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Geo-climatic gradient shapes functional trait variations in Salix eriocephala Michx.

Intraspecific variations in seasonal phenology and growth physiology reflect adaptation to local climate. To explore the patterns of local adaptation along latitudinal and longitudinal clines, we used thirty-four populations of Salix eriocephala sourced from its natural ranges across Canada. The genotypes were examined for 6 phenology and 19 ecophysiology traits over two growing seasons under common garden condition. Photosynthetic assimilation rate (A) increased with increasein latitude when measured during free growth. In spite, the negative correlation between stomatal density and stomatal conductance (gs), higher A is facilitated via larger pore length among genotypes from short growing seasons. In addition, higher A, was positively associated with total leafnitrogen and leaf mass per unit area. No population level differences wereobserved for water use-efficiency ({Delta}13C), however nitrogen isotope discrimination ({delta}15N) displayed latitudinalclines. Growing season phenological traits considered in this study accounted highheritability (H2=0.65-0.94). Melampsora rust infestation also displayed a strong latitudinal cline with high-latitude genotypes being more susceptible. Overall, the results support the hypothesis that functional trait variations are largely explained by climate of origin and facilitate selection of parents with superior adaptive traits in the Canadian willow improvement program forbioenergy and environmental applications.

Plant Biology

Geo-climatic gradient shapes functional trait variations in Salix eriocephala Michx.

Intraspecific variations in seasonal phenology and growth physiology reflect adaptation to local climate. To explore the patterns of local adaptation along latitudinal and longitudinal clines, we used thirty-four populations of Salix eriocephala sourced from its natural ranges across Canada. The genotypes were examined for 6 phenology and 19 ecophysiology traits over two growing seasons under common garden condition. Photosynthetic assimilation rate (A) increased with increasein latitude when measured during free growth. In spite, the negative correlation between stomatal density and stomatal conductance (gs), higher A is facilitated via larger pore length among genotypes from short growing seasons. In addition, higher A, was positively associated with total leafnitrogen and leaf mass per unit area. No population level differences wereobserved for water use-efficiency ({Delta}13C), however nitrogen isotope discrimination ({delta}15N) displayed latitudinalclines. Growing season phenological traits considered in this study accounted highheritability (H2 = 0.65-0.94). Melampsora rust infestation also displayed a strong latitudinal cline with high-latitude genotypes being more susceptible. Overall, the results support the hypothesis that functional trait variations are largely explained by climate of origin and facilitate selection of parents with superior adaptive traits in the Canadian willow improvement program forbioenergy and environmental applications.

Plant Biology

RiVIERA-MT: A Bayesian model to infer risk variants in related traits using summary statistics and functional genomic annotations

Dissecting the physiological circuitry underlying diverse human complex traits associated with heritable common mutations is an ongoing effort. The primary challenge involves identifying the relevant cell types and the causal variants among the vast majority of the associated mutations in the noncoding regions. To address this challenge, we developed an efficient probabilistic framework. First, we propose a sparse group-guided learning algorithm to infer cell-type-specific enrichments. Second, we propose a fine-mapping Bayesian model that incorporates as Bayesian priors the sparse enrichments to infer risk variants. Using the proposed framework to analyze 32 complex human traits revealed meaningful tissue-specific epigenomic enrichments indicative of the relevant disease pathologies. The prioritized variants exhibit prominent tissue-specific epigenomic signatures and significant enrichments for eQTL and conserved elements. Together, we demonstrate the general benefits of the proposed integrative framework in elucidating meaningful tissue-specific epigenomic elements from large-scale correlated annotations and the implicated functional variants for future experimental interrogation.

