bluuebunny/crossref_metadata_2025_split huggingface dataset:
Marker-assisted selection of trees withMALE STERALITY 1inCryptomeria japonicaD. Don
Authors: Moriguchi Yoshinari , Ueno Saneyoshi , Hasegawa Yoichi , Tadama Takumi , Watanabe Masahiro , Saito Ryunosuke , Hirayama Satoko , Iwai Junji , Konno Yukinori 
Published: May 2020

AbstractPractical use of marker-assisted selection (MAS) is limited in conifers because of the difficulty with developing markers due to a rapid decrease in linkage disequilibrium, the limited genomic information available, and the diverse genetic backgrounds among breeding material collections. First, in this study, two families were produced by artificial crossing between two male-sterile trees, Shindai11 and Shindai12, and a plus tree, Suzu-2 (Ms1/ms1) (S11-S and S12-S families, respectively). The segregation ratio between male-sterile and male-fertile trees did not deviate significantly from the expected 1:1 ratio in either family. These results clearly suggested that the male-sterile gene of Shindai11 and Shindai12 isMALE STERALITY 1(MS1). Because some markers reported previously have not been linkage mapped, we constructed a partial linkage map of the region encompassingMS1using the S11-S and S12-S families. For the S11-S and S12-S families, 19 and 18 markers were mapped onto the partial linkage maps ofMS1region, respectively. There was collinearity (conserved gene order) between the two partial linkage maps. Two markers (CJt020762_ms1-1and reCj19250_2335) were mapped to the same position as theMS1locus on both maps. Of these markers, we used CJt020762 for MAS in this study. According to the MAS results for 650 trees from six prefectures of Japan (603 trees from breeding materials and 47 trees from the Ishinomaki natural population), five trees in Niigata Prefecture and one tree in Yamagata Prefecture had heterozygousms1-1, and three trees in Miyagi Prefecture had heterozygousms1-2. The results obtained in this study suggested that there may be geographical hotspots for thems1-1andms1-2alleles. Because MAS can be used effectively to reduce the labor and time required for selection of trees with a male-sterile gene, the number of breeding materials should increase in the future.
A multiplexed, automated evolution pipeline enables scalable discovery and characterization of biosensors
Authors: Townshend Brent , Xiang Joy , Manzanarez Gabriel , Hayden Eric , Smolke Christina 
Published: May 2020

AbstractBiosensors are key components in engineered biological systems, providing a means of measuring and acting upon the large biochemical space in living cells. However, generating small molecule sensing elements and integrating them intoin vivobiosensors have been challenging. Using aptamer-coupled ribozyme libraries and a novel ribozyme regeneration method, we developedde novorapidin vitroevolution of RNA biosensors (DRIVER) that enables multiplexed discovery of biosensors. With DRIVER and high-throughput characterization (CleaveSeq) fully automated on liquid-handling systems, we identified and validated biosensors against six small molecules, including five for which no aptamers were previously found. DRIVER-evolved biosensors were applied directly to regulate gene expression in yeast, displaying activation ratios up to 33-fold. DRIVER biosensors were also applied in detecting metabolite production from a multi-enzyme biosynthetic pathway. This work demonstrates DRIVER as a scalable pipeline for engineeringde novobiosensors with wide-ranging applications in biomanufacturing, diagnostics, therapeutics, and synthetic biology.
Axon morphology is modulated by the local environment and impacts the non-invasive investigation of its structure-function relationship
Authors: Andersson Mariam , Kjer Hans Martin , Rafael-Patino Jonathan , Pacureanu Alexandra , Pakkenberg Bente , Thiran Jean-Philippe , Ptito Maurice , Bech Martin , Dahl Anders Bjorholm , Dahl Vedrana Andersen , Dyrby Tim B. 
Published: May 2020

