bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision not prediction: Body-ownership illusion as a consequence of online precision adaptation under Bayesian inference
Authors: Novický Filip , Meera Ajith Anil , Zeldenrust Fleur , Lanillos Pablo
Published: September 2024

Humans can experience body-ownership of new (external) body parts, for instance, via visuotactile stimulation. While there are models that capture the influence of such body illusions in body localization and recalibration, the computational mechanism that drives the experience of body-ownership of external limbs is still not well understood and under discussion. Here, we describe a mathematical model of this phenomenon via uncertainty minimization. Using the Rubber Hand Illusion (RHI) as a proxy, we show that to properly estimate one’s arm position, an agent infers the least uncertain world model that explains the observed reality through online adaptation of the signals’ relevance, i.e., the precision parameters (inverse variance of the prediction error signal). Our computational model describes that the illusion is triggered when the sensory precision quickly adapts to account for the increase of sensory noise during the physical stimulation of the rubber hand due to the real hand occlusion. This adaptation produces a change in the uncertainty of the body position estimates yielding to a switch of the perceived reality: the ‘rubber hand is the agent’s hand’ becomes the most plausible model (i.e., it has the least posterior uncertainty). Overall, our theoretical account, along with the numerical simulations provided, suggests that while the perceptual drifts in body localization may be driven by prediction error minimization, body-ownership illusions are a consequence of estimating the signals precision, i.e. the uncertainty associated with the prediction error.

Author summary

Understanding how body illusions occur is critical for comprehending body perception and embodiment. These illusions may hide powerful mechanisms of the brain and the body to handle uncertainty and conflicts in the sensory input and to adapt to body changes and world interactions. For instance, in less than one minute of visuotactile stimulation humans can experience body-ownership experiences of fake body parts or even experience that a different body is their own. Here, we present a possible explanation, through computational modeling, of why humans suddenly perceive a fake body part as their own. The proposed underlying process is the tracking of the uncertainty associated with the error between the predicted signals and the current sensory input. Our model describes that while the effect of body mislocalization during body illusions may be driven by prediction error minimization, body ownership illusions are triggered by uncertainty resolution.
High Resolution Class I HLA -A, -B, and -C Diversity in Eastern and Southern African Populations
Authors: Ndhlovu Zaza , Banjoko Alabi W , Ng'uni Tiza , Naidoo Nitalia , Ramsuran Veron , Hyrien Olivier
Published: September 2024

Africa remains significantly underrepresented in high-resolution Human Leukocyte Antigen (HLA) data, despite being one of the most genetically diverse regions in the world. This critical gap in genetic information poses a substantial barrier to HLA-based research on the continent. In this study, Class I HLA data from Eastern and Southern African populations were analyzed to assess genetic diversity across the region. We examined allele and haplotype frequency distributions, deviations from Hardy-Weinberg Equilibrium (HWE), linkage disequilibrium (LD), and conducted neutrality tests of homozygosity across various populations. Additionally, the African HLA data were compared to those of Caucasian and African American populations using the Jaccard index and multidimensional scaling (MDS) methods. The study revealed that South African populations exhibited 50.4% more genetic diversity within the Class I HLA region compared to other African populations. Zambia showed an estimated 36.5% genetic diversity, with Kenya, Rwanda and Uganda showing 35.7%, 34.2%, and 31.1%, respectively. Furthermore, an analysis of in-country diversity among different tribes indicated an average Class I HLA diversity of 25.7% in Kenya, 17% in Rwanda, 2.8% in South Africa, 13.6% in Uganda, and 6.5% in Zambia. The study also highlighted the genetic distinctness of Caucasian and African American populations compared to African populations. Notably, the differential frequencies of disease-promoting and disease-preventing HLA alleles across these populations emphasize the urgent need to generate high-quality HLA data for all regions of Africa and its major ethnic groups. Such efforts will be crucial in enhancing healthcare outcomes across the continent.
The Confidence-Noise Confidence-Boost (CNCB) model of confidence rating data
Authors: Mamassian Pascal , de Gardelle Vincent
Published: September 2024

Over the last decade, different approaches have been proposed to interpret confidence rating judgments obtained after perceptual decisions. One very popular approach is to compute meta-d' which is a global measure of the sensibility to discriminate the confidence rating distributions for correct and incorrect perceptual decisions. Here, we propose a generative model of confidence based on two main parameters, confidence noise and confidence boost, that we call CNCB model. Confidence noise impairs confidence judgements above and beyond how sensory noise affects perceptual sensitivity. The confidence boost parameter reflects whether confidence uses the same information that was used for perceptual decisions, or some new information. This CNCB model offers a principled way to estimate a confidence efficiency measure that is a theory-driven alternative to the popular M-ratio. We then describe two scenarios to estimate the confidence boost parameter, one where the experiment uses more than two confidence levels, the other where the experiment uses more than two stimulus strengths. We also extend the model to continuous confidence ratings and describe how a non-linear mapping can be estimated between objective and subjective confidence probabilities. Altogether, the CNCB model should help interpret confidence rating data at a deeper level. This manuscript is accompanied by a toolbox that will allow researchers to estimate all the parameters of the CNCB model in confidence ratings datasets. Some examples of re-analyses of previous datasets are provided in the Appendix.
Changes in flexibility but not in compactness underlie the thermal adaptation of prokaryotic adenylate kinases
Authors: Kontopoulos Dimitrios - Georgios , Patmanidis Ilias , Barraclough Timothy G. , Pawar Samraat
Published: September 2024

