bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the selection pressure and evolutionary rate of proteins on the non-neutral hypothesis of synonymous mutations
Authors: Ye Jiachen , Cui Chunmei , Fan Rui , Cui Qinghua 
Published: April 2024

AbstractThe Nonsynonymous/Synonymous substitution rate ratio (Ka/Ks) is a commonly used metric to estimate the selection pressure and evolutionary rate of proteins in comparative genomics, which plays critical roles in molecular evolution in both biology and medicine. A fundamental assumption of Ka/Ks is that synonymous mutations are evolutionarily neutral and not subject to natural selection as they do not alter protein sequences and function. However, a number of studies have demonstrated that synonymous mutations are non-neutral and may lead to diseases through a number of mechanisms, such as altering miRNA regulation. This further implies that synonymous mutations also participate in the process of natural selection and thus Ka/Ks should be redefined as well. For this purpose, here we propose an improved Ka/Ks ratio,iKa/Ks, which re-computed the neutral substitution rate by taking the altered status of miRNA binding into consideration, and thereby incorporate the impact of synonymous mutations on miRNA regulation. As a result,iKa/Ks shows better performance than Ka/Ks when comparing them using their correlation with expression distance. Moreover, case studies showed thatiKa/Ks is able to identify the positive/negative selection genes that are missed by Ka/Ks. For example, TMEM72/Tmem72 is estimated to be positively selected byiKa/Ks (1.13) but negatively selected by the conventional Ka/Ks ratio (0.21). Further evidence showed its rapid evolution, which further support the power of the new algorithm.
Tracking small animals in complex landscapes: a comparison of localisation workflows for automated radio telemetry systems
Authors: Rueda-Uribe Cristina , Sargent Alyssa J. , Echeverry-Galvis María Ángela , Camargo-Martínez Pedro A. , Capellini Isabella , Lancaster Lesley T. , Rico-Guevara Alejandro , Travis Justin M. J. 
Published: April 2024

AbstractAutomated radio telemetry systems (ARTS) have the potential to revolutionise our understanding of animal movement by providing a near-continuous record of individual locations in the wild. However, localisation error in data generated by ARTS can be very high, especially in natural landscapes with complex vegetation structure and topography. This curtails the ecological questions that may be addressed with this technology. Here, we set up an ARTS grid in a valley with heterogeneous vegetation cover in the Colombian high Andes and applied an analytical pipeline to test the effectiveness of localisation methods. We performed calibration trials to simulate animal movement in high-or low-flight, or walking on the ground, and compared workflows with varying decisions related to signal cleaning, selection, smoothing, and interpretation, along with four multilateration approaches. We also quantified the influence of spatial features on the system’s accuracy. We tested the grid by deploying tags on two high-altitude hummingbirds, the Great Sapphirewing (Pterophanes cyanopterus) and Bronze-tailed Thornbill (Chalcostigma heteropogon). Results showed large variation in localisation error, ranging from only 0.4–43.4 m from known locations up to 474–1929 m, depending on the localisation method used. The lowest average median error across calibration tracks was 105 m. In particular, we found that the selection of higher radio signal strengths and data smoothing based on the temporal autocorrelation in movement data are useful tools to improve accuracy. Moreover, the variables that significantly influence localisation error include terrain ruggedness, height of movement, vegetation type, and the location of animals inside or outside the grid area. In the case of our study system, thousands of location points were successfully estimated for two hummingbird species that previously lacked movement ecology data. Our case study on hummingbirds suggests ARTS grids can be used to estimate small animals’ home ranges, associations with vegetation types, and seasonality in occurrence. We present a comparative localisation pipeline, highlighting the variety of possible decisions while processing radio signal data. Overall, this study provides guidance to improve the resolution of location estimates, broadening the application of this tracking technology in the study of the spatial ecology of wild populations.
An experimental approach to study multi-species interactions implicated in Fusarium-Head Blight complex assembly in wheat
Authors: Corrales Gutiérrez Miguel Ángel , Kaur Harleen , Desiderio Francesca , Douchkov Dimitar Kostadinov , Zhan Jiasui , Vélëz Heriberto , Bourras Salim 
Published: April 2024

