bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Drug-Drug Interaction Prediction Using Deep Attention Neural Networks
Authors: Liu Shichao , Zhang Yang , Cui Yuxin , Qiu Yang , Deng Yifan , Zhang Wen , Zhang Zhongfei 
Published: March 2021

AbstractDrug-drug interactions are one of the main concerns in drug discovery. Accurate prediction of drug-drug interactions plays a key role in increasing the efficiency of drug research and safety when multiple drugs are c o-prescribed. With various data sources that describe the relationships and properties between drugs, the comprehensive approach that integrates multiple data sources would be considerably effective in making high-accuracy prediction. In this paper, we propose a Deep Attention Neural Network based Drug-Drug Interaction prediction framework, abbreviated as DANN-DDI, to predict unobserved drug-drug interactions. First, we construct multiple drug feature networks and learn drug representations from these networks using the graph embedding method; then, we concatenate the learned drug embeddings and design an attention neural network to learn representations of drug-drug pairs; finally, we adopt a deep neural network to accurately predict drug-drug interactions. The experimental results demonstrate that our model DANN-DDI has improved prediction performance compared with state-of-the-art methods. Moreover, the proposed model can predict novel drug-drug interactions and drug-drug interaction-associated events.
Florigen governs shoot regeneration
Authors: Kutsher Yaarit , Fisler Michal , Faigenboim Adi , Reuveni Moshe 
Published: March 2021

AbstractIt is widely known that during the reproductive stage (flowering), plants do not root well. Most protocols of shoot regeneration in plants utilize juvenile tissue. Adding these two realities together encouraged us to studied the role of florigen in shoot regeneration. Mature tobacco tissue that expresses the endogenous tobacco florigen mRNA regenerates poorly, while juvenile tissue that does not express the florigen regenerates shoots well. Inhibition of Nitric Oxide (NO) synthesis reduced shoot regeneration as well as promoted flowering and increased tobacco florigen level. In contrast, the addition of NO (by way of NO donor) to the tissue increased regeneration, delayed flowering, reduced tobacco florigen mRNA. Ectopic expression of florigen genes in tobacco or tomato decreased regeneration capacity significantly. Overexpression pearPcFT2gene increased regeneration capacity. During regeneration, florigen mRNA was not changed. We conclude that florigen presence in mature tobacco leaves reduces roots and shoots regeneration and is the possible reason for the age-related decrease in regeneration capacity.
Targeting CISH enhances natural cytotoxicity receptor signaling and reduces NK cell exhaustion to improve solid tumor immunity
Authors: Bernard P-L. , Delconte R. B. , Pastor S. , Laletin V. , Costa Da Silva C. , Goubard A. , Josselin E. , Castellano R. , Krug A. , Vernerey J. , Devillier R. , Olive D. , Verhoeyen E. , Vivier E. , Huntington N. D. , Nunès J. A. , Guittard G. 
Published: March 2021

