bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended Graphical Lasso for Multiple Interaction Networks for High Dimensional Omics Data
Authors: Xu Yang , Jiang Hongmei , Jiang Wenxin 
Published: February 2021

AbstractThere has been a spate of interest in association networks in biological and medical research, for example, genetic interaction networks. In this paper, we propose a novel method, the extended joint hub graphical lasso (EDOHA), to estimate multiple related interaction networks for high dimensional omics data across multiple distinct classes. To be specific, we construct a convex penalized log likelihood optimization problem and solve it with an alternating direction method of multipliers (ADMM) algorithm. The proposed method can also be adapted to estimate interaction networks for high dimensional compositional data such as microbial interaction networks. The performance of the proposed method in the simulated studies shows that EDOHA has remarkable advantages in recognizing class-specific hubs than the existing comparable methods. We also present three applications of real datasets. Biological interpretations of our results confirm those of previous studies and offer a more comprehensive understanding of the underlying mechanism in disease.Author summaryReconstruction of multiple association networks from high dimensional omics data is an important topic, especially in biology. Previous studies focused on estimating different networks and detecting common hubs among all classes. Integration of information over different classes of data while allowing difference in the hub nodes is also biologically plausible. Therefore, we propose a method, EDOHA, to jointly construct multiple interaction networks with capacity in finding different hub networks for each class of data. Simulation studies show the better performance over conventional methods. The method has been demonstrated in three real world data.
Between virus correlations in the outcome of infection across host species: evidence of virus genotype by host species interactions
Authors: Imrie Ryan M. , Roberts Katherine E. , Longdon Ben 
Published: February 2021

AbstractVirus host shifts are a major source of outbreaks and emerging infectious diseases, and predicting the outcome of novel host and virus interactions remains a key challenge for virus research. The evolutionary relationships between host species can explain variation in transmission rates, virulence, and virus community composition between hosts, but the potential for different viruses to interact with host species effects has yet to be established. Here, we measure correlations in viral load of fourCripavirusisolates across experimental infections of 45Drosophilidaehost species. We find positive correlations between every pair of viruses tested, suggesting that broadly susceptible host clades could act as reservoirs and donors for certain types of viruses. Additionally, we find evidence of genotype-by-genotype interactions between viruses and host species, highlighting the importance of both host and virus traits in determining the outcome of virus host shifts. More closely related viruses tended to be more strongly correlated, providing tentative evidence that virus evolutionary relatedness may be a useful proxy for determining the likelihood of novel virus emergence, which warrants further research.Impact SummaryMany new infectious diseases are caused by viruses jumping into novel host species. Estimating the probability that jumps will occur, what the characteristics of new viruses will be, and how they are likely to evolve after jumping to new host species are major challenges. To solve these challenges, we require a detailed understanding of the interactions between different viruses and hosts, or metrics that can capture some of the variation in these interactions. Previous studies have shown that the evolutionary relationships between host species can be used to predict traits of infections in different hosts, including transmission rates and the damage caused by infection. However, the potential for different viruses to influence the patterns of these host species effects has yet to be determined. Here, we use four viruses of insects in experimental infections across 45 different fruit fly host species to begin to answer this question. We find similarities in the patterns of replication and persistence between all four viruses, suggesting susceptible groups of related hosts could act as reservoirs and donors for certain types of virus. However, we also find evidence that different virus genotypes interact in different ways with some host species. Viruses that were more closely related tended to behave in similar ways, and so we suggest that virus evolutionary relatedness may prove to be a useful metric for predicting the traits of novel infections and should be explored further in future studies.
Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology
Authors: Santos Nuno Brito , Vaz da Silva Zoé Enderlin , Gomes Catarina , Reis Celso A. , Amorim Maria João 
Published: February 2021

AbstractClearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infectionin vivo,via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that it exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads but rather on the host resilience to infection and may have direct implications in zoonotic influenza transmissions.Author summaryExacerbated complement activation and immune deregulation are at the basis of several pathologies induced by respiratory viruses. Here, we report that complement decay-accelerating factor (DAF), which inhibits complement activation in healthy cells, increases disease severity upon Influenza A virus (IAV) infection. Remarkably, DAF interaction with IAV proteins, hemagglutinin (HA) and neuraminidase (NA), resulted in excessive complement activation and recruitment of innate and adaptive immune cells, without affecting viral loads. Furthermore, we observed that viral NA directly cleaves DAF and promotes complement activation, providing a possible link between IAV-DAF interaction and pathology. Therefore, our results unveil a novel pathway that could modulate disease severity, which may help to understand the increased pathogenicity of zoonotic and pandemic IAV infections.
Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons
Authors: Pham Andrew H. , Mitchell Jennifer , Botto Sara , Pryke Kara M. , Defilippis Victor R. , Hancock Meaghan H. 
Published: February 2021

