bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining mechanistic and machine learning models for predictive engineering and optimization of tryptophan metabolism
Authors: Zhang Jie , Petersen Søren D. , Radivojevic Tijana , Ramirez Andrés , Pérez-Manríquez Andrés , Abeliuk Eduardo , Sánchez Benjamín J. , Costello Zak , Chen Yu , Fero Michael J. , Martin Hector Garcia , Nielsen Jens , Keasling Jay D. , Jensen Michael K. 
Published: September 2020

AbstractThrough advanced mechanistic modeling and the generation of large high-quality datasets, machine learning is becoming an integral part of understanding and engineering living systems. Here we show that mechanistic and machine learning models can be combined to enable accurate genotype-to-phenotype predictions. We use a genome-scale model to pinpoint engineering targets, efficient library construction of metabolic pathway designs, and high-throughput biosensor-enabled screening for training diverse machine learning algorithms. From a single data-generation cycle, this enables successful forward engineering of complex aromatic amino acid metabolism in yeast, with the best machine learning-guided design recommendations improving tryptophan titer and productivity by up to 74 and 43%, respectively, compared to the best designs used for algorithm training. Thus, this study highlights the power of combining mechanistic and machine learning models to effectively direct metabolic engineering efforts.
A machine learning Automated Recommendation Tool for synthetic biology
Authors: Radivojević Tijana , Costello Zak , Workman Kenneth , Garcia Martin Hector 
Published: September 2020

AbstractSynthetic biology allows us to bioengineer cells to synthesize novel valuable molecules such as renewable biofuels or anticancer drugs. However, traditional synthetic biology approaches involve ad-hoc engineering practices, which lead to long development times. Here, we present the Automated Recommendation Tool (ART), a tool that leverages machine learning and probabilistic modeling techniques to guide synthetic biology in a systematic fashion, without the need for a full mechanistic understanding of the biological system. Using sampling-based optimization, ART provides a set of recommended strains to be built in the next engineering cycle, alongside probabilistic predictions of their production levels. We demonstrate the capabilities of ART on simulated data sets, as well as experimental data from real metabolic engineering projects producing renewable biofuels, hoppy flavored beer without hops, fatty acids, and tryptophan. Finally, we discuss the limitations of this approach, and the practical consequences of the underlying assumptions failing.
A data-driven simulation platform to predict cultivars’ performances under uncertain weather conditions
Authors: de los Campos Gustavo , Pérez-Rodríguez Paulino , Bogard Matthieu , Gouache David , Crossa José 
Published: September 2020

AbstractIn most crops, genetic and environmental factors interact in complex ways giving rise to substantial genotype-by-environment interactions (G×E). We propose that computer simulations leveraging field trial data, DNA sequences, and historical weather records can be used to tackle the longstanding problem of predicting cultivars’ future performances under largely uncertain weather conditions. We present a computer simulation platform that uses Monte Carlo methods to integrate uncertainty about future weather conditions and model parameters. We use extensive experimental wheat yield data (n = 25,841) to learn G×E patterns and validate, using left-trial-out cross-validation, the predictive performance of the model. Subsequently, we use the fitted model to generate circa 143 million grain yield data points for 28 wheat genotypes in 16 locations in France, over 16 years of historical weather records. The phenotypes generated by the simulation platform have multiple downstream uses; we illustrate this by predicting the distribution of expected yield at 448 cultivar-location combinations and performing means-stability analyses.
Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism
Authors: Ramaswami Gokul , Won Hyejung , Gandal Michael J. , Haney Jillian , Wang Jerry C. , Wong Chloe C. Y. , Sun Wenjie , Prabhakar Shyam , Mill Jonathan , Geschwind Daniel H. 
Published: September 2020

