bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating inDrosophila
Authors: Pooryasin Atefeh , Fiala André 
Published: September 2015

Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, inDrosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin-releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors.SIGNIFICANCE STATEMENTAn animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organismDrosophila melanogaster, we find that activating large proportions of serotonin-releasing neurons induces behavioral quiescence. Moreover, distinct serotonin-releasing neurons that we genetically isolated and identified negatively affect aspects of mating behavior, but not food uptake. This demonstrates that individual serotoninergic neurons can modulate distinct types of behavior selectively.
Kappa Opioid Receptor-Induced Aversion Requires p38 MAPK Activation in VTA Dopamine Neurons
Authors: Ehrich Jonathan M. , Messinger Daniel I. , Knakal Cerise R. , Kuhar Jamie R. , Schattauer Selena S. , Bruchas Michael R. , Zweifel Larry S. , Kieffer Brigitte L. , Phillips Paul E.M. , Chavkin Charles 
Published: September 2015

The endogenous dynorphin-κ opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38α MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38α MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR−/−mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38α MAPK activation did not. Surprisingly, while p38α MAPK inactivation blocked U50,488-CPA, p38α MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38α MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that κ opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38α MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release.SIGNIFICANCE STATEMENTKappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of κ receptor activation required arrestin-dependent p38α MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective κ opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects.
Representation of Muscle Synergies in the Primate Brain
Authors: Overduin Simon A. , d'Avella Andrea , Roh Jinsook , Carmena Jose M. , Bizzi Emilio 
Published: September 2015

Evidence suggests that the CNS uses motor primitives to simplify movement control, but whether it actually stores primitives instead of computing solutions on the fly to satisfy task demands is a controversial and still-unanswered possibility. Also in contention is whether these primitives take the form of time-invariant muscle coactivations (“spatial” synergies) or time-varying muscle commands (“spatiotemporal” synergies). Here, we examined forelimb muscle patterns and motor cortical spiking data in rhesus macaques (Macaca mulatta) handling objects of variable shape and size. From these data, we extracted both spatiotemporal and spatial synergies using non-negative decomposition. Each spatiotemporal synergy represents a sequence of muscular or neural activations that appeared to recur frequently during the animals' behavior. Key features of the spatiotemporal synergies (including their dimensionality, timing, and amplitude modulation) were independently observed in the muscular and neural data. In addition, both at the muscular and neural levels, these spatiotemporal synergies could be readily reconstructed as sequential activations of spatial synergies (a subset of those extracted independently from the task data), suggestive of a hierarchical relationship between the two levels of synergies. The possibility that motor cortex may execute even complex skill using spatiotemporal synergies has novel implications for the design of neuroprosthetic devices, which could gain computational efficiency by adopting the discrete and low-dimensional control that these primitives imply.SIGNIFICANCE STATEMENTWe studied the motor cortical and forearm muscular activity of rhesus macaques (Macaca mulatta) as they reached, grasped, and carried objects of varied shape and size. We applied non-negative matrix factorization separately to the cortical and muscular data to reduce their dimensionality to a smaller set of time-varying “spatiotemporal” synergies. Each synergy represents a sequence of cortical or muscular activity that recurred frequently during the animals' behavior. Salient features of the synergies (including their dimensionality, timing, and amplitude modulation) were observed at both the cortical and muscular levels. The possibility that the brain may execute even complex behaviors using spatiotemporal synergies has implications for neuroprosthetic algorithm design, which could become more computationally efficient by adopting the discrete and low-dimensional control that they afford.
Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1
Authors: Bukhari Noreen , Burman Poromendro N. , Hussein Ayan , Demars Michael P. , Sadahiro Masato , Brady Daniel M. , Tsirka Stella E. , Russo Scott J. , Morishita Hirofumi 
Published: September 2015

Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA-dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1-tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders.SIGNIFICANCE STATEMENTExperience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain in correlation with the decline in cortical plasticity when mice are raised in standard cages. We demonstrated that removal of Lynx1, one of negative regulators of plasticity, unmasks experience-dependent tPA elevation in visual cortex of adult mice reared in standard cages. This proteolytic elevation facilitated dendritic spine reduction and ocular dominance plasticity in adult visual cortex. This is the first demonstration of adult brain to retain the intrinsic capacity to elevate tPA in an experience-dependent manner but is effectively limited by Lynx1. tPA-Lynx1 may potentially be a new candidate mechanism for interventions that were shown to activate plasticity in adult brain.
Whitman’s Atlantic Noise
Authors: Hanlon Christopher 
Published: September 2015

