bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turbulent adaptive landscape shaped size evolution in modern ocean giants
Authors: Burin Gustavo , Park Travis , James Tamora D. , Slater Graham J. , Cooper Natalie 
Published: September 2022

ABSTRACTAdaptive landscapes are central to evolutionary theory, forming a conceptual bridge between micro- and macro-evolution1–4. Evolution by natural selection across an adaptive landscape should drive lineages towards fitness peaks, shaping the distribution of phenotypic variation within and among clades over evolutionary timescales5. Constant shifts in selection pressures mean the peaks themselves also evolve through time4, thus a key challenge is to identify these ‘ghosts of selection past’. Here, we characterise the global and local adaptive landscape for total length in cetaceans (whales and dolphins) across their ~ 53 million year evolutionary history, using 345 living and fossil taxa. We analyse shifts in long-term mean size6and directional changes in average trait values7using cutting-edge phylogenetic comparative methods. We demonstrate that the global macroevolutionary adaptive landscape of cetacean body size is relatively flat, with very few peak shifts after cetaceans colonised the oceans. Local peaks represent trends along branches linked to specific adaptations such as deep diving. These results contrast with previous studies using only extant taxa8, highlighting the vital role of fossil data for understanding macroevolutionary dynamics. Our results indicate that adaptive peaks are constantly changing and are associated with subzones of local adaptations, resembling turbulent waters with waves and ripples, creating moving targets for species adaptation. In addition, we identify limits in our ability to detect some evolutionary patterns and processes, and suggest multiple approaches are required to characterise complex hierarchical patterns of adaptation in deep-time.
Are brain displacements and pressures within the parenchyma induced by surface pressure differences? A computational modelling study
Authors: Piersanti Eleonora , Rognes Marie E. , Vinje Vegard 
Published: September 2022

AbstractThe intracranial pressure is implicated in many homeostatic processes in the brain and is a fundamental parameter in several diseases such as e.g. idiopathic normal pressure hydrocephalus (iNPH). The presence of a small but persistent pulsatile intracranial pulsatile transmantle pressure gradient (on the order of a few mmHg/m at peak) has recently been demonstrated in iNPH subjects. A key question is whether pulsatile ICP and displacements can be induced by a small pressure gradient originating from the brain surface e.g. pial arteries alone. In this study, we model the brain parenchyma as either a linearly elastic or a poroelastic medium and impose a pulsatile pressure gradient acting between the ventricular and the pial surfaces. Using this high-resolution physics-based model, we compute the effect of the pulsatile pressure gradient on parenchyma displacement, volume change, fluid pressure, and fluid flux. The resulting displacement field is pulsatile and in qualitatively and quantitatively good agreement with the literature, both with elastic and poroelastic models. However, the pulsatile forces on the boundaries are not sufficient for pressure pulse propagation through the brain parenchyma. Our results suggest that pressure differences originating over the brain surface via e.g. pial artery pulsatility are not sufficient to drive interstitial fluid (ISF) flow within the brain parenchyma and that potential pressure gradients found within the parenchyma rather arise from local pressure pulsations of blood vessels within the brain parenchyma itself.
Preclinical shortwave infrared tumor screening and resection via pHLIP ICG under ambient lighting conditions
Authors: Mc Larney Benedict Edward , Kim Mijin , Roberts Sheryl , Skubal Magdalena , Hsu Hsiao-Ting , Ogirala Anuja , Pillarsetty NagaVaraKishore , Heller Daniel , Lewis Jason S. , Grimm Jan 
Published: September 2022

AbstractThere is a critical need to improve optical imaging that will lead to its widespread acceptance for routine clinical procedures. Shortwave infrared (SWIR, 900–1700nm) imaging has demonstrated clear advantages over visible and near-infrared imaging (reduced autofluorescence with improved contrast, resolution, and sensitivity at tissue depth). Here we show that the previously reported compound, pH low insertion peptide (pHLIP) conjugated to indocyanine green (ICG, pHLIP ICG) currently in clinical trials, serves as an excellent candidate for SWIR imaging protocols. SWIR’s increased sensitivity enabled preclinical tumor screening and resection at exposure times as low as 0.1 ms with acceptable signal-to-noise and contrast-to-noise ratios. Imaging was performed under ambient lighting conditions, and SWIRs sensitivity enabled an extended surgical resection window up to 96 hrs post injection in an orthotopic breast cancer mouse model. This work provides a direct precedent for the clinical translation of SWIR pHLIP ICG imaging for cancer resection.One Sentence SummarySWIR imaging under ambient lighting is highly sensitive to pHLIP ICG, a cancer targeting fluorescent agent currently under clinical investigation.
Single-cell transcriptomics of resected human traumatic brain injury tissues reveals acute activation of endogenous retroviruses in oligodendroglia
Authors: Garza Raquel , Sharma Yogita , Atacho Diahann , Thiruvalluvan Arun , Hamdeh Sami Abu , Jönsson Marie , Horvath Vivien , Adami Anita , Ingelsson Martin , Jern Patric , Hammell Molly Gale , Englund Elisabet , Kirkeby Agnete , Jakobsson Johan , Marklund Niklas 
Published: September 2022

AbstractTraumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used snRNA-seq to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linkedin vitrousing human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides a unique insight into the initiating events of the neuroinflammatory response in TBI, which has new therapeutic implications.
Distinguishing between histories of speciation and introgression using genomic data
Authors: Hibbins Mark S. , Hahn Matthew W. 
Published: September 2022

AbstractIntrogression creates complex, non-bifurcating relationships among species. At individual loci and across the genome, both introgression and incomplete lineage sorting interact to produce a wide range of different gene tree topologies. These processes can obscure the history of speciation among lineages, and, as a result, identifying the history of speciation vs. introgression remains a challenge. Here, we use theory and simulation to investigate how introgression can mislead multiple approaches to species tree inference. We find that arbitrarily low amounts of introgression can mislead both gene tree methods and parsimony methods if the rate of incomplete lineage sorting is sufficiently high. We also show that an alternative approach based on minimum gene tree node heights is inconsistent and depends on the rate of introgression across the genome. To distinguish between speciation and introgression, we apply supervised machine learning models to a set of features that can easily be obtained from phylogenomic datasets. We find that multiple of these models are highly accurate in classifying the species history in simulated datasets. We also show that, if the histories of speciation and introgression can be identified, PhyloNet will return highly accurate estimates of the contribution of each history to the data (i.e. edge weights). Overall, our results highlight the promise of supervised machine learning as a potentially powerful complement to phylogenetic methods in the analysis of introgression from genomic data.
Evolutionary rates in human amyloid proteins reveal their intrinsic metastability
Authors: Zea Diego Javier , Mac Donagh Juan , Benitez Guillermo , Donadio Cristian Guisande , Marchetti Julia , Palopoli Nicolas , Fornasari María Silvina , Parisi Gustavo 
Published: September 2022

AbstractThe emerging picture of protein nature reveals its intrinsic metastability. According to this idea, although a protein is kinetically trapped in a local free energy minimum that defines its native state, those kinetic barriers can be overcome by a complex mixture of the protein’s intrinsic properties and environmental conditions, promoting access to more stable states such as the amyloid fibril. Proteins that are strongly driven towards aggregation in the form of these fibrils are called amyloidogenic. In this work we study the evolutionary rates of 81 human proteins for which an in vivo amyloid state is supported by experiment-based evidence. We found that these proteins evolve faster when compared with a large dataset of ∼16,000 reference proteins from the human proteome. However, their evolutionary rates were indistinguishable from those of secreted proteins that are already known to evolve fast. After analyzing different parameters that correlate with evolutionary rates, we found that the evolutionary rates of amyloidogenic proteins could be modulated by factors associated with metastable transitions such as supersaturation and conformational diversity. Our results showcase the importance of protein metastability in evolutionary studies.
The functional impact of rare variation across the regulatory cascade
Authors: Li Taibo , Ferraro Nicole , Strober Benjamin J. , Aguet Francois , Kasela Silva , Arvanitis Marios , Ni Bohan , van de Wiel Laurens , Hershberg Elliot , Ardlie Kristin , Arking Dan E. , Beer Rebecca L. , Brody Jennifer , Blackwell Thomas W , Clish Clary , Gabriel Stacey , Gerszten Robert , Guo Xiuqing , Gupta Namrata , Johnson W. Craig , Lappalainen Tuuli , Lin Henry J. , Liu Yongmei , Nickerson Deborah A. , Papanicolaou George , Pritchard Jonathan K. , Qasba Pankaj , Shojaie Ali , Smith Josh , Sotoodehnia Nona , Taylor Kent D. , Tracy Russell P. , Van Den Berg David , Wheeler Matthew , Rich Stephen S. , Rotter Jerome I. , Battle Alexis , Montgomery Stephen B. 
Published: September 2022

AbstractEach human genome has tens of thousands of rare genetic variants; however, identifying impactful rare variants remains a major challenge. We demonstrate how use of personal multi-omics can enable identification of impactful rare variants by using the Multi-Ethnic Study of Atherosclerosis (MESA) which included several hundred individuals with whole genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, ten years apart. We evaluated each multi-omic phenotype’s ability to separately and jointly inform functional rare variation. By combining expression and protein data, we observed rare stop variants 62x and rare frameshift variants 216x as frequently as controls, compared to 13x to 27x for expression or protein effects alone. We developed a Bayesian hierarchical model to prioritize specific rare variants underlying multi-omic signals across the regulatory cascade. With this approach, we identified rare variants that exhibited large effect sizes on multiple complex traits including height, schizophrenia, and Alzheimer’s disease.
Structure and Function of Gli123 Involved in Mycoplasma mobile Gliding
Authors: Matsuike Daiki , Tahara Yuhei O , Nonaka Takahiro , Wu Heng Ning , Hamaguchi Tasuku , Kudo Hisashi , Hayashi Yuuki , Arai Munehito , Miyata Makoto 
Published: September 2022

