bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity increases yield but reduces reproductive effort in crop mixtures
Authors: Chen Jianguo , Engbersen Nadine , Stefan Laura , Schmid Bernhard , Sun Hang , Schöb Christian 
Published: June 2020

AbstractResource allocation to reproduction is a critical trait for plant fitness1,2. This trait, called harvest index in the agricultural context3–5, determines how plant biomass is converted to seed yield and consequently financial revenue of numerous major staple crops. While plant diversity has been demonstrated to increase plant biomass6–8, plant diversity effects on seed yield of crops are ambiguous9. This discrepancy could be explained through changes in the proportion of resources invested into reproduction in response to changes in plant diversity, namely through changes of species interactions and microenvironmental conditions10–13. Here we show that increasing crop plant diversity from monoculture over 2- to 4-species mixtures increased annual primary productivity, resulting in overall higher plant biomass and, to a lesser extent, higher seed yield in mixtures compared with monocultures. The difference between the two responses to diversity was due to a reduced reproductive effort of the eight tested crop species in mixtures, possibly because their common cultivars have been bred for maximum performance in monoculture. While crop diversification provides a sustainable measure of agricultural intensification14, the use of currently available cultivars may compromise larger gains in seed yield. We therefore advocate regional breeding programs for crop varieties to be used in mixtures that should exploit facilitative interactions15among crop species.
Complete Chloroplast Genomes ofSaccharum giganteum,Saccharum longisetosum,Cleistachne sorghoides, Sarga timorense, Narenga porphyrocomaandTripsacum dactyloides. Comparisons with ITS phylogeny and Placement withinSaccharum
Authors: Evans Dyfed Lloyd , Hughes Ben 
Published: June 2020

AbstractThe first complete chloroplast and Internal Transcribed Sequence (ITS) cassette sequences for the species:Saccharum giganteum,Saccharum longisetosum,Cleistachne sorghoides, Saccharum narengaandTripsacum dactyloidesare presented. Corresponding sequences for a new isolate ofSarga timorensewere assembled. Phylogenetic analyses placeS. giganteum,S. longisetosumandS. narengawithin the Saccharinae but distinct from Saccharum, whilstC. sorghoidesemerges as a member of genusSargaandTripsacum datyloidesas a member of the Tripsacinae. Comparison of chloroplast and ITS phylogenies reveal complex reticulate evolution within the Saccharinae, withS. giganteum,S. longisetosumandS. narenga, despite having the same base chromosome count (15) having different evolutionary origins; making them members of different genera and not members of genusSaccharum. The importance of reticulate evolution in the origins of Andropogoneae, particularly the Saccharinae and the unique positions ofSaccharumandMiscanthusis discussed.
A circulating T-cell differentiation marker to predict response to immune checkpoint inhibitors
Authors: Yamauchi Takayoshi , Hoki Toshifumi , Oba Takaaki , Jain Vaibhav , Chen Hongbin , Attwood Kristopher , Battaglia Sebastiano , George Saby , Chatta Gurkamal , Puzanov Igor , Morrison Carl , Odunsi Kunle , Segal Brahm H. , Dy Grace K. , Ernstoff Marc S. , Ito Fumito 
Published: June 2020

AbstractImmune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery of blood-based biomarkers that reflect dynamic change of the tumor microenvironment, and predict response to ICI will markedly improve current treatment regimens. Here, we investigated a role of CX3C chemokine receptor 1 (CX3CR1), a marker of T-cell differentiation, in predicting response to ICI therapy. Successful treatment of tumor-bearing mice with ICI increased the frequency and T-cell receptor clonality of the peripheral CX3CR1+CD8+T-cell subset that included an enriched repertoire of tumor-specific and tumor-infiltrating CD8+T cells. Furthermore, an increase in the frequency of the CX3CR1+subset in circulating CD8+T cells early after initiation of anti-PD-1 therapy correlated with response and survival in patients with non-small cell lung cancer (NSCLC). Taken together, these data support T-cell CX3CR1 expression as a blood-based dynamic biomarker to predict response to ICI therapy.
Brain-predicted age associates with psychopathology dimensions in youth
Authors: Cropley Vanessa L. , Tian Ye , Fernando Kavisha , Sina Mansour L. , Pantelis Christos , Cocchi Luca , Zalesky Andrew 
Published: June 2020

