bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic sensory disinhibition contributes to intrusive re-experiencing in combat veterans
Authors: Clancy Kevin J. , Albizu Alejandro , Schmidt Norman B. , Li Wen 
Published: April 2019

ABSTRACTIntrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder (PTSD). In contrast to abstract, verbal intrusions in other affective disorders, intrusive re-experiencing in PTSD is characterized by vivid sensory details as “flashbacks”. While prevailing PTSD models largely focus on dysregulated emotional processes, we hypothesize that deficient sensory inhibition in PTSD could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions of trauma. In 86 combat veterans, we examined resting-state alpha (8-12 Hz) oscillatory activity (in both power and posterior→frontal connectivity), given its key role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. A subset (N = 35) of veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed a strong association between intrusive re-experiencing symptoms and attenuated resting-state posterior→frontal alpha connectivity, which were both correlated with olfactory trauma memory (but not emotional response). Importantly, olfactory trauma memory was further identified as a full mediator of the relationship between alpha connectivity and intrusive re-experiencing in these veterans, suggesting that deficits in intrinsic sensory inhibition can contribute to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and spontaneously activating sensory representations of trauma, impaired sensory inhibition can constitute a sensory mechanism of intrusive re-experiencing in PTSD.HIGHLIGHTSAlpha oscillations (indexing sensory inhibition) measured in 86 combat veteransRe-experiencing symptom severity was associated with attenuated alpha connectivityTrauma memory for, not emotional response to, odors mediated this relationshipTrauma memories may arise via disinhibited activation of sensory representationsSensory systems may be novel target for intrusive re-experiencing symptom treatment
Increased nitrogen fixation and remobilization may contribute to higher seed protein without a yield penalty in a soybean introgression line
Authors: Locke Anna M. , Ramirez Martha E. 
Published: April 2019

AbstractThe development of soybean varieties with higher seed protein concentration has been hindered by a negative correlation between seed protein concentration and yield. Benning HP, a genotype that breaks this tradeoff, contains a high protein allele introgressed into the cultivar Benning. Because seed protein is thought to be limited by N, field and growth chamber experiments were performed to identify the N flux(es) that enable Benning HP’s increased seed protein without a yield penalty. When the N source was completely controlled in growth chambers, Benning HP was able to fix more N than its recurrent parent, but this response depended on the strain of the rhizobia symbiont and was not observed at all developmental stages. In the field, Benning HP remobilized N from its leaves at a higher rate during seed fill, but this response was only observed in one of the years studied. These results demonstrate that Benning HP has higher potential for N fixation and N remobilization from vegetative tissue compared to its lower protein recurrent parent, but those traits are not consistently expressed and may depend on environmental and sink control.
Home, head direction stability and grid cell distortion
Authors: Sanguinetti-Scheck Juan Ignacio , Brecht Michael 
Published: April 2019

AbstractThe home is a unique location in the life of humans and animals. Numerous behavioral studies investigating homing indicate that many animals maintain an online representation of the direction of the home, a home vector. Here we placed the rat’s home cage in the arena, while recording neurons in the animal’s parasubiculum and medial entorhinal cortex. From a pellet hoarding paradigm it became evident that the home cage induced locomotion patterns characteristic of homing behaviors. We did not observe home-vector cells. We found that head-direction signals were unaffected by home location. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated towards the home. These effects appeared to be geometrical in nature rather than a home-specific distortion. Our work suggests that medial entorhinal cortex and parasubiculum do not contain an explicit neural representation of the home direction.
Multi-disease associated risk locus inIL6represses the anti-inflammatory geneGPNMBthrough chromatin looping and recruiting MEF2-HDAC complex
Authors: Kong Xiufang , Sawalha Amr H 
Published: April 2019

AbstractWe have previously revealed a genetic association between Takayasu arteritis and a non-coding genetic variant in an enhancer region withinIL6(rs2069837 A/G). The risk allele in this variant (allele A) has a protective effect against chronic viral infection and cancer. Using a combination of experimental and bioinformatics tools, we identified the monocyte/macrophage anti-inflammatory geneGPNMB, ∼520kb away, as a target gene regulated by rs2069837. We revealed preferential recruitment of myocyte enhancer factor 2-histone deacetylase (MEF2-HDAC) repressive complex to the Takayasu arteritis risk allele. Further, we demonstrated suppression of GPNMB expression in monocyte-derived macrophages from healthy individuals with the AA compared to AG genotype, which was reversed by histone deacetylase inhibition. Our data suggest that the A allele in rs2069837 represses the expression of GPNMB by recruiting MEF2-HDAC complex, enabled through a long-range intra-chromatin looping mediated by CTCF. Suppression of this anti-inflammatory gene might mediate increased susceptibility in Takayasu arteritis and enhance protective immune responses in chronic infection and cancer. Our data highlight long-range chromatin interactions in functional genomic studies.
Towards HCP-Style Macaque Connectomes: 24-Channel 3T Multi-Array Coil, MRI Sequences and Preprocessing
Authors: Autio Joonas A. , Glasser Matthew F. , Ose Takayuki , Donahue Chad J. , Bastiani Matteo , Ohno Masahiro , Kawabata Yoshihiko , Urushibata Yuta , Murata Katsutoshi , Nishigori Kantaro , Yamaguchi Masataka , Hori Yuki , Yoshida Atsushi , Go Yasuhiro , Coalson Timothy S. , Jbabdi Saad , Sotiropoulos Stamatios N. , Smith Stephen , Van Essen David C. , Hayashi Takuya 
Published: April 2019

