bluuebunny/crossref_metadata_2025_split huggingface dataset:
Huntingtin CAG expansion impairs germ layer patterning in synthetic human gastruloids through polarity defects
Authors: Galgoczi Szilvia , Ruzo Albert , Markopoulos Christian , Yoney Anna , Phan-Everson Tien , Haremaki Tomomi , Metzger Jakob J. , Etoc Fred , Brivanlou Ali H. 
Published: February 2021

AbstractHuntington’s disease (HD) is a fatal neurodegenerative disorder caused by an expansion of the CAG repeats in the Huntingtin gene (HTT). While HD has been shown to have a developmental component, how early during human embryogenesis the HTT-CAG expansion can cause embryonic defects remains unknown. Here, we demonstrate a specific and highly reproducible CAG length-dependent phenotypic signature in a synthetic model for human gastrulation derived from human embryonic stem cells (hESCs). Specifically, we observed a reduction in the extension of the ectodermal compartment that is associated with enhanced ACTIVIN signaling. Surprisingly, rather than a cell-autonomous effect, tracking the dynamics of TGFβ signaling demonstrated that HTT-CAG expansion perturbs the spatial restriction of ACTIVIN response. This is due to defects in the apicobasal polarization in the context of the polarized epithelium of the gastruloid, leading to ectopic subcellular localization of TGFβ receptors. This work refines the earliest developmental window for the prodromal phase of HD to the first two weeks of human development as modeled by our gastruloids.
Derived loss of signal complexity and plasticity in a genus of weakly electric fish
Authors: Saenz David E. , Gu Tingting , Ban Yue , Winemiller Kirk O. , Markham Michael R. 
Published: February 2021

AbstractSignal plasticity can maximize the usefulness of costly animal signals such as the electric organ discharges (EODs) of weakly electric fishes. Some species of the order Gymnotiformes rapidly alter their EOD amplitude and duration in response to circadian cues and social stimuli. How this plasticity is maintained across related species with different degrees of signal complexity is poorly understood. In one genus of weakly electric gymnotiform fish (Brachyhypopomus) only one species,B. bennetti, produces a monophasic signal while all other species emit complex biphasic or multiphasic EOD waveforms produced by two overlapping but asynchronous action potentials in each electric organ cell (electrocyte). One consequence of this signal complexity is the suppression of low-frequency signal content that is detectable by electroreceptive predators. In complex EODs, reduction of the EOD amplitude and duration during daytime inactivity can decrease both predation risk and the metabolic cost of EOD generation. We compared EOD plasticity and its underlying physiology inBrachyhypopomusfocusing onB. bennetti. We found thatB. bennettiexhibits minimal EOD plasticity, but that its electrocytes retained vestigial mechanisms of biphasic signaling and vestigial mechanisms for modulating the EOD amplitude. These results suggest that this species represents a transitional phenotypic state within a clade where signal complexity and plasticity were initially gained and then lost. We discuss potential the roles of signal mimicry, species recognition, and sexual selection in maintaining the monophasic EOD phenotype in the face of detection by electroreceptive predators.
Repurposing of Synaptonemal Complex Proteins for Kinetochores in Kinetoplastida
Authors: Tromer Eelco C. , Wemyss Thomas A. , Waller Ross F. , Akiyoshi Bungo 
Published: February 2021