Understanding the structural changes that enable enzymes to remain active in extreme thermal conditions is of broad scientific interest for both fundamental and applied biological research. Three key mechanisms that underlie the thermal adaptation of enzymes are modifications in structural flexibility, compactness, and the contacts formed among amino acids. However, most previous studies on these topics have been limited to small sample sizes or a narrow taxonomic focus, and the importance of these factors to thermal adaptation remains poorly understood. In this study, we combined molecular dynamics simulations and phylogenetic comparative analyses to thoroughly analyse the structural factors underlying thermal adaptation in adenylate kinase—a key enzyme involved in cellular energy balance and homeostasis—across 70 prokaryotic species. We detect systematic increases in the flexibility of the enzyme with temperature, both across and within species. In contrast, structural compactness appears to be almost completely independent of temperature. Finally, we uncover a remarkable diversity in the number and types of amino acid contacts observed in different adenylate kinases that cannot be explained solely by temperature. Our results suggest that there are multiple paths toward the adaptation of prokaryotic adenylate kinases to extreme thermal environments and that these paths are generally accessible through changes in flexibility.

Lay summary

The structure of a given enzyme can vary considerably among species, reflecting local environmental conditions to an extent. To this day, we do not have a clear picture of the impacts of the thermal environment on enzyme structure. To fill this gap, we performed a structural comparison of the enzyme adenylate kinase (ADK) from 70 species of bacteria and archaea. We find that rises in temperature tend to increase the flexibility of the enzyme. However, at any given temperature, ADKs from cold environments tend to be more flexible than those from hot environments. In contrast, the compactness of the enzyme did not vary consistently with temperature. Finally, we found that the pattern of amino acid contacts can vary dramatically across ADKs of different species, in a manner that cannot be predicted by temperature alone. Overall, our study shows that there are multiple ways to evolve an enzyme structure that can tolerate extreme temperatures, with a key constraint being maintaining sufficient flexibility at temperatures typically experienced by each species.
Inferring long-term and short-term determinants of genetic diversity in honey bees: Beekeeping impact and conservation strategies
Authors: Leroy Thibault , Faux Pierre , Basso Benjamin , Eynard Sonia , Wragg David , Vignal Alain
Published: September 2024

Bees are vital pollinators in natural and agricultural landscapes around the globe, playing a key role in maintaining flowering plant biodiversity and ensuring food security. Among the honey bee species, the Western honey bee (Apis mellifera) is particularly significant, not only for its extensive crop pollination services but also for producing economically valuable products such as honey. Here, we analyzed whole-genome sequence data from fourApisspecies to explore how honey bee evolution has shaped current diversity patterns. Using Approximate Bayesian Computation, we first reconstructed the demographic history ofA. melliferain Europe, finding support for postglacial secondary contacts, therefore predating human-mediated transfers linked to modern beekeeping. However, our analysis of recent demographic changes then reveals significant bottlenecks due to beekeeping practices, which have notably affected genetic diversity. Black honey bee populations from conservatories, particularly those on islands, exhibit considerable genetic loss, raising concerns about the long-term effectiveness of current conservation strategies. Additionally, we observed a high degree of conservation in the genomic landscapes of nucleotide diversity across the four species, despite a divergence gradient spanning over 15 million years, consistent with a long-term conservation of the recombination landscapes. Taken together, our results provide the most comprehensive assessment of diversity patterns in honey bees to date and offer insights into the optimal management of resources to ensure the long-term persistence of honey bees and their invaluable pollination services.
Loss or redistribution? A better way of estimating regional changes in animal distribution and numbers caused by increased human activities
Authors: Mercker Moritz , Peschko Verena , Borkenhagen Kai , Markones Nele , Schwemmer Henriette , Dierschke Volker , Garthe Stefan
Published: September 2024

A differentiated understanding of how regional human activities affect the spatial distribution and numbers of animals within specific areas of interest is of great ecological importance. Estimating these effects from empirical data is challenging however, because human activities can affect animals in qualitatively different ways and on different spatial and temporal scales. In addition, spatio-temporal animal abundance is frequently influenced by factors intrinsic and extrinsic to the area of interest, potentially confounding impact studies, e.g., based on trends.

In this study, we synergistically combined regression and mechanistic modelling to separate these different influences. We first used partial differential equations to simulate various potential animal redistribution patterns affected by regional human activities. We then selected appropriate patterns as predictors in regression-based species distribution models, together with additional anthropogenic and natural covariates. The simultaneous consideration of large-scale (number-conserving) animal reorganisation, their regional loss or gain, and the influence of additional environmental covariates eventually allowed the generation of qualitative and quantitative estimates and predictions of human-induced changes.