Bioinformatics

Auditory Nerve Stochasticity Impedes Category Learning: the Role of Cochlear Nucleus and Inferior Colliculus in Stabilising Auditory Nerve Firing

It is well known that auditory nerve (AN) fibers overcome bandwidth limitations through the \"volley principle\", a form of multiplexing. What is less well known is that the volley principle introduces a degree of unpredictability into AN neural firing patterns which makes even simple stimulus categorization tasks difficult. We use a physiologically grounded, unsupervised spiking neural network model of the auditory brain with STDP learning to demonstrate that plastic auditory cortex is unable to learn even simple auditory object categories when exposed to the raw AN firing input without subcortical preprocessing. We then demonstrate the importance of non-plastic subcortical preprocessing within the cochlear nucleus (CN) and the inferior colliculus (IC) for stabilising and denoising AN responses. Such preprocessing enables the plastic auditory cortex to learn efficient robust representations of the auditory object categories. The biological realism of our model makes it suitable for generating neurophysiologically testable hypotheses.

Neuroscience

Higher stress and immunity responses are associated with higher mortality in reef-building coral exposed to a bacterial challenge

Understanding the drivers of intraspecific variation in susceptibility is essential to manage increasingly frequent coral disease outbreaks. We challenged replicate fragments of eight Acropora millepora genotypes with Vibrio spp. to quantify variation in lesion development and to identify host and coral-associated microbial community properties associated with resistance. While Vibrio spp. remained relatively rare in the microbiome of challenged corals, other stress-associated microbial taxa significantly increased in abundance. Contrary to expectations, higher constitutive immunity and more active immune responses did not confer higher resistance to bacterial challenge. Furthermore, more pronounced gene expression responses to bacterial challenge were associated with higher rather than lower mortality. A newly developed gene expression assay based on two genes related to inflammation and immune responses, deleted in malignant brain tumors 1 and a matrix metalloproteinase, predicted mortality under Vibrio treatment both in the initial experiment and in a validation experiment involving another 20 A. millepora genotypes. Instead of mounting more robust responses, resistant corals were largely unaffected by the bacterial challenge and maintained gene expression signatures of healthier condition, including elevated fluorescent proteins and ribosomal biosynthesis along with diminished ubiquitination. Overall, our results support the view that coral disease and mortality is commonly due to opportunistic pathogens exploiting physiologically compromised hosts rather than specific infections, and show, contrary to the prevailing wisdom, that greater immune responses do not necessarily translate into greater disease resistance.

Ecology

Unsupervised Learning of Temporal Features for Word Categorization in a Spiking Neural Network Model of the Auditory Brain

The nature of the code used in the auditory cortex to represent complex auditory stimuli, such as naturally spoken words, remains a matter of debate. Here we argue that such representations are encoded by stable spatio-temporal patterns of firing within cell assemblies known as polychronous groups, or PGs. We develop a physiologically grounded, unsupervised spiking neural network model of the auditory brain with local, biologically realistic, spike-time dependent plasticity (STDP) learning, and show that the plastic cortical layers of the network develop PGs which convey substantially more information about the speaker independent identity of two naturally spoken word stimuli than does rate encoding that ignores the precise spike timings. We furthermore demonstrate that such informative PGs can only develop if the input spatio-temporal spike patterns to the plastic cortical areas of the model are relatively stable.\n\nAuthor SummaryCurrently we still do not know how the auditory cortex encodes the identity of complex auditory objects, such as words, given the great variability in the raw auditory waves that correspond to the different pronunciations of the same word by different speakers. Here we argue for temporal information encoding within neural cell assemblies for representing auditory objects. Unlike the more traditionally accepted rate encoding, temporal encoding takes into account the precise relative timing of spikes across a population of neurons. We provide support for our hypothesis by building a neurophysiologically grounded spiking neural network model of the auditory brain with a biologically plausible learning mechanism. We show that the model learns to differentiate between naturally spoken digits \"one\" and \"two\" pronounced by numerous speakers in a speaker-independent manner through simple unsupervised exposure to the words. Our simulations demonstrate that temporal encoding contains significantly more information about the two words than rate encoding. We also show that such learning depends on the presence of stable patterns of firing in the input to the cortical areas of the model that are performing the learning.