AbstractAxonal conduction velocity, which ensures efficient function of the brain network, is related to axon diameter. Non-invasive, in vivo axon diameter estimates can be made with diffusion magnetic resonance imaging, but the technique requires 3D validation. Here, high resolution, 3D synchrotron X-ray Nano-Holotomography images of white matter samples from the corpus callosum of a monkey brain reveal that blood vessels, cells and vacuoles affect axonal diameter and trajectory. Within single axons, we find that the variance in diameter and conduction velocity correlates with the mean diameter, contesting the value of precise diameter determination in larger axons. These complex 3D axon morphologies drive previously reported 2D trends in axon diameter and g-ratio. Furthermore, we find that these morphologies bias the estimates of axon diameter with diffusion magnetic resonance imaging and, ultimately, impact the investigation and formulation of the axon structure-function relationship.
HSP90 facilitates oncogenic alterations of metabolism in B-cell lymphomas
Authors: Calvo-Vidal M. Nieves , Zamponi Nahuel , Krumsiek Jan , Stockslager Max A. , Revuelta Maria V. , Phillip Jude M. , Marullo Rossella , Kotlov Nikita , Patel Jayeshkumar , Yang Shao Ning , Yang Lucy , Taldone Tony , Thieblemont Catherine , Leonard John P. , Martin Peter , Inghirami Giorgio , Chiosis Gabriela , Manalis Scott R. , Cerchietti Leandro 
Published: May 2020

ABSTRACTHSP90 is critical for maintenance of the cellular proteostasis. In cancer cells, HSP90 also becomes a nucleating site for the stabilization of multiprotein complexes including signaling pathways and transcription complexes. Here, we described a novel role of HSP90 in the cytosolic compartmentalization of metabolic pathways in proliferating cancer cells. We found that HSP90 assists in the organization of metabolic enzymes into non-membrane-bound functional compartments termed metabosomes. Under experimental conditions that conserved the cellular proteostasis, we demonstrated that the compartmentalizing activity of HSP90 is critical to sustain the coordinated synthesis of multiple metabolites required for energy production, maintenance of the cellular biomass and secretion of immunometabolites. Conversely, inhibition of the nucleating capacity of HSP90 modified the topology of cytosolic metabosomes before protein degradation was apparent decreasing the efficiency of MYC-driven metabolic pathways. Inhibition of HSP90 decreases cancer metabolism in B-cell lymphoma cells and patients providing a novel mechanism of activity for this class of drugs.
Complement factor C1q mediates chronic neuron loss and inflammation post-brain injury
Authors: Holden Stephanie S , Aboubakr Oumaima , Higashikubo Bryan , Cho Frances S , Chang Andrew H , Morningstar Allison , Mathur Vidhu , Kuhn Logan J , Suri Poojan , Sankaranarayanan Sethu , Andrews-Zwilling Yaisa , Aronica Eleonora , Yednock Ted , Paz Jeanne T 
Published: May 2020

ABSTRACTWhile traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of cortical injury that does not directly damage subcortical structures, we found a chronic increase in C1q expression specifically in the corticothalamic circuit. Increased C1q expression co-localized with neuron loss and chronic inflammation, and correlated with altered cortical rhythms. Blocking C1q counteracted most of these outcomes, suggesting that C1q is a disease modifier in TBI. Since the corticothalamic circuit is important for sensory processing, attention, cognition, and sleep, all of which can be impaired by TBI, this circuit could be a new target for treating TBI-related disabilities.
Conserved Roles for Receptor Tyrosine Kinase Extracellular Regions in Regulating Receptor and Pathway Activity
Authors: Gonzalez-Magaldi Monica , McCabe Jacqueline M. , Cartwright Haley N. , Sun Ningze , Leahy Daniel J. 
Published: May 2020

SummaryReceptor Tyrosine Kinases (RTKs) comprise a diverse group of cell-surface receptors that mediate key signaling events during animal development and are frequently activated in cancer. Ligand-induced dimerization is the canonical mechanism by which RTKs are thought to be activated. We show here that deletion of the extracellular regions of 10 RTKs representing 7 RTK classes or their substitution with the dimeric immunoglobulin Fc region results in constitutive receptor phosphorylation but fails to result in phosphorylation of downstream signaling effectors Erk or Akt. Conversely, substitution of RTK extracellular regions with the extracellular region of the Epidermal Growth Factor Receptor (EGFR) results in increases in Erk and/or Akt phosphorylation in response to EGF. These results indicate that the activation signal generated by the EGFR extracellular region is capable of activating at least 7 different RTK classes. Failure of phosphorylated Fc-RTK chimeras to stimulate phosphorylation of downstream effectors indicates that either dimerization and receptor phosphorylationper seare insufficient to activate signaling or constitutive dimerization leads to pathway inhibition.
Switching On Static Gene Regulatory Networks to Compute Cellular Decisions
Authors: Pavillet Clara E. , Voukantsis Dimitrios , Buffa Francesca M. 
Published: May 2020

