Change in Buchan vowel harmony

English is not typically considered to be a vowel harmony language, and yet one of its cousins, Buchan Scots, clearly shows vowel-harmonic patterns. This involves a type of height harmony which is blocked by certain consonants and consonant clusters (which do not form a natural class). The front vowel /ɪ/ has historically functioned as a high vowel but seems to have changed into a non-high vowel in the inland dialectal variant. This article considers whether this change has also occurred in the costal variant of the dialect. From newly collected data, I observe that /ɪ/ continues to behave as a high vowel in the Buchan Scots spoken on the coast. However, there are some indications that the group of blocking consonants is shifting to include simple nasals and /r/. While simple nasals have been documented as blocking consonants in some varieties, /r/ has not

Systems level circuit model of C. elegans undulatory locomotion: mathematical modeling and molecular genetics

To establish the relationship between locomotory behavior and dynamics of neural circuits in the nematode C. elegans we combined molecular and theoretical approaches. In particular, we quantitatively analyzed the motion of C. elegans with defective synaptic GABA and acetylcholine transmission, defective muscle calcium signaling, and defective muscles and cuticle structures, and compared the data with our systems level circuit model. The major experimental findings are: (i) anterior-to-posterior gradients of body bending flex for almost all strains both for forward and backward motion, and for neuronal mutants, also analogous weak gradients of undulatory frequency, (ii) existence of some form of neuromuscular (stretch receptor) feedback, (iii) invariance of neuromuscular wavelength, (iv) biphasic dependence of frequency on synaptic signaling, and (v) decrease of frequency with increase of the muscle time constant. Based on (i) we hypothesize that the Central Pattern Generator (CPG) is located in the head both for forward and backward motion. Points (i) and (ii) are the starting assumptions for our theoretical model, whose dynamical patterns are qualitatively insensitive to the details of the CPG design if stretch receptor feedback is sufficiently strong and slow. The model reveals that stretch receptor coupling in the body wall is critical for generation of the neuromuscular wave. Our model agrees with our behavioral data(iii), (iv), and (v), and with other pertinent published data, e.g., that frequency is an increasing function of muscle gap-junction coupling.Comment: Neural control of C. elegans motion with genetic perturbation

sy680 is a novel allele of pkd-2

A new allele of pkd-2 was isolated in a behavioral genetic screen for male mating defects, and found to result in a substitution of Arginine for Glycine in the equivalent of human PKD2 alanine 615. The C. elegans ortholog of polcystin-2 is encoded by pkd-2 (Barr et al., 2001). From an EMS screen of a plg-1; him-5 strain for male mating defective mutants and a secondary behavioral screen for defects in discrete steps of male mating behavior, namely response to contact to hermaphrodites and vulval location (described in Schindelman et al., 2006), we identified a new allele of pkd-2 based on mapping and complementation. sy680 fails to complement pkd-2(sy606) for defects in response to contact with hermaphrodite and vulval location. Here we report the sequence of this allele. PCR amplification and sequencing of pkd-2 exons indicated that there was a c-->t transition in the transcribed DNA strand (g-->a in the pkd-2 sense strand; Figure 1A). This change leads to an altered codon, a Glycine to Arginine substitution the PKD-2 protein. This position corresponds to A615 of the human protein (Figure 1B)

A new mutation with a polycystin phenotypic spectrum in Caenorhabditis elegans

lov-1 and pkd-2, which encode the C. elegans orthologs of human polycystin-1 and -2, are necessary for three particular aspects of male mating behavior. In a screen for male mating defective mutants with similar spectrum of mating defects, we identified a mutation that apparently defines a new locus, lov-3. We isolated the sy682 mutation in an ethyl-methane sulphonate (EMS)-screen of Caenorhabditis elegans strain PS1395 [genotype: plg-1(e2001d); him-5(e1490)] for mutant males that do not mate efficiently and hence do not form plugs on hermaphrodites (Liu et al, 2017). sy682 is defective in the males’ response to contact with hermaphrodite and in vulval location (Table 1). The vulval location defect is failing to stop at the vulva. These two phenotypes are associated with lov-1 (Barr, 1999) and pkd-2 loss-of-function mutations (Barr et al. 2001; Whittaker et al., 2017). sy682 maps to the X chromosome and thus is distinct from lov-1 and pkd-2, so it defines a likely new locus, lov-3

