bluuebunny/crossref_metadata_2025_split huggingface dataset:
Culture system for longitudinal monitoring of bone remodelingex vivo
Authors: Cramer E.E.A. , Hermsen K.C.J. , Kock L.M. , Ito K. , Hofmann S. 
Published: October 2023

AbstractTo quantify and visualize both bone formation and resorption within osteochondral explants culturedex vivois challenging with the current analysis techniques. An approach that enables monitoring of bone remodeling dynamics is longitudinal micro-computed tomography (µCT), a non-destructive technique that relies on repeated µCT scanning and subsequent registration of consecutive scans. In this study, a two-compartment culture system suitable for osteochondral explants that allowed for µCT scanning duringex vivoculture was established. Explants were scanned repeatedly in a fixed orientation, which allowed assessment of bone remodeling due to adequate image registration. Using this method, bone formation was found to be restricted to the outer surfaces when cultured statically. To demonstrate that the culture system could capture differences in bone remodeling, explants were cultured statically and under dynamic compression as loading promotes osteogenesis. No quantitative differences between static and dynamic culture were revealed. Still, only in dynamic conditions, bone formation was visualized on trabecular surfaces located within the inner cores, suggesting enhanced bone formation towards the center of the explants upon mechanical loading. Taken together, theex vivoculture system in combination with longitudinal µCT scanning and subsequent registration of images demonstrated potential for evaluating bone remodeling within explants.
Quantifiable TCR repertoire changes in pre-diagnostic blood specimens among high-grade ovarian cancer patients
Authors: Yu Xuexin , Ye Jianfeng , Hathaway Cassandra A. , Tworoger Shelley , Lea Jayanthi , Li Bo 
Published: October 2023

AbstractHigh grade serous ovarian cancer (HGOC) is a major cause of death in women. Early detection of HGOC usually leads to a cure, yet it remains a clinical challenge with over 90% HGOCs diagnosed at advanced stages. This is mainly because conventional biomarkers are not sensitive to detect the microscopic yet metastatic early HGOC lesions. In this study, we sequenced the blood T cell receptor (TCR) repertoires of 466 ovarian cancer patients and controls, and systematically investigated the immune repertoire signatures in HGOCs. We observed quantifiable changes of selected TCRs in HGOCs that are reproducible in multiple independent cohorts. Importantly, these changes are stronger during stage I. Using pre-diagnostic patient blood samples from the Nurses’ Health Study, we confirmed that HGOC signals can be detected in the blood TCR repertoire up to 4 years proceeding conventional diagnosis. Our findings may provide the basis of an immune-based HGOC early detection criterion.Statement of significanceWe made an unprecedented discovery that a strong and quantifiable change in the blood TCR repertoire occurs 4 to 2 years before high grade ovarian cancers could be diagnosed with conventional clinical tests. This finding might be useful to develop novel screening biomarkers to detect early-stage ovarian cancers.
On metallic luster and iridescence in animal coloration
Authors: Nordén Klara K. , Steiner Raphael S. , Stephenson Anna B. , Stoddard Mary Caswell 
Published: October 2023

AbstractSome structural colors in nature are frequently described as metallic. For example, hummingbird plumage, jewel beetles andMorphobutterflies have this attribute. While much attention has been paid to describing the often-shifting hues of these structural colors, there has been little interest in explaining why they appear metallic. In this paper, we argue that the metallic luster (the metallic appearance or sheen) of some structural colors arises in part from a combination of two factors: a colored specular reflection and a very low diffuse reflection. Reflections with these characteristics are found in metals and are distinct from other material reflections in nature. We propose that metallic luster can be classified based on these two reflectance properties (colored specular reflection and low diffuse reflection). We also suggest that some of the ambiguity surrounding the term “iridescent structural color” can be traced to the frequent confounding of metallic luster with a common definition of iridescence: a shift of peak spectral wavelength (often referred to as hue) with viewing angle. We show using optical models and cross-polarization imaging of bird plumage that two types of structural colors that are often classified as “iridescent” and “non-iridescent” both display iridescence—but only one type has metallic luster. By considering metallic luster and iridescence separately, we simultaneously clarify terminology in structural colors and open up many new lines of inquiry regarding the perception of metallic luster in animals.
Dynamic trait distribution as a source for shifts in interaction strength and population density
Authors: Jackson Zachary , Xue BingKan 
Published: October 2023