AbstractBackgroundThis study aims to investigate whether dimensional constructs of psychopathology relate to advanced, attenuated or normal patterns of brain development, and to determine whether these constructs share common neurodevelopmental profiles.MethodsPsychiatric symptom ratings from 9312 youths (8-21 years) were parsed into 7 independent dimensions of clinical psychopathology representing conduct, anxiety, obsessive-compulsive, attention, depression, bipolar, and psychosis symptoms. Using a subset of this cohort with structural MRI (n=1313), a normative model of brain morphology was established and the model was then applied to predict the age of youth with clinical symptoms. We investigated whether the deviation of brain-predicted age from true chronological age, called the brain age gap, explained individual variation in each psychopathology dimension.ResultsIndividual variation in the brain age gap significantly associated with clinical dimensions representing psychosis (t=3.16,p=0.0016), obsessive-compulsive symptoms (t=2.5,p=0.01), and general psychopathology (t=4.08,p<0.0001). Greater symptom severity along these dimensions was associated with brain morphology that appeared older than expected for typically developing youth of the same age. Psychopathology dimensions clustered into two modules based on shared brain loci where putative accelerated neurodevelopment was most prominent. Patterns of morphological development were accelerated in frontal cortices for depression, psychosis and conduct symptoms (Module I), whereas acceleration was most evident in subcortex and insula for the remaining dimensions (Module II).ConclusionsOur findings suggest that advanced brain development, particularly in frontal cortex and subcortical nuclei, underpins clinical psychosis and obsessive-compulsive symptoms in youth. Psychopathology dimensions share common neural substrates, despite representing clinically independent symptom profiles.
Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife
Authors: Chen Dongsheng , Sun Jian , Zhu Jiacheng , Ding Xiangning , Lan Tianming , Zhu Linnan , Xiang Rong , Ding Peiwen , Wang Haoyu , Wang Xiaoling , Wu Weiying , Qiu Jiaying , Wang Shiyou , Li Haimeng , An Fuyu , Bao Heng , Zhang Le , Han Lei , Zhu Yixin , Wang Xiran , Wang Feiyue , Yuan Yuting , Wu Wendi , Sun Chengcheng , Lu Haorong , Wu Jihong , Sun Xinghuai , Zhang Shenghai , Sahu Sunil Kumar , Chen Haixia , Fang Dongming , Luo Lihua , Zeng Yuying , Wu Yiquan , Cui ZeHua , He Qian , Jiang Sanjie , Ma Xiaoyan , Feng Weimin , Xu Yan , Li Fang , Liu Zhongmin , Chen Lei , Chen Fang , Jin Xin , Qiu Wei , Yang Huanming , Wang Jian , Hua Yan , Liu Yahong , Liu Huan , Xu Xun 
Published: June 2020

AbstractA few animals have been suspected to be intermediate hosts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a large-scale single-cell screening of SARS-CoV-2 target cells on a wide variety of animals is missing. Here, we constructed the single-cell atlas for 11 representative species in pets, livestock, poultry, and wildlife. Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Furthermore, we screened the expression patterns of receptors for 144 viruses, resulting in a comprehensive atlas of virus target cells. Taken together, our work provides a novel and fundamental strategy to screen virus target cells and susceptible species, based on single-cell transcriptomes we generated for domesticated animals and wildlife, which could function as a valuable resource for controlling current pandemics and serve as an early warning system for coping with future infectious disease threats.
HYD3, a conidial hydrophobin of the fungal entomopathogenMetarhizium acriduminduces the immunity of its specialist host locust
Authors: Jiang Zeyuan , Ligoxygakis Petros , Xia Yuxian 
Published: June 2020

AbstractConidial hydrophobins in fungal pathogens of plants1,2, insects3,4, and humans5,6are required for fungal attachment and are associated with high virulence. They are believed to contribute to the pathogenesis of infection by preventing immune recognition5,6. Here, we refute this generalisation offering a more nuanced analysis. We show that MacHYD3, a hydrophobin located on the conidial surface of the specialist entomopathogenic fungusMetarhizium acridum, activates specifically the humoral and cellular immunity of its own host insect,Locusta migratoria manilensis(Meyen) but not that of other non-host insects. When topically applied to the cuticle, purified MacHYD3 improved the resistance of locusts to both specialist and generalist fungal pathogens but had no effect on the fungal resistance of other insects, includingSpodoptera frugiperdaandGalleria mellonella. Hydrophobins extracted from the generalist fungal pathogensM. anisopliaeandBeauveria bassianahad no effect on the resistance of locusts to fungal infection. Thus, the host locust has evolved to recognize the conidial hydrophobin of its specialist fungal pathogen, whereas conidial hydrophobins from generalist fungi are able to evade recognition. Our results distinguish the immunogenic potential of conidial hydrophobins between specialist and generalist fungi.
Divide and conquer – machine-learning integrates mammalian, viral, and network traits to predict unknown virus-mammal associations
Authors: Wardeh Maya , Blagrove Marcus S.C. , Sharkey Kieran J. , Baylis Matthew 
Published: June 2020