Neuroscience

Temperature-induced transcriptional responses of the deep-biosphere bacterium, Kosmotoga olearia, illuminate its adaptation to growth from 20 ° to 79°

Temperature is one of the defining parameters of an ecological niche. Most organisms thrive within a temperature range that rarely exceeds [~] 30{degrees}C, but the deep subsurface bacterium Kosmotoga olearia can grow over a temperature range of 59{degrees}C (20{degrees}C -79{degrees}C). To identify genes correlated with this flexible phenotype, we compared transcriptomes of K. olearia cultures grown at its optimal 65{degrees}C to those at 30{degrees}C, 40{degrees}C, and 77{degrees}C. The temperature treatments affected expression of 573 of 2,224 K. olearia genes. Notably, this transcriptional response elicits re-modeling of the cellular membrane and changes in metabolism, with increased expression of genes involved in energy and carbohydrate metabolism at high temperatures and up-regulation of amino acid metabolism at lower temperatures. At sub-optimal temperatures, many transcriptional changes were similar to those observed in mesophilic bacteria at physiologically low temperatures, including up-regulation of typical cold stress genes and ribosomal proteins. Comparative genomic analysis of additional Thermotogae genomes, indicate that one of K. olearia's strategies for low temperature growth is increased copy number of some typical cold response genes through duplication and/or lateral acquisition. At 77{degrees}C one third of the up-regulated genes are of hypothetical function, indicating that many features of high temperature growth are unknown.

Evolutionary Biology

Evolutionary genomics of peach and almond domestication

The domesticated almond [Prunus dulcis (L.) Batsch] and peach [P. persica (Mill.) D. A. Webb] originate on opposite sides of Asia and were independently domesticated approximately 5000 years ago. While interfertile, they possess alternate mating systems and differ in a number of morpholog-ical and physiological traits. Here we evaluated patterns of genome-wide diversity in both almond and peach to better understand the impacts of mating system, adaptation, and domestication on the evolution of these taxa. Almond has [~]7X the genetic diversity of peach, and high genome-wide FST values support their status as separate species. We estimated a divergence time of approximately 8 Mya, coinciding with an active period of uplift in the northeast Tibetan Plateau and subsequent Asian climate change. We see no evidence of bottleneck during domestication of either species, but identify a number of regions showing signatures of selection during domestication and a significant overlap in candidate regions between peach and almond. While we expected gene expression in fruit to overlap with candidate selected regions, instead we find enrichment for loci highly differentiated between the species, consistent with recent fossil evidence suggesting fruit divergence long preceded domestication. Taken together this study tells us how closely related tree species evolve and are domesticated, the impact of these events on their genomes, and the utility of genomic information for long-lived species. Further exploration of this data will contribute to the genetic knowledge of these species and provide information regarding targets of selection for breeding application and further the understanding of evolution in these species.

Evolutionary Biology

Optimization of an anti Staphylococcus antibiotic produced by tropical soil dwelling Streptomyces parvulus

An antibiotic produced by strain Streptomyces parvulus showing activity against Staphylococcus citreus was subjected to various optimization parameters for enhancing its production. Nutritional and physiological parameters produced by S. parvulus under shaken flask conditions were determined. Optimization of these parameters led to 11% increase in antibiotic activity with a mean zone of inhibition of 42 mm.\n\nHighest antibiotic production was obtained at 250 rpm for 14 days with optimum temperature of 28{degrees}C and pH 7. Kuster#x2019;s modified medium containing glycerol 0.7% (v/v), casein 0.03% (w/v), NaCl 0% (w/v), phosphate 0.25% (w/v), KNO3 0.1% (w/v) and CaCO3 0.0015% (w/v) concentration was found ideal.