AbstractIntraspecific trait variation has been increasingly recognized as an important factor in determining species interaction and diversity. Eco-evolutionary models have studied the distribution of trait values within a population that changes over the generations as a result of selection and heritability. Non-heritable traits that can change within the lifetime, such as behavior, can cause trait-mediated indirect effects, often studied by modeling the dynamics of a homogeneous trait. Complementary to these two approaches, we study the distribution of traits within a population and its dynamics on short timescales due to ecological processes. We consider several mechanisms by which the trait distribution can shift dynamically: phenotypic plasticity within each individual, differential growth among individuals, and preferential consumption by the predator. Through a simple predator-prey model that explicitly tracks the trait distribution within the prey, we illustrate some unusual consequences of trait shifts, including the healthy herd effect and the emergent promotion of the prey by the predator. We analyze the cause of these phenomena by identifying the density and trait effects from the predator. Our results show that intraspecific trait variation and the dynamics of its distribution can lead to the modification of species interactions and result in outcomes that are otherwise unexpected.
Genome-wide analysis of transcription-coupled repair reveals novel transcription events inCaenorhabditis elegans
Authors: Kose Cansu , Lindsey-Boltz Laura A. , Sancar Aziz , Jiang Yuchao 
Published: October 2023

ABSTRACTBulky DNA adducts such as those induced by ultraviolet light are removed from the genomes of multicellular organisms by nucleotide excision repair, which occurs through two distinct mechanisms, global repair, requiring the DNA damage recognition-factor XPC (xeroderma pigmentosum complementation group C), and transcription-coupled repair (TCR), which does not. TCR is initiated when elongating RNA polymerase II encounters DNA damage, and thus analysis of genome-wide excision repair in XPC-mutants only repairing by TCR provides a unique opportunity to map transcription events missed by methods dependent on capturing RNA transcription products and thus limited by their stability and/or modifications (5’-capping or 3’- polyadenylation). Here, we have performed the eXcision Repair-sequencing (XR-seq) in the model organismCaenorhabditis elegansto generate genome-wide repair maps from a wild-type strain with normal excision repair, a strain lacking TCR (csb-1), or one that only repairs by TCR (xpc- 1). Analysis of the intersections between thexpc-1XR-seq repair maps with RNA-mapping datasets (RNA-seq, long- and short-capped RNA-seq) reveal previously unrecognized sites of transcription and further enhance our understanding of the genome of this important model organism.
Assessing rapid adaptation through epigenetic inheritance: a new experimental approach
Authors: Chávez Alexandra , Huber Meret 
Published: October 2023