We exemplarily applied our approach to investigate the current and future impact of increasing offshore wind farm (OWF) implementation in the German North Sea on common murres (Uria aalge) during autumn. OWFs constructed up to 2019 reduced common murre numbers in German waters by 18.3%. If the planned OWF priority and reservation areas outlined in the German Marine Spatial Plan are implemented, the predicted loss would increase to 77.7%. Notably, these predictions did not include additional anthropogenic activities or further plans for OWF installation, which could together lead to the almost complete disappearance of common murres from the German North Sea.

By directly comparing predicted animal numbers and distributions in hypothetical scenarios with and without human pressures, the presented method allows us to measure and predict the effects of human activities on regional trends and large-scale reorganisation. This in turn helps us to quantify and predict the impact of planned human activities on wildlife, including in the context of the current rapid expansion of alternative energies.
The spatial reference frame of history-driven distractor suppression and target enhancement
Authors: Ilksoy Yayla A. , van Moorselaar Dirk , Los Sander A. , Theeuwes Jan
Published: September 2024

The world around us is inherently structured and often repetitive. Research has shown that we can implicitly learn to prioritize relevant objects and locations while filtering out distracting information, creating an integrated priority map for attention allocation. The current study examines whether these attentional biases are tied to environment-dependent (allocentric) or viewpoint-dependent (egocentric) coordinates. The search display consisted of six stimuli that were surrounded by a wheel and square frame. In two experiments, either a distractor or a target appeared more frequently in one location, leading to the suppression or enhancement of that location, respectively. Learning blocks were followed by test blocks, where the surrounding frame rotated, creating egocentric-matching and allocentric-matching locations. These experiments showed that both target and distractor learning relied on an egocentric reference frame only. In follow-up experiments, the likely target and distractor location rotated dynamically with the frame during learning. This revealed that participants can learn to enhance a likely target location in an object-centered, allocentric manner. We hypothesized that while space-based learning feeds into a priority map reliant on an egocentric reference frame, object-based learning allows for implicit prioritization of subparts of objects independent of their spatial orientation.

Public significance statement

Attention is shaped by past experiences, guiding us to suppress locations likely to contain distractors while enhancing locations likely to contain relevant information. This study explores how these attentional biases behave when the search environment is viewed from different perspectives. Do these biases persist relative to our viewpoint, or do they remain stable within the environment? The findings reveal that implicitly suppressed and enhanced locations are tied to viewpoint-dependent coordinates. However, attentional biases can also be formed in an object-centered manner, where a likely target location within an object is prioritized, irrespective of the orientation of that object.
MHC heterozygosity may increase subordinate but not alpha male siring success in white-faced capuchin monkeys (Cebus imitator)
Authors: Buckner Janet C. , Jack Katharine M. , Buehler Margaret , Melin Amanda D. , Schoof Valérie A. M. , Wikberg Eva C. , Hernandez Saul Cheves , Fedigan Linda M. , Lynch Jessica W.
Published: September 2024

The genes of the major histocompatibility complex (MHC) are vital to vertebrate immunity and may influence mate choice in several species. The extent to which the MHC influences female mate choice in primates remains poorly understood, and studies of MHC-based mate choice in platyrrhines are especially rare. White-faced capuchin monkeys (Cebus imitator) reside in multimale-multifemale groups where alpha males sire most of the offspring. In this study, we investigated the roles of social dominance, relatedness, and MHC genotypes in determining which mating pairs produced offspring in wild white-faced capuchins in the Sector Santa Rosa (SSR), Área de Conservación Guanacaste, Costa Rica. We find that males in this population do not differ significantly in MHC metrics based on their social status or siring success. Using mixed conditional logit models and generalized linear models, we find that alpha males that are distantly related to reproducing females are significantly more likely to sire offspring while MHC metrics do not predict the probability of siring offspring, or becoming an alpha male. However, we do find some evidence that subordinate males heterozygous at MHC loci sire significantly more offspring than homozygous subordinates. Further, one-sided binomial simulations reveal that offspring are more frequently heterozygous at MHC loci than expected given the gene pool. We conclude that in this population with limited genomic variation, females may preferentially mate with MHC-diverse subordinate males when related to the alpha, leading to increased probabilities of MHC-diverse offspring.
Probability of outbreaks of forest insects in Europe: a generic model calibrated on six forest insect profiles
Authors: Collot Dorian , Robinet Christelle
Published: September 2024