ABSTRACTOur knowledge of viral host ranges remains limited. Completing this picture by identifying unknown hosts of known viruses is an important research aim that can help identify zoonotic and animal-disease risks. Furthermore, such understanding can be used to mitigate against viral spill-over from animal reservoirs into human population. To address this knowledge-gap we apply a divide-and-conquer approach which separates viral, mammalian and network features into three unique perspectives, each predicting associations independently to enhance predictive power. Our approach predicts over 20,000 unknown associations between known viruses and mammalian hosts, suggesting that current knowledge underestimates the number of associations in wild and semi-domesticated mammals by a factor of 4.3, and the average mammalian host-range of viruses by a factor of 3.2. In particular, our results highlight a significant knowledge gap in the wild reservoirs of important zoonotic and domesticated mammals’ viruses: specifically, lyssaviruses, bornaviruses and rotaviruses.
Protein citrullination was introduced into animals by horizontal gene transfer from cyanobacteria
Authors: Cummings Thomas F. M. , Gori Kevin , Sanchez-Pulido Luis , Gavriilidis Gabriel , Moi David , Wilson Abigail R. , Murchison Elizabeth , Dessimoz Christophe , Ponting Chris P. , Christophorou Maria A. 
Published: June 2020

AbstractProtein post-translational modifications (PTMs) add an enormous amount of sophistication to biological systems but their origins are largely unexplored. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is particularly enigmatic in an evolutionary context. The citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates but absent from yeast, worms and flies. Here, we map the surprising evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterialPADIsthat excludes fungal and other bacterial homologues. The animal and cyanobacterial PADIs share unique, functionally relevant synapomorphies that are absent from all other homologues. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be approximately 1 billion years old, far younger than the 3.35-4.52 billion years known to separate bacterial and eukaryotic lineages. Under an assumption of vertical descent, PADI sequence change is anachronistically slow during this evolutionary time frame, even when compared to mitochondrial proteins, products of likely endosymbiont gene transfer and some of the most highly conserved proteins in life. The consilience of evidence indicates thatPADIswere introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial protein is enzymatically active and can citrullinate eukaryotic proteins, suggesting that thePADIHGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification with clear relevance in human physiology and disease.
Prediction of Individual Breast Cancer Evolution to Surgical Size
Authors: Axenie Cristian , Kurz Daria 
Published: June 2020

AbstractModelling surgical size is not inherently meant to replicate the tumor’s exact form and proportions, but instead to elucidate the degree of the tissue volume that may be surgically removed in terms of improving patient survival and minimize the risk that subsequent operations will be needed to eliminate all malignant cells entirely. Given the broad range of models of tumor growth, there is no specific rule of thumb about how to select the most suitable model for a particular breast cancer type and whether that would influence its subsequent application in surgery planning. Typically, these models require tumor biologydependent parametrization, which hardly generalizes to cope with tumor heterogeneity. In addition, the datasets are limited in size, owing to the restricted or expensive measurement methods. We address the shortcomings that incomplete biological specifications, the variety of tumor types, and the limited size of the data bring to existing mechanistic tumor growth models and introduce a Machine Learning model for the PRediction of INdividual breast Cancer Evolution to Surgical Size (PRINCESS). This is a data-driven model based on neural networks capable of unsupervised learning of cancer growth curves. PRINCESS learns the temporal evolution of the tumor along with the underlying distribution of the measurement space. We demonstrate the superior accuracy of PRINCESS, against four typically used tumor growth models, in learning tumor growth curves from a set of four clinical breast cancer datasets. Our experiments show that, without any modification, PRINCESS can accurately predict tumor sizes while being versatile between breast cancer types.
State-dependent cortical unit activity reflects dynamic brain state transitions in anesthesia
Authors: Lee Heonsoo , Wang Shiyong , Hudetz Anthony G. 
Published: June 2020