AbstractEpigenetic inheritance is hypothesized to mediate rapid adaptation to stresses via two fundamentally different routes: first, through spontaneous epimutations that arise in a largely stochastic manner in the presence or absence of stress; if these spontaneous epimutations are heritable and beneficial, they may be selected upon (“stochastic route”); and second, through environment-induced epialleles that arise uniformly among individuals; if heritable, these epialleles may lead to stress adaptation even in the absence of selection (“deterministic route”). Testing and teasing apart these two routes is challenging, largely because a suitable experimental approach is lacking.Here, we propose an experimental approach that allows to simultaneously assess the contribution of the stochastic and deterministic route. The essence of the approach is to manipulate the efficacy of selection through the population size and thereby to test whether selection is required for adaptation (stochastic route). To this end, genetically uniform populations are grown under different environments across multiple generations (“pre-treatment”) at two different population sizes: in large populations, in which selection is effective; and in small populations, in which drift overcomes the effect of selection. If the deterministic route contributes to adaptation, variation in fitness, phenotypes or epigenetic marks will arise between the small populations of the different pre-treatments. If the stochastic route contributes to adaptation, variation will arise between the small and large population within each pre-treatment. As a proof-of-principle, we tested whether small and large monoclonal populations of the aquatic duckweedSpirodela polyrhizamay adapt to copper excess outdoors.After five to seven generations of pre-treatment and a subsequent multi-generational growth under control conditions, large populations outperformed small populations under copper excess. Furthermore, small populations pre-treated with copper excess tended to have higher fitness under copper excess than small populations pre-treated under control conditions. These data suggest that both the stochastic and deterministic route may alter plant fitness under recurring stress.The proposed approach will allow to experimentally evaluate whether species may adapt to stresses through either stochastic and deterministic epigenetic changes, which is fundamental to understand whether and how epigenetic inheritance may lead to rapid stress adaptation.
Metabolic bypass rescues aberrant S-nitrosylation-induced TCA cycle inhibition and synapse loss in Alzheimer’s disease human neurons
Authors: Andreyev Alexander Y. , Yang Hongmei , Doulias Paschalis-Thomas , Dolatabadi Nima , Zhang Xu , Luevanos Melissa , Blanco Mayra , Baal Christine , Putra Ivan , Nakamura Tomohiro , Ischiropoulos Harry , Tannenbaum Steven R. , Lipton Stuart A. 
Published: October 2023

SUMMARYIn Alzheimer’s disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, is still lacking. Here, comparing isogenic wild-type and AD mutant human induced pluripotent stem cell (hiPSC)-derived cerebrocortical neurons (hiN), we found evidence for compromised mitochondrial energy in AD using the Seahorse platform to analyze glycolysis and oxidative phosphorylation (OXPHOS). Isotope-labeled metabolic flux experiments revealed a major block in activity in the tricarboxylic acid (TCA) cycle at the α-ketoglutarate dehydrogenase (αKGDH)/succinyl coenzyme-A synthetase step, metabolizing α-ketoglutarate to succinate. Associated with this block we found aberrant protein S-nitrosylation of αKGDH subunits that are known to inhibit enzyme function. This aberrant S-nitrosylation was documented not only in AD-hiN but also in postmortem human AD brains vs. controls, as assessed by two separate unbiased mass spectrometry platforms using bothSNOTRAP identification of S-nitrosothiols and chemoselective-enrichment of S-nitrosoproteins. Treatment with dimethyl succinate, a cell-permeable derivative of a TCA substrate (downstream to the block, resulted in partial rescue of mitochondrial bioenergetic function as well as reversal of synapse loss in AD-hiN. Our findings have therapeutic implications that rescue of mitochondrial energy metabolism can ameliorate synaptic loss in hiPSC-based models of AD.
Long chain monomethyl branched-chain fatty acid levels in human milk vary with gestational weight gain
Authors: O’Sullivan Aifric , Brady Emer , Lafferty Lucy , O’Shea Fiona , O’Regan Zoe , Meurs Noah , Baldini Michelle , Gengatharan Jivani , Metallo Christian M. , Wallace Martina 
Published: October 2023