AbstractChromosome segregation in eukaryotes is driven by a macromolecular protein complex called the kinetochore that connects centromeric DNA to microtubules of the spindle apparatus. Kinetochores in well-studied model eukaryotes consist of a core set of proteins that are broadly conserved among distant eukaryotic phyla. In contrast, unicellular flagellates of the class Kinetoplastida have a unique set of kinetochore components. The evolutionary origin and history of these kinetochores remains unknown. Here, we report evidence of homology between three kinetoplastid kinetochore proteins KKT16–18 and axial element components of the synaptonemal complex, such as the SYCP2:SYCP3 multimers found in vertebrates. The synaptonemal complex is a zipper-like structure that assembles between homologous chromosomes during meiosis to promote recombination. Using a sensitive homology detection protocol, we identify divergent orthologues of SYCP2:SYCP3 in most eukaryotic supergroups including other experimentally established axial element components, such as Red1 and Rec10 in budding and fission yeast, and the ASY3:ASY4 multimers in land plants. These searches also identify KKT16–18 as part of this rapidly evolving protein family. The widespread presence of the SYCP2-3gene family in extant eukaryotes suggests that the synaptonemal complex was likely present in the last eukaryotic common ancestor. We found at least twelve independent duplications of the SYCP2-3gene family throughout the eukaryotic tree of life, providing opportunities for new functional complexes to arise, including KKT16–18 inTrypanosoma brucei. We propose that kinetoplastids evolved their unique kinetochore system by repurposing meiotic components of the chromosome synapsis and homologous recombination machinery that were already present in early eukaryotes.
Systems-wide analysis of the GATC-binding nucleoid-associated protein Gbn and its impact onStreptomycesdevelopment
Authors: Du Chao , Willemse Joost , Erkelens Amanda M. , Carrion Victor J. , Dame Remus T. , van Wezel Gilles P. 
Published: February 2021

ABSTRACTBacterial chromosome structure is organized by a diverse group of proteins collectively referred to as nucleoid-associated proteins (NAPs). Many NAPs have been well studied in Streptomyces, including Lsr2, HupA, HupS, and sIHF. Here, we show that SCO1839 represents a novel family of Actinobacteria NAPs and recognizes a consensus sequence consisting of GATC followed by (A/T)T. The protein was designated Gbn forGATC-bindingNAP. Deletion ofgbnled to alterations in development and antibiotic production inStreptomyces coelicolor. Chromatin immunoprecipitation sequencing (ChIP-Seq) detected more than 2800 binding regions, encompassing some 3600 GATCWT motifs, which comprise 55% of all such motifs in theS. coelicolorgenome. DNA binding of Gbn in vitro increased DNA stiffness but not compaction, suggesting a role in regulation rather than chromosome organization. Transcriptomics analysis showed that Gbn binding generally leads to reduced gene expression. The DNA binding profiles were nearly identical between vegetative and aerial growth. Exceptions are SCO1311 and SCOt32, for a tRNA editing enzyme and a tRNA that recognises the rare leucine codon CUA, respectively, which nearly exclusively bound during vegetative growth. Taken together, our data show that Gbn is a highly pleiotropic NAP that impacts growth and development in streptomycetes.IMPORTANCEA large part of the chemical space of bioactive natural products is derived from Actinobacteria. Many of the biosynthetic gene clusters for these compounds are cryptic, in others words, they are expressed in nature but not in the laboratory. Understanding the global regulatory networks that control gene expression is key to the development of approaches to activate this biosynthetic potential. Chromosome structure has a major impact on the control of gene expression. In bacteria, the organization of chromosome structure is mediated by a diverse group of proteins referred to collectively as nucleoid-associated proteins (NAPs), which play an important role in the control of gene expression, nucleoid structure and DNA repair. We here present the discovery of a novel and extremely pleiotropic NAP, which we refer to as Gbn. Gbn is a sporulation-specific protein that occurs only in the Actinobacteria and binds to GATC sequences, with a subtle but broad effect on global gene expression. The discovery of Gbn is a new step towards better understanding of how gene expression and chromosome structure is governed in antibiotic-producing streptomycetes.
Trophic resources of the edaphic microarthropods: a worldwide review of the empirical evidence
Authors: Velazco Víctor Nicolás , Saravia Leonardo Ariel , Coviella Carlos Eduardo , Falco Liliana Beatriz 
Published: February 2021

