bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feeling left out or just surprised? Neural correlates of social exclusion and over-inclusion in adolescence
Authors: Cheng Theresa W. , Vijayakumar Nandita , Flournoy John C. , Op de Macks Zdena , Peake Shannon J. , Flannery Jessica E. , Mobasser Arian , Alberti Sarah L. , Fisher Philip A. , Pfeifer Jennifer H. 
Published: January 2019

AbstractSocial belonging is an important human drive that influences mood and behavior. Neural responses to social exclusion are well-characterized, but the specificity of these responses to processing rejection-related affective distress is unknown. The present study compares neural responses to exclusion and over-inclusion, a condition that similarly violates fairness expectations but does not involve rejection, with a focus on implications for models of dorsal anterior cingulate cortex (dACC) and anterior insula (AI) function. In an fMRI adaptation of the Cyberball paradigm with adolescents 11.1-17.7 years of age (N=69), we employed parametric modulators to examine scaling of neural signal with cumulative exclusion and inclusion events, an approach that overcomes arbitrary definitions of condition onsets/offsets imposed on fluid, continuous gameplay. We identified positive scaling of dACC and posterior insula response with cumulative exclusion events, but these same regions exhibited trending signal decreases with cumulative inclusion events. Furthermore, areas within the dACC and insula also responded to context incongruency (throws to the participant in the exclusion run; throws between computer players in the over-inclusion run). Taken together, these findings caution against interpretations that responses in these regions uniquely reflect aspects of affective distress within social rejection paradigms. We further identified that the left ventrolateral PFC, rostromedial PFC, and left intraparietal sulcus responded similarly to cumulative exclusion and inclusion. These findings shed light on which neural regions exhibit patterns of differential sensitivity to exclusion or over-inclusion, as well as those that are more broadly engaged by both types of social interaction.
Enhancer viruses and a transgenic platform for combinatorial cell subclass-specific labeling
Authors: Graybuck Lucas T. , Daigle Tanya L. , Sedeño-Cortés Adriana E. , Walker Miranda , Kalmbach Brian , Lenz Garreck H. , Nguyen Thuc Nghi , Garren Emma , Kim Tae Kyung , Siverts La’ Akea , Bendrick Jacqueline L. , Zhou Thomas , Mortrud Marty , Yao Shenqin , Cetin Ali H. , Larsen Rachael , Esposito Luke , Gore Bryan , Szelenyi Eric , Morin Elyse , Mich John K. , Dee Nick , Goldy Jeff , Smith Kimberly , Yao Zizhen , Gradinaru Viviana , Sunkin Susan M. , Lein Ed , Levi Boaz P. , Ting Jonathan T. , Zeng Hongkui , Tasic Bosiljka 
Published: January 2019

SummaryThe rapid pace of cell type identification by new single-cell analysis methods has not been met with efficient experimental access to the newly discovered types. To enable flexible and efficient access to specific neural populations in the mouse cortex, we collected chromatin accessibility data from individual cells and clustered the single-cell data to identify enhancers specific for cell classes and subclasses. When cloned into adeno-associated viruses (AAVs) and delivered to the brain by retro-orbital injections, these enhancers drive transgene expression in specific cell subclasses in the cortex. We characterize several enhancer viruses in detail to show that they result in labeling of different projection neuron subclasses in mouse cortex, and that one of them can be used to label the homologous projection neuron subclass in human cortical slices. To enable the combinatorial labeling of more than one cell type by enhancer viruses, we developed a three-color Cre-, Flp- and Nigri-recombinase dependent reporter mouse line,Ai213. The delivery of three enhancer viruses driving these recombinases via a single retroorbital injection into a singleAi213transgenic mouse results in labeling of three different neuronal classes/subclasses in the same brain tissue. This approach combines unprecedented flexibility with specificity for investigation of cell types in the mouse brain and beyond.
Identifying Genomic Islands with Deep Neural Networks
Authors: Assaf Rida , Xia Fangfang , Stevens Rick 
Published: January 2019