AbstractCytokine inducible SH2-containing protein (CISH) is a natural killer (NK) cell negative regulator of cytokine signaling pathway. To further understand CISH functions in NK cells, we developed a conditionalCish-deficient mouse model in NK cells (Cishfl/flNcr1Ki/+). We detected no developmental or homeostatic difference in NK cells.However, global gene expression ofCishfl/flNcr1Ki/+NK cells compared toCish+/+Ncr1Ki/+NK cells revealed upregulation of pathways and genes associated with NK cell cycling and activation. We show that CISH does not only regulate interleukin-15 (IL-15) signaling pathways but also natural cytotoxicity receptors (NCR) pathways. Indeed, CISH protein expression level increases upon NCR triggering. PrimedCishfl/flNcr1Ki/+NK cells display increased activation upon NCR stimulation.Cishfl/flNcr1Ki/+NK cells display lower activation thresholds andCishfl/flNcr1Ki/+mice are more resistant to tumor metastasis. Remarkably, we found thatCishfl/flNcr1Ki/+mice were also more resistant to primary breast cancer growth in addition to superior control of spontaneous tumor metastasis. CISH deletion favors NK cell accumulation to the primary tumor, optimizes NK cell killing properties and decreases TIGIT immune checkpoint receptor expression, limiting NK cell exhaustion. Finally, we argue that specifically enhancing NK cell function is sufficient to boost anti-tumor response to both primary and secondary tumor models. Using CRISPRi, we then targetedCISHin human NK-92 or primary NK cells. According to the results in our mouse model, CISH deletion favors NCR signaling and anti-tumor functions in human NK cells. Our results validate CISH as an emerging therapeutic target to enhance NK cell immunotherapy.
Loss of glutamate transportereaat2aleads to aberrant neuronal excitability, recurrent epileptic seizures and hypoactivity
Authors: Hotz Adriana L. , Jamali Ahmed , Rieser Nicolas N. , Niklaus Stephanie , Aydin Ecem , Myren-Svelstad Sverre , Lalla Laetitia , Jurisch-Yaksi Nathalie , Yaksi Emre , Neuhauss Stephan C.F. 
Published: March 2021

ABSTRACTAstroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Hence, an impairment in EAAT2 function could lead to an imbalanced neural network excitability. Here, we investigated the functional alterations of neuronal and astroglial networks associated with the loss of function in the astroglia predominanteaat2agene in zebrafish. We observed thateaat2a-/-mutant zebrafish larvae display recurrent spontaneous and light-induced seizures in neurons and astroglia, which coincide with an abrupt increase in extracellular glutamate levels. In stark contrast to this hyperexcitability, basal neuronal and astroglial activity was surprisingly reduced ineaat2a-/-mutant animals, which manifested in decreased overall locomotion. Our results reveal an essential and mechanistic contribution of EAAT2a in balancing brain excitability, and its direct link to epileptic seizures.
Differential detection ofTomato mosaic virus(ToMV) andTomato brown rugose fruit virus(ToBRFV) using CRISPR-Cas12
Authors: Alon Dan , Hak Hagit , Bornstein Menachem , Pines Gur , Spiegelman Ziv 
Published: March 2021

AbstractCRISPR/Cas12-based detection is a novel approach for efficient, sequence-specific identification of viruses. Here we adopt the use of CRISPR/Cas12a to identify theTomato brown rugose fruit virus(ToBRFV), a new and emergingTobamoviruscausing substantial damage to the global tomato industry. Specific guide RNAs (gRNAs) were designed to detect either ToBRFV or the closely relatedTomato mosaic virus(ToMV). This technology enabled the differential detection of ToBRFV and ToMV. Sensitivity assays revealed that viruses can be detected from 15-30 ng of RT-PCR product, and that specific detection could be achieved from a mix of ToMV and ToBRFV. In addition, we show that this method enabled the identification of ToBRFV in samples collected from commercial greenhouses. These results demonstrate a new method for species-specific detection of plant viruses. This could provide a platform for the development of efficient and user-friendly ways to distinguish between closely related strains and resistance-breaking pathogens.
Parasitic wasps do not lack lipogenesis
Authors: Ruther Joachim , Prager Lorena , Pokorny Tamara 
Published: March 2021