Christopher Hanlon, “Whitman’s Atlantic Noise” (pp. 194–220)
This essay considers Walt Whitman’s “A Word Out of the Sea,” from the 1860 edition of Leaves of Grass, for its aural qualities—acoustically twittering birds, the hissing “undertone” of the ocean, for example—linking the poem to a wider antebellum interest in the electronic noise of telegraphy. I argue that this poem’s auditory effects bring Whitman into discussion with many others during the 1850s and 1860s who were interested in the sonic qualities of telegraphic noise quite apart from the words those noises encoded. Calling upon an array of cultural documents including songsheets, poems, fiction, and technical commentary, I suggest that “A Word Out of the Sea” condenses a singular moment in American intellectual life wherein the widespread deployment of telegraphic technology honed much interest in the interplay of sound and meaning. In this way, “A Word Out of the Sea” helps further current discussions over the resonance of nineteenth-century information technology among U.S. commentators (including poets), first-generation users who were less constantly focused than we might suppose upon the epistemological ramifications of the telegraph as a harbinger of unthinkably efficient, global communication. In many other ways, these observers of the telegraph were just as struck by the telegraph’s ontological properties, and especially the kinds of sounds it generated.
SUMO-Enriched Proteome for Drosophila Innate Immune Response
Authors: Handu Mithila , Kaduskar Bhagyashree , Ravindranathan Ramya , Soory Amarendranath , Giri Ritika , Elango Vijay Barathi , Gowda Harsha , Ratnaparkhi Girish S 
Published: September 2015

Abstract
Small ubiquitin-like modifier (SUMO) modification modulates the expression of defense genes in Drosophila, activated by the Toll/nuclear factor-κB and immune-deficient/nuclear factor-κB signaling networks. We have, however, limited understanding of the SUMO-modulated regulation of the immune response and lack information on SUMO targets in the immune system. In this study, we measured the changes to the SUMO proteome in S2 cells in response to a lipopolysaccharide challenge and identified 1619 unique proteins in SUMO-enriched lysates. A confident set of 710 proteins represents the immune-induced SUMO proteome and analysis suggests that specific protein domains, cellular pathways, and protein complexes respond to immune stress. A small subset of the confident set was validated by in-bacto SUMOylation and shown to be bona-fide SUMO targets. These include components of immune signaling pathways such as Caspar, Jra, Kay, cdc42, p38b, 14-3-3ε, as well as cellular proteins with diverse functions, many being components of protein complexes, such as prosß4, Rps10b, SmD3, Tango7, and Aats-arg. Caspar, a human FAF1 ortholog that negatively regulates immune-deficient signaling, is SUMOylated at K551 and responds to treatment with lipopolysaccharide in cultured cells. Our study is one of the first to describe SUMO proteome for the Drosophila immune response. Our data and analysis provide a global framework for the understanding of SUMO modification in the host response to pathogens.
Genomic-Enabled Prediction of Ordinal Data with Bayesian Logistic Ordinal Regression
Authors: Montesinos-López Osval A , Montesinos-López Abelardo , Crossa José , Burgueño Juan , Eskridge Kent 
Published: September 2015

AbstractMost genomic-enabled prediction models developed so far assume that the response variable is continuous and normally distributed. The exception is the probit model, developed for ordered categorical phenotypes. In statistical applications, because of the easy implementation of the Bayesian probit ordinal regression (BPOR) model, Bayesian logistic ordinal regression (BLOR) is implemented rarely in the context of genomic-enabled prediction [sample size (n) is much smaller than the number of parameters (p)]. For this reason, in this paper we propose a BLOR model using the Pólya-Gamma data augmentation approach that produces a Gibbs sampler with similar full conditional distributions of the BPOR model and with the advantage that the BPOR model is a particular case of the BLOR model. We evaluated the proposed model by using simulation and two real data sets. Results indicate that our BLOR model is a good alternative for analyzing ordinal data in the context of genomic-enabled prediction with the probit or logit link.
Genes with Restricted Introgression in a Field Cricket (Gryllus firmus/Gryllus pennsylvanicus) Hybrid Zone Are Concentrated on the X Chromosome and a Single Autosome
Authors: Maroja Luana S , Larson Erica L , Bogdanowicz Steven M , Harrison Richard G 
Published: September 2015

AbstractCharacterizing the extent of genomic differentiation between recently diverged lineages provides an important context for understanding the early stages of speciation. When such lineages form discrete hybrid zones, patterns of differential introgression allow direct estimates of which genome regions are likely involved in speciation and local adaptation. Here we use a backcross experimental design to construct a genetic linkage map for the field crickets Gryllus firmus and Gryllus pennsylvanicus, which interact in a well-characterized hybrid zone in eastern North America. We demonstrate that loci with major allele frequency differences between allopatric populations are not randomly distributed across the genome. Instead, most are either X-linked or map to a few small autosomal regions. Furthermore, the subset of those highly differentiated markers that exhibit restricted introgression across the cricket hybrid zone are also concentrated on the X chromosome (39 of 50 loci) and in a single 7-cM region of one autosome. Although the accumulation on the sex chromosome of genes responsible for postzygotic barriers is a well-known phenomenon, less attention has been given to the genomic distribution of genes responsible for prezygotic barriers. We discuss the implications of our results for speciation, both in the context of the role of sex chromosomes and also with respect to the likely causes of heterogeneous genomic divergence. Although we do not yet have direct evidence for the accumulation of ecological, behavioral, or fertilization prezygotic barrier genes on the X chromosome, faster-X evolution could make these barriers more likely to be X-linked.
Genetic Networks Required to Coordinate Chromosome Replication by DNA Polymerases α, δ, and ε in Saccharomyces cerevisiae
Authors: Dubarry Marion , Lawless Conor , Banks A Peter , Cockell Simon , Lydall David 
Published: September 2015