AbstractBackgroundHorizontal gene transfer is the main source of adaptability for bacteria, through which genes are obtained from different sources including bacteria, archaea, viruses, and eukaryotes. This process promotes the rapid spread of genetic information across lineages, typically in the form of clusters of genes referred to as genomic islands (GIs). Different types of GIs exist, often classified by the content of their cargo genes or their means of integration and mobility. Various computational methods have been devised to detect different types of GIs, but no single method currently is capable of detecting all GIs.ResultsWe propose a method, which we call Shutter Island, that uses a deep learning model (Inception V3, widely used in computer vision) to detect genomic islands. The intrinsic value of deep learning methods lies in their ability to generalize. Via a technique called transfer learning, the model is pre-trained on a large generic dataset and then re-trained on images that we generate to represent genomic fragments. We demonstrate that this image-based approach generalizes better than the existing tools.ConclusionsWe used a deep neural network and an image-based approach to detect the most out of the correct GI predictions made by other tools, in addition to making novel GI predictions. The fact that the deep neural network was retrained on only a limited number of GI datasets and then successfully generalized indicates that this approach could be applied to other problems in the field where data is still lacking or hard to curate.
Waterborne, abiotic and other indirectly transmitted (W.A.I.T.) infections are defined by the dynamics of free-living pathogens and environmental reservoirs
Authors: Miller-Dickson Miles D. , Meszaros Victor A. , Baffour-Awuah Francis , Almagro-Moreno Salvador , Brandon Ogbunugafor C. 
Published: January 2019

AbstractWhile the ecology of infectious disease is a rich field with decades worth of empirical evidence and theory, there are aspects that remain relatively under-examined. One example is the importance of the free-living survival stage of certain pathogens, and especially is cases where they are transmitted indirectly between hosts through an environmental reservoir intermediate. In this study, we develop an integrated, broadly applicable mathematical method to examine diseases fitting this description—the waterborne, abiotic and other indirectly transmitted (W.A.I.T.) infection framework. To demonstrate its utility, we construct realistic models of two very different epidemic scenarios: cholera in a densely populated setting with limited access to clean drinking water and hepatitis C virus in an urban setting of injection-drug users. Using these two exemplars, we find that the W.A.I.T. model fortifies the centrality of reservoir dynamics in the “sit and wait” infection strategy, and provides a way to simulate a diverse set of intervention strategies.
In vitro implementation of robust gene regulation in a synthetic biomolecular integral controller
Authors: Agrawal Deepak K. , Marshall Ryan , Noireaux Vincent , Sontag Eduardo D 
Published: January 2019

ABSTRACTFeedback mechanisms play a critical role in the maintenance of cell homeostasis in the presence of disturbances and uncertainties. Motivated by the need to tune the dynamics and improve the robustness of synthetic gene circuits, biological engineers have proposed various designs that mimic natural molecular feedback control mechanisms. However, practical and predictable implementations have proved challenging because of the complexity of synthesis and analysis of complex biomolecular networks. Here, we analyze and experimentally validate a first synthetic biomolecular controller executedin vitro.The controller is based on the interaction between a sigma and an anti-sigma factor, which ensures that gene expression tracks an externally imposed reference level, and achieves this goal even in the presence of disturbances. Our design relies upon an analog of the well-known principle of integral feedback in control theory. We implement the controller in anEscherichia colicell-free transcription-translation (TXTL) system, a platform that allows rapid prototyping and implementation. Modeling and theory guide experimental implementation of the controller with well-defined operational predictability.
A role for ATP Citrate Lyase in cell cycle regulation during myeloid differentiation
Authors: Rhee Jess , Solomon Lauren A. , DeKoter Rodney P. 
Published: January 2019