Initiation of male sperm-transfer behavior in Caenorhabditis elegans requires input from the ventral nerve cord

BACKGROUND: The Caenorhabditis elegans male exhibits a stereotypic behavioral pattern when attempting to mate. This behavior has been divided into the following steps: response, backing, turning, vulva location, spicule insertion, and sperm transfer. We and others have begun in-depth analyses of all these steps in order to understand how complex behaviors are generated. Here we extend our understanding of the sperm-transfer step of male mating behavior. RESULTS: Based on observation of wild-type males and on genetic analysis, we have divided the sperm-transfer step of mating behavior into four sub-steps: initiation, release, continued transfer, and cessation. To begin to understand how these sub-steps of sperm transfer are regulated, we screened for ethylmethanesulfonate (EMS)-induced mutations that cause males to transfer sperm aberrantly. We isolated an allele of unc-18, a previously reported member of the Sec1/Munc-18 (SM) family of proteins that is necessary for regulated exocytosis in C. elegans motor neurons. Our allele, sy671, is defective in two distinct sub-steps of sperm transfer: initiation and continued transfer. By a series of transgenic site-of-action experiments, we found that motor neurons in the ventral nerve cord require UNC-18 for the initiation of sperm transfer, and that UNC-18 acts downstream or in parallel to the SPV sensory neurons in this process. In addition to this neuronal requirement, we found that non-neuronal expression of UNC-18, in the male gonad, is necessary for the continuation of sperm transfer. CONCLUSION: Our division of sperm-transfer behavior into sub-steps has provided a framework for the further detailed analysis of sperm transfer and its integration with other aspects of mating behavior. By determining the site of action of UNC-18 in sperm-transfer behavior, and its relation to the SPV sensory neurons, we have further defined the cells and tissues involved in the generation of this behavior. We have shown both a neuronal and non-neuronal requirement for UNC-18 in distinct sub-steps of sperm-transfer behavior. The definition of circuit components is a crucial first step toward understanding how genes specify the neural circuit and hence the behavior

Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

Background: Caenorhabditis elegans gene-based phenotype information dates back to the 1970’s, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results: We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO). The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions: We provide a phenotype ontology (WPO) that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and interoperability across the different Model Organism Databases (MODs) and other biological databases. This standardized phenotype ontology will therefore allow for more complex data queries and enhance bioinformatic analyses

Automatic categorization of diverse experimental information in the bioscience literature

Background: Curation of information from bioscience literature into biological knowledge databases is a crucial way of capturing experimental information in a computable form. During the biocuration process, a critical first step is to identify from all published literature the papers that contain results for a specific data type the curator is interested in annotating. This step normally requires curators to manually examine many papers to ascertain which few contain information of interest and thus, is usually time consuming. We developed an automatic method for identifying papers containing these curation data types among a large pool of published scientific papers based on the machine learning method Support Vector Machine (SVM). This classification system is completely automatic and can be readily applied to diverse experimental data types. It has been in use in production for automatic categorization of 10 different experimental datatypes in the biocuration process at WormBase for the past two years and it is in the process of being adopted in the biocuration process at FlyBase and the Saccharomyces Genome Database (SGD). We anticipate that this method can be readily adopted by various databases in the biocuration community and thereby greatly reducing time spent on an otherwise laborious and demanding task. We also developed a simple, readily automated procedure to utilize training papers of similar data types from different bodies of literature such as C. elegans and D. melanogaster to identify papers with any of these data types for a single database. This approach has great significance because for some data types, especially those of low occurrence, a single corpus often does not have enough training papers to achieve satisfactory performance. Results: We successfully tested the method on ten data types from WormBase, fifteen data types from FlyBase and three data types from Mouse Genomics Informatics (MGI). It is being used in the curation work flow at WormBase for automatic association of newly published papers with ten data types including RNAi, antibody, phenotype, gene regulation, mutant allele sequence, gene expression, gene product interaction, overexpression phenotype, gene interaction, and gene structure correction. Conclusions: Our methods are applicable to a variety of data types with training set containing several hundreds to a few thousand documents. It is completely automatic and, thus can be readily incorporated to different workflow at different literature-based databases. We believe that the work presented here can contribute greatly to the tremendous task of automating the important yet labor-intensive biocuration effort