AbstractFusarium Head Blight (FHB) is a major disease of cereal crops present everywhere where wheat is produced. A complex of several, distinctly different, species from the genusFusariumare responsible for causing the disease, with important taxa beingF. graminearum,F. culmorum, andF. avenaceum. FHB is an adult stage, late season disease affecting wheat at anthesis. However, recent discoveries are now challenging the basic assumption that anthers and spikes are the only ecological niches relevant for resistance to FHB. Most prominently, it has been established that pathogens typically occurring earlier in the season, such asZymoseptoria tritici, induce strong systemic changes in the plant immune system, that expand way beyond their primary ecological niche. Furthermore, taxa implicated in FHB can be isolated from virtually all wheat tissues, including typical blotch symptoms on wheat leaves. Strikingly, such important biological observations about the complex lifestyle of FHB causing taxa are overlooked as potential targets in resistance breeding. In this work we present a simplified approach allowing the dissection of the intricate lifestyles of the FHB causingFusariumtaxa. In doing so, we provide an experimental proof-of-concept that systemic signals fromZ. triticican affect the basic response of wheat toF. graminearum. We further demonstrate that differences inFusariumspecies composition affect the outcome of the interaction in a genotype-specific manner. We argue that efforts to study hidden layers of the biology of FHB associated taxa are crucial to developing new resistance breeding strategies, based on a better understanding of the genetic drivers of the disease.
Vestibular-derived internal models in active self-motion estimation
Authors: van Helvert Milou J.L. , Selen Luc P.J. , van Beers Robert J. , Medendorp W. Pieter 
Published: April 2024

AbstractSelf-motion estimation is thought to depend on sensory information as well as on sensory predictions derived from motor feedback. In driving, the vestibular afference can in principle be predicted based on the steering motor commands if an accurate internal model of the steering dynamics is available. Here, we used a closed-loop steering experiment to examine whether participants can build such an internal model of the steering dynamics. Participants steered a motion platform on which they were seated to align their body with a memorized visual target. We varied the gain between the steering wheel angle and the velocity of the motion platform across trials in three different ways: unpredictable (white noise), moderately predictable (random walk), or highly predictable (constant gain). We examined whether participants took the across-trial predictability of the gain into account to control their steering (internal model hypothesis), or whether they simply integrated the vestibular feedback over time to estimate their travelled distance (path integration hypothesis). Results from a trial series regression analysis show that participants took the gain of the previous trial into account more when it followed a random walk across trials than when it varied unpredictably across trials. Furthermore, on interleaved trials with a large jump in the gain, participants made fast corrective responses, irrespective of gain predictability, suggesting they also rely on vestibular feedback. These findings suggest that the brain can construct an internal model of the steering dynamics to predict the vestibular reafference in driving and self-motion estimation.
The Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO): Design and Baseline Characteristics for a Birth Cohort Study of Early-life Viral Respiratory Illnesses and Airway Dysfunction in Puerto Rican Children
Authors: Witonsky Jonathan I. , Elhawary Jennifer R. , Eng Celeste , Oh Sam S. , Salazar Sandra , Contreras Maria G. , Medina Vivian , Secor Elizabeth A. , Zhang Priscilla , Everman Jamie L. , Fairbanks-Mahnke Ana , Pruesse Elmar , Sajuthi Satria P. , Chang Chih-Hao , Guerrero Tsunami Rosado , Fuentes Keyshla Canales , Lopez Natalie , Montanez-Lopez Chris Angely , Otero Richeliz Alfonso , Rivera Raymarie Colon , Rodriguez Leysha , Vazquez Gabriela , Hu Donglei , Huntsman Scott , Jackson Nathan D. , Li Yingchun , Morin Andrew , Nieves Natalie A. , Rios Cydney , Serrano Gonzalo , Williams Blake J. M. , Ziv Elad , Moore Camille M. , Sheppard Dean , Burchard Esteban Gonzalez , Seibold Max A. , Rodriguez Santana Jose R. 
Published: April 2024