AbstractMacaque monkeys are an important model species for understanding cortical organization of primates, yet tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the relatively thin macaque cortex, high spatial, temporal, and angular resolutions are required while maintaining high signal-to-noise ratio to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enabled adaptation of the Human Connectome Project (HCP) image acquisition protocols to the macaque brain. We also adapted HCP preprocessing methods optimized for the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provided high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold acceleration for dMRI and fMRI, respectively. Automated parcellation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available for humans.Highlights➢24-channel 3T MR receive coil designed for the smaller macaque brain.➢In vivo macaque imaging protocols adapted according to guidelines from the HCP.➢Parallel imaging yields five- and four-fold acceleration in fMRI and dMRI sampling.➢HCP’s minimal preprocessing and denoising pipelines adapted for macaques.➢The multi-modal MRI data show considerable promise for HCP-style analyses.
Pigeon foot feathering reveals conserved limb identity networks
Authors: Boer Elena F. , Van Hollebeke Hannah F. , Park Sungdae , Infante Carlos R. , Menke Douglas B. , Shapiro Michael D. 
Published: April 2019

AbstractThe tetrapod limb is a stunning example of evolutionary diversity, with dramatic variation not only among distantly related species, but also between the serially homologous forelimbs (FLs) and hindlimbs (HLs) within species. Despite this variation, highly conserved genetic and developmental programs underlie limb development and identity in all tetrapods, raising the question of how limb diversification is generated from a conserved toolkit. In some breeds of domestic pigeon, shifts in the expression of two conserved limb identity transcription factors,PITX1andTBX5, are associated with the formation of feathered HLs with partial FL identity. To determine how modulation ofPITX1andTBX5expression affects downstream gene expression, we compared the transcriptomes of embryonic limb buds from pigeons with scaled and feathered HLs. We identified a set of differentially expressed genes enriched for genes encoding transcription factors, extracellular matrix proteins, and components of developmental signaling pathways with important roles in limb development. A subset of the genes that distinguish scaled and feathered HLs are also differentially expressed between FL and scaled HL buds in pigeons, pinpointing a set of gene expression changes downstream ofPITX1andTBX5in the partial transformation from HL to FL identity. We extended our analyses by comparing pigeon limb bud transcriptomes to chicken, anole lizard, and mammalian datasets to identify deeply conservedPITX1- andTBX5-regulated components of the limb identity program. Our analyses reveal a suite of predominantly low-level gene expression changes that are conserved across amniotes to regulate the identity of morphologically distinct limbs.Summary statementIn feather-footed pigeons, mutant alleles ofPITX1andTBX5drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.
Flexible neural connectivity under constraints on total connection strength
Authors: Ocker Gabriel Koch , Buice Michael A. 
Published: April 2019