ABSTRACTMycoplasma mobile is a fish pathogen that glides on solid surfaces by means of a unique mechanism. The gliding machinery of M. mobile is composed of internal and surface structures. In the present study, we focused on the function and structure of Gli123, a surface protein that is essential for the localization of other surface proteins. The amino acid sequence of Gli123, which is 1128 amino acids long, contains lipoprotein-specific repeats. We isolated the native Gli123 protein from M. mobile cells and a recombinant protein, rGli123, from Escherichia coli. The isolated rGli123 complemented a non-binding and non-gliding mutant of M. mobile that lacked Gli123. Circular dichroism and rotary-shadowing electron microscopy (EM) showed that rGli123 has a structure that is not significantly different from that of the native protein. Rotary-shadowing EM suggested that the molecules changed their shape between globular and rod-like structures, depending on the ionic strength of the solution. Negative-staining EM coupled with single-particle analysis revealed that Gli123 forms a globular structure featuring a small protrusion with dimensions of 20.0, 14.5, and 16.0 nm. Small-angle X-ray scattering analyses indicated a rod-like structure composed of several tandem globular domains with total dimensions of approximately 34 nm length and 4 nm width. Both molecular structures were suggested to be dimers based on the predicted molecular size and structure. Gli123 may have evolved by multiplication of repeating lipoprotein units and acquired clumping role of surface proteins.IMPORTANCEMycoplasmas are pathogenic bacteria that are widespread in animals. They are characterized by small cell and genome sizes but are equipped with unique abilities to escape host immunity, such as surface variation and gliding. Here, we focused on a surface-localizing protein that is essential for Mycoplasma mobile gliding. The findings of this study suggested that the protein undergoes drastic conformational changes between its rod-like and globular structures. These changes may be caused by a repetitive structure common in the surface proteins that is responsible for the modulation of the cell surface structure and related to the assembly process for the surface gliding machinery. An evolutionary process for this unique mycoplasma gliding mechanism has also been suggested in the present study.
More than 90% of nacre matrix proteins are composed of silk-like proteins
Authors: Liu Xiaojun , Yin Zehui , Ma Zhuojun , Liang Jian , Yao Liping , Zhang Rongqing 
Published: September 2022

AbstractA proteome is a powerful tool to study nacre biomineralization that occurs in an ordered microenvironment composed mainly of proteins and polysaccharides. As more and more proteins are detected, new questions arise about which proteins are responsible for forming this microenvironment. In this study, shell matrix proteins (SMPs) of nacre were analyzed using label-free quantitative proteome. A total of 99.89% of the insoluble nacre SMPs were composed of silk-like proteins, chitin-binding proteins, and cysteine-rich SMPs, which were responsible for organic framework assembly. A total of 99.34% of the soluble nacre SMPs were composed of silk-like proteins and chitin-binding proteins, which were responsible for forming protein gel filling in organic frameworks. The content of silk-like proteins was more than 90% in both insoluble and soluble nacre SMPs. As organic frameworks and protein gel together constructed a microenvironment for calcium carbonate biomineralization, these results provided a novel understanding of nacre formation.
Effect of cognitive reserve on physiological measures of cognitive workload in older adults with cognitive impairments
Authors: Devos Hannes , Gustafson Kathleen , Liao Ke , Ahmadnezhad Pedram , Kuhlmann Emily , Estes Bradley , Martin Laura E. , Mahnken Jonathan D. , Brooks William M. , Burns Jeffrey M. 
Published: September 2022

AbstractBackgroundCognitive reserve may protect against cognitive decline. However, its effect on physiological measures of cognitive workload in adults with cognitive impairments is unclear.ObjectiveThe aim was to determine the association between cognitive reserve and physiological measures of cognitive workload in older adults with and without cognitive impairments.Methods29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MOCA scores 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MOCA 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve.ResultsHigher CRIq total scores were associated with larger P3 ERP amplitude (p=0.048), independent of cognitive status (p=0.80), task demand (p=0.003), and electrode site (p<0.0001). This relationship was mainly driven by Work Activity (p=0.0005). Higher CRIq total scores also correlated with higher mean ICA (p = 0.002), regardless of cognitive status (p=0.29) and task demand (p=0.12). Both Work Activity (p=0.0002) and Leisure Time (p=0.045) impacted ICA. No relationship was found between CRIq and P3 latency.ConclusionCognitive reserve affects cognitive workload and neural efficiency, regardless of cognitive status. Future longitudinal studies should investigate the causal relationship between cognitive reserve and physiological processes of neural efficiency across cognitive aging.
Distinct selection signatures during domestication and improvement in crops: a tale of two genes in mungbean
Authors: Lin Ya-Ping , Chen Hung-Wei , Yeh Pei-Min , Anand Shashi S. , Lin Jiunn , Li Juan , Noble Thomas , Nair Ramakrishnan , Schafleitner Roland , Samsonova Maria , Bishop-von-Wettberg Eric , Nuzhdin Sergey , Ting Chau-Ti , Lawn Robert J. , Lee Cheng-Ruei 
Published: September 2022