ABSTRACTHow anesthesia affects cortical neuronal spiking and information transfer could help understand the neuronal basis of conscious state. Recent investigations suggest that global state of the anesthetized brain is not stationary but changes spontaneously at a fixed level of anesthetic concentration. How cortical unit activity changes with dynamically transitioning brain states under anesthesia is unclear. We hypothesized that distinct cortical states are characterized by distinct neuronal spike patterns. Extracellular unit activity was measured with sixty-four-channel silicon microelectrode arrays in cortical layers 5/6 of primary visual cortex of chronically instrumented, freely moving male rats (N = 7) during stepwise reduction of the anesthetic desflurane (6, 4, 2, and 0%). Unsupervised machine learning applied to multi-unit spike patterns revealed five distinct brain states of which four occurred at various anesthetic concentrations and shifted spontaneously. In deeper anesthesia states, the number of active units and overall spike rate decreased while the remaining active units showed increased bursting (excitatory neurons), spike timing variability, unit-to-population correlation and unit-to-unit transfer entropy, especially among putative excitatory units, despite the overall decrease in transfer entropy. A novel desynchronized brain state with increased spike timing variability, entropy and electromyographic activity that occurred mostly in deep anesthesia was discovered. These results provide evidence for distinct unit activity patterns associated with spontaneous changes in local cortical brain states at stationary anesthetic conditions. The appearance of a paradoxical, desynchronized brain state in deep anesthesia contends the prevailing view of monotonic dose-dependent anesthetic effects on the brain.SIGNIFICANCE STATEMENTRecent studies suggest that spontaneous changes in brain state occur under anesthesia. However, the spiking behavior of cortical neurons associated with such state changes has not been investigated. We found that local brain states defined by multi-unit activity had non-unitary relationship with the current anesthetic level. A paradoxical brain state displaying asynchronous firing pattern and high electromyographic activity was found unexpectedly at high-dose anesthesia. In contrast, the synchronous fragmentation of neuronal spiking appeared to be a robust signature of the state of anesthesia. The findings challenge the assumption of monotonic, anesthetic dose-dependent behavior of cortical neuron populations. They enhance the interpretation of neuroscientific data obtained under anesthesia and understanding of the neuronal basis of anesthetic-induced state of unconsciousness.
Requirement ofIrf6andEsrp1/2in frontonasal and palatal epithelium to regulate craniofacial and palate morphogenesis in mouse and zebrafish
Authors: Carroll Shannon H. , Macias Trevino Claudio , Li Edward B-H , Kawasaki Kenta , Alhazmi Nora , Hallett Shawn , Cotney Justin , Carstens Russ P. , Liao Eric C. 
Published: June 2020

ABSTRACTOrofacial clefts are among the most common human congenital malformations.Irf6andEsrp1are two key genes important for palate development, conserved across vertebrates. In the zebrafish, we found that irf6 regulates the expression ofesrp1. Using RNAscope, we detailed overlappingIrf6andEsrp1/2gene expression in the mouse frontonasal prominence ectoderm, lambda joint periderm, palate and lip epithelium. In the zebrafish,irf6andesrp1/2share expression in the pre-gastrulation periderm and the embryonic frontonasal ectoderm, oral epithelium ventral to the anterior neurocranium (ANC), and the developing stomodeum. Genetic disruption ofirf6andesrp1/2in the zebrafish resulted in cleft of the ANC. In theesrp1/2zebrafish mutant, cleft of the mouth opening formed and appeared to tether into the ANC cleft. Lineage tracing of the anterior cranial neural crest cells revealed that cleft of the ANC resulted not from migration defect, but from impaired chondrogenesis. Molecular analysis of the aberrant cells localized within the ANC cleft revealed that this cell population espressessox10, col1a1andirf6and is adjacent to cells expressing epithelialkrt4. Detailed morphogenetic analysis of mouseIrf6mutant revealed mesenchymal defects not observed in theEsrp1/2mutant. Analysis of breeding compoundIrf6;Esrp1;Esrp2mutant suggests that these genes interact where the triple mutant is not observed. Taken together, these studies highlight the complementary analysis ofIrf6andEsrp1/2in mouse and zebrafish models and captured an unique aberrant embryonic cell population that contributes to cleft pathogenesis. Future work characterizing this unqiuesox10+, col1a1+, irf6+ cell population will yield additional insight into cleft pathogenesis.
β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture
Authors: Mahmood Syed Raza , Xie Xin , El Said Nadine Hosny , Gunsalus Kristin C. , Percipalle Piergiorgio 
Published: June 2020

Abstractβ-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can affect the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2 in a dosage-dependent manner. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings support a novel role for β-actin-dependent chromatin remodeling in shaping the chromatin landscape and regulating genes involved in development and differentiation.
The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2
Authors: Zimniak Melissa , Kirschner Luisa , Hilpert Helen , Seibel Jürgen , Bodem Jochen 
Published: June 2020

AbstractTo circumvent time-consuming clinical trials, testing whether existing drugs are effective inhibitors of SARS-CoV-2, has led to the discovery of Remdesivir. We decided to follow this path and screened approved medications “off-label” against SARS-CoV-2. In these screenings, Fluoxetine inhibited SARS-CoV-2 at a concentration of 0.8µg/ml significantly, and the EC50 was determined with 387ng/ml. Fluoxetine is a racemate consisting of both stereoisomers, while the S-form is the dominant serotonin reuptake inhibitor. We found that both isomers show similar activity on the virus. Fluoxetine treatment resulted in a decrease in viral protein expression. Furthermore, Fluoxetine inhibited neither Rabies virus, human respiratory syncytial virus replication nor the Human Herpesvirus 8 or Herpes simplex virus type 1 gene expression, indicating that it acts virus-specific. We see the role of Fluoxetine in the early treatment of SARS-CoV-2 infected patients of risk groups.