AbstractDifferentiation of myeloid progenitor cells into macrophages is accompanied by increased PU.1 concentration and increasing cell cycle length, culminating in cell cycle arrest. Induction of PU.1 expression in a cultured myeloid cell line expressing low PU.1 concentration results in decreased levels of mRNA encoding ATP-Citrate Lyase (ACL) and cell cycle arrest. ACL is an essential enzyme for generating acetyl-CoA, a key metabolite for the first step in fatty acid synthesis as well as for histone acetylation. We hypothesized that ACL may play a role in cell cycle regulation in the myeloid lineage. In this study, we found that acetyl-CoA or acetate supplementation was sufficient to rescue cell cycle progression in cultured BN cells treated with an ACL inhibitor or induced for PU.1 expression. Acetyl-CoA supplementation was also sufficient to rescue cell cycle progression in BN cells treated with a fatty acid synthase (FASN) inhibitor. We demonstrated that acetyl-CoA was utilized in both fatty acid synthesis and histone acetylation pathways to promote proliferation. Finally, we found thatAclymRNA transcript levels decrease during normal macrophage differentiation from bone marrow precursors. Our results suggest that regulation of ACL activity is a potentially important point of control for cell cycle regulation in the myeloid lineage.
Automated Brain Masking of Fetal Functional MRI
Authors: Rutherford Saige , Sturmfels Pascal , Angstadt Mike , Hect Jasmine , Wiens Jenna , van den Heuval Marion , Scheinost Dustin , Thomason Moriah , Sripada Chandra 
Published: January 2019

AbstractFetal resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a critical new approach for characterizing brain development before birth. Despite rapid and widespread growth of this approach, at present we lack neuroimaging processing pipelines suited to address the unique challenges inherent in this data type. Here, we solve the most challenging processing step, rapid and accurate isolation of the fetal brain from surrounding tissue across thousands of non-stationary 3D brain volumes. Leveraging our library of 1,241 manually traced fetal fMRI images from 207 fetuses (gestational age 24-39 weeks, M=30.9, SD=4.2), we trained a Convolutional Neural Network (CNN) that achieved excellent performance across two held-out test sets from separate scanners and populations. Furthermore, we unite the auto-masking model with additional fMRI preprocessing steps from existing software and provide insight into our adaptation of each step. This work represents an initial advancement towards a fully comprehensive, open source workflow for fetal functional MRI data preprocessing.
Detection of cross-contamination and strong mitonuclear discordance in two species groups of sawfly genus Empria (Hymenoptera, Tenthredinidae)
Authors: Prous Marko , Min Lee Kyung , Mutanen Marko 
Published: January 2019

AbstractIn several sawfly taxa strong mitonuclear discordance has been observed, with nuclear genes supporting species assignments based on morphology, whereas the barcode region of the mitochondrial COI gene suggesting different relationships. As previous studies were based on only few nuclear genes, the causes and the degree of mitonuclear discordance remain ambiguous. Here, we obtain genomic-scale ddRAD data together with Sanger sequencing of mitochondrial COI and two to three nuclear protein coding genes to investigate species limits and mitonuclear discordance in two closely related species groups within the sawfly genusEmpria. As found previously based on nuclear ITS and mitochondrial COI sequences, species are in most cases supported as monophyletic based on previous and new nuclear data reported here, but not based on mitochondrial COI. This mitonuclear discordance can be explained by occasional mitochondrial introgression with little or no nuclear gene flow, a pattern that might be common in haplodiploid taxa with slowly evolving mitochondrial genomes. Some species inE. immersagroup are not recovered as monophyletic also based on nuclear data, but this could partly be because of unresolved taxonomy. Preliminary analyses of ddRAD data did not recover monophyly ofE. japonicawithinE. longicornisgroup (three Sanger sequenced nuclear genes strongly supported monophyly), but closer examination of the data and additional Sanger sequencing suggested that both specimens were substantially (possibly 10–20% of recovered loci) cross-contaminated. A reason could be due to specimen identification tag jumps during sequencing library preparation of pooled specimens that in previous studies have been shown to affect up to 2.5% of the sequenced reads. We provide an R script to examine patterns of identical loci among the specimens and estimate that cross-contamination rate is not unusually high for our ddRAD dataset as a whole (based on counting identical sequences betweenimmersaandlongicornisgroups that are well separated from each other and probably do not hybridise). The high rate of cross-contamination for bothE. japonicaspecimens might be explained by small number of recovered loci (~1000) compared to most other specimens (>10 000 in some cases) because of poor sequencing results. We caution drawing unexpected biological conclusions when closely related specimens are pooled before sequencing and tagged only at one end of the molecule or at both ends using unique combination of limited number of tags (less than the number of specimens).
Alpha-Synuclein is a Target of Fic-mediated Adenylylation/AMPylation: Implications for Parkinson’s Disease
Authors: Sanyal Anwesha , Dutta Sayan , Chandran Aswathy , Koller Antonius , Camara Ali , Watson Ben G. , Sengupta Ranjan , Ysselstein Daniel , Montenegro Paola , Cannon Jason , Rochet Jean-Christophe , Mattoo Seema 
Published: January 2019