Abstract

Insect pests are one of the major threats to forests. Although invasive species cause more and more impacts, native species could also generate temporary very high damages. The population dynamics of insects relies on several factors, going from weather to stand conditions. Due to global change, insects could face conditions they have never encountered before, leading to unusual population outbreaks. Forest managers need to consider these possible emerging pests but predicting insect outbreaks is still very challenging. In this context, we have developed a mathematical model at the crossroad of statistical and mechanistic models to describe the likelihood of outbreaks for a set of 6 insect profiles: bark beetles, longhorn beetles, tortrix moth, other moths, aphids, and Hymenoptera. This model describes the probability of occurrence of an outbreak at a given time and at a given area, based on several conditions. It has been built and parametrized on the most documented orders of European forest pests. Parametrization for these species’ profiles can be used as a baseline to explore the risk of outbreaks for closely related pest species. We provide an illustration of the model application for the oak processionary moth,Thaumetopoea processionea, which reach epidemic levels in north-western Europe. This generic outbreak model is particularly performant to point out some years or areas as unlikely for an outbreak, and thus targets correctly factors that inhibit outbreaks. It is still at an exploratory level and should be further improved for an operational use in forest stand surveillance and management.
British Version of the Iowa Test of Consonant Perception
Authors: Guo Xiaoxuan , Benzaquén Ester , Holmes Emma , Choi Inyong , McMurray Bob , Bamiou Doris-Eva , Berger Joel I , Griffiths Timothy D
Published: September 2024

The Iowa Test of Consonant Perception (ITCP) is a single-word closed-set speech- in-noise test with well-balanced phonetic features that provides a reliable testing option for real-world listening.Objectives.The current study aimed to establish a UK version of the test (B-ITCP) based on the British received pronunciation.Design.We conducted a validity test with 46 participants using the B-ITCP test, a sentence-in- noise test, and audiogram.Results.The B-ITCP demonstrated excellent test-retest reliability, cross-talker validity, and good convergent validity, consistent with the US results.Conclusions.These findings suggest that B-ITCP is a reliable measure of speech-in-noise perception, to facilitate comparative or combined studies in USA and UK. All materials (application and scripts) to run or construct the B-ITCP and ITCP are freely available online.
Identification of small molecule enhancers of NK cell tumoricidal activity via a tumor microenvironment-mimicking co-culture assay
Authors: Binici Aylin , Hennes Elisabeth , Koska Sandra , Niemann Jens , Reich Alisa , Pfaff Christiane , Sievers Sonja , Kahnt Astrid S. , Thomas Dominique , Ziegler Slava , Watzl Carsten , Waldmann Herbert
Published: September 2024

The tumor microenvironment (TME) is a pro-cancerous niche harboring immunosuppressive factors that are secreted by cancer cells and the surrounding cancer-supportive tissue, such as kynurenine, prostaglandin E2 and transforming growth factor β (TGFβ). These factors dampen the activity of cytotoxic lymphocytes like natural killer (NK) cells, allowing evasion of immune cell-mediated killing. To identify small molecules that counteract the immunosuppressive effect of the TME and restore NK cell-mediated cytotoxicity, we developed a phenotypic co-culture assay of cancer cells and primary lymphocytes suitable for medium-throughput screening. We discovered small molecules that restore NK cell-mediated cytotoxicity through diverse mechanisms. The potent TGFβ type I receptor (TGFβR-1) inhibitor, RepSox, stood out as superior to other TGFβR-1 inhibitors due to its ability to abolish the effects of both inhibitory factors used in our setup. This mode of action goes beyond TGFβR-1 inhibition and is related to the simultaneous abrogation of cyclooxygenase 1 (COX1) activity.
Myosin XVA isoforms participate in the mechanotransduction-dependent remodeling of the actin cytoskeleton in auditory stereocilia
Authors: López-Porras Ana I. , Kruse Ava M. , McClendon Mark T. , Vélez-Ortega A Catalina
Published: September 2024

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx, which regulates the morphology of the actin cytoskeleton in the shorter ‘transducing’ stereocilia. However, the molecular mechanisms involved in this novel type of activity-driven plasticity in the stereocilium cytoskeleton are currently unknown. Here, we tested the contribution of myosin XVA (MYO15A) isoforms. We used electron microscopy to evaluate morphological changes in the cytoskeleton of auditory hair cell stereocilia after the pharmacological blockage of resting MET currents in cochlear explants from mice that lacked one or all isoforms of MYO15A. Hair cells lacking functional MYO15A isoforms did not exhibit MET-dependent remodeling in their stereocilia cytoskeleton. In contrast, hair cells that only lack the long isoform of MYO15A exhibited increased MET-dependent stereocilia remodeling, including remodeling in stereocilia from the tallest ‘non-transducing’ row of the bundle. We conclude that MYO15A isoforms not only enable but also fine-tune the MET-dependent remodeling of the actin cytoskeleton in transducing stereocilia and contribute to the stability of the tallest row.
Astrocytic Regulation of Cocaine Locomotor Sensitization in EcoHIV Infected Mice
Authors: Xie Qiaowei , Dasari Rohan , Namba Mark D. , Buck Lauren A. , Side Christine M. , Park Kyewon , Jackson Joshua G. , Barker Jacqueline M.
Published: September 2024