Microbiology

Disorder Atlas: a web service for the proteome-based interpretation of intrinsic disorder predictions

BackgroundIntrinsically disordered proteins lack a stable three-dimensional structure under physiological conditions. While this property has gained considerable interest within the past two decades, disorder poses substantial challenges to experimental characterization efforts. In effect, numerous computational tools have been developed to predict disorder from primary sequences, however, interpreting the output of these algorithms remains a challenge.\n\nResultsHere, we present Disorder Atlas, web-based software that facilitates the interpretation of intrinsic disorder predictions using proteome-based descriptive statistics. This service is also equipped to facilitate large-scale systematic exploratory searches for proteins encompassing disorder features of interest, and further allows users to browse the prevalence of multiple disorder features at the proteome level. Disorder Atlas is freely available for non-commercial users at http://www.disorderatlas.org.\n\nConclusionDisorder Atlas enables a standardized interpretation of intrinsic disorder predictions, and provides researchers with a tool to assess disorder on multiple scales.

Bioinformatics

Decoding the Infant Mind: Multichannel Pattern Analysis (MCPA) using fNIRS

The MRI environment restricts the types of populations and tasks that can be studied by cognitive neuroscientists (e.g., young infants, face-to-face communication). FNIRS is a neuroimaging modality that records the same physiological signal as fMRI but without the constraints of MRI, and with better spatial localization than EEG. However, research in the fNIRS community largely lacks the analytic sophistication of analogous fMRI work, restricting the application of this imaging technology. The current paper presents a method of multivariate pattern analysis for fNIRS that allows the authors to decode the infant mind (a key fNIRS population). Specifically, multi-channel pattern analysis (MCPA) employs a correlation-based decoding method where a group model is constructed for all infants except one; both average patterns (i.e., infant-level) and single trial patterns (i.e., trial-level) of activation are decoded. Between subjects decoding is a particularly difficult task, because each infant has their own somewhat idiosyncratic patterns of neural activation. The fact that our method succeeds at across-subject decoding demonstrates the presence of group-level multi-channel regularities across infants. The code for implementing these analyses has been made readily available online to facilitate the quick adoption of this method to advance the methodological tools available to the fNIRS researcher.

Neuroscience

A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity

Candidate enhancers can be identified on the basis of chromatin modifications, the binding of chromatin modifiers and transcription factors and cofactors, or chromatin accessibility. However, validating such candidates as bona fide enhancers requires functional characterization, typically achieved through reporter assays that test whether a sequence can drive expression of a transcriptional reporter via a minimal promoter. A longstanding concern is that reporter assays are mainly implemented on episomes, which are thought to lack physiological chromatin. However, the magnitude and determinants of differences in cis-regulation for regulatory sequences residing in episomes versus chromosomes remain almost completely unknown. To address this question in a systematic manner, we developed and applied a novel lentivirus-based massively parallel reporter assay (lentiMPRA) to directly compare the functional activities of 2,236 candidate liver enhancers in an episomal versus a chromosomally integrated context. We find that the activities of chromosomally integrated sequences are substantially different from the activities of the identical sequences assayed on episomes, and furthermore are correlated with different subsets of ENCODE annotations. The results of chromosomally-based reporter assays are also more reproducible and more strongly predictable by both ENCODE annotations and sequence-based models. With a linear model that combines chromatin annotations and sequence information, we achieve a Pearsons R2 of 0.347 for predicting the results of chromosomally integrated reporter assays. This level of prediction is better than with either chromatin annotations or sequence information alone and also outperforms predictive models of episomal assays. Our results have broad implications for how cis-regulatory elements are identified, prioritized and functionally validated.

Genomics

HydDB: A web tool for hydrogenase classification and analysis

H2 metabolism is proposed to be the most ancient and diverse mechanism of energy-conservation. The metalloenzymes mediating this metabolism, hydrogenases, are encoded by over 60 microbial phyla and are present in all major ecosystems. We developed a classification system and web tool, HydDB, for the structural and functional analysis of these enzymes. We show that hydrogenase function can be predicted by primary sequence alone using an expanded classification scheme (comprising 29 [NiFe], 8 [FeFe], and 1 [Fe] hydrogenase classes) that defines 11 new classes with distinct biological functions. Using this scheme, we built a web tool that rapidly and reliably classifies hydrogenase primary sequences using a combination of k-nearest neighbors algorithms and CDD referencing. Demonstrating its capacity, the tool reliably predicted hydrogenase content and function in 12 newly-sequenced bacteria, archaea, and eukaryotes. HydDB provides the capacity to browse the amino acid sequences of 3248 annotated hydrogenase catalytic subunits and also contains a detailed repository of physiological, biochemical, and structural information about the 38 hydrogenase classes defined here. The database and classifier are freely and publicly available at http://services.birc.au.dk/hyddb/