AbstractEpidemiologic studies demonstrate an association between early-life respiratory illnesses (RIs) and the development of childhood asthma. However, it remains uncertain whether these children are predisposed to both conditions or if early-life RIs induce alterations in airway function, immune responses, or other human biology that contribute to the development of asthma. Puerto Rican children experience a disproportionate burden of early-life RIs and asthma, making them an important population for investigating this complex interplay. PRIMERO, thePuerto Rican Infant Metagenomics and Epidemiologic Study of Respiratory Outcomes, recruited pregnant women and their newborns to investigate how the airways develop in early life among infants exposed to different viral RIs, and will thus provide a critical understanding of childhood asthma development. As the first asthma birth cohort in Puerto Rico, PRIMERO will prospectively follow 2,100 term healthy infants. Collected samples include post-term maternal peripheral blood, infant cord blood, the child’s peripheral blood at the year two visit, and the child’s nasal airway epithelium, collected using minimally invasive nasal swabs, at birth, during RIs over the first two years of life, and at annual healthy visits until age five. Herein, we describe the study’s design, population, recruitment strategy, study visits and procedures, and primary outcomes.
Intergenerational transmission of complex traits and the offspring methylome
Authors: Hagenbeek Fiona A. , Pool René , Van Asselt Austin J. , Ehli Erik A. , Smit August B. , Bartels Meike , Hottenga Jouke Jan , Dolan Conor V. , van Dongen Jenny , Boomsma Dorret I. 
Published: April 2024

AbstractThe genetic makeup of parents can directly or indirectly affect their offspring phenome through genetic transmission or via the environment that is influenced by parental heritable traits. Our understanding of the mechanisms by which indirect genetic effects operate is limited. Here, we hypothesize that one mechanism is via the offspring methylome. To test this hypothesis, polygenic scores (PGSs) for schizophrenia, smoking initiation, educational attainment (EA), social deprivation, body mass index (BMI), and height were analyzed in a cohort of 1,528 offspring and their parents (51.5% boys, mean [SD] age = 10 [2.8] years). We modelled parent and offspring PGSs on offspring buccal-DNA methylation, accounting for the own PGS of offspring, and found significant associations between parental PGSs for schizophrenia, EA, BMI, and height, and offspring buccal methylation sites, comprising 16, 2, 1, and 6 sites, respectively (alpha = 2.7 × 10−5). More DNA methylation sites were associated with maternal than paternal PGSs, possibly reflecting the maternal pre- and periconceptional environment or stronger maternal involvement in shaping the offspring’s environment during early childhood.
Validation of plasmonic-based biosensors for rapid and sensitive detection of rabbit hemorrhagic and foot-and-mouth disease viruses in biological samples
Authors: Urbinati Chiara , Di Giovanni Vittoria , Pezzoni Giulia , Capucci Lorenzo , Rusnati Marco 
Published: April 2024

ABSTRACTBiosensing technologies and monoclonal antibodies (MAbs) are gaining increasing importance as powerful tools in the field of virology. Surface plasmon resonance (SPR) is an optical biosensing technology already used in virus detection and in the screening of MAbs of diagnostic and therapeutic value. Rabbit haemorrhagic disease virus 2 (RHDV) and foot-and-mouth disease virus (FMDV) are top veterinary issues for whom, the development of novel methods for their detection in biological samples represents a priority with important livestock healthcare and economic implications. With these premises, here we prepared a series of SPR biosensors containing RHDV2 or its 6S subunit immobilized to the surface by different strategies. The biosensors were then used to characterize the binding capacity of a panel of anti-RHDV2 MAbs. From the comparison of the results obtained, the biosensor composed of intact RHDV2 captured with catcher-MAb covalently immobilized to the surface showed the best analytical performances, that were retained also when the same strategy was adopted to prepare a biosensor containing a different virus (namely, FMVD). The results obtained are discussed in view of the exploitation of SPR in the rapid, sensitive and resilient detection of viruses in biological materials and in the screening of antiviral MAbs libraries.
Cold induces brain region-selective cell activity-dependent lipid metabolism
Authors: Min Hyeonyoung , Yang Yale Y , Yang Yunlei 
Published: April 2024

