Carboxy-Terminal Truncation Activates glp-1 Protein to Specify Vulval Fates in Caenorhabditis elegans

The glp-1 and lin-12 genes encode homologous transmembrane proteins that may act as receptors for cell interactions during development. The glp-1 product is required for induction of germ-line proliferation and for embryogenesis. By contrast, lin-12 mediates somatic cell interactions, including those between the precursor cells that form the vulval hypodermis (VPCs). Here we analyse an unusual allele of glp-1, glp-1(q35), which displays a semidominant multivulva phenotype (Muv), as well as the typical recessive, loss-of-function Glp phenotypes (sterility and embryonic lethality). We find that the effects of glp-1(q35) on VPC development mimic those of dominant lin-12 mutations, even in the absence of lin-12 activity. The glp-1(q35) gene bears a nonsense mutation predicted to eliminate the 122 C-terminal amino acids, including a ProGluSerThr (PEST) sequence thought to destabilize proteins. We suggest that the carboxy terminus bears a negative regulatory domain which normally inactivates glp-1 in the VPCs. We propose that inappropriate glp-1(q35) activity can substitute for lin-12 to determine vulval fate, perhaps by driving the VPCs to proliferate

Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions

During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ~500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus

When Models Interact with their Subjects: The Dynamics of Model Aware Systems

A scientific model need not be a passive and static descriptor of its subject. If the subject is affected by the model, the model must be updated to explain its affected subject. In this study, two models regarding the dynamics of model aware systems are presented. The first explores the behavior of "prediction seeking" (PSP) and "prediction avoiding" (PAP) populations under the influence of a model that describes them. The second explores the publishing behavior of a group of experimentalists coupled to a model by means of confirmation bias. It is found that model aware systems can exhibit convergent random or oscillatory behavior and display universal 1/f noise. A numerical simulation of the physical experimentalists is compared with actual publications of neutron life time and {\Lambda} mass measurements and is in good quantitative agreement.Comment: Accepted for publication in PLoS-ON

Investigation of Quasi--Realistic Heterotic String Models with Reduced Higgs Spectrum

Quasi--realistic heterotic-string models in the free fermionic formulation typically contain an anomalous U(1), which gives rise to a Fayet-Iliopolous term that breaks supersymmetry at the one--loop level in string perturbation theory. Supersymmetry is restored by imposing F- and D-flatness on the vacuum. In Phys. Rev. D 78 (2008) 046009, we presented a three generation free fermionic standard-like model which did not admit stringent F- and D-flat directions, and argued that the all the moduli in the model are fixed. The particular property of the model was the reduction of the untwisted Higgs spectrum by a combination of symmetric and asymmetric boundary conditions with respect to the internal fermions associated with the compactified dimensions. In this paper we extend the analysis of free fermionic models with reduced Higgs spectrum to the cases in which the SO(10) symmetry is left unbroken, or is reduced to the flipped SU(5) subgroup. We show that all the models that we study in this paper do admit stringent flat directions. The only examples of models that do not admit stringent flat directions remain the strandard-like models of reference Phys. Rev. D 78 (2008) 046009.Comment: 38 pages, 1 figur

A functional-cognitive framework for attitude research

In attitude research, behaviours are often used as proxies for attitudes and attitudinal processes. This practice is problematic because it conflates the behaviours that need to be explained (explanandum) with the mental constructs that are used to explain these behaviours (explanans). In the current chapter we propose a meta-theoretical framework that resolves this problem by distinguishing between two levels of analysis. According to the proposed framework, attitude research can be conceptualised as the scientific study of evaluation. Evaluation is defined not in terms of mental constructs but in terms of elements in the environment, more specifically, as the effect of stimuli on evaluative responses. From this perspective, attitude research provides answers to two questions: (1) Which elements in the environment moderate evaluation? (2) What mental processes and representations mediate evaluation? Research on the first question provides explanations of evaluative responses in terms of elements in the environment (functional level of analysis); research on the second question offers explanations of evaluation in terms of mental processes and representations (cognitive level of analysis). These two levels of analysis are mutually supportive, in that better explanations at one level lead to better explanations at the other level. However, their mutually supportive relation requires a clear distinction between the concepts of their explanans and explanandum, which are conflated if behaviours are treated as proxies for mental constructs. The value of this functional-cognitive framework is illustrated by applying it to four central questions of attitude research

Cosmological perturbations in a healthy extension of Horava gravity

In Horava's theory of gravity, Lorentz symmetry is broken in exchange for renormalizability, but the original theory has been argued to be plagued with problems associated with a new scalar mode stemming from the very breaking of Lorentz symmetry. Recently, Blas, Pujolas, and Sibiryakov have proposed a healthy extension of Horava gravity, in which the behavior of the scalar mode is improved. In this paper, we study scalar modes of cosmological perturbations in extended Horava gravity. The evolution of metric and density perturbations is addressed analytically and numerically. It is shown that for vanishing non-adiabatic pressure of matter the large scale evolution of cosmological perturbations converges to that described by a single constant, $\zeta$, which is an analog of a curvature perturbation on the uniform-density slicing commonly used in usual gravitational theories. The subsequent evolution is thus determined completely by the value of $\zeta$.Comment: 10 pages, 4 figures; v2: published versio

Detailed balance condition and ultraviolet stability of scalar field in Horava-Lifshitz gravity

Detailed balance and projectability conditions are two main assumptions when Horava recently formulated his theory of quantum gravity - the Horava-Lifshitz (HL) theory. While the latter represents an important ingredient, the former often believed needs to be abandoned, in order to obtain an ultraviolet stable scalar field, among other things. In this paper, because of several attractive features of this condition, we revisit it, and show that the scalar field can be stabilized, if the detailed balance condition is allowed to be softly broken. Although this is done explicitly in the non-relativistic general covariant setup of Horava-Melby-Thompson with an arbitrary coupling constant $\lambda$, generalized lately by da Silva, it is also true in other versions of the HL theory. With the detailed balance condition softly breaking, the number of independent coupling constants can be still significantly reduced. It is remarkable to note that, unlike other setups, in this da Silva generalization, there exists a master equation for the linear perturbations of the scalar field in the flat Friedmann-Robertson-Walker background.Comment: Some typos are corrected. To appear in JCA

Fast Low-to-High Confinement Mode Bifurcation Dynamics in a Tokamak Edge Plasma Gyrokinetic Simulation

Transport barrier formation and its relation to sheared flows in fluids and plasmas are of fundamental interest in various natural and laboratory observations and of critical importance in achieving an economical energy production in a magnetic fusion device. Here we report the first observation of an edge transport barrier formation event in an electrostatic gyrokinetic simulation carried out in a realistic diverted tokamak edge geometry under strong forcing by a high rate of heat deposition. The results show that turbulent Reynolds-stress-driven sheared E×B flows act in concert with neoclassical orbit loss to quench turbulent transport and form a transport barrier just inside the last closed magnetic flux surface