AbstractFatty acids are crucial primary metabolites for virtually any creature on earth. Therefore, most organisms do not rely exclusively on nutritional supply with fatty acids but have the ability to synthesize fatty acids and triacylglycerides de novo from carbohydrates, a process called lipogenesis. The ubiquity of lipogenesis has been questioned by a series of studies reporting that many parasitic wasps (parasitoids) do not accumulate lipid mass despite having unlimited access to sugar. This has been interpreted as an evolutionary metabolic trait loss in parasitoids. Here, we demonstrate de novo biosynthesis of fatty acids from13C-labeled α-D-glucose in eleven species of parasitoids from six families. We furthermore show with the model organismNasonia vitripennisthat lipogenesis occurs even when lipid reserves are still intact, but relative13C-incorporation rates increase in females with widely depleted fat reserves. Therefore, we conclude that the presumed “lack of lipogenesis” in parasitoids needs to be re-evaluated.
Dietary habits of free-ranging banded langur (Presbytis femoralis) in a secondary-human modified forest in Johor, Malaysia
Authors: Najmuddin Mohd Faudzir , Haris Hidayah , Norazlimi Noratiqah , Ruslin Farhani , Matsuda Ikki , Md-Zain Badrul Munir , Abdul-Latiff Muhammad Abu Bakar 
Published: March 2021

ABSTRACTBanded langurs,Presbytis femoralis, are distributed in southern Peninsular Malaysia, i.e., Johor and its borders including Singapore. It has been estimated that there are only < 250 mature individuals ofP. femoralisin Malaysia and Singapore, and it is currently assessed as Critically Endangered. The dietary information ofP. femoralisand even other closely related species has rarely been reported. This study, therefore, aimed to describe their dietary habits and discuss interaction between their feeding behaviour and its surrounding. This study was conducted from February to November 2018, with 15 sampling days each month. We collected a total of 186 sighting hours, using a scan sampling method with 10-min intervals, on a five-langur focal group. We have identified 29 species with 47 items consumed by the banded langur, mostly young leaves (51 %) followed by fruits (45 %), and flowers (3.8 %). The study group spent slightly more time consuming non-cultivated plants but relied on cultivated plants for the fruits. Over 75% of fruit feeding involved consuming cultivar plants; in most cases (73%), they ate only the pulp, not the seeds. Since the cultivated plants was planted in human settlement, there is an urgent need to implement conservation measures to untangle the human-langur conflicts for instance, reforestation of a buffer region using non-cultivated plants. There is a potential for building upon our new findings with more detailed investigations, such as more extensive ecological factors influencing the dietary adaptation which would be necessary to support conservation efforts and management decisions of this species.
A millennium of increasing ecosystem diversity until the mid-20thcentury
Authors: Martins Inês S. , Dornelas Maria , Vellend Mark , Thomas Chris D. 
Published: March 2021

AbstractLand-use change is widely regarded as a simplifying and homogenising force in nature. In contrast, analysing global land-use reconstructions from the 10thto 20thcenturies, we found progressive increases in the number, evenness, and diversity of ecosystems (including human-modified land-use types) across the globe. Ecosystem diversity increased more rapidly after ∼1700CE, then slowed or partially reversed (depending on the metric) following the mid-20thcentury acceleration of human impacts. Differentiation also generally increased across space, with homogenization only evident in the presence-absence analysis of ecosystem types at the global scale. Our results suggest that human land-use changes have primarily driven increases in ecosystem diversity over the last millennium.
Fitness costs and benefits of gene expression plasticity in rice under drought
Authors: Groen Simon C. , Hamann Elena , Ćalić Irina , Cochran Colleen , Konshok Rachel , Purugganan Michael D. , Franks Steven J. 
Published: March 2021

AbstractGenome-wide gene expression changes in response to environmental variability have been widely documented, but we lack detailed and comprehensive understanding of the interplay between this form of phenotypic plasticity and natural selection. Selection on expression plasticity may be limited by environment-specific costs, and plasticity may in turn affect selection on baseline expression levels. Here, we address this fundamental issue by measuring selection on drought-induced plasticity of leaf transcripts in field-grown rice populations. Selection disfavored switching off housekeeping genes under drought. This stress-induced dysregulation did not constrain selection on baseline transcript levels, suggesting compensatory evolution may be possible. Selection rarely acted strongly on individual transcripts but worked polygenically on gradual (continuous) plasticity of co-expressed gene modules regulating photosynthesis via known drought-responsive transcription factors. Finally, selection was tied to inefficient gene architectural features and metabolic costs of expression. Our study provides a genome-wide view of costs and benefits of gene expression plasticity.
Population differences in the length and early-life dynamics of telomeres among European pied flycatchers
Authors: Kärkkäinen Tiia , Laaksonen Toni , Burgess Malcolm , Cantarero Alejandro , Martínez-Padilla Jesús , Potti Jaime , Moreno Juan , Thomson Robert L. , Tilgar Vallo , Stier Antoine 
Published: March 2021