AbstractIt has been well documented that cold is an enhancer of lipid metabolism in peripheral tissues, yet its effect on central nervous system lipid dynamics is underexplored. It is well recognized that cold acclimations enhance adipocyte functions, including white adipose tissue (WAT) lipid lipolysis and beiging, and brown adipose tissue (BAT) thermogenesis in mammals. However, it remains unclear whether and how lipid metabolism in the brain is also under the control of cold acclimations. Here, we show that cold exposure predominantly increases the expressions of the lipid lipolysis genes and proteins within the paraventricular nucleus of the hypothalamus (PVH). Mechanistically, we find that cold activates cells within the PVH and pharmacological inactivation of cells blunts cold-induced effects on lipid peroxidation, accumulation of lipid droplets (LDs), and lipolysis in the PVH. Together, these findings suggest that PVH lipid metabolism is cold sensitive and integral to cold-induced broader regulatory responses.
Direct and indirect striatal projecting neurons exert strategy-dependent effects on decision-making
Authors: Chaves Rodriguez Elena , Naudé Jérémie , Rial Daniel , de Kerchove d’Exaerde Alban 
Published: April 2024

ABSTRACTThe striatum plays a key role in decision-making, with its effects varying with anatomical location and direct and indirect pathway striatal projecting neuron (d- and i-SPN) populations. Using a mouse gambling task with a reinforcement-learning model, we described of individual decision-making profiles as a combination of three archetypal strategies: Optimizers, Risk-averse, Explorers. Such strategies reflected stable differences in the parameters generating decisions (sensitivity to the reward magnitude, to risk or to punishment) derived from a reinforcement-learning model of animal choice. Chemogenetic manipulation showed that dorsomedial striatum (DMS) neurons substantially impact decision-making, while the nucleus accumbens (NAc) and dorsolateral striatum neurons (DLS) have lesser or no effects, respectively. Specifically, DMS dSPNs decrease risk aversion by increasing the perceived value of risky choices, while DMS iSPNs emphasize large gains, affecting decisions depending on decision-making profiles. Hence, we propose that striatal populations from different subregions influence distinct decision-making parameters, leading to profile-dependent choices.
Opposing actions of co-released GABA and neurotensin on the activity of preoptic neurons and on body temperature
Authors: Tabarean Iustin V. 
Published: April 2024

AbstractNeurotensin (Nts) is a neuropeptide acting as a neuromodulator in the brain. Pharmacological studies have identified Nts as a potent hypothermic agent. The medial preoptic area, a region that plays an important role in the control of thermoregulation, contains a high density of neurotensinergic neurons and Nts receptors. The conditions in which neurotensinergic neurons play a role in thermoregulation are not known. In this study optogenetic stimulation of preoptic Nts neurons induced a small hyperthermia.In vitro, optogenetic stimulation of preoptic Nts neurons resulted in synaptic release of GABA and net inhibition of the preoptic pituitary adenylate cyclase-activating polypeptide (PACAP) neurons firing activity. GABA-A receptor antagonist or genetic deletion of VGAT in Nts neurons unmasked also an excitatory effect that was blocked by a Nts receptor 1 antagonist. Stimulation of preoptic Nts neurons lacking VGAT resulted in excitation of PACAP neurons and hypothermia. Mice lacking VGAT expression in Nts neurons presented changes in the fever response and in the responses to heat or cold exposure as well as an altered circadian rhythm of body temperature. Chemogenetic activation of all Nts neurons in the brain induced a 4-5 °C hypothermia, which could be blocked by Nts receptor antagonists in the preoptic area. Chemogenetic activation of preoptic neurotensinergic projections resulted in robust excitation of preoptic PACAP neurons. Taken together our data demonstrate that endogenously released Nts can induce potent hypothermia and that excitation of preoptic PACAP neurons is the cellular mechanism that triggers this response.
Lateral Entorhinal Cortex Dysfunction in Alzheimer’s disease Mice
Authors: Raghuraman Radha , Aoun Andrew , Herman Mathieu , Shetler Oliver , Nahmani Eden , Hussaini S. Abid 
Published: April 2024

