bluuebunny/crossref_metadata_2025_split huggingface dataset:
The best of both worlds: A new lipid complex has micelle and bicelle-like properties
Authors: Rieth Monica D. 
Published: October 2018

AbstractBicelles have been demonstrated to be a valuable tool for studying membrane protein interactions and structure in vitro. They are distinguished by a distinct lipid bilayer that mimics the plasma membrane of cells making it more native-like than its detergent micelle counter-part. Bicelles are typically comprised of a long-chain phospholipid such as dimyristoylphosphatidylcholine (DMPC) and a short-chain phospholipid such as dihexanoylphosphatidylcholine (DHPC). When mixed together in solution DMPC-DHPC bicelles assume a discoidal structure comprised of a heterogeneous arrangement where the short-chain lipids gather around the rim of the disk and the long-chain lipids form the flat, planar, bilayer region. In this study, the nonionic surfactant, C8E5, was used to prepare mixtures with DMPC to determine if it adopts properties similar to bicelles with a q ≥ 0.5. At q ≥ 0.5, DMPC-DHPC bicelles are bilayered and DMPC is sequestered from the detergent micelle-like DHPC. Mixtures of DMPC and C8E5 were prepared at various q values, a parameter used to describe the mole ratio of DMPC to DHPC in the preparation of bicelles. Employing biophysical methods like dynamic light scattering, 31P-NMR and analytical ultracentrifugation, properties of these lipid-detergent complexes are described. Interestingly they adopted a spherical-shaped micellar structure morphology and did not assume a discoidal shape typical of bicelles at q ≥ 0.5. However, they appear to retain bilayer-like properties that may prove beneficial for in vitro biophysical studies of membrane proteins.
Histone acetyltransferase inhibition rescues differentiation of emerin-deficient myogenic progenitors
Authors: Bossone Katherine A. , Ellis Joseph A. , Holaska James M. 
Published: October 2018

ABSTRACTIntroductionEmery-Dreifuss Muscular Dystrophy (EDMD) is a disease characterized by skeletal muscle wasting, major tendon contractures, and cardiac conduction defects. Mutations in the gene encoding emerin cause EDMD1. Our previous studies suggested emerin activation of Histone Deacetylase 3 (HDAC3) to reduce Histone 4-Lysine 5 (H4K5) acetylation (ac) is important for myogenic differentiation.MethodsPharmacological inhibitors (Nu9056, L002) of histone acetyltransferases targeting acetylated H4K5 were used to test if increased acetylated H4K5 was responsible for the impaired differentiation seen in emerin deficient myogenic progenitors.ResultsNu9056 and L002 rescued impaired differentiation in emerin deficiency. SRT1720, which inhibits the NAD+-dependent deacetylase Sirtuin 1 (SIRT1), failed to rescue myotube formation.DiscussionWe conclude emerin regulation of HDAC3 activity to affect H4K5 acetylation dynamics is important for myogenic differentiation. Targeting H4K5ac dynamics represents a new strategy for ameliorating the skeletal muscle wasting seen in EDMD1.
Cell-type-specific resolution epigenetics without the need for cell sorting or single-cell biology
Authors: Rahmani Elior , Schweiger Regev , Rhead Brooke , Criswell Lindsey A. , Barcellos Lisa F. , Eskin Eleazar , Rosset Saharon , Sankararaman Sriram , Halperin Eran 
Published: October 2018

AbstractHigh costs and technical limitations of cell sorting and single-cell techniques currently restrict the collection of large-scale, cell-type-specific DNA methylation data. This, in turn, impedes our ability to tackle key biological questions that pertain to variation within a population, such as identification of disease-associated genes at a cell-type-specific resolution. Here, we show mathematically and empirically that cell-type-specific methylation levels of an individual can be learned from its tissue-level bulk data, conceptually emulating the case where the individual has been profiled with a single-cell resolution and then signals were aggregated in each cell population separately. Provided with this unprecedented way to perform powerful large-scale epigenetic studies with cell-type-specific resolution, we revisit previous studies with tissue-level bulk methylation and reveal novel associations with leukocyte composition in blood and with rheumatoid arthritis. For the latter, we further show consistency with validation data collected from sorted leukocyte sub-types. Corresponding software is available from: https://github.com/cozygene/TCA.
The biodiversity benefit of native forest over Grain-for-Green plantations
Authors: Wang Xiaoyang , Hua Fangyuan , Wang Lin , Wilcove David S. , Yu Douglas W 
Published: October 2018