AbstractBreastfeeding is an important determinant of infant health and there is immense interest in understanding its metabolite composition so that key beneficial components can be identified. The aim of this research was to measure the fatty acid composition of human milk in an Irish cohort where we examined changes depending on lactation stage and gestational weight gain trajectory. Utilising a chromatography approach optimal for isomer separation, we identified 44 individual fatty acid species via GCMS and showed that monomethyl branched-chain fatty acids(mmBCFA’s), C15:0 and C16:1 are lower in women with excess gestational weight gain versus low gestational weight gain. To further explore the potential contribution of the activity of endogenous metabolic pathways to levels of these fatty acids in milk, we administered D2O to C57BL/6J dams fed a purified lard based high fat diet (HFD) or low-fat diet during gestation and quantified the total andde novosynthesized levels of fatty acids in their milk. We found thatde novosynthesis over three days can account for between 10 and 50% of mmBCFAs in milk from dams on the low-fat diet dependent on the branched-chain fatty acid species. However, HFD fed mice had significantly decreasedde novosynthesized fatty acids in milk resulting in lower total mmBCFAs and medium chain fatty acid levels. Overall, our findings highlight the diverse fatty acid composition of human milk and that human milk mmBCFA levels differ between gestational weight gain phenotypes. In addition, our data indicates thatde novosynthesis contributes to mmBCFA levels in mice milk and thus may also be a contributory factor to mmBCFA levels in human milk. Given emerging data indicating mmBCFAs may be beneficial components of milk, this study contributes to our knowledge around the phenotypic factors that may impact their levels.
Computing the inducibility of B cell lineages under a context-dependent model of affinity maturation: Applications to sequential vaccine design
Authors: Mathews Joseph , Van Itallie Elizabeth , Wiehe Kevin , Schmidler Scott C. 
Published: October 2023

AbstractA key challenge in B cell lineage-based vaccine design is understanding theinducibilityof target neutralizing antibodies. We approach this problem through the use of detailed stochastic modeling of the somatic hypermutation process that occurs during affinity maturation. Under such a model, sequence mutation rates arecontext-dependent, rendering standard probability calculations for sequence evolution intractable. We develop an algorithmic approach to rapid, accurate approximation of key marginal sequence likelihoods required to inform modern sequential vaccine design strategies. These calculated probabilities are used to define an inducibility index for selecting among potential targets for immunogen design. We apply this approach to the problem of choosing targets for the design of boosting immunogens aimed at elicitation of the HIV broadly-neutralizing antibody DH270min11.Author summaryVaccine effectiveness relies on inducing the immune system to generate protective antibodies. Because antibodies are generated by random processes coupled to positive selection, the ability to induce certain rare but desirable antibodies can be limited by the inherent probability of occurrence. We use computational modeling to estimate the probability of antibody occurrence, and demonstrate the use of these estimates in designing vaccine regimens which maximize the probability of induction of broadly neutralizing antibodies.
Osteochondral fluid transport in an ex vivo system
Authors: Hislop Brady David , Mercer Ara K. , Whitley Alexandria G. , Myers Erik P. , Heveran Chelsea M. , June Ronald K. 
Published: October 2023

AbstractObjectiveAlterations to fluid transport from bone-to-cartilage may contribute to the development of osteoarthritis. However, many questions remain about fluid transport between these tissues. The objectives of this study were to (1) test for diffusion of 3kDa molecular tracers from bone-to-cartilage and (2) assess potential differences in bone-to-cartilage fluid transport between different loading conditions.DesignOsteochondral cores extracted from bovine femurs (N=8 femurs, 10 cores/femur) were subjected to either no-load (i.e., pure diffusion), pre-load only, or cyclic compression (5±2% or 10±2% strain) in a two-chamber transport system with the bone compartment filled with a 3kDa tracer. Tracer concentrations in the cartilage compartment were measured every 5 minutes for 120 minutes. Tracer concentrations were analyzed for differences in beginning, peak and equilibrium concentrations, loading effects, and time-to-peak tracer concentration.ResultsPeak tracer concentration in the cartilage compartment was significantly higher compared to beginning and equilibrium tracer concentrations indicating fluid transport from bone to cartilage. Cartilage-compartment tracer concentration was influenced by strain magnitude, but no time-to-peak relationship was found when comparing strain magnitudes.ConclusionThis study shows that osteochondral fluid transport occurs from bone-to-cartilage with 3kDa dextran molecules. These are much larger molecules to move between bone and cartilage than previously reported. Further these results demonstrate the potential for cyclic compression to impact osteochondral fluid transport. Determining the baseline osteochondral fluid transport in healthy tissues is crucial to elucidating the potential mechanisms of progression and onset of osteoarthritis.
Combined studies of N170/M170 responses to single letters and pseudoletters
Authors: Toussi Nima , Takai Osamu , Bann Sewon , Rowe Jacob , Hildebrand Andrew-John I. , Herdman Anthony 
Published: October 2023