AbstractNeural computation is determined by neuron dynamics and circuit connectivity. Uncertain and dynamic environments may require neural hardware to adapt to different computational tasks, each requiring different connectivity configurations. At the same time, connectivity is subject to a variety of constraints, placing limits on the possible computations a given neural circuit can perform. Here we examine the hypothesis that the organization of neural circuitry favors computational flexibility: that it makes many computational solutions available, given physiological constraints. From this hypothesis, we develop models of the degree distributions of connectivity based on constraints on a neuron’s total synaptic weight. To test these models, we examine reconstructions of the mushroom bodies from the first instar larva and the adult Drosophila melanogaster. We perform a Bayesian model comparison for two constraint models and a random wiring null model. Overall, we find that flexibility under a homeostatically fixed total synaptic weight describes Kenyon cell connectivity better than other models, suggesting a principle shaping the apparently random structure of Kenyon cell wiring. Furthermore, we find evidence that larval Kenyon cells are more flexible earlier in development, suggesting a mechanism whereby neural circuits begin as flexible systems that develop into specialized computational circuits.Author summaryHigh-throughput electron microscopic anatomical experiments have begun to yield detailed maps of neural circuit connectivity. Uncovering the principles that govern these circuit structures is a major challenge for systems neuroscience. Healthy neural circuits must be able to perform computational tasks while satisfying physiological constraints. Those constraints can restrict a neuron’s possible connectivity, and thus potentially restrict its computation. Here we examine simple models of constraints on total synaptic weights, and calculate the number of circuit configurations they allow: their computational flexibility. We propose probabilistic models of connectivity that weight the number of synaptic partners according to computational flexibility under a constraint and test them using recent wiring diagrams from a learning center, the mushroom body, in the fly brain. We compare constraints that fix or bound a neuron’s total connection strength to a simple random wiring null model. Of these models, the fixed total connection strength matched the overall connectivity best in mushroom bodies from both larval and adult flies. We also provide evidence suggesting that neural circuits are more flexible in early stages of development and lose this flexibility as they grow towards specialized function.
WRKY1 mediates transcriptional crosstalk between light and nitrogen signaling pathways in Arabidopsis thaliana
Authors: Heerah Sachin , Katari Manpreet , Penjor Rebecca , Coruzzi Gloria , Marshall-Colon Amy 
Published: April 2019

ABSTRACTPlant responses to multiple stimuli must be integrated to trigger transcriptional cascades that lead to changes in plant metabolism and development. Light (L) and nitrogen (N) are two signaling pathways that are intimately connected to each other and to plant energy status. Here, we describe the functional role of the WRKY1 transcription factor in mediating the regulation between L and N signaling pathways in Arabidopsis thaliana. WRKY1 participates in genome-wide transcriptional reprogramming in leaves in response to individual and combined L and N signals. A regulatory network was identified, consisting of 724 genes regulated by WRKY1 and involved in both N and L signaling pathways. The loss of WRKY1 gene function has marked effects on the L and N response of genes involved in N uptake and assimilation (primary metabolism) as well as stress response pathways (secondary metabolism). Our results support a model in which WRKY1 enables plants to activate genes involved in the recycling of cellular carbon resources when L is limiting but N is abundant, and up-regulate amino acid metabolism genes when both L and N are limiting. In this potential energy conservation mechanism, WRKY1 integrates responses to N and light-energy status to trigger changes in plant metabolism.SummaryBased on transcriptome analysis, the WRKY1 transcription factor mediates regulation of nitrogen and light signaling pathways in a potential energy conservation mechanism.
Comparative genomic analysis reveals a monophyletic cold adapted Arthrobacter cluster from polar and alpine regions
Authors: Shen Liang , Liu Yongqin , Xu Baiqing , Wang Ninglian , Anslan Sten , Ren Ping , Liu Fei , Zhou Yuguang , Liu Qing 
Published: April 2019

AbstractDecrease in the frequency of arginine and increase in lysine are the trends that have been identified in the genomes of cold adapted bacteria. However, some cold adapted taxa show only limited or no detectable changes in the frequencies of amino acid composition. Here, we examined Arthrobacter spp. genomes from a wide range of environments on whether the genomic adaptations can be conclusively identified across genomes of taxa from polar and alpine regions. Phylogenetic analysis with a concatenated alignment of 119 orthologous proteins revealed a monophyletic clustering of seven polar and alpine isolated strains. Significant changes in amino acid composition related to cold adaptation were exclusive to seven of the twenty-nine strains from polar and alpine regions. Analysis of significant indicator genes and cold shock genes also revealed that clear differences could only be detected in the same seven strains. These unique characteristics may result from a vast exchange of genome content at the node leading to the monophyletic cold adapted Arthrobacter cluster predicted by the birth-and-death model. We then experimentally validated that strains with significant changes in amino acid composition have a better capacity to grow at low temperature than the mesophilic strains.ImportanceAcquisition of novel traits through horizontal gene transfer at the early divergence of the monophyletic cluster may accelerate their adaptation to low temperature. Our study reached a clear relationship between adaptation to cold and genomic features and would advanced in understanding the ambiguous results produced by the previous studies on genomic adaption to cold temperature.
Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection
Authors: van Hoek Monique L. , Kaushal Akanksha , Bishop Barney M. , Barksdale Stephanie M. 
Published: April 2019