Cocaine use disorder (CUD) is highly comorbid with HIV infection and worsens HIV outcomes. Preclinical research on the outcomes of HIV infection may yield crucial information on neurobehavioral changes resulting from chronic drug exposure in people living with HIV (PLWH). Repeated exposure to cocaine alters behavioral responses to cocaine. This includes development of cocaine locomotor sensitization – or increased locomotor responses to the same doses of cocaine - which depends on nucleus accumbens (NAc) neural plasticity. NAc astrocytes are key regulators of neural activity and plasticity, and their function can be impaired by cocaine exposure and HIV infection, thus implicating them as potential regulators of HIV-induced changes in behavioral response to cocaine. To characterize the effects of HIV infection on cocaine locomotor sensitization, we employed the EcoHIV mouse model to assess changes in locomotor responses after repeated cocaine (10mg/kg) exposure and challenge. EcoHIV infection potentiated expression of cocaine sensitization. We also identified EcoHIV-induced increases in expression of the astrocytic nuclear marker Sox9 selectively in the NAc core. To investigate whether modulation of NAc astrocytes could reverse EcoHIV-induced deficits, we employed a chemogenetic approach. We found that chemogenetic activation of NAc astrocyte Gq signaling attenuated EcoHIV-enhanced cocaine sensitization. We propose that HIV infection contributes to cocaine behavioral sensitization and induces adaptations in NAc astrocytes, while promoting NAc astrocytic Gq-signaling can recover EcoHIV-induced behavioral changes. These findings identify potential cellular substrates of disordered cocaine-driven behavior in the context of HIV infection and point toward strategies to reduce cocaine-related behavior in PLWH.
Rhizobacteria prime the activation of defence and nutritional responses to suppress aphid populations on barley
Authors: Mbaluto Crispus M. , Zytynska Sharon E.
Published: September 2024

Interactions between plant and soil microbes are widespread and modulate plant-insect herbivore interactions. Still, it remains unclear how these shapes the overall plant defence responses and the mechanisms involved.

Here, we performed bioassays with barley (Hordeum vulgare) plants to study the underlying molecular pathways induced by two rhizobacteria,Acidovorax radicisorBacillus subtilis,against the phloem feeding aphidSitobion avenaeover three timepoints.

Root colonization byA. radicisorB. subtilissuppressed aphid populations on barley. Analysis of differentially expressed genes and co-expressed gene modules revealed a combination of rhizobacteria and aphid induced plant responses. Aphid feeding triggered distinct plant responses in rhizobacteria-inoculated barley compared to controls, in phytohormone, glutathione, and phenylpropanoid pathways within 24 hours. By day 7, stronger responses were observed in phenylpropanoid and nutrient pathways. By day 21, changes occurred in flavonoid pathways and genes related to tissue damage and repair.

Our study suggests that rhizobacteria inoculation of barley against aphids is dynamic and acts through several molecular pathways to induce plant resistance (defences) and tolerance (nutrition and growth) to aphids. Future research holds promise for exploiting these interactions for sustainable crop protection and pest management in agriculture.
The flexible stalk domain of sTREM2 modulates its interactions with phospholipids in the brain
Authors: Saeb David , Lietzke Emma E. , Fuchs Daisy I. , Aldrich Emma C. , Bruce Kimberley D. , Sprenger Kayla G.
Published: September 2024

The microglial surface protein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) plays a critical role in mediating brain homeostasis and inflammatory responses in Alzheimer’s disease (AD). The soluble form of TREM2 (sTREM2) exhibits neuroprotective effects in AD, though the underlying mechanisms remain elusive. Moreover, differences in ligand binding between TREM2 and sTREM2, which have major implications for their roles in AD pathology, remain unexplained. To address these knowledge gaps, we conducted the most computationally intensive molecular dynamics simulations to date of (s)TREM2, exploring their interactions with key damage- and lipoprotein-associated phospholipids and the impact of the AD-risk mutation R47H. Our results demonstrate that the flexible stalk domain of sTREM2 serves as the molecular basis for differential ligand binding between sTREM2 and TREM2, facilitated by its role in stabilizing the Ig-like domain and altering the accessibility of canonical ligand binding sites. We identified a novel ligand binding site on sTREM2, termed the ‘Expanded Surface 2’, which emerges due to competitive binding of the stalk with the Ig-like domain. Additionally, we observed that the stalk domain itself functions as a site for ligand binding, with increased binding in the presence of R47H. This suggests that sTREM2’s neuroprotective role in AD may, at least in part, arise from the stalk domain’s ability to rescue dysfunctional ligand binding caused by AD-risk mutations. Lastly, our findings indicate that R47H-induced dysfunction in membrane-bound TREM2 may result from both diminished ligand binding due to restricted complementarity-determining region 2 loop motions and an impaired ability to differentiate between ligands, proposing a novel mechanism for loss-of-function. In summary, these results provide valuable insights into the role of sTREM2 in AD pathology, laying the groundwork for the design of new therapeutic approaches targeting (s)TREM2 in AD.
New loci and candidate genes in spring two-rowed barley detected through meta-analysis of a field trial European network
Authors: Montardit-Tarda Francesc , Casas Ana M , Thomas William TB , Schnaithmann Florian , Sharma Rajiv , Shaaf Salar , Campoli Chiara , Russell Joanne , Ramsay Luke , Delbono Stefano , Jääskeläinen Marko , Paul Maitry , Stoddard Frederick L , Visioni Andrea , Flavell Andrew J , Pillen Klaus , Kilian Benjamin , Graner Andreas , Rossini Laura , Waugh Robbie , Cattivelli Luigi , Schulman Alan H , Tondelli Alessandro , Igartua Ernesto
Published: September 2024