ABSTRACTAimChina’s Grain-for-Green Program (GFGP) is the largest reforestation program in the world and has been operating since 1999. The GFGP has promoted the establishment of tree plantations over the preservation of diverse native forest. In a previous study (Hua et al. 2016, Nat Comms 7:12717), we showed that native forest supports higher species richnesses of birds and bees than do GFGP plantations. We also showed that ‘mixed-plantation’ GFGP plantations, which are mostly made up of two to five neighboring monoculture stands of different tree species, planted in checkboard fashion, support a level of bird (but not bee) species richness that is higher than any of the individual GFGP monocultures, although still below that of native forest. To better protect terrestrial biodiversity, which is an important objective of China’s land-sustainability spending, we recommended that the GFGP should firstly prioritize native forest conservation and regeneration and secondly promote checkerboard planting arrangements over monocultures. Here, we use metabarcoding of arthropod biodiversity to test the generality of these results and policy recommendations.LocationSichuan, ChinaMethodsWe used COI-amplicon sequencing (‘metabarcoding’) of bulk samples of arthropods that were collected with pan traps in native forest, cropland, mixed plantations, and monocultures.ResultsNative forest supports the highest overall levels of arthropod species richness and diversity, followed by cropland and mixed plantations, followed by bamboo monoculture, followed by the other monocultures. Also, the arthropod community in mixed plantations shares more species with native forest than do any of the monocultures. Together, these results show a biodiversity value of mixed plantations for arthropods that is higher than that previously indicated by bees alone.Main conclusionThese results strengthen our original policy recommendations of (1) promoting the conservation and expansion of native forest and (2) promoting mixed-plantation arrangements. The value of this added metabarcoding-based analysis is that these policy prescriptions are now also based on a dataset that includes over 500 species-resolution taxa, ranging across the Arthropoda.
Pogz deficiency leads to abnormal behavior, transcription dysregulation and impaired cerebellar physiology
Authors: Suliman Reut , Title Ben , Cohen Yahel , Tal Maayan , Tal Nitzan , Gudmundsdottir Bjorg , Gudmundsson Kristbjorn O. , Keller Jonathan R , Huang Guo-Jen , Yarom Yosef , Shifman Sagiv 
Published: October 2018

AbstractGenes implicated in autism spectrum disorder (ASD) are enriched with chromatin regulators, but the mechanisms leading to the abnormal behavior and cognition are still unclear. Animal models are crucial for studying the effects of mutations on brain function and behavior. We generated conditional knockout mice with brain-specific mutation in Pogz, a heterochromatin regulator recurrently mutated in ASD and other neurodevelopmental disorders, and demonstrated that these mice display phenotypes that resemble the human condition. Pogz deficiency led to smaller brain, growth impairment, motor learning deficits, and increased social interactions that mimic the human overly friendly phenotype. At the molecular level, reporter assay indicated that POGZ functions as a negative regulator of transcription through its interaction with HP1 proteins. In accordance, we found a significant upregulation of gene expression, most notably in the cerebellum. Furthermore, Pogz deficiency was associated with a significant reduction in the firing frequency of simple and complex spikes in cerebellar Purkinje cells with no changes in their intrinsic properties. Overall, our findings support a mechanism linking heterochromatin dysregulation to cerebellar circuit dysfunction and to motor and social abnormalities in ASD.
Condensin II inactivation in interphase does not affect chromatin folding or gene expression
Authors: Abdennur Nezar , Schwarzer Wibke , Pekowska Aleksandra , Shaltiel Indra Alon , Huber Wolfgang , Haering Christian H , Mirny Leonid , Spitz François 
Published: October 2018