AbstractEcosystem sustainable use requires reliable information about its biotic and abiotic structure and functioning. Accurate knowledge of trophic relations is central for the understanding of ecosystem dynamics, which in turn, is essential for food web stability analyzes and the development of sustainable practices. There is a rapid growth in the knowledge on how belowground biodiversity regulates the structure and functioning of terrestrial ecosystems. Although, the available information about trophic relationships is hard to find and fragmented. This gathering the information available worldwide about the food resources of soil mesofauna. From the 3105 hits of the initial search on food resources of soil microarthropods, only a total of 196 published works related particular species, genera, and families to particular trophic resources, the majority of them dealing with soils of the Palearctic region. From the 196 publications we extracted 3009 records relating specific taxonomic groups to their trophic resources, 20% mention saprophytic fungi as a food resource, 16% cite microfauna, 11% mention bacteria, 10% litter and 5% cite Mycorrhizal fungi. The available information was highly skewed, the 73.71% comes from Acari, and within these, 50.62% correspond just to Sarcoptiformes. For Collembola, the literature is scarce, the majority coming from Arthropleona. This review highlights the general lack of information relating species, genera, and families of the soil mesofauna to specific trophic resources. It also highlights that available research mostly comes from European sites, with the use of trophic resources by the mesofauna of the majority of the soils in other parts of the world still largely unknown.
An MILP Model for Corn Planting and Harvest Scheduling Considering Storage Capacity and Growing Degree Units
Authors: Khalilzadeh Zahra , Wang Lizhi 
Published: February 2021

AbstractCorn planting and harvest scheduling is an important problem due to having a significant impact on corn yield, balancing the capacities for harvest, transport, and storage operations. Different corn hybrids also have different planting window and poor planting and harvest schedules may cause erratic weekly harvest quantities and logistical and productivity issues. In the 2021 Syngenta Crop Challenge, Syngenta released several large datasets that recorded the historical daily growing degree units (GDU) of two sites and provided planting window, required GDUs, and harvest quantity of corn hybrids planted in these two sites. Then, participants of this challenge were asked to schedule planting and harvesting dates of corn hybrids under two storage capacity scenarios so that facilities are not over capacity in harvesting weeks and have consistent weekly harvest quantities. The two storage capacity scenarios include: (1) planting and harvest scheduling given the maximum storage capacity, and (2) planting and harvest scheduling without maximum storage capacity to determine the lowest possible capacity for each site. In this paper, we propose two mixed integer linear programming (MILP) models for solving this problem considering both the storage capacity and the uncertainty in GDUs. Our results indicate that our proposed models can provide optimal planting and harvest scheduling under different GDU possibilities which ensures consistent weekly harvest quantities that are below the maximum capacity.
Cold adapted desiccation-tolerant bacteria isolated from polar soils presenting high resistance to anhydrobiosis
Authors: Nóbrega Felipe , Duarte Rubens T. D. , Torres-Ballesteros Adriana M. , Queiroz Luciano Lopes , Whyte Lyle G. , Pellizari Vivian H. 
Published: February 2021