ABSTRACTDuring disease, cells experience various stresses that manifest as an accumulation of misfolded proteins and eventually lead to cell death. To combat this stress, cells activate a pathway called UPR (Unfolded Protein Response) that functions to maintain ER (endoplasmic reticulum) homeostasis and determines cell fate. We recently reported a hitherto unknown mechanism of regulating ER stress via a novel post-translational modification (PTM) called Fic-mediated Adenylylation/AMPylation. Specifically, we showed that the human Fic (filamentation induced by cAMP) protein, HYPE/FicD, catalyzes the addition of an AMP (adenosine monophosphate) to the ER chaperone, BiP, to alter the cell’s UPR-mediated response to misfolded proteins. Here, we report that we have now identified a second target for HYPE - alpha-Synuclein (αSyn), a presynaptic protein involved in Parkinson’s disease (PD). Aggregated αSyn has been shown to induce ER stress and elicit neurotoxicity in PD models. We show that HYPE adenylylates αSyn and reduces phenotypes associated with αSyn aggregation in vitro, suggesting a possible mechanism by which cells cope with αSyn toxicity.HIGHLIGHTSAggregated forms of the presynaptic protein αSyn cause neurotoxicity and induce ER stress in cellular and animal models of Parkinson’s disease.We have identified αSyn as a novel target for the human Fic protein, HYPE, a key regulator of ER homeostasis.HYPE adenylylates αSyn and reduces the aggregation of recombinant αSynFic-mediated adenylylation/AMPylation is a possible mechanism by which cells cope with αSyn toxicity.Graphic Abstract
Clustering and rapid long-range motility behavior of bacteria by type IV pili
Authors: Madukoma Chinedu S. , Soto Nydia Morales , Mattingly Anne E. , Lee Shaun W. , Shrout Joshua D. 
Published: January 2019

AbstractMany organisms coordinate to move and colonize over surfaces. Bacteria such as Pseudomonas aeruginosa exhibit such surface motility as a precursor step to forming biofilms. Here we show a group surface motility where small groups of P. aeruginosa use their type IV pili (TFP) appendages over long-distances. Small cell clusters employ their TFP to move multiple cell lengths in fractions of a second and form new multicellular groups. Given the length scale and speed of displacement, cells appear to “snap” to a new position and then resume their previous behavior. The same long range TFP action also leads to rapid community contraction of sparsely arranged cell clusters. Cluster development and snapping motility does not require exogenous DNA or extracellular polysaccharides.
Longitudinal Trajectory of Early Functional Recovery in Patients with First Episode Psychosis
Authors: Hall Mei-Hua , Holton Kristina M , Öngu□r Dost , Montrose Debra , Keshavan Matcheri S. 
Published: January 2019

BackgroundThere is a large variability in the recovery trajectory and outcome of first episode of psychosis [FEP] patients. To date, individuals’ outcome trajectories at early stage of illness and potential risk factors associated with a poor outcome trajectory are largely unknown. This study aims to apply three separate predictors (positive symptoms, negative symptoms, and soft neurological signs) to identify homogeneous function outcome trajectories in patients with FEP using objective data-driven methods, and to explore the potential risk /protective factors associated with each trajectory.MethodsA total of 369 first episode patients (93% antipsychotic naive) were included in the baseline assessments and followed-up at 4-8 weeks, 6 months, and 1 year. K means cluster modelling for longitudinal data (kml3d) was used to identify distinct, homogeneous clusters of functional outcome trajectories. Patients with at least 3 assessments were included in the trajectory analyses (N=129). The Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Neurological examination abnormalities (NEA) were used as predictors against Global Assessment of Functioning Scale (GAF).ResultsIn each of the three predictor models, four distinct functional outcome trajectories emerged: “Poor”, “Intermediate”, “Good” and “Catch-up”. Individuals with male gender; ethnic minority status; low premorbid adjustment; low executive function/IQ, low SES, personality disorder, substance use history may be risk factors for poor recovery.ConclusionsFunctioning recovery in individuals with FEP is heterogeneous, although distinct recovery profiles are apparent. Data-driven trajectory analysis can facilitate better characterization of individual longitudinal patterns of functioning recovery.
Data driven analysis reveals shared transcriptome response and immune cell composition across aetiologies of critical illness
Authors: Zador Zsolt , Landry Alexander , Balas Michael , Marshall John C. , Cusimano Michael D. 
Published: January 2019