This study contributes new knowledge on quantitative trait loci (QTLs) and candidate genes for adaptive traits and yield in two-rowed spring barley. A meta-analysis of a network of field trials, varying in latitude and sowing date, with 151 cultivars across several European countries, increased QTL detection power compared to single-trial analyses. The traits analysed were heading date (HD), plant height (PH), thousand-grain weight (TGW), and grain yield (GY). Breaking down the analysis by the main genotype-by-environment trends revealed QTLs and candidate genes specific to conditions like sowing date and latitude. A historical look on the evolution of QTL frequencies revealed that early selection focused on PH and TGW, likely due to their high heritability. GY selection occurred later, facilitated by reduced variance in other traits. The study observed that favourable alleles for plant height were often fixed before those for grain yield and TGW. Some regions showed linkage in repulsion, suggesting targets for future breeding. Several candidate genes were identified, including known genes and new candidates based on orthology with rice. Remarkably, thedeficiensallele of geneVrs1, appears associated to higher GY. These findings provide valuable insights for barley breeders aiming to improve yield, and other agronomic traits.

Highlight

A dense genome-wide meta-analysis provides new QTLs, reveals breeding history trends and identifies new candidate genes for yield, plant height, grain weight and heading time of spring barley.
A generalizable normative deep autoencoder for brain morphological anomaly detection: application to the multi-site StratiBip dataset on bipolar disorder in an external validation framework
Authors: Sampaio Inês Won , Tassi Emma , Bellani Marcella , Benedetti Francesco , Nenadic Igor , Phillips Mary , Piras Fabrizio , Yatham Lakshmi , Bianchi Anna Maria , Brambilla Paolo , Maggioni Eleonora
Published: September 2024

The heterogeneity of psychiatric disorders makes researching disorder-specific neurobiological markers an ill-posed problem. Here, we face the need for disease stratification models by presenting a generalizable multivariate normative modelling framework for characterizing brain morphology, applied to bipolar disorder (BD). We employed deep autoencoders in an anomaly detection framework, combined with a confounder removal step integrating training and external validation.

The model was trained with healthy control (HC) data from the human connectome project and applied to multi-site external data of HC and BD individuals. We found that brain deviating scores were greater, more heterogeneous, and with increased extreme values in the BD group, with volumes prominently from the basal ganglia, hippocampus and adjacent regions emerging as significantly deviating. Similarly, individual brain deviating maps based on modified z scores expressed higher abnormalities occurrences, but their overall spatial overlap was lower compared to HCs.

Our generalizable framework enabled the identification of subject- and group-level brain normative-deviating patterns, a step forward towards the development of more effective and personalized clinical decision support systems and patient stratification in psychiatry.
Next-generation Cu(II) selective peptide shuttles prevent Cu(Aβ)-induced toxicity and microglial activation in organotypic hippocampal slices
Authors: Okafor Michael , Schmitt David , Gasman Stéphane , Raibaut Laurent , Hureau Christelle , Faller Peter , Vitale Nicolas
Published: September 2024

Alzheimer’s disease (AD) remains the most prevalent neurodegenerative disease with hallmarks including the apparition, in specific areas of the brain, of intracellular neurofibrillary tangles and extracellular amyloid plaques. The latter result from an abnormal metabolism of Amyloid-β precursor protein (APP) leading to its accumulation in plaques.Ex vivoanalysis of AD patients’ brains, show an abnormally elevated concentration of metals including Cu, Zn and Fe in these plaques. Some studies have also demonstrated altered Cu levels in the entire brain and more specifically in regions heavily affected in AD. These modifications are often accompanied by a decline in neuronal Cu levels and by an increase in the proportion of extracellular labile Cu, which in turn promotes reactive oxygen species formation. To correct this Cu dyshomeostasis, we designed and synthesized novel Cu(II)-selective peptide shuttles, capable of swiftly retrieving Cu from extracellular Aβ and subsequently transporting and releasing Cu inside cells. We demonstrate here the capacity of this new Cu-shuttles, DapHH-αR5W4NBDand HDapH-αR5W4NBD, to protect organotypic hippocampal slices (OHSCs) from Cu(Aβ)-induced insult and their capability to rescues Cu-induced microglial activation and proliferation.
Humidity as a zeitgeber for circadian entrainment of insect systems
Authors: Chen Shyh-Chi , Goodhart Grace , Eaton Daniel , Catlett Nathan , Cady Tabitha , Tran Hannah , Lutz Luke E. , Wang Lyn , Girard Ella , Savino Jaida , Perry Jodi , Hall Libby , Bidiwala Amena , Tarter Emma , Tompkin Joshua , Greene Nina , Benoit Joshua B.
Published: September 2024