AbstractLife on Earth is strictly dependent on liquid water. In polar terrestrial environments, water exists in solid state during almost the entire year. Polar microorganisms have not only to adjust their metabolism to survive at subzero temperatures, but also need to cope with extremely dry conditions. We investigated the presence of desiccation-adapted bacteria in Arctic permafrost and Antarctic surface soils and characterized their survivability to dryness. We selected desiccation tolerant cells by treating the soils with chloroform prior to cultivation, in order to mimic the stress of low water activity for long periods. From over 1000 colonies from different samples, 23 unique strains were selected and identified as members of phylaFirmicutes, ProteobacteriaandActinobacteria. About 60% of the strains survived after 50 days in anhydrobiosis. The competence to withstand desiccation varied between close related strains isolated from different locations, bringing the question if environmental conditions may play a role in the observed desiccation tolerance. Survivability was also affected by the solution in which the cells were suspended before drying; R2B medium being more protective than water. This is the first time that chloroform was used to select desiccation tolerant microorganisms from polar soils. The collection of polar microorganisms described herein opens the possibility of further experiments aiming to investigate the resistance mechanisms of polar anhydrobionts. Desiccation tolerance is fundamental to the survivability of microorganisms to the space environment and at the surface of thin-atmosphere planets like Mars. Therefore, the selected strains may open a road to better understand the limits of cold adapted life on Earth and beyond, and compare mechanisms of resistance with anhydrobionts from divergent extreme environments.
Human immunoglobulin from transchromosomic bovines hyperimmunized with SARS-CoV-2 spike antigen efficiently neutralizes viral variants
Authors: Liu Zhuoming , Wu Hua , Egland Kristi A. , Gilliland Theron C. , Dunn Matthew D. , Luke Thomas C. , Sullivan Eddie J. , Klimstra William B. , Bausch Christoph L. , Whelan Sean P. J. 
Published: February 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with amino-acid substitutions and deletions in spike protein (S) can reduce the effectiveness of monoclonal antibodies (mAbs) and may compromise immunity induced by vaccines. We report a polyclonal, fully human, anti-SARS-CoV-2 immunoglobulin produced in transchromosomic bovines (Tc-hIgG-SARS-CoV-2) hyperimmunized with two doses of plasmid DNA encoding the SARS-CoV-2 Wuhan strain S gene, followed by repeated immunization with S protein purified from insect cells. The resulting Tc-hIgG-SARS-CoV-2, termed SAB-185, efficiently neutralizes SARS-CoV-2, and vesicular stomatitis virus (VSV) SARS-CoV-2 chimerasin vitro. Neutralization potency was retained for S variants including S477N, E484K, and N501Y, substitutions present in recent variants of concern. In contrast to the ease of selection of escape variants with mAbs and convalescent human plasma, we were unable to isolate VSV-SARS-CoV-2 mutants resistant to Tc-hIgG-SARS-CoV-2 neutralization. This fully human immunoglobulin that potently inhibits SARS-CoV-2 infection may provide an effective therapeutic to combat COVID-19.
The Human walking kinematic model combined with upper and lower limb movement
Authors: Chen Xin , Hong Bin , Lin Zhangxi , Hou Jing , Lv ShunYa , Gao Zhendong 
Published: February 2021

AbstractThe purpose of this study is to build a relatively complete human walking kinematic model. This model is combined with the rolling-foot model (lower limb) and multi-rod swinging model (upper limb) connected by COM. We calculated the velocity of COM and other critical joints of the upper limb by marker point capture experiment using the high-speed camera. This research shows that the hand joint velocity measured through the experiment can achieve high coincidence with that calculated by the theoretical model given specific inputs. Moreover, the common pattern of upper limb angles is also studied for an accurate description. The proposed kinematic model is expected to forecast desired motion intention for better compliance by the rehabilitation and assistive robots.
The impact of mobility network properties on predicted epidemic dynamics in Dhaka and Bangkok
Authors: Brown Tyler S. , Engø-Monsen Kenth , Kiang Mathew V. , Mahmud Ayesha S. , Maude Richard J. , Buckee Caroline O. 
Published: February 2021

1AbstractProperties of city-level commuting networks are expected to influence epidemic potential of cities and modify the speed and spatial trajectory of epidemics when they occur. In this study, we use aggregated mobile phone user data to reconstruct commuter mobility networks for Bangkok (Thailand) and Dhaka (Bangladesh), two megacities in Asia with populations of 16 and 21 million people, respectively. We model the dynamics of directly-transmitted infections (such as SARS-CoV2) propagating on these commuting networks, and find that differences in network structure between the two cities drive divergent predicted epidemic trajectories: the commuting network in Bangkok is composed of geographically-contiguous modular communities and epidemic dispersal is correlated with geographic distance between locations, whereas the network in Dhaka has less distinct geographic structure and epidemic dispersal is less constrained by geographic distance. We also find that the predicted dynamics of epidemics vary depending on the local topology of the network around the origin of the outbreak. Measuring commuter mobility, and understanding how commuting networks shape epidemic dynamics at the city level, can support surveillance and preparedness efforts in large cities at risk for emerging or imported epidemics.
Fingerprinting and behavioural prediction rest on distinct functional systems of the human connectome
Authors: Mantwill Maron , Gell Martin , Krohn Stephan , Finke Carsten 
Published: February 2021