Abstract
Three major DNA polymerases replicate the linear eukaryotic chromosomes. DNA polymerase α-primase (Pol α) and DNA polymerase δ (Pol δ) replicate the lagging-strand and Pol α and DNA polymerase ε (Pol ε) the leading-strand. To identify factors affecting coordination of DNA replication, we have performed genome-wide quantitative fitness analyses of budding yeast cells containing defective polymerases. We combined temperature-sensitive mutations affecting the three replicative polymerases, Pol α, Pol δ, and Pol ε with genome-wide collections of null and reduced function mutations. We identify large numbers of genetic interactions that inform about the roles that specific genes play to help Pol α, Pol δ, and Pol ε function. Surprisingly, the overlap between the genetic networks affecting the three DNA polymerases does not represent the majority of the genetic interactions identified. Instead our data support a model for division of labor between the different DNA polymerases during DNA replication. For example, our genetic interaction data are consistent with biochemical data showing that Pol ε is more important to the Pre-Loading complex than either Pol α or Pol δ. We also observed distinct patterns of genetic interactions between leading- and lagging-strand DNA polymerases, with particular genes being important for coupling proliferating cell nuclear antigen loading/unloading (Ctf18, Elg1) with nucleosome assembly (chromatin assembly factor 1, histone regulatory HIR complex). Overall our data reveal specialized genetic networks that affect different aspects of leading- and lagging-strand DNA replication. To help others to engage with these data we have generated two novel, interactive visualization tools, DIXY and Profilyzer.
The Nature, Extent, and Consequences of Genetic Variation in the opa Repeats of Notch in Drosophila
Authors: Rice Clinton , Beekman Danielle , Liu Liping , Erives Albert 
Published: September 2015

Abstract
Polyglutamine (pQ) tracts are abundant in proteins co-interacting on DNA. The lengths of these pQ tracts can modulate their interaction strengths. However, pQ tracts &gt;40 residues are pathologically prone to amyloidogenic self-assembly. Here, we assess the extent and consequences of variation in the pQ-encoding opa repeats of Notch in Drosophila melanogaster. We use Sanger sequencing to genotype opa sequences (5′-CAX repeats), which have resisted assembly using short sequence reads. While most sampled lines carry the major allele opa31 encoding Q13HQ17 or the opa32 allele encoding Q13HQ18, many lines carry rare alleles encoding pQ tracts &gt;32 residues: opa33a (Q14HQ18), opa33b (Q15HQ17), opa34 (Q16HQ17), opa35a1/opa35a2 (Q13HQ21), opa36 (Q13HQ22), and opa37 (Q13HQ23). Only one rare allele encodes a tract &lt;31 residues: opa23 (Q13–Q10). This opa23 allele shortens the pQ tract while simultaneously eliminating the interrupting histidine. We introgressed these opa variant alleles into common backgrounds and measured the frequency of Notch-type phenotypes. Homozygotes for the short and long opa alleles have defects in embryonic survival and sensory bristle organ patterning, and sometimes show wing notching. Consistent with functional differences between Notch opa variants, we find that a scute inversion carrying the rare opa33b allele suppresses the bristle patterning defect caused by achaete/scute insufficiency, while an equivalent scute inversion carrying opa31 manifests the patterning defect. Our results demonstrate the existence of potent pQ variants of Notch and the need for long read genotyping of key repeat variables underlying gene regulatory networks.
Genomic Correlates of Virulence Attenuation in the Deadly Amphibian Chytrid Fungus,Batrachochytrium dendrobatidis
Authors: Refsnider Jeanine M , Poorten Thomas J , Langhammer Penny F , Burrowes Patricia A , Rosenblum Erica Bree 
Published: September 2015

AbstractEmerging infectious diseasespose a significant threat to global health, but predicting disease outcomes for particular species can be complicated when pathogen virulence varies across space, time, or hosts. The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) has caused worldwide declines in frog populations. Not only do Bd isolates from wild populations vary in virulence, but virulence shifts can occur over short timescales when Bd is maintained in the laboratory. We leveraged changes in Bd virulence over multiple generations of passage to better understand mechanisms of pathogen virulence. We conducted whole-genome resequencing of two samples of the same Bd isolate, differing only in passage history, to identify genomic processes associated with virulence attenuation. The isolate with shorter passage history (and greater virulence) had greater chromosome copy numbers than the isolate maintained in culture for longer, suggesting that virulence attenuation may be associated with loss of chromosome copies. Our results suggest that genomic processes proposed as mechanisms for rapid evolution in Bd are correlated with virulence attenuation in laboratory culture within a single lineage of Bd. Moreover, these genomic processes can occur over extremely short timescales. On a practical level, our results underscore the importance of immediately cryo-archiving new Bd isolates and using fresh isolates, rather than samples cultured in the laboratory for long periods, for laboratory infection experiments. Finally, when attempting to predict disease outcomes for this ecologically important pathogen, it is critical to consider existing variation in virulence among isolates and the potential for shifts in virulence over short timescales.