Humidity levels, like light and temperature, fluctuate daily yet are less predictable; however, whether humidity entrains circadian clocks and enables animals to synchronize behaviors to environmental variations remains unknown. Here, we investigate the circadian humidity entrainment in various insects. Multiple species robustly respond to humidity cycles, and when the humidity cue is removed, their rhythmic behaviors continue, suggesting that humidity-associated rhythmic activities are under circadian control. Moreover, theDrosophilaclock and hygrosensation mutants lack rhythmic activities during and after humidity entrainment, indicating that the core clock components and hygrosensors are essential to circadian entrainment. Our findings identify that humidity serves as a novel zeitgeber for circadian entrainment for insects that could have broad applicability and importance among animal systems.

One Sentence Summary

Humidity entrainment of the circadian clock enables the synchronization of insect behaviors to environments.
Metapipeline-DNA: A Comprehensive Germline & Somatic Genomics Nextflow Pipeline
Authors: Patel Yash , Zhu Chenghao , Yamaguchi Takafumi N. , Wang Nicholas K. , Wiltsie Nicholas , Gonzalez Alfredo E. , Winata Helena K. , Zeltser Nicole , Pan Yu , Mootor Mohammed Faizal Eeman , Sanders Timothy , Kandoth Cyriac , Fitz-Gibbon Sorel T. , Livingstone Julie , Liu Lydia Y. , Carlin Benjamin , Holmes Aaron , Oh Jieun , Sahrmann John , Tao Shu , Eng Stefan , Hugh-White Rupert , Pashminehazar Kiarod , Park Andrew , Beshlikyan Arpi , Jordan Madison , Wu Selina , Tian Mao , Arbet Jaron , Neilsen Beth , Bugh Yuan Zhe , Kim Gina , Salmingo Joseph , Zhang Wenshu , Haas Roni , Anand Aakarsh , Hwang Edward , Neiman-Golden Anna , Steinberg Philippa , Zhao Wenyan , Anand Prateek , Tsai Brandon L. , Boutros Paul C.
Published: September 2024

DNA sequencing continues to get cheaper and faster. In parallel, algorithmic innovations have allowed inference of a wide range of nuclear, mitochondrial, somatic and evolutionary from DNA sequencing data. To make automated, high-quality DNA sequencing more readily available, we created an extensible Nextflow meta-pipeline called metapipeline-DNA. Metapipeline-DNA supports processing raw sequencing reads through alignment, variant detection, quality control and subclonal reconstruction. Each step supports quality-control, data-visualization and multiple algorithms. Metapipeline-DNA is cloud-compatible and highly configurable, with options to subsect, optimize and optimize analyses, including with automated failure-recovery. Metapipeline-DNA enables high-scale, fault-tolerant, comprehensive analysis of genome sequencing.

Availability

Metapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is available athttps://github.com/uclahs-cds/metapipeline-DNA.
A highly active bacterial actin actuates the polymerization of another isoform essential for swimming motility ofSpiroplasma
Authors: Takahashi Daichi , Kiyama Hana , Matsubayashi Hideaki , Fujiwara Ikuko , Miyata Makoto
Published: September 2024

Spiroplasmais a wall-less helical bacterium that is characterized by a unique swimming motility involving five isoforms of the bacterial actin MreBs (SMreB1-5). The functions of SMreBs are unique in the MreB family proteins, as their counterparts in walled-bacteria are involved in maintaining the cell shape by scaffolding the cell-wall synthesis complex through their static properties.In vitroanalyses of individual SMreBs provide clues to understand the detailed molecular mechanism ofSpiroplasmaswimming. However, the purification difficulties have hamperedin vitroanalyses of one of the SMreBs, SMreB1, which drives the swimming. Here, we isolated soluble SMreB1 ofSpiroplasma eriocheiris(SpeMreB1) and evaluated its activity. SpeMreB1 was expressed as a fusion with a solubilization-tag, ProteinS (PrS), which allowed us to purify it in the soluble fraction. SpeMreB1 exhibited the highest phosphate release rate and the fold changes of critical concentrations for polymerization across the nucleotide states among the MreB family proteins. SpeMreB1 interacted with polymerized SpeMreB5, another SMreB essential forSpiroplasmaswimming. In the AMPPNP- or ADP-bound state, SpeMreB1 decreased the amount of SpeMreB5 filaments, possibly reflecting their disassembly. Regardless of the nucleotide state, SpeMreB1 bound to negatively charged lipids. These results suggest that SpeMreB1 utilizes its highest activity to manage SpeMreB5 filaments underneath the cell membrane to driveSpiroplasmaswimming.
Restoration of 3-D structure of insect flight muscle from a rotationally averaged 2-D X-ray diffraction pattern
Authors: Iwamoto Hiroyuki
Published: September 2024