ABSTRACTThe prediction of inter-individual behavioural differences from neuroimaging data is a rapidly evolving field of research, focusing on individualised methods to describe human brain organisation on the single-subject level. One method that harnesses such individual signatures is functional connectome fingerprinting, which can reliably identify individuals from large study populations. While connectome fingerprints have been previously associated with individual cognitive function, these associations rest on indirect evidence.Contrasting with these previous reports, here we systematically investigate the link between connectome fingerprints and the prediction of behaviour on different levels of brain network organisation (individual edges, network interactions, topographical organisation, and edge variability), using 339 resting-state fMRI datasets from the Human Connectome Project.Our analysis revealed a significant divergence between connectivity signatures that discriminate between individuals and those predictive of behaviour on all levels of network organisation. Across different parcellation schemes, thresholds and prediction algorithms, we consistently find fingerprints in higher-order multimodal association cortices, while neural correlates of behaviour display a more variable topological distribution. Furthermore, we find the standard deviation of connections between subjects to be significantly higher in fingerprinting than in prediction, making inter-individual connection variability a possible separating marker.These results demonstrate that participant identification and behavioural prediction involve highly distinct functional systems of the human connectome, suggesting that connectome fingerprints are not as functionally relevant as previously believed. The present study thus calls for a re-evaluation of the significance of functional connectivity fingerprints in personalized medicine.
A non-structural pure enzyme protein forms a LCST type of stimuli-responsive and reversible hydrogel with novel structure and catalytic activity
Authors: Nie J. , Zhang X. , Liu Y. , Schroer M.A. , Wang W. , Ren J. , Svergun D.I. , Zeng A.-P. 
Published: February 2021

AbstractHydrogels have a wide range of applications such as in biomedicine, cosmetics and soft electronics. Compared to polymer hydrogels based on covalent bonding, protein hydrogels offer distinct advantages owing to their biocompatibility and better access to molecular engineering. However, pure and natural protein hydrogels have been seldom reported except for structural proteins like collagen and silk fibrin. Here, we report the unusual ability and mechanism of a unique natural enzyme, lipoate-protein ligase A (LplA) ofE. colito self-assemble into a stimuli-responsive and reversible hydrogel of the low critical solution temperature (LCST) type. This is the first globular and catalytic protein found to form a hydrogel in response to temperature, pH and the presence of ions. Protein structure based analysis reveals the key residues responsible for the gel formation and mutational studies confirms the essential roles of hydrogen bonding between the C-terminal domains and electrostatic interactions in the N-terminal domains. Characterization of phase transitions of wild type LplA and its mutants using small angle X-ray scattering (SAXS) yields details of the gelation process from initial dimer formation over a pre-gel-state to full network development. Further electron microscopic analyses and modeling of SAXS data suggest an unusual interlinked ladder-like structure of the macroscopic crosslinking network with dimers as ladder steps. The unique features of this first reported protein hydrogel may open up hitherto inaccessible applications, especially those taking advantage of the inherent catalytic activity of LplA.
Mechanism of dopamine binding and allosteric modulation of the human D1 dopamine receptor
Authors: Zhuang Youwen , Krumm Brian , Zhang Huibing , Zhou X. Edward , Wang Yue , Huang Xi-Ping , Liu Yongfeng , Cheng Xi , Jiang Yi , Jiang Hualiang , Zhang Cheng , Yi Wei , Roth Bryan L. , Zhang Yan , Xu H. Eric. 
Published: February 2021

AbstractDopamine is an essential neurotransmitter, which functions are mediated by five G protein-coupled receptors, dopamine D1 to D5 receptors (D1R-D5R) in mammals. Among them, D1R is the most abundantly expressed dopamine receptor in the CNS and is the central receptor mediating excitatory dopamine signaling in multiple dopaminergic pathways. Dysregulation of D1R signaling has been directly linked to Parkinson’s disease (PD), schizophrenia, and drug abuse. Due to its fundamental functions in human diseases, D1R has long been the subject of intensive drug development effort toward the treatment of neuropsychiatric diseases. Here, we report the structures of D1R-Gs complex bound to endogenous agonist dopamine and synthetic agonist SKF81297, both with positive allosteric modulator LY3154207. These structures reveal the basis of dopamine recognition, the binding and potential allosteric regulation of DRD1 PAM LY3154207, and provide structural templates for design of subtype-selective D1R ligand for drug discovery targeting DRD1 for treating various CNS diseases.