AbstractMotivationGene networks are complex sets of regulators and interactions that govern cellular processes. Their perturbations can disrupt regular biological functions, translating into a change in cell behaviour and ability to respond to internal and external cues. Computational models of these networks can boost translation of our scientific knowledge into medical applications by predicting how cells will behave in health and disease, or respond to stimuli such as a drug treatment. The development of such models requires effective ways to read, manipulate and analyse the increasing amount of existing, and newly deposited gene network data.ResultsWe developed BioSWITCH, a command-line program using the BioPAX standardised language to “switch on” static regulatory networks so that they can be executed in GINML to predict cellular behaviour. Using a previously published haematopoiesis gene network, we show that BioSWITCH successfully and faithfully automates the network de-coding and re-coding into an executable logical network. BioSWITCH also supports the integration of a BioPAX model into an existing GINML graph.AvailabilitySource code available athttps://github.com/CBigOxf/BioSWITCH.Contactclara.pavillet@msdtc.ox.ac.uk;francesca.buffa@oncology.ox.ac.uk
Identifying drug response by combining measurements of the membrane potential, the cytosolic calcium concentration, and the extracellular potential in microphysiological systems
Authors: Jæger Karoline Horgmo , Charwat Verena , Wall Sam , Healy Kevin E. , Tveito Aslak 
Published: May 2020

AbstractCardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) offer a new means to study and understand the human cardiac action potential, and can give key insight into how compounds may interact with important molecular pathways to destabilize the electrical function of the heart. Important features of the action potential can be readily measured using standard experimental techniques, such as the use of voltage sensitive dyes and fluorescent genetic reporters to estimate transmembrane potentials and cytosolic calcium concentrations. Using previously introduced computational procedures, such measurements can be used to estimate the current density of major ion channels present in hiPSC-CMs, and how compounds may alter their behavior. However, due to the limitations of optical recordings, resolving the sodium current remains difficult from these data. Here we show that if these optical measurements are complemented with observations of the extracellular potential using multi electrode arrays (MEAs), we can accurately estimate the current density of the sodium channels. This inversion of the sodium current relies on observation of the conduction velocity which turns out to be straightforwardly computed using measurements of extracellular waves across the electrodes. The combined data including the membrane potential, the cytosolic calcium concentration and the extracellular potential further opens up for the possibility of accurately estimating the effect of novel drugs applied to hiPSC-CMs.
Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis
Authors: Pando-Naude Victor , Toxto Sebastian , Fernandez-Lozano Sofia , Parsons E. Christine , Alcauter Sarael , Garza-Villarreal Eduardo A. 
Published: May 2020

AbstractSubstance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and negative emotional state. Repeated use of a substance results in synaptic and morphological changes, secondary to toxicity and SUD pathology in the dopamine striato-thalamo-cortical and limbic pathways. These neuroadaptations seem to vary between studies, which could be related to divergent effects of substances, consumption severity or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registrationCRD42017071222). Fifty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 538 foci, 88 experiments and 4370 participants. We found convergence and divergence in brain regions and volume effects (higher vs lower volume) in GM and WM depending on the severity of consumption pattern and type of substance. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate distinctive brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.
The genome sequence ofAloe verareveals adaptive evolution of drought tolerance mechanisms
Authors: Jaiswal Shubham K. , Chakraborty Abhisek , Mahajan Shruti , Kumar Sudhir , Sharma Vineet K. 
Published: May 2020