Bioinformatics

Foxc1 Controls Cell Fate Decisions During Transforming Growth Factor β Induced Epithelial to Mesenchymal Transition Through the Regulation of Fibroblast Growth Factor Receptor 1 Expression.

Epithelial to mesenchymal transition (EMT) is an important physiological process that drives tissue formation during development but also contributes to disease pathogenesis including fibrosis and cancer metastasis. The forkhead box transcription factor gene FOXC1 is an important developmental regulator in the generation of mesenchymal cells necessary in the formation of the anterior segment of the eye, the craniofacial skeleton and the meninges. Recently elevated expression of FOXC1 has been detected in several metastatic cancers that have undergone EMT events. We sought to determine the role of FOXC1 in the initiation of EMT events using NMuMG cells treated with TFG{beta}1. We found that although Foxc1 expression was increased following TFG{beta}1 induced EMT, Foxc1 was not required for this induction. Instead we propose that Foxc1 is required for the specification of the mesenchyme cell type, promoting an activated fibroblast phenotype over a myofibroblast phenotype following the initiation of EMT. This cells type specification was achieved through the regulation of Fibroblast growth factor (Fgfr) 1 expression. Using an RNA sequencing approach, we determined that levels of Fgfr1 normally activated upon TFG{beta}1 treatment were reduced in Foxc1-knockdown cells. Through chromatin immunoprecipitation experiments we determined that FOXC1 could bind to an Fgfr1 upstream regulatory region. Furthermore, expression of the myofibroblast marker -smooth muscle actin (SMA) was elevated in Foxc1 knockdown cells. Finally we determined that FGF2 mediated three dimensional migratory ability was greatly impaired in Foxc1-knockdown cells. Together these results define a role for Foxc1 in specifying a mesenchymal cell type following TFG{beta}1 mediated EMT events.

Cell Biology

Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians

Norepinephrine/noradrenaline is a neurotransmitter implicated in arousal and other aspects of vertebrate behavior and physiology. In invertebrates, adrenergic signaling is considered absent and analogous functions are performed by the biogenic amines octopamine and its precursor tyramine. These chemically similar transmitters signal by related families of GPCR in vertebrates and invertebrates, suggesting that octopamine/tyramine are the invertebrate equivalents of vertebrate norepinephrine. However, the evolutionary relationships and origin of these transmitter systems remain unclear. Using phylogenetic analysis and receptor pharmacology, here we establish that norepinephrine, octopamine, and tyramine receptors coexist in some marine invertebrates. In the protostomes Platynereis dumerilii (an annelid) and Priapulus caudatus (a priapulid) we identified and pharmacologically characterized adrenergic 1 and 2 receptors that coexist with octopamine , octopamine {beta}, tyramine type 1, and tyramine 2 receptors. These receptors represent the first examples of adrenergic receptors in protostomes. In the deuterostome Saccoglossus kowalewskii (a hemichordate), we identified and characterized octopamine , octopamine {beta}, tyramine type 1, and tyramine 2 receptors, representing the first example of these receptors in deuterostomes. S. kowalewskii also has adrenergic 1 and 2 receptors, indicating that all three signaling systems coexist in this animal. In phylogenetic analysis, we also identified adrenergic and tyramine receptor orthologs in xenacoelomorphs. Our results clarify the history of monoamine signaling in bilaterians. Since all six receptor families (two each for octopamine and tyramine and three for norepinephrine) can be found in representatives of the two major clades of Bilateria, the protostomes and the deuterostomes, all six receptors coexisted in the protostome-deuterostome last common ancestor. Adrenergic receptors were lost from most insects and nematodes and tyramine and octopamine receptors were lost from most deuterostomes. This complex scenario of differential losses cautions that octopamine signaling in protostomes is not a good model for adrenergic signaling in deuterostomes, and that the studies of marine animals where all three transmitter systems coexist will be needed for a better understanding of the origin and ancestral functions of these transmitters.