AbstractAutism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome and transcriptome. Focusing on this convergent subtype, we substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and identify an enrichment of ASD genetic risk variants in hyperacetylated noncoding regulatory regions linked to neuronal genes. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.
Transition from light diffusion to localization in three-dimensional amorphous dielectric networks near the band edge
Authors: Haberko Jakub , Froufe-Pérez Luis S. , Scheffold Frank 
Published: September 2020

AbstractLocalization of light is the photon analog of electron localization in disordered lattices, for whose discovery Anderson received the Nobel prize in 1977. The question about its existence in open three-dimensional materials has eluded an experimental and full theoretical verification for decades. Here we study numerically electromagnetic vector wave transmittance through realistic digital representations of hyperuniform dielectric networks, a new class of highly correlated but disordered photonic band gap materials. We identify the evanescent decay of the transmitted power in the gap and diffusive transport far from the gap. Near the gap, we find that transport sets off diffusive but, with increasing slab thickness, crosses over gradually to a faster decay, signaling localization. We show that we can describe the transition to localization at the mobility edge using the self-consistent theory of localization based on the concept of a position-dependent diffusion coefficient.
Trait phenomenological control predicts experience of mirror synaesthesia and the rubber hand illusion
Authors: Lush P. , Botan V. , Scott R. B. , Seth A. K. , Ward J. , Dienes Z. 
Published: September 2020

AbstractIn hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) — which are experienced as involuntary — according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353 participants), we report substantial relationships between hypnotisability and experimental measures of experiential change in mirror-sensory synaesthesia and the rubber hand illusion comparable to relationships between hypnotisability and individual hypnosis scale items. The control of phenomenology to meet expectancies arising from perceived task requirements can account for experiential change in psychological experiments.
The atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication
Authors: Fumagalli Amos , Heuninck Joyce , Pizzoccaro Anne , Moutin Enora , Koenen Joyce , Séveno Martial , Durroux Thierry , Junier Marie-Pierre , Schlecht-Louf Géraldine , Bachelerie Francoise , Schütz Dagmar , Stumm Ralf , Smit Martine J. , Guérineau Nathalie C. , Chaumont-Dubel Séverine , Marin Philippe 
Published: September 2020

AbstractThe atypical chemokine receptor 3 (ACKR3) plays a pivotal role in directing the migration of various cellular populations and its over-expression in tumors promotes cell proliferation and invasiveness. The intracellular signaling pathways transducing ACKR3-dependent effects remain poorly characterized, an issue we addressed by identifying the interactome of ACKR3. Here, we report that recombinant ACKR3 expressed in HEK293T cells recruits the gap junction protein Connexin 43 (Cx43). Cx43 and ACKR3 are co-expressed in mouse brain astrocytes and human glioblastoma cells and form a complex in embryonic mouse brain. Functional in vitro studies show enhanced ACKR3 interaction with Cx43 upon ACKR3 agonist stimulation. Furthermore, ACKR3 activation promotes β-arrestin2- and dynamin-dependent Cx43 internalization to inhibit gap junctional intercellular communication in primary astrocytes. These results demonstrate a functional link between ACKR3 and gap junctions that might be of pathophysiological relevance.
Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor
Authors: Liu Jianlin , Adhav Ragini , Miao Kai , Su Sek Man , Mo Lihua , Chan Un In , Zhang Xin , Xu Jun , Li Jianjie , Shu Xiaodong , Zeng Jianming , Zhang Xu , Lyu Xueying , Pardeshi Lakhansing , Tan Kaeling , Sun Heng , Wong Koon Ho , Deng Chuxia , Xu Xiaoling 
Published: September 2020