SummaryCondensin complexes have been proposed to play a prominent role in interphase chromatin organization and control of gene expression. Here, we report that the deletion of the central condensin II kleisin subunit Ncaph2 in differentiated mouse hepatocytes does not lead to significant changes in chromosome organization or in gene expression. Both observations challenge current views that implicate condensin in interphase chromosomal domain formation and in enhancer-promoter interactions. Instead, we suggest that the previously reported effects of condensin perturbation may result from their structural role during mitosis, which might indirectly impact the re-establishment of interphase chromosomal architecture after cell division.
Single cell analyses of the effects of Amyloid-beta42 and Interleukin-4 on neural stem/progenitor cell plasticity in adult zebrafish brain
Authors: Cosacak Mehmet Ilyas , Bhattarai Prabesh , Zhang Yixin , Kizil Caghan 
Published: October 2018

AbstractNeural stem cells (NSCs) constitute the reservoir for new cells and might be harnessed for stem cell-based regenerative therapies. Zebrafish has remarkable ability to regenerate its brain by inducing NSC plasticity upon Alzheimer’s pathology. We recently identified that NSCs enhance their proliferation and neurogenic outcome in an Amyloid-beta42-based (Aβ42) experimental Alzheimer’s disease model in zebrafish brain and Interleukin-4 (IL4) is a critical molecule for inducing NSC proliferation in AD conditions. However, the mechanisms by which Aβ42 and IL4 affect NSCs remained unknown. Using single cell transcriptomics, we determined distinct subtypes of NSCs and neurons in adult zebrafish brain, identified differentially expressed genes after Aβ42 and IL4 treatments, analyzed the gene ontology and pathways that are affected by Aβ42 and IL4, and investigated how cell-cell communication is altered through secreted molecules and their receptors. Our results constitute the most extensive resource in the Alzheimer’s disease model of adult zebrafish brain, are likely to provide unique insights into how Aβ42/IL4 affects NSC plasticity and yield in novel drug targets for mobilizing neural stem cells for endogenous neuro-regeneration.
Inferring Population Genetics Parameters of Evolving Viruses Using Time-series Data
Authors: Zinger Tal , Pennings Pleuni S. , Stern Adi 
Published: October 2018

1AbstractWith the advent of deep sequencing techniques, it is now possible to track the evolution of viruses with ever-increasing detail. Here we present FITS (Flexible Inference from Time-Series) – a computational framework that allows inference of either the fitness of a mutation, the mutation rate or the population size from genomic time-series sequencing data. FITS was designed first and foremost for analysis of either short-term Evolve & Resequence (E&R) experiments, or for rapidly recombining populations of viruses. We thoroughly explore the performance of FITS on noisy simulated data, and highlight its ability to infer meaningful information even in those circumstances. In particular FITS is able to categorize a mutation as Advantageous, Neutral or Deleterious. We next apply FITS to empirical data from an E&R experiment on poliovirus where parameters were determined experimentally and demonstrate extremely high accuracy in inference. We highlight the ease of use of FITS for step-wise or iterative inference of mutation rates, population size, and fitness values for each mutation sequenced, when deep sequencing data is available at multiple time-points.AvailabilityFITS is written in C++ and is available both with a highly user friendly graphical user interface but also as a command line program that allows parallel high throughput analyses. Source code, binaries (Windows and Mac) and complementary scripts, are available from GitHub at https://github.com/SternLabTAU/FITS.Contactsternadi@tau.ac.il
Isolating syntax in natural language: MEG evidence for an early contribution of left posterior temporal cortex
Authors: Flick Graham , Pylkkänena Liina 
Published: October 2018