AbstractTelomere length and shortening rate are increasingly used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Both early-life conditions and growth, and later-life stressors can create variation in telomere shortening rate. Studies on between- population telomere length and dynamics are scarce, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. The pied flycatcher (Ficedula hypoleuca) is a passerine bird breeding across Eurasia (from Spain to western Siberia) and migrating through the Iberian Peninsula to spend the non-breeding period in sub-Saharan Africa. Thus, different populations show marked differences in migration distance. We studied the large-scale variation of telomere length and early-life dynamics in the pied flycatcher by comparing six European populations across a north- south gradient (Finland, Estonia, England, and Spain) predicting negative effect of migration distance on adult telomere length, and of nestling growth on nestling telomere dynamics. There were clear population differences in telomere length, with English birds from mid-latitudes having the longest telomeres. Telomere length did not thus show consistent latitudinal variation and was not linearly linked to differences in migration distance. Early-life telomere shortening rate tended to vary between populations. Fast growth was associated with shorter telomeres in the early life, but faster nestling growth affected telomeres more negatively in northern than southern populations. While the sources of between-population differences in telomere-related biology remain to be more intensively studied, our study illustrates the need to expand telomere studies at the between-population level.
Micrometer-resolution reconstruction and analysis of whole mouse brain vasculature by synchrotron-based phase-contrast tomographic microscopy
Authors: Miettinen Arttu , Zippo Antonio G. , Patera Alessandra , Bonnin Anne , Shahmoradian Sarah H. , Biella Gabriele E. M. , Stampanoni Marco 
Published: March 2021

AbstractNervous tissue metabolism is mainly supported by the dense thread of blood vessels which mainly provides fast supplies of oxygen and glucose. Recently, the supplying role of the brain vascular system has been examined in major neurological conditions such as the Alzheimer’s and Parkinson’s diseases. However, to date, fast and reliable methods for the fine level microstructural extraction of whole brain vascular systems are still unavailable. We present a methodological framework suitable for reconstruction of the whole mouse brain cerebral microvasculature by X-ray tomography with the unprecedented pixel size of 0.65 μm. Our measurements suggest that the resolving power of the technique is better than in many previous studies, and therefore it allows for a refinement of current measurements of blood vessel properties. Relevant insights emerged from analyses characterizing the regional morphology and topology of blood vessels. Specifically, vascular diameter and density appeared non-homogeneously distributed among the brain regions suggesting preferential sites for high-demanding metabolic requirements. Also, topological features such as the vessel branching points were non-uniformly distributed among the brain districts indicating that specific architectural schemes are required to serve the distinct functional specialization of the nervous tissue. In conclusion, here we propose a combination of experimental and computational method for efficient and fast investigations of the vascular system of entire organs with submicrometric precision.
Single-cell transcriptome profiling simulation reveals the impact of sequencing parameters and algorithms on clustering
Authors: Liu Yunhe , Shi Bisheng , Wu Aoshen , Peng Xueqing , Yuan Zhenghong , Liu Gang , Liu Lei 
Published: March 2021