ABSTRACTAloe verais a species from Asphodelaceae plant family having unique characteristics such as drought resistance and also possesses numerous medicinal properties. However, the genetic basis of these phenotypes is yet unknown, primarily due to the unavailability of its genome sequence. In this study, we report the firstAloe veradraft genome sequence comprising of 13.83 Gbp and harboring 86,177 coding genes. It is also the first genome from the Asphodelaceae plant family and is the largest angiosperm genome sequenced and assembled till date. Further, we report the first genome-wide phylogeny of monocots withAloe verausing 1,440 one-to-one orthologs that resolves the genome-wide phylogenetic position ofAloe verawith respect to the other monocots. The comprehensive comparative analysis ofAloe veragenome with the other available high-quality monocot genomes revealed adaptive evolution in several genes of the drought stress response, CAM pathway, and circadian rhythm inAloe vera. Further, genes involved in DNA damage response, a key pathway in several biotic and abiotic stress response mechanisms, were found to be positively selected. This provides the genetic basis of the evolution of drought stress tolerance capabilities ofAloe vera. This also substantiates the previously suggested notion that the evolution of unique characters in this species is perhaps due to selection and adaptive evolution rather than the phylogenetic divergence or isolation.
Population studies of the wild tomato species Solanum chilense reveal geographically structured major gene-mediated pathogen resistance
Authors: Kahlon Parvinderdeep S. , Seta Shallet Mindih , Zander Gesche , Scheikl Daniela , Hückelhoven Ralph , Joosten Matthieu H. A. J. , Stam Remco 
Published: May 2020

AbstractNatural plant populations encounter strong pathogen pressure and defense-associated genes are known to be under different selection pressure dependent on the pressure by the pathogens. Here we use wild tomato Solanum chilense populations to investigate natural resistance against Cladosporium fulvum, a well-known pathogenic fungus of domesticated tomatoes. We show that populations of S. chilense differ in resistance against the pathogen. Next, we explored the underlying molecular processes in a species wide-context. Then, focusing on recognition of the two prominent avirulence factors secreted by C. fulvum (Avr4 and Avr9) in central and northern populations of S. chilense we observed high complexity in the cognate homologues of Cladosporium resistance (Hcr9) locus underlying the recognition of these effectors. Presence of canonical genomic regions coding for Cf-4 and Cf-9, two major dominant resistance genes in the Hcr9 locus recognizing Avr4 and Avr9, respectively, does not meet prediction from Avr response phenotypes. We find both genes in varying fractions of the plant populations and we show possible co-existence of two functionally active resistance genes, previously thought to be allelic. Additionally, we observed the complete local absence of recognition of additional Avr proteins of C. fulvum. In the southern populations we attribute this to changes in the coregulatory network. As a result of loss of pathogen pressure or adaptation to extreme climatic conditions. This may ultimately explain the observed pathogen susceptibility in the southern populations. This work puts major gene mediated disease resistance in an ecological context.
In vivocontactless brain stimulation via non-invasive and targeted delivery of magnetoelectric nanoparticles
Authors: Nguyen Tyler , Gao Jianhua , Wang Ping , Nagesetti Abhignyan , Andrews Peter , Masood Sehban , Vriesmann Zoe , Liang Ping , Khizroev Sakhrat , Jin Xiaoming 
Published: May 2020