ABSTRACTSyntax is the engine that allows us to create an infinitude of linguistic expressions, and the construction of syntactic structures, such as noun phrases and verb phrases, is considered a fundamental component of language processing. Nevertheless, insights concerning the neurobiological basis of syntax have remained elusive, in part because it is difficult to isolate syntax from semantic composition. Consequently, many studies of syntax have relied on meaningless artificial stimuli, such as jabberwocky expressions or artificial grammars. However, while pure manipulations of syntax are challenging to design, natural language grammars do have a sparse set of constructions presenting this possibility. Here we examined one such case, English post-nominal adjectives (mountain TALL enough for a strenuous hike), which were contrasted with semantically parallel but structurally simpler noun-adjective sequences in an MEG experiment. We observed a sharp activity increase in the left posterior temporal lobe (PTL) when syntactic composition was more straightforward, approximately 200 ms after adjective onset. The semantic fit between the noun and adjective was also varied, but this affected anterior temporal cortex, consistent with prior work. These findings offer a unique demonstration of the relevance of posterior temporal cortex for syntactic processing in natural language. We also present connectivity evidence that the syntax-related PTL responses were relayed to ipsilateral inferior frontal and anterior temporal regions. The combined results draw an initial picture of the rapid spatio-temporal dynamics of the syntactic and semantic composition network in sentence processing.
A multifaceted approach for analyzing complex phenotypic data in rodent models of autism
Authors: Das Ishita , Estevez Marcel A. , Sarkar Anjali A. , Banerjee-Basu Sharmila 
Published: October 2018

AbstractAutDB features a modular framework that aims at collating multifactorial risk factors associated with autism spectrum disorder (ASD). The animal model (AM) module of AutDB was first developed for mouse models of genes and CNVs associated with ASD (Kumar et al., 2011). Subsequently, environmentally induced rodent models were introduced to capture the full spectrum of risk-factors associated with ASD, along with idiopathic models represented by inbred strains. Using the data systematically annotated in AutDB, we depict the intricate trends in the research findings based on rodent models of ASD. We identify the top 30 most frequently studied phenotypes extracted from 911 genetic, 269 induced and 17 inbred rodent models of ASD extracted from 787 publications. As expected, many of these include animal model equivalents of the ‘core’ phenotypes associated with ASD, as well as several comorbid features of ASD including anxiety, seizures and motor-control deficits. Uniquely, AutDB curates rescue models where various treatment strategies were used in rodent ASD models to alleviate ASD-relevant phenotypes. We further examine ASD models based on 52 genes and 2 CNV loci to identify 24 pharmaceutical agents that were used in 2 or more paradigms for testing their efficacy. As a case study, we analyze various Shank3 mouse models providing a high-resolution view of thein vivorole of this high-confidence ASD gene. Together, this resource provides a snapshot of genetic and induced models of ASD within a shared annotation platform to examine the complex meshing of diverse ASD-associated risk-factors.
Converging roles of glutamate receptors in domestication and prosociality
Authors: O’Rourke Thomas , Boeckx Cedric 
Published: October 2018

AbstractThe present paper highlights the prevalence of signals of positive selection on genes coding for glutamate receptors—most notably kainate and metabotropic receptors—in domesticated animals and anatomically modern humans. Relying on their expression in the central nervous system and phenotypes associated with mutations in these genes, we claim that regulatory changes in kainate and metabotropic receptor genes have led to alterations in limbic function and Hypothalamic-Pituitary-Adrenal axis regulation, with potential implications for the emergence of unique social behaviors and communicative abilities in (self-)domesticated species.
Magnetophospenes in humans exposed to ELF MF up to 50 mT, a threshold study
Authors: Legros A , Modolo J , Corbacio M , Goulet D , Plante M , Souques M , Deschamps F , Ostiguy G , Lambrozo J , Thomas AW 
Published: October 2018

AbstractAlthough magnetophosphene perception is the most reliable reported effect on acute human neurophysiological responses to extremely low frequency (ELF) magnetic field (MF) exposure, current knowledge is based on small sample size, non-replicated experiments. In this study, we established MF levels triggering magnetophosphenes at 20, 50, 60 and 100 Hz in humans. Magnetophosphene perception and EEG were collected in 55 magnetic flux density conditions randomly delivered in each frequency group (2 experiments, total n=145). Results indicate that threshold values 1) need to be reported as a function of dB/dt instead of flux density, and 2) are frequency-dependent (higher sensitivity to lower frequencies). No clear trend was found in EEG data.
Illumina-based sequencing framework for accurate detection and mapping of influenza virus defective interfering particle-associated RNAs
Authors: Alnaji Fadi G. , Holmes Jessica R. , Rendon Gloria , Vera J. Cristobal , Fields Chris , Martin Brigitte E. , Brooke Christopher B. 
Published: October 2018