AbstractSepsis and trauma are frequent and challenging health problems in critical care. The diversity of patient response to these conditions complicates both disease management and outcome prediction. Whole blood transcriptomics allows the analysis of response in the critically ill at a molecular level. Prior results in this field demonstrate robust and diverse genomic response in the acute phase and others have shown shared biological mechanisms across wide disease aetiologies. We hypothesize that specific biological mechanisms, particularly those related to immune processes, are shared between sepsis and trauma cohorts. These may serve as universal markers for patients vulnerable to a complicated clinical course and/or mortality. We present a systems level analysis of gene expression for a total of 317 patients with abdominal sepsis (51), pulmonary sepsis (108) or trauma (158) and compare them to healthy controls (68). Our results confirm that immune processes are shared across disease aetiologies in critical illnesses. We identify two consistent and distinct subgroups of critical illness: 1) increased dendritic cell and CD4 T helper fractions but suppressed neutrophils and 2) high neutrophils and otherwise suppressed leukocyte fractions. These subgroups validate in an independent cohort of 181 paediatric patients suffering from septic shock of diverse aetiologies. Furthermore, we found immune and inflammatory processes derived from gene co-expression networks were downregulated in subgroup 1. This paralleled prior results which find similar leukocyte configuration by deconvolving whole blood transcriptomics, and this leukocyte configuration associates with greater susceptibility to multi organ failure. We are the first to identify a patient subgroup with a preserved leukocyte configuration across aetiologies of critical illness, which may serve as a universal predictor of complicated clinical course/poor outcome.
Elucidating small RNA pathways in Arabidopsis thaliana egg cells
Authors: Sprunck Stefanie , Urban Marc , Strieder Nicholas , Lindemeier Maria , Bleckmann Andrea , Evers Maurits , Hackenberg Thomas , Möhle Christoph , Dresselhaus Thomas , Engelmann Julia C. 
Published: January 2019

SummarySmall RNA pathway components and small RNA profiles of flowering plant egg cells are largely unexplored, mainly because they are not easily accessible but deeply buried inside the ovary.We describe here the utilization of proliferating callus tissue that adopted transcriptome features of Arabidopsis egg cell as a tool to explore small RNA pathway components and small RNA profiles in egg cells. We furthermore complement our studies with mRNA-Seq data from isolated Arabidopsis egg cells and provide data validation by promoter-reporter studies and whole mount in situ hybridization.Sequencing of small RNA libraries demonstrate the predominance of TE-derived siRNAs in the egg cell-related callus. TE-features and expression profiles suggest post-transcriptional silencing of activated Gypsy-like LTR retrotransposons, whereas the majority of class II DNA transposons belonging to Copia, CACTA, hAT-like and Mutator superfamilies are subjected to transcriptional silencing.Small RNA-seq furthermore led to the identification of differentially expressed known and novel miRNAs whose expression in the egg cell was verified by small RNA whole mount in situ hybridization. Both the strong expression of miRNAs in the egg-cell-adjoining synergids and the secretion of miRNAs into the micropyle suggest hitherto undescribed roles for these accessory cells in intercellular communication with the egg cell and the arriving pollen tube.In conclusion, our datasets provide valuable and comprehensive resources to study small RNA pathways and small-RNA-mediated epigenetic reprogramming during egg cell differentiation and the onset of plant embryogenesis.