AbstractIn Alzheimer’s disease (AD), the formation of amyloid beta (Aβ) and neurofibrillary tangles (NFTs) leads to neuronal loss in entorhinal cortex (EC), a crucial brain region for memory and navigation. These pathological changes are concurrent with the onset of memory impairments in AD patients with symptoms of forgetfulness such as misplacing items, disorientation in familiar environments etc. The lateral EC (LEC) is associated with non-spatial memory processing including object recognition. Since some LEC neurons fire in response to objects (object cells) while others fire at locations previously occupied by objects (trace cells), pathology in this region could lead to dysfunction in object-location coding. In this paper we show that a transgenic AD mouse model, EC-App/Tau, which expresses both APP and tau primarily in the EC region, have deficits in LEC-specific memory tasks. Using in vivo single-unit electrophysiology recordings we show that LEC neurons are hyperactive with low information content and high sparsity compared to the controls indicating poor firing fidelity. We finally show that object cells and trace cells fire less precisely in the EC-App/Tau mice compared to controls indicating poor encoding of objects. Overall, we show that AD pathology causes erratic firing of LEC neurons and object coding defects leading to LEC-specific memory impairment.
A nutrient-dependent foraging phenotype ofS. coelicolorexhibits enhanced antimicrobial activity and is common across the genus
Authors: Söderholm Niklas , Tanner Hugh , Sandblad Linda 
Published: April 2024

SUMMARYSpecies of the genusStreptomycesare filamentous bacteria mainly residing in soils. The capacity of streptomycetes to adapt to various environments is reflected in the sheer size of their genomes and the number of encoded regulatory proteins. The nutrient-rich laboratory conditions significantly differ from the natural habitat of streptomycetes and fail to stimulate their full range of adaptive behaviors; as a result, the majority of biosynthetic gene clusters remain silent. Moreover, the use of rich media has led to the assumption that nutrient depletion ultimately promotes sporulation. However, we demonstrate thatS. coelicolorcolonies can respond to nutrient depletion by undergoing a previously unidentified phenotypic transition termed “foraging” due to its submerged and continuous growth on depleted media. The foraging phenotype is distinctly different from conventional phenotypes in terms of colony morphology, genomic stability, and metabolomic profile. This adaptation to nutrient deprivation through foraging is found throughout theStreptomycesphylogeny, indicating that the phenotype is highly conserved. Furthermore, foragingS. coelicolorgains the ability to inhibit molds and enhanced competitive activity against both gram-negative and gram-positive bacteria is detected in other species. These findings highlight how morphological adaptations of streptomycetes in nutrient-limited environments alter secondary metabolite production, enabling the screening of novel antimicrobial activities. These discoveries have implications ranging from the basic biology of streptomycetes to drug discovery and microbial ecology.
Genetic properties underlying transcriptional variability across different perturbations
Authors: Tsuru Saburo , Furusawa Chikara 
Published: April 2024

AbstractThe rate and direction of phenotypic evolution depend on the availability of phenotypic variants induced genetically or environmentally. It is widely accepted that organisms do not display uniform phenotypic variation, with certain variants arising more frequently than others in response to genetic or environmental perturbations. Previous studies have suggested that gene regulatory networks channel both environmental and genetic influences. However, how the gene regulatory networks influence phenotypic variation remains unclear. To address this, we characterize transcriptional variations inEscherichia coliunder environmental and genetic perturbations. Based on the current understanding of transcriptional regulatory networks, we identify genetic properties that explain gene-to-gene differences in transcriptional variation. Our findings highlight the role of gene regulatory networks in shaping the shared phenotypic variability across different perturbations.