Evolutionary Biology

Resource ratios determine nutrient limitation of primary productivity in the ocean

What is the ultimate limiting nutrient in the ocean? The dominant theory, which was first proposed by Redfield and later formalized by Tyrrell[1, 2], states that despite the scarcity of fixed nitrogen (N) in the surface ocean, phosphorus (P) availability ultimately determines primary productivity. Two recent findings directly challenge the assumptions of the Redfield-Tyrrell paradigm: the discovery of systematic variations of phytoplankton cellular N:P:Fe and widespread iron-limitation of phytoplankton. Here we use a simple model of nitrogen, phosphorus, and iron (Fe) cycling to show how the resource demand ratios and biogeography of phytoplankton interact with external resource supply ratios to govern nutrient cycling and primary productivity. We find that all three nutrients can limit global primary productivity, and that the ratio of geochemical supply to biological demand of each nutrient in each ocean region determines the limiting nutrients, with nitrogen N fixation providing a mechanism for the cycles to interact. These results have important consequences for our understanding of biogeochemical cycles, ocean-atmosphere interactions, marine ecology, and the response of ocean ecosystems to climate change. Our work demonstrates the importance of resource ratios and suggests that future studies of the physiological and geochemical regulation of these ratios are indispensable to building accurate theories and future predictions of nutrient cycling and primary productivity.

Ecology

Beyond APs and VPs: evidences of chaos and self-organized criticality in electrical signals in plants.

Studies on plant electrophysiology are mostly focused on specific traits of action potentials (APs) and/or variation potentials (VPs), often in single cells. Inspired by the complexity of the signaling network in plants and by analogies with some traits of neurons in human brains, we have sought for evidences of high complexity in the electrical dynamics of plant signaling, beyond APs and VPs responses. Thus, from EEG-like data analyses of soybean plants, we showed consistent evidences of chaotic dynamics in the electrical time series. Furthermore, we have found that the dynamic complexity of electrical signals is affected by the plant physiological conditions, decreasing when plant was stressed. Surprisingly, but not unlikely, we have observed that, after stimuli, electrical spikes arise following a power law distribution, which is indicative of self-organized criticality (SOC). Since, as far as we know, these were the first evidences of chaos and SOC in plant electrophysiology, we have asked follow-up questions and we have proposed new hypotheses, seeking for improving our understanding about these findings.

Plant Biology

Gene regulation mechanism in drought-responsive grapevine leaves as revealed by transcriptomic analysis

Grapevine is economically important and widely cultivated fruit crop, which is seriously hampered by drought worldwide. It is necessary to understand the impact of glitches incurred by the drought on grapevine genetic resources. Therefore, in the present study RNA-sequencing analysis was performed using cDNA libraries constructed from both drought-stress and control plants. Results yielded, a total of 12,451 differentially expressed genes (DEGs) out of which 8,022 genes were up-regulated and 4,430 were down-regulated. Further physiological and biochemical analyses were carried out to validate the various biological processes involved in the development of grapevine in response to drought stress. Results also showed that decrease in rate of stomatal conductance in-turn decrease the photosynthetic activity and CO2 assimilation rate in the grapevine leaves and most ROS detoxification systems, including stress enzymes, stress related proteins and secondary metabolites were strongly induced. Moreover, various hormones were known to be induced in the present study in response to drought. Overall the present study concludes that these DEGs play both positive and negative role in drought tolerance by regulating different biological pathways of grapevine. However our findings have provided valuable gene information for future studies of abiotic stress in grapevine and other fruit crops.

Molecular Biology