AbstractHuman cytomegalovirus (HCMV) microRNAs (miRNAs) significantly rewire host signaling pathways to support the viral lifecycle and regulate host cell responses. Here we show that SMAD3 expression is regulated by HCMV miR-UL22A and contributes to the IRF7-mediated induction of type I IFNs and IFN-stimulated genes (ISGs) in human fibroblasts. Addition of exogenous TGFβ interferes with the replication of a miR-UL22A mutant virus in a SMAD3-dependent manner in wild type fibroblasts, but not in cells lacking IRF7, indicating that downregulation of SMAD3 expression to limit IFN induction is important for efficient lytic replication. These findings uncover a novel interplay between SMAD3 and innate immunity during HCMV infection and highlight the role of viral miRNAs in modulating these responses.Author SummaryCells trigger the interferon (IFN) response to induce the expression of cellular genes that limit virus replication. In turn, viruses have evolved numerous countermeasures to avoid the effects of IFN signaling. Using a microRNA (miRNA) mutant virus we have uncovered a novel means of regulating the IFN response during human cytomegalovirus (HCMV) infection. Lytic HCMV infection induces the production of TGFβ, which binds to the TGFβ receptor and activates the receptor-associated SMAD SMAD3. SMAD3, together with IRF7, induces the expression of IFNβ and downstream IFN-stimulated genes in human fibroblasts. To counteract this, HCMV miR-UL22A, along with other HCMV gene products, directly targets SMAD3 for downregulation. Infection of fibroblasts with a miR-UL22A mutant virus results in enhanced type I IFN production in a SMAD3-dependent manner and the virus is impaired for growth in the presence of TGFβ, but only when both SMAD3 and IRF7 are present, highlighting the unique interaction between TGFβ and innate immune signaling.
Trial-by-trial fluctuations in post-stimulus attention during memory encoding predict subsequent associative context memory performance
Authors: Elshiekh Abdelhalim , Rajah M. Natasha 
Published: February 2021

AbstractEpisodic memory formation rate varies over time partly due to fluctuations in attentional state during memory encoding. Emerging evidence suggests that fluctuations in pre- and/or post-stimulus attention during encoding impact subsequent memory performance. It remains unclear how these fluctuations may differentially impact the subsequent retrieval of items alone, compared to items + their contextual details (associative context memory). In this study, we explored this in 30 healthy younger adults (21-34 years old). We developed the Montreal Attention at Encoding (MAET) task where on each encoding trial, participants responded as quickly as possible to a central fixation cross that expanded in size after a random duration. They then had to encode a picture of an object and its spatial location. Memory for the object-location associations was tested during retrieval. Response time (RT) to the fixation cross presented prior to each object gauged pre-stimulus attention levels on a trial-by-trial basis, while RT to the fixation cross that ensued each object indexed post-stimulus attention levels. Within-subject logistic regressions were used to predict context and item memory performance from pre- and post-stimulus RTs. Results revealed that encoding pre-stimulus attentional levels did not differentially predict context vs. item memory. However, post-stimulus RTs did predict subsequent context retrieval such that, longer post-stimulus RT to the fixation was related to poorer subsequent context retrieval. This study introduces a novel paradigm for investigating the impact of attentional state at encoding on subsequent memory performance and indicate a link between post-stimulus delays in attention-related RT and associative encoding success.
Probe the effect of clustering on EphA2 receptor signaling efficiency by subcellular control of ligand-receptor mobility
Authors: Chen Zhongwen , Oh Dongmyung , Biswas Kabir H. , Zaidel-Bar Ronen , Groves Jay T. 
Published: February 2021