ABSTRACTDespite of scRNA-seq analytic algorithms developed, their performance for cell clustering cannot be quantified due to the unknown “true” clusters. Referencing the transcriptomic heterogeneity of cell clusters, a “true” mRNA number matrix of cell individuals was defined as ground truth. Based on the matrix and real data generation procedure, a simulation program (SSCRNA) for raw data was developed. Subsequently, the consistence between simulated data and real data was evaluated. Furthermore, the impact of sequencing depth, and algorithms for analyses on cluster accuracy was quantified. As a result, the simulation result is highly consistent with that of the real data. It is found that mis-classification rate can be attributed to multiple reasons on current scRNA platforms, and clustering accuracy is not only sensitive to sequencing depth increasement, but can also be reflected by the position of the cluster on TSNE plot. Among the clustering algorithms, Gaussian normalization method is more appropriate for current workflows. In the clustering algorithms, k-means&louvain clustering method performs better in dimension reduced data than full data, while k-means clustering method is stable under both situations. In conclusion, the scRNA simulation algorithm developed restores the real data generation process, discovered impact of parameters on mis-clustering, compared the normalization/clustering algorithms and provided novel insight into scRNA analyses.
Bloom syndrome helicase contributes to germ line development and longevity in zebrafish
Authors: Annus Tamás , Müller Dalma , Jezsó Bálint , Ullaga György , Harami Gábor M. , Orbán László , Kovács Mihály , Varga Máté 
Published: March 2021

AbstractRecQ helicases - also known as the ‘guardians of the genome’ - play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis and shortened life expectancy brought on by genomic instability. We show that zebrafishblmmutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlikefancgenes andrad51, however,blmappears to effect its function independent oftp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.
Climate Change Controls Phosphorus Transport from the Watershed into Lake Kinneret (Israel)
Authors: Gophen Moshe 
Published: March 2021

AbstractPart of the Kinneret watershed, the Hula Valley, was modified from wetlands – shallow lake for agricultural cultivation. Enhancement of nutrient fluxes into Lake Kinneret was predicted. Therefore, a reclamation project was implemented and eco-tourism partly replaced agriculture. Since the mid-1980s, regional climate change has been documented. Statistical evaluation of long-term records of TP (Total Phosphorus) concentrations in headwaters and potential resources in the Hula Valley was carried out to identify efficient management design targets. Significant correlation between major headwater river discharge and TP concentration was indicated, whilst the impact of external fertilizer loads and 50,000 winter migratory cranes was probably negligible. Nevertheless, confirmed severe bdamage to agricultural crops carried out by cranes led to their maximal deportation and optimization of their feeding policy. Consequently, the continuation of the present management is recommended.
Integration of plant carbohydrate dynamics by Fourier polynomials
Authors: Seydel Charlotte , Biener Julia , Brodsky Vladimir , Eberlein Svenja , Nägele Thomas 
Published: March 2021

AbstractQuantification of system dynamics is a central aim of mathematical modelling in biology. Defining experimentally supported functional relationships between molecular entities by mathematical terms enables the application of computational routines to simulate and analyse the underlying molecular system. In many fields of natural sciences and engineering, trigonometric functions are applied to describe oscillatory processes. As biochemical oscillations occur in many aspects of biochemistry and biophysics, Fourier analysis of metabolic functions promises to quantify, describe and analyse metabolism and its reaction towards environmental fluctuations. Here, Fourier polynomials were developed from experimental time-series data and combined with block diagram simulation of plant metabolism to study heat shock response of photosynthetic CO2assimilation and carbohydrate metabolism. Findings suggest that increased capacities of starch biosynthesis stabilize photosynthetic CO2assimilation under transient heat exposure. Among soluble sugars, fructose concentrations were observed to fluctuate least under heat exposure which might be the consequence of high respiration rates under elevated temperature. Finally, Col-0 and two mutants ofArabidopsis thalianawith deficiencies in starch and sucrose metabolism were discriminated by fundamental frequencies of Fourier polynomials across different experiments. This suggests balance modelling based on Fourier polynomials as a suitable approach for mathematical analysis of dynamic plant-environment interactions.HighlightA balance equation model is developed to quantify effects of transient heat exposure on plant carbon assimilation. The model is based on Fourier polynomials for quantitative assessment of system dynamics.