AbstractSingle-cell whole-exome sequencing (scWES) is a powerful approach for deciphering intratumor heterogeneity and identifying cancer drivers. So far, however, simultaneous analysis of single nucleotide variants (SNVs) and copy number variations (CNVs) of a single cell has been challenging. By analyzing SNVs and CNVs simultaneously in bulk and single cells of premalignant tissues and tumors from mouse and human BRCA1-associated breast cancers, we discover an evolution process through which the tumors initiate from cells with SNVs affecting driver genes in the premalignant stage and malignantly progress later via CNVs acquired in chromosome regions with cancer driver genes. These events occur randomly and hit many putative cancer drivers besides p53 to generate unique genetic and pathological features for each tumor. Upon this, we finally identify a tumor metastasis suppressor Plekha5, whose deficiency promotes cancer metastasis to the liver and/or lung.
Face selective patches in marmoset frontal cortex
Authors: Schaeffer David J. , Selvanayagam Janahan , Johnston Kevin D. , Menon Ravi S. , Freiwald Winrich A. , Everling Stefan 
Published: September 2020

AbstractIn humans and macaque monkeys, socially relevant face processing is accomplished via a distributed functional network that includes specialized patches in frontal cortex. It is unclear whether a similar network exists in New World primates, who diverged ~35 million years from Old World primates. The common marmoset is a New World primate species ideally placed to address this question given their complex social repertoire. Here, we demonstrate the existence of a putative high-level face processing network in marmosets. Like Old World primates, marmosets show differential activation in anterior cingulate and lateral prefrontal cortices while they view socially relevant videos of marmoset faces. We corroborate the locations of these frontal regions by demonstrating functional and structural connectivity between these regions and temporal lobe face patches. Given the evolutionary separation between macaques and marmosets, our results suggest this frontal network specialized for social face processing predates the separation between Platyrrhini and Catarrhini.
Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism
Authors: Zulkifli Mohammad , Neff John K. , Timbalia Shrishiv A. , Garza Natalie M. , Chen Yingqi , Watrous Jeramie D. , Murgia Marta , Trivedi Prachi P. , Anderson Steven K. , Tomar Dhanendra , Nilsson Roland , Madesh Muniswamy , Jain Mohit , Gohil Vishal M. 
Published: September 2020

AbstractMitochondria house evolutionarily conserved pathways of carbon and nitrogen metabolism that drive cellular energy production. Mitochondrial bioenergetics is regulated by calcium uptake through the mitochondrial calcium uniporter (MCU), a multi-protein complex whose assembly in the inner mitochondrial membrane is facilitated by the scaffold factor MCUR1. Intriguingly, many fungi that lack MCU contain MCUR1 homologs, suggesting alternate functions. Herein, we characterize Saccharomyces cerevisiae homologs Put6 and Put7 of MCUR1 as regulators of mitochondrial proline metabolism. Put6 and Put7 are tethered to the inner mitochondrial membrane in a large hetero-oligomeric complex, whose abundance is regulated by proline. Loss of this complex perturbs mitochondrial proline homeostasis and cellular redox balance. Yeast cells lacking either Put6 or Put7 exhibit a pronounced defect in proline utilization, which can be corrected by the heterologous expression of human MCUR1. Our work uncovers an unexpected role of MCUR1 homologs in mitochondrial proline metabolism.
Comparative analysis of rhizosphere soil physiochemical characteristics and microbial communities between rusty and healthy ginseng root
Authors: Bian Xingbo , Xiao Shengyuan , Zhao Yan , Xu Yonghua , Yang He , Zhang Lianxue 
Published: September 2020