AbstractOur long-term goal is to identify new antimicrobial peptides that might be effective against pneumonicFrancisellainfection in mice. Previously, our group searched the peptidome of the American alligator for novel cationic antimicrobial peptides and identified a naturally-occurring C-terminal fragment of apolipoprotein C-1, which we called Apo6. This peptide was found to have antibacterial activity against the ESKAPE pathogens, including those exhibiting multi-drug resistance. In this work, we tested Apo6 and synthetic derivatives for antibacterial activity againstFrancisella tularensisincluding the virulent strainF. tularensisSchuS4.Francisellais inherently highly resistant to the cyclic peptide polymyxin antibiotics and beta-lactam antibiotics. We found that our synthetic peptide derivatives (called GATR peptides), designed with increased hydrophobicity and charge, had generally strongerin vitroantimicrobial activity againstFrancisellathan the parent peptide Apo6. The GATR peptides had a greater effect on the bacterial membrane than the Apo6 peptide and were able to bindFrancisellaLPS, suggesting their mechanism of action againstFrancisella. Cytotoxicity experiments showed low cytotoxicity for most of the GATR peptides, and whole organism toxicity studies in the waxworm allowed us to down-select to two our lead peptides, GATR-3 and GATR-6. These peptides were tested in a murine pulmonary tularemia model. We found that the GATR-3 peptide rescued 50-60% of mice from lethal tularemia infection when administered systemically through the intraperitoneal route. This peptide is a candidate for further pre-clinical studies for a potential peptide-based approach to tularemia.
Putative cis-regulatory elements predict iron deficiency responses in Arabidopsis roots
Authors: Schwarz Birte , Azodi Christina B. , Shiu Shin-Han , Bauer Petra 
Published: April 2019

AbstractIron (Fe) is a key cofactor in many cellular redox processes, including respiration and photosynthesis. Plant Fe deficiency (-Fe) activates a complex regulatory network which coordinates root Fe uptake and distribution to sink tissues, while avoiding over-accumulation of Fe and other metals to toxic levels. In Arabidopsis (Arabidopsis thaliana), FIT (FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR), a bHLH transcription factor (TF), is required for up-regulation of root Fe acquisition genes. However, other root and shoot -Fe-induced genes involved in Fe allocation and signaling are FIT-independent. The cis-regulatory code, i.e. the cis-regulatory elements (CREs) and their combinations that regulate plant -Fe-responses, remains largely elusive. Using Arabidopsis genome and transcriptome data, we identified over 100 putative CREs (pCREs) that were predictive of -Fe-induced up-regulation of genes in root tissue. We used large-scale in vitro TF binding data, association with FIT-dependent or FIT-independent co-expression clusters, positional bias, and evolutionary conservation to assess pCRE properties and possible functions. In addition to bHLH and MYB TFs, also B3, NAC, bZIP, and TCP TFs might be important regulators for -Fe responses. Our approach uncovered IDE1 (Iron Deficiency-responsive Element 1), a -Fe response CRE in grass species, to be conserved in regulating genes for biosynthesis of Fe-chelating compounds also in Arabidopsis. Our findings provide a comprehensive source of cis-regulatory information for -Fe-responsive genes, that advances our mechanistic understanding and informs future efforts in engineering plants with more efficient Fe uptake or transport systems.One sentence summary>100 putative cis-regulatory elements robustly predict Arabidopsis root Fe deficiency-responses in computational models, and shed light on the mechanisms of transcriptional regulation.
AGO1x prevents dsRNA-induced interferon signaling to promote breast cancer cell proliferation
Authors: Ghosh Souvik , Guimaraes Joao C , Lanzafame Manuela , Schmidt Alexander , Syed Afzal Pasha , Dimitriades Beatrice , Börsch Anastasiya , Ghosh Shreemoyee , Correia Ana Luisa , Danner Johannes , Meister Gunter , Terracciano Luigi M. , Piscuoglio Salvatore , Zavolan Mihaela 
Published: April 2019

AbstractInitially reported for viral RNA, elongation of polypeptide chains beyond the stop codon (translational readthrough (TR)) also occurs on eukaryotic transcripts. TR diversifies the proteome and can modulate protein levels 1-6. Here we report that AGO1x, a conserved TR isoform of Argonaute 1, is generated in highly proliferative breast cancer cells, where it curbs accumulation of double stranded RNAs, the induction of the interferon response and apoptosis. In contrast to other mammalian Argonaute protein family members with primarily cytoplasmic functions, AGO1x localizes to the nucleus, in the vicinity of nucleoli. We identify a novel interaction of AGO1x with the Polyribonucleotide Nucleotidyltransferase 1, depletion of either protein leading to dsRNA accumulation and impaired cell proliferation. Our study thus uncovers a novel function of an Argonaute protein outside of the miRNA effector pathway, in buffering dsRNA-induced interferon responses. As AGO1x expression is tightly linked to breast cancer cell proliferation, our study suggests a new direction for limiting tumor growth.