AbstractThe mechanisms and consequences of defective interfering particle (DIP) formation during influenza virus infection remain poorly understood. The development of next generation sequencing (NGS) technologies has made it possible to identify large numbers of DIP-associated sequences, providing a powerful tool to better understand their biological relevance. However, NGS approaches pose numerous technical challenges including the precise identification and mapping of deletion junctions in the presence of frequent mutation and base-calling errors, and the potential for numerous experimental and computational artifacts. Here we detail an Illumina-based sequencing framework and bioinformatics pipeline capable of generating highly accurate and reproducible profiles of DIP-associated junction sequences. We use a combination of simulated and experimental control datasets to optimize pipeline performance and demonstrate the absence of significant artifacts. Finally, we use this optimized pipeline to generate a high-resolution profile of DIP-associated junctions produced during influenza virus infection and demonstrate how this data can provide insight into mechanisms of DIP formation. This work highlights the specific challenges associated with NGS-based detection of DIP-associated sequences, and details the computational and experimental controls required for such studies.
Bodily sensations in social scenarios: Where in the body?
Authors: Novembre Giovanni , Zanon Marco , Morrison India , Ambron Elisabetta 
Published: October 2018

ABSTRACTBodily states are fundamental to emotions′ emergence and are believed to constitute the first step in the chain of events that culminate in emotional awareness. Recent works have given fresh support to this view by showing that distinct topographical maps can be derived to describe how basic and more complex emotions are represented in the body. However, it is still unclear whether these bodily maps can also extend to emotions experienced specifically within social interactions and how these representations relate to basic emotions. To address this issue, we used the emBODY tool to obtain high-resolution bodily maps that represent the body activation and deactivation experienced by healthy participants in social scenarios depicting establishment or loss of social bonds. We show that clear patterns of activation/deactivation across the body emerge depending on the valence and on the characteristics of the single social scenarios, but also a common activation of head, chest and limbs across scenarios. Furthermore, we showed that maps related to complex social scenarios are strongly correlated with bodily states experienced in basic emotions, suggesting that the patterns of body activation/deactivation found for social scenarios might represent a combination of different basic emotions these experiences elicit. Our data tackle conscious emotional experiences and show for the first time how ′painful′ social events are felt on the body, providing findings that complement verbal reports and neuroimaging data on social rejection. Furthermore, they show that bodily feelings related to complex social scenarios, despite referring to unified independent emotional states, are also related to bodily correlates of basic emotions.
The mouse HP1 proteins are essential for preventing liver tumorigenesis
Authors: Saksouk Nehmé , Hajdari Shefqet , Pratlong Marine , Barrachina Célia , Graber Céline , Zavoriti Aliki , Sarrazin Amélie , Pirot Nelly , Noël Jean-Yohan , Khellaf Lakhdar , Fabbrizio Eric , Julien Eric , Cammas Florence M. 
Published: October 2018

AbstractChromatin organization is essential for appropriate interpretation of the genetic information. Here, we demonstrated that the chromatin associated proteins HP1 are dispensable for cell survival but are essential within hepatocytes to prevent liver tumor development. Molecular characterization of pre-malignant HP1-Triple KO livers revealed that HP1 are essential for the maintenance of the structural organization of heterochromatin but surprisingly, not for several well known heterochromatin functions such as the maintenance of the genome stability nor the regulation of major satellite repeat expression within liver. We further show that some specific retrotransposons, mainly of the ERV family, get reactivated in HP1-TKO livers correlating, in some cases, with the activation of the adjacent genes. We present evidence that this reactivation of ERV relies on the HP1-dependent ability of the corepressor TRIM28 to regulate KRAB-ZFP repressive activity. Intriguingly, we found that in contrast to the observation in young animals, the HP1-dependent maintenance of ERV silencing becomes independent of TRIM28 in old animals. Finally, we showed that HP1 are also essential directly or indirectly for the regulation of single genes with most of them having well characterized functions in liver homeostasis such as regulation of the redox and endoplasmic reticulum equilibrium, lipid metabolism and steroid biosynthesis.Altogether, our findings indicate that HP1 proteins, through the modulation of multiple chromatin-associated events both within the heterochromatic and euchromatic compartments, act as guardians of liver homeostasis to prevent tumor development.