ABSTRACTTo read efficiently, individuals must be able to rapidly identify letters within their visual networks, which occurs through forming line segments into letters and then letters into words. The temporal processes and utilized brain areas that engage in this process are widely thought to be left-lateralized within the brain. However, a range of studies demonstrate that the processing of unfamiliar stimuli, such as pseudoletters, is temporally delayed and bilaterally processed when compared to letters. The present study investigated the contributions of both hemispheres and how these interactions impact the temporal dynamics of implicit visual processing of single-letters as compared to unfamiliar pseudoletters (false fonts). The results of 5 “in-house” studies are presented within a meta-analysis (synthesis analysis), 3 High-density EEG studies and 2 MEG studies. Of the 3 EEG studies, 2 focused on measuring event related potentials (ERPs) while the participants performed an orthographic discrimination task (letters vs pseudoletters) and the other was a target detection task in which the participants detected infrequent, simple perceptual targets within a series of pseudoletter and letter strings. Of the 2 MEG studies, one was a discrimination task and the other a target detection task. Delayed N170 waveforms to pseudoletters as compared to letters were exhibited across all studies. Lateralization of the ERP differences between letter-evoked and pseudoletter-evoked responses were bilaterally distributed, whereas lateralization measure separately for letters and pseudoletters were primarily left-lateralized. As a whole, these in-house studies indicate that ERPs to letters occur earlier than to pseudoletters, and that interpretation of hemispheric laterality depends on whether the researcher is assessing ERP differences between letters and pseudoletters or the ERP waveforms of the separate letter and pseudoletter conditions.
Spatial organization of collective food distribution in a paper wasp society
Authors: Sharma Nitika , Gadagkar Raghavendra 
Published: October 2023

AbstractIn social insect colonies, food transferred through space and time via nestmates carries both nutrition and information. We study the mechanism of spatio-temporal coordination (or the lack thereof) between multiple wasps for them to optimally solve the problem of feeding randomly placed larvae in a social insect colony. We followed each morsel of food brought into semi-natural colonies of the tropical paper waspRopalidia marginata,in each of 36 feeding bouts until the food was exhausted. We found that most acts of feeding larvae are performed by wasps that unload food from foragers, but unloading itself is highly skewed among individuals. We also found that larvae closer to the nest center were fed more frequently than those at the periphery, irrespective of their developmental stage. This differential feeding may have fitness consequences as it is known that well-fed larvae become voracious feeders as adults and have a higher likelihood to become reproductives. Using the analogies of the travelling salesman problem and the Hamiltonian path problem, we showed that individuals which disburse food to more larvae within a feeding bout adopted paths that were considerably shorter than expected by chance while the distinction between adopted and random routes was not as pronounced when the number of larvae fed in a bout was fewer. There was no spatial segregation between wasps feeding larvae in parallel, possibly building redundancy and avoiding larval starvation across bouts. Understanding the spatial organization of food transfer may be a key to understanding how insect societies achieve efficient social organization and division of labor.SignificanceThe limited studies on within-nest spatial organization of food distribution have been performed on ants and not primitively eusocial insects like wasps that contain randomly placed yet trackable larvae within the colony. We address the gap in a holistic understanding of spatial organization of food distribution through our study in the social waspRopalidia marginata. Through the lens of task partitioning, colony-level larval landscape, and spatial strategies adopted at individual and collective scales, our study presents one of the most detailed account of behavioral and spatio-temporal data mapping sources and sinks of food in a colony chronologically. We found that feeding routes adopted by wasps while feeding randomly placed larvae within a colony may not be a result of random walk but instead the degrees of route optimization based on the food load available to distribute within each feeding bout. We suggest paper wasp colonies to be ideal model systems for spatial studies owing to their observable colony sizes and randomly placed brood. Understanding the mechanism of colony-level problem solving by individuals with limited local information has widespread real-life applications besides a better understanding of social organization in colonies of social insects.