AbstractClustering of ligand:receptor complexes on the cell membrane is widely presumed to have functional consequences for subsequent signal transduction. However, it is experimentally challenging to selectively manipulate receptor clustering without altering other biochemical aspects of the cellular system. Here, we develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly one micron and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions. Applying this approach to characterize the ephrinA1:EphA2 signaling system reveals that EphA2 clustering enhances receptor phosphorylation. Single molecule imaging clearly resolves increased molecular binding dwell time at EphA2 clusters for both Grb2:SOS and NCK:NWASP signaling modules. This type of intracellular comparison enables a substantially higher degree of quantitative analysis than is possible when comparisons must be made between different cells and essentially eliminates the effects of cellular response to ligand manipulation.
The winding roads to adulthood: a twin study
Authors: Rimfeld Kaili , Malancini Margherita , Packer Amy E. , Gidziela Agnieszka , Allegrini Andrea G. , Ayorech Ziada , Smith-Woolley Emily , McMillan Andrew , Ogden Rachel , Dale Philip S. , Eley Thalia C. , Plomin Robert 
Published: February 2021

AbstractIn the 21stcentury, emerging adulthood has stretched from the late teens through the twenties. Although this extended transition to adulthood can create stress, it can also offer opportunities to explore vocations and relationships that provide a better fit to individuals’ proclivities, including their genetic propensities.Here we report the results of the first systematic investigation of genetic and environmental influences on 57 psychological traits covering major issues in emerging adulthood such as aspirations, thoughts and attitudes, relationships and personality. We also investigate how these traits relate to physical and mental health, educational attainment and wellbeing using a sample of nearly 5000 pairs of UK twins aged 21-25 from the Twins Early Development Study.All 57 traits showed significant genetic influence, with an average heritability of 34% (SNP heritability ∼10%). Most of the variance (59% on average) was explained by non-shared environmental influences. These diverse traits were associated with mental health (average correlation .20), wellbeing (.16), physical health (.12) and educational attainment (.06). Shared genetic factors explained the majority of these correlations (∼50%). Together, these emerging adulthood traits explained on average 30% of the variance in the outcomes (range = 8 to 69%), suggesting that these traits relate to the outcomes additively.We conclude that the environmental uncertainties of emerging adulthood in the 21stcentury do not diminish the importance of genetics. As adolescents travel down long and winding roads to adulthood, their trip is substantially influenced by genetic proclivities that nudge them down different paths leading to different destinations.
Characterization of heliorhodopsins detected via functional metagenomics in freshwater Actinobacteria, Chloroflexi and Archaea
Authors: Chazan Ariel , Rozenberg Andrey , Mannen Kentaro , Nagata Takashi , Tahan Ran , Yaish Shir , Larom Shirley , Inoue Keiichi , Béjà Oded , Pushkarev Alina 
Published: February 2021

AbstractRhodopsins are widespread in microbes residing in diverse aquatic environments across the globe. Recently, a new unusual rhodopsin family, the heliorhodopsins (HeRs), was discovered, distributed among diverse bacteria, archaea, eukarya and even viruses. Here, using functional metagenomics on samples from Lake Ha’Hula and Ein Afek reserve, we found and characterized ten HeRs representing divergent members of the family. The expressed HeRs absorb light in the green and yellow wavelengths and originate from Actinobacteria, Chloroflexi and Archaea. The photocycle of the HeR from Chloroflexi revealed a low accumulation of the M-intermediate that we connect to the lack of two conserved histidine residues in transmembrane helices 1 and 2 in this protein. Another of HeR, from Actinobacteria, exhibited an unusually fast photocycle (166 ms, 5 times faster than HeR-48C12). To further explore the still unresolved question of the HeR function, we performed an analysis of protein families among genes neighboring HeRs, in our clones and thousands of other microbes. This analysis revealed a putative connection between HeRs and genes involved in oxidative stress. At the same time, very few protein families were found to distinguish genes surrounding prokaryotic HeRs from those surrounding rhodopsin pumps. The strongest association was found with the DegV family involved in activation of fatty acids and uncharacterized family DUF2177, which allowed us to hypothesize that HeRs are involved in membrane lipid remodeling. This work further establishes functional metagenomics as a simple and fruitful method of screening for new rhodopsins.SignificanceThe recently discovered divergent rhodopsin family of heliorhodopsins is abundant in freshwater environments. In this study, we sampled a habitat rich in dissolved organic matter to increase our chances of finding spectrally shifted rhodopsins. Using functional metagenomics, diverse heliorhodopsins absorbing green and yellow light were discovered. The metagenomic clones originated from diverse prokaryotic groups: Actinobacteria, Chloroflexi and even Archaea, emphasizing the versatility of theE. coliexpression system used. Photocycles of representative heliorhodopsins were measured and exhibited diverse kinetic characteristics. Analysis of genes neighboring heliorhodopsins in diverse prokaryotes revealed their putative connection to membrane lipid re-modeling and oxidative stress. Our findings suggest that functional metagenomics is a productive method for the discovery of new and diverse rhodopsins.
Distinct metabolic flux modes through the tricarboxylic acid cycle in mesophyll and guard cells revealed by GC-MS-based13C-positional isotopomer analysis
Authors: G. Daubermann André , F. Lima Valéria , Schwarzländer Markus , Erban Alexander , Kopka Joachim , Fernie Alisdair R. , Anjos Leticia dos , Daloso Danilo M. 
Published: February 2021