Screening for C. elegans male copulation-defective mutants by the mating plug phenotype

We describe an efficient screen for male mating defective mutants in Caenorhabditis elegans. We report the isolation of 20 alleles that confer specific mating defects. In a previously reported screen (Hajdu-Cronin et al, 2017), we isolated 19 Cod (for copulation defective) strains in which morphologically wild-type males fail to mate. Failure to mate could conceivably result from defects in any step of the mating process: response, turning, vulva location, spicule insertion, and sperm transfer. By observation, we identified mutants defective in each of these steps except for vulva location. We believe that this was due to both redundancy of sensory structures mediating this step and our stringent screening conditions. To address this, we modified the Cod screen, using the strain plg-1(e2001d); him-5(e1490), in which the presence of a copulatory "plug" over the hermaphrodite vulva provides a visible marker for successful mating (Hodgkin and Doniach, 1997). We backcrossed plg-1(e2001d) four times into him-5(e1490) to make strain PS1395, the parent of our initial screen (sy4xx series). We subsequently repeated our screen after re-isolating a plg-1(e2001d); him-5(e1490) strain PS3696 that had consistent mating behavior and brood size (PS3696 is the parental background for the sy6xx series). Since we select for whether males are able to mate with their moving siblings as opposed to paralyzed hermaphrodites, we expected to isolate more subtle Cod mutants (such as incompletely penetrant vulva location defects). The screen would also allow for the identification of plug formation defective and hermaphrodite-specific mating defective strains. In one PS3696 screen, of 1400 F2 clones, 5% were non-Plg, 280 were then examined for behavior; we kept 69 as candidates; eight had strong phenotypes and normal morphology and were given allele names (sy678, sy680, sy681, sy682, sy683, sy684, sy685, and sy678). sy681 turned out to have the same molecular lesion as sy680 and was discarded. Overall, we isolated 20 Cod mutants from several screens including several pilot screens (Table 1). sy671 was isolated in this screen and found to be an allele of unc-18 (Schindelman et al., 2006)

Paired and LIM class homeodomain proteins coordinate differentiation of the C. elegans ALA neuron

The ancient origin of sleep is evidenced by deeply conserved signaling pathways regulating sleep-like behavior, such as signaling through the Epidermal growth factor receptor (EGFR). In Caenorhabditis elegans, a sleep-like state can be induced at any time during development or adulthood through conditional expression of LIN-3/EGF. The behavioral response to EGF is mediated by EGFR activity within a single cell, the ALA neuron, and mutations that impair ALA differentiation are expected to confer EGF-resistance. Here we describe three such EGF-resistant mutants. One of these corresponds to the LIM class homeodomain (HD) protein CEH-14/Lhx3, and the other two correspond to Paired-like HD proteins CEH-10/Chx10 and CEH-17/Phox2. Whereas CEH-14 is required for ALA-specific gene expression throughout development, the Prd-like proteins display complementary temporal contributions to gene expression, with the requirement for CEH-10 decreasing as that of CEH-17 increases. We present evidence that CEH-17 participates in a positive autoregulatory loop with CEH-14 in ALA, and that CEH-10, in addition to its role in ALA differentiation, functions in the generation of the ALA neuron. Similarly to CEH-17, CEH-10 is required for the posterior migration of the ALA axons, but CEH-14 appears to regulate an aspect of ALA axon outgrowth that is distinct from that of the Prd-like proteins. Our findings reveal partial modularity among the features of a neuronal differentiation program and their coordination by Prd and LIM class HD proteins