AbstractGinseng rusty root (GRR) symptom is one of the primary diseases of ginseng. There has been a problem of ginseng rusty root, leading to a severe decline in the quality of ginseng. To clarify the relationship between root symptoms of ginseng rust and soil, the physical and chemical properties, enzyme activity, community structure and microbial diversity of GRR and healthy ginseng (HG) rhizosphere soil were analyzed and compared. The pH and redox potential (Eh) of GRR soil decreased, and the contents of total phosphorus (TP), available phosphorus (AP), and available potassium (AK) decreased. The activity of catalase and phosphatase and invertase was lower than that of HG groups. Besides, the microbial community of GRR rhizosphere soil changes much, and its abundance and diversity are significantly reduced. The community structure of GRR rhizosphere soil also shows apparent differences, and the samples of the HG group gathered together, and the samples of the GRR group were dispersed. In general, GRR was closely associated with decreases in soil pH and Eh; decreases in TP, AP, and AK; decreases in the activity of several enzymes. Additionally, it is strongly associated with an increase in pathogenic microorganisms such as Ilyonectria and a reduction of beneficial microorganisms such as Tremellomycetes Acidobacteria subgroup 6 and Gemmatimonadetes.
Efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins
Authors: Abi Habib Joanna , De Plaen Etienne , Stroobant Vincent , Zivkovic Dusan , Bousquet Marie-Pierre , Guillaume Benoît , Wahni Khadija , Messens Joris , Busse Antonia , Vigneron Nathalie , Van den Eynde Benoit J. 
Published: September 2020

AbstractThe proteasome is responsible for selective degradation of proteins. It exists in mammalian cells under four main subtypes, which differ by the combination of their catalytic subunits: the standard proteasome (β1–β2–β5), the immunoproteasome (β1i–β2i–β5i) and the two intermediate proteasomes (β1–β2–β5i and β1i–β2–β5i). The efficiency of the four proteasome subtypes to degrade ubiquitinated or oxidized proteins remains unclear. Using cells expressing exclusively one proteasome subtype, we observed that ubiquitinated p21 and c-­myc were degraded at similar rates, indicating that the four 26S proteasomes degrade ubiquitinated proteins equally well. Under oxidative stress, we observed a partial dissociation of 26S into 20S proteasomes, which can degrade non-ubiquitinated oxidized proteins. Oxidized calmodulin and hemoglobin were best degraded in vitro by the three β5i-containing 20S proteasomes, while their native forms were not degraded. Circular dichroism analyses indicated that ubiquitin-independent recognition of oxidized proteins by 20S proteasomes was triggered by the disruption of their structure. Accordingly, β5i-containing 20S proteasomes degraded unoxidized naturally disordered protein tau, while 26S proteasomes did not. Our results suggest that the three β5i-containing 20S proteasomes, namely the immunoproteasome and the two intermediate proteasomes, might help cells to eliminate proteins containing disordered domains, including those induced by oxidative stress.
Ecological parameter reductions, environmental regimes, and characteristic process diagram of carbon dioxide fluxes in coastal salt marshes
Authors: Ishtiaq Khandker S. , Abdul-Aziz Omar I. 
Published: September 2020

AbstractWe investigated the ecological parameter reductions (termed “similitudes”) and characteristic patterns of the net uptake fluxes of carbon dioxide (CO2) in coastal salt marshes using dimensional analysis method from fluid mechanics and hydraulic engineering. Data collected during May–October, 2013 from four salt marshes in Waquoit Bay and adjacent estuary, Massachusetts, USA were utilized to evaluate the theoretically-derived dimensionless flux and various ecological driver numbers. Two meaningful dimensionless groups were discovered as the light use efficiency number (LUE = CO2 normalized by photosynthetically active radiation) and the biogeochemical number (combination of soil temperature, porewater salinity, and atmospheric pressure). A semi-logarithmic plot of the dimensionless numbers indicated the emergence of a characteristic diagram represented by three distinct LUE regimes (high, transitional, and low). The high regime corresponded to the most favorable (high temperature and low salinity) condition for CO2 uptake, whereas the low regime represented an unfavorable condition (low temperature and high salinity). The analysis identified two environmental thresholds (soil temperature ~ 17 °C and salinity ~ 30 ppt), which dictated the regime transitions of CO2 uptake. The process diagram and critical thresholds provide important insights into the CO2 uptake potential of coastal wetlands in response to changes in key environmental drivers.
Identification of volatile components from oviposition and non-oviposition plants of Gasterophilus pecorum (Diptera: Gasterophilidae)
Authors: Zhou Ran , Zhang Ke , Zhang Tiange , Zhou Tong , Chu Hongjun , Ge Yan , Wang Chen , Li Kai 
Published: September 2020