Summary13C-Metabolic flux analysis (13C-MFA) have greatly contributed to revealing the regulation of plant metabolism. However, mass spectrometry (MS) approaches have hitherto been limited in their power to deduce flux information due to lack of positional information.Here we established an MS-based13C-positional isotopomer labelling approach and performed a multi-species/cell-types analysis based on previous13C-MFA to compare flux modes through the tricarboxylic acid (TCA) cycle and associated pathways in mesophyll (MCs) and guard cells (GCs).Both cell types showed high13C-enrichment in pyruvate. However, GCs and sink MCs, but not source MCs showed high13C-incorporation into Glu/Gln following provision of13C-sucrose. Only GCs showed higher13C-enrichment in the carbon 1 atom of Gln, which is derived from PEPc-mediated CO2fixation. Increased13C-enrichment in the carbon 1 of Glu was also observed in bothtrxo1andntra ntrbmutants, but not in wild type Arabidopsis plants, following provision of13C-glucose.Our results suggest that the mitochondrial thioredoxin system restricts the fluxes from PEPc and glycolysis to Glu in illuminated MCs and reveal that fluxes throughout the TCA cycle of GCs resemble those of sink MCs but operate different non-cyclic flux modes to support Gln synthesis in the light.
A mixture of generative models strategy helps humans generalize across tasks
Authors: Herce Castañón Santiago , Cardoso-Leite Pedro , Altarelli Irene , Green C. Shawn , Schrater Paul , Bavelier Daphne 
Published: February 2021

AbstractWhat role do generative models play in generalization of learning in humans? Our novel multi-task prediction paradigm—where participants complete four sequence learning tasks, each being a different instance of a common generative family—allows the separate study ofwithin-task learning(i.e., finding the solution to each of the tasks), andacross-task learning(i.e., learning a task differently because of past experiences). The very first responses participants make in each task are not yet affected by within-task learning and thus reflect their priors. Our results show that these priors change across successive tasks, increasingly resembling the underlying generative family. We conceptualize multi-task learning as arising from a mixture-of-generative-models learning strategy, whereby participants simultaneously entertain multiple candidate models which compete against each other to explain the experienced sequences. This framework predicts specific error patterns, as well as a gating mechanism for learning, both of which are observed in the data.
Drought is a stronger driver of plant morphology and nutritional composition than warming in two common pasture species
Authors: Catunda Karen L. M. , Churchill Amber C. , Zhang Haiyang , Power Sally A. , Moore Ben D. 
Published: February 2021

AbstractUnder warmer and drier future conditions, global livestock and dairy production are threatened by impacts on the productivity and nutritional quality of pastures. However, morphological and nutritional adjustments within plants in response to warming and drought vary among species and less is known how these relate to production and forage quality. To investigate this, we grew two common pasture species, tall fescue (Festuca arundinacea: grass) and lucerne (Medicago sativa: legume), in a climate-controlled facility, under different temperatures (ambient and elevated) and watering regimes (well-watered and droughted). We found that drought had a strong negative impact on biomass production, morphology and nutritional quality while warming only significantly affected both species when response metrics were considered in concert, although to a lesser degree than the drought. Furthermore, interactions between warming and drought were only seen for lucerne, with the greatest reduction in biomass and most dead material and dry matter content. In tall fescue, drought had bigger impacts on nutritional composition than morphological traits, while in lucerne, drought affected all morphological traits and most nutritional parameters. These findings suggest that in future climate scenarios, drought may be a stronger driver of changes in the morphology and nutritional composition of pasture grasses and legumes, compared to modest levels of warming.