AbstractDomestication and improvement are two crucial processes underlying the evolution of crops. Domestication transformed wild plants into a utilizable form for humans; improvement refined cultivars adapting to distinct environments and local preferences. Using whole-genome re-sequencing of Vigna radiata, we investigated the demographic history and compared the genetic footprints of domestication and improvement. The Asian wild population migrated to Australia at about 50 kya, and domestication happened in Asia about 9 kya selecting for non-shattering pods. The key candidate gene for this trait, VrMYB26a, has lower expression in cultivars, consistent with the reduced polymorphism in the promoter region reflecting hard selective sweep. The determinate stems were later selected as an improvement phenotype and associated with the gene VrDet1. Two ancient haplotypes reducing gene expression exhibit intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in soft selective sweep. Our results suggest domestication and improvement may leave different genomic signatures of selection, reflecting the fundamental differences in the two processes and highlighting the limitations of genome-scan methods relying on hard selective sweep.
When Abstract Becomes Concrete: Naturalistic Encoding of Concepts in the Brain
Authors: Kewenig Viktor , Vigliocco Gabriella , Skipper Jeremy I 
Published: September 2022

AbstractLanguage is acquired and processed in complex and dynamic naturalistic contexts, involving simultaneous processing of connected speech, faces, bodies, objects, etc.. How words and their associated concepts are encoded in the brain during real-world processing is still unknown. Here, the representational structure of concrete and abstract concepts was investigated during movie watching to address the extent to which brain responses dynamically change depending on visual context. First, across contexts, concrete and abstract concepts are shown to encode different experience-based information in separable sets of brain regions. However, these differences are reduced when multimodal context is considered. Specifically, the response profile of abstract words becomes more concrete-like when these are processed in visual scenes highly related to their meaning. Conversely, when the visual context is unrelated to a given concrete word, the activation pattern resembles more that of abstract conceptual processing. These results suggest that while concepts generally encode habitual experiences, the underlying neurobiological organisation is not fixed but depends dynamically on available contextual information.
A widespread family of phage-inducible chromosomal islands only steals bacteriophage tails to spread in nature
Authors: Alqurainy Nasser , Miguel-Romero Laura , Moura de Sousa Jorge , Chen John , Rocha Eduardo P.C. , Fillol-Salom Alfred , Penadés José R 
Published: September 2022

AbstractPhage satellites interfere with helper phage packaging through the production of small-capsids, where only satellites can be packaged. So far, in all the analysed systems, the satellite-sized capsids are composed of phage proteins. Here we report the first demonstration that a family of phage-inducible chromosomal island (PICIs), a type of satellites, encodes all the proteins required for both the production of the small-sized capsids and the exclusive packaging of the PICIs into these capsids. Therefore, this new family, that we have named cf-PICIs (capsid forming PICIs), only requires phage tails to generate infective PICI particles. Remarkably, the representative cf-PICI reproduces without cost for their helper phages, suggesting that the relationship between these elements is not parasitic but commensalistic. Finally, our phylogenomic studies indicate that cf-PICIs are present both in Gram-positive and Gram-negative bacteria and have evolved at least three times independently to spread widely into the satellite universe.
A link between genotype and cellular architecture in microbiome members as revealed by cryo-EM
Authors: Wimmer Benedikt H , Moraïs Sarah , Zalk Ran , Mizrahi Itzhak , Medalia Ohad 
Published: September 2022

AbstractMicrobial taxonomy is not yet sufficient to describe microbe functionality and ecology. Since function is often linked to structure, we sought here to use cryo-electron microscopy and tomography to analyze microbial cellular architecture and correlate it to specific phylogenies and genomes. We cultured and imaged a large collection of microbiota covering 90% of the richness of the core rumen microbiome at the family level, which we selected as a model for our analyses. Based on measurements of several parameters, we found that the structural similarity of microbiota is significantly related to their taxonomic distance, i.e., closely related microbes have similar cellular architectures. However, above the Family level, these similarities end: the structural diversity stops increasing with phylogenetic distance. Our results highlight that cellular architectures could serve as an important parameter in microbial ecology and microbial ecosystems.