AbstractOviposition by Gasterophilus pecorum on shoot tips of Stipa caucasica is a key determinant of its severe infection of the reintroduced Przewalski’s horse (Equus przewalskii). Volatiles in shoots of grasses on which Przewalski’s horse feeds, including S. caucasica at preoviposition, oviposition, and postoviposition stages of G. pecorum, S. caucasica, Stipa orientalis, and Ceratoides latens at the oviposition stage, and S. caucasica in various growth periods, were collected by dynamic headspace adsorption and analyzed by automatic thermal desorption gas chromatography-mass spectrometry. Among five volatiles with highest relative contents under three sets of conditions, caprolactam and 3-hexen-1-ol,(Z)- were common to all samples. Caprolactam was highest in C. latens at oviposition stage of G. pecorum and lowest in S. caucasica at postoviposition stage, and that of 3-hexen-1-ol,(Z)- was lowest in C. latens and highest in S. caucasica at its oviposition stage. Particularly, in S. caucasica during the three oviposition phenological stages of G. pecorum, 3-hexen-1-ol,acetate,(Z)-, 2(5H)-furanone,5-ethyl-, and 3-hexen-1-ol,acetate,(E)- were unique, respectively, to the preoviposition, oviposition, and postoviposition stages; in three plant species during the oviposition stage of G. pecorum, 3-hexen-1-ol,acetate,(Z)-, 3-hexenal, and 1-hexanol were unique to S. orientalis, acetic acid, hexanal, and 2(5H)-furanone,5-ethyl- to S. caucasica, and 1,3,6-octatriene,3,7-dimethyl-, cis-3-hexenyl isovalerate, and acetic acid hexyl ester to C. latens; in S. caucasica, 2-undecanone,6,10-dimethyl- was unique to the early growth period, acetic acid and 2(5H)-furanone,5-ethyl- to the flourishing growth period, and 3-hexen-1-ol,acetate,(Z)- and 1,3,6-octatriene,3,7-dimethyl- to the late growth period. Furthermore, substances specific to S. orientalis and C. latens were also present in S. caucasica, except at oviposition stage. Our findings will facilitate studies on G. pecorum’s adaptation to the arid desert steppe and its future control.
Solvable delay model for epidemic spreading: the case of Covid-19 in Italy
Authors: Dell’Anna Luca 
Published: September 2020

AbstractWe study a simple realistic model for describing the diffusion of an infectious disease on a population of individuals. The dynamics is governed by a single functional delay differential equation, which, in the case of a large population, can be solved exactly, even in the presence of a time-dependent infection rate. This delay model has a higher degree of accuracy than that of the so-called SIR model, commonly used in epidemiology, which, instead, is formulated in terms of ordinary differential equations. We apply this model to describe the outbreak of the new infectious disease, Covid-19, in Italy, taking into account the containment measures implemented by the government in order to mitigate the spreading of the virus and the social costs for the population.
Impairment of synaptic plasticity and novel object recognition in the hypergravity-exposed rats
Authors: Lee Jinho , Jang Doohyeong , Jeong Hyerin , Kim Kyu-sung , Yang Sunggu 
Published: September 2020

AbstractThe gravity is necessary for living organisms to operate various biological events including hippocampus-related functions of learning and memory. Until now, it remains inconclusive how altered gravity is associated with hippocampal functions. It is mainly due to the difficulties in generating an animal model experiencing altered gravity. Here, we demonstrate the effects of hypergravity on hippocampus-related functions using an animal behavior and electrophysiology with our hypergravity animal model. The hypergravity (4G, 4 weeks) group showed impaired synaptic efficacy and long-term potentiation in CA1 neurons of the hippocampus along with the poor performance of a novel object recognition task. Our studies suggest that altered gravity affects hippocampus-related cognitive functions, presumably through structural and functional adaptation to various conditions of gravity shift.