The contractile machinery of muscle, especially that of skeletal muscle, has a very regular array of contractile protein filaments, and gives rise to a complex and informative diffraction pattern when irradiated with X-rays. However, analyzing these diffraction patterns is often challenging because: (1) only rotationally averaged diffraction patterns can be obtained, resulting in a substantial loss of information, and (2) the contractile machinery contains two different sets of protein filaments (actin and myosin) with different helical symmetries. The reflections originating from them often overlap. These problems may be solved if the real-space 3-D structure of the contractile machinery is directly calculated from the diffraction pattern. Here we demonstrate that, by using the conventional phase-retrieval algorithm (hybrid input-output), the real-space 3-D structure of the contractile machinery can be effectively restored from a single rotationally averaged 2-D diffraction pattern. In this calculation, we used an in-silico model of insect flight muscle, which is known for its highly regular structure. We also extended this technique to an experimentally recorded muscle diffraction pattern.
A Computational Framework to Optimize the Mechanical Behavior of Synthetic Vascular Grafts
Authors: Jiang David , Robinson Andrew J , Nkansah Abbey , Leung Jonathan , Guo Leopold , Maas Steve A , Weiss Jeffrey A , Cosgriff-Hernandez Elizabeth M , Timmins Lucas H
Published: September 2024

The failure of synthetic small-diameter vascular grafts has been attributed to a mismatch in the compliance between the graft and native artery, driving mechanisms that promote thrombosis and neointimal hyperplasia. Additionally, the buckling of grafts results in large deformations that can lead to device failure. Although design features can be added to lessen the buckling potential, the addition is detrimental to decreasing compliance (e.g., reinforcing coil). Herein, we developed a novel finite element framework to inform vascular graft design by evaluating compliance and resistance to buckling. A batch-processing scheme iterated across the multi-dimensional design parameter space, which included three parameters: coil thickness, modulus, and spacing. Three types of finite element models were created in FEBio for each unique coil-reinforced graft parameter combination to simulate pressurization, axial buckling, and bent buckling, and results were analyzed to quantify compliance, buckling load, and kink radius, respectively, from each model. Importantly, model validation demonstrated that model predictions agree qualitatively and quantitatively with experimental observations. Subsequently, data for each design parameter combination were integrated into an optimization function for which a minimum value was sought. The optimization values identified various candidate graft designs with promising mechanical properties. Our investigation successfully demonstrated the model-directed framework identified vascular graft designs with optimal mechanical properties, which can potentially improve clinical outcomes by addressing device failure. In addition, the presented computational framework promotes model-directed device design for a broad range of biomaterial and regenerative medicine strategies.
The proteomic landscape and temporal dynamics of mammalian gastruloid development
Authors: Garge Riddhiman K. , Lynch Valerie , Fields Rose , Casadei Silvia , Best Sabrina , Stone Jeremy , Snyder Matthew , McGann Chris D. , Shendure Jay , Starita Lea M. , Hamazaki Nobuhiko , Schweppe Devin K.
Published: September 2024

Gastrulation is the highly coordinated process by which the early embryo breaks symmetry, establishes germ layers and a body plan, and sets the stage for organogenesis. As early mammalian development is challenging to studyin vivo, stem cell-derived models have emerged as powerful surrogates,e.g.human and mouse gastruloids. However, although single cell RNA-seq (scRNA-seq) and high-resolution imaging have been extensively applied to characterize suchin vitroembryo models, a paucity of measurements of protein dynamics and regulation leaves a major gap in our understanding. Here, we sought to address this by applying quantitative proteomics to human and mouse gastruloids at four key stages of their differentiation (naïve ESCs, primed ESCs, early gastruloids, late gastruloids). To the resulting data, we perform network analysis to map the dynamics of expression of macromolecular protein complexes and biochemical pathways, including identifying cooperative proteins that associate with them. With matched RNA-seq and phosphosite data from these same stages, we investigate pathway-, stage- and species-specific aspects of translational and post-translational regulation,e.g.finding peri-gastrulation stages of human and mice to be discordant with respect to the mitochondrial transcriptome vs. proteome, and nominating novel kinase-substrate relationships based on phosphosite dynamics. Finally, we leverage correlated dynamics to identify conserved protein networks centered around congenital disease genes. Altogether, our data (https://gastruloid.brotmanbaty.org/) and analyses showcase the potential of intersectingin vitroembryo models and proteomics to advance our understanding of early mammalian development in ways not possible through transcriptomics alone.
A summary of intraspecific size variation for large odontocetes
Authors: McClure Joseph
Published: September 2024

The study of cetacean size and growth aids in research about their energetics, ecology, evolution, and taxonomy. Data on total body length and mass of large cetaceans is retained in an overwhelming amount of literature and previous reviews are limited in discussing the variation of both length and mass. Nearly all the known published literature was examined to provide a brief but comprehensive summary of the adult size of four large odontocetes. To supplement the existing literature, data from the International Whaling Commission catch database were reviewed and incorporated into analyses to improve descriptions of intraspecific variation in adult size forPhyseter macrocephalus. Regional comparisons of commercial data forP. macrocephalusrevealed apparent differences in adult size that are likely more attributable to catch biases rather than a diagnostic difference in size between populations.