Stephane , Mukhopadhyay Rupak , Ghosh Arkasubhra
Published: April 2024

Abstract

Background

Peripheral artery disease (PAD), a significant health burden worldwide, affects lower extremities due to atherosclerotic changes in the peripheral vessels. Although mechanisms of PAD have been studied, the molecular milieu of the plaques localized within peripheral arteries in patients are not well understood. Thus, to identify PAD lesion specific gene expression profiles precluding genetic, environmental and dietary biases, we studied the transcriptomic profile of plaque tissues normalized to non-plaque tissues from the same donors.

Methods

Transcriptomic analysis of 9 paired samples of PAD patients from south Indian population was performed with institutional ethics approval and written consent. Plaque tissues were histologically confirmed. Expression of a select target gene set was done by qPCR from the same tissues. Bioinformatic and network analyses were performed using various statistical tools.

Results

A total of 296 upregulated, 274 downregulated genes and 186 non-coding RNAs were identified. STAG1, SPCC3, FOXQ1 and E2F3 were key downregulated genes and CD93 was top upregulated gene. Autophagosome assembly, cellular response to UV, cytoskeletal organization, TCR signaling and phosphatase activity were key dysregulated pathways identified in the study. Telomerase regulation and autophagy were identified as novel interacting pathways using network analysis. Plaque tissue was predominantly composed of immune cells and dedifferentiated cell populations indicated by cell specific marker imputed gene expression analysis.

Conclusion

The current study identifies novel genes, non-coding RNAs, associated regulatory pathways and cell composition of the plaque tissue in PAD patients. The autophagy and immunoregulatory genes may drive novel mechanisms resulting in atheroma. These novel interacting networks and genes have the potential for PAD specific therapeutic applications.
Intestinal commensal bacteria promoteBactrocera dorsalislarval development through vitamin B6 synthesis pathway
Authors: Gu Jian , Yao Zhichao , Lemaitre Bruno , Cai Zhaohui , Zhang Hongyu , Li Xiaoxue
Published: April 2024

Background

The gut microbiota can facilitate host growth under nutrient-constrained conditions. However, whether this effect is limited to certain bacterial species remains largely unclear, and the relevant mechanisms remain to be thoroughly investigated.

Results

Here, we found that the microbiota was required forBactrocera dorsalislarval growth under poor diet conditions. Mono-association experiments revealed thatEnterobacteriaceaeand someLactobacillipromoted larval growth. Of 27 tested bacterial strains, 15 strains significantly promoted larval development, and theEnterobacteriaceae cloacaeN29 isolate exhibited the most obvious promoting effect. Bacterial genome-wide association study (GWAS) revealed that the vitamin B6 synthesis pathway was critical forE. cloacaegrowth promotion. The deletion ofpdxAresponsible for the vitamin B6 biosynthesis deprived the mutant strains of larval growth promotion function, indicating thatpdxAgene was crucial for promoting larval growth in the N29 strain. Importantly, supplementation of vitamin B6 to poor diet successfully rescued the axenic larval growth phenotype ofB. dorsalis.

Conclusion

Our results suggest that gut microbes promote insect larval growth by providing vitamin B6 under nutrient scarcity inB. dorsalis.
Determinants of Healthcare Insurance Coverage among Women of Reproductive Age in Tanzania: A Multilevel Mixed Effect Analysis
Authors: Kessy Sanun Ally , Tibenderana Jovin R. , Gimonge Jomo , Moshi Fabiola V
Published: April 2024

Background

Health insurance has been one of the fundamental approaches of financing healthcare for sustainable Development goals (SDGs). There is a paucity of evidence on the determinants of healthcare insurance coverage among women of reproductive age in Tanzania, therefore this study aimed at assessing factors associated with access to health care insurance among women of reproductive age in Tanzania using national Demographic and health survey dataset.

Methodology

This study was an analytical cross-sectional study that utilized nationally representative secondary data sourced from the Tanzania Demographic and Health Surveys (TDHS) of 2022.A weighted sample of 15,254 women of reproductive age (15–49) was included in the study. A multilevel regression analysis was used to examine factors associated with health care insurance coverage. These results were presented using adjusted odds ratio (AOR) with a 95% confidence interval.

Results

In Tanzania the proportion of health insurance coverage among women of reproductive age was 5.8% whereby majority of women subscribing to employer’s insurance (3.9%). Older women (35–49) were more likely to be covered with health insurance compared those aged 15-24 (AOR =2.75, 95% CI: 2.19, 3.45). Similarly, married women had higher likelihood of health insurance coverage compared to unmarried (AOR=1.60, 95% CI: 1.33, 1.92). Furthermore, educated women were more likely to be covered with health insurance than uneducated women (AOR=6.96, 95% CI: 4.74, 10.22). Similarly, women who were exposed to mass media were more likely to be covered with health care insurance compared to unexposed (AOR=1.43, 95% CI: 1.14, 1.78).

Conclusion

Less than ten percent of Tanzanian women of reproductive age (WRA) are registered in health insurance, which is an unacceptably low coverage. This highlights the urgent need to eliminate barriers preventing this population’s access to healthcare in order to achieve Standard Development Goals (SDGs) by 2030. The interplay of socioeconomic factors and access to information underscores the need for multifaceted approaches to enhance healthcare coverage among women of reproductive age in Tanzania.
Early prediction ofMycobacterium tuberculosistransmission clusters using supervised learning models
Authors: Gharamaleki Omid Gheysar , Colijn Caroline , Sekirov Inna , Johnston James C , Sobkowiak Benjamin
Published: April 2024

Identifying individuals with tuberculosis with a high risk of onward transmission can guide disease prevention and public health strategies. Here, we train classification models to predict the first sampled isolates inMycobacterium tuberculosistransmission clusters from demographic and disease data. We find that supervised learning models, in particular balanced random forests, can be used to develop predictive models that discriminate between individuals with TB that are more likely to form transmission clusters and individuals that are likely not to transmit further, with good model performance and AUCs of ≥ 0.75. We also identified the most important patient and disease characteristics in the best performing classification model, including patient demographics, site of infection, TB lineage, and age at diagnosis. This framework can be used to develop predictive tools for the early assessment of a patient’s transmission risk to prioritise individuals for enhanced follow-up with the aim of reducing further transmission.