AbstractNon-invasive brain stimulation is valuable for studying neural circuits and treating various neurological disorders in humans. However, the current technologies usually have low spatial and temporal precision and poor brain penetration, which greatly limit their application. A new class of nanoparticles known as magneto-electric nanoparticles (MENs) can be navigated to a targeted brain region with a magnetic field and is highly efficient in converting an externally applied magnetic wave into local electric fields for neuronal activity modulation. Here we developed a new method to fabricate MENs of CoFe2O4-BaTiO3core-shell structure that had excellent magneto-electrical coupling properties. Using calcium imaging of organotypic and acute cortical slices from GCaMP6s transgenic mice, we demonstrated their efficacy in reliably evoking neuronal responses with a short latency period. Forin vivonon-invasive delivery of MENs to brain, fluorescently labeled MENs were intravenously injected and guided to pass through the blood brain barrier to a targeted brain region by applying a magnetic field gradient. A magnetic field (∼450 Oe at 10 Hz) applied to mouse brain was able to reliably evoke cortical activities, as revealed byin vivotwo-photon and mesoscopic imaging of calcium signals at both cellular and global network levels. The effect was further confirmed by the increased number of c-Fos expressing cells after stimulation. Neither brain delivery of MENs nor the subsequent magnetic stimulation caused any significant increases in the numbers of GFAP and IBA1 positive astrocytes and microglia in the brain. This study demonstrates the feasibility of using MENs as a novel efficient and non-invasive technique of contactless deep brain stimulation that may have great potential for translation.
Telomere length is highly heritable and independent of growth rate manipulated by temperature in field crickets
Authors: Boonekamp Jelle , Rodríguez-Muñoz Rolando , Hopwood Paul , Zuidersma Erica , Mulder Ellis , Wilson Alastair , Verhulst Simon , Tregenza Tom 
Published: May 2020

AbstractMany organisms are capable of growing faster than they do. Restrained growth rate has functionally been explained by negative effects on lifespan of accelerated growth. However, the underlying mechanisms remain elusive. Telomere attrition has been proposed as a causal agent and has been studied in endothermic vertebrates. We established that telomeres exist as chromosomal-ends in a model insect, the field cricket, using terminal restriction fragment andBal 31methods. Telomeres comprised TTAGGn repeats of 38kb on average, more than four times longer than the telomeres of human infants.Bal 31assays confirmed that telomeric repeats were located at the chromosome-ends. We tested whether rapid growth is achieved at the expense of telomere length by comparing crickets reared at 23°C with their siblings reared at 28°C, which grew three times faster. Surprisingly, neither temperature treatment nor age affected average telomere length. Concomitantly, the broad sense heritability of telomere length was remarkably high at ~100%. Despite high heritability, the evolvability (a mean standardized measure of genetic variance) was low relative to that of body mass. We discuss the different interpretations of these scaling methods in the context of telomere evolution. It is clear that some important features of vertebrate telomere biology are evident in an insect species dating back to the Triassic, but also that there are some striking differences. The apparent lack of an effect of growth rate and the total number of cell divisions on telomere length is puzzling, suggesting that telomere length could be actively maintained during the growth phase. Whether such maintenance of telomere length is adaptive remains elusive and requires further study investigating the links with fitness in the wild.
Light-induced difference FTIR spectroscopy of primate blue-sensitive visual pigment at 163 K
Authors: Hanai Shunpei , Katayama Kota , Imai Hiroo , Kandori Hideki 
Published: May 2020

ABSTRACTStructural studies of color visual pigments lag far behind those of rhodopsin for scotopic vision. Using difference FTIR spectroscopy at 77 K, we report the first structural data of three primate color visual pigments, monkey red (MR), green (MG), and blue (MB), where the batho-intermediate (Batho) exhibits photoequilibrium with the unphotolyzed state. This photochromic property is highly advantageous for limited samples since the signal-to-noise ratio is improved, but may not be applicable to late intermediates, because of large structural changes to proteins. Here we report the photochromic property of MB at 163 K, where the BL intermediate, formed by the relaxation of Batho, is in photoequilibrium with the initial MB state. A comparison of the difference FTIR spectra at 77 and 163 K provided information on what happens in the process of transition from Batho to BL in MB. The coupled C11=C12HOOP vibration in the planer structure in MB is decoupled by distortion in Batho after retinal photoisomerization, but returns to the coupled C11=C12HOOP vibration in theall-transchromophore in BL. This suggests that BL harbors a planer all-transconfiguration of retinal. The Batho formation accompanies helical structural perturbation, which is relaxed in BL. The H-D unexchangeable X-H stretch weakens the hydrogen bond in Batho, but strengthens it in BL. Protein-bound water molecules that form an extended water cluster near the retinal chromophore change hydrogen bonds differently for Batho and BL, being stronger in the latter than in the initial state. In addition to structural dynamics, the present FTIR spectra at 163 K show no signals of protonated carboxylic acids as well as 77 K, suggesting that E181 is deprotonated in MB, Batho and BL.